Case Of Renal Medullary Carcinoma Research Articles

Renal medullary carcinoma masquerading as renal infection: a case report

BackgroundRenal medullary carcinoma is a rare and aggressive tumor and often seen in young adults with sickle cell hemoglobinopathies.Case presentationWe report a case of renal medullary carcinoma in a 29-year old male patient with an occupying renal lesion who presented with fever, flank pain and hematuria. The patient received intensive antibiotics treatment, but no improvement was seen. The symptoms disappeared after laparoscopic radical left nephrectomy. Postoperative pathological study showed that the mass was renal medullary carcinoma.ConclusionsOur case suggests that renal medullary carcinoma should be considered in differential diagnoses of patients with occupying renal lesions who have fever of unknown origin.

Abstract 5354: Novel genomic alterations in renal medullary carcinoma tumors

Abstract Introduction: Renal medullary carcinoma (RMC) is an rare but aggressive non-clear cell carcinoma that occurs predominantly in young African American (AA) men who carry the sickle cell trait. Our knowledge of the molecular basis for the initiation and progression of this cancer remains inadequate to establish standard of care treatments. As a result, even with surgery and chemotherapy, outcomes have remained dismal, with a median overall survival of approximately 13 months. Most patients with RMC exhibit deletion of the SMARCB1 gene, which encodes for a subunit of the SWI/SNF chromatin remodeling complex. Subtypes of RMC without SMARCB1 loss but harbor a rare gene fusion between Vinculin and Anaplastic Lymphoma Kinase have also been reported. We hypothesize that whole exome sequencing (WES) of RMC tumors will identify novel genomic alterations responsible for RMC tumor initiation and progression, which may provide actionable targets for treatment. Methods: Formalin fixed paraffin embedded (FFPE) RMC tumor and adjacent tissue specimens of 21 African American patients were obtained from the Joint Pathology Center. DNA were isolated from tumor and normal tissues with the Qiagen FFPE All Prep kit and measured by using the Qubit fluorometer. Integrity of the DNA samples were evaluated by using the Advanced Analytics Fragment Analyzer. WES DNA libraries were prepared from DNA samples that passed quality control using the Illumina TruSeq WES kit. Paired end sequencing (2x75) was performed on the Illumina HiSeq3000 platform. RMC tissues sections were analyzed for the expression of SMARCB1, VHL, HIF2A, AURKA, and EZH2 proteins by immunohistochemistry (IHC). Results: Somatic copy number alterations were estimated from the WES of seven RMC cases. These include recurrent large scale DNA alterations involving chromosome 7 and 8 amplification and chromosome 15 deletion. Focal DNA copy number alterations were also identified in the cohort, including deletion of SMARCB1. Analysis of somatic sequence mutations detected a canonical hotspot mutation (R132C) in IDH1 and recurrent non-silent mutations on RBM47 and NF2. Evaluation by IHC showed the loss of SMARCB1 expression in all cases assayed. Upregulation of EZH2 and AURKA, which are negatively regulated by SMARCB1, were detected in 3 of 21 and 11 of 21 cases, respectively. Focal HIF2A staining was detected in 7 of 21 tumor cases. Conclusions: The recurrent somatic sequence mutations, gene amplifications and deletions identified in this study reveal potential novel oncogenic drivers of RMC. Further validation of these genomic alterations may offer additional insight into the initiation and progression of RMC and provide actionable targets for establishing standard of care treatments. Source of Funding: The work is supported a grant award (HU0001-14-2-0041) to ST from the Collaborative Health Initiative Research Program (CHIRP), a precision medicine-based collaborative effort between the NIH and the DOD. Citation Format: Jesse Fox, Denise Young, Yingjie Song, Heng Cheng Hu, Anthony Soltis, Matthew D. Wilkerson, Clifton L. Dalgard, Inger L. Rosner, Isabell A. Sesterhenn, Shiv Srivastava, Shyh-Han Tan. Novel genomic alterations in renal medullary carcinoma tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5354.

PD46-02 CARCINOMAS OF THE RENAL MEDULLA: A COMPREHENSIVE GENOMIC PROFILING (CGP) STUDY

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2018PD46-02 CARCINOMAS OF THE RENAL MEDULLA: A COMPREHENSIVE GENOMIC PROFILING (CGP) STUDY Stephanie Gleicher, Clarissa Cassol, Joseph Jacob, Oleg Shapiro, Julie Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Siraj Mahamed Ali, Alexa Betzig Schrock, Vincent A. Miller, Philip J. Stephens, Laurie M. Gay, Dmitra Bourboulia, Mehdi Mollapour, Jeffrey S. Ross, and Gennady Bratslavsky Stephanie GleicherStephanie Gleicher More articles by this author , Clarissa CassolClarissa Cassol More articles by this author , Joseph JacobJoseph Jacob More articles by this author , Oleg ShapiroOleg Shapiro More articles by this author , Julie Andrea ElvinJulie Andrea Elvin More articles by this author , Jo-Anne VergilioJo-Anne Vergilio More articles by this author , James SuhJames Suh More articles by this author , Shakti RamkissoonShakti Ramkissoon More articles by this author , Siraj Mahamed AliSiraj Mahamed Ali More articles by this author , Alexa Betzig SchrockAlexa Betzig Schrock More articles by this author , Vincent A. MillerVincent A. Miller More articles by this author , Philip J. StephensPhilip J. Stephens More articles by this author , Laurie M. GayLaurie M. Gay More articles by this author , Dmitra BourbouliaDmitra Bourboulia More articles by this author , Mehdi MollapourMehdi Mollapour More articles by this author , Jeffrey S. RossJeffrey S. Ross More articles by this author , and Gennady BratslavskyGennady Bratslavsky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2150AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) represent rare tumors that arise in the renal medulla and are therapy resistant with rapid progression. The objective of this study is to better define the genomic profile of these tumors. METHODS DNA was extracted from 40 microns of FFPE specimen from refractory CDC (46 cases) and RMC (24 cases). CGP was performed using a hybrid-capture, adaptor ligation based next generation sequencing assay to 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 1). 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 rate of genetic alteration (GA) 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%) cases showing = 20 mut/Mb. None (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 both CDC and 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 RMC also predicts that these tumors may be resistant to immunotherapies. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e891 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Stephanie Gleicher More articles by this author Clarissa Cassol More articles by this author Joseph Jacob More articles by this author Oleg Shapiro More articles by this author Julie Andrea Elvin More articles by this author Jo-Anne Vergilio More articles by this author James Suh More articles by this author Shakti Ramkissoon More articles by this author Siraj Mahamed Ali More articles by this author Alexa Betzig Schrock More articles by this author Vincent A. Miller More articles by this author Philip J. Stephens More articles by this author Laurie M. Gay More articles by this author Dmitra Bourboulia More articles by this author Mehdi Mollapour More articles by this author Jeffrey S. Ross More articles by this author Gennady Bratslavsky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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

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]

Predictive role of PD-L1 expression in the response of renal Medullary carcinoma to PD-1 inhibition

BackgroundRenal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response.Case presentationTwo African-American patients (male and female) with sickle cell trait who presented to our center with hematuria and flank pain were diagnosed with metastatic renal medullary carcinoma. PD-L1 was expressed at rate of 25% and 60% in patient 1 and 2 respectively. Following nephrectomy, they were started on nivolumab. Patient 1 initially responded to the treatment with regression of metastatic lesions. However, following this early response, patient 1 who has been receiving nivolumab for more than 15 months, was noted to have a disease progression. Patient 2 had disease progression after 3 months of nivolumab therapy.ConclusionsAlthough PD-L1 is expressed in these patients with renal medullary carcinoma, response to nivolumab was only observed in patient 1 whose tumor has the lowest rate of PD-L1 expression. This may suggest that in RMC, response to PD-L1 inhibition therapy may not correlate with the rate of PD-L1 expression.

Kidney Cancers in Adolescents & Young Adults

Kidney Cancers in Adolescents & Young Adults

Molecular profiling of renal medullary carcinoma to reveal frequent alterations in chromatin remodeling genes and to identify EZH2 as a relevant therapeutic target.

571 Background: Renal medullary carcinoma (RMC) is a rare and highly aggressive malignancy that affects primarily young adults with sickle cell trait. The prognosis of RMC is poor with a median survival of about 12 months from diagnosis. It has been previously shown that loss of heterozygosity of SMARCB1 occurs in the majority of cases leading to protein loss. However, a comprehensive molecular profiling of this disease remains unknown. Methods: Whole-exome sequencing (WES) of 9 RMC matched tumor-normal cases and 1 unmatched case were performed. In addition, single nucleotide polymorphism (SNP) analysis was done using the Affymetrix SNP 6.0 array. To test differentially expressed genes between RMC cases and normal kidney, RNA sequencing was carried out. The effect of EZH2 inhibition on in vitro RMC tumor cell proliferation was assessed using the MTT assay. Results: WES analysis of 9 paired RMC cases identified 233 non-synonymous somatic mutations (median: 21; range: 12-44). We observed frequent mutations in chromatin remodeling genes in 7 of 10 RMC cases, including mutations in SMARCB1 (n = 2) and SMARCA5 gene (n = 1). SNP analysis demonstrated that only the case with SMARCA5 somatic mutation harbored SMARCB1 monoallelic loss. However, all RMC cases had loss of SMARCB1 protein by immunohistochemistry. Ingenuity pathway analysis using RNA sequencing data identified EZH2 as one of the top over-expressed upstream regulators (Z-score = 3.7; p-value = 1.6x10-6). RT-PCR and western blot analyses confirmed that EZH2 expression is elevated at both mRNA and protein levels corresponding to SMARCB1 loss in RMC tumors. In vitro assessment of a novel RMC tumor cell line derived from the case harboring SMARCB1 deletion showed that EZH2 inhibitor GSK343 inhibited proliferation of this cell line. Conclusions: Our data reveal that 30% of RMC cases showed inactivation of SMARCB1 through somatic mutations or monoallelic loss, suggesting that additional epigenetic mechanisms may lead to gene inactivation. In addition, our data suggest that EZH2 may be a relevant therapeutic target in RMC.

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.

Renal medullary carcinoma and sickle cell trait: A systematic review.

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation.

SMARCB1/INI1 inactivation in renal medullary carcinoma

Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied. Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription. The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities.

Expression of OCT3/4 in Renal Medullary Carcinoma Represents a Potential Diagnostic Pitfall

Renal medullary carcinoma (RMC) is a rare aggressive renal tumor that classically afflicts young black patients with sickle cell trait. The tumor shows overlapping pathologic and clinical characteristics with collecting duct carcinoma and urothelial carcinoma, which often results in a diagnostic conundrum. When the tumor presents in a metastatic site in the absence of a history of renal tumor, germ-cell tumor is often a primary diagnostic consideration, given the young age of most patients. OCT3/4 is an immunohistochemical marker that is routinely used in clinical practice and is widely considered to be a specific marker for germ-cell tumor. We studied the pathologic and immunohistochemical characteristics of 14 cases of RMC. Immunohistochemical staining for OCT3/4 staining was noted in 10/14 RMCs with strong nuclear staining in 8 cases and was absent in all cases of collecting duct carcinoma and urothelial carcinoma. OCT3/4 expression is not specific to germ-cell tumor and is seen in the majority of RMC cases. Caution must be exercised in interpreting the presence of OCT3/4 staining in a poorly differentiated neoplasm, especially at a metastatic site as a germ-cell tumor, as this may represent a potential diagnostic pitfall.

Renal medullary carcinomas: histopathologic phenotype associated with diverse genotypes

Chromosomal abnormalities and gene mutations have become major determinants in the classification of kidney carcinomas. Most renal medullary carcinomas develop in patients with hereditary sickle cell disease, but sporadic cases unassociated with sickle cell disease have also been described, for which underlying genetic abnormality is unknown. We evaluated 3 patients with renal medullary carcinoma (1 patient with sickle cell disease and 2 patients without sickle cell disease) for germ line and somatic mutations in genes commonly involved in pathogenesis of renal carcinomas using denaturing high-performance liquid chromatography and direct sequencing. Chromosomal abnormalities were studied by the conventional cytogenetic and SNP arrays analysis. Expression of hypoxia-inducible factor 1α was examined using immunohistochemistry. Two new mutations in the gene for fumarate hydratase were identified in 1 case of medullary renal carcinoma without sickle cell disease: a germ line mutation in exon 6 (R233H) and an acquired (somatic) mutation in exon 8 (P374S). No fumarate hydratase mutations were identified in the other 2 patients. The second sporadic case of renal medullary carcinoma harbored double somatic mutations in von Hippel-Lindau gene, and renal medullary carcinoma in the patient with sickle cell disease showed von Hippel-Lindau gene promoter methylation (epigenetic silencing). No consistent pattern of chromosomal abnormalities was found between 2 cases tested. All 3 cases showed increased hypoxia-inducible factor 1α expression. Medullary renal carcinomas from patients with or without sickle cell disease show involvement of genes important in hypoxia-induced signaling pathways. Generalized cellular hypoxia (in sickle cell disease) or pseudohypoxia (in tumors with fumarate hydratase and von Hippel-Lindau mutations or epigenetic silencing) may act alone or in concert at the level of medullary tubular epithelium to promote development of this rare type of renal carcinoma, which could then be genetically reclassified as either fumarate hydratase-associated renal carcinomas or high-grade clear cell renal cell carcinomas.

ALK rearrangement in sickle cell trait‐associated renal medullary carcinoma

Renal Medullary Carcinoma (RMC) is an aggressive malignancy that affects young black individuals with sickle cell trait. No effective treatment is available, resulting in an ominous clinical course, with overall survival averaging less than four months. We report rearrangement of the ALK receptor tyrosine kinase in a pediatric case of RMC harboring a t(2;10)(p23;q22) translocation. Mass spectrometry-based proteomic evaluation identified a novel ALK oncoprotein in which the cytoskeletal protein vinculin (VCL) was fused to the ALK kinase domain. The resulting VCL-ALK fusion does not contain known self-association domains, but includes the talin binding domains of vinculin. We demonstrate coprecipitation of strongly tyrosine phosphorylated talins with the VCL-ALK oncoprotein, suggesting that ALK oncogenic crossphosphorylation is mediated by interactions between neighboring VCL-ALK proteins on a talin scaffold. This report widens the spectrum of ALK-related tumors and ALK fusion partners, and provides a rationale for treating RMC with targeted ALK inhibitors.

Carcinome médullaire du rein : rapport d’une rémission sous gemcitabine-cisplatine et revue des perspectives thérapeutiques

We report a case of renal medullary carcinoma concerning a 38-year-old woman. Heterozygote sickle cell trait was noticed in her past medical history. The physical examination was unremarkable. The CT-scan revealed a left renal mass of 48 mm x 20 mm, hypovascularised, located in the lower pole of the kidney with extension into the sinus. There were also enlarged lymph nodes laterally to aortic artery and between the aorta and the vena cava. A left radical nephrectomy with lymphadenectomy was performed. The histological examination with immuno-histo-chemical analysis revealed a renal medullary carcinoma T1N2R0 (TNM 2002). An adjuvant chemotherapy consisting of gemcitabine-cisplatin was administered. A regression of the residual lymph nodes was noticed after the six cycles of chemotherapy and the PET-Scan was negative. The patient underwent a second operation and the residual mass was excised. No tumor cell was found at the histological examination of the residual nodes. The patient had no clinical or radiological symptoms of progression eight months after the radical nephrectomy. We discuss the diagnostic criteria and analyse the therapeutic perspectives.

Renal Medullary Carcinoma: The Bronx Experience

Renal medullary carcinoma (RMC) is a devastating and extremely rare malignancy primarily afflicting young men with sickle cell trait. We present our clinical experience with 9 cases of RMC during a 10-year period and briefly review the published data. A retrospective chart review of 9 cases of RMC during a 10-year period at our institutions was performed. The clinical patient characteristics, presentations, treatments, and outcomes were recorded. The radiographic images and pathologic specimens were reviewed. Applicable studies were selected from a Medline search. All 9 patients had sickle cell trait, the male/female ratio was 6:3, and the age range was 13 to 31 years. All the patients presented with flank pain, two thirds had hematuria, and 3 of the 9 patients presented with a palpable mass. Eight of the nine tumors were right sided, ranging from 4 to 12 cm in the greatest diameter. Of the 9 patients, 7 underwent radical nephrectomy. One patient was deemed to have unresectable disease by the operating surgeon, and one was given initial chemotherapy after biopsy of a metastatic lesion. The neoadjuvant therapies varied. Overall survival ranged from 4 to 16 months, with 2 patients still living at the last follow-up visit. Our urban setting likely explains our relatively large experience with this rare and extremely aggressive tumor. An early diagnosis is critical, and a high index of suspicion should be given to any individual with sickle cell trait and new-onset hematuria, especially in the setting of a right-sided mass. Prospective trials are needed for chemotherapy/immunotherapy, because surgical intervention alone is inadequate.

Renal medullary carcinoma: report of seven cases from Brazil

We report seven cases of renal medullary carcinoma collected from several institutions in Brazil. In spite of a relatively high incidence of sickle cell trait in Brazil, this is a rare tumor. All patients were males between the ages of 8 and 69 years (mean 22 years). From the collected information, the most frequent presenting symptoms were gross hematuria and flank or abdominal pain. The duration of symptoms ranged from 1 week to 5 months. Most of the tumors were poorly circumscribed arising centrally in the renal medulla. Size ranged from 4 to 12 cm (mean 7 cm) and hemorrhage and necrosis were common findings. All seven cases described showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. All cases disclosed the characteristic reticular pattern consisting of tumor cell aggregates forming spaces of varied size, reminiscent of yolk sac testicular tumors of reticular type. Other findings included microcystic, tubular, trabecular, solid and adenoid-cystic patterns, rhabdoid-like cells and stromal desmoplasia. A peculiar feature was suppurative necrosis typically resembling microabscesses within epithelial aggregates. The medullary carcinoma of the 69-year-old patient was associated with a conventional clear cell carcinoma. To our knowledge, this association has not been previously reported and the patient is the oldest in the literature. The survival after diagnosis or admission ranged from 4 days to 9 months. The 8-year-old African–Brazilian patient with a circumscribed mass is alive and free of recurrence 8 years after diagnosis. This case raises the question whether a periodic search for renal medullary carcinoma in young patients who have known abnormalities of the hemoglobin gene and hematuria could result in an early diagnosis and a better survival.

Renal medullary carcinoma: unsuspected diagnosis at stone protocol CT

Renal medullary carcinoma (RMC) is an aggressive neoplasm occurring almost exclusively in adolescents and young adults with sickle cell (SC) hemoglobinopathies, usually sickle cell trait (SCT) or hemoglobin SC disease. The most common presentations are hematuria and flank or abdominal pain. It is a highly malignant tumor, and responses to chemotherapy are rare and transient resulting in a dismal prognosis. A high level of suspicion is necessary when evaluating at risk patients presenting with hematuria or flank pain, as currently it appears that only early diagnosis could potentially alter the outcome of this disease. We report a case of RMC in a young male patient with SCT, who presented to the emergency department with low back pain and microscopic hematuria, clinically mimicking acute obstructing urolithiasis. Our case emphasizes the need to consider alternate diagnoses when evaluating computed tomography scans for acute flank pain.

Cytologic features of renal medullary carcinoma

Renal medullary carcinoma is a rare tumor that is most common in young black men with sickle cell disease or trait. Patients often present with advanced disease at the time of diagnosis, and their prognosis is poor, even with aggressive therapy. The clinical and pathologic features of renal medullary carcinoma have been described in several articles, but reports describing the cytologic features are rare. In the current report, the authors describe the cytologic features of three cases of renal medullary carcinoma. The patients were young black men with sickle cell trait ages 20 years, 33 years, and 33 years. All three patients presented with hematuria, flank pain, and a renal mass. The cytologic specimens from all three patients showed primarily cohesive groups of cells with vacuolated cytoplasm that often displaced or indented the nuclei. The nuclei often had irregular membranes, coarse or vesicular chromatin, and prominent nucleoli. Both of the two patients who were tested with fluorescence in situ hybridization were negative for the bcr/abl rearrangement. Renal medullary carcinoma should be considered in the differential diagnosis of patients who present with hematuria or a renal mass, especially in young black men with sickle cell disease or trait. Cytologically, renal medullary carcinoma cells appear similar to the cells in high-grade carcinoma. Immunohistochemical studies can be helpful in distinguishing renal medullary carcinoma from other poorly differentiated kidney tumors, except for collecting duct carcinoma. The clinical findings are key to diagnosing renal medullary carcinoma.

Renal medullary carcinoma associated with sickle cell trait: radiologic findings.

To correlate the radiologic and pathologic findings in patients with renal medullary carcinoma and sickle cell trait. Radiologic studies of five pathologically proved cases of renal medullary carcinoma were retrospectively correlated with gross pathologic findings. Excretory urograms, computed tomographic (CT) scans, sonograms, photographs of the gross surgical specimens, and an angiogram were available for review. Each case was analyzed for tumor location, pattern of growth, contrast enhancement and echotexture, angiographic pattern, and stage. All tumors arose centrally within the kidney, grew in an infiltrative pattern, and invaded the renal sinus. Caliectasis without pelviectasis was present in three cases. Contrast enhancement and echotexture were heterogeneous in all patients. Tumor necrosis with communication into the collecting system occurred in one patient. The one available angiogram demonstrated hypovascularity. Patients with renal medullary carcinoma share particular demographic, clinical, and radiologic features that might enable radiologists to suggest a specific diagnosis.