Acute Myeloid Leukemia and Other CD56+ Neoplasms With Skin Involvement
Given the association with preexisting hematopoietic neoplasms, all patients with myeloid disorders, including MDS, CMML, AML, myeloproliferative neoplasms, and clonal hematopoiesis who develop skin lesion(s) should undergo a biopsy and evaluation for BPDCN (Box 1). Collaboration with a dermatologist and hematopatholo gist is recommended. The principal differential diagnoses include hematologic malignancies that are CD56 positive and/or present with skin lesions (Table 1). AML can be CD123, CD4, and CD56 positive, and some are CD34 negative. In these cases, myeloperoxidase or lysozyme positivity, or presence of other monocytic/myelomonocytic markers such as CD13, CD15, or CD117 favor a diagnosis of AML over BPDCN. Negativity for CD123 or TCL-1 also favors AML over BPDCN. The most challenging situation is when there are no skin lesions; in those cases, immunophenotyping on bone marrow biopsy immunohistochemistry and flow cytometry must be used to distinguish between AML and BPDCN. Extranodal NK/T-cell lymphoma may involve the skin and express CD56 but is associated with Epstein Barr virus positivity and is CD123 negative. Cutaneous T-cell lymphoma (CTCL) can also be CD56 positive, but expresses mature T-cell markers (CD2, CD3, CD5, CD7, CD8) and is negative for CD123.
Box1. Diagnostic Dilemma: Skin Lesions in a Patient With Myelodysplastic Syndrome
Table1. Hematologic Malignancies That Involve the Skin and are Often CD56+
Mature Plasmacytoid Dendritic Cell Proliferation
Mature plasmacytoid dendritic cell proliferation (MPDCP) is associated with myeloid neoplasms, particularly CMML, MDS, and AML, but can be seen in any myeloid neoplasm and especially those with monocytic differentiation. MPDCP is usually detected as clonally expanded aggregates of pDCs distinguishable from BPDCN by their clustered localization, mature morphology, and CD56 negativity. MPDCPs are characterized by a low Ki-67 proliferation index (< 10%) and they lack TdT. In contrast, in BPDCN, TdT is positive in about one-third of cases, with expression in 10% to 80% of the cells and the Ki-67 proliferation index is 20% to 80%. There is no clear evidence that patients with MPDCP are more likely to develop subsequent BPDCN, but this has not been studied in great depth.
