Choroidal Metastasis From Papillary Renal Cell Carcinomas: A Case Report and a Review of the Literature.

Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.

Eosinophilic Variant of Chromophobe Renal Cell Carcinoma During Pregnancy: A Multidisciplinary Approach and Successful Management in a Tertiary Hospital in Mexico.

Renal cell carcinoma (RCC) is rarely diagnosed during pregnancy and its management represents a challenge as it necessitates considerations for the well-being of both the mother and the developing fetus. Diagnosis can be challenging and is often an incidental finding during routine imaging, which can lead to difficult decision-making. The choice of the ideal imaging study in these cases is a matter of debate. When the tumor is detected at an early stage, radical nephrectomy is indicated. However, there is still controversy regarding whether it should be performed conventionally or laparoscopically, as both techniques have their risks and benefits. In this context, our primary objective was to provide adequate surgical treatment for the patient, while safeguarding fetal health. Here, we present a patient with a history of recurrent miscarriages, in whom a renal tumor was incidentally diagnosed during pregnancy. Adding to the uniqueness of this case, the patient was diagnosed with an eosinophilic variant of chromophobe RCC through histopathological analysis. Our aim is to highlight the controversies surrounding diagnostic and treatment methodologies and to present the surgical techniques employed in this unique situation. This case underscores the importance and need for a multidisciplinary approach, which, in our instance, resulted in favorable outcomes for both maternal and neonatal health.

Immune checkpoint inhibitors in non-conventional histologies of renal-cell carcinoma.

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.

Advanced nccRCC: what therapeutic options in 2022?

Non-clear-cell renal cell carcinomas (nccRCC) represent around 25% of all renal cancers and are a very heterogeneous group of tumours in terms of both biological features and prognosis. Papillary renal cell carcinomas (pRCC) are the most frequent subtype with 15% to 20% of all kidney cancers. Improved biological knowledge of these tumours has led to better identification of each subtype. Among pRCC, some exhibit mutations of the MET oncogene and others mutations of the gene coding for fumarate hydratase. The management of nccRCC, in particular the pRCC subtype, has evolved considerably in recent times, spearheaded by the advent of targeted therapies including anti-angiogenics but also new immunotherapy agents. Several studies have in the last few years prompted a new standard of care for these nccRCC. We propose to present throughout this article the latest available efficacy data on different compounds assessed in the treatment of the most frequent nccRCC, including the pRCC, chromophobe carcinoma, collecting duct carcinoma, MiT family translocation renal cell carcinoma and renal medullary carcinoma subtypes.

Characterization of PD-1 and PD-L1 Expression in Papillary Renal Cell Carcinoma: Results of a Large Multicenter Study.

BACKGROUND: Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce. PATIENTS AND METHODS: Patients' sample collection was a joint collaboration of the nationwide PANZAR consortium - a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells. RESULTS: Of 374 pRCC specimens, 204 type 1 and 97 type 2 were evaluable for PD-1 and PD-L1 expression analysis. In total, PD-1 and PD-L1 expression were found in 8 (4.9%) of 162 and 12 (7.2%) of 166 evaluable pRCC type 1 specimens. Comparably, PD-1 and PD-L1 expression were found in 2 (2.4%) of 83 and 5 (6.2%) of 81 evaluable pRCC type 2 specimens. Hardly any clinically relevant associations between PD-1 and PD-L1 positivity and clinicopathologic or clinical courses were observed, neither in pRCC type 1 nor type 2. CONCLUSION: The analysis of a large pRCC cohort from a multicenter consortium revealed no impact of PD-1/PD-L1 expression on prognosis in patients with pRCC with predominantly limited disease status, neither for type 1 nor type 2. However, the impact of PD-1 and PD-L1 in more advanced pRCC disease needs further elucidation.

Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review.

BACKGROUND: Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metastatic nccRCC. METHODS: We conducted a systematic review according to PRISMA guidelines. Any type of study reporting the use of pazopanib in metastatic renal cell carcinoma including cases with non-clear cell histology was eligible. RESULTS: In all, 15 studies were included in our analysis, including a total of 318 nccRCC patients treated with pazopanib. Most studies were retrospective (n = 12); three were prospective trials. The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81-89%, median progression free survival of 8.1-16.5 months and median overall survival of 17.3-31.0 months. Grade 3-4 adverse events rates were 21-55%. CONCLUSION: The present review provides for the first time a systematic summary of evidence about the possible use of pazopanib as first-line treatment for nccRCC, with a favorable outcome despite the low strength of evidence. Pazopanib could be considered as a possible therapeutic option in this setting.

Delayed Recurrence of Chromophobe Renal Cell Carcinoma Presenting as Metastatic Duodenal Ulcer.

Renal cancers are one of the common causes of cancer-related morbidity and mortality worldwide. Most primary cases are localized at presentation and are treated with partial or radical nephrectomy with curative intent. However, renal cell carcinoma (RCC) is known for its potential recurrence, sometimes several years after initial management. Many of these recurrent cases commonly metastasize to the liver, kidney, or bone and herald a poor prognosis. We present a case study of nonclear cell RCC, which recurred 33 years after nephrectomy and masqueraded as a duodenal ulcer -- an extremely rare site for metastasis. This is unique as it describes a presentation only sparingly documented in the medical literature and highlights a more extended period of recurrence than currently reported. Moreover, our patient's tumor was chromophobe cell variety, a rare sub-type of nonclear cell RCC, which to our knowledge has never been known to cause duodenal metastasis. Studies have implicated a prognostic role of lymph node involvement at the time of initial diagnosis to predict future recurrence. This case is a drop in the mighty ocean to prompt further investigation on the utility of life-long surveillance protocols and further research evaluating the role of lymph node dissection in preventing such recurrences and high mortality.