Breast cancer is the most common malignancy in women worldwide. It is the leading cause of cancer death in women in less developed countries and the second cause of cancer death in more developed regions. Currently, the use of breast fine needle aspiration cytology (FNAC) varies greatly between hospitals and cities and between developed and developing countries. It offers many advantages such as it is minimally invasive, causes minimal physical and psychological discomfort and is highly acceptable to patients¹. The numerous merits of FNAC in the initial evaluation of breast lesions are significant to physicians practicing in resource-limited healthcare settings, as it offers the opportunity to provide an efficacious diagnostic service that may otherwise be unavailable or unaffordable.² The IAC Yokohama System for Reporting Breast Cytopathology includes the indications for breast FNAC cytology, the techniques of FNAC, smear making, material handling, a reproducible standardized reporting system, the use of ancillary diagnostic and prognostic tests, and correlation with clinical workup algorithms which  will facilitate clinicians in understanding the use of FNAC cytology in breast pathology.³ The system has established uniform terminology for five defined categories for breast FNAC with stratified associated risks of malignancy (ROM) and management recommendations.⁴ The standardized structured report should state one of these five descriptive terms as a diagnosis. A laboratory and its cytopathologists should be able to select either “insufficient” or “inadequate” and use this term consistently. The term “non-diagnostic” is used in various reporting systems in different ways and is not recommended. We believe that the cumulative data on the utility of the IAC Yokohama System from multiple institutions across various countries might aid in the improvement and revision of the proposed system.⁵

Objectives

Primary Objectives

1. To categorize the breast FNAC cases according to Yokohama system and compare them with radiological findings and with the gold standard.
2. To calculate the risk of malignancy (ROM) of each category.

Secondary objective

To calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy for all categories.

It is a descriptive study (diagnostic test evaluation) done in the Department of Pathology, Sree Gokulam Medical College and Research Foundation from December 2022 to August 2024. The study population included all patients with breast lumps referred from the surgery OPD for FNAC who had undergone radiological evaluation. The inclusion criteria included all patients with breast lumps presenting for breast FNAC, and the exclusion criteria were patients without radiological evaluation, male breast lump cases, uncooperative patients, and patients falling under the BIRADS 1 category. A consecutive sampling method was adopted. The sample size was estimated as 82 assuming a sensitivity 91.6%, a precision 6% and a desired confidence level of 95%. Study variables included age, clinical diagnosis, FNAC, IAC Yokohama category, USG/mammogram, BIRADS grading system, and histopathological diagnosis. The study commenced after getting clearance from the institutional ethical committee. No specific ethical issues were related to the study, as it did not need any extra intervention in the study population. Fine needle aspiration was done on patients referred from the surgery OPD presenting with breast lumps who had already undergone radiologic evaluation (USG/Mammogram). Radiologically, breast lesions are reported according to BIRADS. FNAC was done using a 22 G needle, the alcohol fixed  smears were stained with Papanicolaou stain and dry smears with Giemsa stain. The smears were studied under light microscopy (10x, 40x). The cytological findings were recorded and classified according to IAC Yokohama system for reporting breast cytopathology. The cytology report was then compared with radiological findings and histopathology findings. The risk of malignancy was calculated. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were also calculated. Microsoft Office Excel was used for handling and preparing data. SPSS software was used for analysis of data. Standard descriptive analysis was performed. Sensitivity, specificity, PPV, NPV and diagnostic accuracy were calculated with the histologic diagnosis being the gold standard.

Total 82 patient samples were included in our study. Majority of the patients belonged to age group 40-60. The clinical history included lump in the breast (84%), pain (11%) and nipple discharge (5%). The 68% of patient population had no comorbidities and 44% were postmenopausal. When we analyzed the specimen laterality of our study group, 63% patients had specimens which belong to right side and for 34%, it belonged to left side. 46 patients (56%) had size of their lump > 2cm. 44% patients had their lump size less than 2cm. The distribution of categories according to IAC Yokohama system were as follows: Insufficient 12 (14.5%), benign 41 (50%), atypical probably benign 8 (10%), suspicious of malignancy 2(2.5%) and malignant 19 (23%). The rate of insufficient specimen 14.5% indicates that in our specimen we had a considerable number of non-diagnostic smears. The patient belonging to benign group (41 patients) were higher than  malignant group (19 patients). Majority (35%) patients belong to BIRADS category II. Only 10% belonged to BIRADS category V. Out of total 82 patients, 22 (24.5%) and 25 (30.5%) patients belonged to BIRADS category III and IV. The gold standard for comparison of cytology classification and BIRADS category is histopathology. Out of  82 patients, 55% specimen belonged to benign category. Only 45% patients had malignancy on histopathology. Our study also included final diagnosis of the samples collected. Out of 82 samples, fibroadenoma was the final diagnosis in 30 patients and was the most common diagnosis. Fibrocystic disease was seen in 10 patients (12). Among the malignant diseases, lobular carcinoma was the most common diagnosis and was seen in 15 patients (18%). Invasive ductal carcinoma was the second common among the malignant category and was seen in 12 patients (14.5%). Medullary carcinoma and metaplastic carcinoma  was diagnosed on histopathology in 4 and 3 patients respectively. Phylloides tumor was seen in only 3 patients. (Figure 1)

The risk of malignancy was 100% in the Suspicious and Malignant category. In our study, ROM was only 14.6% in benign category. The category Atypical, probably benign has 37.5% risk of being malignant. There is more than 50% risk in insufficient category. The sensitivity and specificity of cytology is reported as 56.7% and 100%. The positive predictive value is found to be 100%. (Table 2) The sensitivity and specificity of radiology classification (BIRADS) is found to be 78.3% and 91.1%. The PPV and NPV are 87.8% and 83.6% respectively. (Table 4)

Table 1: Risk of Malignancy

Table 2: Positive predictive value

Table 3: Comparison of IAC Yokohama Category with BIRADS

Table 4: Sensitivity, Specificity, Positive predictive value and Negative Predictive Value of BIRADS

Breast lesions are not necessarily malignant and are mostly benign and there is a grey zone between the two. All the breast lesions usually undergo triple assessment, which includes clinical, radiological and pathological examination to ensure a more accurate diagnosis and  thus help in precise treatment. FNAC of breast lumps is a rapid, simple, affordable, and safe diagnostic tool to determine the nature of breast lumps. Although Core Needle Biopsy has replaced FNAC in the developed world, FNAC is still the preferred technique for initial assessment in a resource-limited country like India, with very limited use of Core Needle Biopsy perhaps due to its higher expense. The value of breast FNAC should be reconsidered not only in under-resourced countries but also in more developed regions, especially in the context of ''one-stop'' diagnostic clinics and for the initial evaluation of breast lesions.⁶ Despite FNAC being a simple and cost-effective procedure with a short turnaround time, usage of core needle biopsy has gained popularity as it allows the assessment of histological grade and hormonal status. When used in concordance with clinical and radiological findings, the sensitivity and specificity of FNAC is comparable to that of core needle biopsy.⁴ FNAC can also be used to assess ER/PR/Her2 status through immunohistochemistry on cell blocks as is done in tertiary centre.⁷ FNAC has a very crucial role to play, especially in a tertiary care centre where it is not feasible to take an adequate number of core needle biopsies in each patient with a breast lump due to time and cost limitations. Moreover, it is easier to perform in experienced hands and more cost effective as compared to core needle biopsies. Despite it being a rapid test, turnaround time can be further reduced using rapid on-site evaluation. FNA for evaluation of breast lumps except in cases of atypical or suspicious categories where it is followed up by a core needle biopsy for confirmation.⁷ IAC Yokohama system aims to establish a comprehensive and standardized reporting of breast FNAC, facilitating the reproducibility of reports across institutions and better communication between pathologists and attending clinicians , thus expediting the delivery of optimal patient care. There is also recommendation on the utilization of rapid on-site evaluation (ROSE) whenever feasible to reduce the rate of insufficient FNAC and accelerating the triage of patients for CNB and ancillary testing of biomarkers, if required⁸. This newly proposed IAC Yokohama System also provides enhanced communication between pathologists and attending clinicians and enables better interinstitutional interchange for the benefit of patient care.⁶ In our study most of the patients belonged to the age group of 40-60 years in contrast to the 17% of cases which belonged to age group more than 60 years. The distribution of IAC Yokohama breast cytology reporting system categories in our study compared to other study are shown in table below. Our study was in concordance with study by Mirabi et al, Makkar et al and Chauhan et al^9,10. Insufficient category in our study constitutes a significant 14.5% of the total cases. The study published by Wong et al and Marabi et al had 11% of cases in insufficient category.  In study by Dixit et al, Insufficient category constitutes 7.4%⁶.  This may be due to various contributing factors such as hypocellularity, erroneous aspiration, smearing technique and staining procedure. Also, the nondiagnostic rates are higher in clinically benign breast lesions particularly due to the cellular composition of the lesions themselves; for instance lipomas or sclerotic/fibrotic lesions. (Table 5) A low proficiency in sampling and smearing technique of palpable breast lesions by the surgeons in training may also be a reason for the high insufficient results. This proportion of cases in Category I (Insufficient material) can be reduced by the implementation of the rapid on-site evaluation (ROSE) whenever possible by the cytopathologist. The benign category constitutes 50% of the total case in our category. Our result is similar to cases published by Marabi M et al (56.6%) and Makkar et al (54.5%). The percentage of cases in Atypia, probably benign is in concordance with study published by authors Montezuma et al and Deshpande et ^{al3, 11}. The study published by authors Wong et al, and Chauhan et al is matching our results of 2.5% cases in Suspicious of Malignancy category^4,10,. In our study 45% of cases were diagnosed as malignant on histopathology. This could possibly be due to including more cases in perimenopausal age group and lump in breast as presenting complaint. In general, the ROM has been shown to provide guidance for the clinical management of patients.  In our study, 7 out of 12 cases in insufficient category are found to be malignant. The risk of malignancy in insufficient category was calculated as 58.3%. The study by Hoda et al also has high risk of malignancy for the insufficient category¹². Our result was also in concordance with the study by Agarwal et al, Sarangi S et al and Sundar et al with above 30% ROM for insufficient category.  In our study, none of the cases in suspicious of malignant and malignant category are diagnosed as benign on histopathology. Our study showed a result like studies by authors namely Montezuma et al, Wong et al, Ahuja et al, Deshpande et al and Dixit et al. In study by Deshpande et al diagnosing the malignant cases was more in C4 category compared to C3 category. Our study showed ROM for atypia and suspicious category as 37.5% and 100% respectively. The study recommended that further investigations such as CNB or trucut biopsy should be done in the gray zone lesions to arrive at accurate diagnosis¹¹. (Table 6) The specificity and positive predictive value of 100% was seen in our study. This is comparable with studies published by Hoda S et al, Dixit et al and Wong et al^4,6,12. The sensitivity and negative predictive value of cytology was found to be low compared to rest of published studies. The sensitivity, specificity, positive predictive value, and negative predictive values are high and comparable to international studies as shown in the table below. (Table 7) Fibroadenoama was the most common diagnosis seen in our study. This was in concordance with study by Dixit et al⁶. Lobular carcinoma and invasive ductal carcinoma are the common malignant diagnosis in our study⁶.  Fibrocystic disease seen in 12% of patients. (Figure 1: Final Diagnosis)

Table 5: Comparison of IAC Yokahama category distribution

Table 6: Comparison of Risk of Malignancy

Table 7: Comparison of Sensitivity, Specificity, Positive Predictive Value and Negative Predictive value.

FNAC is a reliable, well tolerated diagnostic modality which can be used in diagnosis of breast lesions. FNAC can be used to arrive at a diagnosis. In situations where the patient is too sick and other more invasive methods cannot be used, FNAC becomes the diagnostic modality of choice for the initial management of such patients. The turnaround time with FNAC is less thus helping in the overall management of patients. Following the IAC Yokohama system, FNA is a useful tool and requires specific training & ongoing experience. Therefore, this newly proposed IAC Yokohama system for reporting breast cytopathology is a simple system that allows greater diagnostic clarity and, consequently, better communication between pathologist and treating clinician, also helps in predicting the ROM

Conflict of interest: The authors declare no conflict of interest

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