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Notes: We present a case of phenytoin-induced toxic epidermal necrolysis resulting in 60–70% skin involvement. Systemic corticosteroids and prophylactic antibiotics used initially were discontinued, and subsequent management concentrated on intensive supportive treatment. The patient survived, but is left with disabling ocular complications.

Notes: Background Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited. Objectives To investigate genetic aberrations in CTCL. Methods We analysed 18 cases of Sézary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies. Results CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean ± SD number of CIs per sample was 1·8 ± 2·4, with losses (1·2 ± 2·0) slightly more frequent than gains (0·6 ± 1·0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25). Conclusions These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies.

Notes: Background The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non-Hodgkin’s lymphoma and relapsed chronic lymphocytic leukaemia. Objectives To test the efficacy of this combination in 12 patients with cutaneous T-cell lymphoma (CTCL). Methods Nine patients with erythrodermic CTCL were identified for the study, eight of whom met the criteria for Sézary syndrome (SS), and three with tumour-stage mycosis fungoides (MF). Patients received intravenous fludarabine and cyclophosphamide 3 days monthly for 3–6 months. Results Six patients tolerated at least three cycles. Five with SS had a response (one had a complete clinical response and four a partial response) and one patient with MF had stable disease. The mean duration of the response was 10 months. Six patients had treatment withdrawn, five due to bone marrow suppression and one due to progressive disease. No difference in pretrial parameters were found in those who had treatment withdrawn and those who tolerated at least three courses. Survival since the trial was similar in both groups at 11 months. Conclusions These data indicate that the combination of fludarabine with cyclophosphamide may be of clinical benefit in patients with SS but does not affect patient survival. As with other multiagent chemotherapy regimens, bone marrow toxicity is a common and severe side-effect. These data suggest that this regimen should be considered palliative and should be reserved for patients with refractory disease without bone marrow suppression.

Notes: Background The t(14;18)(q32;q21) chromosomal translocation is found in the majority of nodal follicular lymphomas and in a lower percentage of systemic high-grade diffuse large B-cell lymphomas. The translocation results in the juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy chain joining region on chromosome 14. Bcl-2 protein prevents apoptosis and the translocation leads to overexpression of a functionally normal Bcl-2 protein that prevents apoptosis of neoplastic cells. Objectives The purpose of our study was to analyse cases of primary cutaneous B-cell lymphoma (PCBCL) for the presence of the t(14;18) translocation and to correlate the results with Bcl-2 expression and histological subtype. Methods Forty-four cutaneous B-cell lymphoid proliferations (36 PCBCL, four follicular B-cell lymphomas with cutaneous presentation and four reactive B-cell infiltrates) were analysed by polymerase chain reaction amplification and polyacrylamide gel electrophoresis using consensus primers for the joining region on the immunoglobulin heavy chain gene in combination with either a primer for the major breakpoint region (MBR) or the minor cluster region (mcr) on chromosome 18. Results None of 36 PCBCL analysed demonstrated a t(14;18) translocation; however, three of four systemic follicular B-cell lymphomas presenting in the skin were found to have a translocation in the MBR, which was confirmed by sequence analysis. Correlation with Bcl-2 immunostaining showed that of seven patients with high-grade cutaneous diffuse large B-cell lymphoma, four were Bcl-2 positive but had no evidence of a t(14;18) translocation. In the five cases classified as primary cutaneous follicle centre cell lymphoma, the neoplastic cells within the germinal centres failed to express Bcl-2. However, Bcl-2-positive neoplastic cells were present in all four cases of systemic follicular lymphoma, including the case that did not show a t(14;18) translocation. In all cases of marginal zone lymphoma the marginal zone lymphocytes were Bcl-2 positive. Conclusions These findings indicate that the t(14;18) translocation does not occur in PCBCL, which suggests the involvement of different pathogenetic mechanisms compared with their nodal counterparts. Furthermore, the detection of a t(14;18) translocation in cutaneous B-cell lymphoma should suggest the presence of systemic disease, which underlies the need for exhaustive staging procedures.

Notes: We present a ease of malignant carcinoid initially diagnosed as rosacea. This patient was later found to have an additional functioning parathyroid tumour. Although a pituitary tumour was nor identified, the association represents a probable case of multiple endocrine neoplasia type 1 (MEN 1). This autosomal dominant syndrome is characterized by tumours of the pancreas, parathyroid and pituitary. Inoperable carcinoid rumour is best treated with a long-acting somatostatin analogue, octreotide. A diagnosis of MKN I has important connotations for the proband's first-degree relatives, who should be entered into an appropriate screening programme.

Notes: Summary Waldenstrom's macroglobulinaemia has been associated with a variety of cutaneous manifestations. We report a patient with an acquired bullous disorder associated with skin fragility and IgM kappa paraprotein. Immunofluorescence studies demonstrated bright linear deposition of IgM along the basement membrane zone (BMZ), around dermal blood vessels and on arrector pili muscles. Weak keratinocyte cell surface staining with IgM was also noted. There was no deposition of complement or other immunogiobulins. Indirect immunotluorescent studies revealed a circulating IgM anti-BMZ antibody (titre 1/200), which bound to both the roof and the floor of a 1 mol/l NaCI split skin substrate. Immunoblotting analysis ofthe patient's serum, with both epidermal and dermal extracts, was negative. Treatment with a combination of prednisolone and azathioprine was successful. We suggest that this IgM kappa paraprotein has a low affinity for an undefined epitope within the lamina lucida, which has produced a subepidermal bullous disorder associated with skin fragility.

Notes: Summary Anticonvulsants can cause a characteristic hypersensitivity reaction. This multisystem reaction typically presents as fever, mucocutaneous eruptions, lymphadenopathy and hepatitis. There is cross-reactivity between different anticonvulsants. which complicates subsequent therapy. We report three cases to illustrate both the typical features, and less common complications, of this under-recognized and life-threatening syndrome.

Notes: Three patients with cutaneous T-cell lymphoma (CTCL) are reported who had concurrent B-cell chronic lymphocytic leukaemia (B-CLL). The separate lineage and clonal nature of the individual lymphoid malignancies were confirmed by gene-rearrangement analysis. The chronology of the illnesses did not support the hypothesis that CTCL predisposes to the development of B-cell proliferative disorders. There was no clear association with immunosuppressive therapy, and HTLV-1 studies were negative in all patients. Consequently, we speculate that a lymphoid stem cell defect, which may lead to the development of either aberrant B- or T-cell clones, may be responsible for such cases of dual lymphoid neoplasia.