Xanthomatous Giant Cell Renal Cell Carcinoma: Another Morphologic Form of TSC -associated Renal Cell Carcinoma.
Adolescent
Adult
Biomarkers, Tumor
/ genetics
Carcinoma, Renal Cell
/ pathology
Child
Female
Giant Cells
/ pathology
Glycoproteins
Humans
Keratin-20
Ki-67 Antigen
Kidney Neoplasms
/ pathology
Male
TOR Serine-Threonine Kinases
/ genetics
Tuberous Sclerosis
Tuberous Sclerosis Complex 1 Protein
Young Adult
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 11 2022
01 11 2022
Historique:
pubmed:
9
8
2022
medline:
19
10
2022
entrez:
8
8
2022
Statut:
ppublish
Résumé
Over the past decade, several distinct novel renal epithelial neoplasms driven by underlying tuberous sclerosis comples ( TSC)/ mammalian target of rapamycin (MTOR) pathway mutations have been described. We report herein two distinctive TSC2 -mutated renal cell carcinomas which do not fit any previously described entity. The two renal carcinomas occurred in young patients (ages 10 and 31 y), and were characterized by highly permeative growth within the kidney with metastases to perirenal lymph nodes. The neoplastic cells were predominantly large, multinucleated giant cells having variably eosinophilic to xanthomatous cytoplasm with basophilic stippling and frequent vacuolization. While the discohesive nature of the neoplastic cells, xanthomatous cytoplasm, immunoreactivity for histiocytic markers and minimal immunoreactivity for conventional epithelial markers raised the possibility of a histiocytic neoplasm, multifocal immunoreactivity for cytokeratin 20 helped establish their epithelial nature. Despite the aggressive growth pattern of these neoplasms and lymph node metastases, mitotic figures were rare and Ki-67 indices were low (<1%). One patient with follow-up shows no evidence of disease seven years after nephrectomy with no adjuvant therapy. Next-generation sequencing demonstrated TSC2 mutations in each case. By immunohistochemistry, downstream markers of mTOR pathway activation S6K1, 4EBP1, and glycoprotein nonmetastatic melanoma protein B were all highly expressed in these neoplasms, suggesting mTOR pathway activation as the neoplastic driver. While the cytokeratin 20 immunoreactivity and focal basophilic cytoplasmic stippling suggest a relationship to eosinophilic solid and cystic renal cell carcinoma, and cytoplasmic vacuolization suggests a relationship to eosinophilic vacuolated tumor, these neoplasms appear to be distinctive given their permeative growth patterns and predominant xanthomatous giant cell morphology. Addition of cytokeratin 20 to a panel of epithelial markers helps avoid misdiagnosis in such cases.
Identifiants
pubmed: 35941720
doi: 10.1097/PAS.0000000000001940
pii: 00000478-202211000-00011
doi:
Substances chimiques
Biomarkers, Tumor
0
Glycoproteins
0
Keratin-20
0
Ki-67 Antigen
0
TSC1 protein, human
0
Tuberous Sclerosis Complex 1 Protein
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1554-1561Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: Supported in part by Dahan Translocation Carcinoma Fund and Joey’s Wings (P.A.).
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