Lymphomatoid Papulosis Lesions Research Articles

Diagnostic Value of Plasmacytoid Dendritic Cells in Differentiating Pityriasis Lichenoides et Varioliformis Acuta From Lymphomatoid Papulosis.

Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) can often demonstrate clinical and histopathologic overlap. A recent study demonstrated significant plasmacytoid dendritic cell (pDC) recruitment in lesions of PLEVA, whereas another study reported minimal pDC recruitment in lesions of LyP. To confirm the possible diagnostic value of pDCs in differentiating PLEVA and LyP, we compared the presence and distribution of pDCs and myxovirus protein A (MxA) expression (an indirect assessment of pDC activity). In total, 19 cases of PLEVA (16 patients) and 14 cases of LyP (11 patients) were examined using immunohistochemical stains for anti-blood-derived dendritic cell antigen-2 and MxA. Individual semiquantitative scoring systems were used to assess the immunohistochemical results, and a Mann-Whitney test with a subsequent 2-tailed P test was performed for statistical analysis. No statistically significant difference in the number of pDCs in both groups was found. However, most PLEVA cases (84%) demonstrated intense and diffuse MxA expression, whereas LyP cases (71%) demonstrated weak patchy staining (P < 0.007). Our study suggests that although additional studies may be needed to determine whether pDCs are more relevant to the pathogenesis of PLEVA or LyP, pDC activity through MxA staining may play a role in differentiating PLEVA from LyP and may serve as a platform for additional studies.

Nitrogen mustard gel-induced inflammation triggers lymphomatoid papulosis in patients with mycosis fungoides.

Lymphomatoid papulosis (LyP) is a paraneoplastic primary cutaneous CD30+ lymphoproliferative disorder (LPD) that has been associated with malignant lymphomas, most commonly mycosis fungoides (MF). We observed 10 patients with MF who developed severe inflammation after using nitrogen-mustard (NM) gel from 1 to 8months and who developed LyP. We hypothesized that NM gel produced local inflammation, which induced CD30 expression in malignant T cells in situ leading to the appearance of LyP papules. The high frequency of induction of LyP lesions in patients with severe inflammation while on treatment with NM gel suggests an association between inflammatory stimuli and development of LyP. Our observation provides insight into the pathogenesis of CD30+ LPD.

Survival in Mycosis Fungoides and Sezary Syndrome: How Can We Predict Outcome?

Early-stage mycosis fungoides (MF) has been associated with long survival. A recent meta-analysis including 6,279 patients with MF and Sezary syndrome found that about 10-20% of stage IB patients don't survive 5 years, whereas patients with advanced-stage MF and Sezary syndrome have a 5-year survival chance of about 20-60%. Identifying prognostic markers to better identify those at risk of limited survival may allow improved management choices and this, coupled with newer treatments, could improve survival.

Common origin of sequential cutaneous CD30+ lymphoproliferations with nodal involvement evidenced by genome‐wide clonal evolution

This study sought to clarify the molecular pathways underlying the putative evolution from lymphomatoid papulosis (LyP) to cutaneous anaplastic large-cell lymphoma (c-ALCL) and lymph node invasion (LNI). We analysed nine sequential tumours from the same patient presenting with parallel evolution of LyP (n=3) and c-ALCL (n=1) with LNI (n=1), combined with systemic diffuse large B-cell lymphoma (DLBCL) (n=4). Clonality analysis showed a common clonal T-cell origin in the five CD30+ lesions, and a common clonal B-cell origin in the four DLBCL relapses. Array-comparative genomic hybridisation and targeted next-generation sequencing analysis demonstrated relative genomic stability of LyP lesions as compared with clonally related anaplastic large-cell lymphoma (ALCL) tumours, which showed 4q and 22q13 deletions involving the PRDM8 and TIMP3 tumour suppressor genes, respectively. The three analysed CD30+ lesions showed mostly private (specific to each sample) genetic alterations, suggesting early divergence from a common precursor. In contrast, DLBCL tumours showed progressive accumulation of private alterations, indicating late divergence. Sequential cutaneous and nodal CD30+ tumours were clonally related. This suggests that LyP, c-ALCL and LNI represent a continuous spectrum of clonal evolution emerging from a common precursor of cutaneous CD30+ lymphoproliferations. Therefore, nodal ALCL tumours in the context of LyP should be considered as a form of transformation rather than composite lymphoma.

Lymphomatoid Papulosis in Children and Adolescents: A Systematic Review.

Lymphomatoid papulosis (LyP) is a lymphoproliferative disorder that is rare among adults and even rarer among children. In adults, LyP is associated with an increased risk of secondary lymphomas. The aim of this systematic review was to describe the clinical and histopathological features of LyP in children, to assess the risk of associated lymphomas, and to compare the disease to the adult form. A systematic review was conducted using the MEDLINE (PubMed), EMBASE, Scopus, and Cochrane databases from inception to June 2015. Articles were included if data were extractable from studies, case series, and single reports of pediatric LyP patients. A total of 251 children and adolescents with LyP were identified, with the mean age at diagnosis being 9.3±4.6 years (n=187). The female to male ratio was 1:1.4, and the majority of children reported on were Caucasian (n=74, 85.1%). The predominant histologic subtype was type A (n=106, 79.1%). Clinically, LyP lesions presented as erythematous papules or nodules, appearing preferentially on the extremities and the trunk. LyP has to be differentiated from pityriasis lichenoides (PL) and primary cutaneous anaplastic large cell lymphoma (ALCL). PL and associated lymphomas were diagnosed before, with, and after LyP in 19 and 14 cases, respectively. Of the 14 subjects with associated lymphomas, two children developed systemic ALCL. LyP has to be differentiated from ALCL to avoid erroneous treatments. Due to the increased risk of development of non-Hodgkin lymphomas, lifelong follow-up and proper patient counseling are warranted.

Frequency and Risk Factors for Associated Lymphomas in Patients With Lymphomatoid Papulosis.

Lymphomatoid papulosis (LyP) is classified as an indolent cutaneous lymphoma, but outcome dramatically worsens if LyP is associated with lymphoma. The frequency of this association remains unclear in the literature. Here, we assess the frequency and risk factors of association between LyP and another lymphoma in an 11-year retrospective study conducted in 8 dermatology departments belonging to the French Study Group on Cutaneous Lymphoma (FSGCL). Patients with LyP were identified and data extracted from the FSGCL registry between 1991 and 2006. Patients were followed up to January 2014. Age, sex, number of skin lesions, histologic subtype, and genotype were recorded at baseline. Risk factors were determined using univariate and multivariate analysis. Cumulative probability of association was calculated using the Kaplan-Meier method. We observed 52 cases of lymphomas (cutaneous, n = 38; systemic, n = 14) in 44 of 106 patients (41%). Lymphoma diagnosis was concomitant with or prior to LyP diagnosis in 31 cases and occurred during the course of LyP in 21 cases (cutaneous, n = 14; systemic, n = 7; median delay: 5 years; interquartile range: 1.5-7 years). In multivariate analysis, main prognostic factors for association between LyP and another lymphoma were older age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.01-1.08; p = .011) and presence of a T-cell clone in LyP lesions (OR: 7.55; 95% CI: 2.18-26.18; p = .001). Older age and presence of a T-cell clone in LyP lesions are risk factors for associated lymphomas in patients with LyP. These findings should help to identify patients who require close management in clinical practice. The management of lymphomatoid papulosis (LyP) is that of an indolent cutaneous lymphoma, based on its excellent prognosis. However, this good prognosis is altered if LyP is associated with lymphoma. Furthermore, risk factors for and frequency of this association remain unclear in the literature. The results presented here demonstrate a high rate of association between LyP and other lymphomas (41%) as well as a long median delay of occurrence (5 years), which emphasizes the need for prolonged follow-up of patients with LyP. Moreover, two main risk factors (i.e., older age and presence of a T-cell clone in LyP lesions) are highlighted, which should help clinical practitioners to identify patients who require close management.

Shared clonality in distinctive lesions of lymphomatoid papulosis and mycosis fungoides occurring in the same patients suggests a common origin.

Lymphomatoid papulosis (LyP) lies within the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Approximately 10% to 15% of patients with LyP develop other lymphomas, most commonly mycosis fungoides (MF), suggesting a biological relationship between these distinctive diseases. Here, we describe the clinical and histopathologic features of 11 patients who had both LyP and MF, including a total of 30 biopsy specimens (14 LyP and 16 MF). Clinically, LyP lesions were characterized by clustered papules undergoing spontaneous regression and were classified as type A (n = 11), type C (n = 2), or type D (n = 1). All cases of MF were characterized clinically by patch/plaque disease, were stage I or II at the time of diagnosis, and consisted of a CD4-predominant epidermotropic T-cell infiltrate. We used polymerase chain reaction-based methods to assess the TCR-β chain (TCRB) and TCR-γ chain (TCRG) in both LyP and MF lesions of all patients. Monoclonal TCR gene rearrangements were detected in 13 LyP lesions from 10 of 11 patients and in 14 MF lesions from 10 of 11 patients. All 10 patients in whom their skin lesions carried monoclonal TCR gene rearrangements exhibited overlapping clones in both their LyP and MF lesions; additional non-overlapping clones were identified in 3 LyP lesions from 2 patients and 1 MF lesion from another patient. The demonstration of shared monoclonal T-cell receptor gene rearrangements in LyP and MF lesions in almost all patients suggests a common origin between these distinctive clinicopathological diseases.

Association of clinicopathological characteristics with secondary neoplastic lymphoproliferative disorders in patients with lymphomatoid papulosis

Lymphomatoid papulosis (LyP) refers to an indolent cutaneous lymphoma. The association of prognostic clinicopathological risk factors with a second hematologic malignancy has not yet been determined. We investigated the prognostic effect of clinicopathological characteristics on the occurrence of a second lymphoma, as well as the first-line treatment, in 24 patients diagnosed with LyP using logistic regression models. We showed that lymphoma occurrence was associated with a lower mean age at onset of LyP symptoms, histological types B and C, head-located LyP lesions and a higher frequency of LyP recurrences. In multivariate analyses, histologic type A was associated with a lower risk of second lymphoma (odds ratio [OR] = 0.12, 95% confidence interval [CI] 0.014–0.98; p = 0.045) adjusting for age of LyP first symptomatology, and an important increased lymphoma-free survival rate (long-rank test; p = 0.06). Clinicopathological characteristics are important in defining the clearance or persistence of LyP lesions and may predict the occurrence of a second lymphoma.

Lymphomatoid papulosis in association with mycosis fungoides: A clinical and histopathologic review of five Taiwanese cases

Lymphomatoid papulosis (LyP) is a cutaneous CD30+ lymphoproliferative disorder characterized by recurrent, self-healing lesions with a chronic clinical course. Approximately 10–20% of the patients have lymphomas, including mycosis fungoides (MF). LyP in association with MF is not well documented in Taiwan. We aimed to describe the clinicopathologic characteristics of LyP with MF in a Taiwanese case series of LyP. A retrospective clinicopathologic study was performed on cases of LyP with MF diagnosed in our Department during the period 1990–2012. The diagnosis of LyP and MF were based on their characteristic clinical and pathologic features as well as correlation with the clinical course of the specific skin lesions. A total of 24 cases of LyP (10 males and 14 females, age 18–63 years, mean 40.4 years) were included. Multiple biopsies were often done in individual patients during the clinical course to establish the diagnosis of LyP and MF. LyP was further classified pathologically as type A ( n = 16), B ( n = 3), C ( n = 3), and mixed type with A&B ( n = 1) and A&C ( n = 1). Five cases (21%) also had MF; two had juvenile-onset LyP and three had juvenile-onset MF (one with hypopigmented MF, one with hyperpigmented MF, two with CD8+ LyP, and two with CD8+ MF). In the case of juvenile-onset hypopigmented CD8+ MF, the patient developed CD8+ LyP 25 years after the onset of MF and died of aggressive epidermotropic CD8+ lymphoma involving the skin and lung. MF occurred in five of the 24 cases (21%) in the present series of LyP. These five cases had several unusual clinical and pathologic features, including subtle or uncommon skin manifestation of MF and more frequent juvenile-onset and CD8 phenotype of LyP and/or MF lesions. Long-term follow-up and repeated biopsy of selected skin lesions are necessary for correct diagnosis and proper treatment of both diseases.

Investigation of molluscum contagiosum virus, orf and other parapoxviruses in lymphomatoid papulosis

Lymphomatoid papulosis (LyP) is a primary cutaneous CD30+ lymphoproliferative disorder with large, atypical CD-30+ cells, which despite their ominous appearance, also occur in reactive processes, such as CD30+ cutaneous lymphoid hyperplasia. As most causes of CD30+ cutaneous lymphoid hyperplasia are viral,1 we explored the possibility that poxvirus or parapoxvirus could be detected in lesions of LyP. Following University of Iowa Institutional Review Board approval, nine patients with a diagnosis of LyP that had available skin tissue blocks were included. For negative controls, two scar tissue samples were included. DNA was extracted from formalin-fixed, paraffin-embedded slides. Tissue was dewaxed by addition of xylene, vortexing, and centrifuging; xylene was removed and the pellet was rehydrated in 100% ethanol. After vortexing, centrifugation, and air drying, the sample was resuspended in digestion buffer and was incubated at 55°C for 4–6 hrs. Chelex-100 (BioRad) was added to a final concentration of 5%. The mixture was boiled 8 min, chilled 2 min, and centrifuged for 5 min at 4°C. The supernatant was transferred to a fresh centrifuge tube as template. Quantitative real-time polymerase chain reaction (q-PCR) was performed to detect Molluscum contagiosum virus p43K gene2; 10 ul of DNA was used in each assay. To ensure sufficient DNA was present and amplification was not due to presence of an inhibitor, the single copy RNaseP gene was detected by amplification of the DNA sample using a TaqMan RNaseP detection reagent kit (Applied Biosystems). A plasmid containing MCV p43K gene served as a positive control2. Parapoxvirus generic and orf virus specific q-PCR assays were also performed on the extracted DNA3, with positive controls using nucleic acid from Ovine Ecthyma Vaccine (Colorado Serum Company) and orf virus. No molluscum contagiosum, parapoxvirus generic, or orf virus DNA was detected the LyP samples or scars. Of the many infectious conditions associated with CD30+ cutaneous lymphoid hyperplasias, the most commonly associated viruses have been parapoxviruses (28.5%), herpes simplex and varicella zoster viruses (25%), and molluscum contagiosum virus (10.7%)1. Extrapolating these findings to true CD30+ lymphoproliferative disorders, previous studies have explored the possibility that LyP may represent a virally-induced cutaneous lymphoid hyperplasia. One analysis of LyP specimens by PCR demonstrated one out of nine LyP samples with detectable HHV 6 DNA, but no detectable HSV 1 and 2 or EBV DNA. 4. Recently, biopsy specimens of cutaneous lymphomas (including 3 cases of LyP) were assayed for Merkel cell polyoma virus, human polyomavirus type 6, human polyoma virus type 7, and trichodysplasia spinulosa-associated polyoma virus DNA by q- PCR; the cases of LyP were negative for all viral types5. As LyP and parapoxvirus and poxvirus virally-mediated CD30+ cutaneous lymphoid hyperplasias share overlapping clinical features (papular lesions, generally indolent course) and pathologic features (large, atypical CD30+ lymphoid infiltrates), LyP appears an intriguing candidate for induction by viral infection. However, the lack of detection of viral DNA in our LyP specimens argues against a link between parapoxviruses or molluscum contagiosum virus and LyP, although the role of sampling and stage of lesions should be considered.

Results of a Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders

AbstractAbstract 3688 Introduction:Brentuximab vedotin is a conjugate of CD30 monoclonal antibody (cAC10) and the tubulin inhibitor, monomethyl auristatin E (MMAE) which targets the cell surface antigen CD30. Responses in CD30+ relapsed/refractory Hodgkin lymphoma (HL; ORR 75%) and anaplastic large T-cell lymphoma (ALCL; ORR 86%) were reported. Study design:To determine the safety and efficacy of brentuximab vedotin, we conducted a Phase II investigator initiated open label clinical trial in patients with primary cutaneous CD30+ lymphoproliferative disorders (self-regressing lymphomatoid papulosis (LyP) or primary cutaneous pc-ALCL) and CD30+ mycosis fungoides (MF) with or without large cell transformation. Eligibility was based on ECOG < 2, need for systemic therapy, expression of CD30 in baseline skin lesion by immunohistochemistry, > 10 lesions of active or scarring LyP, pc-ALCL without generalized nodes, and CD30+ MF stage > IB with ≥ 1 prior topical or systemic therapy. Brentuximab vedotin at 1.8 mg/kg was infused over 30 min every 21 days up to 8 doses with an option of up to 8 more doses for patients with PR or two cycles past a complete response. Patients receiving at least 2 doses were evaluable for response measured as 50% decrease in active lesion number (LyP), tumor measurements (pc-ALCL), or modified skin weighted assessment tool mSWAT (MF). Biopsies were taken at pre-study, day 1, and to confirm response or disease progression to correlate response with CD30 expression. Results:Among 46 patients receiving at least one dose there are currently 38 evaluable patients: 21 females and 25 males whose median age is 59.5 years (range 31–86 years). Their clinical diagnoses are 27 MF, 3 pc-ALCL, 9 LyP, 6 LyP/MF, and 1 pc-ALCL/LyP/MF. The overall response rate is 63% (24/38) with CR of 32% (12/38) (Table 1). Evaluable MF patients (n=24) divided into three groups based on intensity of CD30+ expression in skin tumor cells at baseline, had response rates of 30% (low < 10%; n=10), 37.5% (medium >10-<50%; n=8) and 50% (high >50%; n=6). Complete responses were noted in all primary and secondary LyP patients as well as CD30+ tumors in pc-ALCL and MF patients. Time to response for LyP and ALCL was 3 wks (range 3–6) with median duration of response (DOR) of 22 wks (range 9–30). Time to response was 12 wks (range 3–25) and median duration of response for MF was 12 wks patients (range 6–32).Table 1:Response to Brentuximab Vedotin by Clinical DiagnosisPrimary DiagnosisTotal ptsResponse 63% (24/38)Secondary ResponseTime to Response (wks)DOR (wks)Mycosis Fungoides249 PR, 1 CR38%12 (R 3–25)12 (R 6–32)Lymphomatoid Papulosis65 CR, 1 PR100%3 (R 3–6)22 (R 9–30)ALCL11 CR100%3 (R 3)18LyP & MF75 CR, 2 PR100%5 MF PR 1 SD, 1PD3 (R 3–6)18 (R18–44)The most common related adverse events of any grade were neuropathy (38%), drug rash (27%), diarrhea (24%), fatigue (24%), alopecia (16%), myalgias (16%), and nausea (14%). Grade 3–4 events were neutropenia (n=3), nausea (n=2), chest pain (n=2), deep vein thrombosis (n=1), transaminitis (n=1) and dehydration (n=1). Dose reductions to 1.2 mg/kg were made for grade 2 neuropathy (n=2), transaminitis (n=1) and arthralgias and fatigue (n=1). One pc-ALCL patient with tumor regression died from infection after one dose; one withdrew due to infusion reaction. Conclusion:This phase II clinical trial demonstrates that brentuximab vedotin is an effective and safe targeted therapy for the spectrum of CD30+ CTCLs - MF, pc-ALCL, and LyP with an overall response rate of 63% in all evaluable patients and 100% in LyP/pc-ALCL. Although highest response rates correlated with highest CD30+ expression, low expression patch/plaque MF responded following additional treatment cycles. Disclosures:Duvic:seattle genetics: Consultancy, Research Funding. Off Label Use: This is a conjugated antibody approved for HD and ALCL tested in a phase II trial for another indication - CTCL CD30+. Tetzlaff:Seattle Genetics: Consultancy.

Outcome of patients treated with a single-fraction dose of radiation for lymphomatoid papulosis.

e18523 Background: Lymphomatoid Papulosis (LYP) is a primary cutaneous CD30+ lymphoproliferative disorder and a radiosensitive tumor. Treatment with radiation is typically given in multiple fractions for patients presenting with symptomatic unilesional or multilesional disease. However, a single fraction of radiation is more convenient to the patient. The purpose of this retrospective review was to evaluate the clinical response to a single fraction of radiation for palliation of symptomatic LYP lesions. Methods: The records of 8 (5 female, 3 male) patients with LYP, treated with a single or multi-fractionated palliative radiation therapy between 10/2001 and 9/2011, were reviewed. All patients had received multiple previous treatments such as chemotherapy, PUVA, topical nitrogen mustard, and UVB. A total of 19 sites with disease were given the following single doses: 700 (n=3) and 800 (n=16). In the earlier years, a total of 6 sites with disease were given 250 cGy in 18 fractions for a total dose of 4500 cGy. Radiation therapy was administered with electrons to 20 sites and with photons to 5. A bolus was used in most cases to increase the radiation dosage to the skin. Results: Minimum and median follow-up were 1 and 43 months (range, 1 - 120), respectively. Median age of the patients was 65 (range, 24 - 83). For disease sites receiving a single fraction therapy, a complete response (CR) was seen in 17 of the 19 sites (89.5%), and a partial response (PR) was seen in an additional 2 of the 19 sites (10.5%). Therefore, the overall response rate was 100%. For the disease sites receiving multi-fractionated therapy, a CR was seen in 6 of the 6 sites (100%). Evaluation of patient characteristics and treatment did not reveal any differences between patients achieving a CR or PR. Conclusions: For previously treated, radiation-naıve LYP lesions, palliative radiation therapy with single fractions of 700 - 800 cGy is associated with an excellent CR and is a convenient and cost effective strategy.

CD30+ Neoplasms of the Skin

Cutaneous T-cell lymphomas (CTCLs) are subdivided by lesion morphology, behavior, and surface receptors. Mycosis fungoides (MF) and Sézary syndrome (SS) are derived from CD4+ effector or central memory T-cells respectively. MF presents clinically as patches, plaques, or tumors, and SS presents with erythroderma. After MF/SS, the next most common CTCLs are CD30+ lymphoproliferative disorders: self-regressing lymphomatoid papulosis (LyP) or tumors of anaplastic large-cell lymphoma (ALCL), which express high levels of tumor necrosis factor death receptor member 8, also called CD30. Although MF is not considered to be a CD30+ lymphoproliferative disorder, MF may co-exist with LyP lesions, and MF may express CD30, especially in the setting of large-cell transformation. The development of targeted therapy for CD30+ CTCLs will help in understanding the importance of the CD30 death receptor in pathogenesis and will improve treatment options.

Selective IgM Deficiency in CD30+ Cutaneous Lymphoproliferative Disorder

Primary cutaneous anaplastic large cell lymphoma with local lymph node involvement was diagnosed in a 13-year-old boy with an ulcerative facial lesion and a history of skin lesions of lymphomatoid papulosis. The tumor regressed with chemotherapy. He continued to develop recurrent self-limited lesions of lymphomatoid papulosis , with a halo surrounding these lesions during the healing phase. He developed selective immunoglobulin M deficiency with decline in levels even 4 years after the chemotherapy with no recurrent infections noted and adequate IgG response to immunizations. Both peripheral blood IgM+ and memory B cells were low, suggesting a possible cause-effect relationship between selective immunoglobulin M deficiency and chronic CD30+ cutaneous lymphoproliferative disorders.

CD8+ Lymphomatoid Papulosis

Lymphomatoid papulosis (LyP) is defined as a histologically malignant, but clinically benign condition. It can appear as erythematous pink to purple papules or nodules. Immunophenotyping studies of the lymphomatoid papulosis lesions have shown a predominance of a CD4 expression and negativity for CD8. However, a positive CD8 expression has rarely been reported for LyP. Herein we report on a case of CD8 positive lymphomatoid papulosis in a 43-year-old man. The patient presented with erythematous, asymptomatic papules on the left axilla and thigh. Histopathologically, there was a wedge-shaped infiltrate composed of a mixture of various cell types, including lymphocytes, histiocytes, neutrophils and large atypical lymphoid cells. Immunophenotyping revealed the neoplastic cells were positive for CD3, CD8 and CD30 and they were negative for CD4, CD20 and CD56.

P107 Clinical, immunophenotypical and molecular analysis of a series of patients with poikilodermatous mycosis fungoides

Introduction Poikilodermatous mycosis fungoides (PFM) is an uncommon variant of MF, characterized by poikilodermia, atrophy, mottled dyspigmentation and telangectases. Aim To analyze cases of PMF diagnosed at the lymphoma clinic of Andreas Sygros Hospital, in relation to their clinical presentation, immunophenotypic and molecular characteristics and disease course. Methods All patients with PFM were retrospectively evaluated. Patients with predominantly poikilodermatous lesions of MF were selected. Information on clinical, histological, immunohistochemical and molecular data were recorded, in addition to information on treatment and follow up. Results Eleven patients (4 males and 7 females) with PMF were identified. The mean age at diagnosis was 33.5 years (range 10–75 years). Ten out of 11 patients had early stage disease (IB) and one patient presented with tumors accompanying widespread poikilodermia (stage IIB). Two patients had associated lesions typical of lymphomatoid papulosis (LyP). In 45.5% of patients (5 of 11), the atypical lymphocytes were predominantly CD4-positive, whereas the same proportion of patients (5 of 11) had a cytotoxic phenotype. Finally, aberrant CD4-CD8- phenotype was found in one patient, while in seven patients there was a loss of CD7 antigen. PCR analysis disclosed the presence of clonal rearrangements of the genes of TcRγ receptor in 8 out of 11 skin biopsies. Following diagnosis, 8 patients were treated with PUVA. Of these, six showed complete resolution of skin lesions, one partial remission and one progressive disease. Two patients showed stable disease after UBV-NB and acitretin 35 mg/day respectively. Finally, patient with tumor stage MF underwent electron beam radiotherapy on tumors followed by PUVA plus interferon a-2b 5 MU tiw, with disease progression after 5 months of treatment. Conclusion Our data suggest that PMF is commonly diagnosed at a young age and can be frequently accompanied by LyP lesions. A cytotoxic immunophenotype is also more common in PMF. Patients with PMF respond well to phototherapy and may have a good overall prognosis.

Lymphomatoid Papulosis Followed by Anaplastic Large Cell Lymphoma in a Pediatric Patient

Lymphomatoid papulosis (LyP) is a benign, self-healing, papular eruption that can wax and wane over time. Transformation to T-cell lymphoma has been well documented in 10% to 20% of adults with LyP. However, this transformation rarely occurs in patients younger than 20 years of age. Here, we present the first known pediatric patient in Korea, a 12-year-old boy who developed a subcutaneous nodule on the scrotum 13 months after papulonecrotic lesions of LyP were identified on both lower extremities and face. Histological and immunohistochemical examination of the subcutaneous nodule revealed anaplastic large cell lymphoma (ALCL). A T-cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in the two specimens, indicating that a common T-cell clone had proliferated over time in both the LyP and ALCL lesions.

Lymphomatoid Papulosis in Children: Report of 9 Cases and Review of the Literature

Background Lymphomatoid papulosis is a rare CD30+ T-cell lymphoproliferative disease with an excellent prognosis. It is usually seen in adults and is rare in children. The clinical and pathologic manifestations and the risk of progression to other types of lymphoma are thus not clearly defined in the pediatric age group. Objective To describe the characteristics of lymphomatoid papulosis in a group of children and perform a review of the literature. Patients and methods A retrospective study was performed of 9 patients under 18 years of age diagnosed with lymphomatoid papulosis and treated in our department between 1995 and 2009 Results The study included 7 boys and 2 girls aged between 2 and 17 years. Lesions compatible with pityriasis lichenoides acuta appeared before the lymphomatoid papulosis in 2 cases and afterwards in 1 case. The lymphomatoid papulosis lesions resolved spontaneously, leaving postinflammatory hyperpigmentation (77%) or hypopigmentation (23%). Scarring occurred in 77% of cases. Histologically, all cases showed features compatible with lymphomatoid papulosis type A. Molecular studies showed monoclonality in all 3 cases in which this technique was performed. Conclusions Lymphomatoid papulosis is a rare disease in childhood and the manifestations are similar to the adult form. This lymphoproliferative disease, occasionally associated with pityriasis lichenoides acuta, has histological features compatible with a type A or histiocytoid pattern. Progression to other lymphoproliferative disorders during followup is less common in the childhood form than in adults. The frequent association of pityriasis lichenoides acuta and lymphomatoid papulosis observed in our study, and the difficulty distinguishing between these 2 conditions in some cases, suggest that these diseases could be part of a single clinical-pathological spectrum.

Persistent agmination of lymphomatoid papulosis evolving to classical lesions of lymphomatoid papulosis

Persistent agmination of lymphomatoid papulosis evolving to classical lesions of lymphomatoid papulosis

Clinical characteristics and course of CD8+ cytotoxic variant of mycosis fungoides: a case series of seven patients

Fewer than 5% of cases of mycosis fungoides (MF) present with a cytotoxic/suppressor CD8+ phenotype which, despite immunophenotypic similarities with CD8+ aggressive lymphomas, is regarded as a phenotypic variant of MF. Poikilodermatous MF showing a CD8+ phenotype has been reported to have a nonaggressive clinical behaviour and a good response to psoralen plus ultraviolet A treatment. To perform a retrospective study of CD8+ MF cases diagnosed in the skin lymphoma clinic of Andreas Sygros Hospital. We analysed the clinical characteristics, the immunophenotypic and molecular indices, as well as the clinical course of these patients. Seven cases of CD8+ MF (6.5% of all cases of cutaneous T-cell lymphoma) were diagnosed during 2002-2007. One of seven patients had stage IA, five stage IB and one stage IIB disease. Clinical characteristics were variable: four of seven patients presented with poikilodermatous plaques (in one of them lesions of lymphomatoid papulosis with CD8+ phenotype coexisted), one patient with classic MF, one with plantar MF and one with follicular MF. The time period between disease onset and diagnosis was long for most patients (up to 33 years). All patients received the recommended treatment according to TNM staging. Five of seven patients had complete remission, one partial response and one stable disease. Special clinical characteristics, such as hyperpigmentation and poikiloderma, are often noted in CD8+ MF cases. In our series CD8+ MF presented with a long-standing disease and indolent course suggesting that CD8+ cytotoxic immunophenotype may represent a marker of mild biological behaviour.