CD4+ CD56+ Cutaneous Neoplasms: A Distinct Hematological Entity?

Abstract

We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells.

WHO-EORTC classification for cutaneous lymphomas

“…2,4,5,10 Recent studies suggest, however, that this favorable prognosis is restricted to small/medium-sized pleomorphic CTCLs with a CD4 ϩ T-cell phenotype, in particular those that present with localized disease, in contrast to those with a CD8 ϩ T-cell phenotype. 11 Moreover, the EORTC category of CD30 Ϫ large-cell CTCLs has become quite heterogeneous through the recognition of new diagnostic categories, such as subcutaneous panniculitis-like T-cell lymphoma (SPTL), [12][13][14][15][16][17] extranodal NK/T-cell lymphoma, nasal type, [18][19][20] CD4 ϩ /CD56 ϩ hematodermic neoplasm (blastic NK-cell lymphoma), [21][22][23][24] aggressive epidermotropic CD8 ϩ Table 1 Granulomatous slack skin 4 Ͻ 1 100…”

“…3 More recent studies suggest derivation from a plasmacytoid dendritic cell precursor. 23,24 "CD4 ϩ /CD56 ϩ hematodermic neoplasm" 22 and "early plasmacytoid dendritic cell leukemia/lymphoma" 23 have been suggested as more appropriate terms for this condition.…”

CD4+CD56+CD68+Hematopoietic Tumor of Probable Plasmacytoid Monocyte Derivation with Weak Expression of Cytoplasmic CD3

“…Recently a few reports described certain groups of hematopoietic neoplasia that coexpress CD56 and CD4. These tumors are TdT-negative blastic NK cell lymphoma (27), cutaneous monomorphous CD4+ CD56+ large cell lymphoma (28), and agranular CD4+ CD56+ hematodermic neoplasm, which commonly involve the skin at the time of presentation (29). Although these tumors show slight difference in their immunophenotype, they appear to be closely related.…”

Long‐term remission of blastic natural killer‐cell lymphoma after autologous peripheral blood stem‐cell transplantation

“…Blastic natural killer (NK)-cell lymphoma is a rare disease and seems to be identical to primary cutaneous CD4 + CD56 + hematolymphoid neoplasm [1]. The clinical course of blastic NK-cell lymphoma is usually aggressive and the prognosis is very poor [2][3][4].…”

“…Successful allogeneic hematopoietic stem-cell transplantation may be essential for long-term survival of patients with this disorder. However, most patients are middle-aged or elderly, and suitable donors may not always be available [1,5]. We performed autologous peripheral blood stem-cell transplantation (APBSCT) with conditioning of high-dose chemotherapy in combination with total-body irradiation (TBI) in a patient with blastic NK-cell lymphoma in remission.…”