Comprehensive profiling of renal medullary and collecting duct carcinomas.

572 Background: Renal medullary carcinoma (RMC) is an aggressive malignancy affecting predominantly young African Americans with sickle cell trait (SCT) or disease (SCD), while a pathologically similar collecting duct carcinoma (CDC) affects patients without sickle cell trait. Clinical responses to chemotherapy and IL-2 in RMC/CDC are poor and novel therapies are needed. Methods: 9 patients with RMC (ages 13-58 y. o., all male) and 15 patients (ages 26-74 y. o., M:F = 13:2) with collecting duct carcinoma (CDC) were studied. Expression of PD-L1 was evaluated with 2 monoclonal antibodies (SP142 and SP263) and tumor infiltrating lymphocytes (TIL) were evaluated for PD1 expression (MRQ-22 antibody) using immunohistochemistry (IHC). Additional studies included ALK protein expression (D5F3 antibody), gene translocation (break apart FISH), next generation sequencing (NGS), and microsatellite instability (MSI). Results: Cancer cell PD-L1 expression above the threshold ( ≥ 2+, ≥ 5%) was seen in 7/9 RMC and 5/13 CDC cases. Concordance between 2 PD-L1 antibodies was 94.4%. PD-1+ TIL were absent in 6/18 cases and variably present in 12/18 cases (from 1 to > 15 TIL/40x power field). No MSI was detected in any of the cases tested (0/6). No case expressed ALK protein, but one case of CDC showed ALK gene re-arrangement. Mutations were identified in SMARCB1, FH, TP53 (3x), ATM, BRCA2, CHEK2 (2x), NF2 (3x), SETD2, and CDKN2A. No mutations in VHL or KDR were detected. One patient with RMC (and SCT) achieved complete clinical remission after treatment with bevacizumab plus paclitaxel. Conclusions: RMC and CDC strongly express PD-L1 in the majority of cases (12/22), suggesting that these patients may benefit from targeting the PD-L1/PD1 interaction. The absence of MSI in these cancers indicates a different mechanism of PD-L1 upregulation from colorectal carcinomas. Consistent with our previous study that showed frequent activation of (pseudo)hypoxia-induced pathways in RMCs (Human Pathology 2011;42:1979), we describe a case of RMC successfully treated with anti-VEGF therapy.

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Renal Medullary Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0492-rs ◽

2019 ◽

Vol 143 (12) ◽

pp. 1556-1561 ◽

Cited By ~ 4

Author(s):

Alexis Elliott ◽

Evelyn Bruner

Keyword(s):

Sickle Cell ◽

Sickle Cell Trait ◽

Collecting Duct ◽

Malignant Neoplasm ◽

Young Male ◽

Medullary Carcinoma ◽

Malignant Rhabdoid Tumor ◽

Duct Carcinoma ◽

Renal Medullary Carcinoma ◽

Time Of Presentation

Renal medullary carcinoma, also referred to as the seventh sickle cell nephropathy, typically affects young African Americans with sickle cell trait, or, less frequently, patients with sickle cell disease. The existence of renal medullary carcinoma without a concomitant hemoglobinopathy is a topic of controversy. The typical patient is a young male of African or Mediterranean descent, with hematuria and/or flank pain. Most patients have metastatic disease at the time of presentation. The tumor is characteristically a poorly circumscribed mass in the medullary region, commonly showing variable amounts of hemorrhage and necrosis. Microscopically, a characteristic reticular or cribriform pattern with a striking desmoplastic stromal response and a robust mixed inflammatory infiltrate is observed. Collecting duct carcinoma, malignant rhabdoid tumor, urothelial carcinoma, and other subtypes of renal cell carcinoma are in the differential diagnosis. Because of the advanced stage of disease at presentation and the aggressive nature of this malignant neoplasm, survival is poor even with chemotherapy; however, isolated reports of prolonged survival have been documented.

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Collecting Duct Carcinoma and Renal Medullary Carcinoma

The Kidney ◽

10.1007/978-1-4939-3286-3_8 ◽

2016 ◽

pp. 109-123

Author(s):

Jamie Koo ◽

Christopher P. Filson ◽

Jiaoti Huang ◽

Allan J. Pantuck

Keyword(s):

Collecting Duct ◽

Medullary Carcinoma ◽

Duct Carcinoma ◽

Collecting Duct Carcinoma ◽

Renal Medullary Carcinoma

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Comprehensive genomic profiling of metastatic collecting duct carcinoma, renal medullary carcinoma, and clear cell renal cell carcinoma

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2020.12.009 ◽

2021 ◽

Author(s):

Gennady Bratslavsky ◽

Stephanie Gleicher ◽

Joseph M. Jacob ◽

Thomas H. Sanford ◽

Oleg Shapiro ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clear Cell ◽

Collecting Duct ◽

Medullary Carcinoma ◽

Genomic Profiling ◽

Cell Renal Cell Carcinoma ◽

Duct Carcinoma ◽

Collecting Duct Carcinoma ◽

Renal Medullary Carcinoma ◽

Comprehensive Genomic Profiling

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Collecting Duct Carcinoma Versus Renal Medullary Carcinoma

The American Journal of Surgical Pathology ◽

10.1097/pas.0000000000000222 ◽

2014 ◽

Vol 38 (7) ◽

pp. 871-874 ◽

Cited By ~ 62

Author(s):

Mahul B. Amin ◽

Steven C. Smith ◽

Abbas Agaimy ◽

Pedram Argani ◽

Eva Marie Compérat ◽

...

Keyword(s):

Collecting Duct ◽

Medullary Carcinoma ◽

Duct Carcinoma ◽

Collecting Duct Carcinoma ◽

Renal Medullary Carcinoma

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Survival benefit in bevacizumab-based therapy in sickle cell trait patients diagnosed with renal medullary carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16096 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16096-e16096 ◽

Cited By ~ 3

Author(s):

E. D. Johnson ◽

N. N. Tannir ◽

K. A. Olejeme ◽

C. J. Logothetis ◽

E. Jonasch

Keyword(s):

Median Survival ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Collecting Duct ◽

Medullary Carcinoma ◽

Drug Combinations ◽

Disease Stage ◽

Cancer Center ◽

Renal Medullary Carcinoma ◽

Black Patients

e16096 Background: Renal medullary carcinoma (RMC) is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, primarily sickle cell trait. This is a rare and highly aggressive tumor that is shown to be most resistant to chemotherapy. In an effort to evaluate treatment outcomes, we retrospectively examined those patients diagnosed with RMC who were treated with and without bevacizumab based regimens. Methods: We reviewed the genitourinary medical oncology database at M. D. Anderson Cancer Center for patient diagnosed between 1999–2008 with histology proven RMC. Vital statistics of birth and death dates were noted. In addition, detailed chemotherapy regimen as well as medical and radiological data were also obtained. Results: All patients had metastatic disease (stage IV) to at least one distant site at presentation. Distant sites included bone, liver or lungs. A sample of five black males 5/9 (53%) were treated with therapy that included a 2 or 3 drug combinations of Adriamycin, Taxol, Gemzar, cisplatin, or Gleevac. Median survival was 12.7 months (3.2–22.2) while median age was 31 year (28–59). Only 4/9 (47%) patients received bevacizumab based therapy in a 2 or 3 drug combinations with Gemzar, Xeloda, cisplatin, or Taxol. In this group, 50% were females, median age of 36 years (33–39) and median survival of 18.5 months (15.5–22.8). Conclusions: Sickle cell trait was confirmed for all in this group diagnosed with RMC. 8/9 of these patients were black and 1/9 South-Asian. The group that received bevacizumab based therapy had a median survival of 5.8 months longer. Future studies, including genetic studies on the tumor types are essential to determining the SNP profiles of renal cell carcinoma in black patients. Furthermore, a prospective multicenter trial should be developed to evaluate the efficacy of bevacizumab based regimens in renal medullary carcinoma in this population. No significant financial relationships to disclose.

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Carcinomas of the renal medulla: A comprehensive genomic profiling (CGP) study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.640 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 640-640

Author(s):

Gennady Bratslavsky ◽

Joseph M Jacob ◽

Oleg Shapiro ◽

Julia Andrea Elvin ◽

Jo-Anne Vergilio ◽

...

Keyword(s):

Targeted Therapies ◽

Sickle Cell Trait ◽

Collecting Duct ◽

Renal Medulla ◽

Medullary Carcinoma ◽

High Status ◽

Duct Carcinoma ◽

Ffpe Specimen ◽

Comprehensive Genomic Profiling ◽

Tumor Types

640 Background: Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) represent rare tumors that arise in the renal medulla are therapy resistant tumors that progress rapidly. Methods: DNA was extracted from 40 microns of FFPE specimen from refractory CDC (46 cases) and RMC (24 cases). CGPwas performed using a hybrid-capture, adaptor ligation based next generation sequencing assayto a mean coverage depth of > 800X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. Microsatellite instability status (MSI) was determined on 114 loci. Results: All CDC patients were older and more frequently male (Table). Sickle cell trait was identified in both CDC and RMC, but far more frequently associated with RMC. All (100%) of CDC and RMC were clinically advanced Stage III and IV tumors with the primary tumor used for CGP in 70% of cases and a metastasis biopsy was sequenced in 30%. All (100%) CDC and RMC were intermediate (Grade 3) or high grade (Grade 4). In both tumor types, the GA/tumor was relatively low and there were no (0%) VHL GA. SMARCB1 GA were significantly more frequent in RMC than CDC but common in both tumors. Targeted therapies for kinase ( EGFR, RET) and MTOR ( NF2, TSC2) pathways were more frequent in CDC than RMC. At 1.8 mut/Mb, the median TMB was low for both tumor types with no (0%) of cases showing≥20 mut/Mb. No (0%) of the CDC or RMC cases featured MSI-high status. Conclusions: In addition to their histologic differences, the frequencies and types of GA seen in CDC differ significantly from that seen in RMC. The opportunities for biomarker driven targeted therapies for bothCDCand RMC appear limited with rare opportunities to target GA in TKGFR and MTOR pathways for CDC. Similarly, the relatively low TMB and absence of MSI-High status in CDC and RMCalso predicts that these tumors may be resistant to immunotherapies.[Table: see text]

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