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Introduction: Mycosis fungoides (MF) is the most common primary skin T-cell lymphoma, which is characterized for a heterogeneous clinical expressivity., Objective: To report clinical variants and sociodemographic characteristics in patients with MF under the care of a dermatological hospital., Methods: 290 patients with MF clinical and histopathological diagnosis attended to over the course of 11 years were included. Sociodemographic description of patients was made, who were classified according to clinical and histopathological variants., Results: MF was recorded in 57.9 % of women and 42 % of men. The most common clinical variant was the classic type in 46.2 %; dyschromic variants accounted for 35.2 %, out of which hypopigmented MF was the most representative (17.6 %); poikilodermatous MF accounted for 4.1 %, and folliculotropic, for 3.1%. The papular variant occurred in six patients (2.1 %), the single-plaque variety in three (1%), and the ichthyosiform, syringotropic and granulomatous slack skin varieties occurred in one patient each. The granulomatous variant was found in 0.7 %, and 1.4 % had erythroderma., Conclusions: The most common MF clinical variant was classic plaque stage, followed by dyschromic variants. Other clinical variants accounted for 18.6 %., (Copyright: © 2020 Permanyer.)

Syringotropic mycosis fungoides (MF) is classified under folliculotropic MF. Although there is significant overlap between the 2, this study demonstrates that folliculotropism is frequently present in syringotropic MF, and when not present, the specimen did not include a follicle to examine. In addition, few of the pathology reports mentioned folliculotropism or syringotropism, although this is an important prognostic feature.

Non-Hodgkin's lymphoma (NHL) encompasses a diverse collection of systemic and primary cutaneous lymphomas. Cutaneous T-cell lymphomas (CTCLs) represent about 13% of all NHLs, which are further subdivided into a heterogeneous group with vastly different presentations and histologic features. Diagnosis requires integration of clinical, pathologic, and molecular features. Among CTCLs, mycosis fungoides and Sézary syndrome are the most prevalent. Treatment is aimed at limiting morbidity and halting disease progression. Hematopoietic stem cell transplantation is the only therapy with curative intent., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, typically presents in its early stage as inflammatory erythematous patches or plaques, with epidermotropism as the histopathologic hallmark of the disease. Over the past 30 years, numerous atypical types of MF, which deviate from the classic Alibert-Bazin presentation of the disease, have been described. These variants can simulate a wide variety of benign inflammatory skin disorders either clinically, both clinically and histopathologically, or mainly histopathologically. We have summarized the many faces of the disease, which set MF as a "great imitator," with special focus on the differential diagnosis and its benign mimickers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Our current mycosis fungoides (MF) and Sézary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sézary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry. No large study comparing blood-class as defined by Sézary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p < 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis. For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4+CD7-or CD4+CD26-where B0<250/μL, B1 = 250/μl-<1000/μL and B2≥1000/μL plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification. There is no curative therapy for CTCL yet, so that treatment currently aims at improving symptoms and quality of life as well as reducing relapse rates. The treatment has to be stage-adapted. Therapeutic options comprise skin-directed as well as systemic treatment. In early stages, phototherapy and local steroids are the first-line therapeutic options. For the therapy of higher stages, interferon alpha and the RXR-specific retinoid bexarotene are used as first-line medications. Second-line treatment comprises monochemotherapy with agents like gemcitabine or liposomal doxorubicine. Nevertheless, the high relapse rates in higher stages make novel alternative treatment options necessary. As future therapy, especially the fusion protein brentuximab-vedotin directed against CD30 shows promising potential in clinical studies.

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. The clinical course of the disease is typically characterized by progression from a nonspecific phase of erythematous macules to the appearance of plaques and ultimately, in some patients, tumors. However, numerous clinical and histopathologic variants of MF with specific therapeutic and prognostic implications have been described in recent decades. Clarification of the differential diagnosis can be frustrated by the wide range of clinical manifestations and histopathologic patterns of cutaneous infiltration, particularly in the early phases of the disease. In this paper, we review the main clinical, histopathologic, and immunohistochemical characteristics of the variants of MF described in the literature in order to facilitate early diagnosis of the disease., (Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: Forkhead box protein 3-positive (FoxP3(+) ) T cell lymphoma, in the absence of human T cell lymphotrophic virus type 1 (HTLV-1) infection, is rare and its clinicopathological characteristics still remain unclear. The aim of this study was to elucidate its characteristics., Methods and Results: We describe here 11 cases of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) and two cases of mycosis fingoides (MF) which were positive for FoxP3. The median age of the 11 PTCL-NOS cases was 65 years (range: 48-80 years), and all the patients were male. Eight patients (80%) showed stages III/IV disease, and six (60%) were categorized as high-intermediate/high-risk groups according to the International Prognostic Index. Two cases of MF were 57- and 59-year-old males. Both cases were categorized as stage IA, according to International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. Immunohistochemically, all the cases were negative for cytotoxic molecule marker, and nine (75%) were αβ T cell type. Scattered Epstein-Barr virus (EBV)-infected cells were detected in four cases of PTCL-NOS, implying the reactivation of EBV caused by the immunodeficient status of the patients., Conclusions: FoxP3(+) PTCL-NOS constitute a minor phenotypical subtype with poor prognosis and EBV reactivation in some. Conversely, two cases of MF showed an indolent clinical course which was different from previously reported cutaneous T cell lymphoma (CTCL) cases., (© 2015 John Wiley & Sons Ltd.)

Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on clinical lesion type and evaluation of findings on light microscopic examination, immunohistochemistry and molecular analysis of representative skin biopsies. The evaluation, classification, and staging system is unique for mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of cutaneous T-cell lymphoma (CTCL) versus the other subtypes of Non-MF/Non-SS CTCL and the subtypes of cutaneous B-cell lymphoma (CBCL). Since current treatment is stage-based, it is particularly important that the correct diagnosis and stage be ascertained initially. The purpose of this article is to review the current evaluation, diagnosis, classification, staging, assessment techniques, and response criteria for the various types of both T-cell and B-cell PCLs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous, they can be indistinguishable histologically. Lymphomatoid papulosis rarely requires systemic treatment; however, multifocal primary cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation of mycosis fungoides are typically treated systemically. As CD30⁺ LPDs are rare, there is little published evidence to support a specific treatment algorithm. Most studies are case reports, small case series, or retrospective reviews. This article discusses various treatment choices for each of the CD30⁺ disorders and offers practical pearls to aid in choosing an appropriate regimen., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In recent years, the distinction between idiopathic follicular mucinosis (FM) and lymphoma-associated follicular mucinosis (LAFM) has been made through assessment of T-cell receptor gene rearrangement, flow cytometry, and immunohistochemistry. These methods, among others, have mostly identified monoclonality as a defining characteristic of LAFM; however, this finding cannot be considered conclusive, as monoclonality also has been described in benign inflammatory dermatoses such as lichen planus and idiopathic FM. Pure histologic diagnosis also is unreliable in many cases, as the histologic patterns of idiopathic FM and LAFM overlap. In this article, we discuss the importance of close clinical follow-up in patients with patch-stage mycosis fungoides (MF) or FM who have had a nondiagnostic histopathologic evaluation. We also highlight the value of ancillary testing, including T-cell receptor gene rearrangement, flow cytometry, and immunohistochemistry, as a component in the diagnostic process rather than the sole diagnostic moiety. Diagnosis and classification of idiopathic FM and LAFM continue to pose challenges for dermatologists, oncologists, and pathologists, and no single diagnostic tool is sufficient in providing diagnostic certainty; rather, a collective evaluation of pathologic, molecular, and clinical criteria is required. Currently, classification of idiopathic FM and LAFM incorporates clinical information and histologic assessment, but little consideration is given to the implications of the diagnosis from the patient's perspective. Revisiting histologic classification of these entities while incorporating the patient's perspective may prove beneficial to dermatologists as well as patients.

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 type E (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.

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. A new form of incipient MF has recently been described: papular MF. Herein, we report a case and propose a literature review., Patients and Methods: A 63-year-old man presented with erythematous and non-pruritic papular lesions of the trunk. The general examination was unremarkable. A skin biopsy showed moderately dense epidermotropic lymphocytic infiltration consistent with MF. Screening for CD30 was negative. Treatment with an extremely potent corticosteroid (clobetasol, one application per day) seemed effective, with almost complete disappearance of the lesions., Discussion: Many clinical variants of the initial stages of MF have been described, one of the most recent of which is papular mycosis fungoides (PMF), of which 10 cases are reported in the literature. PMF begins clinically with an erythematous, non-pruritic and chronic papular rash that is not associated with the classic erythematous-squamous lesions of incipient MF. There appears to be no predominance of gender, and the age of onset ranges from 31 to 63 years. Histological examination of the PMF lesions revealed an epidermotropic subepidermal infiltrate composed predominantly of CD4+T-cells. The prognosis appeared good with the treatments conventionally used for incipient MF. PMF is likened to a form of incipient MF with a good prognosis. Associated classic MF lesions comprising erythematous-squamous plaques have been described as the condition progresses. Differential diagnoses include pilotropic MF, pityriasis lichenoides chronica, pityriasis lichenoides varioliformis acuta, and especially type B lymphomatoid papulosis, the histopathological findings of which may be close to PMF., Conclusion: Papular MF would appear to be a papular variant of incipient MF with a good prognosis. However, it is necessary to obtain clinical and disease progression data for a greater number of patients in order to better characterize this entity., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Cutaneous T-cell lymphomas are rare, distinct forms of non-Hodgkin's lymphomas. Of which, mycosis fungoides (MF) and Sézary syndrome (SS) are two of the most common forms. Careful, clear classification and staging of these lymphomas allow dermatologists to commence appropriate therapy and allow correct prognostic stratification for those patients affected. Of note, patients with more advanced disease will require multi-disciplinary input in determining specialist therapy. Literature has been summarized into an outline for classification/staging of MF and SS with the aim to provide clinical dermatologists with a concise review.

Background: Although patients with mycosis fungoides (MF) typically experience an indolent disease course, a minority undergo a process of large-cell transformation (LCT), which often heralds more aggressive disease and shortened survival. Regrettably, most dermatologists are unfamiliar with LCT, and even fewer understand how to recognize it clinically. Because a diagnosis of LCT typically triggers more aggressive therapy and/or referral to cutaneous T-cell lymphoma (CTCL) centers, it is paramount for clinicians to be able to recognize suspect lesions visually., Objective: LCT is diagnosed histologically; however, diagnostic biopsy is performed only if transformed lesions are suspected clinically. Because the literature provides little information on what clinical features should lead to suspicion of LCT, we sought to identify and categorize the presentations of LCT to aid in its recognition., Methods: We identified 14 patients with biopsy-proven LCT confirmed by a board-certified dermatopathologist experienced with this diagnosis. The clinical presentations of LCT, timing of its evolution, and treatment regimens were evaluated by chart and photograph review., Results: We devised 3 categories that clinically represent LCT: (1) LCT occurring as a new, solitary nodule within a classic MF patch or plaque, (2) LCT occurring as abrupt onset of multiple scattered papules and/or nodules without spontaneous resolution, and (3) LCT occurring within new or enlarging tumors., Limitations: A larger number of reviewed cases might reveal additional clinical presentations of LCT., Conclusions: Dermatologists may use our categories of clinical indicators to recognize and diagnose LCT earlier, allowing implementation of more aggressive treatment regimens when appropriate., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and has protean clinicopathological manifestations. Follicular or folliculotropic MF (FMF) is a rare variant, which histopathologically is characterized by pronounced folliculotropism of neoplastic T cells, with or without follicular mucinosis, and clinically by an impaired prognosis compared to classic MF. In contrast, unilesional MF is a very rare variant with an excellent prognosis, with a single case of large-cell transformation reported to date. The combination of folliculotropic and unilesional MF is very unusual, with only two cases reported to date. Here we report two patients with unilesional folliculotropic MF with progression to tumor stage in both patients. To the best of our knowledge, this is the first report on the disease evolution with large-cell transformation and progression of unilesional FMF. Complete remission was achieved by local radiation therapy in both patients. The differential diagnoses, classification and implications for the treatment of unilesional FMF as well as the pertinent literature are discussed., (Copyright © 2012 John Wiley & Sons A/S.)

Hypopigmented mycosis fungoides (MF) is a relatively uncommon variant of cutaneous lymphoma that is mostly seen in darker skin types. We present a novel and unique clinical presentation in an African-American female patient, consisting of regular hypopigmented annular rings in areas of normal skin and in more typical hypopigmented patches of MF. The lesions appeared diffusely on all extremities, anterior chest and back. Histopathologic examination showed an atypical lymphocytic infiltrate at the dermal-epidermal junction with epidermotropism and few Pautrier's collections. The patient was otherwise healthy and improved with narrowband ultraviolet (UV)-B. This case represents a presentation of a most unusual variant of hypopigmented MF, for which we propose the name 'annular hypopigmented MF'., (Copyright © 2012 John Wiley & Sons A/S.)

Introduction: Cutaneous syringotropic T-cell lymphoma is a rare form of lymphoma. We report a case involving a misleading cutaneous presentation on the sole of the foot., Patients and Methods: A 55-year-old woman presented discrete coalescent papules on her left foot, having an anhidrotic appearance, for which a number of antifungal treatments had been given without success. The skin biopsy revealed CD4+ T lymphocytic dermal infiltrate, mainly near the sweat glands, with syringotropism. The diagnosis of syringotropic T-cell lymphoma was reinforced by the presence of dominant cutaneous T-lymphocyte clone in the skin biopsy. Staging tests were negative. Treatment was initiated with an extremely potent (class IV) dermal corticosteroid., Discussion: Syringotropic T-cell lymphoma is an extremely rare form of cutaneous lymphoma similar in presentation to mycosis fungoides, characterised by the mainly perisudoral and syringotropic nature of the lymphocytic infiltrate. The value of this case report lies in the extremely mild nature of the misleading skin lesions, which could only be diagnosed through biopsy. Treatment for this condition is not as yet codified due to the extremely low number of cases reported in the literature., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

Mycosis fungoids can present with various clinical and histological features, with only a few of them being recognized as distinct entities in the current WHO and EORTC classifications. Histologically, mycosis fungoids (MF) usually show a superficial perivascular or band-like lymphocytic infiltrate with epidermotropism. We here report two cases of a rare histological variant of MF, called interstitial in the literature. Our first patient, a 71-year-old male, had a previously diagnosed MF, which clinically evolved towards nodules, showing histologically an interstitial lymphocytic infiltrate without epidermotropism and without large cell transformation. The second patient was a 64-year-old female with widespread plaques and nodules. Histologically, a dense dermal interstitial infiltrate was observed, with foci of epidermotropism, without large cell transformation. At relapse after treatment, she presented with plaques, papules and nodules, histologically showing a slight interstitial lymphocytic infiltrate that resembled granuloma annulare or inflammatory morphea. In both patients, clinical aspect suggested MF and a dominant T-cell clone was found in lesional skin. Nodules in MF are not always the hallmark of large cell transformation, but may correspond to unusual interstitial lesions. Diagnosis of such rare variant may be difficult and requires a good clinical pathological correlation together with the search for foci of epidermotropism on skin biopsy and for a dominant cutaneous T-cell clone., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

A rare variant of mycosis fungoides (MF) characterized by prominent involvement of the eccrine glands with syringometaplasia has been reported in the past as "syringolymphoid hyperplasia with alopecia," "syringotropic cutaneous T-cell lymphoma," "adnexotropic T-cell lymphoma," or "syringotropic MF." The clinicopathologic features of this variant are not well understood, and only a few case reports or small series have been published to date. We reviewed the clinicopathologic features of 14 patients with syringotropic MF (male:female=10:4; median age, 59 years; mean age, 57.8; age range, 33 to 83 y). Six patients had variably large, solitary patches or plaques, located on the thigh (n=3), arm, trunk, or eyebrow (1 each). The other 8 patients had multiple, mostly generalized lesions. A history of MF was known in 4 of these 8 patients. With the exception of 1 biopsy specimen that was too superficial and did include the eccrine secretory coils but not the eccrine glands, all cases showed prominent involvement of the eccrine glands. Variable degrees of syringometaplasia ranging from small to large epithelial complexes were present in all specimens. The eccrine glands and syringometaplastic structures were surrounded by dense lymphoid infiltrates with prominent epitheliotropism. Concomitant involvement of the epidermis and of the hair follicles was observed in 13 and 8 biopsies, respectively. This is the largest series of syringotropic MF, showing that this is a rare variant of the disease with peculiar clinicopathologic features. Dermatologists and dermatopathologists should be aware of this rare variant of MF to avoid delayed diagnosis and treatment.

Syringotropic cutaneous T-cell lymphoma (CTCL) is a rare form of CTCL characterized histologically by infiltrates of atypical lymphocytes located primarily in and around hyperplastic eccrine glands and ducts. Currently, syringotropic CTCL is classified as a histopathologic variant of folliculotropic mycosis fungoides (MF); however, the relationship between these two entities remains tenuous. We report two additional cases of syringotropic CTCL and review the differences between these two subtypes of MF with regard to epidemiology, clinical features, prognosis, and treatment. Based on these data, we conclude that syringotropic CTCL should be classified as a distinct variant of MF separate from folliculotropic MF.

Terminological confusion with benign dermatosis, such as parapsoriasis en plaques, makes it difficult to diagnose mycosis fungoides in the early patch stage. Early diagnosis of mycosis fungoides (MF) is important for deciding on type of therapy, prognosis and for further follow-up. However, until recently, there has been no consensus on criteria that would help in diagnosing the disease early. Some believe that large plaque parapsoriasis (LPP) should be classified with early patch stage of MF and should be treated aggressively. However, there is no firm clinical or laboratory criteria to predict which LPP will progress to MF and we can only discuss about statistical probability. Moreover, long-term outcome analysis of even patch stage of MF is similar to that of control population. We therefore believe that LPP should be considered as a separate entity at least to prevent the patient from being given a frightening diagnosis. We also feel that patients need not be treated with aggressive therapy for LPP and will need only a close follow-up. This article emphasizes the criteria for diagnosing early MF and has highlighted the importance of considering LPP as a distinct benign entity.

Although primary cutaneous lymphomas (PCL) are the second most common group of extra-nodal non-Hodgkin lymphomas, few epidemiological data are available in the literature, and most of them are provided by large databases from population-based cancer registries in the US or patients attending a single institution. We conducted this study to investigate the epidemiological and clinical features of PCL diagnosed in the department of Doubs from 1980 to 2003. Data were collected from the Doubs cancer registry from 1980 to 2003. Seventy-one patients with PCL were investigated. 82% were cutaneous T-cell lymphoma (CTCL) and 18% were cutaneous B-cell lymphoma (CBCL). Among CTCL, mycosis fungoides (MF) represented 58% and Sezary syndrome 10%. The standardised incidence rate of PCL was 0.42 for 100 000 person-years and significantly increased from 0.21 in 1980-1984 to 0.70 in 2000-2003 (p <0.05). The incidence rate of CTCL was 0.34 for 100 000 person-year and significantly increased from 0.2 to 0.57 (p <0.05). For MF and CBCL, the incidence rates were 0.20 and 0.08, respectively and did not vary significantly from 1980-1984 to 2000-2003. Five-year survival was 64.5% for PCL patients similar to MF patients. Our results provide updated data on the incidence of PCL in France.

Background: Primary cutaneous marginal zone lymphoma is recognized as a unique subset of low-grade cutaneous B-cell lymphoma with indolent course in the current World Health Organization-European Organization on Research and Treatment of Cancer classification system. However, few large series on this entity have been reported, including the new TNM (tumor, (lymph) node, metastasis) classification for non-mycosis fungoides cutaneous lymphomas., Objective: We aimed to characterize the clinical features including new TNM classification for non-mycosis fungoides cutaneous lymphomas, as well as outcomes and responses to therapy in 30 patients with primary cutaneous marginal zone lymphoma., Results: Primary cutaneous marginal zone lymphoma typically presents with deep-seated nodular or papular lesions on the upper extremities or trunk (25/30). Disease course is indolent and none of 30 patients died of disease. Sustainable complete remissions were obtained only in patients with T1a (n = 3) and T2a (n = 1) disease. Most patients have persistent stable disease independent of treatment. Two patients developed systemic disease and 5 developed large cell transformation., Limitations: The average follow-up time was 63 months (range, 3-204 months). Longer follow-up time is needed to determine whether patients with untreated persistent stable disease are at greater risk relative to patients treated aggressively early in the disease course., Conclusions: Primary cutaneous marginal zone lymphoma is a distinct subtype of marginal zone lymphoma with an indolent disease course. Patients with T1a or T2a disease (ie, single lesions or a localized cluster of lesions) may achieve sustained complete remission, whereas patients with multiple nonlocalized lesions are unlikely to maintain complete remission independent of treatment modality. Systemic involvement is typically preceded by large cell transformation and may be an indication for more systemic therapy. Death from disease is rare.

Clinical, prognostic and therapeutic features of 54 primary cutaneous marginal zone B-cell lymphoma (pcMZL), follicle centre lymphoma (pcFCL) and diffuse large B-cell lymphoma, leg type (pcDLBL) were analysed applying the WHO-EORTC classification for cutaneous lymphomas and the new TNM staging scheme of the International Society of Cutaneous Lymphomas. Solitary (T1) or regionally clustered (T2) tumors were observed in pcMZL and pcFCL. Disseminated tumors (T3 stage) were found in 26% of patients with pcMZL and in one patient with pcDLBL. A complete remission was achieved in 41% of the patients. Three of 7 patients (43%) with pcDLBL died due to lymphoma. The new TNM staging system is easily applicable for disease documentation, but our relatively small number of patients in each T stage does not allow the assessment of its prognostic value. Surgical excision or radiotherapy is highly effective in pcMZL and pcFCL.

The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.

Currently availabel staging systems for non-Hodgkin lymphomas are not useful for clinical staging classification of most primary cutaneous lymphomas. The tumor, node, metastases (TNM) system used for mycosis fungoides (MF) and Sézary syndrome (SS) is not appropriate for other primary cutaneous lymphomas. A usable, unified staging system would improve the communication about the state of disease, selection of appropriate management, standardization of enrollment/response criteria in clinical trials, and collection/analysis of prospective survival data. Toward this goal, during the recent meetings of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC), the representatives have established a consensus proposal of a TNM classification system applicable for all primary cutaneous lymphomas other than MF and SS. Due to the clinical and pathologic heterogeneity of the cutaneous lymphomas, the currently proposed TNM system is meant to be primarily an anatomic documentation of disease extent and not to be used as a prognostic guide.

Cases drawn from Session 5 of the 2005 Society for Hematopathology/European Association for Haematopathology Workshop on progress in T-cell and natural killer (NK)-cell malignancies are used as a framework to review the current classification of T-cell and NK-cell malignancies in skin. In comparison with the typical pattern and course of mycosis fungoides (MF), selected variants of MF that can be difficult to diagnose are discussed. Cutaneous CD30+ lymphoproliferative disorders are also presented in detail. Particular focus is placed on the recognition of rare but clinically more aggressive cytotoxic lymphomas in the skin. Overall, diagnostic pitfalls and new information regarding disease pathogenesis brought up by the Workshop cases are provided. In addition, a general approach to the diagnosis of cutaneous T-cell lymphomas is discussed.

Background: The relative incidence of malignant lymphoma subtypes differs according to geographic location. This study investigated the epidemiology of cutaneous lymphoma subtypes in Japan and compared it with other countries., Methods: Sixty-two patients with cutaneous lymphoma attending the Department of Dermatology, National Hospital Organization Hokkaido Cancer Center were reviewed. The World Health Organization classification of hematopoietic and lymphoid malignancies was adopted., Results: Of the 62 patients, 31 had primary cutaneous lymphoma (PCL) and 31 had secondary cutaneous lymphoma (SCL). T- and natural killer (NK)-cell lymphoma accounted for 80% of PCL, of which, mycosis fungoides accounted for almost 35%. Of the 31 patients with secondary cutaneous lymphoma, 17 patients (54%) had T- and NK-cell lymphoma, including nine adult T-cell leukemia/lymphoma patients, and 14 patients (46%) had B-cell lymphoma, including 11 diffuse large B-cell lymphoma patients. The majority of patients with SCL and NK-cell lymphoma with primary or secondary skin lesions had a poor outcome., Conclusions: PCL in this study showed a similar incidence to that of other institutions in Japan, while also demonstrating different frequencies from that of other countries, suggesting that the relative frequency of different PCL subtypes differ according to geographical location, similar to previous reports of systemic malignant lymphoma.

Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.

Following consensus meetings of the two parent organizations, a new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high-grade treatment for low-grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma. In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. In early stages of the disease many different clinicopathologic variants have been observed., Observation: We report 6 patients with early manifestations of MF characterized by the sole presence of papules which, unlike the papules of lymphomatoid papulosis, did not show a tendency for spontaneous resolution. Histologic examination confirmed the diagnosis of MF in all cases. Immunohistochemical staining for CD30 was negative in all cases. Follow-up data showed the nonaggressive behavior of the disease, confirming that the lesions were not manifestations of advanced MF., Conclusion: Papular MF is a new variant of early MF characterized by the presence of papules in the absence of more conventional early lesions (patches) of the disease. This variant should be added to the long list of clinicopathologic subtypes of MF.

In this historical review I will synopsize the original articles by Lloyd W. Ketron and M.H. Goodman who described Ketron-Goodman disease, by Frederic Woringer and Pierre Kolopp who described Woringer-Kolopp disease, and by Otto Braun-Falco and colleagues who described pagetoid reticulosis. In their publications, each of these authors reported on one patient. I will review the clinical picture of the three patients, their histopathology, and the pathogenesis of each disease as suggested by the above authors. Then the views of others that have written on the subject recently will be reviewed particularly as to their conception of the diseases. Publications that describe the histopathology of the patch (early) stage of mycosis fungoides will be redacted to compare it to the histopathology of Ketron-Goodman disease, Woringer-Kolopp disease, and pagetoid reticulosis. I will discuss whether any or all of them are diseases sui generis, whether they are one, two, or three entities, or whether any or all are but forms of mycosis fungoides.

Cutaneous lymphomas represent a heterogeneous group of T-, NK- and B-cell neoplasms, with mycosis fungoides (MF) being the most common subtype. MF has a plethora of clinicopathological manifestations. Many variants of this lymphoma differ substantially from the 'classical' Alibert-Bazin disease and are therefore sometimes referred to as 'atypical' forms of the disease. This review addresses the whole clinicopathological spectrum of mycosis fungoides with respect to epidemiology, clinical, histopathological, immunophenotypic and genotypic features and the clinical course and prognosis of its variants: classical, erythrodermic, follicular, syringotropic, bullous/vesicular, granulomatous, poikilodermic, hypo- and hyperpigmented, unilesional, palmoplantar, hyperkeratotic/verrucous, vegetating/papillomatous, ichthyosiform, pigmented purpura-like, pustular and mucosal involvement in MF.

Confusion abounds regarding the terms "follicular mucinosis" and "alopecia mucinosa," not only concerning definition and essential character, but of relationships between themselves on one hand and between themselves and mycosis fungoides on the other. We address here those issues in methodical fashion, first in historical perspective by review, scrupulously and critically, of what has been said in the many articles devoted to the subject; we next tell how the terms "alopecia mucinosa" and "follicular mucinosis" came to be and how they are employed currently; we then set forth our own observations pertinent to clinical, histopathologic, and biologic aspects of the condition called, conventionally, "alopecia mucinosa," those observations based on our own findings in sections of tissue cut from 54 biopsy specimens taken from 45 patients, all of them having been signed out previously as "follicular mucinosis;" we proceed to forge clinico-pathologic correlation of lesions in 14 of those 45 patients, utilizing assessments, by examination grossly and microscopically, of attributes in the very same lesion. Last, we propose a concept, and a terminology that derives from it, that synthesizes all that is known now about "alopecia mucinosa" and "follicular mucinosis," in particular the relationship of "alopecia mucinosa" to mycosis fungoides, including "follicular," "syringotropic," and erythrodermic manifestations of it. In short, we affirm that so-called alopecia mucinosa is but one of many morphologic manifestations of mycosis fungoides.

Mycosis fungoides is a low-grade lymphoproliferative disorder caused by CD4+ lymphocytes. It is the most common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize to the skin and produce patches, plaques, tumors, or erythroderma. Diagnosis of early mycosis fungoides can be difficult due to the nonspecific nature of cutaneous and histologic findings. However, recent advances in the application of histologic criteria, coupled with molecular biology tools such as immunophenotyping and polymerase chain reaction, have improved diagnostic accuracy. Independent prognostic factors include the extent and nature of skin involvement, the presence of extracutaneous disease, blood involvement, age > or = 60 years, and lactate dehydrogenase elevation. Accordingly, patients with limited patches and/or plaques (stage IA or IIA) experience long-term survival comparable to that of matched controls. The median survival is 11 years for patients with extensive patch/plaque (stage IB or IIA), 3.2 years for those with cutaneous tumors (stage IIB), 4.6 years for those with erythroderma (stage III), 1.2 years for those with pathologic nodal involvement (stage IVA), and 0.9 years for those with visceral disease (stage IVB). Over time, mycosis fungoides may progress to Sézary syndrome or transform to large-cell histology.

Mycosis fungoides (MF) is the most frequent type of cutaneous T-cell lymphoma, whose diagnosis and study is hampered by its morphologic similarity to inflammatory dermatoses (ID) and the low proportion of tumoral cells, which often account for only 5% to 10% of the total tissue cells. cDNA microarray studies using the CNIO OncoChip of 29 MF and 11 ID cases revealed a signature of 27 genes implicated in the tumorigenesis of MF, including tumor necrosis factor receptor (TNFR)-dependent apoptosis regulators, STAT4, CD40L, and other oncogenes and apoptosis inhibitors. Subsequently a 6-gene prediction model was constructed that is capable of distinguishing MF and ID cases with unprecedented accuracy. This model correctly predicted the class of 97% of cases in a blind test validation using 24 MF patients with low clinical stages. Unsupervised hierarchic clustering has revealed 2 major subclasses of MF, one of which tends to include more aggressive-type MF cases including tumoral MF forms. Furthermore, signatures associated with abnormal immunophenotype (11 genes) and tumor stage disease (5 genes) were identified.

Objective: To determine the clinicopathologic features and the disease course of patients with follicular mycosis fungoides (MF)., Design: A multicenter, 14-year, retrospective cohort analysis., Setting: Dutch Cutaneous Lymphoma Group., Patients: Fifty-one patients with the clinicopathologic features of follicular MF with (n = 49) or without (n = 2) associated follicular mucinosis. Follow-up data were compared with those of 158 patients with the classic epidermotropic type of MF, including 122 patients with generalized plaque-stage MF (T2 N0 M0) and 36 patients with tumor-stage MF (T3 N0 M0)., Observations: Characteristic clinical features not or rarely observed in classic MF were the preferential localization of the skin lesions in the head and neck region (45 of 51 patients), the presence of follicular papules, alopecia, acneiform lesions, mucinorrhoea, and often severe pruritus. Characteristic histologic findings were the presence of perifollicular neoplastic infiltrates with a variable degree of folliculotropism, but generally no epidermotropism, follicular mucinosis (49 of 51 cases), and often a considerable admixture of eosinophils and plasma cells. Response on initial treatment, risk of disease progression (development of extracutaneous disease and/or death from lymphoma), and disease-specific and overall survival of patients with follicular MF were worse than in classic MF patients. The actuarial disease-specific survival was 68% at 5 years and 26% at 10 years., Conclusions: Follicular MF shows distinctive clinicopathologic features, is more refractory to treatment, and has a worse prognosis than the classic type of MF; it should be considered a distinct type of cutaneous T-cell lymphoma. Based on these results and those of other studies, we suggest the term follicular MF for cases with or without associated follicular mucinosis.

Background: The spectrum of mycosis fungoides is exceedingly broad. Many different variants have been described, based on both clinical appearance and histological pattern. A rare form which shows preferential infiltration of hair follicles by malignant lymphocytes is follicular mycosis fungoides., Methods: We reviewed our experience with nine cases of follicular mycosis fungoides., Results: The unifying feature was infiltration of the hair follicle epithelium by atypical lymphocytes causing varying degrees of damage to the hair follicles. In some specimens the lymphocytes displayed only minor atypia leading to a misinterpretation as pseudolymphoma. Gene rearrangement studies were particularly helpful for establishing a diagnosis of malignant lymphoma. Additionally, epidermotropism of lymphocytes, eosinophils and mucin deposition were present to varying degrees. Mucin makes the distinction from mycosis fungoides-associated follicular mucinosis difficult. We found both dermal mucin and a follicular mucinosis pattern present at different stages of disease in the same patient., Conclusions: We suggest the term mycosis fungoides-associated follicular mucinosis should be replaced by follicular mycosis fungoides in future lymphoma classification schemes.

Background: Despite refinements in the diagnosis of cutaneous T-cell lymphoma (CTCL), since 1979 there have been no changes to the staging of CTCL used to classify mycosis fungoides and Sézary syndrome., Objective: We reviewed the current staging of CTCL and examined the usefulness of a new staging scheme for mycosis fungoides and Sézary syndrome., Methods: We determined overall survival of 450 patients with mycosis fungoides and Sézary syndrome using the current and modified staging classifications., Results: There were no significant differences between survival of patients with stage IB (patches/plaques involving greater than 10% body surface area) and IIA (peripheral adenopathy) disease and of patients with stage IIB (tumor) and III (erythroderma) disease. There was a significant difference in survival between patients with extensive patch versus extensive plaque stage disease. Modification of the current classification by splitting T2 into patch versus plaque stage disease and incorporating tumors and erythroderma into stage III proved superior to the current scheme in predicting overall survival., Conclusion: Modification of the current staging classification for CTCL yields subgroups useful in the prognostic assessment of CTCL.

Erythrodermic cutaneous T-cell lymphoma (CTCL) includes patients with erythrodermic mycosis fungoides who may or may not exhibit blood involvement and Sézary syndrome and in whom hematological involvement is, by definition, present at diagnosis. These patients were stratified into 5 hematologic stages (H0-H4) by measuring blood tumor burden, and these data were correlated with survival. The study identified 57 patients: 3 had no evidence of hematologic involvement (H0), 8 had a peripheral blood T-cell clone detected by polymerase chain reaction (PCR) analysis of the T-cell receptor gene and less than 5% Sézary cells on peripheral blood smear (H1), and 14 had either a T-cell clone detected by Southern blot analysis or PCR positivity with more than 5% circulating Sézary cells (H2). Twenty-four patients had absolute Sézary counts of more than 1 x 10(9) cells per liter (H3), and 8 patients had counts in excess of 10 x 10(9) cells per liter (H4). The disease-specific death rate was higher with increasing hematologic stage, after correcting for age at diagnosis. A univariate analysis of 30 patients with defined lymph node stage found hematologic stage (P =.045) and lymph node stage (P =.013) but not age (P =.136) to be poor prognostic indicators of survival. Multivariate analysis identified only lymph node stage to be prognostically important, although likelihood ratio tests indicated that hematologic stage provides additional information (P =.035). Increasing tumor burden in blood and lymph nodes of patients with erythrodermic CTCL was associated with a worse prognosis. The data imply that a hematologic staging system could complement existing tumor-node-metastasis staging criteria in erythrodermic CTCL.

Large numbers of CD30-positive tumor cells are not typically observed in mycosis fungoides (MF), but CD30 expression may occur on large cells of MF that have transformed into high-grade large cell lymphoma. Of 202 patch/plaque phase MF cases studied by immunohistochemistry, we encountered 4 patients with patch-phase MF at stage Ia or Ib, whose lesions contained a high proportion (greater than 50%) of CD30-positive tumor cells within the epidermis. The morphologic and immunohistochemical features of these four cases were otherwise similar to those of other patch-phase MF cases, and were different from those of pagetoid reticulosis. More importantly, the clinical behavior of these cases did not differ from that of other cases of early MF without CD30 expression. The mechanism underlying the high levels of CD30 expression by epidermotropic tumor cells is unknown. With increased use of the CD30 immunohistochemical stain in the diagnosis of cutaneous lymphomas, similar cases are likely to be encountered, and perhaps will be evaluated for their clinical behavior.