mTOR eosinophilic renal cell carcinoma: a distinctive tumor characterized by mTOR mutation, loss of chromosome 1, cathepsin-K expression, and response to target therapy

In the spectrum of oncocytic renal neoplasms, a subset of tumors with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamycin (mTOR) and hitherto clinical indolent behavior has been described. Three cases (2F,1 M) with histologically documented metast...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2023-12, Vol.483 (6), p.821-833
Main Authors: Caliò, Anna, Marletta, Stefano, Settanni, Giulio, Rizzo, Mimma, Gobbo, Stefano, Pedron, Serena, Stefanizzi, Lavinia, Munari, Enrico, Brunelli, Matteo, Marcolini, Lisa, Pesci, Anna, Fratoni, Stefano, Pierconti, Francesco, Raspollini, Maria Rosaria, Marchetti, Antonio, Doglioni, Claudio, Amin, Mahul B., Porta, Camillo, Martignoni, Guido
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - genetics
Carcinoma, Renal Cell - metabolism
Chromosome 1
Chromosomes, Human, Pair 1 - metabolism
Gene expression
Humans
Immunohistochemistry
Inhibitors
Kidney cancer
Kidney Neoplasms - drug therapy
Kidney Neoplasms - genetics
Kidney Neoplasms - metabolism
Leukocytes (eosinophilic)
Liver
Liver Neoplasms - drug therapy
Liver Neoplasms - genetics
Lymph nodes
Medicine
Medicine & Public Health
Metastases
Metastasis
MTOR Inhibitors
Mutation
Neoplasms
Next-generation sequencing
Nucleoli
Original Article
Pathology
Pax8 protein
Rapamycin
Renal cell carcinoma
Skull
TOR protein
TOR Serine-Threonine Kinases - genetics
Tumors
Vimentin
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Summary:In the spectrum of oncocytic renal neoplasms, a subset of tumors with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamycin (mTOR) and hitherto clinical indolent behavior has been described. Three cases (2F,1 M) with histologically documented metastases (lymph node, skull, and liver) were retrieved and extensively investigated by immunohistochemistry, FISH, and next-generation sequencing. Tumors were composed of eosinophilic cells with prominent nucleoli (G3 by ISUP/WHO) arranged in solid to nested architecture. Additionally, there were larger cells with perinuclear cytoplasmic shrinkage and sparse basophilic Nissl-like granules, superficially resembling the so-called spider cells of cardiac rhabdomyomas. The renal tumors, including the skull and liver metastases, showed immunoexpression PAX8, CK8-18, and cathepsin-K, and negativity for vimentin. NGS identified mTOR genetic alterations in the three cases, including the skull and liver metastases. One patient was then treated with Everolimus (mTOR inhibitors) with clinical response (metastatic tumor shrinkage). We present a distinct renal tumor characterized by high-grade eosinophilic cells, cathepsin-K immunohistochemical expression, and harboring mTOR gene mutations demonstrating a malignant potential and showing responsiveness to mTOR inhibitors.
ISSN:0945-6317
1432-2307
DOI:10.1007/s00428-023-03688-2