Cutaneous Lymphoproliferative Diseases Research Articles

Five paediatric patients with mycosis fungoides and our approach to provide age-appropriate information and psychological support.

Cutaneous lymphoproliferative diseases in childhood are rare and they are clinically and pathologically heterogeneous, which makes their diagnosis challenging. Although there is limited long-term data and guidance on management, evidence suggests these to be different conditions from cutaneous lymphoma in adults, highlighting the need for age-appropriate patient information. We present clinical outcomes for our paediatric cohort of five patients with mycosis fungoides, emphasizing that despite diagnostic delays, mycosis fungoides in this age group tends to yield a good prognosis. It remains uncommon to provide clinical expertise together with psychological support in a dermatology paediatric service. Here, we provide our experience in offering this combined service. In conjunction with these patients, we have co-produced an accessible patient information leaflet targeted at a younger audience for support and to clarify potential misconceptions from a diagnosis of cutaneous lymphoma.

Photodynamic Therapy as an Effective Treatment for Cutaneous Lymphomas.

Topical photodynamic therapy (PDT) is a non-invasive treatment modality frequently used in dermatology to treat superficial skin cancers but also some inflammatory or infectious dermatoses. PDT appears a more and more promising therapeutic option also for cutaneous lymphomas, either of T- or B-cell origin. It is a well-tolerated treatment and has excellent cosmetic outcomes, less side effects compared to other therapies (steroids, surgery, radiotherapy, and so on), no particular contraindications, and is easily repeatable in case of relapses. However, how PDT works in the treatment of cutaneous lymphoproliferative diseases is poorly understood and the literature data are still controversial. Further randomized, controlled clinical trials involving a greater number of patients and centers with a long follow-up are necessary to assess the efficacy of PDT and establish a unique standardized treatment protocol in relation to the lymphomatous disease and the type, thickness, and location of the lesions.

Modern possibilities of therapy for primary cutaneous T-cell lymphomas: the first results of the use of brentuximab vedotin in the Russian Federation

Background. Primary cutaneous T-cell lymphomas are rare heterogeneous group of lymphoproliferative diseases characterized by primarily involving skin and subcutaneous adipose tissue. Half of these cases are mycosis fungoides (MF), for about 25% are cutaneous CD30+ lymphoproliferative diseases (CD30+ LPD): primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis (LyP). During the initiating treatment of patients with MF and Szary syndrome (SS), carried out on the territory of the Russian Federation, for about 30% of patients are resistant to various therapeutic effects, especially in the later stages. The problem of the treatment of CD30+ LPD is extracutaneous dissemination in case of pcALCL, steadily relapsing course of LyP without symptom-free intervals. These characteristics of the therapy of cutaneous lymphomas demand for the need to search for new treatment options. Brentuximab vedotin, according to the results of the international randomized ALCANZA trial, has shown high efficiency in the treatment of cutaneous T-cell lymphoproliferative diseases. Aim. To evaluate the efficacy of brentuximab vedotin application in patients with cutaneous T-cell lymphomas in adverse risk group received at least one line of systemic therapy. Materials and methods. The study included 21 patients: 16 men and 5 women. The diagnosis of MF was verified in 8 patients, SS in 5 patients, cutaneous CD30+ LPD in 6 patients (5 patients pcALCL, 1 patient LyP) and a primary cutaneous peripheral T-cell lymphoma, unspecified in 2 patients. The diagnosis of cutaneous T-cell lymphoma was verified on the basis of the anamnesis of the disease, on the character of cutaneous lesions, on histological, immunohistochemical and in some cases on molecular genetic testing of the biopted sample of the skin (the assessment of T-cell receptor gene rearrangement). Results. The late stages of the disease were diagnosed in 12 of 13 patients with MF/SS. Extracutaneous lesions were diagnosed in 57% of cases. The median of prior lines therapy was 3 (18 variants of treatment). The overall response to the treatment was achieved in 91% of cases (in 19 of 21 patients): the complete remission was obtained in 53% of cases, very good partial remission in 31% of cases and partial remission in 16% of cases. The progression of the disease was determined in 2 patients (after the first and fourth cycles). Some patients with partial remission as a result of therapy using brentuximab vedotin had the additional therapy (radiation therapy, interferon , the cycles of systemic therapy) and these acts gave an option of achieving deeper antitumor response. The early relapse was diagnosed in 2 of 19 patients who had responded to the treatment. The treatment tolerability was acceptable, and the toxicity did not exceed the already known one described in earlier studies. Thus, the stable overall antitumor response had been persisting in 89% of patients (the median of the observation was 10 months). Conclusion. The use of targeted therapy with brentuximab vedotin gave an option of achieving high treatment results in group of patients with advanced stages of the disease and inefficiency of several lines of therapy.

Hydroa vacciniforme-like lymphoproliferative disorder: A study of clinicopathology and whole-exome sequencing in Chinese patients

BackgroundHydroa vacciniforme-like lymphoproliferative disorder (HVLPD) encompasses a rare group of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases. ObjectiveTo define the clinical and pathologic characteristics of HVLPD and to identify mutant genes that may be related to the development of HVLPD. MethodsClinical data and archived formalin-fixed, paraffin-embedded tissue were obtained from 19 patients. Specimens were analyzed by immunohistochemistry and in situ hybridization to detect EBV-encoded RNA (EBER1/2) and for T cell receptor (TCR) gene rearrangements. Whole-exome sequencing (WES) analysis was also performed in this study. ResultsThirteen patients survived between 3–58 months (median, 21 months) during the follow-up. Six patients who were almost adults (>15 years old) and died of the disease presented with facial edema. Lactate dehydrogenase (LDH) levels were elevated, and the TCR gene rearrangement test was positive more frequently in the patients who died. Compared with Chinese patients in a similar previous report, our patients had significantly higher proliferation (in all cases, the Ki-67 index was greater than 10 %) and a more aggressive clinical course. Moreover, after WES and Sanger verification, STAT3, IKBKB, ELF3, CHD7, KMT2D, ELK1, RARB and HPGDS were screened out in our patients. ConclusionsHVLPD refers to a heterogeneous group of cutaneous lymphoproliferative diseases with different clinical and pathological features that affect patient outcomes. Gene mutations may be correlated with the development of HVLPD, and our study may provide new therapeutic targets for HVLPD.

Type A lymphomatoid papulosis: subclassification of lymphomatoid papulosis and histopathologic differential diagnosis of anaplastic large cell lymphoma

Lymphomatoid papulosis is a chronic self-regressing papulonecrotic or papulonodular skin disease with histologicfeatures suggestive of a malignant lymphoma. It is part of a spectrum of CD30-positive cutaneous lymphoproliferativediseases, is considered as one of indolent cutaneous T-cell lymphomas. The disease is characterized by recurrentcrops of pruritic papules at different stages of development that predominantly arise on the trunk and proximalextremities. Clinicopathologically, lymphomatoid papulosis should be differentiated from anaplastic large cell lymphoma.Continued observation of all patients is essential because lymphomas develop in 20% of the patients with lymphomatoidpapulosis. Herein, we present two cases of type A lymphomatoid papulosis proven by the histopathologic examination.

Hypopigmented interface T-cell dyscrasia: a form of cutaneous T-cell dyscrasia distinct from hypopigmented mycosis fungoides.

Hypopigmentation in cutaneous T-cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre-lymphomatous T-cell dyscrasia falling under the designation of the so-called hypopigmented interface variant of T-cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T-cell dyscrasia as its own entity apart from other T-cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T-cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo-protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low-grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T-cell dyscrasia is a distinct entity separate from and rarely progressive to MF.

Asynchronous Presentation of Follicle Center Lymphoma and Reactive Lymphoid Hyperplasia of the Ocular Adnexa

Although ocular lymphoproliferative diseases may be rarely encountered by dermatopathologists, the frequency may increase particularly as more and more subspecialties rely on dermatopathology services. Emerging data suggest that there are some similarities between ocular and cutaneous lymphoproliferative diseases with respect to their clinical behavior, prognosis, and cytogenetics. In this case report, a patient with ocular follicle center lymphoma who subsequently developed ocular reactive lymphoid hyperplasia is presented with an accompanying review of the literature on the subjects. The encounter of both follicular center lymphoma and reactive lymphoid hyperplasia in the same patient provides a rare opportunity to compare and contrast the clinical, histological, and immunohistochemical findings of the respective lymphoproliferative diseases situated at opposite ends of the spectrum.

Pityriasis Lichenoides and Cutaneous T Cell Lymphoma: An Update on the Diagnosis and Management of the Most Common Benign and Malignant Cutaneous Lymphoproliferative Diseases in Children

Although more common with advanced age, the entire spectrum of benign and malignant cutaneous lymphoproliferative disorders can present in the pediatric population. Nevertheless, these conditions are often mistaken for other more common, benign dermatoses, resulting in delayed diagnosis. Standardized management of these conditions is also lacking. The purpose of this review is to provide an update on the most common benign and malignant cutaneous lymphoproliferative disorders in children: pityriasis lichenoides and mycosis fungoides. The presentation, evaluation and management of each of these conditions are discussed.

Combating Cancer Predisposition in Association With Idiopathic Immune Deficiency: A Recurrent Nodal and Cutaneous T-Cell Lymphoproliferative Disease in a Patient With Cartilage-Hair Hypoplasia

Address for correspondence: Mervi Taskinen, MD, Department of Pediatrics, Children’s Hospital, Helsinki University Central Hospital, PO Box 281 and 00029 HUS, Helsinki, Finland Clinical Pra ● Cartilage-hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by severe short-limbed short stature and hypoplastic hair. CHH is a primary immunodeficiency syndrome with impairment of cellular immunity in more than 85% of the patients. In addition, CHH is a cancer syndrome, with a 7-fold increase in incidence of cancer. The most frequent cancer diagnoses have been non-Hodgkin lymphoma of B-cell origin and basal cell carcinoma. ● We report on a male patient with CHH who developed 2 clinically distinct and altering CD30 T-cell lym-

Evaluation of the ICDP–UEMS Dermatopathology Examination

A detailed analysis of the results of the international annual International Committee for Dermatopathology-Union Européene des Médecins Specialistes dermatopathology examination was undertaken to identify clues for further improvement. The analysis covered 5 consecutive years (2006-2010) and involved a total of 860 questions (591 common questions and 269 uncommon questions) and 181 participants. It focused on the overall performance of the participants, the performance per part of the examination (theoretical or practical), the performance per format of question (multiple choice or open), the performance per dermatopathological topic, and the performance per professional background (dermatologist or pathologist). The overall performance of the participants was high (on average 75% correct answers in 2006 and 85% correct answers in the subsequent years). In the theoretical part of the examination, the topics of vascular diseases and lichenoid dermatoses scored better than the average of all topics, and the topics of cutaneous lymphoproliferative diseases and melanocytic disorders scored worse. In the first practical part (interpretation of images), dermatologists outperformed pathologists, especially on providing a diagnosis (open question format) of clinical images. In the second practical part (microscopical examination), the topics of vascular diseases, granulomatous diseases, including necrobiotic and degenerative and metabolic diseases scored better than the average of all topics, and the topic of infectious diseases scored worse. The results of this detailed analysis provide an excellent feedback to the examination committee that will be used to consider the adjustment of parts and/or topics of the examination that showed a deviant performance by the participants. In addition, it is recommended to give more attention to the postgraduate education of certain dermatopathological topics, including cutaneous lymphoproliferative diseases, melanocytic disorders, and infectious diseases.

Atypical Molluscum Contagiosum Accompanied by CD30‐Positive Lymphoid Infiltrates

Atypical presentations of molluscum contagiosum require histophathologic examination and may show pleomorphic lymphocytic infiltrates of a reactive nature, mimicking cutaneous lymphoproliferative diseases. Serial sections of specimens or polymerase chain reactions to show T-cell receptor clonality may be helpful for differential diagnosis. We report a case of atypical molluscum contagiosum accompanied by atypical lymphocytic infiltration showing CD30 positivity.

EB病毒感染相关的皮肤淋巴增殖性疾病二例

：Objective To report 2cases of Epstein-Barr virus-associated cutaneous lymphoproliferative disease (LPD) and toevaluate their relationship with chronic active Epstein-Barr virus (CAEBV)infection.Methods The clinical data on, laboratory examination findings in, treatment andtherapeutic response of 2cases of LPD were analyzed. Results Both the patients had chronicintermittent fever, lymphadenopathy, recurrent lesions including papules, papulovesicles,necrosis and variola-like scar in light-exposed and unexposed areas. Pathologically, therewas a dermal infiltrate of pleomorphic lymphoid cells with the involvement of perivasculararea and some subcutaneous tissue. Immunohistochemical staining showed that most of theinfiltrating lymphoid cells were positive for CD8, PCR revealed no TCR-γ gene rearrangement, and in situhybridization for EBV was positive. The copy of EBV DNA was above the normal range in theperipheral blood from both patients. Clinical status was improved after glucocorticoidtreatment. Conclusion The biologic behavior of LPD appears to be a chronic and indolentcourse and is closely associated with CAEBV. Key words: Lymphoproliferative disorders; Herpesvirus 4, human

Imatinib Mesylate Induced Gastric B-Cell Lymphoma

Purpose: Imatinib mesylate is a common first-line treatment for chronic myelogenous leukemia (CML). We present the first case, to our knowledge, of a CML patient treated with imatinib mesylate who developed gastric lymphoma. A 53-year-old man with a history of CML was taking imatinib mesylate with confirmed hematological and cytogenetic remission. However, the patient developed diffuse abdominal pain with associated bloody stools. A colonoscopy done 5-years previously showed only hemorrhoids and a benign colon polyp. An esophagogastroduodenoscopy (EGD) done during the same time showed gastric erythema and erosive duodenitis. A new outpatient EGD showed a large, fungating, non-circumferential mass at the incisura (Figure A). The patient had a laparoscopic abdominal exploration which showed a large gastric mass in the body of the stomach, extending into the antrum midway between the lesser and greater curvature. The mass was not removed surgically. In situ staining for Epstein Barr Virus (EBV) confirmed high-grade Burkitt's gastric lymphoma. Fluorescence in situ hybridization (FISH) of the biopsy revealed a genetically distinct neoplasm from CML. Imatinib mesylate was stopped and he received a different chemotherapy regimen for two courses. Follow-up EGD two months later showed only a large gastric ulcer at incisura angularis (Figure B); the mass dramatically decreased in size. Imatinib mesylate, a tyrosine kinase inhibitor, is a first-line chemotherapy agent used in the treatment of CML. It acts to inhibit the tyrosine kinase activity of this disease. The development of a de novo lymphoma and cutaneous EBV-positive B-cell lymphoproliferative disease in CML patients treated by imatinib have been reported, but it is very uncommon. In this case, the EBV gastric lymphoma occurred during imatinib treatment and resolved significantly after stopping treatment; it is thought the modulation of T-cell function by imatinib was the fulcrum point in the development of EBV-gastric lymphoma. In addition, the CML showed genetic and hematological remission, so the concern of a blast crisis forming was mitigated. To our knowledge, this is the first report of gastrointestinal Burkitt's lymphoma development after prolonged treatment with imatinib mesylate and is an important complication of therapy in CML.Figure A: Burkitt's lymphoma seen in stomach Figure B. Reduction of Burkitt's lymphoma in stomach.

Indolent cutaneous T‐cell lymphoma presenting as cutaneous lymphocytosis in dogs

Cutaneous lymphoproliferative diseases encompass a spectrum of lesions, ranging from self-limiting, reactive infiltrates to high-grade lymphomas. In humans, cutaneous lymphocytosis (CL) refers to self-limiting or slowly progressive monomorphic lymphocytic infiltrates of mostly unknown cause. It morphologically mimics cutaneous lymphoma. CL in cats also is a slowly progressive disease. Immunophenotyping and clonality testing of feline CL support an indolent lymphoma for the majority of cases studied. This study reports CL in dogs. Erythematous, scaly and alopecic macules, patches or plaques were present in eight dogs. Breed predilection was not observed; six of eight dogs were females; and ages ranged from 5 to 14 years. Diffuse monomorphic non-epitheliotropic infiltrates of CD3(+) (eight of eight), CD45(-) (four of eight) or CD45(+/-) (four of eight) and CD45RA(-) (seven of eight) T lymphocytes were present in the superficial and mid-dermis. Further immunophenotyping of five cases revealed TCR-gammadelta(+) T cells (one of five) or TCR-alphabeta(+) (four of five) T cells. TCR-alphabeta(+) populations were either CD8(+) (two of four) or CD4(-)CD8(-) (2/4). Clonality testing found clonal (seven of eight) or pseudoclonal (one of eight) rearrangement of the TCR-gamma locus of the lesional T cells. Prednisone, prednisolone and methylprednisolone acetate were the most commonly administered drugs. The lesions remained stable for long periods up to 6 years. Five dogs were euthanized due to progression of the skin lesions (three of five), peripheral lymphadenopathy of unknown origin (one of five) or high-grade lymphoma (one of five). One dog was lost for follow-up and two dogs are still alive (17 and 9 months after diagnosis). Canine CL is best considered an initially indolent lymphoma, with slow progression and a potential for progression to high-grade lymphoma.

Usefulness of a program of neoplasia surveillance in liver transplantation. A preliminary report

De novo malignancies are frequent complications after liver transplantation. Aim of the study is to evaluate whether a surveillance program for malignancy may improve patient survival. We have compared the survival after the diagnosis of malignancy (excluding cutaneous and hepatobiliary carcinomas and lymphoproliferative disease) of patients with symptomatic or incidental malignancies with patients with neoplasia diagnosed on screening. Two hundred and eighty patients with a follow-up greater than three months were followed for a median of 77.5 months (total follow-up: 1515 patient-yr). Thirty-three patients developed 41 malignancies. When compared with general population, the entire cohort of liver transplant recipients had a significantly higher risk of malignancy (relative risk: 2.34), gastrointestinal tract (relative risk: 2.52), urological tract (relative risk: 2.94) and head and neck cancer (relative risk: 4.14), and cancer-related death (relative risk: 2.35). All nine patients diagnosed with cancer with active screening are currently alive and free of malignancy after a median follow-up of 25 months. By contrast, 18/24 patients with diagnosis of cancer prompted by symptoms or incidentally diagnosed died as a consequence of the cancer (median survival: 13.5 months). The difference in survival between both groups was significant (p = 0.002). In conclusion, a close surveillance protocol for the diagnosis of malignancy could be life-saving in liver transplant recipients.

Evaluation of the role of human herpes virus 6 and 8 in parapsoriasis

The aetiology of mycosis fungoides and parapsoriasis (which may be considered as an early stage of mycosis fungoides) remains debated. Previous recent studies have suspected the involvement of viral agents and particularly human herpes viruses (HHV).The aim of the present study was to screen for the presence of HHV-6 and HHV-8 genome in parapsoriasis samples. Fifty paraffin-embedded samples from skin biopsies of parapsoriasis were retrospectively collected from archival files in our Dermatology department. Total DNA was extracted from samples using the phenol-chloroform method and the presence of viral genomes was screened using real-time PCR. Forty nine out of the fifty tissue samples of parapsoriasis were interpretable, they were all found negative for HHV-6 and HHV-8. This study does not confirm the suspected role of HHV-6 or -8 in parapsoriasis. HHV-8 has been the most studied virus in parapsoriasis and more widely in cutaneous lymphoproliferative diseases and our results are in agreement with most of the studies which found none or few HHV-8 in more advanced stages of cutaneous lymphoproliferative diseases. Concerning HHV-6, our study is the first one investigating the presence of this virus in lesional tissue samples of patients with parapsoriasis. In conclusion, parapsoriasis does not seem to be associated with either HHV-6 or HHV-8.

A Distinct Entity in the Spectrum of the CD30+ Cutaneous Lymphoproliferative Diseases: Oligolesional Nodules With Pseudoepitheliomatous Hyperplasia Followed by Spontaneous Resolution

Pseudoepitheliomatous hyperplasia (PEH) in biopsies of CD30+ anaplastic large-cell lymphoma (ALCL) is present infrequently and is of unknown prognostic value and significance. Our goal was to review the clinicopathologic features of cases of ALCL with PEH, study their course, and review the literature on the subject. Biopsy specimens of all cases of CD30+ lymphoproliferative disorders (59) were retrieved from the files of Yale Dermatopathology Laboratory over a 17-year period and reviewed. We identified 4 cases of ALCL (7%) exhibiting prominent PEH. All 4 patients presented with 1 or 2 nodules. In 2 patients, the lesions spontaneously regressed within a few months after initial diagnosis. One patient chose to have an excision in which only a small number of CD30+ cells were present. We were unable to obtain follow-up for the fourth patient. In the spectrum of CD30+ lymphoproliferative disorders, cases of ALCL with PEH are infrequent. In addition to the 4 cases described here, in our review of the literature we found 35 cases of ALCL with PEH. Most of these patients present with 1 or a few lesions. In the majority of these cases, the lesions started showing evidence of clinical spontaneous regression and even complete resolution within a few months of initial diagnosis. The clinicopathologic correlation between ALCL and PEH has not been emphasized. Because most of these cases follow a relatively benign clinical course, we recommend a more conservative approach in the clinical management of these patients.

SGN-30: a basis for the effective treatment of CD30 positive hematopoietic malignancies

Background: Patients with high-risk, relapsed or refractory Hodgkin lymphoma, those with systemic anaplastic large-cell lymphoma, and those with primary cutaneous CD30-positive disorders are in need of novel therapies. CD30, a common marker in these malignancies, is a reasonable immunologic target given its restricted expression in normal states. SGN-30 is a chimeric antibody targeting CD30. Objective: Review of data regarding SGN-30, including structure, mechanism of action, pharmacokinetics, efficacy in different patient groups, safety, and tolerability. Method: The medical literature and available abstracts regarding SGN-30 are reviewed. Conclusion: SGN-30 may be efficacious through multiple mechanisms of action. The most efficacious dose has yet to be determined. Given the long drug half-life, short infusions may be administered every 2 – 3 weeks. The highest response rate was seen in patients with primary cutaneous CD30-positive lymphoproliferative disease and encouraging results were seen in patients with relapsed or refractory systemic anaplastic large-cell lymphoma. Most responses in Hodgkin lymphoma were stable disease. Despite a majority of patients having had stem cell transplantation, the drug was well tolerated. There are in vivo and in vitro data that SGN-30 may be synergistic with chemotherapy.

Analysis of Primary CD30+ Cutaneous Lymphoproliferative Disease and Survival From the Surveillance, Epidemiology, and End Results Database

Primary CD30+ cutaneous lymphoproliferative disease (PCLPD) is a spectrum of indolent cutaneous T-cell lymphomas. The primary intention of the analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database was to report epidemiologic information and overall survival of patients with PCLPD. We investigated the SEER database from 1973 to 2004 and performed univariable and multivariable survival analysis. A total of 268 cases of PCLPD were recorded from 1973 to 2004. Median age at diagnosis was 61 years (range, 5 to 98 years). Among cases, 58% were male, and 42% female. Race distribution was 87% white, 7% black, and 4% Asian/Pacific Islander. A total of 157 patients had primary, localized PCLPD. For the total population (N = 268), overall survival at 3 years was 81% (95% CI, 74% to 87%). Population-matched relative survival at 3 years was 87% (SE, 3.6%). Disease-specific survival at 5 years was 92% (95% CI, 86% to 95%). Head and neck skin site predicted for inferior overall survival in patients with primary, localized PCLPD on univariable analysis (hazard ratio [HR] = 4.4; P = .008; 95% CI, 1.5 to 13.2), and was suggestive of decreased overall survival on multivariate analysis (HR = 3.0; P = .06; 95% CI, 0.95 to 9.7). Localized PCLPDs are rare diseases with an excellent overall survival and occur more frequently in whites and in men. Head and neck skin primary site may be associated with poorer survival. CONCLUSIONS regarding subsets demonstrating association with survival should be taken with caution, given the small number of deaths analyzed.

Reversal of multifocal cutaneous lymphoproliferative disease associated with Epstein-Barr virus after withdrawal of methotrexate therapy for rheumatoid arthritis

Patients treated with immunosuppressive agents are prone to developing lymphoproliferative disorders, in particular Epstein-Barr virus-associated lymphoproliferative disease. This complication was reported first in post-transplanted patients treated with cyclosporine, and, more recently, in patients receiving long-term methotrexate therapy for inflammatory disease. We describe the case of a 70-year-old female patient with multifocal cutaneous lymphoproliferative disease occurring in the course of long-term, weekly methotrexate therapy for rheumatoid arthritis. Immunohistochemical study revealed the presence of latent membrane protein within neoplastic cells. Cutaneous lesions initially continued to increase in number and size in the first 2 months and finally disappeared completely within 5 months after discontinuation of methotrexate. The patient is now in complete remission with 12-months' follow-up. Despite initial progression after cessation of immunosuppressive therapy, Epstein-Barr virus-induced lymphoproliferative disease may disappear completely within months, thus avoiding pointless chemotherapy.