Breast core biopsy is one of the major nonoperative methods of diagnosis. Increasingly, there is also a need to provide prognostic data to facilitate timely patient management. We present the results from 500 patients with invasive breast carcinoma, who underwent core biopsy followed by a therapeutic surgical procedure. Grade and type of the invasive and in situ carcinoma, together with the presence or absence of vascular invasion, were determined in both biopsy and definitive surgical excision and the results compared. There was 67% agreement with overall grade (kappa value 0.48), with scores for tubule formation, pleomorphism, and mitotic scoring achieving values of 82%, 73%, and 58%, respectively. Only 60% of grade 1 and 2 carcinomas showed concordance, but 84% of grade 3 tumors showed agreement between core and excision results. Tumor typing, vascular invasion, and grading of ductal carcinoma in situ had agreement values of 74%, 69%, and 65%, respectively. The major problem with assessing prognostic factors on needle biopsy specimens is undersampling of the most informative areas. However, in those patients in whom preoperative assessment of prognostic factors is most likely to be beneficial, i.e., those with grade 3 carcinomas, a high level of agreement was achieved in this large study.

Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5‐year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology – the biological basis and clinical relevance of its seven sub‐categories are currently unclear. By establishing the Asia‐Pacific MBC (AP‐MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan‐cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for ‘mixed’ MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis‐1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed‐type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan‐cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

No abstract

Tumours of perivascular epithelioid cells (PEComas) are being increasingly reported at visceral and somatic sites. Both benign and malignant variants have been identified, although clinical follow-up is often limited, which prevents meaningful predictions of behavior. We report the case of a malignant soft tissue PEComa with histologically confirmed regional lymph node metastases and radiologically confirmed pulmonary metastases. The light microscopic appearance and immunohistochemical profile (HMB-45, smooth muscle actin positive) and electron microscopic appearance support perivascular epithelioid cell differentiation.