Tall cell carcinoma with reversed polarity is a rare, low-grade breast carcinoma with variable morphology and a characteristic molecular profile. Diagnosis on core-needle biopsy is challenging due to architectural overlap with benign and low-grade papillary lesions. We report a 42-year-old woman with a right breast lump in whom this diagnosis was established on core-needle biopsy through integrated histological, immunohistochemical, and molecular assessment. The tumour showed tall columnar cells with focal reversed nuclear polarity, keratin 5/6 positivity with strong S100 and anti-mitochondrial antibody expression, moderate oestrogen receptor positivity, and absence of myoepithelial markers. Molecular testing identified an IDH2 R172 mutation, confirming the diagnosis. This is a notable example of oestrogen receptor-positive tall cell carcinoma with reversed polarity. While most such tumours are triple-negative, the oestrogen receptor positivity, which initially led to consideration of papilloma with usual ductal hyperplasia, does not preclude the diagnosis. Accurate preoperative diagnosis is essential to avoid misclassification and to guide appropriate surgical management. The patient underwent wide local excision with sentinel lymph-node biopsy, with adjuvant radiotherapy and endocrine therapy recommended, and no recurrence at last follow-up. This report demonstrates that the diagnosis can be reliably established on limited biopsy material when morphological, immunophenotypic, and molecular data are integrated. We also provide a diagnostic algorithm for papillary neoplasms with unusual morphology.
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Muthyala et al. (2026) studied this question.
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