Cyto-Morphological Correlation of Indeterminate C3 (Atypical) and C4 (Suspicious) Categories in Fine Needle Aspiration Cytology of the Breast


In 1996, to harmonize the reporting system of breast lesions on fine-needle aspiration cytology (FNAC), National Cancer Institute (NCI) proposed five categories from C1-C5. C3 and C4 categories are noted to be ambiguous during histopathological correlation, hence “grey-zoned.” There have been limited researches regarding its usefulness and its histopathological correlation. This study was undertaken to evaluate C3 and C4 categories and to correlate with histopathological examination. This perspective and retrospective study was undertaken for two years. Forty cases of C3 and 32 cases of C4 were retrieved from a total of 602 cases of breast FNAC. Histopathological follow-up and correlation were available in 30 cases of C3 and 15 cases of category C4 and were selected for further study. On the histopathological correlation of the C3 category, 22 (73.3%) cases turned out to be benign, and 8 (26.7%) cases revealed malignant diagnosis, and among the C4 category, 2 (13.3%) cases revealed benign findings, and 13(86.7%) of the cases showed malignancy. This difference was statistically significant (P<0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the C4 category in the diagnosis of malignancy were 61.9%, 91.6%, 86.6%, and 73.3%, respectively. FNAC is a simple, rapid, cost-effective, and accurate method to diagnose easily accessible breast swellings. However, one should be aware of its limitations as well. Our study supports maintaining C3 and C4 categories, as there was a statistically significant difference in benign & malignant diagnosis for these categories.


1. Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017;13:289-95.
2. Kocjan G. Needle aspiration cytology of the breast: Current perspective on the role in diagnosis and management. Acta Med Croatica 2008;62:391-401.
3. The uniform approach to breast fine-needle aspiration biopsy. National Cancer Institute Fine-Needle Aspiration of Breast Workshop Subcommittees. Diagn Cytopathol 1997;16:295-311.
4. Howell LP. Equivocal diagnoses in breast aspiration biopsy cytology: Sources of uncertainty and the role of “atypical/indeterminate” terminology. Diagn Cytopathol 1999;21:217-22.
5. Kanhoush R, Jorda M, Gomez-Fernandez C, Wang H, Mirzabeigi M, Ghorab Z, Ganjei‐Azar P. Atypical and suspicious diagnoses in breast aspiration cytology-is there a need for two categories? Cancer 2004;102:164-7.
6. Kalhan S, Dubey S, Sharma S, Dudani S, Preeti, Dixit M. Significance of nuclear morphometry in cytological aspirates of breast masses. J Cytol 2010;27:16-21.
7. Shabb NS, Boulos FI, Abdul-Karim FW. Indeterminate and erroneous fine-needle aspirates of breast with focus on the ‘true gray zone’: A review. Acta Cytol 2013;57:316-31.
8. Bansal C, Pujani M, Sharma KL, Srivastava AN, Singh US. Grading systems in the cytological diagnosis of breast cancer: A review. J Can Res Ther 2014;10:839-45.
9. Madan M, Sharma M, Piplani S, Manjari M, Sharma N, Goyal S. Evaluation of fine needle aspiration cytology in the diagnosis of suspicious/gray zone lesions in breast lesions and its histopathological correlation. Ann Pathol Lab Med 2016;3:A573-6.
10. Yusuf I, Atanda AT, Imam MI. Cyto-morphologic correlation of equivocal C3 and C4 breast lesions. Arch Int Surg 2014;4:131-5.
11. Kumar R. A Clinicopathologic study of breast lumps in Bhairahwa, Nepal. Asian Pac J Cancer Prev 2010;11:855-8.
12. Rahman MZ, Islam S. Fine needle aspiration cytology of palpable breast lump: A study of cases. Surgery: Current Research 2013;S12:001.
13. Nguansangiam S, Jesdapatarakul S, Tangjitgamol S. Accuracy of fine needle aspiration cytology from breast masses in Thailand. Asian Pac J Cancer Prev 2009;10:623-6.
14. Chaiwun B, Settakorn J, Ya-in C, Wisedmongkol W, Rangdaeng S, Thorner P. Effectiveness of fine-needle aspiration cytology of breast: Analysis of 2,375 cases from northern Thailand. Diagn Cytopathol 2002;26:201-5.
15. Chaiwun B, Sukhamwang N, Lekawanvijit S,Sukapan K, Rangdaeng S, Muttarak M. Atypical and suspicious categories in fine needle aspiration cytology of the breast: histological and mammographical correlation and clinical significance. Singapore Med J 2005;46:706-9.
16. Deb RA, Matthews P, Elston CW, Ellis IO, Pinder SE. An audit of equivocal (C3) and suspicious (C4) categories in fine needle aspiration cytology of the breast. Cytopathology 2001;12:219-26.
17. Goyal P, Sehgal S, Ghosh S, Aggarwal D, Shukla P, Kumar A, et al. Histopathological correlation of atypical (C3) and suspicious (C4) categories in fine needle aspiration cytology of breast. Int J Breast Cancer 2013;2013:965498.
18. Arul P, Masilamani S, Akshatha C. Fine needle aspiration cytology of atypical (C3) and suspicious (C4) categories in the breast and its histopathologic correlation. J Cytol 2016;33:76-9.
19. Khan A, Jamali R, Jan M, Tasneem M. Correlation of fine needle aspiration cytology and histopathology diagnosis in the evaluation of breast lumps. Int J Med Stud 2014;2:40-3.
20. Yeoh GP, Chan KW. Fine needle aspiration of breast masses: An analysis of 1533 cases in private practice. Hong Kong Med J 1998;4:283-8.
21. Silverman JF, Saad RS. Breast. In: Bibbo M, Wilbur D, eds. ComprehensiveCytopathology. 3rd ed. Philadelphia, PA: Saunders Elsevier, 2008:713-72.
22. Mitra S, Dey P. Grey zone lesions of breast: Potential areas of error in cytology. J Cytol 2015;32:145‐52.
23. Kachewar SS, Dongre SD. Role of triple test score in the evaluation of palpable breast lump. Indian J Med Paediatr Oncol 2015;36:123-7.
24. Stanley MW, Tani EM, Skoog L. Fine-needle aspiration of fibroadenomas of the breast with atypia: A spectrum including cases that cytologically mimic carcinoma. Diagn Cytopathol 1990;6:375-82.
25. Bhattarai S, Kapila K, Verma K. Phyllodes tumor of the breast. A cytohistologic study of 80 cases. Acta Cytol 2000;44:790-96.
IssueVol 59, No 3 (2021) QRcode
Fine-Needle aspiration cytology (FNAC) Histopathological correlation Benign Malignant

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DIXIT N, BANSAL V, BHARTI R, SHARMA P. Cyto-Morphological Correlation of Indeterminate C3 (Atypical) and C4 (Suspicious) Categories in Fine Needle Aspiration Cytology of the Breast. Acta Med Iran. 59(3):148-154.