Non Neoplastic Cytology A Comprehensive Guide 1St Edition Syed M Gilani Online Ebook Texxtbook Full Chapter PDF

Non-Neoplastic Cytology: A
Comprehensive Guide 1st Edition Syed

M. Gilani
Visit to download the full and correct content document:
https://ebookmeta.com/product/non-neoplastic-cytology-a-comprehensive-guide-1st-e
dition-syed-m-gilani/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...
Cancer Consult: Expertise in Clinical Practice, Volume

2: Neoplastic Hematology & Cellular Therapy, 2nd
Edition Syed A. Abutalib
https://ebookmeta.com/product/cancer-consult-expertise-in-
clinical-practice-volume-2-neoplastic-hematology-cellular-
therapy-2nd-edition-syed-a-abutalib/
Diagnostic EMQs: A Comprehensive Collection for Medical

Examinations 1st Edition Syed Hussain
https://ebookmeta.com/product/diagnostic-emqs-a-comprehensive-
collection-for-medical-examinations-1st-edition-syed-hussain/
Primary Mathematics 3A Hoerst
https://ebookmeta.com/product/primary-mathematics-3a-hoerst/
Equine Hematology Cytology and Clinical Chemistry 2nd

Edition Raquel M. Walton (Editor)
https://ebookmeta.com/product/equine-hematology-cytology-and-
clinical-chemistry-2nd-edition-raquel-m-walton-editor/
Pharmaceutical Vendors Approval Manual: A Comprehensive
Quality Manual for API and Packaging Material Approval
1st Edition Erfan Syed Asif
https://ebookmeta.com/product/pharmaceutical-vendors-approval-
manual-a-comprehensive-quality-manual-for-api-and-packaging-
material-approval-1st-edition-erfan-syed-asif/
A Comprehensive Guide to Solar Energy Systems: With

Special Focus on Photovoltaic Systems 1st Edition
Trevor M. Letcher
https://ebookmeta.com/product/a-comprehensive-guide-to-solar-
energy-systems-with-special-focus-on-photovoltaic-systems-1st-
edition-trevor-m-letcher/
Hoarding Disorder A Comprehensive Clinical Guide 1st

Edition Rodriguez
https://ebookmeta.com/product/hoarding-disorder-a-comprehensive-
clinical-guide-1st-edition-rodriguez/
Network Architect s Guide to 5G A 1st Edition Syed

Farrukh Hassan Alexander Orel Kashif Islam
https://ebookmeta.com/product/network-architect-s-guide-
to-5g-a-1st-edition-syed-farrukh-hassan-alexander-orel-kashif-
islam/
The Bundy Murders A Comprehensive History 2nd Edition

Kevin M Sullivan
https://ebookmeta.com/product/the-bundy-murders-a-comprehensive-
history-2nd-edition-kevin-m-sullivan/
Non-Neoplastic
Cytology
A Comprehensive Guide
Syed M. Gilani
Guoping Cai
Editors
123
Non-Neoplastic Cytology
Syed M. Gilani • Guoping Cai
Editors
Non-Neoplastic Cytology
A Comprehensive Guide
Editors
Syed M. Gilani Guoping Cai
Department of Pathology Department of Pathology
Albany Medical Center, Albany Yale School of Medicine
Medical College New Haven, CT, USA
Albany, NY, USA
ISBN 978-3-031-44288-9 ISBN 978-3-031-44289-6 (eBook)

https://doi.org/10.1007/978-3-031-44289-6
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
transmission or information storage and retrieval, electronic adaptation, computer software, or by similar
or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, expressed or implied, with respect to the material contained herein or for any
errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional
claims in published maps and institutional affiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Paper in this product is recyclable.

Preface
Cytology evaluates cellular details, and in contrast, histology relates to tissue assess-
ment with rather preserved architecture. During daily cytology practice, we fre-
quently encounter certain situations which are often challenging such as
differentiating normal cytology components or nonneoplastic lesions from a neo-
plastic process, abnormality versus artifact, contaminants from lesional sampling,
immunostain expression in unexpected cells, identifying/or characterizing infec-
tious microorganisms, and use of special stains. In-depth knowledge about normal
tissue cytology, the pattern of immunohistochemical expression in various organs,
and recognizing diagnostic pitfalls would help to overcome diagnostically challeng-
ing situations.
This book is formatted to present a detailed and state-of-the-art approach to non-
neoplastic cytology. High-yield content, mostly used in daily practice, is in tabular
format. This book provides detailed information about cytomorphologic features of
infectious microorganisms and the use of special stains, the use of immunohisto-
chemistry along with expression in normal cell types, artifacts/contaminants or inci-
dental findings, and cytomorphologic features of non-tumor-related lesions in an
organ-based structure. There is a further elaboration of differential diagnosis and
mimickers of cytologic material from normal parenchymal tissue, infectious/inflam-
matory conditions, and benign cystic lesions. The last chapter describes a quick
overview of important reference material in tables, which is useful for daily ana-
tomic pathology sign-out. This book provides all practical information about non-
neoplastic cytology in one concise format using tables and images.
Albany, NY, USA Syed M. Gilani

New Haven, CT, USA Guoping Cai
v
Contents
1
Cytology Specimen Collection, Preparation, and Stains�� 1
Zoon Tariq and Syed M. Gilani
2 Urinary Tract Cytology �� 11
Guoping Cai
3 Cervical and Vaginal Cytology�� 35
Tong Sun and Syed M. Gilani
4 Peritoneal Washings and Ovary �� 51
5
Body Cavity Fluid Cytology�� 57
Minhua Wang
6 Salivary Gland�� 73
Syed M. Gilani
7 Thyroid Gland�� 85
Syed M. Gilani
8 Neck Lesions �� 105
Syed M. Gilani
9 Lymph Node �� 113
Omar Al-Rusan and Saja Asakrah
10 Breast�� 141
Osvaldo Hernandez and Aylin Simsir
11 Respiratory Tract �� 189
Ruhani Sardana and Guoping Cai
12 Gastrointestinal Tract�� 217
Rita Abi-Raad
vii
viii Contents
13 Pancreas�� 229
Xi Wang and Guoping Cai
14 Liver and Biliary Tract�� 247
Xi Wang and Guoping Cai
15 Kidney and Adrenal Gland �� 267
Khairya Fatouh and Syed M. Gilani
16 Soft Tissue �� 277
Juan Xing
17 Bone�� 301
Sigfred Lajara
18
Brain and Cerebrospinal Fluid�� 329
Armine Darbinyan, Anita Huttner, and Minhua Wang
19 Quick Review�� 341
Khairya Fatouh and Syed M. Gilani
Index�� 353
Chapter 1
Cytology Specimen Collection,
Preparation, and Stains
Zoon Tariq and Syed M. Gilani
Specimen Collection Techniques [1]
• Slides preparation:
• The appropriate sample should be collected sufficiently for any cytology speci-
men to prepare slides (Table 1.1).
• Each slide should be labeled with at least two patient identifiers [2].
• A small amount of sample should be gently expelled onto a slide with the needle
tip pointing down towards the slide near the frosted edge to give the most space
for subsequent preparation [3].
• “Two-Slide Pull” method: a new clean slide can be used to spread the sample
across the first slide to create a thin, evenly distributed smear with constant gen-
tle pressure, or place the specimen close to the midpoint of the slide and place
another slide on the top of the specimen and gently pull both slides on the oppo-
site direction. This will generate two slides containing the specimen. One slide
can be used for rapid onsite evaluation (ROSE) by airdrying first and then stain-
ing with Diff-Quik stain. In contrast, the other slide should rapidly be fixed using
95% ethyl alcohol or cytology spray fixative.
• For staining details, refer to the specimen preparation section.
Z. Tariq
Department of Pathology, George Washington University, Washington, DC, USA
e-mail: ztariq@mfa.gwu.edu
S. M. Gilani (*)
Department of Pathology, Albany Medical Center, Albany Medical College,
Albany, NY, USA
e-mail: gilanis@amc.edu
© The Author(s), under exclusive license to Springer Nature 1

Switzerland AG 2023
S. M. Gilani, G. Cai (eds.), Non-Neoplastic Cytology,
https://doi.org/10.1007/978-3-031-44289-6_1
2
Table 1.1 Specimen collection techniques
Cytology
technique Procedure Indications/uses Preparation Adequacy criteria Contaminants
Fine needle Image guided: • Diagnosis, staging lung cancer Direct smear, Presence of lesional material Bronchial cells,
aspiration Endobronchial ultrasound • Mediastinal lymphadenopathy ThinPrep, cell block cartilage, upper
(FNA) (EBUS) • Mediastinal mass respiratory tract
• Parenchymal pulmonary epithelial cells
nodules, endobronchial lesions
Image guided: • Primary diagnosis or staging of Presence of lesional cells Oral and GI
Endoscopic ultrasound lesions of gastroesophageal, contaminants
(EUS) pancreaticobiliary, ampullary,
intestinal or rectal area
• Mass in pancreas, gallbladder,
biliary tree, liver
• Some retroperitoneal lesions
Image guided: • Strictures Epithelial cells or lesional GI contaminants
Endoscopic retrograde • Ampullary lesion cells
cholangiopancreatography
(ERCP)
Thyroid Thyroid lesion or nodule ≥6 groups of follicular cells Gel material, skeletal
with ≥10 cells/cluster with muscle
certain exception [4]
Salivary gland Salivary gland lesion or nodule Lesional cells Skin
Only normal salivary gland
elements in context of mass
may not represent lesional
cells [5]
Breast Cystic or mass forming lesion Presence of lesional cells (in Skin
correlation with clinical and
imaging features)
Superficial: Amyloidosis Fibroadipose tissue fragments Skin, muscle
Z. Tariq and S. M. Gilani
Fat pad FNA and associated vessels

Cytology
1
Exfoliative Cervical pap, anal pap Screening for dysplasia or cancer Liquid-based Squamous cells [6] –
cytology infection preparations (LBP: • Conventional:
ThinPrep SurePath): 8000–12,000
Pap • LBP: ≥5000
Anal
• Conventional: 2000–3000
nucleated squamous cells
(NSC)
Urine Screening, infection, neoplasia Voided urine >30 mL [7] –
Cerebrospinal fluid Infection, neoplasia/malignancy – Cartilage, blood
elements
Bronchial lavage Infectious (pneumonia, TB, fungi) >10 alveolar macrophages or Oral contaminants,
Malignancy any abnormality [8] upper respiratory
epithelial cells
Sputum TB, pneumocystis jirovecii (PJP) Preferably macrophages [8] Oral contaminants
(squamous epithelial
cells)
Brushings Bronchial, biliary, esophageal Lesional cells or epithelial
cells
Cytology Specimen Collection, Preparation, and Stains
Washings Bronchial, gastric, colonic, Lesional cells or epithelial

bladder, ureteral cells
Body cavities Pleural, pericardial, peritoneal LBP, cell block Preferably >50–75 mL of Skin, muscle
fluid [9]
Synovial fluid Gout, pseudogout infection – –
Vitreous fluid Infection neoplasia ThinPrep or direct – –
smear
Cyst fluid Malignancy LBP – –
Nipple discharge Malignancy Direct smear – –
(continued)
3
4
Table 1.1 (continued)

Cytology
Touch prep Intraoperative consultation Infection, nonneoplastic, or Direct smear Presence of lesional cells –
or FNA Intraoperative consultation neoplastic processes
procedure and rapid on-site evaluation:
Aims not only to improve
diagnostic yield of the
procedure but to also help
ensure that adequate
material is collected and
allocated for ancillary tests
based on the preliminary
cytologic impression [10]
Z. Tariq and S. M. Gilani
1 Cytology Specimen Collection, Preparation, and Stains 5
• All specimens received directly into the cytopathology lab should be tightly
secured in their respective containers, labeled, and accompanied by an appropri-
ately completed patient requisition form.
• Fixation is in 95% alcohol (ethyl alcohol) for the majority of cases. Alcohol
shrinks the cells making nuclear details clearer. 100% alcohol may be used in
place of 95% ethyl alcohol.
Fine Needle Aspiration (FNA)
• This procedure is used to evaluate either superficial or deep-seated lesions. FNA

of superficial lesions is with or without image guidance, while FNA of deep-
seated lesions is performed under image guidance.
• Pathologists often perform FNA of superficial palpable lesions or fat-pad FNA.
• Superficial palpable lesions are generally aspirated with a 22–25 G needle
attached to a 10–20 cc syringe.
• Some aspirated contents (2–3 drops) are placed onto a glass slide, and two direct
smears are usually prepared using another clear slide. One slide is used for
ROSE, while the other is fixed in alcohol for further evaluation.
• Needles should be rinsed in an appropriate solution or formalin to prepare a cell
block that can be used for ancillary testing.
Exfoliative Cytology
• Gynecologic cytology: Liquid-based gynecological pathology specimens are col-

lected using SurePath or Cytyc ThinPrep preparations for Pap tests.
• Voided urine: Discard first early morning urine; patient voids into specimen con-
tainer; collect urine starting at midstream. Specimens must be submitted imme-
diately to the lab to avoid cellular degeneration. Specimens can be submitted
fresh or in 70% alcohol fixative for possible ancillary testing (FISH analysis).
Cytology preparations of samples are examined for infections or malignancy.
• CSF: Aspirated CSF is evaluated for infection or malignancy.
• Sputum: Specimen is evaluated for infection or neoplastic process; complete
series: early morning specimens each day for 3 days (if suspected tuberculosis).
• Brushings: Specimens are cellular, and mostly CytoLyt solution is used for pres-
ervation, but direct smears can also be prepared. The specimen is examined to
evaluate for infection, nonneoplastic, or neoplastic processes.
• Washings: Bronchial washing is mostly used to evaluate for infection or malig-
nancy. Peritoneal washing is to assess for a neoplastic process.
• Body cavity fluids: ThinPrep or cytospin preparations are commonly used. They
are examined to determine the cause of fluid accumulation (nonneoplastic versus
neoplastic).
–– Direct scrapings: Herpes virus detection: Tzanck test.
6 Z. Tariq and S. M. Gilani
–– Touch imprint: Touch imprint cytology is mostly used either for ROSE or dur-
ing intraoperative frozen sections. The biopsy material is touched or scraped
on the glass slide and is immediately fixed in alcohol with subsequent staining
(Papanicolaou or rapid H&E) or air-dried and then stained with Diff-Quik
stain. Squash preparations are also used (mostly in brain-frozen sections).
Specimen Preparation
• Cytology specimen received in the lab is processed based on the specimen site
and volume. Direct smears from an FNA procedure usually have an air-dried
preparation (Diff-Quik stained) and an alcohol-fixed preparation
(Papanicolaou stain).
• Specimens may be concentrated by centrifugation to obtain a cell pellet.
• Papanicolaou (Pap) stain.
–– This staining technique is helpful for optimal visualization of cancer cells
exfoliated from epithelial surfaces of the body.
–– The polychrome staining reaction is helpful in highlighting cytologic fea-
tures, chromatin and cytoplasmic details.
–– Procedure.
Fixation: Coplin jar with 95% ethyl alcohol (5–15 min).
Hydration: running water.
Nuclear staining: Harris hematoxylin (1–5 min).
Rinse: running water.
Scott’s tap water/distilled water.
Rinse: running water.
Rinse: 95% ethyl alcohol, two changes (10 dips).
Cytoplasmic staining: OG-6 for 30 s to a min.
Rinse solution: 95% ethyl alcohol, three changes (10 dips).
Cytoplasmic staining: EA-50 for 5 min.
Rinse: 95% ethyl alcohol, three changes (10 dips).
Final dehydration: 100% ethyl alcohol (10 dips).
Clearing: xylene, three changes.
Coverslip.
• Diff-Quik stain.
–– Use for ROSE, evaluate the cytoplasmic details, infectious organisms, and
hematological elements.
–– Procedure.
Fixative solution (methanol) for 30 s to 1 min.
Solution I (eosinophilic) 10 dips.
Solution II (basophilic) 10 dips.
Rinse slides in running water.
Coverslip.
• Rapid H&E stain.

–– The method is used mostly for intraoperative frozen sections and ROSE.
–– Nuclei stain blue; overstaining with hematoxylin results in dark nuclear stain-
ing and vice versa.
Cytoplasm/other tissue elements, including RBCs, stain pink; overstaining
with eosin results in dark cytoplasmic staining.
• Cell block.
–– A cell block may be prepared from any fluid, washing, brushing, or FNA, with
the added benefit that this procedure obtains any tissue which may be present
in the specimen. Cell block material can be used for ancillary testing if
required.
–– Procedure.
Centrifuge the specimen to obtain a pellet which includes the following
procedure: Add 10 mL of absolute alcohol and centrifuge it, and gradually
decant the supernatant. Add 15–20 mL formalin, again centrifuge it and
pour supernatant. Add HistoGel drops to the pellet and then refrigerate it
for a few minutes. Put the pellet in the cassette and submit it for processing.
Special Stains
Workup Stain Uses Positive interpretation

Infectious Ziehl-Neelsen Acid fast organisms Red rod-shaped
organisms Modified Acid fast organisms organisms on a blue
Ziehl-Neelsen background
Kinyoun Acid fast organisms Red organisms on a
blue-green background
Fite Mycobacteria leprae Red organisms on a
blue background
Auramine-rhodamine Acid fast organisms Yellow-red
fluorescence
Grocott’s Fungi especially PJP Black organisms on
methenamine silver pale green background
(GMS)
Periodic acid Schiff Fungi; polysaccharides; neutral Magenta-red organisms
(PAS) mucosubstances, basement on blue-green
membrane background
Brown-Hopps Bacteria Gram+: Blue
Gram–: Red
Brown-Brenn Bacteria Gram+: Purple-blue
Gram–: Pink-red
Warthin-starry Spirochetes, helicobacter pylori Dark brown-black
organisms on pale
yellow background
Workup Stain Uses Positive interpretation

Other Alcian blue Acid mucopolysaccharides; for Acid mucins: Blue
Cryptococcus spp.
Cresyl violet Neurons (Nissl substance) Granular purple-blue
neuropil
Fontana Masson Melanin, argentaffin cell Melanin: Brown-black;
granules (of carcinoid tumor) on pale pink
background
PAS with diastase To differentiate mucin from Light pink (replaces
digestion glycogen, fungal infections, deep magenta of PAS
Whipple’s disease only)
Masson’s trichrome Connective tissue/vasculature, Collagen: Blue; nuclei:
collagen, fibrosis Brown/black; muscle:
Red; cytoplasm: Pink
Von Kossa Calcium deposits Gray-black calcium
deposits on light pink
background
Reticulin Reticulin fibers (tumor Black fibers on
architecture) gray-pink background
Luxol fast blue Myelin in nerves Myelin: Blue-green
Neuropil: Pink
Verhoeff’s elastic Elastic fibers Elastic fibers: Black
stain Collagen: Red
Bielschowsky silver Nerve fibers (neurofibrillary Black nerve fibers
stain tangles in Alzheimer’s disease)
Oil red O Lipid, lipid laden macrophages Red
Prussian blue Iron (hemosiderin) Bright blue on pink
background
Congo red Amyloid Salmon-pink and green
birefringence under
polarized light
Thioflavin-T Amyloid Bright yellow-green
fluorescence on black
background
Mayer Mucicarmine Acid mucopolysaccharides; Red on yellow
epithelial mucin; for background
Cryptococcus spp.
Bile Bilirubin Emerald green
Rhodanine Copper Bright red
Myeloperoxidase Myeloid lineage, MPO Blue-green or brown, if
(MPO) deficiency present
Sudan black B Neutral lipids Black granular
Leukocyte alkaline Alkaline phosphatase activity Brown-black granules
phosphatase
Toluidine blue Mast cells Dark rose-violet on a
blue background
Movat pentachrome Collagen, elastic fibers, muscle, Elastic fibers-black
and mucin Collagen-yellow
Mucin- blue
Muscle-red
Immunohistochemistry
• An important development in cytopathology is the application of immunohisto-

chemical staining (IHC) techniques on direct smears and ThinPrep slides, along
with the traditional use on cell block material.
• Specimens with limited material or with no cell block can further be evaluated by
performing stain on additional ThinPrep slide (such as PTH stain for parathy-
roid, calcitonin stain for medullary thyroid carcinoma).
• On cytology preparation (direct smear or ThinPrep), interpretation of IHCs with
nuclear staining pattern is more straightforward.
Limitation
• Polyclonal antibodies are more sensitive and bind with more epitopes. Titration
should be done cautiously to avoid overstaining (false positives).
• Monoclonal antibodies are more homogeneous and specific against a single
epitope.
• Cytoplasmic or membranous staining interpretation on ThinPrep or direct smear
slides is often challenging.
• Fixative-related issues: Alcohol fixative versus formalin fixative.
Acknowledgments None.
Conflict of Interest None.
References
1. VanderLaan PA. Molecular markers: implications for cytopathology and specimen collection.
Cancer Cytopathol. 2015;123(8):454–60.
2. Al-Abbadi MA. Basics of cytology. Avicenna J Med. 2011;1(1):18–28.
3. Abele JS, Miller TR, King EB, Lowhagen T. Smearing techniques for the concentration of
particles from fine needle aspiration biopsy. Diagn Cytopathol. 1985;1(1):59–65.
4. Cibas ES, Ali SZ. The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid.
2017;27(11):1341–6.
5. Rossi ED, Faquin WC. The Milan system for reporting salivary gland cytopathology
(MSRSGC): an international effort toward improved patient care-when the roots might be
inspired by Leonardo da Vinci. Cancer Cytopathol. 2018;126(9):756–66.
6. Nayar R, Wilbur DC. The pap test and Bethesda 2014. Cancer Cytopathol. 2015;123(5):271–81.
7. Zare S, Mirsadraei L, Reisian N, Liao X, Roma A, Shabaik A, Hasteh F. A single institutional
experience with the Paris system for reporting urinary cytology: correlation of cytology and
histology in 194 cases. Am J Clin Pathol. 2018;150(2):162–7.
8. Guidelines of the Papanicolaou Society of Cytopathology for the examination of cytologic
specimens obtained from the respiratory tract. Papanicolaou society of cytopathology task
force on standards of practice. Diagn Cytopathol. 1999;21(1):61–9.
9. Pinto D, Chandra A, Crothers BA, Kurtycz DFI, Schmitt F. The international system for
reporting serous fluid cytopathology-diagnostic categories and clinical management. J Am Soc
Cytopathol. 2020;9(6):469–77.
10. Collins BT, Chen AC, Wang JF, Bernadt CT, Sanati S. Improved laboratory resource utiliza-
tion and patient care with the use of rapid on-site evaluation for endobronchial ultrasound fine
needle aspiration biopsy. Cancer Cytopathol. 2013;121(10):544–51.
Chapter 2
Urinary Tract Cytology
Guoping Cai
Anatomy and histopathology of Urinary Tract
The urinary system is composed of the kidney, ureter, urinary bladder, and urethra.
These organs are connected via the epithelium-lined urinary tract in the renal caly-
ces, renal pelvis, ureter, urinary bladder, and urethra.
Urothelium:
The urothelium, lining almost the entire urinary tract except for distal urethra, is
approximately three to eight cells thick, composed of superficial, intermediate, and
basal cells (Fig. 2.1). The superficial cells, termed umbrella cells, have abundant
eosinophilic cytology and large nuclei with frequent binucleation and multinucle-
ation. The intermediate or pyramidal cells are relatively uniform and have a fair
amount of eosinophilic cytoplasm, well-defined cell borders, and oval nuclei. The
basal cells are small and have low cytoplasmic to nuclear ratios and round to
oval nuclei.
Squamous epithelium:
The distal urethra is lined by squamous epithelium (Fig. 2.2), morphologically
like the squamous mucosa lining in other organ systems. Squamous epithelium,
likely metaplastic in nature, is commonly seen in the trigone region of the urinary
bladder, especially in women.
G. Cai (*)
Department of Pathology, Yale School of Medicine, New Haven, CT, USA
e-mail: guoping.cai@yale.edu

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-44289-6_2
12 G. Cai
Fig. 2.1 Urothelial lining

in the urinary bladder. The
epithelium is composed of
5–7 layers of epithelial
cells with dense cytoplasm,
oval nuclei, fine granular
chromatin, and small
nucleoli. There are
umbrella cells in the top
layer of the epithelium
Fig. 2.2 Squamous

epithelial lining in the
urethra. The epithelium is
composed of polygonal
epithelial cells with
gradual maturation from
the base towards to the
surface. The squamous
cells have dense
cytoplasm, round or oval
nuclei, finely coarse
chromatin, and small
nucleoli. Intercellular
bridges are notably seen
Sampling Methods
The cytology specimens from the urinary tract include voided urine, catheterized
urine, and the samples collected by wash and brushing techniques [1]. Each of these
sampling techniques has its own advantages and disadvantages (Table 2.1). Knowing
the nature of sample collection methods may help avoid diagnostic pitfalls in the
cytological evaluation of urine specimens.
2
Table 2.1 Comparison of urine sample collection methods1

Utility Advantage Disadvantage Diagnostic Pitfall
Voided urine Screening test for hematuria Easy and inexpensive sample Low cellularity Difficult to differentiate
Follow-up for patients with collection Degenerative changes low-grade tumors from reactive
urothelial malignancy Representative of entire urinary Contaminants commonly changes
tract seen
Catheterized urine Urinary tract evaluation when Easy and inexpensive sample Catheterization induced Over-interpretation of
urinary catheter in place collection reactive changes cytological and architectural
Contamination less likely Clusters of urothelial cells atypia related to

Less degenerative changes commonly seen instrumentation
Wash specimen Evaluation of upper urinary tract Less degenerative changes Complicated procedure Over-interpretation of
lesions Contamination less likely Instrumentation artifacts architectural atypia related to
Evaluation of urinary bladder Evaluation of specific location instrumentation
when no gross lesions identified Correlation with clinical and
during cystoscopy imaging findings
Brush specimen Evaluation of upper urinary tract Less degenerative changes Complicated procedure Over-interpretation of
lesions Contamination less likely Instrumentation artifacts architectural atypia related to
Evaluation of urinary bladder Evaluation of specific location instrumentation
when no gross lesions identified Correlation with clinical and
during cystoscopy imaging findings
Ileal conduit urine Follow-up for patients with Easy and inexpensive sample Marked degenerative Over-interpretation of
cystectomy collection changes degenerative changes as tumor
Obscuring bacteria and/or diathesis
inflammatory cells
13
14 G. Cai
Voided Urine
The most common cytology specimen from urinary tract is voided urine, which is
collected by far the easiest and least expensive method. The cells in voided urine
samples may be sourced from the entire urinary tract, including upper urinary tract
(renal pelvis and ureter) and lower urinary tract (urinary bladder and urethra),
although most cells are likely of urinary bladder origin. The cells in voided urine
samples are mostly dispersed single cells (Fig. 2.3); however, clusters of epithelial
cells can be seen in neoplastic as well as nonneoplastic conditions such as inflam-
mation, infection, and urolithiasis (Fig. 2.4). It is important in urine cytology to
avoid making the diagnosis of a papillary tumor solely based on the presence of
urothelial cell clusters [1] [2].
Ileal conduit urine is a special form of voided urine samples. The samples are
collected from patients who have undergone cystectomy. The cells in the ileal con-
duit urine samples often show marked degenerative changes, mostly of intestinal
epithelial origin (Fig. 2.5) [3].
Catheterized Urine
The sample is collected via a catheter. The cells in catheterized urine sample are
primarily from the urinary bladder where the catheter is placed. Compared to voided
urine, catheterized urine specimen more likely has clusters of urothelial cells and
shows more reactive changes (Fig. 2.6).
Fig. 2.3 Voided urine.

Dispersed single urothelial
cells composed of
predominantly
intermediate urothelial
cells with scattered
umbrella cells and rare
basal cells
2 Urinary Tract Cytology 15
Fig. 2.4 Voided urine. A three-dimensional luster of urothelial cells. Urothelial cells are small
with slightly hyperchromatic nuclei
Fig. 2.5 Ileal conduit

urine. Markedly
degenerated epithelial cells
with apoptotic bodies and
scattered inflammatory
cells
16 G. Cai
Fig. 2.6 Catheterized

urine with reactive
changes. Loosely cohesive
group of urothelial cells
with enlarged nuclei and
conspicuous nucleoli. An
umbrella cell with
binucleation is seen
a b
Fig. 2.7 Bladder wash specimen. (a) Clusters of intermediate urothelial cells with scattered
umbrella cells and rare basal cells. (b) A papillary cluster of urothelial cells with enlarged nuclei
and conspicuous nucleoli
Wash Specimen
Washing can be applied to a specific part of the urinary tract. In urinary bladder,
wash or barbotage can be performed during or prior to cystoscopy. Wash can also be
performed for the space-occupied lesions or stricture in upper urinary tract via ret-
rograde catheterization. In general, wash specimens show less degenerative changes
but more instrumentation artifacts (Fig. 2.7). For the upper urinary lesions, correla-
tion with clinical and imaging findings is always recommended.
Fig. 2.8 Ureteral brush

specimen. A cluster of
intermediate urothelial
cells with scattered
umbrella cells and rare
basal cells
Brush Specimen
For the space-occupied lesions or structure in the upper urinary tract, direct sam-
pling of the lesions can be performed by brushing technique via retrograde catheter-
ization. Like wash specimens, brush specimens also show less degenerative changes
but more instrumentation artifacts (Fig. 2.8). Again, for the upper urinary lesions,
correlation with clinical and imaging findings is always recommended.
Normal Urine Cytology
Adequacy
Currently, there is no well-established criteria for a specific number of cells for

adequacy assessment, but a minimal volume of 30 ml for cytological evaluation of
voided urine sample has been recommended [4]. Identification of any abnormal
cells is considered adequate even when urine sample is less than 30 ml. For instru-
mented urine specimens, specific volume or cellularity requirement has not been
well established. There is one study suggesting a threshold of at least 20 well-
preserved, well-visualized urothelial cells per 10 high-power fields [5].
18 G. Cai
Urothelial Cells
The number and types of urothelial cells in a specimen are largely dependent on
sample collection methods. Voided urine specimens are almost exclusively com-
posed of single cells with considerable variations in cellularity. Instrumented sam-
ples often cellular with urothelial cell clusters as a common finding. Superficial and
intermediate urothelial cells are the common cell types in voided urine specimens
while the basal urothelial cells are more frequently seen in instrumented samples,
often forming clusters with intermediate urothelial cells. (Table 2.2).
Superficial Urothelial Cells
Superficial umbrella cells are the largest urothelial cells (Fig. 2.9). These cells are
polygonal and have abundant homogenous cytoplasm, occasionally with cytoplas-
mic vacuolation. The nuclei are round or oval with smooth nuclear contours,
coarsely granular chromatin, and occasional conspicuous nucleoli. Binucleation
and multinucleation are frequently seen. Although the nuclei of superficial urothe-
lial cells, even in the single nucleated form, are larger those in the intermediate or
basal cells, the superficial urothelial cells have low nuclear to cytoplasmic ratios due
to abundant cytoplasm.
Intermediate Urothelial Cells
Intermediate urothelial cells are smaller than superficial urothelial cells (Fig. 2.10).
These cells have fair amount of dense cytoplasm, resulting in well-defined cell bor-
ders. The nuclei are predominantly oval in shape with slightly irregular nuclear
contours, fine granular chromatin, and inconspicuous nucleoli. Nuclear membrane
irregularity such as nuclear grooves may become more obvious in urothelial cell
clusters in instrumented samples.
Table 2.2 Cytomorphologic features of urothelial cells

Superficial Cells Intermediate Cells Basal Cells
Size Large Intermediate Small
Cytoplasm Abundant, vacuolated Modest, dense Scant, dense
Nuclei Larger, round Medium, oval Smaller, round to oval
Nuclear to Low Medium High
cytoplasmic ratio
Binucleation or Frequent Absent Absent
multinucleation
Nuclear contour Smooth Slightly irregular Smooth
Chromatin Coarsely granular Fine granular Fine granular
Nucleoli Occasional conspicuous Inconspicuous Inconspicuous
a b
Fig. 2.9 Umbrella cells. (a) Umbrella cells with abundant cytoplasm, large round nuclei, and
occasional binucleation. (b) Multinucleated umbrella cells
a b
Fig. 2.10 Intermediate urothelial cells. (a) Dispersed polygonal urothelial cells with moderate
amount of cytoplasm and round to oval nuclei. (b) Predominant intermediate urothelial cells with
rare umbrella and basal cells
Basal Urothelial Cells
Basal cells are the smallest urothelial cells (Fig. 2.11). The cells are round in shape
and have scant dense cytoplasm. The nuclei are round to oval with smooth nuclear
contours, fine granular chromatin, and inconspicuous nucleoli. Although the nuclei
of basal urothelial cells are small, scanty cytoplasm results in relatively high nuclear
to cytoplasmic ratios.
Squamous Cells
Since distal urethra and urinary bladder trigone are lined by squamous epithelial
epithelium, squamous cells are considered as a normal cellular component of urine
specimens. The types of squamous cells may include polygonal superficial cells
with abundant cyanophilic or orangeophilic cytoplasm and small pyknotic nuclei,
intermediate cells with larger vesicular nuclei and occasionally, small parabasal
20 G. Cai
Fig. 2.11 Basal urothelial

cells. A few basal
urothelial cells with scant
cytoplasm and
hyperchromatic nuclei
admixed with
intermediated urothelial
cells
a b
Fig. 2.12 Squamous cell contaminants. (a) Many superficial squamous cells admixed with scat-
tered urothelial cells. (b) Superficial and intermediate squamous cells with thin bacilli, likely of
vaginal contaminant
cells. When appeared in a high number and in women, squamous cells are more
likely to be originated from vaginal contamination. In this setting, squamous cells
may exceed the number of urothelial cells and are often accompanied by abundant
bacteria (Fig. 2.12). To alleviate potential squamous cell contamination, midstream
clean catch urine is highly recommended.
Other Cells
Renal tubular cells may, although infrequently, be present in urine specimens. The
renal tubular cells have granular cytoplasm and round nuclei, present singly, or
associated with renal casts, which might be under reported in urine specimens [6,
7]. Spermatozoa may also be identified in urine samples, sometimes associated with
seminal vesicle epithelial cells (Fig. 2.13).
a b
Fig. 2.13 Spermatozoa and seminal vesicle epithelial cells. (a) A ball of spermatozoa with rare
large, degenerated cells. (b) Large seminal vesicle cells with intracytoplasmic lipofusion pigment
a b
Fig. 2.14 Colored crystals. (a, b) Multi-shaped crystals with light brown color. (c) Crystals are
polarizable and show reflectile feature
Crystals
The presence of crystals in urine specimens is a common finding. The crystals are
composed of variable chemicals, varying in color and shape (Table 2.3) [8]. The
colored crystals include uric acid, ammonium biurate, bilirubin, leucine, and sulfa
crystals (Fig. 2.14). Calcium oxalate, calcium phosphate, calcium carbonate, triple
22 G. Cai
phosphate, hippuric acid, tyrosine, cholesterol, and cysteine crystals are colorless
and translucent (Fig. 2.15). The pH value in urine samples is the most important
factor which helps formation of crystals [9, 10]. Most crystals are polarizable under
a b
c d
Fig. 2.15 Colorless crystals. (a–d) Translucent crystals in a variety shapes. (e) Crystals are polar-
izable and show refractive feature
2
Table 2.3 Crystals in urine specimens

Crystals Composition pH Shape Color Significance
Uric acid – Acidic Rhomboid, four-sided plates Yellow-light brown Possibly urate
nephrolithiasis, tumor
lysis syndrome
Calcium oxalate Monohydrate or Acidic or alkaline Monohydrate: Dumbbells Colorless Possibly ethylene glycol
dihydrate calcium Dihydrate: Octahedral, ingestion (monohydrate)

oxalate envelope
Triple phosphate Magnesium, Alkaline Prism-shaped like a coffin lid Colorless Possibly infection by
ammonium, phosphate urease-producing
bacteria
Calcium phosphate – Neutral or alkaline Blunt ended needles Colorless
Calcium carbonate – Alkaline Large dumbbells, spheres Colorless
with radial striations
Hippuric acid – Acidic or neutral Needle-like Colorless
Ammonium biurate – Alkaline Spherical bodies with Brown or yellow brown Possibly predisposed to
irregular protrusions urate urolithiasis
Bilirubin Conjugated bilirubin Acidic Clumped needles Yellow Severe hepatic disorders
Cholesterol – Acidic Rectangular, notched plates Colorless Nephritic syndrome
Sulfa Sulfonamide Acidic or neutral Rosettes or sheaves of small Brown Likely administration of
needles the drug
Leucine – Acidic or neutral Spheres with concentric Yellowish brown Possibly liver disorders
circles or radial striations
Cysteine – Acidic Hexagonal Colorless Diagnostic of cystinuria
Tyrosine – Acidic or neutral Fine needles forming clumps Colorless or yellow Possibly tyrosinemia or
or rosettes liver disorders
23
24 G. Cai
polarized lens. The presence of crystals in urine specimens is usually of no diagnos-

tic significance [11]. However, certain types of crystals may be associated with
disease conditions or drug administration [12]. There is a possible but not definite
linkage between the presence of crystals in urine specimens and occurrence of uro-
lithiasis [11, 13].
Contaminants
Urine samples may be contaminated during specimen collection or processing at

lab. Instrumentation is the primary source of urine contaminants. Surgical powder
and lubricant gel are commonly seen in instrumented, catheterized or wash/brush,
urine samples. Lubricant gel may form structures that mimic the eggs of parasites
(Fig. 2.16). Alternaria, the brown and septated fungal organism, may occasionally
be seen in urine specimens, which is the contaminant from lab water supply. In addi-
tion, bacterial and fungal overgrowth can occur when urine samples are left too long
in room temperature, a pitfall for bacterial or fungal infection in the urinary tract
(Fig. 2.17). Absence of a significant inflammatory component is a clue for the over-
growth rather than actual infection.
Reactive Changes
Reactive changes are the common findings in urine samples, which may be associ-
ated with degeneration, inflammation, infection, or therapies. Urolithiasis, stent
placement, instrumentation, and surgical interventions may also cause significant
cellular changes (Table 2.4). Benign-appearing glandular cells may be present in
urine samples, likely because of cystitis glandularis.
a b
Fig. 2.16 Lubricant gel material. (a) Blue colored gel material with a few groups of urothelial
cells. (b) Gel material shows a shape like parasite egg
Fig. 2.17 Bacterial

overgrowth. Colonies of
cocci bacteria with absence
of inflammation in the
background
Table 2.4 Cytomorphologic features of urothelial cell degeneration, polyomavirus infection, and
high-grade urothelial carcinoma
Polyomavirus High-grade
Degeneration Infection Urolithiasis Urothelial Carcinoma
Architecture Almost exclusively Almost Single cells and Single cells and
single cells exclusively occasional occasional clusters
single cells clusters
Cell size Small Small to Small to Large
intermediate intermediate
Nuclei Small, Enlarged, ground Enlarged, Large, variable in
hyperchromatic glass appearance prominent size, coarse
nucleoli chromatin, prominent
nucleoli
Cytoplasm Modest, vacuolated, Scant, dense, or Modest, dense, Scant, dense
Melamed-Wolinska vacuolated or vacuolated
bodies
Background Inflammation absent Inflammation Inflammation Inflammation,
or present necrosis
Degenerative Changes
Cellular degeneration is frequently encountered when evaluating urine specimens,

especially those voided urine samples collected first in the morning. Degenerated
urothelial cells showed loss of cellular details including enlarged pyknotic nuclei
with hyperchromasia and smudged chromatin. Intracytoplasmic eosinophilic inclu-
sions, as known as Melamed-Wolinska bodies, are frequently identified (Fig. 2.18)
[14, 15]. These cytoplasmic inclusions can be found in both degenerating benign
and malignant urothelial cells which have no significant diagnostic value but may
suggest a urothelial origin [14, 16].
26 G. Cai
a b
Fig. 2.18 Degenerative changes. (a, b) Degenerated urothelial cells show smudged chromatin and
single or multiple round eosinophilic or blue intracytoplasmic inclusions (Melamed-
Wolinska bodies)
Another example of degenerative changes is seen in ileal conduct samples where

the glandular epithelium lined small bowel undergoes marked degenerative changes
due to urine toxic environment. Therefore, the cellular element of ileal conduit urine
specimen is mostly of small bowel origin. These epithelial cells are present single
and in cluster. Due to degeneration, the cells are poorly preserved and do not show
their usual columnar morphology. Instead, the epithelial cells are round or oval with
degenerative granular cytoplasm, resembling histiocytes (Fig. 2.19). These cellular
changes must be differentiated from urothelial carcinoma that might represent
tumor reoccurrence in ileal conduit or derive from upper urinary tract [17, 18].
Abundant bacteria may be seen in the background. The cellular degeneration and
bacteria may be alleviated or ceased long after radical surgical procedure.
Reactive Changes
Reactive changes can be caused by inflammation, infection, urolithiasis, treat-

ments, or instrumentation. The common cellular features of reactive changes may
include cytomegaly, nuclear enlargement, and prominent nucleoli although the cel-
lular details may differ under specific conditions. In addition to urothelial cells,
there may be an increase in the number of squamous cells, some in metaplastic
in nature.
Acute and chronic inflammation is often caused by urinary tract infection or
other nonspecific disorders, manifested by reactive epithelial changes and abundant
inflammatory cells seen in the background (Fig. 2.20). In acute inflammation, neu-
trophils are the predominant inflammatory cells while the immune cells in chronic
inflammation are dominated by lymphocytes. Granulomatous inflammation is a
special form of chronic inflammation that is characterized by the presence of epithe-
lioid histocytes with or without multinucleated giant cells. Although granulomatous
a b
Fig. 2.19 Degenerated cells in ileal conduit specimen. (a) A loose group of epithelial cells with
marked degenerative changes and cellular debris. (b) Bacterial colonies with degenerated urothe-
lial cells. (c) Mucin-like material with degenerated urothelial cells
a b
Fig. 2.20 Acute and chronic inflammation. (a) Abundant neutrophils. (b) Granuloma - a cluster of
epithelioid histiocytes
inflammation is a quite common finding in patients with urothelial carcinoma fol-

lowing BCG treatment or transurethral tumor resection, granulomas are rarely iden-
tified in voided urine specimens. The presence of numerous eosinophils may suggest
eosinophilic cystitis which is most seen in patients who receive cautery treatment.
28 G. Cai
Polyomavirus, the BK strain, is the prototype of virus that is associated with

urinary tract infection. The classic cytopathic effect induced by this virus are the
eccentrically located enlarged nuclei with homogenous intranuclear inclusions
(packed by viral particles) and thickened nuclear membrane (nuclear membrane
with marginalized/condensed chromatin) (Fig. 2.21) [19]. Other less commonly
seen cytopathic changes associated with polyomavirus infection include the nuclei
with central homogenous intranuclear inclusions surrounded by irregular and
incomplete halo (cytomegalovirus-like), nuclei with coarsely granular and clumped
(spider web) chromatin, and multinucleated nuclei with granular chromatin. It is
worth noting that polyomavirus infection is not a significant finding unless it occurs
in immunocompromised patients including those with renal transplant, human
immunodeficiency virus infection or post-chemotherapy [20–23]. The potential pit-
fall is that the cells with polyomavirus cytopathic effects may mimic high-grade
urothelial carcinoma, known as decoy cells [24]. Besides polyomavirus, adenovi-
rus, cytomegalovirus, and herpes virus are the other viruses that can infect urinary
tract. The koilocytic changes in squamous cells may be due to polyomavirus infec-
tion in squamous epithelium of the urethra but may more likely be resulted from
vaginal/vulvar squamous cell contamination.
Bacterial infection is more likely seen in women, primarily involving lower uri-
nary tract. Urinary tract stricture, catheterization, and malignant neoplasms are con-
tributing factors that predispose patients for urinary tract infection. When infection
persists, bacteria can reach retrogradely the upper urinary tract resulting in pyelone-
phritis. Bacterial infection is almost always associated with significant inflamma-
tory responses, mostly in the form of acute inflammation but may also be chronic
inflammation. Bacterial organisms, either cocci or rods, could be identified in urine
specimens (Fig. 2.22). The presence of bacteria in urine specimens is not always
resulted from urinary tract bacterial infection. The differential diagnosis may
include vaginal contamination and bacterial overgrowth. The former is featured
with abundant squamous cells with or without associated inflammatory while
inflammatory cell component is virtually absent in bacterial overgrowth.
a b
Fig. 2.21 Polyomavirus cytopathic effects. (a) Scattered urothelial cells with intranuclear homog-
enized nuclei and marginalized chromatin. (b) A urothelial cell with intranuclear spider-web
nucleus and marginalized chromatin
a b
Fig. 2.22 Bacteria in urine samples. (a) Bacterial colonies and urothelial cells. (b) Coccus bacte-
ria and inflammatory cells. (c) Thin bacterial rods with squamous cells, likely vaginal
contaminants
Compared to bacterial infection, fungal infection is much less common in uri-

nary tract. Candida is the most common fungal organism found in urine specimen.
Candida includes yeast and pseudo-hyphae form organisms which can recognized
on routine Papanicolaou-stained preparation with no need for special stain
(Fig. 2.23). Other fungal infections such as aspergillosis, histoplasmosis, cryptococ-
cosis, and blastomycosis are rarely seen. Fungal infection is often accompanied by
variable cellular changes and inflammatory infiltration. Alternaria, a brown septated
fungal organism, is a common lab contaminant.
Schistosoma haematobium is the most described parasite infection in urine spec-
imens although the infection is limited to certain geographic location or to the indi-
viduals who have travel history. This organism is often identified by revelation of its
ova which is characterized by a terminal spine. The most significant factor in iden-
tifying S. haematobium is association of its infection with squamous cell carcinoma
of the urinary bladder although it is rare. A far more common finding is the presence
of reactive metaplastic squamous cells. Trichomonas vaginalis is another parasite
which can be seen in urine specimens usually due to vaginal contamination in
female patients.
Bacillus Calmette-Guerin (BCG) treatment is a commonly used therapy for
patients with urothelial carcinoma. Intra-vesicular administration of BCG induces
30 G. Cai
a b
Fig. 2.23 Candida in urine samples. (a) Yeast-form Candida fungi with squamous cells and uro-
thelial cells. (b) Candida pseudo-hyphae with squamous cells
Fig. 2.24 Therapy-related

reactive changes. Scattered
urothelial cells with
enlarged nuclei, prominent
nucleoli, and cytoplasmic
vacuoles. Background
inflammation
granulomatous inflammation in the wall of urinary bladder, like those of tuberculo-

sis. The urine specimens from patients who receive BCG treatment show reactive
urothelial cells and mixed inflammatory cells, it is however unusual to see granulo-
mas, especially in voided urine samples [25].
Chemotherapy and radiation can cause similar reactive changes in urothelial
cells. The reactive changes include cytomegaly, marked cytoplasmic vacuolization,
nuclear enlargement, and prominent nucleoli (Fig. 2.24). Pyknotic nuclei and apop-
totic bodies may also be present. It is advised to cautiously interpret the cytological
atypia in the setting of post-chemotherapy or radiation to avoid diagnostic pitfall for
urothelial carcinoma [26].
Urolithiasis may cause significant changes in urothelial cells, even atypical. The
possible changes include nuclear enlargement, hyperchromasia, coarse chromatin,
and prominent nucleoli (Fig. 2.25). The presence of urolithiasis-associated cyto-
logical atypia may pose diagnostic challenge for the differential diagnosis of
a b
Fig. 2.25 Reactive changes related to urolithiasis. (a) Urothelial cells with increased nuclear to
cytoplasmic ratios and nuclear hyperchromasia. (b) Urothelial cells with abundant cytoplasm,
enlarged nuclei, and prominent nucleoli. Crystals present
urothelial carcinoma [27, 28]. It should be kept in mind that urothelial carcinoma
and urolithiasis may coexist [27].
Clusters of Urothelial Cells
A urothelial cell cluster is referred as a three-dimensional group of urothelial cells

in cytological specimens (Fig. 2.26). The presence of urothelial cell clusters in
voided urine specimens may be considered as an abnormal finding but it alone is
rarely indicative of urothelial carcinoma [29, 30]. Urothelial cell clusters are more
often seen in the specimens related to urolithiasis, and instrumentation and should
be differentiated from urothelial tumors, especially low-grade papillary urothelial
neoplasm (Table 2.5) [31, 32].
Instrumentation procedures such as catheterization, wash and brush can artifi-
cially introduce clusters of urothelial cells in collected specimens. The urothelial
cells in clusters often consist of superficial, intermediate, and basal cells and show
no significant cytological changes. No real fibrovascular cores are identified within
the urothelial cell clusters.
Urolithiasis-associated changes include architectural and cytological atypia
[28]. The presence of clustered urothelial cell groups in voided urine samples is a
common finding in patients with urolithiasis. The clustered urothelial cells can
demonstrate an architecture of three-dimensional groups or papillary clusters. In
addition to the architectural changes, the cells may also show nuclear changes
including nuclear enlargement, hyperchromasia, and nucleoli but smooth nuclear
membranes.
Low-grade urothelial neoplasm is the tumor with papillary proliferation of uro-
thelium and mild cytological atypia [32]. Clustered urothelial groups with true
fibrovascular core are commonly seen in instrumented urine samples but rarely
32 G. Cai
a b
Fig. 2.26 Urothelial cell clusters. (a) Voided urine showing a urothelial cell cluster with enlarged
nuclei and conspicuous nucleoli. (b) Instrumented urine showing gel material and a papillary clus-
ter of urothelial cells with enlarged nuclei
Table 2.5 Possible causes of urothelial cell clusters in urine specimens

Low-grade Papillary
Instrumentation Urolithiasis Urothelial Neoplasm
Architecture Three-dimensional Three-dimensional cluster Three-dimensional cluster,
cluster papillary clusters
Cell Superficial, Predominant intermediate Homogenous urothelial cells
composition intermediate, and cells with or without superficial
basal cells cells
Fibrovascular Absent Absent Likely present
core
Cellular None or minimal Nuclear enlargement, Nuclear enlargement,
changes smooth nuclear contours, irregular nuclear contours,
hyperchromasia, increased nuclear to
prominent nucleoli cytoplasmic ratios,
hyperchromasia
Background Clean Inflammatory Clean or inflammatory
identified voided urine specimens, which make a diagnosis of low-grade urothelial

neoplasm in voided samples quite challenging. The tumor cells of low-grade papil-
lary neoplasm show increased nuclear to cytoplasmic ratios, irregular nuclear con-
tours, and hyperchromasia [33–35].
Acknowledgments None.
Conflict of Interest None.

References
1. Koss LGMM. Koss’ diagnostic cytology and its histopathologic bases. 5th ed. Philadelphoa:
Lippincott, Williams & Wilkins; 2006.
2. Wojcik EM. What should not be reported as atypia in urine cytology. J Am Soc Cytopathol.
2015;4(1):30–6.
3. Ajit D, Dighe SB, Desai SB. Cytology of lleal conduit urine in bladder cancer patients: diag-
nostic utility and pitfalls. Acta Cytol. 2006;50(1):70–3.
4. VandenBussche CJ, Rosenthal DL, Olson MT. Adequacy in voided urine cytology specimens:
the role of volume and a repeat void upon predictive values for high-grade urothelial carci-
noma. Cancer Cytopathol. 2016;124(3):174–80.
5. Prather J, Arville B, Chatt G, et al. Evidence-based adequacy criteria for urinary bladder bar-
botage cytology. J Am Soc Cytopathol. 2015;4(2):57–62.
6. Chawla LS, Dommu A, Berger A, Shih S, Patel SS. Urinary sediment cast scoring index for
acute kidney injury: a pilot study. Nephron Clin Pract. 2008;110(3):c145–50.
7. Poloni JAT, de Oliveira VA, Dos Santos CRM, Simundic AM, Rotta LN. Survey on report-
ing of epithelial cells in urine sediment as part of external quality assessment programs in
Brazilian laboratories. Biochem Med (Zagreb). 2021;31(2):020711.
8. Lee AJ, Yoo EH, Bae YC, Jung SB, Jeon CH. Differential identification of urine crystals with
morphologic characteristics and solubility test. J Clin Lab Anal. 2022;36(11):e24707.
9. Grases F, Costa-Bauzá A, Gomila I, Ramis M, García-Raja A, Prieto RM. Urinary pH and
renal lithiasis. Urol Res. 2012;40(1):41–6.
10. Højgaard I, Fornander AM, Nilsson MA, Tiselius HG. The effect of pH changes on the crystal-
lization of calcium salts in solutions with an ion composition corresponding to that in the distal
tubule. Urol Res. 1999;27(6):409–16.
11. Torous VF, Dodd LG, McIntire PJ, Jiang XS. Crystals and crystalloids in cytopathology: inci-
dence and importance. Cancer Cytopathol. 2022;130(10):759–70.
12. Frochot V, Daudon M. Clinical value of crystalluria and quantitative morphoconstitutional
analysis of urinary calculi. Int J Surg. 2016;36(Pt D):624–32.
13. Hoffman A, Braun MM, Khayat M. Kidney Disease: Kidney Stones. FP Essent. 2021;509:
33–8.
14. Rashidi B, Tongson-Ignacio JE. Melamed-Wolinska bodies in urine cytology an interesting
aggregate in a degenerated urothelial cell. Diagn Cytopathol. 2011;39(2):117.
15. Ayra P, Khalbuss WE, Monaco SE, Pantanowitz L. Melamed-Wolinska bodies. Diagn
Cytopathol. 2012;40(2):150–1.
16. Renshaw AA, Madge R, Granter SR. Intracytoplasmic eosinophilic inclusions (Melamed-
Wolinska bodies). Association with metastatic transitional cell carcinoma in pleural fluid. Acta
Cytol. 1997;41(4):995–8.
17. Chen H, Liu L, Pambuccian SE, Barkan GA, Quek ML, Wojcik EM. Urine cytology in moni-
toring recurrence in urothelial carcinoma after radical cystectomy and urinary diversion.
18. Xing J, Roy S, Monaco SE, Pantanowitz L. Cytohistologic correlation of recurrent urothelial
carcinoma detected in urinary diversion specimens. Cancer Cytopathol. 2017;125(2):120–7.
19. Singh HK, Bubendorf L, Mihatsch MJ, Drachenberg CB, Nickeleit V. Urine cytology findings
of polyomavirus infections. Adv Exp Med Biol. 2006;577:201–12.
20. Ramos E, Drachenberg CB, Wali R, Hirsch HH. The decade of polyomavirus BK-associated
nephropathy: state of affairs. Transplantation. 2009;87(5):621–30.
21. Batal I, Franco ZM, Shapiro R, et al. Clinicopathologic analysis of patients with BK viruria
and rejection-like graft dysfunction. Hum Pathol. 2009;40(9):1312–9.
22. Xing J, Procop GW, Reynolds JP, Chiesa-Vottero A, Zhang Y. Diagnostic utility of urine
cytology in early detection of polyomavirus in transplant patients. J Am Soc Cytopathol.
2017;6(1):28–32.
34 G. Cai
23. Chantziantoniou N, Joudeh AA, Hamed RMA, Al-Abbadi MA. Significance, cytomorphology
of decoy cells in polyomavirus-associated nephropathy: review of clinical, histopathological,
and virological correlates with commentary. J Am Soc Cytopathol. 2016;5(2):71–85.
24. Allison DB, Olson MT, Lilo M, Zhang ML, Rosenthal DL, VandenBussche CJ. Should the
BK polyomavirus cytopathic effect be best classified as atypical or benign in urine cytology
specimens? Cancer Cytopathol. 2016;124(6):436–42.
25. Takashi M, Schenck U, Koshikawa T, Nakashima N, Ohshima S. Cytological changes induced
by intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer. Urol Int.
2000;64(2):74–81.
26. Nguyen L, Nilforoushan N, Krane JF, Bose S, Bakkar R. Should "suspicious for high-grade
urothelial carcinoma" and "positive for high-grade urothelial carcinoma" remain separate cat-
egories? Cancer Cytopathol 2021;129(2):156–163.
27. Beyer-Boon ME, Cuypers LH, de Voogt HJ, Brussee JA. Cytological changes due to urinary
calculi: a consideration of the relationship between calculi and the development of urothelial
carcinoma. Br J Urol. 1978;50(2):81–9.
28. Kannan V, Gupta D, Calculus artifact. A challenge in urinary cytology. Acta Cytol.
1999;43(5):794–800.
29. Onur I, Rosenthal DL, VandenBussche CJ. Benign-appearing urothelial tissue fragments in
noninstrumented voided urine specimens are associated with low rates of urothelial neoplasia.
30. Wojcik EM, Kurtycz DFI, Rosenthal DL. We'll always have Paris the Paris system for report-
ing urinary cytology 2022. J Am Soc Cytopathol. 2022;11(2):62–6.
31. Kannan V, Bose S. Low grade transitional cell carcinoma and instrument artifact. A challenge
in urinary cytology. Acta Cytol. 1993;37(6):899–902.
32. Raab SS, Lenel JC, Cohen MB. Low grade transitional cell carcinoma of the bladder.
Cytologic diagnosis by key features as identified by logistic regression analysis. Cancer.
1994;74(5):1621–6.
33. Zhang ML, Rosenthal DL, VandenBussche CJ. The cytomorphological features of low-grade
urothelial neoplasms vary by specimen type. Cancer Cytopathol. 2016;124(8):552–64.
34. Bansal S, Pathuthara S, Joseph S, Dighe S, Menon S, Desai SB. Is diagnosis of low-grade
urothelial carcinoma possible in urine cytology? J Cytol. 2021;38(2):64–8.
35. Chandler JB, Colunga M, Celli R, Lithgow MY, Baldassarri RJ. Applicability of the Paris
system for veterans: high rates of undiagnosed low-grade urothelial neoplasia. J Am Soc
Cytopathol. 2021;10(4):357–65.
Chapter 3
Cervical and Vaginal Cytology
The Bethesda system provides a uniform reporting system for cervical cytology
specimens. Recommended adequacy for liquid-based preparation is at least 5000
squamous cells, and for conventional smears is between 8000 and 12,000 squamous
cells [1] (Fig. 3.1).
Fig. 3.1 Unsatisfactory

for evaluation due to lack
of sufficient squamous
component
(ThinPrep × 40)
T. Sun (*)
Department of Pathology, Yale School of Medicine, New Haven, CT, USA
e-mail: tong.sun@yale.edu
S. M. Gilani
Department of Pathology, Albany Medical Center, Albany Medical College,
Albany, NY, USA

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-44289-6_3
36 T. Sun and S. M. Gilani
Different Preparations and Screening Procedures [2] (Table 3.1)
Two commonly used techniques for collecting Pap smears are liquid-based and
conventional.
• Conventional Smear
Often obtained using the combination of a spatula and brush.
• Liquid-Based Cytology
It can provide the opportunity to prepare duplicate slides and cell blocks and
the option of additional testing, including HPV, chlamydia, and gonorrhea. It is
also a substrate for automated screening devices.
–– ThinPrep uses a methanol-based preservative solution (PreservCyt Solution).
The preparation method involves dispersion, and cell collection, followed by
cell transfer to slides.
–– SurePath uses an ethanol-based preservative solution. The preparation method
involves vortexing, disaggregation, and transfer to a sedimentation tube, and
a pallet is obtained, sedimentation by gravity, followed by cell deposition and
Papanicolaou staining.
Table 3.1 Cervical cancer screening guidance (American Society for Colposcopy and Cervical
Pathology 2021) [3]
1. In an age group less than 25 years, no screening is suggested
2. The preferred screening method for age groups between 25 and 65 years is HPV testing
alone (using an FDA-approved platform) every 5 years. However, other acceptable options
are using the Co-test method (HPV and cytology) every 5 years or every 3 years with
cytology alone
3. In those over 65 years old, no screening is required if prior screening is negative. This
negative screening includes two negative primary HPV tests, or two negative co-tests, or
three negative cytology alone tests within the last 10 years (with the most recent test within
the past 3–5 years)
3 Cervical and Vaginal Cytology 37
ormal Elements (Superficial, Intermediate, Parabasal,

N
and Navicular) [1, 4]
• Squamous cells include basal cells, parabasal cells, and intermediate cells.
Basal cells are usually small cells along the basement membrane and resem-
ble small histocytes, as seen in the atrophic specimen primarily as syncytial
aggregates.
Parabasal cells are the first to acquire squamous features, dense cytoplasm,
and distinct cell boundaries. In addition, they have moderately abundant cyto-
plasm and round to oval nuclei. Parabasal cell predominates in atrophic speci-
mens and can also be seen in postpartum conditions or related to the intake of
oral contraception (progesterone).
Intermediate cells provide essential nuclear size reference (average 35mm2,
the size of a red blood cell). Intermediate cells have abundant and transparent
cytoplasm. Any squamous nucleus significantly larger and more hyperchromatic
than an intermediate cell is likely a dysplastic cell.
Superficial cells have pyknotic nuclei and delicate transparent cytoplasm.
• Endocervical cells are cohesive fat sheets or strips of uniform cells, appearing
“honeycomb” pattern (opposing view) or “picket fence” pattern (side view). The
cell shape (nuclei and cytoplasm) can be tall columnar and may have abundant
mucinous cytoplasm.
Reactive endocervical cells can have significant nuclear enlargement, hyper-
chromasia, and prominent nucleoli but maintain smooth nuclear membranes and
fine chromatin, abundant cytoplasm with distinct cell borders, low nuclear/cyto-
plasmic ratios, and without crowding or overlapping [5]. In addition, they can
show binucleation or multinucleation and should not be confused with herpes
virus changes.
• Endometrial cells.
Exfoliated endometrial cells can be seen if a Pap sample is taken during the
first 12 days of the menstrual cycle. Morphologically, they appear as a spherical
cluster, small cells with a dark nucleus and scant cytoplasm. They are associated
with menstrual cycle changes, endometrial pathology (such as endometritis,
endometrial polyps, or neoplasia), and exogenous changes (intrauterine devices,
IUDs, and others). Exodus represents a group of endometrial cells with endome-
trial stroma (darker area) in the center surrounded by endometrial glandular cells
(Fig. 3.2). Directly sampled endometrial cells present large and small tissue frag-
ments with a combination of glands and stroma.
Endometrial cells are needed to be reported in women 45 years of age or
older. The differential diagnoses of exfoliated endometrial cells include high-
grade intraepithelial lesion (HSIL), squamous cell carcinoma, adenocarcinoma
in situ (AIS), endometrial carcinoma and rarely a small cell carcinoma.
38 T. Sun and S. M. Gilani
Fig. 3.2 Cluster of

endometrial cells with dark
central area and lighter
periphery (SurePath × 400)
Benign Findings [1, 4] (Table 3.2)
• Parakeratosis is a benign reactive change caused by chronic irritation. It usually

shows keratinized squamous cells with dense organophilic cytoplasm and small
pyknotic nuclei. However, if nuclear atypia is present, then the term “atypical
parakeratosis” is used and categorized as “epithelial cell abnormality” such as
ASCUS (atypical squamous intraepithelial lesion) or SIL (squamous intraepithe-
lial lesion), depending on the extent of the abnormality.
• Hyperkeratosis is a benign response of stratified squamous epithelium due to
chronic mucosal irritation, as in uterine prolapse. Squamous cells manifested as
anucleate, mature, polygonal isolated cells or plaques of tightly adherent isolated
cells. Differential diagnosis includes contaminated cells of the skin.
• Atrophic changes happen in late post-menopause (Fig. 3.3), postpartum
(Fig. 3.4), lactation, and childhood (except newborn). Atrophic changes can
show nuclear enlargement with mild hyperchromasia. However, the nuclear
membrane is still uniform, and the chromatin is evenly distributed but often
smudgy. There are usually syncytial groups of parabasal cells and may show
background inflammation and cell degeneration. A granular basophilic back-
ground may be present, and mummified parabasal cells, “blue blobs,” can be
evident. The differential diagnosis includes endometrial cells, HSIL, or
malignancy.
• Pregnancy-related changes include a predominance of intermediate cells and an
increase in navicular cells (glycogenated intermediate cells). Other changes and
cell types seen in pregnancy are as follows: Syncytiotrophoblastic cells, decidual
cells, arias-stella reaction, and cockleburs.
Another random document with
no related content on Scribd:
and the several answers which were returned by each of the
martyrs. I copy from Baronius the most important of these. They
were arrested while they were celebrating the Lord’s sacrament
according to custom.[514] The following is the charge on which they
were arrested: They had celebrated the Collectam Dominicam
against the command of the emperors.[515] The proconsul asked the
first whether he had celebrated the Collectam, and he replied that he
was a Christian, and had done this.[516] Another says, “I have not
only been in the Collecta, but I have celebrated the Dominicum with
the brethren because I am a Christian.”[517] Another says we have
celebrated the Dominicum, because the Dominicum cannot be
neglected.[518] Another said that the Collecta was made (or
observed) at his house.[519] The proconsul questioning again one of
those already examined, received this answer: “The Dominicum
cannot be disregarded, the law so commands.”[520] When one was
asked whether the Collecta was made (or observed) at his house, he
answered, “In my house we have celebrated the Dominicum.” He
added, “Without the Dominicum we cannot be,” or live.[521] To
another, the proconsul said that he did not wish to know whether he
was a Christian, but whether he participated in the Collecta. His reply
was: “As if one could be a Christian without the Dominicum, or as if
the Dominicum can be celebrated without the Christian.”[522] And he
said further to the proconsul: “We have observed the Collecta most
sacredly; we have always convened in the Dominicum for reading
the Lord’s word.”[523] Another said: “I have been in [literally, have
made] the Collecta with my brethren, I have celebrated the
Dominicum.”[524] After him another proclaimed the Dominicum to be
the hope and safety of the Christian, and when tortured as the
others, he exclaimed, ”I have celebrated the Dominicum with a
devoted heart, and with my brethren I have made the Collecta
because I am a Christian.”[525] When the proconsul again asked one
of these whether he had conducted the Dominicum, he replied that
he had because Christ was his Saviour.[526]
I have thus given the substance of this famous examination, and
have set before the reader the references therein made to the
Dominicum. It is to be observed that Collecta is used as another
name for Dominicum. Now does Baronius use either of these words
to signify Lord’s day? It so happens that he has defined these words
with direct reference to this very case no less than seven times. Now
let us read these seven definitions:—
When Baronius records the first question addressed to these
martyrs, he there defines these words as follows: “By the words
Collectam, Collectionem, and Dominicum, the author always
understands the sacrifice of the Mass.”[527] After recording the words
of that martyr who said that the law commanded the observance of
the Dominicum, Baronius defines his statement thus: “Evidently the
Christian law concerning the Dominicum, no doubt about celebrating
the sacrifice.”[528] Baronius, by the Romish words sacrifice and Mass
refers to the celebration of the Lord’s supper by these martyrs. At the
conclusion of the examination, he again defines the celebration of
the Dominicum. He says: “It has been shown above in relating these
things that the Christians were moved, even in the time of severe
persecution, to celebrate the Dominicum. Evidently, as we have
declared elsewhere in many places, it was a sacrifice without
bloodshed, and of divine appointment.”[529] He presently defines
Dominicum again, saying, “Though it is a fact that the same
expression was employed at times with reference to the temple of
God, yet since all the churches upon the earth have united in this
matter, and from other things related above, it has been sufficiently
shown concerning the celebration of the Dominicum, that only the
sacrifice of the Mass can be understood.”[530] Observe this last
statement. He says though the word has been employed to
designate the temple of the Lord, yet in the things here related it can
only signify the sacrifice of the Mass. These testimonies are
exceedingly explicit. But Baronius has not yet finished. In the index
to Tome 3, he explains these words again with direct reference to
this very martyrdom. Thus under Collecta is this statement: “The
Collecta, the Dominicum, the Mass, the same [a. d.] 303, xxxix.”[531]
Under Missa: “The Mass is the same as the Collecta, or Dominicum
[a. d.], 303, xxxix.”[532] Under Dominicum: “To celebrate the
Dominicum is the same as to conduct the Mass [a. d.], 303, xxxix.;
xlix.; li.”[533]
It is not possible to mistake the meaning of Baronius. He says that
Dominicum signifies the Mass! The celebration of the supper by
these martyrs was doubtless very different from the pompous
ceremony which the church of Rome now observes under the name
of Mass. But it was the sacrament of the Lord’s supper, concerning
which they were tested, and for observing which they were put to a
cruel death. The word Dominicum signifies “the sacred mysteries,”
as Ruinart defines it; and Baronius, in seven times affirming this
definition, though acknowledging that it has sometimes been used to
signify temple of God, plainly declares that in this record, it can have
no other meaning than that service which the Romanists call the
sacrifice of the Mass. Gilfillan had read all this, yet he dares to quote
Baronius as saying that these martyrs were tested by the question,
“Have you kept Lord’s day?” He could not but know that he was
writing a direct falsehood; but he thought the honor of God, and the
advancement of the cause of truth, demanded this act at his hands.
Before Gilfillan wrote his work, Domville had called attention to the
fact that the sentence, “Dominicum servasti?” does not occur in the
Acta Martyrum, a different verb being used every time. But this is the
popular form of this question, and must not be given up. So Gilfillan
declares that Baronius uses it in his record of the martyrdoms in a. d.
303. But we have cited the different forms of question recorded by
Baronius, and find them to be precisely the same with those of the
Acta Martyrum. “Dominicum servasti?” does not occur in that
historian, and Gilfillan, in stating that it does, is guilty of untruth. This,
however, is comparatively unimportant. But for asserting that
Baronius speaks of Lord’s day under the name of Dominicum,
Gilfillan stands convicted of inexcusable falsehood in matters of
serious importance.
CHAPTER XVI.
ORIGIN OF FIRST-DAY OBSERVANCE.
Sunday a heathen festival from remote antiquity—Origin of the name—

Reasons which induced the leaders of the church to adopt this festival
—It was the day generally observed by the Gentiles in the first
centuries of the Christian era—To have taken a different day would
have been exceedingly inconvenient—They hoped to facilitate the
conversion of the Gentiles by keeping the same day that they
observed—Three voluntary weekly festivals in the church in memory
of the Redeemer—Sunday soon elevated above the other two—
Justin Martyr—Sunday observance first found in the church of Rome
—Irenæus—First act of papal usurpation was in behalf of Sunday—
Tertullian—Earliest trace of abstinence from labor on Sunday—
General statement of facts—The Roman church made its first great
attack upon the Sabbath by turning it into a fast.
The festival of Sunday is more ancient than the Christian religion,
its origin being lost in remote antiquity. It did not originate, however,
from any divine command nor from piety toward God: on the
contrary, it was set apart as a sacred day by the heathen world in
honor of their chief god, the sun. It is from this fact that the first day
of the week has obtained the name of Sunday, a name by which it is
known in many languages. Webster thus defines the word:—
“Sunday; so called because this day was anciently

dedicated to the sun or to its worship. The first day of the
week; the Christian Sabbath; a day consecrated to rest from
secular employments, and to religious worship; the Lord’s
day.”
And Worcester, in his large dictionary, uses similar language:—
“Sunday; so named because anciently dedicated to the sun

or to its worship. The first day of the week; the Christian
Sabbath, consecrated to rest from labor and to religious
worship; the Lord’s day.”
These lexicographers call Sunday the Christian Sabbath, etc.,

because in the general theological literature of our language, it is
thus designated, though never thus in the Bible. Lexicographers do
not undertake to settle theological questions, but simply to define
terms as currently used in a particular language. Though all the other
days of the week have heathen names, Sunday alone was a
conspicuous heathen festival in the days of the early church. The
North British Review, in a labored attempt to justify the observance
of Sunday by the Christian world, styles that day, “The wild solar
holiday [i. e., festival in honor of the sun] of all pagan times.”[534]
Verstegan says:—
“The most ancient Germans being pagans, and having

appropriated their first day of the week to the peculiar
adoration of the sun, whereof that day doth yet in our English
tongue retain the name of Sunday, and appropriated the next
day unto it unto the especial adoration of the moon, whereof it
yet retaineth with us, the name of Monday; they ordained the
next day to these most heavenly planets to the particular
adoration of their great reputed god, Tuisco, whereof we do
yet retain in our language the name of Tuesday.”[535]
The same author thus speaks concerning the idols of our Saxon
ancestors:—
“Of these, though they had many, yet seven among the rest
they especially appropriated unto the seven days of the
week.... Unto the day dedicated unto the especial adoration of
the idol of the sun, they gave the name of Sunday, as much
as to say the sun’s day or the day of the sun. This idol was
placed in a temple, and there adored and sacrificed unto, for
that they believed that the sun in the firmament did with or in
this idol correspond and co-operate.”[536]
Jennings makes this adoration of the sun more ancient than the
deliverance of Israel from Egypt. For, in speaking of the time of that
deliverance, he speaks of the Gentiles as,
“The idolatrous nations who in honor to their chief god, the

sun, began their day at his rising.”[537]
He represents them also as setting apart Sunday in honor of the

same object of adoration:—
“The day which the heathens in general consecrated to the

worship and honor of their chief god, the sun, which,
according to our computation, was the first day of the
week.”[538]
The North British Review thus defends the introduction of this

ancient heathen festival into the Christian church:—
“That very day was the Sunday of their heathen neighbors

and respective countrymen; and patriotism gladly united with
expediency in making it at once their Lord’s day and their
Sabbath.... If the authority of the church is to be ignored
altogether by Protestants, there is no matter; because
opportunity and common expediency are surely argument
enough for so ceremonial a change as the mere day of the
week for the observance of the rest and holy convocation of
the Jewish Sabbath. That primitive church, in fact, was shut
up to the adoption of the Sunday, until it became established
and supreme, when it was too late to make another alteration;
and it was no irreverent nor undelightful thing to adopt it,
inasmuch as the first day of the week was their own high day
at any rate; so that their compliance and civility were
rewarded by the redoubled sanctity of their quiet festival.”[539]
It would seem that something more potent than “patriotism” and

“expediency” would be requisite to transform this heathen festival
into the Christian Sabbath, or even to justify its introduction into the
Christian church. A further statement of the reasons which prompted
its introduction, and a brief notice of the earlier steps toward
transforming it into a Christian institution, will occupy the remainder
of this chapter. Chafie, a clergyman of the English Church, in 1652,
published a work in vindication of first-day observance, entitled, “The
Seventh-day Sabbath.” After showing the general observance of
Sunday by the heathen world in the early ages of the church, Chafie
thus states the reasons which forbid the Christians attempting to
keep any other day:—
“1. Because of the contempt, scorn, and derision they

thereby should be had in, among all the Gentiles with whom
they lived.... How grievous would be their taunts and
reproaches against the poor Christians living with them and
under their power for their new set sacred day, had the
Christians chosen any other than the Sunday.... 2. Most
Christians then were either servants or of the poorer sort of
people; and the Gentiles, most probably, would not give their
servants liberty to cease from working on any other set day
constantly, except on their Sunday.... 3. Because had they
assayed such a change it would have been but labor in vain;
... they could never have brought it to pass.”[540]
Thus it is seen that at the time when the early church began to
apostatize from God and to foster in its bosom human ordinances,
the heathen world—as they had long done—very generally observed
the first day of the week in honor of the sun. Many of the early
fathers of the church had been heathen philosophers. Unfortunately
they brought with them into the church many of their old notions and
principles. Particularly did it occur to them that by uniting with the
heathen in the day of weekly celebration they should greatly facilitate
their conversion. The reasons which induced the church to adopt the
ancient festival of the heathen as something made ready to hand,
are thus stated by Morer:—
“It is not to be denied but we borrow the name of this day

from the ancient Greeks and Romans, and we allow that the
old Egyptians worshiped the sun, and as a standing memorial
of their veneration, dedicated this day to him. And we find by
the influence of their examples, other nations, and among
them the Jews themselves, doing him homage;[541] yet these
abuses did not hinder the fathers of the Christian church
simply to repeal, or altogether lay by, the day or its name, but
only to sanctify and improve both, as they did also the pagan
temples polluted before with idolatrous services, and other
instances wherein those good men were always tender to
work any other change than what was evidently necessary,
and in such things as were plainly inconsistent with the
Christian religion; so that Sunday being the day on which the
Gentiles solemnly adored that planet, and called it Sunday,
partly from its influence on that day especially, and partly in
respect to its divine body (as they conceived it), the Christians
thought fit to keep the same day and the same name of it, that
they might not appear causelessly peevish, and by that
means hinder the conversion of the Gentiles, and bring a
greater prejudice than might be otherwise taken against the
gospel.”[542]
In the time of Justin Martyr, Sunday was a weekly festival, widely

celebrated by the heathen in honor of their god, the sun. And so, in
presenting to the heathen emperor of Rome an “Apology” for his
brethren, Justin takes care to tell him thrice that the Christians held
their assemblies on this day of general observance.[543] Sunday
therefore makes its first appearance in the Christian church as an
institution identical in time with the weekly festival of the heathen,
and Justin, who first mentions this festival, had been a heathen
philosopher. Sixty years later, Tertullian acknowledges that it was not
without an appearance of truth that men declared the sun to be the
god of the Christians. But he answered that though they worshiped
toward the east like the heathen, and devoted Sunday to rejoicing, it
was for a reason far different from sun-worship.[544] And on another
occasion, in defending his brethren from the charge of sun-worship,
he acknowledges that these acts, prayer toward the east, and
making Sunday a day of festivity, did give men a chance to think the
sun was the God of the Christians.[545] Tertullian is therefore a
witness to the fact that Sunday was a heathen festival when it
obtained a foothold in the Christian church, and that the Christians,
in consequence of observing it, were taunted with being sun-
worshipers. It is remarkable that in his replies he never claims for
their observance any divine precept or apostolic example. His
principal point was that they had as good a right to do it as the
heathen had. One hundred and twenty one years after Tertullian,
Constantine, while yet a heathen, put forth his famous edict in behalf
of the heathen festival of the sun, which day he pronounced
“venerable.” And this heathen law caused the day to be observed
everywhere throughout the Roman Empire, and firmly established it
both in Church and State. It is certain, therefore, that at the time of
its entrance into the Christian church, Sunday was an ancient weekly
festival of the heathen world.
That this heathen festival was upon the day of Christ’s resurrection
doubtless powerfully contributed to aid “patriotism” and “expediency”
in transforming it into the Lord’s day or Christian Sabbath. For, with
pious motives, as we may reasonably conclude, the professed
people of God early paid a voluntary regard to several days,
memorable in the history of the Redeemer. Mosheim, whose
testimony in behalf of Sunday has been presented already, uses the
following language relative to the crucifixion day:—
“It is also probable that Friday, the day of Christ’s

crucifixion, was early distinguished by particular honors from
the other days of the week.”[546]
And of the second century, he says:—
“Many also observed the fourth day of the week, on which

Christ was betrayed; and the sixth, which was the day of his
crucifixion.”[547]
Dr. Peter Heylyn says of those who chose Sunday:—
“Because our Saviour rose that day from amongst the

dead, so chose they Friday for another, by reason of our
Saviour’s passion; and Wednesday on the which he had been
betrayed: the Saturday, or ancient Sabbath, being meanwhile
retained in the eastern churches.”[548]
Of the comparative sacredness of these three voluntary festivals,

the same writer testifies:—
“If we consider either the preaching of the word, the

ministration of the sacraments, or the public prayers: the
Sunday in the eastern churches had no great prerogative
above other days, especially above the Wednesday and the
Friday, save that the meetings were more solemn, and the
concourse of people greater than at other times, as is most
likely.”[549]
And besides these three weekly festivals, there were also two
annual festivals of great sacredness. These were the Passover and
the Pentecost. And it is worthy of special notice that although the
Sunday festival can be traced no higher in the church than Justin
Martyr, a. d. 140, the Passover can be traced to a man who claimed
to have received it from the apostles. See chapter thirteen. Among
these festivals, considered simply as voluntary memorials of the
Redeemer, Sunday had very little pre-eminence. For it is well stated
by Heylyn:—
“Take which you will, either the fathers or the moderns, and
we shall find no Lord’s day instituted by any apostolical
mandate; no Sabbath set on foot by them upon the first day of
the week.”[550]
Domville bears the following testimony, which is worthy of lasting

remembrance:—
“Not any ecclesiastical writer of the first three centuries

attributed the origin of Sunday observance either to Christ or
to his apostles.”[551]
“Patriotism” and “expediency,” however, erelong elevated

immeasurably above its fellows that one of these voluntary festivals
which corresponded to “the wild solar holiday” of the heathen world,
making that day at last “the Lord’s day” of the Christian church. The
earliest testimony in behalf of first-day observance that has any
claim to be regarded as genuine is that of Justin Martyr, written
about a. d. 140. Before his conversion, he was a heathen
philosopher. The time, place, and occasion of his first Apology or
Defense of the Christians, addressed to the Roman Emperor, is thus
stated by an eminent Roman Catholic historian. He says that Justin
Martyr
“Was at Rome when the persecution that was raised under

the reign of Antoninus Pius, the successor of Adrian, began to
break forth, where he composed an excellent apology in
behalf of the Christians.”[552]
Of the works ascribed to Justin Martyr, Milner says:—
“Like many of the ancient fathers he appears to us under

the greatest disadvantage. Works really his have been lost;
and others have been ascribed to him, part of which are not
his; and the rest, at least, of ambiguous authority.”[553]
If the writings ascribed to him are genuine, there is little propriety
in the use made of his name by the advocates of the first-day
Sabbath. He taught the abrogation of the Sabbatic institution; and
there is no intimation in his words that the Sunday festival which he
mentions was other than a voluntary observance. Thus he
addresses the emperor of Rome:—
“And upon the day called Sunday, all that live either in city
or country meet together at the same place, where the
writings of the apostles and prophets are read, as much as
time will give leave; when the reader has done, the bishop
makes a sermon, wherein he instructs the people, and
animates them to the practice of such lovely precepts: at the
conclusion of this discourse, we all rise up together and pray;
and prayers being over, as I now said, there is bread and
wine and water offered, and the bishop, as before, sends up
prayers and thanksgivings, with all the fervency he is able,
and the people conclude all with the joyful acclamation of
Amen. Then the consecrated elements are distributed to, and
partaken of, by all that are present, and sent to the absent by
the hands of the deacons. But the wealthy and the willing, for
every one is at liberty, contribute as they think fitting; and this
collection is deposited with the bishop, and out of this he
relieves the orphan and the widow, and such as are reduced
to want by sickness or any other cause, and such as are in
bonds, and strangers that come from far; and, in a word, he is
the guardian and almoner to all the indigent. Upon Sunday we
all assemble, that being the first day in which God set himself
to work upon the dark void, in order to make the world, and in
which Jesus Christ our Saviour rose again from the dead; for
the day before Saturday he was crucified, and the day after,
which is Sunday, he appeared unto his apostles and disciples,
and taught them what I have now proposed to your
consideration.”[554]
This passage, if genuine, furnishes the earliest reference to the
observance of Sunday as a religious festival in the Christian church.
It should be remembered that this language was written at Rome,
and addressed directly to the emperor. It shows therefore what was
the practice of the church in that city and vicinity, but does not
determine how extensive this observance was. It contains strong
incidental proof that apostasy had made progress at Rome; the
institution of the Lord’s supper being changed in part already to a
human ordinance; water being now as essential to the Lord’s supper
as the wine or the bread. And what is still more dangerous as
perverting the institution of Christ, the consecrated elements were
sent to the absent, a step which speedily resulted in their becoming
objects of superstitious veneration, and finally of worship. Justin tells
the emperor that Christ thus ordained; but such a statement is a
grave departure from the truth of the New Testament.
This statement of reasons for Sunday observance is particularly
worthy of attention. He tells the emperor that they assembled upon
the day called Sunday. This was equivalent to saying to him, We
observe the day on which our fellow-citizens offer their adoration to
the sun. Here both “patriotism” and “expediency” discover
themselves in the words of Justin, which were addressed to a
persecuting emperor in behalf of the Christians. But as if conscious
that the observance of a heathen festival as the day of Christian
worship was not consistent with their profession as worshipers of the
Most High, Justin bethinks himself for reasons in defense of this
observance. He assigns no divine precept nor apostolic example for
this festival. For his reference to what Christ taught his disciples, as
appears from the connection, was to the general system of the
Christian religion, and not to the observance of Sunday. If it be said
that Justin might have learned from tradition what is not to be found
in the New Testament relative to Sunday observance, and that after
all Sunday may be a divinely-appointed festival, it is sufficient to
answer, 1. That this plea would show only tradition in favor of the
Sunday festival. 2. That Justin Martyr is a very unsafe guide; his
testimony relative to the Lord’s supper differs from that of the New
Testament. 3. That the American Tract Society, in a work which it
publishes against Romanism, bears the following testimony relative
to the point before us:—
“Justin Martyr appears indeed peculiarly unfitted to lay

claim to authority. It is notorious that he supposed a pillar
erected on the island of the Tiber to Semo Sanchus, an old
Sabine deity, to be a monument erected by the Roman people
in honor of the impostor Simon Magus. Were so gross a
mistake to be made by a modern writer in relating a historical
fact, exposure would immediately take place, and his
testimony would thenceforward be suspected. And assuredly
the same measure should be meted to Justin Martyr, who so
egregiously errs in reference to a fact alluded to by Livy the
historian.”[555]
Justin assigns the following reasons in support of Sunday

observance: “That being the first day in which God set himself to
work upon the dark void in order to make the world, and in which
Jesus Christ our Saviour rose again from the dead.” Bishop Jeremy
Taylor most fittingly replies to this:—
“The first of these looks more like an excuse than a just

reason; for if anything of the creation were made the cause of
a Sabbath, it ought to be the end, not the beginning; it ought
to be the rest, not the first part of the work; it ought to be that
which God assigned, not [that] which man should take by way
of after justification.”[556]
It is to be observed, therefore, that the first trace of Sunday as a

Christian festival is found in the church of Rome. Soon after this
time, and thenceforward, we shall find “the bishop” of that church
making vigorous efforts to suppress the Sabbath of the Lord, and to
elevate in its stead the festival of Sunday.
It is proper to note the fact also that Justin was a decided
opponent of the ancient Sabbath. In his “Dialogue with Trypho the
Jew” he thus addressed him:—
“This new law teaches you to observe a perpetual Sabbath;

and you, when you have spent one day in idleness, think you
have discharged the duties of religion.... If any one is guilty of
adultery, let him repent, then he hath kept the true and
delightful Sabbath unto God.... For we really should observe
that circumcision which is in the flesh, and the Sabbath, and
all the feasts, if we had not known the reason why they were
imposed upon you, namely, upon the account of your
iniquities.... It was because of your iniquities, and the
iniquities of your fathers, that God appointed you to observe
the Sabbath.... You see that the heavens are not idle, nor do
they observe the Sabbath. Continue as ye were born. For if
before Abraham there was no need of circumcision, nor of the
sabbaths, nor of feasts, nor of offerings before Moses; so now
in like manner there is no need of them, since Jesus Christ,
the Son of God, was by the determinate counsel of God, born
of a virgin of the seed of Abraham without sin.”[557]
This reasoning of Justin deserves no reply. It shows, however, the

unfairness of Dr. Edwards, who quotes Justin Martyr as a witness for
the change of the Sabbath;[558] whereas Justin held that God made
the Sabbath on account of the wickedness of the Jews, and that he
totally abrogated it in consequence of the first advent of Christ; the
Sunday festival of the heathen being evidently adopted by the
church at Rome from motives of “expediency” and perhaps of
“patriotism.” The testimony of Justin, if genuine, is peculiarly valuable
in one respect. It shows that as late as a. d. 140 the first day of the
week had acquired no title of sacredness; for Justin several times
mentions the day: thrice as “the day called Sunday” and twice as
“the eighth day;” and by other terms also, but never by any sacred
name.[559]
The next important witness in behalf of first-day sacredness is thus
presented by Dr. Edwards:—
“Hence Irenæus, bishop of Lyons, a disciple of Polycarp,
who had been the companion of the apostles, a. d. 167, says
that the Lord’s day was the Christian Sabbath. His words are,
‘On the Lord’s day every one of us Christians keeps the
Sabbath, meditating on the law and rejoicing in the works of
God.’”[560]
This testimony is highly valued by first-day writers, and is often

and prominently set forth in their publications. Sir Wm. Domville,
whose elaborate treatise on the Sabbath has been several times
quoted, states the following important fact relative to this quotation:
—
“I have carefully searched through all the extant works of

Irenæus and can with certainty state that no such passage, or
any one at all resembling it, is there to be found. The edition I
consulted was that by Massuet (Paris, 1710); but to assure
myself still further, I have since looked to the editions by
Erasmus (Paris, 1563), and Grabe (Oxford, 1702), and in
neither do I find the passage in question.”[561]
It is a remarkable fact that those who quote this as the language of

Irenæus, if they give any reference, cite their readers to Dwight’s
Theology instead of referring them to the place in the works of
Irenæus where it is to be found. It was Dr. Dwight who first enriched
the theological world with this invaluable quotation. Where, then, did
Dwight obtain this testimony which has so many times been given as
that of Irenæus? On this point Domville remarks:—
“He had the misfortune to be afflicted with a disease in his

eyes from the early age of twenty-three, a calamity (says his
biographer) by which he was deprived of the capacity for
reading and study.... The knowledge which he gained from
books after the period above mentioned [by which the editor
must mean his age of twenty-three] was almost exclusively at
second hand, by the aid of others.”[562]
Domville states another fact which gives us unquestionably the

origin of this quotation:—
“But although not to be found in Irenæus, there are in the

writings ascribed to another father, namely, in the interpolated
epistle of Ignatius to the Magnesians, and in one of its
interpolated passages, expressions so clearly resembling
those of Dr. Dwight’s quotation as to leave no doubt of the
source from which he quoted.”[563]
Such, then, is the end of this famous testimony of Irenæus, who

had it from Polycarp, who had it from the apostles! It was furnished
the world by a man whose eyesight was impaired; who in
consequence of this infirmity took at second hand an interpolated
passage from an epistle falsely ascribed to Ignatius, and published it
to the world as the genuine testimony of Irenæus. Loss of eyesight,
as we may charitably believe, led Dr. Dwight into the serious error
which he has committed; but by the publication of this spurious
testimony, which seemed to come in a direct line from the apostles,
he has rendered multitudes as incapable of reading aright the fourth
commandment, as he, by loss of natural eyesight, was of reading
Irenæus for himself. This case admirably illustrates tradition as a
religious guide; it is the blind leading the blind until both fall into the
ditch.
Nor is this all that should be said in the case of Irenæus. In all his
writings there is no instance in which he calls Sunday the Lord’s day!
And what is also very remarkable, there is no sentence extant written
by him in which he even mentions the first day of the week![564] It
appears, however, from several statements in ancient writers, that he
did mention the day, though no sentence of his in which it is
mentioned is in existence. He held that the Sabbath was a typical
institution, which pointed to the seventh thousand years as the great
day of rest to the church;[565] he said that Abraham was “without
observance of Sabbaths;”[566] and yet he makes the origin of the
Sabbath to be the sanctification of the seventh day.[567] But he
expressly asserts the perpetuity and authority of the ten
commandments, declaring that they are identical with the law of
nature implanted from the beginning in mankind, that they remain
permanently with us, and that if any one does not observe them he
has no salvation.[568]
It is a remarkable fact that the first instance upon record in which
the bishop of Rome attempted to rule the Christian church was by an
edict in behalf of Sunday. It had been the custom of all the
churches to celebrate the passover, but with this difference: that
while the eastern churches observed it upon the fourteenth day of
the first month, no matter what day of the week this might be, the
western churches kept it upon the Sunday following that day; or
rather, upon the Sunday following Good Friday. Victor, bishop of
Rome, in the year 196,[569] took upon him to impose the Roman
custom upon all the churches; that is, to compel them to observe the
passover upon Sunday. “This bold attempt,” says Bower, “we may
call the first essay of papal usurpation.”[570] And Dowling terms it the
“earliest instance of Romish assumption.”[571] The churches of Asia
Minor informed Victor that they could not comply with his lordly
mandate. Then, says Bower:—
“Upon the receipt of this letter, Victor, giving the reins to an

impotent and ungovernable passion, published bitter
invectives against all the churches of Asia, declared them cut
off from his communion, sent letters of excommunication to
their respective bishops; and, at the same time, in order to
have them cut off from the communion of the whole church,
wrote to the other bishops, exhorting them to follow his
example, and forbear communicating with their refractory
brethren of Asia.”[572]
The historian informs us that “not one followed his example or
advice; not one paid any sort of regard to his letters, or showed the
least inclination to second him in such a rash and uncharitable
attempt.” He further says:—
“Victor being thus baffled in his attempt, his successors

took care not to revive the controversy; so that the Asiatics
peaceably followed their ancient practice till the Council of
Nice, which out of complaisance to Constantine the Great,
ordered the solemnity of Easter to be kept everywhere on the
same day, after the custom of Rome.”[573]
The victory was not obtained for Sunday in this struggle, as Heylyn
testifies,
“Till the great Council of Nice [a. d. 325] backed by the

authority of as great an emperor [Constantine] settled it better
than before; none but some scattered schismatics, now and
then appearing, that durst oppose the resolution of that
famous synod.”[574]
Constantine, by whose powerful influence the Council of Nice was

induced to decide this question in favor of the Roman bishop, that is,
to fix the passover upon Sunday, urged the following strong reason
for the measure:—
“Let us then have nothing in common with the most hostile

rabble of the Jews.”[575]
This sentence is worthy of notice. A determination to have nothing

in common with the Jews had very much to do with the suppression
of the Sabbath in the Christian church. Those who rejected the
Sabbath of the Lord and chose in its stead the more popular and
more convenient Sunday festival of the heathen, were so infatuated
with the idea of having nothing in common with the Jews, that they
never even questioned the propriety of a festival in common with the
heathen.
This festival was not weekly, but annual; but the removal of it from
the fourteenth of the first month to the Sunday following Good Friday
was the first legislation attempted in honor of Sunday as a Christian
festival; and as Heylyn quaintly expresses it, “The Lord’s day found it
no small matter to obtain the victory.”[576] In a brief period after the
Council of Nice, by the laws of Theodosius, capital punishment was
inflicted upon those who should celebrate the feast of the passover
upon any other day than Sunday.[577] The Britons of Wales were
long able to maintain their ground against this favorite project of the
Roman church, and as late as the sixth century “obstinately resisted
the imperious mandates of the Roman pontiffs.”[578]
Four years after the commencement of the struggle just narrated,
bring us to the testimony of Tertullian, the oldest of the Latin fathers,
who wrote about a. d. 200. Dr. Clarke tells us that the fathers “blow
hot and cold.” Tertullian is a fair example of this. He places the origin
of the Sabbath at the creation, but elsewhere says that the patriarchs
did not keep it. He says that Joshua broke the Sabbath at Jericho,
and afterward shows that he did not break it. He says that Christ
broke the Sabbath, and in another place proves that he did not. He
represents the eighth day as more honorable than the seventh, and
elsewhere states the reverse. He states that the law is abolished,
and in other places teaches its perpetuity and authority. He declares
that the Sabbath was abrogated by Christ, and afterward asserts that
“Christ did not at all rescind the Sabbath,” but imparted “an additional
sanctity” to “the Sabbath day itself, which from the beginning had
been consecrated by the benediction of the Father.” And he goes on
to say that Christ “furnished to this day divine safeguards—a course
which his adversary would have pursued for some other days, to
avoid honoring the Creator’s Sabbath.”
This last statement is very remarkable. The Saviour furnished
additional safeguards to the Creator’s Sabbath. But “his adversary”
would have done this to some other days. Now it is plain, first, that
Tertullian did not believe that Christ sanctified some other day to take

Non Neoplastic Cytology A Comprehensive Guide 1St Edition Syed M Gilani Online Ebook Texxtbook Full Chapter PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Non Neoplastic Cytology A Comprehensive Guide 1St Edition Syed M Gilani Online Ebook Texxtbook Full Chapter PDF

Uploaded by

Copyright:

Available Formats

Non-Neoplastic Cytology: A

Comprehensive Guide 1st Edition Syed

Cancer Consult: Expertise in Clinical Practice, Volume

Diagnostic EMQs: A Comprehensive Collection for Medical

Primary Mathematics 3A Hoerst

Equine Hematology Cytology and Clinical Chemistry 2nd

A Comprehensive Guide to Solar Energy Systems: With

Hoarding Disorder A Comprehensive Clinical Guide 1st

Network Architect s Guide to 5G A 1st Edition Syed

The Bundy Murders A Comprehensive History 2nd Edition

ISBN 978-3-031-44288-9 ISBN 978-3-031-44289-6 (eBook)

Paper in this product is recyclable.

Albany, NY, USA Syed M. Gilani

Zoon Tariq and Syed M. Gilani

Specimen Collection Techniques [1]

© The Author(s), under exclusive license to Springer Nature 1

Fat pad FNA and associated vessels

Washings Bronchial, gastric, colonic, Lesional cells or epithelial

Table 1.1 (continued)

Fine Needle Aspiration (FNA)

• This procedure is used to evaluate either superficial or deep-seated lesions. FNA

• Gynecologic cytology: Liquid-based gynecological pathology specimens are col-

• Rapid H&E stain.

Workup Stain Uses Positive interpretation

Workup Stain Uses Positive interpretation

• An important development in cytopathology is the application of immunohisto-

Conflict of Interest None.

Anatomy and histopathology of Urinary Tract

© The Author(s), under exclusive license to Springer Nature 11

Fig. 2.1 Urothelial lining

Fig. 2.2 Squamous

Table 2.1 Comparison of urine sample collection methods1

Contamination less likely Clusters of urothelial cells atypia related to

Fig. 2.3 Voided urine.

Fig. 2.5 Ileal conduit

Fig. 2.6 Catheterized

Fig. 2.8 Ureteral brush

Normal Urine Cytology

Currently, there is no well-established criteria for a specific number of cells for

Superficial Urothelial Cells

Intermediate Urothelial Cells

Table 2.2 Cytomorphologic features of urothelial cells

Basal Urothelial Cells

Fig. 2.11 Basal urothelial

Table 2.3 Crystals in urine specimens

dihydrate calcium Dihydrate: Octahedral, ingestion (monohydrate)

polarized lens. The presence of crystals in urine specimens is usually of no diagnos-

Urine samples may be contaminated during specimen collection or processing at

Fig. 2.17 Bacterial

Cellular degeneration is frequently encountered when evaluating urine specimens,

Another example of degenerative changes is seen in ileal conduct samples where

Reactive changes can be caused by inflammation, infection, urolithiasis, treat-

inflammation is a quite common finding in patients with urothelial carcinoma fol-

Polyomavirus, the BK strain, is the prototype of virus that is associated with

Compared to bacterial infection, fungal infection is much less common in uri-

Fig. 2.24 Therapy-related

granulomatous inflammation in the wall of urinary bladder, like those of tuberculo-

Clusters of Urothelial Cells

A urothelial cell cluster is referred as a three-dimensional group of urothelial cells

Table 2.5 Possible causes of urothelial cell clusters in urine specimens

identified voided urine specimens, which make a diagnosis of low-grade urothelial

Conflict of Interest None.

Tong Sun and Syed M. Gilani

Albany, NY, USA Syed M. Gilani

Specimen Collection Techniques [1]

Fine Needle Aspiration (FNA)

Anatomy and histopathology of Urinary Tract

Normal Urine Cytology

Superficial Urothelial Cells

Intermediate Urothelial Cells

Basal Urothelial Cells

Clusters of Urothelial Cells

Different Preparations and Screening Procedures [2] (Table 3.1)

ormal Elements (Superficial, Intermediate, Parabasal,

Benign Findings [1, 4] (Table 3.2)