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Notes: We report two patients with primary cutaneous B-cell lymphoma who were treated with rituximab, a new anti-CD20 monoclonal antibody. The first patient, who had a diffuse large B-cell lymphoma of the lower leg, achieved an 85% improvement. The second patient, who had a primary cutaneous B-cell lymphoma, which had undergone high-grade transformation and systemic spread, achieved a minor response of approximately 30%. Both patients subsequently relapsed. The first patient achieved complete clearance with a second course of rituximab given with systemic chemotherapy, but again relapsed. Treatment with rituximab has been reported to produce response rates of 48% in relapsed systemic low-grade or follicular lymphoma, but there are no previous reports of the use of rituximab in primary cutaneous B-cell lymphoma.

Notes: We describe two men with multiple erythematous dermal nodules which were clinically and histologically consistent with a diagnosis of primary cutaneous immunocytoma. Both patients exhibited the very unusual feature of secondary anetoderma occurring in spontaneously resolving lesions. There is one previous report of anetoderma in association with a plasmacytoma. The pathogenesis remains unknown but release of cytokines such as interleukin-6 may be implicated.

Notes: Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is a condition which occurs on the glans penis of older men and may be associated with the development of a verrucous carcinoma. A role for human papillomavirus (HPV) in the aetiology of verrucous carcinoma has been implicated and several different HPV types have been found. We report a 74-year-old man who developed a verrucous carcinoma within an area of PKMB on the glans penis. Using a broad-spectrum polymerase chain reaction technique for identifying HPV, the epidermis of the area of PKMB and of the verrucous carcinoma were examined and no HPV DNA was identifiable. These results suggest that there is no part for HPV in the pathogenesis of PKMB or its transformation to verrucous carcinoma.

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: Summary Background Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin. In the World Health Organization classification of T-cell and natural killer cell lymphoma it is listed as an example of extranodal lymphoma. In practice, however, it is most likely to present to a dermatologist. Objectives To describe the clinicopathological, immunophenotypic and molecular features of six U.K. patients with SPTCL. Methods The clinical, histological and immunophenotypic features were reviewed. T-cell receptor (TCR) gene analysis was performed on blood and tissue samples using polymerase chain reaction/single-strand conformational polymorphism analysis of the TCR-γ gene using consensus primers. In situ hybridization was performed on lesional skin to detect mRNA for Epstein–Barr virus (EBV). Results All patients presented with subcutaneous nodules, plaques or ulceration, and three had systemic symptoms. All biopsies exhibited an infiltrate of medium to large pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. Five showed areas of necrosis, but only one showed marked cytophagia. In three cases the neoplastic cells did not express TCR-β. One was strongly p53 positive, and the other two were CD56 positive. Both these patients showed epidermal involvement with lichenoid changes histologically, and both developed the haemophagocytic syndrome. The other three cases were TCR-β positive, CD8 positive and CD56 negative. All cases were positive with pan T-cell markers and also for the cytotoxic granule protein T-cell intracellular antigen-1 and granzyme B. All cases were EBV negative both by immunostaining (latent membrane protein-1) and by in situ hybridization (EBV-encoded mRNA). TCR gene analysis revealed a T-cell clone in four of five cases; two of these patients had an identical T-cell clone in the peripheral blood. The median survival was 16 months. However, two of the three TCR-β-negative patients have died, whereas none of the TCR-β-positive patients has died. Conclusions This is the first series of SPTCL patients to be reported in the U.K. and the data support the view that there are two subsets of SPTCL: those derived from γδ T cells which carry a poor prognosis, and are usually CD56 positive, and a more indolent group derived from αβ T cells.

Notes: Background  BCL2 is upregulated in nodal and extranodal B-cell non-Hodgkin's lymphomas, with a consequent antiapoptotic effect. However, loss of BCL2 has also been noted in some malignancies, suggesting a different molecular pathogenesis.Objectives  To investigate genomic and protein expression status of BCL2 and to compare the results with that of JUNB in primary cutaneous lymphomas (PCLs).Methods  We analysed gene copy number of BCL2 and JUNB in 88 DNA samples from 80 patients with PCL consisting of Sézary syndrome/mycosis fungoides (SS/MF), primary cutaneous B-cell lymphoma (PCBCL) and primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) by the use of real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Real-time PCR and IHC findings were subsequently compared with the results of additional fluorescent in situ hybridization (FISH) analysis of 23 cases of SS and Affymetrix cDNA expression microarray study of two primary cutaneous T-cell lymphoma (CTCL) cell lines.Results  Real-time PCR analysis showed loss of BCL2 gene copy number in 22 of 80 PCL cases (28%), including 17 of 42 SS/MF, three of 13 C-ALCL and two of 33 PCBCL samples, and gain of BCL2 in four PCBCL samples. Gain of JUNB was identified in 18 of 71 PCL cases (25%), including nine of 35 SS/MF, seven of 13 C-ALCL and two of 31 PCBCL samples. IHC analysis revealed absent nuclear expression of BCL2 protein in 47 of 73 PCL cases, comprising 28 of 36 SS/MF, eight of eight C-ALCL and 11 of 29 PCBCL cases. In contrast, BCL2 protein expression was detected in 26 of 73 PCL cases, consisting of 18 of 29 PCBCL and eight of 36 SS/MF cases. JUNB protein expression was present in tumour cells from 30 of 33 of SS/MF and eight of eight C-ALCL, and was absent in tumour cells from 18 of 27 PCBCL cases. A comparison between BCL2 and JUNB revealed loss of BCL2 and gain of JUNB in five of 35 SS/MF samples, and expression of JUNB protein and absent BCL2 expression in 25 SS/MF and eight of eight C-ALCL cases. In contrast, expression of BCL2 and absent JUNB expression were detected in 67% of PCBCL cases. Additional FISH analysis revealed deletion of BCL2 in 19 of 23 SS cases (83%), including eight cases with BCL2 loss shown by real-time PCR. Furthermore, Affymetrix expression microarray demonstrated decreased expression of proapoptotic and antiapoptotic genes involved in BCL2 signalling pathways such as BOK, BIM, HRK, RASA1 and STAT2 in two CTCL cell lines with BCL2 loss and absent BCL2 expression. Increased expression of JUNB was also identified in the MF cell line.Conclusions  These findings provide a comprehensive assessment of BCL2 and JUNB status in PCL, and suggest that there is a selection pressure in a subset of CTCL cases for tumour cells showing BCL2 loss and upregulation of JUNB primarily through chromosomal deletion and amplification, respectively.

Notes: Summary Background Some lymphomas express natural killer (NK)-cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T-cell neoplasm, including blastic NK-cell lymphoma, which characteristically presents with cutaneous lesions. Objectives To describe the clinical, pathological and molecular features in six cases of CD56+ lymphoma with cutaneous presentation. Methods The clinical, histopathological and immunophenotypic features of six patients were reviewed. In addition, in situ hybridization (ISH) to identify Epstein–Barr virus (EBV) mRNA, and polymerase chain reaction analysis to identify the presence of a clonal population of T cells or B cells were performed on lesional skin. Results All patients presented with widespread nodules and plaques, which in five cases were a characteristic purple colour. Four patients developed disseminated disease, three with neurological involvement. These four patients died between 14 and 46 months following diagnosis (median 30 months). In four of six cases the histopathological and immunohistological features were in keeping with a blastic NK-cell lymphoma. No clonal immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement was detected in the four cases consistent with an origin from NK cells. A further case fitted the criteria for an extranodal NK/T-cell lymphoma of nasal type and was also the only case to show evidence of EBV mRNA by ISH. A clonal T-cell population was identified in the final case. This patient also exhibited molecular evidence of a clonal B-cell population and a t(14;18) translocation confirmed by sequence analysis. Conclusions Our data confirm that NK-cell lymphomas presenting in the skin are a heterogeneous group, and that in the U.K., blastic NK-cell lymphoma is more common than extranodal NK/T-cell lymphoma of nasal type. These lymphomas pursue an aggressive course, with rapid development of disseminated disease, and resistance to chemotherapy. Detailed immunophenotyping is needed to distinguish the different types. Our molecular data indicate that blastic NK-cell lymphoma cases lack clonal TCR/IgH gene rearrangements consistent with an NK-cell origin. Our ISH findings indicate that EBV plays a pathogenetic role only in extranodal NK/T-cell lymphoma of nasal type.