ABSTRACT
During routine dermatologic examination, a 77-year-old male was noted to have a firm blue subcutaneous nodule on his right lateral upper back. His past medical history included metastatic melanoma of unknown primary involving right and left axillary lymph nodes, treated with ipilimumab/nivolumab with complete response, and subsequent primary uveal melanoma. The subcutaneous nodule was located near his previous right axillary scar for metastatic melanoma. Excision of the nodule showed a plexiform neoplasm involving mid and deep dermis composed of spindle and epithelioid atypical cells admixed with numerous melanophages. Central necrosis was present. Immunohistochemical studies revealed the tumor cells to be diffusely positive for HMB45, with retained expression of BAP1 and p16. The tumor cells were negative for PRAME, nuclear expression of ß-catenin, LEF1, and BRAF V600E. Molecular studies demonstrated BAP1 and GNA11 somatic mutations, a profile different from that exhibited by his prior melanoma. Collectively, these data were interpreted as a metastasis from uveal melanoma and not a recurrence of his metastatic likely cutaneous melanoma after complete response to immunotherapy. This case emphasizes the importance of molecular studies for definitive diagnosis in challenging clinical situations, especially when there is discordance among histopathological, immunohistochemical, and molecular studies. Integration of clinical, histopathological, and molecular features is warranted.
Subject(s)
High-Throughput Nucleotide Sequencing , Melanoma , Skin Neoplasms , Ubiquitin Thiolesterase , Uveal Neoplasms , Humans , Male , Melanoma/genetics , Melanoma/diagnosis , Melanoma/pathology , Melanoma/secondary , Aged , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/secondary , Skin Neoplasms/diagnosis , Skin Neoplasms/metabolism , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , High-Throughput Nucleotide Sequencing/methods , Uveal Neoplasms/genetics , Uveal Neoplasms/pathology , Uveal Neoplasms/diagnosis , Uveal Neoplasms/secondary , Uveal Neoplasms/metabolism , Tumor Suppressor Proteins/genetics , Mutation , GTP-Binding Protein alpha Subunits/genetics , Nivolumab/therapeutic use , Neoplasms, Unknown Primary/pathology , Neoplasms, Unknown Primary/genetics , Neoplasms, Unknown Primary/diagnosisABSTRACT
ABSTRACT: Richter syndrome (RS) describes a phenomenon in which a patient with chronic lymphocytic leukemia (CLL) develops an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). Reports of cutaneous RS remain exceedingly rare. We report a 61-year-old woman with relapsed/refractory CLL presenting with several subcutaneous nodules on her arms and legs and a single dermal plaque on her abdomen. Skin biopsy revealed a diagnosis of DLBCL, ABC-type, and her clinical status rapidly deteriorated following diagnosis. We review the variety of clinical presentations of cutaneous RS, its association with CLL, risk factors for RS development in CLL patients, and the distinctive histopathologic and immunophenotypic features of DLBCL. We hope to highlight the importance of prompt skin biopsy in patients with CLL presenting with progressive skin lesions and increase awareness of this aggressive clinical syndrome.