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Medullary sponge kidney (MSK) is an uncommon kidney malformation, characterized by cystic dilatation of the precalyceal papillary collecting ducts. Urography and computed tomography scan represent the gold standard to detect this congenital disorder. A clear diagnosis is not always feasible, especially in the presence of a concomitant renal mass, which in turn can be difficult to detect in MSK patients. When conventional imaging is inconclusive, a renal biopsy can be considered in doubtful cases. Here, we report a unique case of a Bellini duct carcinoma in a patient with MSK and we review the literature on this complex condition.

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Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment.

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INTRODUCTION: Rare genitourinary tumors are lacking of randomized and observational data. We aimed to describe the clinical characteristics and outcomes of patients with collecting duct carcinoma (CDC) through the Meet-URO 23/I-RARE database. MATERIALS AND METHODS: We performed a multicentric retrospective-prospective study within the Meet-URO network, enrolling patients from March 2021 (retrospectively up from 2011) until March 2023. The primary objective was to describe the clinical characteristics of patients with CDC, the secondary objectives were to assess the oncological outcomes in terms of relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to treatment. RESULTS: 37 patients with CDC were enrolled. Four patients underwent only surgery, 33 received first-line systemic therapy. Median OS was 22.1 months (95% CI, 8.9-31.9). Median RFS for patients with localized disease at onset (n = 30) was 3.7 months (95% CI, 1.9-12.8), median PFS for first-line treatment was 3.3 months (95% CI, 2.7-9.9), with an ORR of 27%. Female sex and good performance status (PS) were associated with longer PFS (P = .072 and P < .01, respectively) and OS (P = .030 and P = .141, respectively). CONCLUSIONS: Patients with CDC had dismal prognosis, with scarce benefit from the available treatments. Female sex and good PS seemed to be associated with better prognosis.

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Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

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Synchronous renal malignancies are seldom encountered or diagnosed post-renal resection. A combination of renal cell carcinoma (RCC) and urothelial carcinoma (UC) is most commonly reported. Typically, the RCC subtype is clear-cell RCC; however, a combination of collecting duct carcinoma (CDC) and UC has rarely been reported in the existing literature. Here, we present two cases of synchronous renal malignancy, specifically a combination of CDC and UC, in the ipsilateral kidney.

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Introduction: Renal collecting duct carcinoma is often found in advanced cancers and has a poor prognosis. Here, we present the case of symptomatic metastatic collecting duct carcinoma in which we observed an initial therapeutic effect of immune checkpoint inhibitors plus tyrosine kinase inhibitors. Case presentation: The patient was a 69-year-old male who was referred to our hospital for examination of a right chest tumor and related pain. Contrast-enhanced computed tomography and tumor biopsy were performed, leading to a diagnosis of collecting duct carcinoma. A combination of pembrolizumab plus axitinib was initiated as first-line therapy; right chest pain decreased, and tumor shrinkage was observed. Seven months after treatment initiation, tumor progression was noted. Cabozantinib was initiated as second-line therapy; however, was discontinued due to patient fatigue. The patient died 15 months after the initiation of treatment. Conclusion: For symptomatic metastatic collecting duct carcinoma, pembrolizumab plus axitinib may have initial therapeutic effects.

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Vascular endothelial growth factor receptor tyrosine kinase inhibitors are known to cause perforation as one of their severe side effects, and postoperative and postradiation therapy are known risk factors. However, there are few studies on perforation following tumor shrinkage. A 78-year-old woman with postoperative recurring left collecting duct carcinoma of the right hilar lymph nodes and mediastinum underwent eight courses of nivolumab plus cabozantinib, resulting in tumor shrinkage. Three days after the last administration, she developed fever and cough and was hospitalized for right lobar pneumonia. The patient received long-term antibiotics for bronchial fistula with the destruction of the bronchial wall and secondary lung abscess. When using nivolumab plus cabozantinib combination therapy for a tumor with bronchial invasion, physicians should be aware of bronchial perforation as the tumor shrinks.

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BACKGROUND: Collecting duct carcinoma (CDC) is a rare renal tumor, originating from the distal collecting duct. CDC rarely presents as a primary tumor outside the renal system. CASE PRESENTATION: In this study, we report a rare case of collecting duct carcinoma, with an initial presentation of retroperitoneal lymph node metastasis, and no identifiable primary renal tumor on CT, at the time of diagnosis. The patient was a 64-year-old man presenting with lower back pain. Preoperative CT showed a round, soft tissue mass, measuring 6.7 × 4.4 × 3.3 cm, in the left retroperitoneum with no exact occupying lesion in the left kidney. Clinically, ectopic pheochromocytoma was considered to be a differential diagnosis, and tumor resection was performed. Postoperative pathological results demonstrated that the mass was a fused lymph node, and the tumor cells were destroying the structure. The final diagnosis was lymph node metastatic collecting duct carcinoma, by histology and immunohistochemistry. No further treatment was performed as no space occupying lesion was found in the kidney. Three months later, CT was reexamined, and a mass of 3.6 cm in diameter, was found in the lower left kidney, along with multiple soft tissue masses, in the left renal hilum. Considering recurrence or metastasis, the patient was recommended to undergo surgical treatment, but the patient refused. Four months later, CT was re-examined. The tumor had rapidly progressed but the patient refused treatment again. As per the author's press release (eleven months after the first discovery), the patient is still alive. CONCLUSION: CDC is a rare malignant renal carcinoma, with a high chance of rapid progress, regional lymph nodes involvement and metastasis. It presents diagnostic challenges to clinicians and pathologists, particularly, in the absence of radiographically detectable intrarenal lesions. Definite diagnosis is based on pathological examination combined with immunohistochemical staining.

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BACKGROUND: Collecting duct carcinoma (CDC) of the kidney is associated with an aggressive course, limited response to treatment, and poor prognosis. Platinum-based chemotherapy is currently recommended as the first-line treatment in patients with metastatic CDC. Accumulating evidence supports the use of immunotherapy with checkpoint inhibitors as second-line therapy. CASE PRESENTATION: In this case report, we describe the first case of avelumab administration due to disease progression during chemotherapy with gemcitabine and cisplatin in a Caucasian, 71-year-old man presenting with multiple metastases due to CDC of the kidney. The patient initially responded well to four cycles of chemotherapy and his performance status improved. After two additional chemotherapy cycles, the patient presented with new bone and liver metastases (mixed response to chemotherapy with an overall 6-month progression-free survival). We offered him avelumab as a second-line treatment in this setting. The patient received a total of three cycles of avelumab. The disease remained stable (no new metastases during treatment with avelumab), and the patient developed no complications. To alleviate his symptoms, radiation therapy for the bone metastases was decided. Despite successful radiation of the bone lesions and further improvement of symptoms, the patient developed hospital-acquired pneumonia and died approximately ten months after the initial diagnosis of CDC. CONCLUSIONS: Our findings suggest that the applied treatment modality with gemcitabine and cisplatin chemotherapy followed by avelumab was effective in terms of both progression-free survival and quality of life. Still, further studies assessing the use of avelumab in this setting are mandatory.

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The term variant histology renal cell carcinomas (vhRCCs), also known as non-clear cell RCCs, refers to a diverse group of malignancies with distinct biologic and therapeutic considerations. The management of vhRCC subtypes is often based on extrapolating results from the more common clear cell RCC studies or basket trials that are not specific to each histology. The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.

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BACKGROUND: Renal medullary carcinoma (RMC) and collecting duct carcinoma (CDC) are rare entities with a poor outcome. First-line metastatic treatment is based on gemcitabine + platinum chemotherapy (GC) regimen but retrospective data suggest enhanced anti-tumour activity with the addition of bevacizumab. Therefore, we performed a prospective assessment of the safety and efficacy of GC + bevacizumab in metastatic RMC/CDC. METHODS: We conducted a phase 2 open-label trial in 18 centres in France in patients with metastatic RMC/CDC and no prior systemic treatment. Patients received bevacizumab plus GC up to 6 cycles followed, for non-progressive disease, by maintenance therapy with bevacizumab until progression or unacceptable toxicity. The co-primary end-points were objective response rates (ORRs) and progression-free survival (PFS) at 6 months (ORR-6; PFS-6). PFS, overall survival (OS) and safety were secondary end-points. At interim analysis, the trial was closed due to toxicity and lack of efficacy. RESULTS: From 2015 to 2019, 34 of the 41 planned patients have been enroled. After a median follow-up of 25 months, ORR-6 and PFS-6 were 29.4% and 47.1%, respectively. Median OS was 11.1 months (95% confidence interval [CI]: 7.6-24.2). Seven patients (20.6%) discontinued bevacizumab because of toxicities (hypertension, proteinuria, colonic perforation). Grade 3-4 toxicities were reported in 82% patients, the most common being haematologic toxicities and hypertension. Two patients experienced grade 5 toxicity (subdural haematoma related to bevacizumab and encephalopathy of unknown origin). CONCLUSION: Our study showed no benefit for bevacizumab added to chemotherapy in metastatic RMC and CDC with higher than expected toxicity. Consequently, GC regimen remains a therapeutic option for RMC/CDC patients.

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Objective: To explore the clinical, imaging, pathologic features, treatment, and prognostic outcomes in 23 cases of collecting duct carcinoma (CDC) from a single center. Methods: The clinical and imaging findings, pathological features, treatment methods, and outcomes of the 23 patients with CDC confirmed by microscopic examination between 2003 and 2020 at our institution were retrospectively reviewed. Descriptive statistics of demographic and clinical variables were applied. Kaplan-Meier method was used to analyze survival data and log-rank test statistic survival differences between groups. Cox regression analysis was employed to identify variables independently related to overall survival (OS). Results: A total of 23 patients with CDC were identified. The mean age was 50.8 years. Stage III or IV tumors were diagnosed in 82.6% of the patients at diagnosis. The average size of the tumor was 6.58 cm, and the left kidney was more involved than the right. The median OS was 12 months. The OS rates at 1 and 2 years were 43.5% and 26.1%, respectively. Twenty patients underwent nephrectomy, 3 underwent nephroureterectomy, and 9 (39.1%) patients received subsequent therapeutic interventions following surgery. Distant metastasis and no symptoms at initial diagnosis proved to be an independent factor of unfavorable survival in Cox regression analysis. Conclusions: CDC is a rare and highly aggressive malignant renal tumor, and most patients present at an advanced stage at initial diagnosis. More than half of the patients died within 1 year after surgery. Distant metastasis and no clinical symptoms at initial diagnosis were independent risk prognostic factors for patients with CDC.

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Collecting duct carcinoma (also known as Bellini tumour) and renal medullary carcinoma are two extremely rare and aggressive renal cancers. They are both less responsive to conventional treatments used in clear cell renal carcinoma. There are very few studies evaluating their optimal management and currently, at the metastatic stage, polychemotherapy based on platinum salts remains the most widely used. The emergence of new treatments such as anti-angiogenic TKIs, immunotherapy or treatments targeting specific genetic abnormalities, opens up a new field of possibilities in the management of these cancers. The evaluation of the response to these treatments is therefore essential. In this article, we will review the status of their management and the various studies that have evaluated recent treatments in these two cancers.

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For years, prospective randomized clinical trials excluded patients with non-conventional histologies of renal cell carcinoma (RCC). The paucity of data has led to adopting the same treatment strategies used for clear-cell RCC (ccRCC). In the present narrative review, we explored state of the art about use of immune checkpoint inhibitors (ICIs) in variant histologies of RCC. According to the results collected, ICIs as monotherapy showed promising antitumor activity in advanced non-clear cell (ncc)RCC. The objective response rate (ORR) was similar to that observed with single-agent anti-PD-1 in the ccRCC population, either in the first-line or the second-line setting, and responder patients experienced an early and durable benefit. Combined ICI-based strategies have shown increasing evidence in nccRCC and robust results in the sarcomatoid variants of RCC. A definitive recommendation about treating non-conventional histologies, either in adjuvant or metastatic settings, should be supported by more extensive dedicated trials.

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INTRODUCTION: Controlled contemporary analyses of mortality in metastatic collecting duct renal cell carcinoma (mcdRCC) are unavailable. We addressed this knowledge gap and tested rates of treatment and associated mortality in patients with mcdRCC. PATIENTS AND METHODS: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 155 mcdRCC patients. Kaplan-Meier plots and Cox proportional hazards regression models tested the effect of treatment (cytoreductive nephrectomy [CN] alone vs. systemic therapy [ST] alone vs. combination of both CN + ST) on overall mortality (OM). RESULTS: In the overall cohort (n = 155), 57 patients (37%) were treated with combination of both CN + ST, 46 (30%) underwent CN alone, 28 (18%) received ST alone, and 24 (15%) had none/unknown treatment. According to age categories (≤ 59 vs. 60-69 vs. ≥ 70 years), rates of combination of both CN + ST were 45% vs. 45% vs. 14%, respectively. CN alone was the most frequent type of treatment in patients aged ≥ 70 (50%). Median overall survival was 4.0 months for CN alone vs. 5.5 months for ST alone vs. 9.0 months for combination of both CN+ST. In multivariable Cox regression models, where CN alone was the referent, the use of ST alone and combination of both CN + ST were respectively associated with a HR of 0.74 (P = .3) and 0.43 (P < .001), after adjustment for all covariates. CONCLUSIONS: In mcdRCC patients, concomitant use of CN and ST results in lowest mortality, followed by ST alone, and CN alone. In consequence combination of both CN + ST should be recommended whenever applicable.

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INTRODUCTION: Collecting duct carcinoma (CDC) is a rare renal malignancy. We relied on a large population-based cohort to address epidemiology, clinical characteristics, and treatment of CDC patients. We also tested survival in the overall cohort, as well as in stage-specific fashion. MATERIALS AND METHODS: Within Surveillance, Epidemiology, and End Results (2004-2018) database, we identified 399 CDC patients. Based on Kaplan-Meier plots survival estimates, conditional survival rates were derived according to disease stage. Cox regression models tested for predictors of cancer specific mortality (CSM). RESULTS: Overall, 273 (68.4%) patients were male, 236 (59.2%) had T3-4 stages, 148 (37.1%) had lymph node invasion, and 156 (39.1%) had distant metastases at initial diagnosis. Nephrectomy alone was commonest in stage I-II (n = 91/99, 92%) and III (n = 94/116, 81%). Combination of both nephrectomy and systemic therapy was commonest in stage IV (n = 62/172, 36%). In the overall cohort, median cancer specific survival was 18 months. Provided a disease-free interval of 24 months, five-year Kaplan-Meier estimated survival at diagnosis increased from 74.2 to 91.0% in stage I-II, from 31.1 to 65.3% in stage III, and from 6.3 to 34.1% in stage IV. In multivariable Cox regression models addressing CSM, systemic therapy (Hazard Ratio [HR]: 0.47, P = 0.020), nephrectomy (HR: 0.37, P < 0.001) and combination of both (HR: 0.28, P < 0.001) exhibited a strong protective effect. CONCLUSION: Despite its highly aggressive phenotype and dismal survival, CDC is sensitive to nephrectomy and/or systemic therapy. Moreover, even for advanced stage, a more favorable prognosis can be achieved in patients, who benefit of disease-free interval after diagnosis and initial treatment.

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BACKGROUND: The BONSAI phase II trial recently demonstrated the activity of cabozantinib in metastatic collecting duct patients. The outcomes of patients in this setting treated with immunotherapy as second-line is unknown. The aim of the present report was to describe outcomes of patients enrolled in the BONSAI trial that received nivolumab as second-line treatment. MATERIAL AND METHODS: We describe the oncological outcomes in terms of overall response rate, progression-free survival, overall survival and safety. We excluded patients that did not receive any second-line treatment or were treated with agents other than nivolumab. RESULTS: We identified five patients of whom one was excluded due to lack of data. Three patients obtained clinical benefit (one partial response, two stable disease); the second-line progression-free survival (nivolumab) ranged from 2.8 to 19.9 months to and second-line overall survival ranged from 5.1 to 26.5 months. No new safety signals were observed. CONCLUSIONS: Nivolumab may be considered as second-line therapy option after cabozantinib failure in selected metastatic collecting duct carcinoma patients.

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Collecting duct carcinoma (CDC) is an aggressive renal malignancy with limited diagnostic and therapeutic consensus. We report a case of a 69-year-old male with CDC and extensive coagulative necrosis who presented with lower extremity swelling, abdominal distention, and an enlarged left kidney causing grade IV hydronephrosis. Initial treatment with a left percutaneous nephrostomy was followed by clinical deterioration and a diagnosis of emphysematous pyelonephritis. Pathological examination of drainage material revealed extensive coagulative necrosis and was suggestive of a necrotic neoplasm. Subsequent left nephrectomy confirmed CDC with high-grade features, stromal desmoplasia, and extensive coagulative necrosis. Immunohistochemistry studies supported the diagnosis. This study highlights the diagnostic complexity of CDC and emphasizes the need for accurate reporting of atypical presentations. CDC remains a formidable clinical entity with limited treatment options and poor outcomes. Further research is essential to enhance our understanding and management of this rare and aggressive renal malignancy.

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We report a case of collecting duct carcinoma (CDC) in a 60-year-old man who presented with persistent cough, low back pain, and weight loss. Contrast-enhanced CT of chest and abdomen revealed a mass in the medulla of the middle and upper parts of the right kidney, with spread into perirenal tissue, vascular invasion, and distant metastasis. First renal biopsy only showed inflammation. Repeat biopsy and histopathological examination and immunohistochemistry confirmed CDC. The patient died 2 months after diagnosis despite interventional therapy, chemotherapy, and targeted therapy. This case is being reported because of its rarity and unusual presentation.

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Introduction: Immunotherapy-based combinations have become the standard first-line therapy for metastatic renal cell carcinoma. However, combined immunotherapy for renal collecting duct carcinoma had been reported, but its therapeutic efficacy had been unclear. Case presentation: The first case was a 62-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with multiple bone metastases. After 7 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. The second case was a 71-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with lymph node and lung metastases. After 9 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. In both cases, the tumor cell expression of programmed death ligand-1 was negative, and CD4+ and CD8+ cells were observed in the tumor. Conclusion: Combined immunotherapy with pembrolizumab and axitinib may be effective for metastatic renal collecting duct carcinoma.