Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis

INTRODUCTION: Metaplastic breast carcinomas constitute a heterogeneous group of neoplasms, accounting for less than 1% of all invasive mammary carcinomas. Approximately 70–80% of metaplastic breast carcinomas overexpress the epidermal growth factor receptor (EGFR). Human epidermal growth factor receptor (HER)2 and EGFR have attracted much attention in the medical literature over the past few years owing to the fact that humanized monoclonal antibodies against HER2 and therapies directed against the extracellular ligand-binding domain or the intracellular tyrosine kinase domain of EGFR have proven successful in treating certain types of human cancer. We investigated whether HER2 and EGFR overexpression was present and evaluated gene amplification in a series of metaplastic breast carcinomas. METHOD: Twenty-five metaplastic breast carcinomas were immunohistochemically analyzed using a monoclonal antibody (31G7) for EGFR and two antibodies for HER2 (Herceptest and CB11) and scored using the Herceptest scoring system. Gene amplification was evaluated by chromogenic in situ hybridization using Zymed Spot-Light EGFR and HER2 amplification probe. The results were evaluated by bright field microscopy under 40× and 63× objective lenses. RESULTS: Nineteen (76%) metaplastic breast carcinomas exhibited EGFR ovexpression, and among these EGFR amplification (defined either by large gene clusters or >5 signals/nucleus in >50% of neoplastic cells) was detected in seven cases (37%): three carcinomas with squamous differentiation and four spindle cell carcinomas. One case exhibited HER2 overexpression of grade 2+ (>10% of cells with weak to moderate complete membrane staining), but HER2 gene amplification was not detected. CONCLUSION: Metaplastic breast carcinomas frequently overexpressed EGFR, which was associated with EGFR gene amplification in one-third of cases. Our findings suggest that some patients with metaplastic breast carcinomas might benefit from novel therapies targeting EGFR. Because most metaplastic breast carcinomas overexpress EGFR without gene amplification, further studies to evaluate EGFR activating mutations are warranted

An unusually large myofibroblastoma in a male breast: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myofibroblastoma of the breast is a rare benign stromal tumour seen predominantly in men. The gross appearance is that of a well-circumscribed nodule, characteristically small, seldom exceeding 3 cm. We present a case of an unusually large myofibroblastoma, which mimicked a malignant breast tumour.</p> <p>Case presentation</p> <p>A 65-year-old man presented with a rapid enlargement of the right breast over 6 weeks. Examination revealed a firm 15 cm hemispherical lump occupying the whole of the right breast with peau d'orange appearance of the overlying skin and distortion of the nipple. The clinical and radiological features suggested the possibility of sarcoma of the breast. However, a guided Tru-Cut biopsy was inconclusive. A mastectomy was performed to remove the tumour, which weighed more than 2 kg. Histopathology and immunocytochemistry revealed a mixed classical and collagenised type of myofibroblastoma. The patient is well with no evidence of recurrence 5 years after the mastectomy.</p> <p>Conclusion</p> <p>This unexpected presentation of an unusually large myofibroblastoma in a male breast is the largest reported to date. Myofibroblastomas can mimic malignant neoplasms and the clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.</p

Multifocal invasive ductal breast cancer with osteoclast-like giant cells: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, this is the first case report of a multifocal (trifocal) invasive carcinoma of the breast containing osteoclast-like giant cells.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian woman presented for routine mammography screening with three radiodense lesions in the lower inner quadrant of the right breast, a primary breast cancer. Microscopic examination showed three foci of invasive ductal carcinoma with multinucleated osteoclast-like giant cells. Osteoclast-like giant cells in breast cancer are a rare phenomenon. They are described in less than two percent of all breast cancers and occur in association with invasive ductal cancer and invasive lobular cancer. In addition, osteoclast-like giant cells have been described in several sarcomas and metaplastic carcinomas of the breast.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report of a multifocal infiltrating ductal carcinoma of the breast containing osteoclast-like giant cells. This could be an indication for a possible early event in carcinogenesis associated with a biological event or secretion that indicates the differentiation and/or migration of stromal cells or macrophages.</p

Prognostic value of morphology and hormone receptor status in breast cancer - a population based study

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis