Abstract Introduction: Tall cell carcinoma with reversed polarity (TCCRP) is a rare subtype of invasive breast carcinoma with a distinguishing morphogical feature, which is the predilection of nuclei to polarize to the apical pole of tall columnar epithelial cells. These tumours are most commonly associated with IDH2 p.Arg172 hotspot mutations. All reported cases of TCCRP affected women ranging from 39 to 89 years (mean age of 64 years). The tumours presented as a mammographic or palpable mass, only rarely associated with axillary lymph node metastases. TCCRP are usually associated with an indolent clinical course and a favourable prognosis. Morphologically, TCCRP is composed of circumscribed nests of epithelial cells often exhibiting delicate fibrovascular cores, conveying a solid papillary pattern. True papillae and cystic structures containing colloid-like material may be observed in some cases. The tumour cells are tall and columnar, with abundant eosinophilic cytoplasm, containing bland, round to ovoid nuclei disposed at the apical pole of the columnar epithelial cells. Mitotic figures are rare. Most TCCRPs exhibit a triple-negative phenotype and a low (< 20%) Ki-67 proliferation index. Molecular features of TCCRP comprise IDH2 p.Arg172 hotspot mutations, reported in about 84% of the cases studied, as well as PIK3CA missense mutations, identified in about 68% of these tumours. Only one case of TCCRP was associated with IDH1 gene mutations according to the literature. Case report: A 62 year old woman presented with a palpable mass and no axillary adenopathy was identified. Hematoxylin-eosin (HE) stain showed an invasive breast carcinoma, with epithelial tumour cells arranged in a solid and papillary pattern with thin fibrovascular cores. Neoplastic cells are tall and columnar, with abundant eosinophilic cytoplasm and round to ovoid nuclei, exhibiting no pleomorphism and disposed in the apical pole of the cells. Mitotic figures were not detected. Considering the highly suggestive morphology on HE stain, biopsy sample was sent for molecular analysis by next generation sequencing (NGS). Results and discussion: Molecular analysis by NGS using the TruSight Oncology 500 panel (Illumina) revealed the presence of the oncogenic mutations R132C and H1047R in IDH1 and PIK3CA genes, respectively. Contrary to what occurs in almost all cases of Tall cell carcinoma with reversed polarity (TCCRP), in which an oncogenic mutation is described in codon R172 of the IDH2 gene, in this case a mutation was observed in the IDH1 gene. Such a mutation has been described in only one case diagnosed with TCCRP according to the literature, this being the second reported case. Conclusion: This case report aims to warn of the possibility that other driver mutations may be associated with the diagnosis of TCCRP, such as IDH1 R132 and not just IDH2 R172, and that a comprehensive testing approach of the IDH1/2 genes might be more accurate in these cases. Citation Format: Karla Prigenzi, Luiz Gustavo Ferreira Cortes, Paulo Vidal Campregher, João Bosco de Oliveira Filho, Nestor Andrade Piva. TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-12.
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