Epidermotropic Cytotoxic T-cell Lymphoma Research Articles

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19–89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.

Hematopoietic stem cell transplantation in advanced cutaneous T‐cell lymphoma

We retrospectively reviewed data pertaining to five patients with cutaneous T-cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity. Two patients (primary cutaneous anaplastic large cell lymphoma and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma) who responded well to chemotherapy received autologous HSCT: one patient was alive in partial remission and the other died due to therapy-related acute myeloid leukemia without disease relapse. In the remaining three patients with MF or SS, allogeneic HSCT was performed. Although one patient with MF died due to disease progression, the remaining two patients were alive in complete remission. Although there were two deaths in this study, the outcomes were considered satisfactory.

Evaluation of the 2008 World Health Organization classification for non-mycosis fungoides, non-Sezary syndrome T/NK-cell lymphomas with primary cutaneous involvement

Cutaneous non-mycosis fungoides non-Sezary syndrome T/NK cell lymphomas (non-MF/non-SS CTCL) are rare. In 2005, a consensus of the World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC) classifications for primary cutaneous lymphomas was established. These guidelines were then adopted into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008. This study aims to assess the applicability of the WHO 2008 classification in a retrospective series of CTCL cases registered in a reference academic center in Brazil. Twenty-seven patients with non-MF/non-SS CTCL were studied. Clinical, histopathological and immunophenotypical features based on an extensive panel of antibodies were applied to classify the cases according to the WHO, 2008. Overall, diagnostic categories included eight (29.6%) cutaneous anaplastic large-cell lymphoma, five (18.5%) lymphomatoid papulosis, six (22.2%) extranodal natural killer (NK)/T-cell lymphoma, nasal type, five (18.5%) adult T-cell leukemia/lymphoma, one (3.7%) cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma and two (7.4%) of peripheral T-cell lymphoma not otherwise specified (NOS). The WHO classification (2008) was applicable to most cases of non-MF/non-SS CTCL, while some cases remained unclassified and were considered NOS-peripheral T-cell lymphoma. An unexpected high frequency of NK/T-cell lymphoma nasal type was observed.

Cutaneous lymphomas: new entities and rare variants

Primary cutaneous lymphomas are the second most common group of extranodal non-Hodgkin lymphomas. Recently several new variants and entities have been described but have not yet become part of the World Health Organization (WHO) classification. These forms include the granulomatous form of mycosis fungoides, which is associated with a poorer prognosis, as well as indolent CD8+ lymphoproliferations on the head and at acral localizations. Within the group of cutaneous CD30+ lymphoproliferative disorders, new histological types of lymphomatoid papulosis have been identified, such as type D (CD8+ epidermotropic) and typeE (angioinvasive) which simulate aggressive lymphomas. Cutaneous peripheral T-cell lymphomas are a prognostically heterogeneous group of cutaneous lymphomas. The cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are very aggressive neoplasms, whereas cutaneous CD4+ small to medium-sized T-cell lymphoma in its solitary or localized form represents an indolent lymphoproliferation: the terminology, histogenesis and differentiation from nodular T-cell pseudolymphoma are still a matter of debate. Among B-cell lymphomas, disorders associated with Epstein-Barr virus (EBV) are discussed focusing on EBV diffuse large B-cell lymphoma of the elderly and EBV-associated mucocutaneous ulcer. This review describes the clinical, histological and immunophenotypic features of new and rare entities and variants of cutaneous lymphomas and highlights the impact of the clinicopathological correlation in the diagnostic process.

Indolent CD8‐positive T‐cell lymphoid proliferation of the ear: a report of two cases

The current classification of primary cutaneous T-cell lymphoma (CTCL) of the World Health Organization (WHO) includes primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma as a provisional entity awaiting cumulative data. Recent reports identify CD3/CD8-positive clonal T-cell lymphoid proliferations arising in the ear and nose that behave indolently and therefore defy currently established subclassification. Here, we report two cases of clonal CD8-positive/granzyme-B-negative T-cell lymphoid proliferations that arose in the ear and behaved indolently. Collectively, these cases suggest that an additional category of cutaneous indolent CD8-positive T-cell lymphoma may be necessary among the existing classification schemes.

A felületi röntgen irradiáció hatékonyságának értékelése mycosis fungoideses, primer cutan CD8+ agresszív epidermotrop citotoxikus T-sejtes lymphomás, primer cutan anaplasiás nagy sejtes lymphomás és primer cutan marginális zóna B-sejtes lymphomás betegeken

A felületi röntgen irradiáció hatékonyságának értékelése mycosis fungoideses, primer cutan CD8+ agresszív epidermotrop citotoxikus T-sejtes lymphomás, primer cutan anaplasiás nagy sejtes lymphomás és primer cutan marginális zóna B-sejtes lymphomás betegeken

Primary cutaneous aggressive CD8+ epidermotropic cytotoxic T-cell lymphoma: A case report

Primary cutaneous aggressive CD8+ epidermotropic cytotoxic T-cell lymphoma: A case report

Clinicopathological Characteristics and Clinical Course of CD8 Expressing Primary Cutaneous Peripheral T-Cell Lymphomas (CTCL) - Retrospective Case Study

Abstract 5213 Background:CD8-positive primary cutaneous T cell lymphomas (CTCL) are rare disorders and mainly include primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (AECTL) and CD8+ variant mycosis fungoides (MF). In contrast to primary cutaneous CD8+ AECTL, which frequently exhibits strikingly aggressive and unfavorable clinical behavior, CD8+ MF shows debatable clinical course, from an indolent to aggressive behavior. As previously reported, the indolent subtype CD8+ MF occur more frequently in pediatric group, while both clinical subtypes have been observed in adults. Albeit single case studies or small case series have been reported in the literature, it still lacks a large scale of study to enlighten the clinicopathological aspects of CD8+ primary CTCLs, in order to develop the appropriate therapeutic strategies. This study aims to retrospectively review these two entities to demonstrate their clinicopathologic characteristics and to correlate them with the clinical outcome. Design:The hematopathology files from H. Lee Moffitt Cancer Center & Research Institute (PATHNET) and Tianjian Cancer Research Institute were retrieved. The patients with a primary diagnosis of CD8 expressing primary CTCLs, diagnosed and treated between January 2004 and June 2011, were included. Cutaneous involvement by systemic peripheral T-cell lymphoma, primary cutanous gamma delta T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma were excluded. The corresponding patient demographics, laboratory datas, therapeutic strategies and the clinical outcomes were reviewed. All available histology slides, along with all of the ancillary study results were reviewed and correlated with the clinical outcome. Results:Total of 10 cases were included based on the confirmed histomorphological diagnosis. Cases were divided into two groups: 1) CD8+ MF (n=5) and 2) CD8+ non-MF (n=5) including 2 cases with definitive diagnosis of AECTL and 3 cases diagnosed as CD8-positive primary cutaneous T cell lymphoma, not further classifiable. Clinicopathological characteristics including patients' demographic data, diagnosis, site of involvement, treatment, duration of follow up and clinical outcomes are summarized in table 1. The overall survival time for CD8+CTCLs, non-MF type (excluding 1 patient with lost follow up) varied from 5 to 90 months (averaging 20.5 months) while it was shorter in CD8+ MF, 12.6 months (5 to 23 months). Of note, 1 patient with AECTL expired shortly after diagnosis, within 3 months, however; the other one received allogeneic hematopoietic stem cell transplant (allo-HSCT) and has been alive up to date. Conclusion:CD8-positive CTCLs remain a diagnostic challenge. CD8+ MF in adults exhibit dual growth patterns: localized or systemically disseminated disease. The latter could have a very short median overall survival regardless of the aggressive therapies. Allo-HSCT might be beneficial to those with AECTL. Larger series of CD8+ MF should be investigated for molecular gene profiling in order to establish genetic, molecular and phenotypic parameters not only to separate the indolent form from the aggressive subtype, but also to distinguish it from primary cutaneous CD8-positive AECTL.AgeGenderDxStageSites of InvolvementPhenotypeTreatmentFollow up (mon)Outcome153MCD8+ CTCL, not classifiableIRight frontoparietalCD3, CD5, CD8, CD43, TIA-1CHOP x619CR283MCD8+ CTCL, not classifiableIArms and trunkwk CD3, CD7, CD8, CD56, wk TIA,CHOP5AWD371MCD8+ CTCL, not classifiableIIBLeft eyelidCD3, CD8, TIAUV, CVP x 650CR425MAECTLIIIBRight toe, groin LNCD3, CD8, partial CD30RTX, ARA-C, cortisone, allo-HSCT8CR519FAECTLIVSkin, bone and lungCD3, CD5, CD8, TIACHOP X13LFU657MMF, CD8+IIBForeheadCD3, CD8, TIA-1UV, nitrogene mustard18AWD761FMF, CD8+IBLower ext and then diffuseCD3, CD4, CD5, CD8 and weak CD7.UV + Tragretin23CR859MMF, CD8+IBTrunkCD3, CD8, partial CD30NA5LFU919MMF, CD8+IVLeft palate and lungCD45RO, CD8CHOP X4 AND ESHAP X17DOD1032MMF, CD8+IVSkin, cervical LN, BMCD3, CD5, CD8CHOP X 2, HYPERCVAD X 2, VDCLP X 210DODNote: LUF: Lost follow up, AWD: alive with disease, DOD: died of disease, CR: complete remission, LN: lymph node and BM: bone marrow. Disclosures:No relevant conflicts of interest to declare.

Protocol for the Examination of Specimens From Patients With Non-Hodgkin Lymphoma/Lymphoid Neoplasms

Jerry W. Hussong, MD,DDS; DanielA.Arber, MD;Kyle T. Bradley,MD,MS;Michael S. Brown,MD;Chung-Che (Jeff) Chang,MD,PhD; Monica E. de Baca, MD; David W. Ellis, MBBS, FRCPA; Kathryn Foucar, MD; Eric D. Hsi, MD; Elaine S. Jaffe, MD; Michael Lill, MB, BS, FRACP, FRCPA; Stephen P. McClure, MD; L. Jeffrey Medeiros, MD; Sherrie L. Perkins, MD, PhD; for the Members of the Cancer Committee, College of American Pathologists

Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-cell Lymphoma in a Human T-cell Leukaemia Virus Type-1 Carrier

aggressive epidermotropic cy-totoxic T-cell lymphoma is rare, accounting for less than 1% of all cutaneous T-cell lymphoma (CTCL) (1). We report here a case of this type of lymphoma in a human T-cell leukaemia virus type-1 (HTLV-1) carrier. CASe rePorTA 58-year-old Japanese woman visited our hospital in 2006. She first noticed a red plaque on her left thigh approximately ten years previously. The number and the size of the plaques gradually increased despite treatment with topical steroid. At the initial visit, der-matological examination revealed irregularly shaped elevated erythematous plaques and ulcers with pus and crusts on her right breast (Fig. 1a). She also had multiple infiltrated red plaques with scales and crusts on her trunk and thigh (Fig. 1b). No superficial lymph nodes were swollen. Her general condition was good. She was from Kyushu, Japan, an area endemic for HTLV-1, and she was seropositive for the virus. The peripheral white cell count was normal without any atypical lymphocytes. Laboratory values were within normal limits except for a slightly increased level of se-rum soluble IL-2 receptor (965 U/ml, normal: 167–497 U/ml). Systemic examination revealed no visceral involvement. A skin biopsy specimen from the ulcer on the right chest showed diffuse infiltration of leukocytes in the dermis and subcuta-neous tissues. In the upper and middle part of the dermis, there was dense infiltrate of neutrophils, histiocytes and lymphocytes. Approximately half of infiltrating cells were CD3

Primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma: a case report.

A 19-year-old Chinese woman presented with progressive ulcers and recurrent fever for 1 year.The lesions originally began with purplish red maculopapules,then rapidly developed into ulcer with severe pain and spread to the trunk and extremities accompanied by intermittent fever.Histopathology revealed lymphoid infiltration of middle and large atypical T cells throughout the dermis and subcutaneous fat laver along with focal epidermotropism.The lymphoid infiltrates were positive for CD3,CD8,T-cell intercellular antigen(TLA)and T-cell receptor β(TCR-β).Gene analysis showed the rearrangement of T-cell receptor gene.According to the above findings,the patient was diagnosed as primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma. Combined thempy with cyclophosphamide,vincristine,prednisone and bleomycin resulted in partial remission of skin lesions,but she eventually died 22 months after the onset of disease. Key words: Lymphoma,T-cell,cutaneous; T-lymphocytes,cytotoxic

CD8+ Epidermotropic Cytotoxic T-Cell Lymphoma With Peripheral Blood and Central Nervous System Involvement

Most cutaneous T-cell lymphomas demonstrate a malignant population with a CD4(+) phenotype. In rare cases, CD8(+) phenotypes have been described based on immunostaining of skin specimens. Although some CD8(+) lymphomas have an indolent course, others, such as CD8(+) epidermotropic cytotoxic T-cell lymphomas, are typically more aggressive. To our knowledge, involvement of peripheral blood or cerebrospinal fluid with a malignant population of CD8(+) cells demonstrated by flow cytometry and T-cell receptor gene rearrangement has not been previously described. We describe a patient with a CD8(+) cutaneous T-cell lymphoma with an initially indolent course and early stage diagnosed on the basis of a skin biopsy specimen. However, when flow cytometry was performed looking specifically at CD8(+)/CD4(-) cells in the peripheral blood and cerebrospinal fluid, a malignant population of CD8(+)/CD4(-)/CD26(-)/CD7(-) cells was discovered. It is important for prognosis and treatment to be able to identify CD8(+) epidermotropic cytotoxic T-cell lymphoma and separate it from other relatively indolent CD8(+) lymphomas. Furthermore, detection of an abnormal CD8(+)/CD26(-)/CD7(-) T-cell population within the peripheral blood has important prognostic and therapeutic implications. The use of flow cytometry looking for abnormal CD8(+) populations in the peripheral blood or cerebrospinal fluid can assist with this critical information.

Lymphome T cutané épidermotrope cytotoxique CD8+ « agressif » : difficultés de prise en charge chez un malade atteint d’une dystrophie myotonique de Steinert

Primary cutaneous "aggressive" CD8-positive epidermotropic cytotoxic T-cell lymphoma is a rare subset of cutaneous cytotoxic T/NK lymphomas that clearly differs from mycosis fungoides, whether CD4+ or CD8+, by the presence of rapidly evolving tumoral cutaneous lesions, foci of keratinocytes necrosis, a cytotoxic T phenotype and a poor prognosis. A 33-year-old man with Steinert's myotonic dystrophy was referred for evaluation of rapidly worsening cutaneous tumors along with marked deterioration of general status. Clinical, histological and immunohistological data led to the diagnosis of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma. CHOP chemotherapy was effective despite cardiac toxicity in the setting of Steinert's dystrophy, but the patient relapsed and died of pulmonary sepsis after chemotherapy was resumed. The treatment of primary cutaneous epidermotropic CD8+ cytotoxic T-cell lymphoma is not codified. CHOP chemotherapy is usually the first-line therapy but relapses are frequent with median survival of no more than 34 months. In our patient, an additional difficulty was the cardiac toxicity of cytostatic drugs linked to the myopathy which prevented the use of high dosages, requiring a change of therapeutic regimen.

CD8+ Lymphomatoid Papulosis and Its Differential Diagnosis

We describe 5 cases (4 males, 14-43 years old; 1 female, 61 years old) of primary cutaneous T-cell lymphoproliferative lesions expressing a CD8/granzyme/CD30-positive phenotype. Four cases were compatible with lymphomatoid papulosis (LyP) based on the clinical course, which was recurrent asymptomatic papular nodular lesions over years responding to methotrexate; granulomatous inflammation and lack of other inflammatory cell elements were characteristic. In 1 case, an initial erroneous diagnosis was made of aggressive epidermotropic CD8+ T-cell lymphoma. The fifth case in this series was first interpreted as representing primary cutaneous anaplastic large cell lymphoma but was later recategorized as primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma owing to the extent of extracutaneous dissemination, including testicular involvement and disease progression despite chemotherapeutic intervention. Although all cases of LyP showed sharp cytoplasmic membrane staining with perinuclear Golgi accentuation with CD30, the recategorized case of aggressive epidermotropic CD8 cytotoxic T-cell lymphoma manifested only a weak cytoplasmic staining pattern. CD8 LyP defines a distinctive entity with characteristic light microscopic and phenotypic findings and has a predilection for young males. CD30 expression can occur in other forms of CD8 lymphoproliferative disease unrelated to primary cutaneous anaplastic large cell lymphoma or LyP.

Lymphome T cutané épidermotrope CD8+ cytotoxique d’évolution très agressive

Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma is a recently described rare primary cutaneous lymphoma exhibiting aggressive clinical behavior. Only about twenty cases have been described in the literature. Below we report a case involving unusual association of cutaneous vasculitis and lymphoproliferation.A 42-year-old senegalese man was hospitalized for cutaneous nodular lesions, which rapidly spread and became necrotic and ulcerated. he had recent weight loss with fever and multiple enlarged lymph nodes. Cutaneous histological analysis showed epidermotropic dermal infiltrate comprising medium and large cd8+ cytotoxic t-cells of unusual angiocentricity with cutaneous vasculitis and fibrinoid necrosis. the patient died 4 months after initiation of treatment with multi-agent chemotherapy.This patient presented the characteristics of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma described by Berti. The clinical findings in most cases consist of nodular and ulcerative cutaneous lesions. Histologically, the cutaneous infiltrate is composed of pleomorphic lymphocytes with marked and constant epidermotropism. Immunohistochemistry shows lymphocytes expressing a CD8+ phenotype and cytotoxic proteins, which probably accounts for the local and systemic aggressiveness of the disease, as well as the angiodestructive nature of the infiltrate and the necrotic lesions.

Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues.

Cutaneous T-cell lymphoproliferative disorders (CTCLs) remain a subject of confusion and controversy. In this review, the authors discuss diagnostic criteria and classification, including the role of immunohistochemistry and gene rearrangement studies. In addition, cutaneous T-cell pseudolymphomas, the current status of parapsoriasis and other premalignant syndromes, and the clinicopathological variants of mycosis fungoides are discussed. CD30-positive lymphoproliferative disorders and a number of rare variants of CTCL including granulamatous slack skin, subcutaneous (panniculitic) T-cell lymphoma, gamma-delta cutaneous lymphoma, NK/NK-like T-cell lymphoma, and primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphoma are also considered.

Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients

AbstractClassification of primary cutaneous lymphomas (PCLs) is the subject of ongoing controversy. Based on a series of 556 patients, the applicability of the European Organization for Research and Treatment of Cancer (EORTC) classification for PCLs was assessed and compared to the proposed World Health Organization (WHO) classification of hematologic malignancies. The large majority of patients could be properly classified according to the scheme proposed by the EORTC. Comparison of estimated 5-year survival for specific diagnostic categories of PCLs demonstrated nearly complete concordance of the present results with those of the EORTC study for most of the indolent cutaneous T-cell lymphomas and cutaneous B-cell lymphomas, whereas differences were found for mycosis fungoides-associated follicular mucinosis and Sezary syndrome. A few patients with newly described entities (CD8+ epidermotropic cytotoxic T-cell lymphoma, primary cutaneous natural killer/T-cell lymphoma) could not be classified according to the EORTC scheme. Comparison of the EORTC with the WHO classification showed that the EORTC scheme allows a more precise categorization of the patients, especially for cutaneous B-cell lymphoma. In conclusion, the study confirmed that the EORTC classification allows a better management of patients with PCL. Small amendments to that classification should be carried out to account for recently described entities and to unify some of the diagnostic categories.