A skin lesion that catches the eye.

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is rare and only represents 1% of all cutaneous T-cell lymphomas. To our knowledge, only 40 cases have been described. It often presents with generalised skin lesions, preferentially affecting the extremities. There is a well-documented association with haemophagocytic syndrome. Treatment is difficult since PCGD-TCL is often resistant to chemotherapy and radiotherapy. Most case reports describe an aggressive clinical course with an estimated mean survival of 15 months. We present a 72-year-old female patient with stage IV primary cutaneous gamma-delta T-cell lymphoma. Our patient presented with fever, night sweats and multiple skin lesions (figure 1). Computed axial tomography of chest and abdomen revealed multiple solid nodular lesions in both kidneys. During admission a subconjunctival lesion appeared and progressed rapidly (figure 2). Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. Clonal gamma-delta T-cells were also detected by immunohistochemical analysis of peripheral blood and bone marrow. Polymerase chain reaction amplification revealed clonal rearrangement of the T-cell receptor gamma chain gene. These findings together were consistent with stage IV primary cutaneous gamma-delta T-cell lymphoma. The rapid progression of the subconjunctival extra-nodal manifestation is characteristic for the aggressive course of this lymphoma. Our patient was treated with two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). However, her clinical condition deteriorated rapidly. She declined further therapy and died within three months of initial presentation.

6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis.

Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.

Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites.

In B-cell lymphomas, loss of human leukocyte antigen (HLA) class I and II molecules might contribute to immune escape from CD8(+) and CD4(+) cytotoxic T cells, especially because B cells can present their own idiotype. Loss of HLA expression and the possible underlying genomic alterations were studied in 28 testicular, 11 central nervous system, and 21 nodal diffuse large B-cell lymphomas (DLCLs), the first two sites are considered as immune-privileged sites. The analysis included immunohistochemistry, loss of heterozygosity analysis, and fluorescent in situ hybridization (FISH) on interphase cells and isolated DNA fibers. Total loss of HLA-A expression was found in 60% of the extranodal cases and in 10% of the nodal cases (P <.01), whereas loss of HLA-DR expression was found in 56% and 5%, respectively (P <.01). This was accompanied by extensive loss of heterozygosity within the HLA region in the extranodal DLCLs. In 3 cases, retention of heterozygosity for D6S1666 in the class II region suggested a homozygous deletion. This finding was confirmed by interphase FISH that showed homozygous deletions in the class II genes in 11 of the 18 extranodal lymphomas but in none of the 7 nodal DLCLs (P <.001). Mapping by fiber FISH showed variable deletions that always included HLA-DQ and HLA-DR genes. Hemizygous deletions and mitotic recombinations often involving all HLA genes were found in 13 of 18 extranodal and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA class I and II expression might help the B-cell lymphoma cells to escape from immune attack.