Effectuation of International Academy of Cytology Yokahama Reporting System of Breast Cytology to Assess Malignancy Risk and Accuracy.

INTRODUCTION: Recently the International Academy of Cytology (IAC) proposed a new Yokahama reporting system for breast fine-needle aspiration cytology (2019) in order to standardize reporting pattern and to link cytology reporting to management algorithms. AIMS AND
OBJECTIVES: To categorize the samples according to the newly proposed IAC Yokahama reporting system of breast cytology and to assess diagnostic accuracy and corresponding risk of malignancy (ROM) for each category.
MATERIALS AND METHODS: This is a retrospective study of breast cytology cases done at Department of Pathology. The slides are retrieved from pathology archives and classified using a recently proposed IAC, Yokahama reporting system of breast cytology into five categories. The risk of malignancy, sensitivity, specificity, and diagnostic accuracy were estimated on the basis of the final histopathological diagnosis.
RESULTS: Of the 386 cases of breast FNAC, 226 (55.55%) had the corresponding histological diagnosis. The respective ROM for each category was 22.22% for category 1 (insufficient material), 5.32% for category 2 (benign), 26.31% for category 3 (atypical), 100% for category 4 (suspicious for malignancy), and 100 % category 5 (malignant). Malignant cases were considered only when positive tests, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 89.66%, 100%, 100%, 90.2%, and 94.69%, respectively.
CONCLUSIONS: The present study showed statistically significant sensitivity, specificity, and diagnostic accuracy, especially with malignant cases. Hence, using the IAC Yokahama reporting system of breast cytology is effective to standardize the reporting in various institutes and provide clear guidelines to clinician for further management. Copyright:

INTRODUCTION

Fine needle aspiration cytology (FNAC) of breast lumps has gained wide recognition as a simple diagnostic procedure that can segregate lesions into different categories. The prognosis and management of each category differ accordingly. Recently the International Academy of Cytology (IAC) proposed Yokahama reporting system for breast fine-needle aspiration biopsy (FNAB)/cytology (2019) in order to standardize reporting pattern and to link cytology reporting to management algorithms.[1] As there is limited data in literature, the present study was conducted to categorize the cytology samples according to the newly proposed IAC Yokahama reporting system of breast cytology, assess the risk of malignancy (ROM) for each category, and estimate diagnostic accuracy.

MATERIAL AND METHODS

This is a retrospective study conducted on all cases of breast lumps attending the department of Pathology, from January 2018 and June 2020. The study was approved by the institutional ethical committee clearance obtained on 07-Aug-2019. After recording the relevant clinical details, FNAC was performed under aseptic precautions using a 10 ml disposable syringe without local anesthesia and with informed consent. The material was aspirated and character was noted. Routine smears were prepared, fixed in ethyl alcohol, and stained with hematoxylin and eosin. The slides were retrieved from the archives and reported using the recently proposed IAC, Yokahama structured reporting system of breast cytology. Accordingly, the cases are classified into five categories as

Category 1: Insufficient material

Category 2: Benign

Category 3: Atypical, probably benign

Category 4: Suspicious for malignancy, probably in situ or invasive carcinoma

Category 5: Malignant.

The cytology reports were compared with the histopathological diagnosis, which is considered as a gold standard.

Patients of all ages with breast lumps who were willing to undergo FNAC and cases with histopathological diagnosis were included in the study, while the cases without corresponding histological diagnosis were excluded.

The ROM, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were estimated on the basis of the final histopathological diagnosis.

RESULTS

This study was conducted to categorize the breast FNAC by the recent IAC, Yokahama reporting system of breast cytology and to analyze the accuracy and risk of malignancy of each category. Out of 386 breast lumps FNAC, we received 226 (trucut biopsy and specimen) cases for histopathological examination. The age range varied with the youngest of 18 years and the oldest being 83 years. There was slight preponderance in 5th decade [as depicted in Table 1] and on right side (53%).

Table 1

Incidence in various age groups and categories according to IAC Yokahama system of reporting breast cytology

IAC Category Age in years		1 Insufficient	2 Benign	3 Atypical	4 Suspicious for malignancy	5 Malignant Cases	Total
							%
11-20		0	2	3	0	0	5	2.21
21-30		1	16	2	0	2	21	9.29
31-40		3	28	6	2	9	48	21.24
41-50		4	30	5	8	19	66	29.2
51-60		1	12	2	10	26	51	22.57
61-70		0	6	1	9	14	30	13.27
71-80		0	0	0	2	1	3	1.33
81-90		0	0	0	0	2	2	0.89
Total	Cases %	9	94	19	31	73	226/100%
		3.98	41.59	8.41	13.72	32.3

The FNAC results were categorized into five groups of Yokahama reporting system of breast cytology and results were tabulated. Benign group lesions (110 cases) were slightly lower than the malignant lesions (116 cases). The most common lesion in benign was fibroadenoma with 57 cases (51.81%) and in malignant, invasive carcinoma of NST morphology with 106 cases (91.3%). The spectrum of various benign and malignant on histology is depicted in Table 2.

Table 2

Histopathological spectrum of benign and malignant lesions

Benign lesions	Number of cases	Malignant lesions	Number of cases
Fibroadenoma	57	Invasive carcinoma NST	106
Inflammatory	12	Ductal carcinoma in situ	02
Fibrocystic disease	13	Invasive papillary carcinoma	02
Fibroadenosis	14	Lobular carcinoma	02
Benign phyllodes	07	Metaplastic carcinoma	03
Ductal hyperplasia	03	Malignant phyllodes	01
Duct ectasia	02
Duct papilloma	02
Total	110	100%	116

Out of 226 cases, cytohistological concordance was found in 214 (94.69%) cases, whereas 12 (5.3%) cases were discordant as benign. None of the malignant cases were discordant. In 9 cases of insufficient category, two cases turned out to be malignant, while other seven were benign (ROM-22.22%). This is attributed to insufficient material; hence, aspiration from a representative area is required. Among 94 cases of benign category, only 5 were malignant (ROM- 5.32%). Figure 1 shows the discordant cases of category 2. Five of nineteen cases in atypical group turned out to be malignant (ROM-26.31%) and all the 31 cases in suspicious and 73 cases in malignant categories were malignant (ROM -100%) on histopathological examination. Figure 2 shows microscopic and radiological features of a discordant case of atypical category along with microscopic features of category 4 and 5. The risk of malignancy is shown in Table 3.

Figure 1

(a) 400X H and E Category II Cystic lesion with foamy macrophages on cytology turned as (b) 100X H and E Ductal carcinoma in-situ with cystic change on histopathology

Figure 2

(a) 400X H and E, Category III Clusters with intact cell dispersal and pleomorphism, (b) mammogram of the same case BIRRADIV, (c and d) 400X H and E Category IV and V dyscohesive clusters with pleomorphism

Table 3

Risk of malignancy in various categories

IAC category	Number of Cytology cases	Benign	Malignant	Risk of malignancy
1 Insufficient	9	7	2	22.22%
2 Benign	94	89	5	5.32%
3 Atypical	19	14	5	26.31%
4 Suspicious for malignancy	31	0	31	100%
5 Malignant	73	0	73	100%
Total	226	110	116

In this study, histopathological diagnosis was taken as gold standard. The cytological diagnosis of malignancy was considered as positives, while benign as negatives for statistical calculations. True positives (TP) were the cases that are malignant both on cytology and histopathology, true negatives (TN) are cases benign on cytology and histology, and false positives (FP) are malignant on cytology but are benign on histology while false negatives (FN) are cases diagnosed as benign on cytology but later turned out to be malignant on biopsy. In the present study, the total 104 cases were TP, 110 were TN, 12 were FN, and none of the cases were FP. Taken these parameters into consideration, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy in diagnosing breast cytology using Yokahama reporting system were calculated.

DISCUSSION

Fine needle aspiration cytology (FNAC) of the breast is globally one of the most commonly performed fine needle aspirations with a long history of successful application, initially in palpable lesions and then in impalpable lesions using ultrasound guidance.[2] Breast lesions are one of the most common sites sampled by FNAC, especially in developing countries.[3] There are analytical problems in interpreting breast cytology, particularly with inexperienced pathologists and requires specific training in cytopathology.[3] The “gray zone” in breast FNAC includes a broad spectrum ranging from proliferative fibrocystic disease to sclerosing adenosis to malignancy.[4] A structured reporting system requires checklists of cytological features for specific lesions based on an analytical approach using low-power pattern recognition combined with high-power cytological features.[5] In order to stimulate the appropriate use of breast FNAC, improve the reporting of breast FNAC, facilitate the communication between the cytopathologist and the clinical management team, and promote further research into breast disease utilizing FNAC to further benefit patient care, The International Academy of Cytology Executive Council (2016) put together a “Breast Group,” consisting of cytopathologists, surgical pathologists, radiologists, surgeons, and oncologists working in breast care, with the aim of producing a comprehensive and standardized approach to breast FNAC reporting.[13] The breast group established best-practice protocols for the suggested management of each of the five categories with their varying risks of malignancy, while taking into account the vast differences between the developed and developing world in the potential availability of imaging, core needle biopsy (CNB), surgical pathology, and management options. These best-practice guidelines will include the role of FNAC and CNB in the management algorithms and allow for the great variations in medical infrastructure.[67] International Academy of Cytology established a clear categorization of breast reports into five tiers, each with a clear definition and description, and a specified risk of malignancy (ROM). The ROM is then linked with management recommendations. The system also crucially emphasizes that breast FNAC relies on the expertise of those performing the biopsy, making the direct smears, and interpreting the material on the slides, and this requires good initial and ongoing training and clear communication with the clinicians managing patients with breast lesions.

In the present study, all the 226 cases who underwent FNAC for breast lump followed by biopsy, either trucut or excisional surgery were grouped into the following five categories based on the IAC Yokahama reporting system of breast cytology.

The insufficient/inadequate includes slides that are too sparsely cellular or too poorly smeared or fixed to allow a cytomorphological diagnosis.

In the present study, 20 cases were grouped under this category, of which 9 had a histopathological correlation and two cases turned out to be malignant. The ROM in our study was 22.22%, which was higher than the studies done by Montezuma et al.[8] (4.8%) and Wang et al.[9] (2.6%). Inadequate FNAC can be due to lesion characteristics or technical issues. The yield if is not representative will definitely increase the risk of malignancy, hence, not possible to establish ROM. Therefore, aspirator experience, guided FNAC, and immediate cytological assessment with additional repeated aspirates by Rapid On Site Evaluation (ROSE) technique will reduce the misinterpretation of inadequate samples as established by Wang et al.[9] The ROM in a meta-analysis done by Hoda et al.[10] was higher than the present study (30.3%).

The cases with unequivocally benign cytological features which may or may not be diagnostic of a specific benign lesion are included in Category II. This category includes inflammatory lesions, cysts, benign neoplasm, and epithelial hyperplasia. This is the most common group in the present study, which is consistent with Montezuma et al.,[8] and 94 out of 117 cases had correlation. Out of 94 cases, only 5 cases were malignant on histopathology, one case of invasive papillary carcinoma, and two cases of invasive carcinoma NST. The ROM was 5.32%, which is slightly more than the studies done by Montezuma et al.[8] (1.4%) and Wang et al.[9] (1.7%) but correlated with Hoda et al.[10] (4.7%). Out of the three discordant cases, two were cystic and one showed papillary lesion on cytology.

The atypical group includes cases with cytological features predominantly of benign process with single cluster of intact cell dispersal/nuclear enlargement and pleomorphism/high cellularity/necrosis/complex architecture that suggest micropapillary or cribriform proliferation.

In our study, 19 cases were included as atypical, out of which five cases were malignant. The ROM was 26.31% which is significantly higher than other studies done by Montezuma et al.[8] (13%) and Wang et al.[9] (15.7%) but lower than Hoda et al.[10] (51.5%). This can be attributed to the less number of atypical cases in this study.

Management of this group is by correlation of triple test. If clinical and imaging is not atypical, then review after 3–6 months with/without FNAB, and if suspicious or indeterminate, core needle/excision biopsy was advised. In the present study, one discordant case was suspicious on imaging.

In the suspicious of malignancy probably in situ or invasive carcinoma, the cells show some of the cytological features usually found in malignant lesions, but with insufficient malignant features either number or quality to make definite diagnosis of malignancy. There were 31 cases in this category; all of them were malignant on histopathological examination with ROM of 100%. This correlated with Montezuma et al.[8] (97.1%), while ROM of Wang et al.[9] (84.6%) and Hoda et al.[10] (85.4%) were slightly low.

The malignant category shows definite cellular features of malignancy. All the 73 cases included in this category were malignant on histopathology. The ROM was 100%, which is in correlation with other studies, Montezuma et al.[8] (100%), Wang et al.[9] (99.5%), and Hoda et al.[10] (98.7%).

The present study has overall sensitivity, specificity, and positive predictive value, negative predictive value, which was consistent with the studies done by Montezuma et al.,[8] Wang et al.,[9] and Hoda et al.[10]

To the best of our knowledge, there are only two studies in literature describing sensitivity, specificity, and diagnostic accuracy, or positive and negative predictive values, but no literature was found to describe all these parameters based on the IAC Yokahama system of reporting breast cytology.

To conclude breast FNAC is an accurate test enabling effective diagnosis of breast lesions. The present study showed statistically significant sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy, especially with malignant cases. Hence, using the IAC Yokahama reporting system of breast cytology is effective to standardize the reporting in various institutes and provide clear guidelines to clinician for further management. This classification system may be much better for reporting breast lesions as each diagnostic category conveys specific risks of malignancy which provide data that would help in planning the therapeutic approach of the patients.

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Conflicts of interest

There are no conflicts of interest.