Mature T-Cell Lymphoma/Leukemia with a Novel Skap1: Jak2 Fusion

) Mature T-Cell

We present a leukemic mature T-cell neoplasm with cutaneous involvement undergoing Complete Remission (CR) after Alemtuzumab treatment, with peculiar clinical and molecular features not fitting into any of the currently defined subgroups [1,2].

Discussion
We present an intriguing case resembling T-PLL and nonerythrodermic-SS, in which a final diagnosis of unclassified leukemic-mature T-cell neoplasms was made.
Neoplastic cells expressed CD4/CD25/PD1/FOXP3; showed a band-like skin infiltration pattern and were CD7 negative.These data have been described in SS and ATLL patients [3].The latter was excluded due to negativity for HTLV1.CD25 expression is seen in T-PLL cases, while PD1 is usually negative [4].No data regarding FOXP3 expression has been reported in T-PLL cases.CD52 is typically overexpressed in T-PLL but can be seen in other T-cell-lymphomas, including SS [5].On the other hand, phenotype by flow-cytometry could match T-PLL or SS [6] but the morphology of neoplastic cells on blood smears excluded SS and resembled small-cell-variant of T-PLL.
The patient presented a complex karyotype and MYC gene alterations (8q24) with no mutations in JAK-STAT-pathway genes, but a JAK2-gene rearrangement.SS cells are characterized by a complex karyotype with frequent gains in 8q (MYC) [3]; and fusion transcripts [8].JAK2-gene fusions have been described in CD4-positive CTCLs [9,10].However, SKAP1-gene as fusion partner has not been previously reported in lymphomagenesis.Those CTCL cases lacked genomic complexity and involved patients were younger than the average for mycosis fungoides, responded poorly to conventional therapeutic regimens and suffered histological progression with CD30-positive large T-cells in skin and lymph nodes [10].
T-PLL manifests with leukocytosis, lymphadenopathy, extranodal-involvement, hepatosplenomegaly and B-symptoms.In one-third of the patients there are cutaneous manifestations typically involving the face.Staber et al. [7] suggested that no "indolent"-T-PLL cases exist although Stengel et al. [11] described two different prognostic subgroups based on their molecular background.Our patient is alive and well after 2-years on Alemtuzumab therapy, skin involvement being the sole criterion for this treatment [7].Alemtuzumab is also effective in SS patients [5], a disorder characterized by erythroderma and lymphadenopathy, even though rare forms without erythroderma have been reported [12,13].The latter usually complained of pruritus and eventually evolved into conventional SS.
We report an extraordinary case with an unexpected novel gene fusion and excellent clinical outcome.Further cases within this spectrum need to be collected to elucidate whether they constitute a distinct entity.

Figure 1A -
Figure 1A-1C: Clinical appearance of skin erythematous rash at onset.C. Resolution of skin lesions after treatment with alemtuzumab.
Serum-lactate-dehydrogenase levels and B-2-microglobulin levels were normal, and tests for Human-T-Cell Lymphotropic Virus (HTLV1/2), Human Immunodeficiency Virus (HIV) and Epstein -Barr virus (EBV) were negative.Polymerase-Chain-Reaction (PCR) of the T-cell-receptor gamma gene demonstrated an identical clonal-rearrangement on skin and blood.