Fiona Child

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophenotypic and molecular analysis of six patients.

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.

Absence of the t(14;18) chromosomal translocation in primary cutaneous B-cell lymphoma.

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.

Comparative genomic hybridization analysis of primary cutaneous B-cell lymphomas: Identification of common genomic alterations in disease pathogenesis

To investigate genetic alterations in primary cutaneous B‐cell lymphomas (PCBCLs), we have analyzed 29 cases of PCBCL. Comparative genomic hybridization showed chromosome imbalances (CIs) in 12 cases (41%). The mean number of CIs per sample was 2.05 ± 2.97, with gains (1.48 ± 2.38) more frequent than losses (0.56 ± 1.40). The common regions of gains were 18/18q (50%), 7/7p (42%), 3/3q (33%), 20 (33%), 1p (25%), 12/12q (25%), and 13/13q (25%), whereas loss of 6q was frequent (42%). Among the different subsets of PCBCLs, CI was seen in 50% of diffuse large‐cell lymphomas (DLCLs), 33% of marginal zone lymphomas, and 8% of follicle center cell lymphomas and unclassified lymphomas. A similar pattern of CI was observed in these lymphomas, but loss of 6q and gains of 3/3q were present only in DLCLs. Microarray‐based genomic analysis of four DLCL cases identified oncogene gains of SAS/CDK4 (12q13.3) in three cases and MYCL1 (1p34.3), MYC (8q24), FGFR2 (10q26), BCL2 (18q21.3), CSE1L (20q13), and PDGFB (22q12–13) in two cases, whereas losses of AKT1 (14q32.3), IGFR1 (15q25–26), and JUNB (19p13.2) were identified in three cases, and losses of FGR (1p36), ESR (6q25.1), ABL1 (9q34.1), TOP2A (17q21–22), ERBB2 (17q21.2), CCNE1 (19q13.1), and BCR (22q11) were each identified in two cases. In addition, real‐time–polymerase chain reaction detected amplification of BCL2 in 5 of 29 cases. These findings suggest that there are complex but consistent genetic alterations associated with the pathogenesis of PCBCLs.

T‐cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement

Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T‐cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T‐cell receptor (TCR) γ‐gene demonstrated by polymerase chain reaction (PCR)/single‐stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high‐dose etoposide (1·6 g/m2) and granulocyte colony‐stimulating factor (G‐CSF). The apheresis products underwent rigorous T‐cell depletion with immunomagnetic methods. Double CD34‐positive and CD4/CD8‐negative selection achieved a median reduction of 3·89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2–14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T‐cell depleted graft. A T‐cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse‐free survival, most patients achieved good disease control at the time of relapse.

BCL2 and JUNB abnormalities in primary cutaneous lymphomas.

Background  BCL2 is upregulated in nodal and extranodal B‐cell non‐Hodgkins lymphomas, with a consequent antiapoptotic effect. However, loss of BCL2 has also been noted in some malignancies, suggesting a different molecular pathogenesis.

Rituximab in cutaneous B-cell lymphoma: a report of two cases

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.

A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome

BACKGROUND There is no prognostic index for primary cutaneous T-cell lymphomas such as mycosis fungoides (MF) and Sezary syndrome (SS). METHOD Two prognostic indices were developed for early (IA-IIA) and late stage (IIB-IVB) disease based on multivariate data from 1502 patients. End-points included overall survival (OS) and progression free survival (PFS). External validation included 1221 patients. FINDINGS Significant adverse prognostic factors at diagnosis consisted of male gender, age >60, plaques, folliculotropic disease and stage N1/Nx for early stage, and male gender, age >60, stages B1/B2, N2/3 and visceral involvement for late stage disease. Using these variables we constructed two separate models each defined using 3 distinct groups for early and late stage patients: 0-1 (low risk), 2 (intermediate risk), and 3-5 factors (high risk). 10 year OS in the early stage model was 90.3% (low), 76.2% (intermediate) and 48.9% (high) and for the late stage model 53.2% (low), 19.8% (intermediate) and 15.0% (high). For the validation set significant differences in OS and PFS in early stage patients (both p<0.001) were also noted. In late stage patients, only OS differed between the groups (p=0.002). INTERPRETATION This proposed cutaneous lymphoma prognostic index provides a model for prediction of OS in early and late stage MF/SS enabling rational therapeutic choices and patient stratification in clinical trials.

Cutaneous Rosai–Dorfman disease

We report a patient with purely cutaneous Rosai–Dorfman disease (RDD) who presented with a solitary, asymptomatic plaque on the back of her left thigh, with characteristic, large histiocytoid cells exhibiting emperipolesis histologically. Cutaneous lesions occur in 27% of patients with lymph node involvement in RDD however purely cutaneous disease has only been reported on 18 previous occasions. The aetiology is unknown, although it is thought to be a reactive disorder rather than neoplastic, possibly an immunological response to an infectious agent.

Autologous Peripheral Blood Stem Cell Transplantation in Tumor-stage Mycosis Fungoides: Predictors of Disease-free Survival

Abstract: Nine patients with mycosis fungoides (age range 27–67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor‐stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G‐CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patients prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short‐lived in four (median disease‐free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post‐PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor‐stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor‐stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell depletion should be restricted to the CD4 subset.

Skin lesions in adult liver transplant recipients: a study of 100 consecutive patients

Background The surgical advances made in the area of organ transplantation along with the use of more efficacious immunosuppression have meant an increase in patient survival. This longer‐living transplant population has started to exhibit cutaneous problems, some of which lead to an increased mortality while others lead to a decline in the quality of life.