Application of National

Cancer Institute
recommended terminology in
breast cytology

Department of Pathology, Dhanalakshmi Srinivasan Medical College and

Hospital, Siruvachur, Perambalur, Tamil Nadu, India
INTRODUCTION
• Lack of uniformity with regard to the reporting terminology used in breast
cytology by pathologists worldwide miscommunication of results among
health-care providers.
• Fine-needle aspiration cytology (FNAC) valuable tool in the preoperative
assessment of breast masses
• it shows high sensitivity, specificity, and accuracy. 
• minimal to no morbidity, useful for evaluation of local chest wall recurrences, and
allowed to do ancillary techniques, namely, hormone receptor analysis, flow
cytometry, and molecular studies.
• One of the major goals of FNAC is to differentiate benign from malignant lesions.
• However, in certain instances, differentiation of benign from malignant lesion is
not possible due to significant overlap on smears
• (in cases of fibroadenoma and proliferative breast diseases and atypical hyperplasia and
low-grade carcinoma in situ, or in papillary lesions) and
 AIM OF STUDY
• To bring a degree of uniformity to the reporting terminology, the
National Cancer Institute (NCI) proposed five diagnostic categories,
namely,
• unsatisfactory (C1), benign (C2), atypical, probably benign (C3), suspicious,
favor malignancy (C4), and malignant (C5) in 1996.
•  To evaluate the utility and diagnostic accuracy of FNAC in the
evaluation of breast lesions using the NCI recommended terminology
by correlating with histopathological results.
 MATERIALS AND METHODS
• Prospective study  May 2014 and December 2015
•  Total of 523 FNACs were evaluated by pathologists.
• Categorized into C1, C2, C3, C4, and C5 using NCI guidelines proposed in
1996.
• Among 523 patients,
• 286 (54.7%) undergone surgical intervention either by biopsy or mastectomy.
Histopathological examination of these specimens was done, and the results were
compared with cytological diagnoses. The C1 results were excluded from the analysis.
• Patients with C2 and C3 diagnosed by FNAC but diagnosed as malignant lesions on
histopathological examination was considered as false negative, and
• patients with C4 and C5 diagnoses by FNAC but diagnosed as benign lesions on
histopathological examination was considered as false positive.
RESULTS
False positive case - category C5 turned out to be benign. (a) Cytosmear showing discohesive cluster with moderate
nuclear atypia diagnosed as malignant (H and E, ×400). (b) Subsequent histopathological section revealing compressed
ducts surrounded by fibrotic stroma confirmed as fibroadenoma (H and E, ×400)
• The present study showed
• sensitivity of 93.1% (95% CI, 88.2%–95%),
• specificity of 99% (95% CI, 96.8%–99.8%),
• PPV of 97.6% (95% CI, 92.5%–99.6%),
• NPV of 97% (95% CI, 94.9%–97.8%), and
• accuracy of 97.2% for FNAC in the diagnosis of malignant lesions.
• The false positive and false negative rate was 1% and 6.9%, respectively.
 DISCUSSION
• Many countries have now adopted triple approach which comprised clinical breast
examination, imaging (mammography and/or ultrasound) with FNAC as the first-line
pathological investigation in both screening and in symptomatic patients.
• Pathological characterization still plays an essential role in the evaluation of breast
lesions.
• Even though simple, safe, quick, and cost-effective, the role of FNAC has been
challenged of late by results attained by CNB that seems more robust than former.
• CNB is more reliable than FNAC and less invasive than surgical biopsy and allows
clinicians to plan therapeutic treatment certain complications
• FNAC is an easy and safe procedure FNAC maintains tactile sensitivity, allows
multidirectional passes allowing a broader sampling of lesion, and immediate
reporting whenever necessary
•  Categories C1, C2, and C5 comparable to frequencies found by
most of the published studies.
• However, percentages of C3 and C4 were slightly higher than few
studies. This could be due to the level of caution employed by the
pathologists in diagnosing atypical lesions in different settings.
• C3- benign aspirate + combination of nuclear pleomorphism, some loss of cellular
cohesiveness, or nuclear and cytoplasmic changes, and
• C4, if smears showing some atypical cellular features but without definite evidences of
malignancy or aspirate showing some malignant features of greater than those observed
in C3 after clinico-radiological correlation.
• Inadequate rate  nature of the lesion, available technology, experience, and skill of operator.
• nature of lesion (68%) was the most common cause f/b experience of the aspirator (32%) for inadequacy rate.
• C1 consisted of 14 (2.7%); this could be due to nature of the lesions either cystic or sclerotic
breast lesions.
• Categories C2 and C5  diagnostic accuracy. The present study (97.9% and 98.4%).
• Interpretation of C3 and C4 are difficult and confusing because they do not have strict criteria for
diagnosis.
• Stratification of cases C3 and C4 is beneficial either benign (C3) or malignant (C4) outcomes.
• Clubbing of C3 and C4 as a single term called equivocal  CNB or surgical biopsy should be done
for this combined category as the incidence of malignancy is significant in both subgroups.
• Benign outcomes of 47%–87% with C3 and malignant outcomes of 72%–87% with C4 patients
mostly.
• Moreover, C3 still have malignancy in 13%–53% and C4 have benignancy in 13%–28% patients.
• Current study showed 81.8% benign lesions with C3 and 95.2% malignancy with C4, aurthor feel
that it is still useful to maintain the categories C3 and C4 separately.
• False –ve rate6.9% and false positive rate of 1%.
• 3 cases of IDC-NOS underdiagnosed as fibroadenoma
• 1 case of ILC -- fibrocystic disease in C2
• 2 cases of IDC-NOS -- C3 on FNAC, contributing to false negative results.
• Factors --false negative results
• small size of the lesion,
• hypocellularity, and inadequate sampling during aspiration,
• histological tumor types such as low nuclear grade ILC, scirrhous carcinoma,
and well-differentiated intracystic carcinoma.
• sampling error, particularly in small tumor. 
• sclerosed fibroadenoma may not yield sufficient cells to allow a diagnosis by
FNAC. 
• Resemblance of ILC to lymphocytes and its subtle cytological atypia are well-
known diagnostic problems
•  1- C4 and C5 was diagnosed as benign (fibroadenoma) on
histopathology false +ve.
• Fibroadenoma highest false positive and false negative diagnoses.
• cellular discohesiveness and marked pleomorphism leading to wrong
diagnoses of atypical or malignant lesions,as seen in the present study.
• Limitations: atypical ductal hyperplasia, low-grade DCIS, tubular
carcinoma, and some special types of invasive carcinoma can be
difficult.
• carcinoma in situ VS invasive carcinoma CNB is superior to FNAC,