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Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

ABSTRACT: Tall cell carcinoma with reverse polarity is a rare subtype of breast carcinoma with solid and papillary growth and nuclear features reminiscent of those of the tall cell variant of papillary thyroid carcinoma. These tumors harbor recurrent IDH2 R172 hotspot mutations or TET2 mutations, co-occurring with mutations in PI3K pathway genes. Diagnosis of tall cell carcinomas with reverse polarity is challenging in view of their rarity and the range of differential diagnosis. We sought to determine the sensitivity and specificity of IDH2 R172 immunohistochemistry for the detection of IDH2 R172 hotspot mutations in this entity. We evaluated 14 tall cell carcinomas with reverse polarity (ten excision and five core needle biopsy specimens), 13 intraductal papillomas, 16 solid papillary carcinomas, and 5 encapsulated papillary carcinomas by Sanger sequencing of the IDH2 R172 hotspot locus and of exons 9 and 20 of PIK3CA, and by immunohistochemistry using monoclonal antibodies (11C8B1) to the IDH2 R172S mutation. The 14 tall cell carcinomas with reverse polarity studied harbored IDH2 R172 hotspot mutations, which co-occurred with PIK3CA hotspot mutations in 50% of cases. None of the other papillary neoplasms analyzed displayed IDH2 R172 mutations, however PIK3CA hotspot mutations were detected in 54% of intraductal papillomas, 6% of solid papillary carcinomas, and 20% of encapsulated papillary carcinomas tested. Immunohistochemical analysis with anti-IDH2 R172S antibodies (11C8B1) detected IDH2 R172 mutated protein in 93% (14/15) of tall cell carcinomas with reverse polarity samples including excision (n?=?9/10) and core needle biopsy specimens (n?=?5), whereas the remaining papillary neoplasms (n?=?34) were negative. Our findings demonstrate that immunohistochemical analysis of IDH2 R172 is highly sensitive and specific for the detection of IDH2 R172 hotspot mutations, and likely suitable as a diagnostic tool in the evaluation of excision and core needle biopsy material of tall cell carcinomas with reverse polarity.

SUBMITTER: Pareja F

PROVIDER: S-EPMC7286791 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

Pareja Fresia F da Silva Edaise M EM Frosina Denise D Geyer Felipe C FC Lozada John R JR Basili Thais T Da Cruz Paula Arnaud A Zhong Elaine E Derakhshan Fatemeh F D'Alfonso Timothy T Wen Hannah Y HY Giri Dilip D DD Hayes Malcolm M MM Krings Gregor G Bhargava Rohit R Palazzo Juan P JP Rakha Emad A EA Hoda Syed A SA Sanders Melinda E ME Collins Laura C LC Schnitt Stuart J SJ Chen Yunn-Yi YY Weigelt Britta B Jungbluth Achim A AA Reis-Filho Jorge S JS Brogi Edi E

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20200102 6

Tall cell carcinoma with reverse polarity is a rare subtype of breast carcinoma with solid and papillary growth and nuclear features reminiscent of those of the tall cell variant of papillary thyroid carcinoma. These tumors harbor recurrent IDH2 R172 hotspot mutations or TET2 mutations, co-occurring with mutations in PI3K pathway genes. Diagnosis of tall cell carcinomas with reverse polarity is challenging in view of their rarity and the range of differential diagnosis. We sought to determine th ...[more]

PMID: 31896809

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Project description:BackgroundPapillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described.MethodsWe retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure.ResultsThere were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure.ConclusionsThese findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

Dataset Information

Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

Publications

Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

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