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

The actual incidence of bone marrow infiltration of human melanoma in clinical practice is underestimated, given it is found in only 7% of in vivo staging procedures, whereas this percentage increases up to 45% of autopsy cases. We performed a systematic review, in order to highlight the main clinico-pathologic features of melanoma bone marrow metastases (BMM), by reviewing 2.526 studies; seventy-three reports were included in the analysis,reporting a total amount of 146 patients. Moreover, as clinical exemples, we also present a collection of three BMM cases, extracted from our Institutional casistic. We found a slight male prevalence, with a median age at the time of BMM of 56.6 years (range: 3-81 years). The skin was the primary site of involvement in most cases (52%), followed by mucosa in 6 cases (8.8%) and uvea in 14 cases (20.5%), while in 13 cases (19%) the primary site of melanoma was not detected. In 36% of cases, BMM were preceded by lymph node involvement, while 64% of cases did not show nodal metastases, but directly to bone marrow (23%), as well as to other anatomical sites (41%). Presenting symptoms of BMM mostly included pain (60.7%), while anemia was the main laboratory alteration (80%), followed by thrombocytopenia, leukoerythroblastosis, pancytopenia, and leukopenia. A disseminated intravascular coagulation (DIC) was detected in 6 (11%) cases. In 12 cases (23.6%) BMM were amelanotic. The prognosis for BMM is poor, with a median time of survival of only 2 months, since currently conventional therapies for this anatomical site of metastasis are still not very successful, therefore, we stress the importance to evaluate bone marrow as a possible metastatic site in melanoma patients.