Introduction:

Breast lesions in women usually call for medical attention. Most of the breast lesions are benign, albeit currently, breast is the leading site of cancer and cancer related mortality throughout the world and now in India. [1,2] Early and accurate diagnosis of these lesions is critical for selecting appropriate treatment and predicting treatment outcome.

Breast lesions encompass a myriad of morphological entities ranging from non neoplastic, benign to malignant lesions. The standard triple approach for managing patients with breast lump include clinical examination, mammography and biopsy. Despite tru cut biopsy being considered as an integral part of triple test, its utility is limited in resource poor settings. Breast fine needle aspiration cytology (FNAC) has a long history of providing accurate, rapid and cost-effective diagnosis of palpable breast lesions. In resource limited set ups, FNAC still has a major role to play in treatment decisions. [3] Similarly, over recent years, tru cut biopsy has been replaced by FNAC taking into consideration, the feasibility and simplicity of the test. [4,5]

Recently, International Academy of Cytology (IAC) at Yokohama proposed a new reporting system for breast cytology, in order to bring uniformity across the globe.[6] Any new classification system needs to be validated for its practical applicability.

The present study was conducted with the objective to categorize the breast lesions as per this classification and to determine the risk of malignancy in each category as well as the diagnostic efficacy.

Materials and Methods:

The present study was a cross sectional observational analytical study conducted over a duration of two years from January 2020 up to December 2022 in the department of Pathology, Adichunchanagiri Institute of Medical Sciences, BG Nagara, Mandya, Karnataka. Institutional Ethics Committee clearance was obtained. Sampling method adopted was convenient sampling, All consecutive cases presenting with breast lesions in whom FNAC was done in cytopathology during the study period were included in the study. Cases with history of recurrent malignancy, or on chemotherapy/radiotherapy were excluded from the study. Sample size was 296. Demographic details related to each case like age, gender, clinical history, past history, treatment history if any, ultrasound findings if available were obtained from the case records. All 296 FNAC cases were reclassified according to the newly proposed IAC Yokohama reporting system. Histologic samples were considered the gold standard and were available in 88 cases (21.4%).

Statistical analysis:

Statistical analysis was executed using Microsoft Excel 2011. Standard descriptive analysis was performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy ratios were calculated. The risk of malignancy (ROM) was defined for each category as the number of confirmed malignant cases /total number of cases in each diagnostic category. All the suspicious and malignant cases were considered as positive for malignancy. The cases with insufficient material were excluded from statistical analysis.

Results

FNAC of 296 cases were reviewed. Mean age of the patients in the present study was 44 ± 3.2 years. All the cases were females except one being male, with female to male ratio of 20:1. More number of cases presented with lesion in the right breast with a ratio of left to right sided lesion being 1: 2.09. All the cases were unifocal at presentation.

The distribution of cases in individual cytodiagnostic categories as described by Yokohama et al is shown in Table 1. Insufficient material was obtained in 13/296 (4.39%) cases. Benign category included 196/296 (66.21%) cases. 31/296 (10.47%) cases were categorized as atypia. The suspicious category included 4/296 (10.47%) cases, while malignant category included 52/296 (17.56%) cases. In the suspicious category, suspicious for low grade malignancy and suspicious for epithelial malignancy were the diagnosis rendered in 0.67% cases respectively. In malignant category, invasive ductal carcinoma-not otherwise specified was diagnosed in 6.75% cases and ductal carcinoma in 10.81% cases.

Among 31 cases included under atypical category, maximum cases were diagnosed as proliferative breast disease with atypia (8/31) followed by usual ductal hyperplasia with fibroadenoma (6/31). Table 2 shows the breakup of cases in category III.

Graph 1: Showing the distribution of cases in the category III

Out of total 88 (21.4%) cases for which histopathology was available, concordance between FNAC and histopathology diagnosis was obtained in 82 (93.18%) cases, while discordance was noted in 6(6.81%) cases. There were five false negative (1.66%) and one false positive case (0.33%). Table 3 shows histopathologic correlation among 88 cases. Risk of malignancy in each category is shown in Table 4. Atypia and suspicious for malignancy category had ROM of 71.4% and 100% while in malignant category ROM was 96.66%.

Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy was found to be 85.71%, 98.11%, 96.55%, 91.23% and 93.02% respectively.

Discussion

In the present study, we retrospectively classified 296 cases as per the recent IAC Yokohama system, into the five categories and determined the ROM for each category. These categories included insufficient, benign, atypical, suspicious for malignancy and malignancy. The category I, insufficient or inadequate category, included cases wherein the smears show sparse cellularity or which showed drying artifact or hemorrhage obscuring the cellular details. In the present study 4.39% cases had insufficient material. This was in concordance with the reports of Diana M et al and Sunita H et al. [7,8] Bajwa R et al reported slightly higher rate of 13.6% of category I cases. [9] Risk of malignancy was 0% in this category, in the present study, similar to that reported by Poornima et al. [10]

In the present study, 66.21% of the cases were placed in category II, i.e, benign, which was in concordance with that reported by Diana M (73.38%) and Wong S (72%). [7,11] Maximum number of cases in the present study were benign, akin to that reported in literature. [8-11] The most common benign lesion reported in the present study was fibroadenoma (28.06%), followed by benign breast disease (20.40%), fibrocystic change (15.81%), acute mastitis (6.75%) and granulomatous mastitis (3.57%). The spectrum of inflammatory lesions along with lactational changes in shown in Figure 1. Other studies in the literature also observed fibroadenoma as the most common lesion diagnosed in this category. In 55 cases of fibroadenoma, histopathology was obtained and all of these were concordant with the initial FNA diagnosis. ROM in this category was 0.01% in the benign category. Rosa FD et al reported similar ROM for this category. [12]

Fig 1: Smears show neutrophils in acute mastitis. (Hematoxylin and Eosin, x 100) B. Lymphocyte rich smears in chronic mastitis. (Hematoxylin and Eosin, x 400) C. Smears show multinucleate giant cells and epitheloid cells in a mixed inflammatory background in granulomatous mastitis. (Hematoxylin and Eosin, x 100) D. Smear shows foamy histiocytes in a lipid rich background in lactational change. Inset shows bare nuclei with prominent nucleoli (Giemsa, x 100)

Fig 2: Smears show ductal cells with mild nuclear atypia in a case of proliferative breast disease with atypia. (Hematoxylin and Eosin, x 100) B. Smears show ductal cells with holes proliferative breast disease without atypia.(Hematoxylin and Eosin, x 400) C. Smears show stromal fragments with high cellularity from a case of benign phylloides tumor (Hematoxylin and Eosin, x 100) D. Smear shows stromal fragments from a case of benign phylloides tumor showing characteristic condensation of the nuclei beneath the peripheral margin (Giemsa, x 100)

In the present study, 10.47% cases were placed in category III, i.e., atypical category. (Figure 2) This was in accordance with that reported by Rossa FD et al. [12] The prevalence of atypia show a wide range across the literature, from 1% to 13%. The presence of this category which accommodates low risk indeterminate lesions helps cytopathologists avoid diagnostic errors by preventing overdiagnosis in lesions which are predominantly benign with occasional worrisome features and reducing false negative diagnosis. [12] In this category, as shown in graph 1, most common lesions included showed hyperplasia in the form of three dimensional overlapping sheets, holes and swirls. Proliferative disease with atypia were also noted along with one case of spindle cell lesion. This spindle cell lesion was a case with a provisional clinical diagnosis of melanoma, since the lesion was pigmented. FNAC smears of this lesion showed short fascicles of uniform spindle cells showing vague storiform architecture, pigment, touton giant cells and foamy histiocytes. At FNAC a diagnosis of benign spindle cell neoplasm, favouring benign fibrous histiocytoma was made, which was confirmed by subsequent histopathology. (Figure 3) ROM in the present study, in atypical category was 71.4% which was quite high as compared to that in the literature (20.7% to 38%). [13] The high ROM in our study could be due to inclusion of two cases of phylloides tumor in this category, both of which were malignant at histopathology.

Fig 3: Smears show spindle cells in short fascicles  cells with mild nuclear atypia in a case of proliferative breast disease with atypia. (Hematoxylin and Eosin, x 100) B. Smears show ductal cells with holes proliferative breast disease without atypia.(Hematoxylin and Eosin, x 400) C. Smears show stromal fragments with high cellularity from a case of benign phylloides tumor (Hematoxylin and Eosin, x 100) D. Smear shows stromal fragments from a case of benign phylloides tumor showing characteristic condensation of the cells beneath the peripheral margin (Giemsa, x 100)

In the present study, suspicious category included 1.35%. which was similar to that reported by Diana et al, Wong et al and Panwar et al. [7,11,14] However in studies conducted by Modi et al, Bajwa et al Sunita et al and Georgieva et al, authors reported higher number of cases in this category as 6.5%, 9.3%,6.5% and 5.3% respectively. [15-18] The ROM in the suspicious category in the present study was 100%. Similar findings were reported by Tejaswini et al and Monetzuma et al. [7,19] while Hoda et al and Wang et al reported a slightly lower ROM of 85.4% and 84.6% respectively. [11,20]

Malignant category included 17.56% cases in the present study, concurrent with that reported in the literature. ROM in the malignant category in the present study was 100%, similar to that reported by Panwar et al, Hoda et al, Montezuma et al and Wang et al reported a similar ROM of 100%, 98.7%,100% and 99.5% respectively in this category. [7,11,14,20]

Surgery was performed in total 88 (21.4%) cases in the present study. Concordance between FNAC and histopathology diagnosis was obtained in 82 (93.18%) cases, while discordance was noted in 6 (6.81%) cases. There were five false negative (1.66%) and one false positive case (0.33%).

The comparison of sensitivity, specificity, positive predictive value, and negative predictive value of the present study with that reported in the literature, when IAC Yokahama system was applied is shown in Table 5.

To conclude, the high efficacy of FNAC obtained in the present study, when IAC Yokohama reporting system was applied, confirms the usefulness of this scheme in reporting breast lesions. A risk-based stratification is essential in the present era to guide and alert the clinician about the subsequent management plan and the ROM.

References

1. WHO. Breast cancer: prevention and control [Internet]. WHO. [cited 2019 Jul 14]. Available from: http://www.who.int/cancer/detection/breastcancer/en/.
2. Gupta S. Breast cancer: Indian experience, data, and evidence. South Asian J Cancer 2016;5:85.
3. Pandya AN, Shah NP. Breast fine needle aspiration cytology reporting: A study of application of probabilistic approach. Indian Med Gaz 2013;6.
4. Wai CJ, Al-Mubarak G, Homer MJ, Goldkamp A, Samenfeld-Specht M, Lee Y, et al. A modified triple test for palpable breast masses: the value of ultrasound and core needle biopsy. Ann Surg Oncol 2013;20:850-5.
5. Irwig L, Macaskill P, Houssami N. Evidence relevant to the investigation of breast symptoms: the triple test. Breast 2002;11:215-20.
6. Field AS, Raymond WA, Rickard M, Arnold L, Brachtel EF, Chaiwun B, et al. The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology. Acta Cytol 2019;63:257-73.
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 Cytol 2019;63:274–79.
8. Sunita H, Urmila T, Sharma DC. Cytomorphological Study Breast Lesions with Sonomammographic Correlation. Journal of Evolution of Medical and Dental Sciences 2015;4:14137-42.
9. Bajwa R, Tariq Z. Association of fine needle aspiration cytology with tumor size in palpable breast lesions. Biomedica 2010;26:124-29
10. Kamatar PV, Athanikar VS, Dinesh US. Breast Fine needle Aspiration Biopsy Cytology Reporting using International Academy of Cytology Yokohama System-Two Year Retrospective Study in Tertiary Care Centre in Southern India. National Journal of Laboratory Medicine 2019;8:1-3
11. 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 cytopathology: A single institutional retrospective study of the application of the system categories and the impact of rapid onsite evaluation. Acta Cytol 2019;63:280-91.
12. Rosa FD,Migliatico I,Vigliar E,Salatiello M,Pisapia P, Laccarino A, et al. The continuing role of breast fine-needle aspiration biopsy after the introduction of the IAC Yokohama System For Reporting Breast Fine Needle Aspiration Biopsy. Cytopathology 2020;48:1244-53
13. Kocjan G.Fine-needle aspiration cytology. Inadequate rates compromise success. Cytopathology 2003;14:307-08.
14. Panwar H, Ingle P, Santosh T, Singh V, Bugalia A, Hussain N. FNAC of breast lesions with special reference to IAC standardized reporting and comparative study of cytohistological grading of breast carcinoma. J Cytol 2020;37:34-9.
15. Modi P, Haren O, Jignasa B. FNAC as preoperative diagnostic tool for neoplastic and non-neoplastic breast lesions: A teaching hospital experience. Indian J Med Res 2014;4:274-8.
16. Bajwa R, Tariq Z. Association of fine needle aspiration cytology with tumor size in palpable breast lesions. Biomedica 2010;26:124-9.
17. Sunita H, Urmila T, Sharma DC. Cytomorphological study breast lesions with sonomammographic correlation. J Evol Med Dent Sci 2015;4:137-42.
18. Georgieva RD, Obdeijn IM, Jager A, Hooning MJ, Tilanus-Linthorst MM, Van Deurzen CH. Breast fine-needle aspiration cytology performance in the high-risk screening population a study of BRCA1/BRCA2 mutation carrier. Cancer Cytopathol 2013;121:561-7
19. Tejeswini V, Chaitra B, Renuka IV, Laxmi K, Ramya P, Sowjanya KKS. Effectuation of International Academy of Cytology Yokahama Reporting System of Breast Cytology to Assess Malignancy Risk and Accuracy. J Cytol 2021;38:69-73
20. Hoda RS, Brachtel EF. International academy of cytology Yokohama System for reporting breast FNAB cytology: A review of predictive values and risks of malignancy. Acta Cytol 2019;63:292–01.