Breast Fine Needle Aspiration Cytology Reporting : A Study of Application of Probabilistic Approach

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1 54 Original Study Indian Medical Gazette FEBRUARY 2013 Breast Fine Needle Aspiration Cytology Reporting : A Study of Application of Probabilistic Approach Amrish N. Pandya, Professor & Head, IHBT Department, Neelam P. Shah, Resident, Pathology Department Government Medical College, Surat. Abstract Background: This study is based on application of probabilistic approach in reporting of breast fine needle aspiration cytology, its accuracy and correlation with likelihood of carcinoma in histology. Material and Method: Breast cytology was reported according to 1 of 6 categories, positive, suspicious, atypical, proliferative without atypia, unremarkable and unsatisfactory. Histologic correlation was done whenever possible. Results: Out of total 515 cases, 138 were correlated in histology. There were no false positive cases. The probability of finding carcinoma on histology, for suspicious and atypical categories was 94.11% and 75% respectively. All lesions from proliferative without atypia and unremarkable categories were benign on histology. Conclusion: The probabilistic approach is uniform, accurate method and easy to apply in reporting of breast FNAs. Suspicious and atypical categories were associated with increased incidence of carcinoma in histology and therefore such cases should be further evaluated for histology. Keywords breast carcinoma, fine needle aspiration cytology (FNAC), probabilistic approach Introduction A palpable breast lump, whether benign or malignant, is a cause of anxiety to patient. Therefore accurate pathological diagnosis is crucial for further treatment and estimation of an outcome. The trend has now been shifting to a less invasive procedure in its diagnosis. The sensitivity of FNA in diagnosis of breast lesion is % 1. Some cytologic lesions may have features mimicking to those of low grade or sparsely cellular carcinoma. Many authorities recognized this limitation of breast cytology and advised use of categorical or probabilistic approach in reporting of breast FNA to limit false positive or false negative results 2, 3, 4, 5, 6. The aim of scheme proposed by Wang and Ducatman is to categorize a lesion according to likelihood of being a carcinoma on basis of FNA finding rather than to predict precise histologic diagnosis 3. In this study we divide 3,4 breast FNAC in one out of six categories- positive, suspicious, atypical, proliferative without atypia, unremarkable and unsatisfactory; and correlate it with surgical specimen in aspects to predicting likelihood of carcinoma. Material and Method This study was ethically approved by appropriate authority. This was a cross sectional study of 482 patients with palpable breast lump. Out of these 33 patients had bilateral breast lumps. So, total 515 FNAC cases from 482 patients. Both females and males were included in this study. Metastasis in breast, cyst, abscess and fat necrosis were excluded. Out of 515 FNAC cases, 138 were correlated in histology. Remaining was not correlated in histology Address for correspondence: Dr Neelam P Shah, 4th year Resident Pathologist, Pathology Department, Government Medical College, Surat neelampshah84@gmail.com

2 Indian Medical Gazette FEBRUARY because they lost to follow-up for further management. Each patient was subjected to FNAC of breast lump under aseptic precautions after explaining the procedure and taking written consent. FNA was performed by using a 10 ml disposable syringe and 22/23-gauge needle. No local anesthesia was given during the procedure. FNA smears were stained with H & E, Pap & MGG stains. Tissue sections, obtained from mastectomy/lumpectomy specimens were stained with H and E stains. In cytology, lesions were divided according to following criteria 3, 4. c) One cell population refers to one population of atypical epithelial cells, as opposed to mix population of atypical and benign appearing epithelial cells or atypical epithelial cells and stromal cells. d) Hyper cellularity refers to atypical cell population only, rather than increased cellularity due to another component such as inflammatory or stromal cells. 2) Suspicious for carcinoma (see Fig. 2) When any three of the above features for malignancy are present, a suspicious diagnosis is given. 1) Positive for carcinoma (see Fig. 1) - all four of the following criteria must be met. Fig. 1 Smear shows positive cytology having hyper cellular smear, showing many single, loosely cohesive groups of large, pleomorphic duct cells with irregular nuclear margin & coarse chromatin and prominent nucleoli. The histologic diagnosis was infiltrating ductal carcinoma (Pap stain 1000 x) a) Cellular dyshesion refers to presence of abundant single epithelial cells or loosely cohesive groups of epithelial cells (this excludes singly bare bipolar cells and stromal cells). b) Cytologic atypia may be variable but should at least include high nuclear: cytoplasmic ratio and markedly eccentrically located nuclei. Other useful feature which may or may not be present depending on the level of pleomorphism, include nuclear membrane irregularity, coarse and clumped chromatin, multiple and irregular nucleoli. Fig. 2 Smear shows suspicious cytology, with scattered single atypical cells with eccentric nuclei. But lesion lacks hyper cellularity. The histologic diagnosis was infiltrating ductal carcinoma (H & E 1000 x) 3) Epithelial proliferative lesion with atypia (see Fig. 3) This diagnosis is made when specimen is cellular with many epithelial cells and when epithelial cells present in groups show significant crowding and overlapping and/or specimen show one other feature of malignancy (cellular dyshesion, one cell population, cellular atypia ) 4) Epithelial proliferative lesion without atypia (see Fig. 4) This category is used when a specimen is cellular with many epithelial cells and epithelial cells in group show no or mild crowding and overlapping with, obvious myoepithelial cells present. Most fibroadenoma tends to fall in this category.

3 56 Indian Medical Gazette FEBRUARY 2013 Cytologic diagnosis was correlated with surgical specimen whenever possible. Surgical specimens were classified into invasive carcinoma, ductal carcinoma in situ and benign lesion. Probability of carcinoma in histology for each category was calculated in percentages. Observations Fig. 3 Cytology smear shows proliferative breast lesion with atypia. There is cohesive groups of cells with marked crowding, overlapping and mild to moderate atypia. The histologic diagnosis was infiltrating ductal carcinoma. (MGG 400x) Table 1 shows distribution of 515 cases on aspiration cytology and histologic follow- up examination in each category. Table 2 shows correlation of cytologic and histologic diagnosis of breast FNAC along with probability of being carcinoma in histology for each category in this study. There was no false positive diagnosis on cytology. Approximately 94.11% of cases from suspicious category had carcinoma. Approximately 75% from atypical category shows carcinoma. None of the lesions from proliferative breast disease without atypia or unremarkable category shows carcinoma. Fig. 4 Cytology smear shows Proliferative breast lesion without atypia, cohesive group of cells with myoepithelial cells. There is no significant atypia or crowding/overlapping. The histologic diagnosis was fibro adenoma. (MGG 400 x) 5) Unremarkable When none of the four features of carcinoma was present, such lesions were described as unremarkable. 6) Non diagnostic/unsatisfactory If specimen is acellular or extremely hypo cellular and when it does not yield an explanation of lesion based on information provided by clinician, it was reported as unsatisfactory. Discussion Breast cancer is the commonest cancer of urban Indian women and the second commonest in the rural women next to cervical cancer. Owing to the lack of awareness of this disease and in absence of a breast cancer screening program, the majority of breast cancers are diagnosed at a relatively advanced stage 7.

4 Indian Medical Gazette FEBRUARY The rising incidence of breast cancer continues to concern. There are three main objectives for investigations in breast carcinoma, to establish correct diagnosis and staging the disease, to detect breast cancer in very early stage & to predict the prognosis. Triple diagnosis is combination of clinical examination, mammography and FNB. If all three investigations are in agreement that the lesion is either benign or malignant diagnostic accuracy is over 99%.Now, the trend has been shifting to a less invasive procedure in its diagnosis. The sensitivity of FNAC in diagnosis of breast lesion is %. Definitive treatment is often based on cytological diagnosis without histological confirmation, unless there is disagreement between cytology and clinical and/or mammographic assessment 1. Therefore a uniform reporting system with high reproducibility should be used in reporting breast FNAC. National Cancer Institute sponsored consensus conference on breast FNA biopsy in 1996, recommended the classification of breast FNAs into one out of the following 5 categories; benign, atypical, suspicious, malignant, or unsatisfactory 8. A proposal for uniform terminology and reporting of breast fine needle aspirate has provided a practical scheme for classifying breast fine needle aspiration results for reporting and management 3. The criteria proposed by Wang and Ducatman are reproducible, reduces subjectivity and offered a good frame for the implementation of quality control procedure 9. The aim of this scheme is to categorize a lesion according to likelihood of being a carcinoma on basis of FNA findings. The positive for carcinoma category has high specificity and least false positive rate. The suspicious and atypical categories serve maximum sensitivity and indicate uncertainty about diagnosis and required further diagnostic procedure. Proliferative without atypia and unremarkable categories indicate benign lesion. However if aspirate is hypo cellular it must be mentioned in report 3. A gray zone in breast cytology has long been recognized. It is in which an unequivocal diagnosis cannot be reached with fine needle aspiration cytology findings. It is due to overlapping features of benign epithelial proliferative lesion, mostly fibro adenoma, and a well differentiated carcinoma as well as borderline lesions of breast 4, 10. The gray zone in breast fine needle aspiration cytology is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. Diagnosing gray zone pathology as atypical in fine needle

5 58 Indian Medical Gazette FEBRUARY 2013 aspiration cytology causes no delay in treatment as excision biopsy is recommended for all equivocal cases 10. The presence of nuclear pleomorphism, high nuclear: cytoplasmic ratio, epithelial cell atypia, low number of bipolar nuclei and necrosis are useful parameters to predict malignancy in atypical FNAC of breast 11. In this study, 94.11%, 75% lesions are malignant in histology from cytologic suspicious and atypical lesion respectively. Percentages of malignancy in histology from cytological suspicious and atypical lesion in various studies were shown in Table 3. management of any of these categories should base on the result of triple test. There is no false positive lesion in this study. All lesions from positive category are malignant in histology. All lesions from proliferative without atypia and unremarkable category are benign in histology. Out of 12 unsatisfactory cases, 5 cases were correlated in histology. Out of 5, one was fibro adenoma, one was atypical ductal hyperplasia and 3 were infiltrating ductal carcinoma not otherwise specified. So, unsatisfactory smears should be evaluated in conjunction with clinical and imaging appearance. Thus, this probabilistic approach in FNAC provides information about possibility of carcinoma in histology and also provides standardized guideline for breast aspiration reporting. This scheme of reporting is also applicable on male breast lesions 2. There is also interobserver agreement of this scheme of reporting on a set of breast FNAs prepared on thin prep slides 14. Summary Probabilistic approach proposed by Wang and Ducatman has definite cytologic criteria for each category. It is associated with likelihood of histologic finding of carcinoma, also accurate, easy to apply and provides a uniform approach in reporting of breast aspiration. Percentage of malignancy in atypical category is higher compared to other studies. This is because only clinically suspicious lesion in atypical category is evaluated further by histology and remaining was only followed up. Thus like other studies this study also showed that it was essential to have two less definitive categories(suspicious and atypical) and there was a definite difference between them. Possibility of carcinoma on histology for suspicious category is more than atypical cytologic category. Therefore it is worthwhile to keep these two categories separate. This study, like other studies 3, 4, 10, 12, and 13 also suggests that diagnosis of atypia is clinically significant because it is associated with increased likelihood of malignancy and such cases should be evaluated for histology. But, ultimate References 1. Karin Lindholm-Breast. Orell S.R., Sterrett G.F., Whitaker D. Fine needle aspiration cytology. 4th edition. Reed Elsevier India Private Limited, New Delhi: Chapter7, pg.167; MacIntosh R.F., Merrimen J.L., Barnes P.J. Application of the probabilistic approach to reporting Breast fine needle aspiration in males. Acta Cytol. 52: , Wang H.H., Ducatman B.S: Fine needle aspiration of the breast: a probabilistic approach to diagnosis of carcinoma. Acta Cytol. 42(2): , Ayata G., Abu-Jawdeh G.M., Fraser J.L., Garcia L.W., Upton M.P., Wang H.H. Accuracy and consistency in application of a probabilistic approach to reporting

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