Annals of Clinical & Laboratory Science, vol 36, no. 2, 2006
Fig 3. Panel A: the gel picture shows negative gene rearrangement of IgH gene. Lane 1-DNA ladder (50 bp), Lanes 2 and 3-no DNA; Lanes 4 and 5-DNA from benign tonsil; Lanes 6 and 7-DNA from positive control (expected PCR product of 180 bp); Lanes 8 and 9-DNA from the patient’s leukemic cells. Panel B: the gel picture shows negative gene rearrangement of TCR gamma subunit. Lane 1-DNA ladder (50 bp), Lanes 2 and 3-no DNA; Lanes 4 and 5-DNA from benign tonsil; Lanes 6 and 7-DNA from positive control (expected PCR product of 120 bp); Lanes 8 and 9-DNA from the patient’s leukemic cells.
is case illustrates an unusual presentation of an
NK cell lymphoma. Leukemic cells were blast-like and agranular with strong expression of CD4 and CD56 antigens and absence of myeloid, pan-B, or pan-T lymphoid markers. IgH and TCR gene rearrangements by PCR were both negative. Cytogenetic study showed multiple complex chromosomal abnormalities. All of these features are consistent with a blastic NK-cell leukemia/ lymphoma, a distinctive entity in the updated World Health Organization (WHO) classification . e primary leukemic presentation, but without skin lesions, has rarely been reported.
Cases with features of NK cell lymphoma have long been observed. Pretrella et al  first reported a series of cutaneous hematolymphoid tumor with similar immunophenotypic features of NK cell lymphoma (CD56+, CD4+) and the author named the disease as “CD4+CD56+ cutaneous neoplasm.” Subsequently, similar cases have been published [3- 6]. Based on the accumulated data from these cases along with recent research findings, this hematolymphoid tumor has been tentatively assigned a designation of “agranular CD4+CD56+ hematodermic neoplasm” (blastic NK cell lymph- oma).
“Agranular CD4+CD56+ hematodermic neo- plasm” is considered to be a variant of blastic NK cell lymphoma. is disease typically presents with a skin lesion (nodule or plaque), frequently with cytopenia, but with or without lymphadenopathy or splenomegaly. e tumor cells have blast-like/ plasmacytoid morphology with characteristic CD4+ and CD56+ and lack of cytoplasmic granules. Most of the reported cases have shown CD123+. Parenthetically, immunohistochem- istry performed on a bone marrow core biopsy of our patient also revealed the expression of CD123 on the leukemic cells. e tumor cells are also CD45+, CD43+, HLA-Dr+, and in some cases CD68+. ere is absence of pan-T, pan-B, or myelo- monocytic antigens.
Very rarely, CD4+ and CD56+ malignancies have been reported to variably express CD2, cytoplasmic CD3, CD33, and T cell receptor gamma gene rearrangement [7,8]. No recurrent cytogenetic abnormalities were identified so far . Interestingly, all of these so-called “agranular CD4+CD56+ hematodermic neoplasms” end up with prominent blood and marrow involvement. It is conceivable that our case falls within the spectrum of “agranular CD4+CD56+ hematodermic neo- plasm” with predominant blood and bone marrow involvement.
e concept of blastic NK cell lymphoma
originating from precursor NK cells has been challenged in view of recent research [3,6]. It has been proposed that the cell of origin of blastic NK cell lymphoma/“agranular CD4+CD56+ hemato- dermic neoplasm” is related to plasmacytoid mono- cytes/interferon producing cells (PM/IPC) .