Bone marrow findings in metastatic melanoma, including role of BRAF immunohistochemistry

Abstract

Introduction We describe peripheral blood smear, bone marrow morphology, histopathology, immunohistochemistry, including BRAF V600E, and molecular testing results of patients with metastatic melanoma to the bone marrow. Methods We performed a retrospective review for patients with metastatic melanoma to the bone marrow at our institution. Bone marrow morphology, histology, immunophenotyping, and cytogenetic/molecular genetic testing were reviewed, and BRAF V600E immunohistochemistry was performed. Results were compared to the literature. Results We identified four patients with metastatic melanoma to the bone marrow presenting with at least one cytopenia. Two of the four patients had leukoerythroblastosis, with three patients having atypical cells on bone marrow aspirate/touch preparation, and all patients had aggregates of atypical cells on biopsy. Immunohistochemistry for S100, Melan A, and HMB45 confirmed the diagnosis in all patients, and BRAF V600E immunohistochemistry was detected in two of four patients, which correlated with molecular testing findings. Review of the literature found 27 total patients, with normocytic anemia and leukoerythroblastosis as common peripheral blood smear findings. Conclusions Features including cytopenias (typically anemia), leukoerythroblastosis, and morphology of cohesive, large atypical cells in aspirate and biopsy, and immunohistochemical expression for S100, Melan A, and HMB45 were present in patients with metastatic melanoma. BRAF V600E immunohistochemistry is useful as a surrogate marker of molecular results. Regardless of clinical history, at the time of the bone marrow biopsies, hematologic malignancies are in the main differential diagnosis and very rarely included metastatic melanoma, likely due to the under‐recognized metastatic potential of melanoma to the bone marrow.

Bone marrow metastases: a systematic review of a neglected involvement in malignant melanoma

“…1 and Table 1, respectively. The included studies were published from 1941 to date [1,2,4–74], with a peak between 2013 and 2023 (60%; 44/73).…”

“…In this comprehensive systematic review spanning from 1941 to 21 August 2023, we have meticulously analyzed a total of 73 studies encompassing 146 patients with BMM arising from melanoma with three additional cases of our institutions (San Raffaele Hospital, Milano and Papa Giovanni XXIII Hospital, Bergamo) [1,2,4–74]. Historically, bone marrow involvement in melanoma has been considered a relatively infrequent event, occurring in approximately 5–7% of cases [1,2].…”

“…In the context of solid tumor metastasis, a subset of tumor cells has the propensity to home early to the bone marrow. Within this bone marrow microenvironment, these cells enter a state of prolonged quiescence, where they acquire the necessary traits for successful metastatic colonization [30,56]. This concept, termed the premetastatic niche, is also considered relevant in the context of melanoma metastasis to the bone marrow.…”

Case of metastatic melanoma in bone marrow smear

“…Bone marrow metastatic melanoma infiltration is considered infrequent and has been described in a relatively small number of patients. 4 The cell morphological features have been variably reported as large blasts of heterogeneous size, with immature heterogeneous nuclei and basophilic cytoplasm, which contains melanin pigment inclusions in typical cases. S‐100 positivity was not observed in our case, while it is described as frequent in the literature.…”

Diagnosis and treatment of melanoma bone metastasis: A multidisciplinary approach

“…On bone marrow aspirate/touch preparation, isolated tumoral cells or tumoral islands with pleomorphic appearance, voluminous nuclei with atypical mitosis and brown pigment in cytoplasm can be found. Immunohistochemical study is useful in diagnosis of bone metastases from melanoma; it is typically reactive for vimentin, HMB-45, S-100 protein, tyrosinase, melan-A, and microphthalmia transcription factor 20. However, the features and characteristics of bone metastases from melanoma are nonspecific on imaging criteria and they cannot be distinguished from other osteolytic metastases.…”