Search

Objective: To review the presentation and long-term oncologic outcomes of patients with regressed ("burnt out") primary testicular germ cell tumors (GCT). Certain testicular GCT can present with complete regression of the primary tumor. It is not well established if this is associated with more aggressive disease or worse oncologic outcomes., Methods: We queried our prospectively maintained testicular cancer clinical database at a tertiary cancer center and identified patients without prior chemotherapy who had regressed primary GCT at radical orchiectomy from 1990 to 2023. All specimens were reviewed by a genitourinary pathologist at diagnosis. Long-term clinical outcomes were reported by Kaplan-Meier method., Results: Fifty-six patients met inclusion criteria; at diagnosis, 17 had no evidence of extra-testicular disease and 39 had advanced (clinical stage [CS] II+) GCT. All CSx (no viable disease or germ cell neoplasia in situ at orchiectomy, and no evidence of advanced disease) and CS0 patients were managed with surveillance and had 5-year recurrence-free survival (RFS) of 88% (95% CI: 39%, 98%). All patients with CS II+ disease underwent primary treatment with surgery (n = 5) or first-line chemotherapy (n = 34). Two- and 5-year RFS for patients with CSII+ disease was 94% (95% CI: 78%, 98%) and 90% (95% CI: 72%, 97%), respectively., Conclusion: Patients with regressed primary testicular GCT often present with advanced disease, possibly due to lack of early clinical signs from the primary tumor. Our analysis shows excellent long-term oncologic outcomes similar to those reported in the literature for patients with viable primary testicular GCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To report the mutational profile and clinical outcomes of a cohort of patients with KIT-mutant seminomas and nonseminomatous germ-cell tumors (SGCT/NSGCTs)., Patients and Methods: Retrospective cohort study of all patients with KIT-mutant GCTs sequenced at Memorial Sloan Kettering between March 2014 and March 2020. Tumors were assessed with MSK-IMPACT, a DNA next-generation sequencing assay for targeted sequencing of up to 468 key cancer genes., Results: Among 568 patients with GCTs, 8.1% had somatic KIT mutations, including 28 seminomas and 18 mixed/NSGCTs. Exons 17 (67.3%), 11 (22.4%), and 13 (6.1%) were most commonly affected. KIT-mutant cases were enriched for oncogenic RAS/MAPK pathway alterations compared to KIT-wildtype cases (34.8% vs 19.2%, P = .02). Among KIT-mutant cases, concurrent mutations were noted in KRAS (21.7%), RRAS2 (11.8%), CBL (6.5%), NRAS (4.3%), MAP2K1 (2.2%), and RAC1 (2.2%). Mutations in KRAS, RRAS2, and NRAS were mutually exclusive. In all, 73.9% of patients developed metastases and 95.7% received chemotherapy. No patients received KIT-directed tyrosine kinase inhibitors (TKIs). Classification as a NSGCT rather than a SGCT was associated with an increased risk of death (hazard ratio 9.1, 95% confidence interval 1.1-78.4, P = .04) while the presence of a concurrent RAS/MAPK pathway alteration was not (hazard ratio 0.8, 95% confidence interval 0.1-4.3, P = .76)., Conclusion: Mitogenic driver alterations can co-occur with activating KIT mutations, which may explain the lack of efficacy of KIT-directed TKIs in prior trials. Novel KIT-directed TKIs that target exon 17 mutations may benefit chemotherapy-refractory patients with KIT-mutant GCTs without RAS/MAPK alterations. Dual MEK/KIT inhibitor therapy in KIT-mutant GCTs with concurrent RAS/MAPK alterations could also be a plausible therapeutic strategy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess which patients respond best following cytoreductive nephrectomy for renal cell carcinoma (RCC) with sarcomatoid dedifferentiation (sRCC) and whether outcomes are improving over time., Methods: We identified 562 patients with metastatic RCC treated between 1989 and 2018 with cytoreductive nephrectomy. We reviewed baseline clinical and pathologic characteristics, including the presence of sRCC, and metastatic sites at time of nephrectomy. The primary study endpoint was overall survival (OS). Univariate and multivariate Cox-regression analyses were used to identify significant predictors of OS., Results: The study cohort had 192 sRCC patients, with a median age of 59 years. Frequently involved metastatic locations were lung (n = 115), retroperitoneal nodes (n = 63), and axial skeleton (n = 43). Lung metastasis were more prevalent in clear cell histology (P = .0017) whereas nodal involvement was associated with nonclear cell subtypes (P = .0064). Median follow-up was 14 months. Estimated 2- and 5-year OS were 34.1% and 14.8%, respectively. On multivariate analysis, metastases to the liver (HR = 1.64; 95% CI 1.02-2.63; P = .04), lung (HR = 1.50; 95% CI 1.05-2.14; P = .03), retroperitoneal nodes (HR = 1.52; 95% CI 1.03-2.25; P = 0.04) and nonclear cell histology (HR = 1.61; 95% CI 1.10-2.35; P = .01) were associated with worse OS in the sRCC cohort., Conclusion: OS after cytoreductive nephrectomy for sRCC and non-sRCC is improving over time. In patients with sRCC, presentations with unifocal metastasis not involving the liver or lung, clear cell histology and node negative disease have better outcomes following cytoreductive nephrectomy and may yield greater benefit from the procedure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate, in detail, the histopathologic features of metastatic testicular germ cell tumors to retroperitoneal lymph nodes treated with primary retroperitoneal lymph node dissection (RPLND) and correlate the findings with patients' outcomes., Materials and Methods: We studied 183 patients with documented pathologic stage II disease with or without elevated serum tumor markers, selected from 453 patients who underwent primary RPLND at our institution from 1989 to 2002. Tumor type(s), size and extent of disease, and amount of tumor necrosis were assessed and correlated with outcome., Results: Embryonal carcinoma was the most common tumor type, present as the only component in 99 cases (54%) and the predominant tumor type (>50%) in 142 (78%). The number of positive lymph nodes ranged from 1 to 40 from a total of 2-80 lymph nodes examined (median, 28). Extranodal extension (ENE) was identified in 120 cases (66%). Among 73 patients followed up expectantly and with normal serum tumor markers, 19 experienced relapse, the probability of which was higher in patients with more positive nodes, larger metastases, and presence of ENE. However, none of these differences was statistically significant (all P >.2). The predominance of embryonal carcinoma and the presence of tumor necrosis were not significantly associated with outcome., Conclusion: In this cohort, most patients treated with primary RPLND and with positive lymph nodes also had ENE. We did not identify any variables to be significantly associated with relapse after RPLND in patients managed expectantly. Additional studies with more patients are needed to validate our findings., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We report a case of renal cell carcinoma (RCC) with extensive oncocytoid features developing in a 12-year-old African-American boy after chemotherapy for cardiac leiomyosarcoma at 3 months of age. The tumor showed histopathologic features similar to those previously reported in RCC after chemotherapy for neuroblastoma and now considered a specific entity in the World Health Organization classification of renal tumors as "RCC associated with neuroblastoma." Our report expands the spectrum of tumors (beyond neuroblastoma) in which RCCs with such an appearance can arise in the pediatric age group after chemotherapy.

Objectives: To evaluate 5-alpha-reductase (5alphaR) expression in benign and malignant urothelium and to assess the relationship between 5alphaR expression and tumor stage, tumor grade, and clinical outcome in patients with urothelial carcinoma/transitional cell carcinoma., Methods: We performed immunohistochemistry for 5alphaR on 53 urothelial specimens from 36 patients with transitional cell carcinoma treated at our institution between June 2002 and July 2003. For each tumor and the adjacent nontumor urothelium, a semiquantitative staining score was calculated. We used t tests and analysis of variance to compare the staining score across groups. Kaplan-Meier and logistic regression analyses were performed to assess the relationship between 5alphaR expression and clinical outcome., Results: 5alphaR was expressed throughout the non-neoplastic urothelium. Nontumor urothelium had greater mean staining scores than did tumor specimens (160.1 versus 105.5, P <0.01). Low staining scores were associated with high grade (P <0.05), Stage pT3, pT4, and pTis (P <0.05), and disease progression (P <0.05). A staining score less than the median was a risk factor for progression (odds ratio 6.2, P <0.01) on univariate regression analysis. Patients with a staining score less than the median had a greater likelihood of disease progression (log-rank P <0.05) and cause-specific mortality (log-rank P <0.05)., Conclusions: We demonstrated 5alphaR expression in human urothelium and found that expression is decreased in transitional cell carcinoma in relation to tumor grade and stage. Decreased 5alphaR expression was associated with disease progression and cause-specific mortality.

Objectives: To evaluate the expression of the androgen receptor (AR) in transitional cell carcinoma (TCC) of the bladder, and to assess whether its expression correlated with pathologic tumor stage. TCC of the bladder is three times more common in males than in females. The origin of this sex difference in incidence is unknown., Methods: We evaluated tumor specimens from 49 consecutive patients treated for TCC of the bladder at our institution between July 2002 and June 2003. Immunohistochemistry was performed using a monoclonal mouse anti-AR antibody on paraffin-embedded tissue sections of tumors obtained from transurethral resection, radical cystectomy, or resection of metastases. Specimens were assessed for AR expression, and, in tumors that demonstrated AR staining, the percentage of nuclei that stained positive was recorded., Results: Of the 49 tumors, 26 (53.1%) expressed the AR. The percentage of tumors that expressed the AR decreased with increasing pathologic stage, from 88.9% of pTa lesions to 0% of pT3 tumors. Overall, 75% of superficial tumors (pTa + pT1 + carcinoma in situ) expressed the AR compared with 21.4% of invasive tumors (pT2 + pT3; P = 0.002). In addition, among AR-expressing tumors, the mean percentage of nuclei that stained positive for the AR was significantly greater in pTa tumors (62.5%) than in pT1 (31%) or pT2 (20%) tumors (P = 0.005)., Conclusions: We found a decrease in AR protein expression in tumors with increased pathologic stage. Our data suggest that the loss of AR expression is associated with invasive bladder cancer.