ABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as active therapies in the management of advanced RCC. While multiple studies have shown clinical activity of ICIs in clear cell histologies, the evidence to support their use in non-clear cell (ncc) subtypes is based on smaller prospective trials and retrospective analyses. OBJECTIVE: The objective of this review is to summarize the clinical outcomes of ICI-based therapies in ncc-subtypes and in tumors with sarcomatoid/rhabdoid features. METHODS: We performed a systematic literature search using PubMed, Google Scholar and ASCO databases. The keywords "renal cell cancer" and "immune checkpoint inhibitors" and equivalents were used and all original publications between July 2016 and July 2021 were included. RESULTS: We included a total of 14 publications, including two clinical trials and 12 case series. The most frequent histologies were papillary (up to 75-100%), unclassified (up to 34%) and chromophobe (up to 28%). ICI monotherapy showed some activity in both 1st and 2nd line with response rates up to 27%. ICI combination regimens yielded better activity than ICI monotherapy but, overall, a heterogeneous efficacy was noted across histologies. Overall, outcomes of ICIs were superior in tumors with sarcomatoid/rhabdoid features. CONCLUSION: The observed activity of ICI-based therapies was heterogeneous. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation.
ABSTRACT
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare peripheral cytotoxic T-cell lymphoma, clinically resembling panniculitis. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune overactivation, triggered by underlying conditions. SPTCL presenting with HLH may represent a severe and rapidly progressive disease course. Currently, there is no standardized approach to treatment of HLH secondary to underlying SPTCL. A 34-year-old Asian male presented with a several months history of high fevers, weight loss, and nonpruritic purple discoloration of the skin. He had a skin biopsy showing atypical lymphohistiocytic panniculitis with dermal mucinosis and erythrophagocytosis consistent with SPTCL. The patient was initiated on treatment with dexamethasone and cyclosporine A. Almost immediate improvement of his skin lesions was noted and laboratory abnormalities trended toward baseline within 2 weeks. He noted complete symptom resolution after 3 months on therapy. SPTCL may be treated effectively with cyclosporine A and steroids to achieve rapid clinical and symptom management of this rare malignancy.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Lymphoma, T-Cell , Panniculitis , Adult , Cyclosporine/therapeutic use , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphoma, T-Cell/complications , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/drug therapy , Male , Panniculitis/drug therapy , SteroidsABSTRACT
The mixed-lineage leukemia (MLL) protein acts as a histone methyltransferase regulating multiple genetic elements. Rearrangements of the MLL gene result in expression of MLL-fusion proteins that occur in some acute leukemias and are associated with poor prognosis. The MLL protein complex has been shown to interact with the androgen receptor via the MLL-menin subunit, thus promoting gene activation. The presence of MLL translocation has not been previously reported in patients with castrate resistant prostate cancer (CRPC). We describe two cases of metastatic CRPC with a translocation in the MLL gene detected by a specific fluorescent in situ hybridization (FISH) assay. Both patients had an aggressive course and succumbed to the illness.
