PMID- 35941720
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20221215
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 46
IP  - 11
DP  - 2022 Nov 1
TI  - Xanthomatous Giant Cell Renal Cell Carcinoma: Another Morphologic Form of TSC 
      -associated Renal Cell Carcinoma.
PG  - 1554-1561
LID - 10.1097/PAS.0000000000001940 [doi]
AB  - 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.
CI  - Copyright (c) 2022 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Argani, Pedram
AU  - Argani P
AD  - Departments of Pathology.
AD  - Oncology.
FAU - Matoso, Andres
AU  - Matoso A
AD  - Departments of Pathology.
AD  - Oncology.
AD  - Urology, The Johns Hopkins Medical Institutions, Baltimore, MD.
FAU - Pallavajjalla, Aparna
AU  - Pallavajjalla A
AD  - Departments of Pathology.
AD  - Oncology.
FAU - Haley, Lisa
AU  - Haley L
AD  - Departments of Pathology.
AD  - Oncology.
FAU - Tseh-Lin, Ming
AU  - Tseh-Lin M
AD  - Departments of Pathology.
AD  - Oncology.
FAU - Ng, Jessica
AU  - Ng J
AD  - Department of Pathology, Royal Children's Hospital, Melbourne, Australia.
FAU - Chow, C W
AU  - Chow CW
AD  - Department of Pathology, Royal Children's Hospital, Melbourne, Australia.
FAU - Lotan, Tamara
AU  - Lotan T
AD  - Departments of Pathology.
AD  - Oncology.
AD  - Urology, The Johns Hopkins Medical Institutions, Baltimore, MD.
FAU - Mehra, Rohit
AU  - Mehra R
AD  - Department of Pathology, University of Michigan School of Medicine, Michigan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220808
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Glycoproteins)
RN  - 0 (Keratin-20)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (TSC1 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - *Carcinoma, Renal Cell/pathology
MH  - Child
MH  - Female
MH  - Giant Cells/pathology
MH  - Glycoproteins
MH  - Humans
MH  - Keratin-20
MH  - Ki-67 Antigen
MH  - *Kidney Neoplasms/pathology
MH  - Male
MH  - TOR Serine-Threonine Kinases/genetics
MH  - *Tuberous Sclerosis
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Young Adult
COIS- Conflicts of Interest and Source of Funding: Supported in part by Dahan 
      Translocation Carcinoma Fund and Joey's Wings (P.A.).
EDAT- 2022/08/09 06:00
MHDA- 2022/10/19 06:00
CRDT- 2022/08/08 23:55
PHST- 2022/08/09 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/08/08 23:55 [entrez]
AID - 00000478-202211000-00011 [pii]
AID - 10.1097/PAS.0000000000001940 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2022 Nov 1;46(11):1554-1561. doi: 10.1097/PAS.0000000000001940. 
      Epub 2022 Aug 8.