Fine Needle Aspiration

Acta Cytologica 2021;65:463–477 Received: January 22, 2021

Accepted: July 7, 2021
DOI: 10.1159/000518375 Published online: August 27, 2021

Fine-Needle Aspiration Biopsy Cytopathology of

Breast Lesions Using the International Academy
of Cytology Yokohama System and Rapid On-Site
Evaluation: A Single-Institute Experience

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

Neha Agrawal a Kanchan Kothari a Santosh Tummidi b Prashant Sood c
Mona Agnihotri a Vyoma Shah d
aDepartment of Cytopathology, Seth GSMC & KEMH, Parel, Mumbai, India; bDepartment of Pathology,
All India Institute of Medical Sciences (AIIMS), Mangalagiri, India; cDepartment of Microbiology, All India Institute of
Medical Sciences (AIIMS), Bilaspur, India; dSir HN Reliance Foundation Hospital, Mumbai, India

Keywords the curve were computed. Results: A total of 1,147 FNABs

Breast cytopathology · International Academy of Cytology
Yokohama System for Reporting Breast Fine-Needle
Aspiration Biopsy Cytopathology · Rapid on-site evaluation ·
Histopathology
Abstract
Introduction: Breast cancer is rapidly emerging as the lead-
ing cause of cancer in Indian women. Robust cytopathology
and histopathology services are required to tackle this
growing burden. The use of rapid on-site evaluation (ROSE)
and the International Academy of Cytology (IAC) Yokohama
System for Reporting Breast Fine-Needle Aspiration Biopsy
(FNAB) Cytopathology, which offers structured protocols,
are expected to improve breast cytopathology reporting.
Methods: We retrieved the cytopathology slides, catego-
rized them by the IAC Yokohama System and histopathol-
ogy data of all the patients who had been investigated for
breast lesions from September 2016 to December 2018, and
compared the cytopathology and histopathology. Risk of
malignancy (ROM) and performance metrics, like sensitivi-
ty, specificity, predictive values, accuracy, and area under
were evaluated, of which 442 (38.5%) underwent ROSE and
624 (54.4%) histopathology. Reported using IAC categories,
our cohort recorded 4.9% inadequate, 65.3% benign, 7.8%
atypical, 3.3% suspicious for malignancy, and 18.7% malig-
nant lesions. The overall sensitivity and specificity for iden-
tifying in situ and malignant lesions were 99.1% and 99.3%,
respectively, and were substantially improved by ROSE.
ROSE improved the concordance between cytopathology
and histopathology from 76.9% to 90.2%, by reducing inad-
equate (p < 0.001) cases. The ROM increased along a gradi-
ent from inadequate to malignant categories, with the gra-
dient being sharpened by ROSE. The false negativity rate
was 0.7% and false positivity rate 0%. Conclusion: Incorpo-
rating ROSE and the IAC Yokohama System for breast cyto-
pathology reporting improves accurate diagnosis of breast
lesions, prevents missed diagnoses, and provides reliable
estimates of ROM. These protocols also aid in standardizing
a reproducible system for monitoring and auditing of breast
pathology services, identify areas that need strengthening,
and improve training at pathology centers.
© 2021 S. Karger AG, Basel

karger@karger.com © 2021 S. Karger AG, Basel Correspondence to:

www.karger.com/acy Santosh Tummidi, born_vss @ yahoo.co.in
 Introduction
Clinical examination, radiological imaging, and
breast cytopathology with or without core needle bi-
opsy (CNB) comprise the 3 key modalities employed
for diagnosing breast lumps. These modalities aim to
maximize the preoperative identification of malignancy
so that early, definitive, one-stage surgery or appropri-
ate treatment can be offered to the patient [1, 2]. As a
corollary, these diagnostic procedures also aim to ac-
curately recognize benign breast lesions and avoid un-
necessary invasive investigations and anxiety to the
patient [2]. For breast biopsy, fine-needle aspiration
biopsy (FNAB) and CNB offer complementary advan-
tages, and both can be utilized gainfully in different set-
tings. The recent advances in breast cytopathology with
the implementation of rapid on-site evaluation (ROSE)
and the development of the International Academy of
Cytology (IAC) Yokohama System for Reporting Breast
FNAB Cytopathology have structured the reporting of
breast cytopathology with the aim of improving cytopa-
thology procedures, training, interpretation, and diag-
nosis [3, 4].
In recent years, breast cancer has become the most
common malignancy in Indian women, surpassing cer-
vical cancer. An incidence of 2,05,424 new cases of
breast cancer annually is projected in India, comprising
∼29.9% of all malignancies reported in women, with
87,000 annual deaths [5, 6]. FNAB and CNB are crucial
preoperative tests for diagnosing these cases. However,
the accuracy of FNAB depends on several factors, in-
cluding the skill and experience of the operator, the lo-
calization method used, the skill of the pathologist, and
the proportion of symptomatic and nonpalpable lesions
being examined [7, 8]. Since numerous sources of error
can confound these procedures, it is important that the
performance of breast cytopathology is regularly moni-
tored at a center using a standardized and reproducible
system [3, 4, 7]. We undertook this study to incorporate
ROSE and the IAC Yokohama System into our breast
cytopathology protocols, evaluating their impact on the
performance of breast cytopathology versus histopa-
thology in accurately identifying breast malignancies
and providing a patient’s risk of malignancy (ROM) un-
der various IAC categories. This afforded us the oppor-
tunity to upgrade our breast reporting, create a repro-
ducible monitoring and auditing system, and better
identify the areas that need attention for further im-
provement of our services.
464 Acta Cytologica 2021;65:463–477
DOI: 10.1159/000518375
Fig. 1. Distribution of breast lesions observed in this study. All fig-
ures in percentages.
Methods
Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024
This study was carried out at the Seth GSMC & KEM Hospital,
Mumbai, India, which is a tertiary care center catering to a large
population in western India. In order to evaluate the impact of
ROSE and the IAC System on our breast pathology reporting, we
retrieved the cytopathology data of all consecutive patients inves-
tigated for breast lesions between September 2016 and December
2018. Ethics clearance was obtained from the Institute’s Ethics
Committee for retrieving and analyzing this data [EC/OA-
150/2019]. The data was anonymized before undertaking analyses.
All the samples had been collected from the patients for routine
clinical investigation, after informed consent. An attempt was
made to obtain follow-up and any, histopathology report of a bi-
opsy or excision (if performed) in all cases; however, histopathol-
ogy was available only in 624 cases.
Cytopathology Protocols
Guided and nonguided FNAB samples were collected from en-
rolled patients using standard procedures. ROSE was carried out
using 1% aqueous toluidine blue staining. After provisional assess-
ment by ROSE, the slides were subjected to Papanicolaou staining
for standard cytopathology reporting [8]. Air-dried slides were
stained using Giemsa. Special stains like Ziehl-Neelsen, Periodic
acid Schiff’s, Gomori’s methanamine silver stain, and immunocy-
tochemistry were employed on the cytology slides wherever need-
ed and feasible.
Breast cytopathology reporting with and without ROSE, we
used the diagnostic categories recommended by the IAC Yoko-
hama System for Reporting Breast FNAB Cytopathology [1, 3]:
insufficient, benign, atypical, and suspicious for malignancy and
malignant. The histopathology diagnoses were broadly catego-
rized under nonrepresentative, benign, indeterminate, in situ, and
malignant, as has been reported previously [9]. Nonrepresentative
histopathology included cases where there was insufficient mate-
rial to reliably diagnose the lesions. Benign histopathology includ-
ed breast abscess, fibroadenoma, fibrocystic changes, intraductal
papilloma, scar tissue, etc. The indeterminate group included atyp-
ical fibroepithelial lesions, including phyllodes tumor, atypical
ductal hyperplasia, etc. The in situ group included cases where at
least one focuses of in situ pathology in the form of ductal carci-
noma in situ or lobular carcinoma in situ was observed. Finally, the
malignant histopathology group included cases of invasive carci-
Agrawal/Kothari/Tummidi/Sood/
Agnihotri/Shah
 a b

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

c d

Fig. 2. a, b Granulomatous mastitis (IAC II): epithelioid cell granuloma with necrosis and nuclear debris (Tolu-
idine blue, ×200; Papanicolaou, ×400). c Galactocele (IAC II): bluish granular proteinaceous background with
scattered histiocytes (Giemsa, ×100). d Fat necrosis (IAC II):granular necrotic fat fragments and multi nucleated
histiocytes (Papanicolaou, ×400). IAC, International Academy of Cytology.

noma of no special type, medullary carcinoma, mucinous carci-
noma, lobular carcinoma, and non-Hodgkin’s lymphoma.
Statistical Methods
Descriptive statistics were used to describe the patient cohort.
Confusion matrices and heatmaps were computed to compare
how well cytopathology (with and without ROSE) predicted the
diagnostic categories of breast lesions against those assigned by
histopathology. χ2 test was used to compare the performance of
cytopathology with and without ROSE, across different IAC cat-
egories. Performance metrics, including sensitivity, specificity,
positive predictive value (PPV), negative predictive value (NPV),
accuracy, and area under the receiver operating characteristic
curve (AUC) were computed to compare the performance of cy-
topathology against histopathology. The PPV of various IAC cat-
egories for diagnosing in situ or frank malignancy was computed
to estimate the ROM of each category. A p value of <0.05 was
taken as significant. All statistical analyses were performed in R
v3.6.3 and SPSS v23.0.
Results
A total of 1,147 breasts FNAB were examined in this
study. A majority of these specimens were received from
female patients (96.8%, median age: 34.5 years, interquar-
tile range [IQR]: 23–45 years), with remainder of male
patients (3.2%, median age: 45.0 years, interquartile
range: 28–59 years). Breast lesions were equitably distrib-

Breast Cytopathology Performance: Acta Cytologica 2021;65:463–477 465

A Single Institute Experience DOI: 10.1159/000518375
 a b
Fig. 3. a, b Filariasis breast (IAC II): numerous unfertilised eggs of filariasis along with wet mount preparation
showing the adult filaria (Papanicolaou, ×200; Wet mount, ×200). IAC, International Academy of Cytology.
uted with 45.2% arising in the right breast, 51.2% in the
left, and 3.5% were bilateral. Precise quadrant-wise infor-
mation was available in 59.6% of cases and their distribu-
tion is depicted in Figure 1. Of the total 1,147 cases, 442
(38.5%) underwent ROSE. Of the total 1,147 cases, 624
(54.4%) had histopathology follow-up.
Overall, the 1,147 cases were subclassified as 4.9% inad-
equate, 65.3% benign, 7.8% atypical, 3.3% suspicious for
malignancy, and 18.7% malignant. The most common
breast lesion under the benign category was fibroadenoma
(309, 41.3%). Other entities included inflammatory lesions
(47, 6.3%), granulomatous mastitis (26, 3.5%) (Fig. 2a, b),
gynecomastia (23, 3.1%), galactocele (8, 1.1%) (Fig. 2c),
and miscellaneous entities, like keratinous cyst, fat necrosis
(Fig. 2d), and filariasis (Fig. 3a, b). The atypical category
included lesions with atypical cells (44, 48.9%) and fibro-
epithelial lesions (e.g., fibroadenoma vs. low-grade phyl-
lodes) (46, 51.1%). The suspicious for malignancy category
included lesions suspicious for invasive carcinoma no spe-
cial type (30, 79%) and suspicious for papillary carcinoma
(9, 23.6%), and low-grade lymphoma (1, 2.6%). Ductal car-
cinoma was the most common lesion in the malignant cat-
egory accounting for 203 (94.9%) cases followed by muci-
nous carcinoma (2, 0.9%) and malignant phyllodes tumor
(1, 0.5%). The ROM was also assessed for the different cat-
egories and was found to be 16% for the inadequate, 0.7%
for benign, 23.3% for atypical, 94.1% for suspicious for ma-
lignancy, and 100% for the malignant category.
In 705 (61.5%) cases where ROSE was not implement-
ed the categories were as follows: inadequate (48, 6.8%),
466 Acta Cytologica 2021;65:463–477
DOI: 10.1159/000518375
Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024
benign (443, 62.8%), atypical (53, 7.5%), suspicious for
malignancy (31, 4.4%), and malignant (130, 18.4%). Of
these cases without ROSE, histopathology follow-up was
undertaken in 390 (55.3%) cases. Among these, 22 cases
inadequate on cytopathology, were found on histopathol-
ogy to be suspicious/malignant in 5 cases and benign (fi-
broadenoma, galactocele, lipoma, keratinous cyst, etc.) in
the remaining 17 cases. A total of 173 benign cases (39.1%)
had histopathology and only 3 cases showed a discrep-
ancy in classification. Among the atypical, 44 (83.0%) un-
derwent histopathology follow-up and were found to be
indeterminate, in situ or malignant lesions. Of the suspi-
cious of malignancy, 30 (96.8%) cases were followed up
with histopathology and 28 (93.3%) of these revealed in
situ or invasive malignancy. One case of suspected papil-
lary carcinoma reported on cytopathology was later cat-
egorized to be indeterminate as the CNB was reported as
a papillary neoplasm with atypia. Similarly, the malignant
cytopathology group had histopathology follow-up in
121 (93.1%) cases, with malignancy confirmed in 98.3%,
and in 2 cases (1.7%) the CNB yielded a nondiagnostic
sample. The corresponding figures for samples that were
subjected to ROSE are described in detail in the following
paragraphs.
Impact of ROSE
ROSE was carried out in 442 (38.5%) samples yielding
a preliminary diagnosis of inadequate (8, 1.8%), benign
(316, 71.5%), atypical (23, 5.2%), suspicious for malig-
nancy (14, 3.2%), and malignant (81, 18.3%), respectively.
Agrawal/Kothari/Tummidi/Sood/
Agnihotri/Shah

a FNAB, fine-needle aspirate biopsy; ROSE, rapid on-site evalu-
b components of our services in the future.
Fig. 4. Comparison of diagnostic categories assigned by ROSE ver-
sus those assigned by (a) final cytopathology and (b) histopathol-
ogy. ROSE, rapid on-site evaluation.
These preliminary diagnostic categories were compared
against those assigned by final cytopathology and histo-
pathology (Fig. 4). The comparison of ROSE categories
against the final cytopathology categories showed 96.2%
concordance. ROSE categories were compared against
the final categories assigned by histopathology (Fig. 4a,
b). Benign and malignant conditions showed good levels
of congruence with histopathology.
We further evaluated whether performing ROSE im-
proved the final IAC results. For this, we compared the
frequency with which various IAC categories were as-
signed to specimens which had undergone ROSE (442,
38.5%) versus those which had not undergone ROSE
(705, 61.5%) (Table 1). The most significant impact of
ROSE was seen in the reduction of inadequate (p < 0.001)
and suspicious for malignancy (p = 0.010) categories.
ROSE enabled better classification of benign lesions (p =
0.027) but showed little change in the frequency with
which atypical and malignant specimens were catego-
rized.
Breast Cytopathology Performance:
A Single Institute Experience
Table 1. Comparison of FNAB cases distributed across various
cytology categories when evaluated with and without ROSE
Cytology FNAB with FNAB without p value
category ROSE (n = 442), ROSE (n = 705),
n (%) n (%)
Inadequate 8 (1.8) 48 (6.8) <0.001
Benign 306 (69.2) 443 (62.8) 0.027
Atypical 37 (8.4) 53 (7.5) 0.601
Suspicious 7 (1.6) 31 (4.4) 0.010
Malignant 84 (19.0) 130 (18.4) 0.811
ation.
Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024
Performance of Breast Cytopathology versus
Histopathology
We evaluated the performance of breast cytopathology
in our cases against histopathology. This was important
to identify the areas that were lagging behind in our breast
pathology services, and also to establish a reproducible
system incorporating ROSE, the IAC Reporting System
and histopathology to monitor and improve various
We first compared how well cytopathology catego-
rized cases against broad histopathology categories
(Fig. 5). We stratified this by including ROSE in the cyto-
pathology workup (Fig. 5a–c). As is evident from the
heatmaps, ROSE reduced the number of outliers’ diagno-
ses substantially and assigned benign and malignant cat-
egories more accurately. Samples that were subjected to
ROSE showed only 1 benign, 6 atypical, and 1 suspicious
of malignancy case that had to be reclassified on histopa-
thology (Fig. 5a). The single benign case that had to be
reclassified on histopathology showed fat necrosis on
ROSE. It was subjected to CNB due to high clinical sus-
picion and was found to be a malignant lesion. FNAB
most likely had sampled the fat necrosis surrounding the
tumor. Six cases categorized as atypical by ROSE were fi-
broadenomas on histopathology. The young age of the
patients and the marked stromal cellularity had flagged
the mismatch, prompting us to confirm the diagnosis by
histopathology. Three cases with benign, suspicious for
malignancy, and malignant diagnoses on ROSE, could
not be confirmed on histopathology due to nonrepresen-
tative samples and lack of patient follow-up.
In contrast to the above analysis, specimens which did
not undergo ROSE showed a larger number of recatego-
rizations on histopathology. These included 5 inadequate,
4 benign, 16 atypical, 3 suspicious for malignancy, and 2
Acta Cytologica 2021;65:463–477 467
DOI: 10.1159/000518375
 a b c

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

d

Fig. 5. Comparison of diagnoses assigned by cytopathology and histopathology. The first 3 heatmaps compare
diagnostic categories assigned by final cytopathology with ROSE (a), without ROSE (b), and overall (c), versus
the diagnostic categories assigned by histopathology. d Compares the predominant histopathology diagnoses
observed in the study versus the diagnostic categories they were assigned by final cytopathology. DCIS, ductal
carcinoma in situ; FA, fibroadenoma; ROSE, rapid on-site evaluation.

malignant cases which had to be recategorized (Fig. 5b).
The 16 atypical cases showed lactational atypia (Fig. 6a,
b), infarcted fibroadenoma, benign breast changes, and
fat necrosis on histopathology. The 5 inadequate cases all
were malignant, and underscore the importance of ROSE
in assessing adequacy on-site minimizing missed and de-
layed diagnoses.
While the above analysis drew comparisons across
broad categories of cytopathology and histopathology, we
also wanted to assess how specific lesions had fared be-

468 Acta Cytologica 2021;65:463–477 Agrawal/Kothari/Tummidi/Sood/

DOI: 10.1159/000518375 Agnihotri/Shah
 a b
Fig. 6. a, b Lactational change with mild atypia (IAC III)-Mild to moderate nuclear atypia in the ductal epithe-
lial cells with dissociation and milky background (Giemsa, ×400; Papanicolaou, ×400). IAC, International Acad-
emy of Cytology.
tween the 2 techniques: how accurate was cytopathology
(both with and without ROSE) in identifying the most
common lesions (Fig. 5d). We found that a large major-
ity of benign conditions were correctly classified by cyto-
pathology, with 96.2% of fibroadenomas and 100% of
acute and granulomatous mastitis identified accurately.
Only 2.7% of fibroadenomas and 9.8% of benign breast
lesions were labeled atypical on cytopathology. Half
(50.0%) of the fibrocystic lesions and papillomas was clas-
sified as benign or atypical. Other less common benign
entities included lipoma, fat necrosis, galactocele, filaria-
sis, benign fibroepithelial polyps, gynecomastia, adenoli-
poma, and duct ectasia. These were largely (76.3%) iden-
tified correctly by cytopathology (Fig. 5d).
Among breast lesions with indeterminate histopathol-
ogy, low-grade phyllodes tumor was the commonest and
32 (94.1%) of these were classified as atypical on cytopa-
thology and 2 (5.9%) as benign fibroadenomas. The re-
view of these 2 cases showed increased stromal cellularity,
altered stromal-to-epithelial ratio and plump spindle
cells in the background (Fig. 7a–d). Benign phyllodes tu-
mor can be difficult to distinguish from fibroadenoma on
cytopathology [10]. Other less common indeterminate
entities included atypical or suspicious of malignancy le-
sions (Fig. 5d). Our cohort had very few cases of in situ
carcinomas, and 3 (75.0%) of these were flagged as atypi-
cal, suspicious of malignancy, or malignant by cytopa-
thology, with 1 high grade DCIS being misclassified as a
benign lesion on cytopathology (Fig. 5d), which on re-
Breast Cytopathology Performance:
A Single Institute Experience
Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024
view was due to inadequate sampling of a deep-seated le-
sion. Among invasive carcinomas, 187 (82.0%) were cor-
rectly categorized as malignant by cytopathology (Fig. 8a,
b), while the remainder were categorized as atypical 12
(5.3%) or suspicious for malignancy 24 (10.5%). Other
less common malignant lesions, like papillary carcinoma
(Fig. 8c, d), lobular carcinoma, mucinous carcinoma,
non-Hodgkin’s lymphoma (Fig. 9a, b), metaplastic carci-
noma and malignant phyllodes tumor (Fig. 9c, d) were
labeled as malignant (11, 50.0%), or suspicious for malig-
nancy (7, 31.8%) with 4 (18.2%) being classified as atypi-
cal (Fig. 5d). The 16 atypical cases that had been typed as
atypical on FNAB had revealed limited cytological fea-
tures, which could be confirmed as malignant on histo-
pathology (Fig. 5d).
The analysis of breast FNAB against histopathology
excluding the cases excluded final inadequate and atypi-
cal cases (Table 2). We stratified this analysis by 2 sce-
narios. First, how well did cytopathology identify the cas-
es that were eventually flagged in situ or malignant by
histopathology, and how did incorporating ROSE affect
this performance. FNAB picked up malignancies with an
overall 86.1% sensitivity and 99.6% specificity, and ex-
cluded malignancies with a NPV of 89.9%. Importantly,
all of these performance metrics were substantially im-
proved by using ROSE (Table 2). Second, how well did
the IAC categories of suspicious for malignancy and ma-
lignant identify in situ and malignant histopathology? As
would be expected, by widening the net with both suspi-
Acta Cytologica 2021;65:463–477 469
DOI: 10.1159/000518375
 a b

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

c d

Fig. 7. a–d Phyllodes tumor (IAC III)-Large cellular stromal fragments with numerous spindle-shaped nuclei.
Histopathology of the same case revealed cellular stroma with atypia and occasional mitotic figures (Papanico-
laou, ×100, ×200 & ×1,000; H&E, ×200). IAC, International Academy of Cytology.

Table 2. Performance of FNAB in detecting in situ and malignant histopathology, with “inadequate” and “atypical” cytopathology
removed

Malignant cytopathology cases found malignant on Suspicious and malignant cytopathology cases found in situ
histopathology or malignant on histopathology
FNAB with FNAB without all FNAB, FNAB with FNAB without all FNAB,
ROSE, % ROSE, % % ROSE, % ROSE, % %

Sensitivity (95% CI) 92.9 (85.3–97.4) 82.1 (74.8–87.9) 86.1 (80.9–90.3) 98.8 (93.6–100) 99.3 (96.3–100) 99.1 (96.9–99.9)
Specificity (95% CI) 100 (96.7–100) 99.4 (96.8–100) 99.6 (98.1–100) 99.1 (95.1–100) 99.4 (96.8–100) 99.3 (97.5–99.9)
PPV 100 99.2 99.5 98.8 99.3 99.1
NPV 94.9 86.9 89.9 99.1 99.4 99.3
Accuracy 96.9 91.5 93.6 99.0 99.4 99.2
AUC (95% CI) 0.97 (0.93–0.99) 0.91 (0.87–0.94) 0.93 (0.90–0.95) 0.99 (0.96–1.00) 0.99 (0.98–1.00) 0.99 (0.98–1.00)

AUC, area under the curve; CIs, confidence intervals; FNAB, fine-needle aspirate biopsy; NPV, negative predictive value; PPV, positive predictive value;
ROSE, rapid on-site evaluation.

470 Acta Cytologica 2021;65:463–477 Agrawal/Kothari/Tummidi/Sood/

DOI: 10.1159/000518375 Agnihotri/Shah
 a b

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

c d

Fig. 8. a, b Invasive carcinoma of no special type (IAC V): loosely cohesive bizarre ductal epithelial cells with high
N/C ratio, hyperchromatic nuclei and prominent nucleoli (Toluidine blue, ×400; Papanicolaou, ×400). c, d. Pap-
illary carcinoma (IAC V): cellular smears comprising of jigsaw patterned tissue fragments with crowded epithe-
lial cells having enlarged nuclei and high N/C ratio (Papanicolaou, ×100 & ×400). IAC, International Academy
of Cytology.

cious and malignant cases, the performance of FNAB
went substantially up with 99.1% sensitivity and 99.3%
specificity. Incorporating suspicious for malignancy cas-
es in the comparison, the impact of ROSE was minimal
(Table 2).
The performance of FNAB against histopathology was
also analyzed with atypical cytology cases included (Ta-
ble 3). We re-analyzed the above scenarios and found that
cytopathology identified malignancies with an overall
80.5% sensitivity and 99.7% specificity, and NPV of
91.7%, and was substantially improved by ROSE (Ta-
ble 3). When we expanded the definition and compared
the performance of suspicious for malignancy and malig-
nant cases in correctly identifying in situ and malignant
histopathology, we noted a substantial increase in sensi-
tivity (92.4%), specificity (99.4%), and NPV (94.6%). Cas-
es subjected to ROSE again performed better on all met-
rics; however, the gain was smaller due to the inclusion of
atypical and suspicious for malignancy cases in the analy-
sis (Table 3).
Predicting the ROM
A crucial goal of breast cytology and histopathology is
to recognize malignancy in a timely and accurate fashion:
the PPV of the IAC categories yielding a diagnosis of in
situ or invasive carcinoma in histopathology was calcu-

Breast Cytopathology Performance: Acta Cytologica 2021;65:463–477 471

A Single Institute Experience DOI: 10.1159/000518375
Table 3. Performance of FNAB in detecting in situ and malignant histopathology, with “inadequate” cytopathology removed

Malignant cytopathology cases found malignant on Suspicious and malignant cytopathology cases found in situ
histopathology or malignant on histopathology
FNAB with FNAB without all FNAB, % FNAB with FNAB without all FNAB,
ROSE, % ROSE, % ROSE, % ROSE, % %

Sensitivity (95% CI) 91.9 (83.9–96.7) 74.4 (66.9–80.9) 80.5 (75.0–85.2) 96.6 (90.3–99.3) 90.2 (84.5–94.3) 92.4 (88.4–95.4)
Specificity (95% CI) 100 (97.4–100) 99.5 (97.3–100) 99.7 (98.4–100) 99.3 (96.1–100) 99.5 (97.2–100) 99.4 (97.9–99.9)
PPV 100 99.2 99.5 98.8 99.3 99.1
NPV 95.2 83.1 87.7 97.9 92.5 94.6
Accuracy 96.9 88.4 91.7 98.2 95.3 96.4
AUC (95% CI) 0.96 (0.93–0.98) 0.87 (0.83–0.90) 0.90 (0.87–0.92) 0.98 (0.95–0.99) 0.95 (0.92–0.97) 0.96 (0.94–0.97)

AUC, area under the curve; CI, confidence intervals; FNAB, fine-needle aspirate biopsy; NPV, negative predictive value; PPV, positive predictive value;
ROSE, rapid on-site evaluation.

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

a b

c d

Fig. 9. a, b Non-Hodgkin lymphoma (IAC V): dissociated large atypical lymphoid cells on a background of lym-
phoglandular bodies (Giemsa ×40; Papanicolaou, ×400). c, d Malignant phyllodes tumor (IAC V): atypical plump
spindle cells with marked atypia and tumor giant cells (Papanicolaou, ×400). IAC, International Academy of
Cytology

472 Acta Cytologica 2021;65:463–477 Agrawal/Kothari/Tummidi/Sood/

DOI: 10.1159/000518375 Agnihotri/Shah
Table 4. ROM observed under various cytopathological categories for detecting in situ and malignant histopathology

Cytology category FNAB with ROSE FNAB with ROSE FNAB without ROSE All FNAB
ROSE category Final category
cases (%) ROM (%) cases (%) ROM (%) cases (%) ROM (%) cases (%) ROM (%)

Inadequate 3 (1.3) 0 (0.0) 3 (1.3) 0 (0.0) 22 (5.7) 4 (18.2) 25 (4.1) 4 (16.0)

Benign 117 (51.1) 1 (0.9) 111 (48.5) 1 (0.9) 171 (44.5) 1 (0.6) 282 (46.0) 2 (0.7)
Atypical 23 (10.0) 1 (4.3) 30 (13.1) 2 (6.7) 43 (11.2) 15 (34.9) 73 (11.9) 17 (23.3)
Suspicious 8 (3.5) 7 (87.5) 6 (2.6) 5 (83.3) 28 (7.3) 27 (96.4) 34 (5.5) 32 (94.1)
Malignant 78 (34.1) 78 (100.0) 79 (34.5) 79 (100.0) 120 (31.3) 120 (100.0) 199 (32.5) 199 (100.0)

FNAB, fine-needle aspirate biopsy; ROM, risk of malignancy; ROSE, rapid on-site evaluation. Excluding nondiagnostic and lost to
follow up cases.

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

lated and stratified by the application of ROSE (Table 4).
There was a distinct rise in ROM across IAC categories
from inadequate to malignant, and ROSE enhanced this
gradient by minimizing potentially malignant cases in the
inadequate (0%), benign (0.9%), and atypical (4.3%) IAC
categories. In contrast, the specimens which did not un-
dergo ROSE showed a significantly higher ROM in inad-
equate (18.2%) and atypical (34.9%) categories (p < 0.001).
Quality Control Outcomes
A key metric in quality control is the false negative
(FN) rate and is due to operator failure due to poor local-
ization and poor FNAB technique of the sample or inabil-
ity of the pathologist to detect subtle cytopathological fea-
tures of malignancy. International guidelines recom-
mend that FN rates should be <5% [2, 3]. Our pathology
services performed well on this metric with a 0.71%
(2/282) FN rate, with only 2 cases benign by ROSE and/
or final cytopathology and malignant on histopathology
(Fig. 5c). These 2 cases had revealed fat necrosis from
deep-seated breast lumps. A high index of clinical-radio-
logical suspicion ensured that we confirmed these cases
with histopathology.
However, out of the total 749 cases that were catego-
rized as benign on FNAB, only 285 were followed up with
a CNB or excision biopsy based on their clinical-radiolog-
ical suspicions. Of these 285 cases, 282 could be con-
firmed as benign on CNB, but 3 cases were indeterminate
and lost to follow-up. In the remaining 464 cases the
FNAB and clinical-radiological findings were unequivo-
cally diagnostic of benign lesions and were not biopsied
and not followed up for potential FN lesions and late de-
velopment of malignancy in the same quadrant of the
breast. Hence, the FN rate of 0.71% reported in this study
represents only those benign lesions that underwent fur-
ther histopathology examination. An equally important
measure is the false positivity (FP) rate, representing
over-diagnosis and mandate careful auditing. Ideally, FP
rates should be <1% [2, 3], with our cases showing no ma-
lignant categorization on cytopathology to be benign on
histopathology (Fig. 5c).
There are considerable variations in the literature re-
garding insufficient/inadequate rates, which can be due
to the inexperience of FNAB operators, the varying mix
of patients, use of mammographic screening and type of
lesions (palpable or impalpable) vary from 0.7 to 47% [1,
7, 9]. We noted that 4.9% of the total 1,147 FNAB cases
in this study were inadequate and less (1.8%) with ROSE
(Fig. 4). Furthermore, 4.0% of FNAB that ultimately un-
derwent histopathology had been deemed inadequate
(Fig. 5c). We found 0.64% (4) cases with inadequate cy-
topathology to be malignant on histopathology, and 3.3%
(38) were suspicious for malignancy out of the total 1,147
cases. Of the cases which had histopathology, 5.9% had
been flagged as suspicious for malignancy (Fig. 5c). Of the
specimens that underwent ROSE, 3.2% were suspicious
for malignancy (Fig. 4) The ROM for atypical and suspi-
cious of malignancy cases were 23.2% and 94.1%, respec-
tively (Table 5), and are comparable to those previously
reported [2].
Discussion
Breast lumps are common in women of all ages and
breast cancer is the leading cause of cancer in women
worldwide. Breast cancer comprises 23% of cancer bur-
den worldwide, with 2.1 million new cases and 6,27,000
deaths annually [11–14]. FNAB and CNB, along with
mammography and clinical evaluation, form crucial parts

Breast Cytopathology Performance: Acta Cytologica 2021;65:463–477 473

A Single Institute Experience DOI: 10.1159/000518375
Table 5. A comparison of breast cytopathology performance guided by the IAC Yokohama System across recent studies

Madubogwu Arul et al. Montezuma Wong et al. Kamatar Panwar Present

et al. [37] [15] et al. [7] [9] et al. [17] et al. [4] study

Cases, n 180 523 3,625 3,696 470 225 1,147

Study duration, years 1 1.5 10 2.5 1.5 1 2.3
Inadequate, % 15.5 2.7 5.7 11.0 5.0 1.4 4.9
Benign, % 41.8 67.3 73.3 72.0 71.0 82.6 65.3
Atypical, % 4.5 5.2 13.7 4.3 1.0 5.8 7.8
Suspicious, % 3.6 7.8 1.6 2.2 2.0 1.8 3.3
Malignant, % 34.6 17.0 5.5 10.0 21.0 8.4 18.7
Histopathology follow-up, % 61.0 54.7 21.4 19.9 38.0 48.0 54.4
Cytopathology-histopathology concordance, % – – – – 93.2 93.0 90.2
Sensitivity, % 90.0 93.1 98.2 98.8 94.5 100 99.1
Specificity, % 95.5 99.0 54.7 99.4 98.9 97 99.3
PPV, % 94.7 97.6 68.2 96.4 98.5 – 99.1
NPV, % 91.3 97.0 98.6 97.6 95.7 – 99.3

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

Diagnostic accuracy, % 92.9 97.2 68.2 96.2 96.7 93 99.2
ROM
Inadequate, % 47.0 25.0 4.8 2.6 0.0 0.0 16.0
Benign, % 8.6 2.1 1.4 1.7 0.4 0.0 0.7
Atypical, % 40.0 18.0 13.0 15.7 66.0 0.0 23.3
Suspicious, % 50.0 95.0 97.0 84.6 83.0 75.0 94.1
Malignant, % 95.0 98.3 100 99.5 99.0 100 100

PPV, positive predictive value; NPV, negative predictive value; ROM, risk of malignancy.

of the “triple test” for diagnosing breast lumps [9]. FNAB
is sensitive and specific for diagnosing both benign and
malignant breast lesions [9, 10]. It can also reliably pick
up radiologically detectable nonpalpable lesions, and can
achieve sensitivities of up to 90–95% [1, 8, 15–17]. But
FNAB has its limitations and CNB is required to confirm
lesions, such as carcinoma in situ, calcifications, and pro-
liferative tumors [18–20]. However, CNB is not only
more invasive but also remains prohibitively expensive
and inaccessible in low-resource countries, like India [10,
21–23]. FNAB and CNB can complement each other de-
pending on the type of resources available at a health-care
facility, the economic constraints, the nature of a lesion,
the skill of the operator sampling the lesion, and the skill
of the pathologist examining the specimens [24, 25].
The introduction of ROSE and the IAC Yokohama
System for Reporting Breast FNAB Cytopathology have
structured and significantly improved the utility of FNAB
[1]. We studied the impact of these protocols in our breast
FNAB reporting and observed distinct improvements.
ROSE substantially improved the final diagnoses (Fig. 4)
and reduced the discordance between cytopathology and
histopathology (Fig. 5). ROSE significantly reduced inad-
equate sampling and the suspicious for malignancy cat-
egory (Table 1). ROSE reduced the financial burden and
inconvenience of patients from having to revisit. Overall,
ROSE was significantly helpful in ruling out malignant
lesions, but showed no significant improvement in ruling
in malignancy (Table 1). This reflects the spectrum of
breast cases which are predominantly benign with a
smaller proportion of malignancies. It also reflects a ten-
dency to err on the side of caution in our cytology report-
ing. Despite its better performance, a few cases did show
a mismatch between ROSE and the final cytopathology
and/or histopathology diagnosis. These were predomi-
nantly atypical and suspicious lesions, including 10 cases
of low-grade/benign phyllodes tumor which required re-
assignment at final reporting. Another 6 cases suspicious
for malignancy at ROSE were eventually found malignant
by final cytopathology and histopathology.
Breast cytopathology at our center showed overall
high sensitivity (86.1%) and specificity (99.6%) at diag-
nosing malignancies. Including ROSE in the workup,
substantially enhanced the sensitivity (92.9%) and speci-
ficity (100%) of cytopathology (Table 2). Expanding the
net by including both suspicious for malignancy and ma-
lignant cases raised the sensitivity (99.1%) of FNAB fur-
ther, with a specificity of 99.3%. However, with the inclu-
sion of suspicious for malignancy cases, ROSE contrib-
uted negligible improvement in picking up malignant

474 Acta Cytologica 2021;65:463–477 Agrawal/Kothari/Tummidi/Sood/

DOI: 10.1159/000518375 Agnihotri/Shah
cases. This indicates that ROSE helps weed out suspicious
and ambiguous cases early in the workflow (Table 2).
The IAC Yokohama System also helps monitor the
ROM in patients classified under different IAC catego-
ries, enabling the pathologist to better flag the cases that
would need further histopathology confirmation, and
also offer more robust recommendations to the treating
surgeons [1]. We found the ROM increase along a gradi-
ent from inadequate to malignant IAC categories (Ta-
ble 4). However, without ROSE, the ROM among inade-
quate cases jumped to 18.2%, while with ROSE it was
zero. Furthermore, ROSE shifted the ROM gradient
sharply toward the suspicious for malignancy and malig-
nant end of the IAC spectrum, which otherwise spilled
onto the atypical and inadequate categories without
ROSE (Table 4). This underscores the advantage of com-
bining ROSE and the IAC Yokohama System for moni-
toring and predicting the ROM.
The major performance metrics were FN rate (0.71%),
FP rate (0.0%), inadequate rate (4.9%), and suspicious for
malignancy rate (3.3%), and showed further improve-
ments in each of these parameters with ROSE. FNAB is
preferred to CNB partly because of financial and resource
constraints. FNAB is less reliable in the small number of
patients with deep-seated breast lumps surrounded by ex-
cessive fatty tissue, which are at risk of delayed and missed
diagnoses, and after thorough clinical-radiological evalu-
ation should be offered FNAB by an experienced operator
under ultrasound-guidance or immediate CNB [26].
A majority of our patients, including those financially
constrained, often travel several miles to access pathology
services. Even the few cases that get diagnosed as inade-
quate or inconclusive, are missed opportunities because
most of these patients fail to return for follow-up until
much later when the disease has advanced and/or has be-
come unmanageable. Such missed opportunities high-
light the importance of ROSE, regular monitoring of IAC
ROM rates, and early ultrasound-guided FNAB where
CNB is unaffordable.
Moving forward, harnessing long-term follow-up data
will be a goal at our center to bring out the true FN rates
in our patients and further strengthen our services. Be-
sides the above challenges that are unique to low-resource
countries, we also noticed the need to improve supervi-
sion and training of less experienced pathologists. Low-
grade phyllodes tumors are difficult to diagnose on cyto-
pathology, and all suspect cases should be reviewed and
confirmed by an experienced pathologist [10, 27]. Such
measures along with inclusion of ROSE can prevent de-
layed and missed diagnoses.
Breast Cytopathology Performance:
A Single Institute Experience
If a malignant FNAB diagnosis is in accordance with
clinical-radiological findings in the triple test, and mate-
rial is available in the cell block for prognostic markers,
neoadjuvant chemotherapy and surgery can be com-
menced [3, 28]. If the FNAB diagnosis does not correlate
with the clinical and imaging findings, then CNB or sim-
ple excision becomes mandatory [2, 23]. When lymph
nodes are palpable or suspicious on ultrasound, FNAB is
recommended to stage the patient [2, 29, 30].
We compared our findings with other studies and
found largely similar and a few divergent trends (Ta-
ble 5). Several studies have reported similar rates of in-
adequate samples (1.4–5.7%) as reported in our study
(overall 4.9%; 1.8% with ROSE) (Table 5) [4, 7, 15, 17,
31–33]. However, a few studies had recorded much high-
Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024
er rates of inadequate samples (11.0–15.5%) [9, 34, 35].
The IAC Reporting System recommends that operators
should aim for an inadequate sample rate of <5.0%,
which should be even lower if ROSE is implemented [3,
7, 9, 35, 36]. The proportion of benign cases (65.3%) in
our cohort was also similar to that observed in various
studies (41.8–82.6%) (Table 5) [3, 7, 9, 11, 13, 37]. Among
benign cases, fibroadenomas comprised 58.1% of total
cases, which was similar to that noted by previous stud-
ies, 48.8–67.7% [38–40]. Follow-up histopathology was
not required for most benign cases, especially if the pa-
tient was negative on clinical-radiological evaluation for
>6–12 months [3, 41]. The proportion of atypical (7.8%)
and suspicious (3.3%) cases in our study were similar to
that observed in other studies [4, 7, 9, 15, 17, 37], except
a few studies where such cases were recorded in higher
proportions, 10.4–13.7% atypical cases and 9.3–11.0%
suspicious for malignancy cases [4, 34, 42, 43]. The pro-
portion of malignant lesions varied across studies, pos-
sibly reflecting the type of patients being cared for by the
respective centers (Table 5). The overall performance of
cytopathology in accurately diagnosing in situ and ma-
lignant breast lesions in our study was similar [4, 9,15,
17] to better [7, 37] than that observed in contemporary
studies (Table 5).
Conclusion
Our study shows that incorporating the IAC Yokoha-
ma System for Reporting Breast FNAB Cytopathology
with ROSE can improve early and accurate diagnosis of
breast lesions, prevent missed diagnoses, and provide re-
liable estimates of ROM in a given patient population.
This is especially important for low- and middle-income
Acta Cytologica 2021;65:463–477 475
DOI: 10.1159/000518375
countries where CNB is an expensive option. Our results
also demonstrate that these protocols can help create a
standardized and reproducible system for monitoring
and auditing of breast pathology services, which can help
identify the areas that need strengthening and improve
the training being delivered at pathology centers.
Statement of Ethics
Written informed consent was taken from all patients for the
procedure of fine-needle aspiration biopsy. The retrospective anal-
ysis was undertaken after approval from the Institutional Ethics
Committee on human research (EC/OA -150/2019).
Funding Sources
This study received no funding from any source.
Author Contributions
N.A. and K.K. conceptualized and designed the study, per-
formed literature search, and carried out the clinical study. S.T.
carried out data collection, clinical study, preliminary data analy-
sis, and wrote the manuscript. P.S. carried out formal data analysis,
visualization, study design, and wrote the manuscript. M.A. and
V.S. assisted in study design and literature search. All the authors
contributed to the final review and editing of the manuscript.

Data Availability Statement

Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024

Conflict of Interest Statement
All data generated or analyzed during this study are included
The authors declare no conflicts of interest. in this article. Further inquiries can be directed to the correspond-
ing author.

References
1 Field AS. Breast FNA biopsy cytology: current
problems and the International Academy of
Cytology Yokohama standardized reporting
system. Cancer Cytopathol. 2017;125(4):229–
30.
2 Singh N, Wells CA. Assessment of accuracy in
breast cytology. Cytopathology. 2001; 12(4):
211–8.
3 Field AS, Raymond WA, Schmitt F, editors.
The International Academy of Cytology Yo-
kohama system for reporting breast fine nee-
dle aspiration biopsy cytopathology. Switzer-
land: Spinger Nature; 2020.
4 Panwar H, Ingle P, Santosh T, Singh V, Buga-
lia A, Hussain N. FNAC of breast lesions with
special reference to IAC standardized report-
ing and comparative study of cytohistological
grading of breast carcinoma. J Cytol. 2020;
37(1):34–9.
5 Mathur P, Sathishkumar K, Chaturvedi M,
Das P, Sudarshan KL, Santhappan S; ICMR-
NCDIR-NCRP Investigator Group, et al.
Cancer statistics, 2020: report from National
Cancer Registry Programme, India. JCO Glob
Oncol. 2020;6:1063–75.
6 Globocan 2018: India factsheet – India Against
Cancer. Available from: cancerindia.org.in.
7 Montezuma D, Malheiros D, Schmitt FC.
Breast Fine needle aspiration biopsy cytology
using the newly proposed IAC Yokohama
system for reporting breast cytopathology:
the experience of a single institution. Acta Cy-
tol. 2019;63:1–6.
8 Kothari K, Tummidi S, Agnihotri M, Sathe P,
Naik L. This ‘rose’ has no thorns-diagnostic
utility of ‘rapid on-site evaluation’ (rose) in
fine needle aspiration cytology. Indian J Surg
Oncol. 2019;10(4):688–98.
9 Wong S, Rickard M, Earls P, Arnold L, Bako
B, Field AS. The International Academy of
Cytology Yokohama System for reporting
breast fine needle aspiration biopsy cytopa-
thology: a single institutional retrospective
study of the application of the system catego-
ries and the impact of rapid onsite evaluation.
Acta Cytol. 2019;63(4):280–91.
10 Tummidi S, Kothari K, Agnihotri M, Nail L,
Sood P. Fibroadenoma versus phyllodes tu-
mor: a vexing problem revisited. BMC Can-
cer. 2020;20(1):648–60.
11 Colditz G, Chia KS. Invasive breast carcinoma:
introduction and general features. In: Lakhani
SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver
MH, editors. WHO classification of tumours of
the breast. 4th ed. Lyon: IARC. p. 14–31.
12 https: //www.who.int/cancer/prevention/di-
agnosis-screening/breastcancer.
13 Gupta S. Breast cancer: Indian experience,
data, and evidence. South Asian J Cancer.
2016;5(3):85–6.
14 Malvia S, Bagadi SA, Dubey US, Saxena S. Ep-
idemiology of breast cancer in Indian women.
Asia Pac J Clin Oncol. 2017;13(4):289–95.
15 Arul P, Masilamani S. Application of Nation-
al Cancer Institute recommended terminol-
ogy in breast cytology. J Cancer Res Ther.
2017;13(1):91–6.
16 Chakrabarti I. FNAC versus CNB: who wins
the match in breast lesions? J Cytol. 2018
JulSep;35(3):176–8.
17 Kamatar PV, Athanikar VS, Dinesh U. Breast
fine needle aspiration biopsy cytology report-
ing using international academy of cytology
yokohama system-two year retrospective
study in tertiary care centre in Southern India.
Njlm. 2019;8(4):PO01–3.
18 Saha A, Mukhopadhyay M, Das C, Sarkar K,
Saha AK, Sarkar DK. FNAC versus core nee-
dle biopsy: a comparative study in evaluation
of palpable breast lump. J Clin Diagn Res.
2016;10(2):EC05–8.
19 Mitra S, Dey P. Fine-needle aspiration and
core biopsy in the diagnosis of breast lesions:
a comparison and review of the literature. Cy-
tojournal. 2016;13:18.
20 Moschetta M, Telegrafo M, Carluccio DA,
Jablonska JP, Rella L, Serio G, et al. Compari-
son between fine needle aspiration cytology
(FNAC) and core needle biopsy (CNB) in the
diagnosis of breast lesions. G Chir. 2014;
35(7–8):171–6.
21 Tikku G, Umap P. Comparative study of core
needle biopsy and fine needle aspiration cy-
tology in palpable breast lumps: scenario in
developing nations. Turk Patoloji Derg. 2016;
32(1):1–7.
22 Mitra SK, Rajesh R, Mishra RK, Rai P, Va-
hikar S, Singhal P. Comparative evaluation of
FNAC, core needle biopsy and excisional bi-
opsy in subtyping of breast lesions. J Path Mi-
cro. 2016;2(1):9–15.
23 Joshi M, Reddy SJ, Nanavidekar M, Russo JP,
Russo AV, Pathak R. Core biopsies of the
breast: diagnostic pitfalls. Indian J Pathol Mi-
crobiol. 2011;54(4):671–82.
24 Nassar A. Core needle biopsy versus fine nee-
dle aspiration biopsy in breast: a historical
perspective and opportunities in the modern
era. Diagn Cytopathol. 2011;39(5):380–8.
25 Ljung BM, Drejet A, Chiampi N, Jeffrey J,
Goodson WH 3rd, Chew K, et al. Diagnostic
accuracy of fine-needle aspiration biopsy is
determined by physician training in sampling
technique. Cancer. 2001;93(4):263–8.

476 Acta Cytologica 2021;65:463–477 Agrawal/Kothari/Tummidi/Sood/

DOI: 10.1159/000518375 Agnihotri/Shah
26 Farras Roca JA, Tardivon A, Thibault F, El
Khoury C, Alran S, Fourchotte V, et al. Diag-
nostic performance of ultrasound-guided
fine-needle aspiration of nonpalpable breast
lesions in a multidisciplinary setting: the in-
stitute curie’s experience. Am J Clin Pathol.
2017;147(6):571–9.
27 Field AS, Schmitt F, Vielh P. IAC standard-
ized reporting of breast fine-needle aspiration
biopsy cytology. Acta Cytol. 2017;61(1):3–6.
28 Schmitt F, Vielh P. Fine-needle aspiration cy-
tology samples: a good source of material for
evaluating biomarkers in breast cancer. His-
topathology. 2015;66(2):314–5.
29 Gibbons CE, Quinn CM, Gibbons D. Fine-
needle aspiration biopsy management of the
axilla in primary breast carcinoma. Acta Cy-
tol. 2019;63(4):314–8.
30 Boughey JC, Moriarty JP, Degnim AC, Gregg
MS, Egginton JS, Long KH. Cost modeling of
preoperative axillary ultrasound and fine-
needle aspiration to guide surgery for invasive
breast cancer. Ann Surg Oncol. 2010; 17(4):
953–8.
31 Modi P, Haren O, Jignasa B. FNAC as preop-
erative diagnostic tool for neoplastic and non-
neoplastic breast lesions: a teaching hospital
experience. Indian J Med Res. 2014;4:274–8.
Breast Cytopathology Performance:
A Single Institute Experience
32 Haobam S, Thiyam U, Sharma DC. Cytomor-
phologic Al study of breast lesions with so-
nomammographic correlation. J Evol Med
Dent. 2015;4(81):14137–42.
33 Nguansangiam S, Jesdapatarakul S, Tangjit-
gamol S. Accuracy of fine needle aspiration
cytology from breast masses in Thailand.
Asian Pac J Cancer Prev. 2009;10(4):623–6.
34 Bajwa R, Tariq Z. Association of fine needle
aspiration cytology with tumor size in palpa-
ble breast lesions. Biomedica. 2010;26:124–9.
35 Hoda R, Brachtel E. International Academy of
Cytology-Yokohama System for reporting
breast fine-needle aspiration biopsy cytopa-
thology: a review of predictive values and
risks of malignancy. Acta Cytol. 2019; 63(4):
292–301.
36 Field AS, Zarka MA. Breast. In: Field AS,
Zarka MA, editors. Practical cytopathology: a
diagnostic approach to fine needle aspiration
biopsy. Amsterdam: Elsevier; 2017 Chap. 5.
37 Madubogwu CI, Ukah CO, Anyanwu S, Chi-
anakwana GU, Onyiaorah IV, Anyiam D.
Sub-classification of breast masses by fine
needle aspiration cytology. Eur J Breast
Health. 2017;13(4):194–9.
Acta Cytologica 2021;65:463–477
DOI: 10.1159/000518375
38 Singh A, Haritwal A, Murali B. Pattern of
breast lumps and diagnostic accuracy of fine
needle aspiration cytology; a hospital-based
study from Pondicherry, India. Internet J
Pathol. 2010;11(2):1–6.
39 Muddegowda PH, Lingegowda JB, Kurpad R,
Konapur P, Shivarudrappa A, Subramaniam
P. The value of systematic pattern analysis in
FNAC of breast lesions: 225 cases with cyto-
histological correlation. J Cytol. 2011; 28(1):
13–9.
40 Challa VR, Yale Guru BG, Rangappa P, Desh-
mane V, Gayathri DM. Cytological and path-
ological correlation of fnac in assessing breast
lumps and axillary lymph node swellings in a
public sector hospital in India. Patholog Res
Int. 2013;2013:695024.
41 Singh N, Wells CA. Invited review: assess-
ment of accuracy in breast cytology. Cytopa-
thology. 2001;12(4):211–8.
Downloaded from http://karger.com/acy/article-pdf/65/6/463/3899281/000518375.pdf by guest on 01 March 2024
42 Sneige N. Utility of cytologic specimens in the
evaluation of prognostic and predictive fac-
tors of breast cancer: current issues and future
directions. Diagn Cytopathol. 2004; 30(3):
158–65.
43 al-Kaisi N. The spectrum of the “gray zone” in
breast cytology. A review of 186 cases of atyp-
ical and suspicious cytology. Acta Cytol. 1994;
38(6):898–908.
477