Patologi Anatomi

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Slide Tentiran

By: Amgah Alvin Dimas Lily Febby Sofhi Ivan Karina Alung Jalul
Reyhan Nida Nikko Rangga Vincent Yosua Juju
Pemeriksaan PA
Histopathology
histopathology
Histopathology

 Ectom
y
Cytopathology

 Thoracocentesis
 Bilasan Bronkus
 Sikatan Bronkus
 Aspirasi asites
Pewarnaan
sederhana: HE, PAS
Pewarnaan
“kompleks” = IHC
Nasal Polyp

Inverted Papilloma

Bronchioalveolar Carcinoma

Squamous Cell Carcinoma of the

Larynx
Histology
 Overview
• Formation is associated with inflammation,
allergy, or mucoviscidosis (cystic fibrosis)
• With time, they can fill the entire nasal cavity
and even extend upward into the cranial
cavity
 Epidemiology
• Adults 1-4%
• Children 0.1%
• Male:Female 2-4:1
• Increasing incidence with age
 Allergic vs. Non allergic
• 20-50% have asthma • Cystic fibrosis/
• Allergic rhinitis mucoviscidosis (6-48%,
• 8-25% have aspirin polyp muncul pada usia
intolerance muda)
• 50% have alcohol • Samster’s Triad (nasal
intolerance polyposis, asthma and
ASA intolerance
• Young’s Syndrome
• Churg Strauss Disease
(34%)
Inflammation, Definition

• Suffix  -itis
 Classification
Inflammation Acute Healing

Non Specific Chronic Specific

 Three Principal of Inflammation
1. Perubahan diameter pemb. darah
2. Perubahan permeabilitas pemb. darah
3. Emigrasi Leukosit

Ketiga prinsip ini nantinya akan menyebabkan 5

Tanda kardinal Inflamasi
 Functio
Calor Rubor Tumor Dolor laesa
 Jelaskan normal sampai ke
Tumor, Rubor, and Calor Mengumpulkan Tentara
dan membuat tentara bisa masuk
 Leukocyte Recruitment
(Bagaimana tentara masuk ke area peperangan)

Margination  rolling  adhesion  transmigration (diapedesis)

Ditelfon Makrofag Selectin Integrin Chemoattractant
 Inflamasi Kronis
• Penyebab;
– Infeksi persisten
– Mediasi imun (RA)
– Paparan racun jangka panjang
 Hipersensitivitas
• Apa itu hipersensitivitas?
• Apa hubungan hipersensitivitas dengan nasa polyp?
• Kita mendalami reaksi HS tipe 1 dan 4
• Tipe 1 hub dengan polyp
• Tipe 4 hub dengan inflamasi granulomatosa TB
• Kenapa perlu memelajari TB?
 HS1
• Peran Allergen
• Peran sel B
• Peran IgE
• Peran sel mast
• Peran Interleukin
• Peran eosinofil
4
1
Clinical Presentation
• Asymptomatic
• Airway Obstruction
• Postnasal drip
• Dull headache
• Snorring
• Rhinorhea
• Hyposmia/Anosmia
• Epistaxis
• Obstructive Sleep Apnea
• Craniofacial abnormalities
• Optic nerve compression
Macroscopic
• 3-4 cm in length
• Pale smooth, shiny and
edematous exophytic
mass
• Soft when compared to
surrounding mucosa
• Presence of surface
ulceration suspect
bacterial inf.
• Often bilateral
 Microscopic
• Pada sediaan tampak epithel pelapis normal
berupa pseudostratified collumnar bersillia
(respiratory mucosa) dengan penebalan membrana
basalis
• Stroma mengalami edema sehingga tampak
longgar
• Infiltrasi dari sel radang akut maupun kronis,
predominan eosinofil
• Tubulus glandula sero-mucin mengalami
hiperplasia dan dilatasi
Allergic nasal polyp showing a large number of eosinophils and
hyperplasia of mucous glands.
Bizarre stromal cells in a nasal polyp, set against an
edematous and inflammatory background
 Hellquist Classification
• Tipe 1: Polip edematosa eosinofilik
• Tipe 2: Polip fibroinflamatorik netrofilik
• Tipe 3: Hiperplasia glandula serumusinous
• Tipe 4: Polip dengan stroma atipik
 • Polipectomy
Treatment • Nasal drips using ASA
(prednisolone)

• Rarely becomes neoplastic

• Often locally reoccur, due to
Prognosis persistent unknown
pathogenesis
Inverting papilloma, Schneiderian papilloma,
papillomatosis
 Overview
• Benign neoplasms of the respiratory mucosa
most commonly presenting with nasal stuffiness,
nasal obstruction, or epistaxis.
• 2-5 times more common in males, and are found
primarily in the 40-70 year age group.
• Rare tumor, incidence about 1-5% of all primary
nasal tumor
• More common in male patient (M : F = 3.3 :1)
• Approximately 10% of tumor have potential to
transform into malignant
 Overview
• These lesions occur in three forms: exophytic
(most common), endophytic (inverted; most
important bio- logically), and cylindrical
• Mostly UNILATERAL
• Clinical Presentation: Nosebleed, Obstruction,
 Basic of disease
• Have 3 variants :
Fungiform papillomas (32%)
Inverted papillomas (62%)
Oncocytic papillomas (6%)
• Arise from Schneiderian mucosa which lines
the nasal cavity and paranasal sinuses
• Schneiderian mucosa is ectodermal derivation
in contrast to mucosal lining of nasopharynx
which is endodermal derivation
 Etiology
• HPV DNA, often types 6 and 11, has been
identified in the exophytic and endophytic
lesions, but not the cylindrical type
• Some research found evidence of EBV but still
need more proof
• No association with allergy, inflammation,
smoking, noxious environmental agents or
occupation
 • Complaints of recurrent
nasal discharge, epistaxis,
nostril fullness, nasal
airway obstruction, and
headche
• Clinical findings :
– Polypoid mass in nasal
cavity
– CT Scan can show
Clinical feature destruction of nasal wall
and maxillary sinus floor
Macroscopic

• Putih-keruh
 Microscopic
• Sediaan tampak tumor yang terdiri dari proliferasi epithel
pseudostratified collumnar
• Metaplasia squamous dapat terjadi, dibedakan dengan
perubahan polaritas sel
• Tumor tumbuh ke arah stroma namun tidak invasif,
dibuktikan dengan keutuhan membrana basalis
• Dapat ditemukan limfosit, sel plasma dan beberapa
leukosit lainnya pada stroma
• Dapat terjadi bersamaan dengan nasal polyp, maka dapat
ditemukan edema stroma dan infiltrasi sel radang
eosinofil dominan
 Microscopic
• Papillary Variant
– Papillary fronds with fibrovascular cores covered by
epithelium
– 5-20 cells thick
– Epithelium varies from squamous, transitional, to
ciliated pseudostratified columnar
– Scattered mucin-containing cells (from goblet cells)
– Absent of surface keratinization unless the lesion is
irritated or exposed to drying ambient air
– Pathologic mitoses are rare
– Few inflammatory cells unless irritated
• Inverted Variant
– Hyperplastic basement membrane enclosed by
epithelium that grow endophyticly into underlying
stroma
– Epithelium consist of 5-30 cells thick, squamous or
ciliated, and mixed with goblet cells
– 10-20% have surface keratinization
– Few pathologic mitoses
– 5-20% varying degrees of dysplasia
– Stroma ranged from dense to loose and myxoid
– Inflammatory cells may exist, usually neutrophils
 Keganasan pada inverted papilloma
• Apa yang terjadi pada epitel kolumnar yang
terpapar racun/zat karsinogenik?
• Apa yang membedakan inverted papilloma
jinak dengan inverted papilloma yang
mengalami keganasan?
• Apa perbedaan karsinoma dengan karsinoma
in situ?
 • PCR : HPV 6 & 11
Diagnosis • Staining CD 44: positive in malignancy

• Surgery and radiation therapy combination

• For oncocytic and inverted variant: lateral
Treatment rhinotomy and medial maxillectomy with
meticulous removal of all mucosa in the
ipsilateral paranasal sinuses
 Prognosis
• The incidence of malignant change : 2-27%
• 5-year survival rates 60%.
• 3% development of obvious carcinoma months or
years after the excision of a papillomaThis event occurs
in about 3% of all papillomas and is associated with a
25% survival rate.
• 3% presence of focal invasive carcinoma in an
otherwise typical papilloma at the time of the first
excision (excellent prognosis)
• 25% Occurrence of a tumor having a pattern of growth
very similar to that of papilloma but with subtle
cytologic features (indicative of malignancy)  survival
rate for this group poor
Normal Anatomy
Normal Histology
 Lung cancer

Non Small Cell

Small Cell (19%) Other types (1%)
(80%)

Squamous cell or
Undifferentiated Large Cell (10- Adenocarcinoma
epidermoid (25-
(15%) 15%) (40%)
30%)

Classic Bronchoalveolar
Adenocarcinoma carcinoma (10-
(75-90%) 25%)
 Klasifikasi Lung Tumor
• Carcinoma dan non-carcinoma
(epidemiologi)
• Small cell dan non-small cell
(klinis)
• Adenocarcinoma dan non-
adenocarcinoma (terapi)
• Mutasi EGFR KRAS dan Mutasi
ALK (terapi)
• Adenocarcinoma, Squamous cell
carcinoma, small cell carcinoma,
dan undifferentiated/large cell
carcinoma (morfologi mikros) Squamous CC of The Lung
 Overview
Women > men and non smoker
 Precursor : atypical adenomatous hyperplasia (AAH)
 EGFR, K-RAS mutations  targeted therapy
 located more peripherally
 Type: Mucinous & Non Mucinous
 grows slowly but metastasize early
• Subtypes : acinar, papillary, solid,
Bronchioloalveolar
Macroscopic
 single/multiple diffuse nodules
 unite to produce a
pneumonia-like consolidation
 The nodules : mucinous, gray
translucence when secretion
present OR
 solid, gray-white areas  can be
confused with pneumonia
 MICROSCOPIC
• Tumor cells grow along preexisting structures without destruction
of alveolar architecture (lepidic pattern: “butterflies sitting on a
fence”)
• No stromal, vascular, or pleural invasion
Subtypes:
Nonmucinous (60-75%)
Mucinous
 Subtype adenokarsinoma
• asinar (paling sering)
• Bronkhioloalveolar
– Mucinous
– Non-mucinous
• papiller
• solid
• tubuler
Mucinous vs Non Mucinous Type
Non mucinous Mucinous
• Seldomly to • can spread
spread aerogenously
aerogenously, and form satelite
so it is favorable tumor. An
for surgery. extensive
consolidation is
frequently found
in imaging.
 Non-Mucinous Mucinous
• Columnar, peg-shaped, or • Low grade, tall columnar
cuboidal cells cells with basal nuclei and
• Typically shows Clara cell pale cytoplasm, sometimes
and/or type II cell resembling goblet cells
differentiation • cytoplasmic and intra-
• Degree of nuclear atypia alveolar mucin
and nucleolar prominence
is GREATER
Progression
Atypical Adenomatous
Hyperplasia

Adenocarcinoma In Situ

Adenocarcinoma
(Bronchioloalveolar
carcinoma)
Clinical Features
• often asymptomatic
• peripherally located,
grows slower than SCC,
but metastasize wider
and faster. Less likely to
cause atelectasis and
emphysema
• Cough, weight loss,
increase of sputum
production, hemoptysis,
malaise, fever, and
paraneoplastic
syndrome
 Pancoast Tumor
 Located at the lung apex
 Compress the following
structures:
 V. Brachiocephalic
 A Subclavian
 N. Phrenicus
 Brachial plexus
 N. Recurrent laryngeal 
hoarseness
 N. Vagus
 Sympathetic trunk 
Horner's syndrome.
Diagnosis
• Bronchoscopy with
biopsy (definitive
treatment)
• sputum cytology
• Pleural effusion
cytology.
• Imaging : CT, chest
Xray, MRI
 DIAGNOSIS
• Transthoracic Needle Aspiration
• Transthoracal biopsy
• Effusion fluid cytology
• Imaging : CT, chest X-ray
• Molecular Diagnosis: EGFR, ALK, KRAS
 IMMUNOHISTOCHEMISTRY
 PE-10  detect surfactant apoprotein in BAC

 EGFR  for therapy determination

BAC Metastatic
IHC (Nonmucino colorectal
us) adenocarcinoma

CK7 + -

CK20 - +

TTF-1 + -

CDX2 - +
 Cytology
Characteristic:
- Foamy
cytoplasm
- Apical Mucin
- Basal Nuclei
Adenocarcinoma Squamous Cell Carcinoma

Nucleus basal/eccentric Nucleus tengah

Apical Mucin Tidak memiliki mucin

Sitoplasma berbuih Sitoplasma kadang berkeratin

• Semua adenoCA akan membuat tampakan
sitologis yang sama. Harus diketahui tumor
primernya darimana.
• Tumor adenoCA; Prostat, Payudara, ovary,
colorectal, thyroid
• Mutation in EGFR  constitutive activation of EGFR
• Mutation in KRAS (G-protein)  constitutive activation
of signaling pathway downstream of EGFR
 Non-small cell lung cancers have also been linked to
rearrangements of the gene encoding ALK.
 Most common ALK rearrangement fusion between
echinoderm microtubule-associated protein-like 4 (EML4)
and ALK gene on chromosome 2p23
 In cell line and mouse models, EML4-ALK is highly
oncogenic, activates the PI3K-AKT and MAPK-ERK
pathways and induces lung tumors
 EML4-ALK most commonly seen in adenocarcinomas of
nonsmoker or light smokers, without EGFR &KRAS
mutations. **Patients tend to be younger than most
patients with non-small cell lung cancer.
To check EGFR and KRAS mutation;
IHC anti-EGFR
PCR
RT-PCR
DNA Sequencing
Pneumonic like
 THERAPY
 With chemotherapy or
radiotherapy
 Targeted therapy aiming at the
epidermal growth factor receptor
(EGFR)
 Tumor grade is associated with its
sensitivity to chemotherapy.
Lower grade tumors are more
resistant to chemotherapy.

Targeted Therapy
 Cetuximab, panitumumab  MoAb that inhibit EGFR
 Erlotinib, gefitinib  small molecule that inhibit EGFR
 Crizotinib  small molecule that inhibit ALK
 Prognosis
• Solitary lesion  usually excisable, so the
5 year survival rate is about 50-75%. But
generally, the 5 year survival rate is 25%.
• Metastasize (45%) :
- adrenal (>50% )
- liver (30% - 50%)
- brain (20%)
- bone (20%)
• grows slowly but metastasize early
of the larynx
Normal anatomy
Normal Histology
 Overview
• 90% of head and neck tumors
• 4% of all malignancy
• man > woman (2:1)
• most common at >60 y.o.
• alcohol abuse & smoking (excess of G to T
transversions)  90%
 Etiology
• Precursor lesions  Epithelial dysplasia
• Molecular genetic alterations
• modulation of a large number of genes as well as
telomerase re-activation as indicated by hTERT
expression. CCND1, MYC, EGFR, RB1, LOH, TP53 (in
premalignant lesions)
• HPV (16, 18)
Location
• Glottic 60-65 %
• Supraglottic 30-35%
• Transglottic <5%
• Infraglottic <5%
 Clinical Presentation & Diagnosis
• Glottic  Hoarsness • Laryngoscopy + Biopsy
• Supraglottic & • Radiology  MRI / CT
infaglottic  Scan : staging TMN
Odynophagia, • Immunoprofile  CK,
Hemoptysis, Foreign KI67 (mitotic
body sensation, Neck proliferation)
mass • PCR
Macroscopic
• flat plaque with a
welldefined, raised
edge, circuferential, or
polypoid exophytic
appearance  relate to
prognosis
• sometimes ulcerated
• Size 1-4 cm
• Squamous
differentiation
with
keratinization
• Stroma mengalami
penipisan
• atypic, polymorfic,
pleiomorfic, &
mitoses pathology
• Inflitration of
chronic
inflammatory cell
• Desmoplastic area
Patogenesis perubahan histopatologis
• Dari columnar -> skuamous
• Bagaimana suatu epitel columnar terpapar karsinogen
dan racun akhirnya metaplasia menjadi skuamous dan
proliferasi
 Grading & Staging
Grading:
• Three main grading charachteristics of SCC : keratinization,
Intercelullar bridge, mitoses pathology
– Well differentiated SCC Pearl horn M1 <10
– Moderately differentiated SCC intracellular
– Poorly differentiated SCC(–– none)
– Intercelullar bridge (tampak jelas dan banyak – tidak jelas
dan masih ada – tidak tampak sama sekali
– (– M2: 10-18 – M3 >18)
Staging:
 Treatment
• Surgical procedures:
– Cordectomy
– supraglottic laryngectomy
– Hemilaryngectomy
– partial laryngectomy
– total laryngectomy
– Thyroidectomy
– laser surgery
• Radiotherapy
 Prognosis
• The overall 5-year survival rate is 80-85%

Glottic SCC
Supraglottic SCC

Hypopharingeal
SCC Transglottic SCC

Tracheal SCC

Subglottic SCC