Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology

OBJECTIVE: To assess the correlation between cytological diagnoses and histological subtypes of fibroadenoma (FA) and to clarify the cytological features of a specific group of FA displaying variable features similar to fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of this subtype in cytological diagnosis. METHODS: A review of 141 cases of histologically proven FA was performed. We re-classified them into four subtypes according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further selected 92 cases for which both fine needle aspiration (FNA) smears and histological specimens were available. Among them, 18 cases of MFA and their cytological smears were selected for the present study. RESULTS: There was significant correlation between MFA and cytological diagnosis of 'indeterminate' or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses of indeterminate or were included in the category 'suspicious for malignancy'. Smears from MFA revealed high cellularity (9/18 smears had more than 10 epithelial clusters each composed of more than 50 cells), presence of cellular discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%). Anisonucleosis was present in fewer than half the cases and no apparent condensed chromatin was identified. CONCLUSION: We highlight the significance of subclassification of MFA in aspiration cytology of breast. MFA had a significantly higher chance of falling into the 'suspicious for malignancy' or 'indeterminate' diagnostic category in aspiration cytology. It might be a diagnostic challenge for cytopathologist to identify this subtype of FA in FNA smears.     

MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women

Fibroadenoma is the most common type of benign breast tumor, accounting for 90% of benign lesions in India. Somatic mutations in the mediator complex subunit 12 (MED12) gene play a critical role in fibroepithelial tumorigenesis. The current study evaluated the hotspot region encompassing exon 2 of the MED12 gene, in benign and malignant breast tumor tissue from women who presented for breast lump evaluation. A total of 100 (80 fibroadenoma and 20 breast cancer) samples were analyzed by polymerase chain reaction-Sanger sequencing. Sequence variant analysis showed that 68.75% of nucleotide changes were found in exon 2 and the remaining in the adjacent intron 1. Codon 44 was implicated as a hotspot mutation in benign tumors, and 86.36% of the identified mutations involved this codon. An in silico functional analysis of missense mutations using consensus scoring sorting intolerant from tolerant (SIFT), SIFT seq, Polyphen2, Mutation Assessor, SIFT transFIC, Polyphen2 transFIC, Mutation Assesor transFIC, I-Mutant, DUET, PON-PS, SNAP2, and protein variation effect analyzer] revealed that apart from variants involving codon 44 (G44S; G44H), others like V41A and E55D were also predicted to be deleterious. Most of the missense mutations appeared in the loop region of the MED12 protein, which is expected to affect its functional interaction with cyclin C–CDK8/CDK19, causing loss of mediator-associated cyclin depended kinase (CDK) activity. These results suggest a key role of MED12 somatic variations in the pathogenesis of fibroadenoma. For the first time, it was demonstrated that MED12 sequence variations are present in benign breast tumors in the south Indian population.     

Assessment of elastosis in invasive ductal carcinoma of the breast compared to fibroadenoma among Sudanese patients using conventional histochemical methods

We aimed to identify, using histochemical methods, the degree of elastosis in a malignant breast tumor compared to a benign tumor. Sixty-four tissue blocks were used in this study of which 34 (53.1%) were Invasive ductal carcinoma (IDC) (cases) and 30 (46.8%) were fibroadenomas (controls). Examination of Verhoeff's stained sections revealed different grades of elastosis in 29 (85.2%) cases compared to seven (23.3%) in controls. These findings indicated that elastosis was a prominent feature of IDC (p < 0.000). IDC was associated with more frequent occurrence of different grades of elastosis and should, therefore, be considered a valuable histological finding. Nevertheless, more advanced technology for quantitative measurements of the staining density is recommended to confirm this variation.     

Benign phyllodes tumour vs fibroadenoma: FNA cytological differentiation

The differential diagnosis of fibroadenomas vs phyllodes tumours by fine needle aspiration (FNA) cytology is not possible in the majority of cases. The present study aims to look at common and dissimilar features to allow differentiation, if possible. We reviewed the FNA findings of 18 histologically proven phyllodes tumours and 18 fibroadenomas, checking in each case the epithelial features, the stromal features, and any atypia. Using a semi-quantitative score assessed by two observers we were able in most cases to distinguish a phyllodes tumour from a fibroadenoma. The most important criteria were larger stromal fragments, numerous plump stromal bare nuclei, and the higher ratio of stromal bare nuclei to epithelial bare nuclei in phyllodes tumours. In the present study, an original diagnosis of phyllodes tumour was made in 7/18 (38.9%) cases but with our criteria this could be improved to 15/18 (83.3%) cases. Therefore, the presence of specific stromal features in a dimorphic cellular pattern should suggest the correct diagnosis and differentiate its appearance from a cellular fibroadenoma.     

FNA of breast fibroadenoma: observer variability and review of cytomorphology with cytohistological correlation

OBJECTIVE: To determine the observer variability in reporting fibroadenoma of the breast by fine needle aspiration (FNA) and to review the cytomorphological features of the lesion with cytohistological correlation. METHODS: Retrospective analysis of FNA smears from 110 cases diagnosed as fibroadenoma of which surgical pathology follow-up was available in 33. Two pathologists were asked to categorize smears from 67 cases of breast lesions while blinded to the clinical finding as fibroadenoma, epithelial hyperplasia (usual and atypical) and malignant. All fibroadenoma (33) and cancer (15) cases were biopsy-proven. The same set of slides was re-circulated to one of the pathologists, and his first and second round results were compared. RESULTS: Pre-review cytohistological correlation was attained in 32 of 33 cases of fibroadenoma (97%). The overall agreement between the two observers was 87% [Kappa = 0.74, 95% confidence interval (CI) 0.72-0.76]. Cytohistological correlation was achieved in 26 of 33 (79%) cases. Intra-observer agreement was 91% (Kappa = 0.82, 95% CI 0.89-0.93) with cytohistological correlation in 29 of 33 (87%) cases. Causes of diagnostic errors included marked dissociation, pleomorphism, poorly cellular smears from hyalinized fibrodenoma, lacational changes and apocrine metaplasia with cystic changes. Multinucleated giant cells were frequently encountered in FNA smears from fibroadenoma (31.8%), but in none of the lumpectomy specimens. Their histiocytic nature was suggested by immunohistochemistry. CONCLUSION: FNA was a highly sensitive method for the diagnosis of fibroadenoma. Current cytological criteria were reliable and gave high inter- and intra-observer reproducibility.     

Identification of components of fibroadenoma in cytology preparations using texture analysis: a morphometric study

S. Singh and R. Gupta Identification of components of fibroadenoma in cytology preparations using texture analysis: a morphometric study Objectives: To evaluate the utility of image analysis using textural parameters obtained from a co‐occurrence matrix in differentiating the three components of fibroadenoma of the breast, in fine needle aspirate smears. Methods: Sixty cases of histologically proven fibroadenoma were included in this study. Of these, 40 cases were used as a training set and 20 cases were taken as a test set for the discriminant analysis. Digital images were acquired from cytological preparations of all the cases and three components of fibroadenoma (namely, monolayered cell clusters, stromal fragments and background with bare nuclei) were selected for image analysis. A co‐occurrence matrix was generated and a texture parameter vector (sum mean, energy, entropy, contrast, cluster tendency and homogeneity) was calculated for each pixel. The percentage of pixels correctly classified to a component of fibroadenoma on discriminant analysis was noted. Results: The textural parameters, when considered in isolation, showed considerable overlap in their values of the three cytological components of fibroadenoma. However, the stepwise discriminant analysis revealed that all six textural parameters contributed significantly to the discriminant functions. Discriminant analysis using all the six parameters showed that the numbers of pixels correctly classified in training and tests sets were 96.7% and 93.0%, respectively. Conclusion: Textural analysis using a co‐occurrence matrix appears to be useful in differentiating the three cytological components of fibroadenoma. These results could further be utilized in developing algorithms for image segmentation and automated diagnosis, but need to be confirmed in further studies.     

Fine Needle Aspiration of Breast Carcinoma In A Fibroadenoma

A case of concurrent carcinoma of the breast with a fibroadenoma in a 59-year-old woman is described. The diagnosis was made on fine needle aspiration cytology. Despite the rarity of such a lesion, it is felt that a cytological diagnosis of this lesion from a fine needle aspirate specimen is possible.     

Quantitative cytological assessment of Ki67 and AgNORs using computer-digitized image analysis of four clinicopathological breast lesions

Analysis of silver-stained proteins associated with nucleolar organiser regions (AgNORs) is proposed as a marker of cellular proliferation. This study describes the application of AgNORs and Ki67 in breast lesions. Sixty-one cases including fibroadenoma (FA), fibrocystic disease (FCD), ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were studied by image analysis to evaluate quantitative changes in AgNORs in both Ki67-positive, and Ki67-negative smears. The Ki67 index was assessed. Morphometric features of cell nuclei and AgNORs were determined by digitized computer image analysis (Prodit 5.2). The growth fraction was 5.08 for FA, 5.71 for FCD, 16.75 for DCIS and 23.26 for IC. The mean nuclear area was significantly higher in malignant cells than those of fibroadenoma and fibrocystic disease. In Ki67-positive cells the total area, long axis and number of AgNORs increased progressively across disease groups. Eccentricity of AgNORs and AgNORs: nuclear area ratios were significantly increased in malignant breast lesion in comparison with benign lesion in Ki67 positive cells. In Ki67 negative cells, the highest value of AgNORs was observed in DCIS. The AgNORs: nuclear area ratio demonstrated a statistically significant trend across the disease groups. This study demonstrates that the growth fraction, mean nuclear area and selected AgNORs features have potential for differentiating benign from malignant breast tumours.