Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems

BACKGROUND: Cutaneous lymphomas other than mycosis fungoides (MF) are a heterogeneous group with wide variations in clinical presentation, biological behaviour and prognosis. New classification systems have been designed or proposed in recent years, with well-defined disease entities and emphasis on the importance of site. OBJECTIVES: This study aims to analyse a series of non-MF lymphomas in an institution-based dermatological setting in Singapore, based on the European Organization for Research and Treatment of Cancer (EORTC) classification and the World Health Organization (WHO) classification. A secondary objective is to highlight the clinical utility of both classification systems. PATIENTS AND METHODS: Forty cases diagnosed over a 12-year period were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD5, CD8, CD20, CD30, CD43, CD45RO, CD56 and CD68 in paraffin-embedded specimens. The immunohistological diagnosis was correlated with the clinical presentation and staging investigations for the final diagnosis and the course of disease recorded. RESULTS: Non-MF T-cell lymphomas presenting in the skin comprised 31 cases (78%) and were 3(1/2) times more common than B-cell lymphomas, which comprised nine cases (22%). The common subtypes were lymphomatoid papulosis, CD30+ large cell cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma. The commonly ascribed B-cell pattern with infiltrates in the mid and deep dermis and perivascular spaces was seen in 60% of T-cell lymphomas. Overall, there were equal numbers of primary cutaneous T-cell lymphomas and those due to concurrent or secondary cutaneous lymphoma. Five of six cases of subcutaneous panniculitis-like T-cell lymphoma had concurrent cutaneous and systemic involvement and their median survival was 7 months. CONCLUSIONS: The predominance of cutaneous T-cell lymphomas in this case series closely matched that reported from east Asia; cutaneous B-cell lymphomas are much less common than in Europe. The EORTC classification, which is designed only for primary cutaneous lymphomas, should be used in conjunction with the WHO classification because of the high prevalence of cutaneous lymphomas as the secondary site of disease from systemic lymphoma. In addition, subcutaneous panniculitis-like T-cell lymphoma is a primary cutaneous lymphoma where systemic involvement is common at initial presentation. We propose full immunophenotyping and complete clinical evaluation with staging investigations for all patients presenting with cutaneous lymphomas other than MF.     

Relative frequency of the different types of cutaneous T cell and natural killer cell lymphomas in Korea based on the proposed WHO classification and the EORTC classification

The R.E.A.L. classification was largely adopted recently by the proposed WHO classification. The usefulness of this classification in cutaneous T cell and natural killer (NK) cell lymphomas in Korea was evaluated compared to that of the European Organization for Research and Treatment of Cancer (EORTC) classification. Overall, 78 patients with cutaneous T cell and NK cell lymphomas were diagnosed in Asan Medical Center in the 1990's. The clinical records, slides of H&E and immunohistochemical stainings were reviewed. By the proposed WHO classification, mycosis fungoides (20 cases), lymphomatoid papulosis (13 cases), nasal type NK/T-cell lymphoma (10 cases), CD30+ anaplastic large cell lymphoma (8 cases), subcutaneous panniculitis-like T-cell lymphoma (6 cases), peripheral T-cell lymphoma, unspecified (3 cases), Sézary syndrome (1 case) and blastic NK cell lymphoma (1 case) comprised the primary cases. Secondary or undetermined cases included peripheral T-cell lymphoma, unspecified (10 cases), nasal type NK/T-cell lymphoma (5 cases), and angioimmunoblastic T-cell lymphoma (1 case). EORTC classification for cutaneous T cell and NK cell lymphomas did not include nasal and nasal type NK/T-cell lymphomas, unspecified non-pleomorphic T-cell lymphoma, undetermined cases among primary or secondary ones and some rare types of skin lymphomas which can be classified by WHO. The WHO classification is more useful for skin lymphomas in Korea since it encompassed all the various types of skin T cell and NK cell lymphomas in Korea.     

Primary cutaneous T-cell lymphoma occurring after organ transplantation

Lymphoma occurring after organ transplantation has been well described. The majority of cases are B-cell lymphomas and are usually associated with Epstein-Barr virus. Only a minority of posttransplant lymphomas are of T-cell origin, and primary cutaneous T-cell lymphoma (CTCL) is extremely rare. In this article, we report a case of cutaneous peripheral T-cell lymphoma, pleomorphic CD30+ large-cell type, and review the literature relating to posttransplant primary CTCL. Of the 23 cases of posttransplant primary CTCL, 5 patients had erythrodermic disease, and 8 had primary cutaneous anaplastic large cell lymphoma. In addition, there are two cases of mycosis fungoides, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of CD30+ lymphomatoid papulosis, and 6 cases of peripheral T-cell lymphoma, of which 3 were CD30+ large cell lymphomas. Seventeen cases had renal transplants and the majority received both cyclosporine and azathioprine. No consistent viral association was noted among these cases. The sex ratio was 18:5 (male/female), and the mean age at diagnosis was 53 years. Mean time from transplantation to diagnosis is 6.4 years and mean survival time from diagnosis is 14.5 months. The prognoses normally associated with particular subsets of CTCL do not apply in the posttransplant setting.     

The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants

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.     

EORTC classification for primary cutaneous lymphomas: the best guide to good clinical management. European Organization for Research and Treatment of Cancer.

In 1997 the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC) published a proposal for a classification for the group of primary cutaneous lymphomas (1). The EORTC classification is the first and only classification that is designed exclusively for the group of primary cutaneous lymphomas. It is also the only classification that has been clinically validated for this group of diseases. As illustrated by this special issue, this classification has resulted not only in the discussion of the definition and terminology of some types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL), but also in a discussion of whether organ-based classification schemes (separate from existing hematopathologic classification schemes for non-Hodgkin lymphomas) should be used. This article explains why it was necessary to create a separate classification for the group of primary cutaneous lymphomas. A short introduction on the history of the classification of cutaneous lymphomas is provided. Next, the basic principles of the EORTC classification are presented. Finally, controversies between the EORTC classification versus the REAL classification (2) and the proposed WHO classification (3), which still impede the usage of one common classification system, are discussed.     

Primary cutaneous B-cell lymphoma: how useful is the new European Organization for Research and Treatment of Cancer (EORTC) classification?

The classification of non-Hodgkin's lymphoma has undergone extensive revision in recent years, particularly with the development of immunophenotypic and genotypic criteria. While most general pathologists now rely upon the Revised European and American Classification of Lymphoma neoplasms (REAL), the cutaneous lymphoma project group of the European Organization for Research and Treatment of Cancer (EORTC) has put forward its own proposal for the classification of primary cutaneous lymphomas. While this is understandable in the context of cutaneous T-cell lymphoma, the EORTC classification of primary cutaneous B-cell lymphoma has proved more controversial: first, because chromosomal changes are largely excluded; secondly, because follicle centre cell lymphoma in the skin is imprecisely defined; and thirdly, because large B-cell lymphoma of the leg is included as a separate entity. This review identifies the main differences between the two systems of classifying B-cell lymphomas in the skin, and the areas of research required to clarify some of the outstanding issues. Pathologists are unlikely to adopt the EORTC proposals for B-cell neoplasms until these issues have been resolved.     

World Health Organization classification of hematopoietic and lymphoid tissues: implications for dermatology

The new World Health Organization (WHO) classification of hematopoietic and lymphoid malignancy represents the first worldwide consensus document on the classification of lymphoma/leukemia. Its aim is to supercede all existing classification systems, including the Revised European American Classification (REAL), and the organ-based classification of cutaneous lymphoma proposed in 1997 by the European Organization for Research and Treatment of Cancer (EORTC) cutaneous lymphoma project group. This article compares the REAL, EORTC, and WHO classifications with particular reference to cutaneous lymphoma. It identifies those entities that have been adopted from the EORTC classification, and illustrates important new entities in the category of cytotoxic T-/NK-cell lymphomas that characteristically present in the skin or subcutaneous tissue. However, WHO is not an organ-based classification and some categories (eg follicular B-cell lymphoma and peripheral T-cell lymphoma) include both cutaneous and systemic diseases, and these may have very different prognoses. It is, therefore, important that cancer registries are capable of recording sites of involvement for both B- and T-cell lymphomas so that the incidence and prognosis of cutaneous lymphomas can be established from national data sets in future years.     

Clinicopathologic reassessment of non-mycosis fungoides primary cutaneous lymphomas during 17 years

BACKGROUND: New classification systems have recently been proposed for primary cutaneous lymphomas (PCLs). The aim of our study was to evaluate the applicability and significance of the new classification systems to the diagnosis and management of non-mycosis fungoides (non-MF) PCL. METHODS: Immunohistochemical restaining, histological reclassification, and clinical follow-up of all new non-MF PCL cases during 17 consecutive years were performed. The histological reclassification was performed according to the Revised European-American Lymphoma (REAL) classification, except for lymphomatoid papulosis (Lyp), which was included as an indolent lymphoma, according to the European Organization for the Research and Treatment of Cancer (EORTC) classification. RESULTS: During the period 1983-99, 251 new PCL cases were seen, 213 (85%) of which were MF and Sézary syndrome (eight cases), and 38 (15%) of which were non-MF. Of the latter, 20 (53%) were B-cell lymphomas, including eight (40%) follicle center lymphoma, follicular (FCLF), eight (40%) marginal zone lymphoma (MZL), two (10%) diffuse large cell lymphoma, and two (10%) unclassifiable cases. Most or all of the lesions did not stain for CD10, CD43, and bcl-2 protein, and immunostaining for kappa and lambda immunoglobulin light chain restriction was much more useful diagnostically in MZL. Of the 18 primary non-MF cutaneous T-cell lymphomas, 13 (72%) were Lyp, all of which were type A, four (22%) were CD30+ anaplastic large cell lymphoma, and one (6%) was natural killer (NK)/T-cell lymphoma. Except for the NK/T-cell lymphoma, all the other non-MF PCLs had an indolent course. CONCLUSIONS: A minority of the routinely diagnosed PCLs are non-MF, equally divided between B- and T-cell lymphomas. The REAL classification is applicable to the majority, although it does not include entities such as Lyp; the clinical correlations are not as obvious because most of the non-MF PCLs tend to have a relatively indolent course.     

The protean spectrum of non-Hodgkin lymphomas with prominent involvement of subcutaneous fat

BACKGROUND: Subcutaneous T-cell lymphoma (STCL) represents a controversial entity and a confused concept in the field of cutaneous T-cell lymphomas (CTCLs). Recently, alpha/beta+/CD8+ STCL has been recognized by the new World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphomas as a distinct entity in the group of CTCLs. OBSERVATIONS: We reviewed a series of 53 biopsies from 26 patients (F : M = 19:7; median age: 48; range 18-87) of cutaneous B- and T-cell lymphomas characterized by prominent involvement of the subcutaneous tissue. We could classify our cases according to the following seven categories--(i) STCL: n = 16; (ii) extranodal NK/T-cell lymphoma, nasal type: n = 2; (iii) cutaneous gamma/delta T-cell lymphoma: n = 2; (iv) anaplastic CD30+ large T-cell lymphoma: n = 1; (v) diffuse large B-cell lymphoma, secondary cutaneous: n = 3; (vi) lymphoplasmacytic lymphoma, secondary cutaneous: n = 1; (vii) specific cutaneous manifestations of myelogenous leukemia: n = 1. CONCLUSIONS: We demonstrated the protean nature of lymphomas with prominent involvement of the subcutaneous fat tissues. The term STCL should be restricted to a homogeneous group of cases characterized morphologically by an exclusive involvement of subcutaneous tissues, immunohistochemically by a T-cytotoxic alpha/beta phenotype, and biologically by a relatively good prognosis.     

The applicability of the new WHO-EORTC classification of primary cutaneous lymphomas to a single referral center

Recent years have witnessed differences between the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) classification systems of primary cutaneous lymphomas (PCLs). Recently, a joint WHO-EORTC classification system for PCLs has been reached. This study was performed to assess the applicability of this new classification to a single referral center. All new PCL cases, excluding mycosis fungoides and Sezary syndrome, who were referred from 1999 to 2005 were included. The histological, immunohistochemical stainings and molecular studies were reviewed, and additional stains were performed as needed. The cases were then reclassified according to the WHO-EORTC classifications. The clinical files were also studied, and the patients were followed up clinically. There were 43 new non-mycosis fungoides/Sezary syndrome PCLs, including 29 B-cell lymphomas of which 14 were follicle center lymphoma, 10 marginal zone lymphoma, 4 diffuse large-B-cell lymphoma, leg type, and 1 diffuse large-B-cell lymphoma, other. The 14 T-cell lymphomas included 5 cases of lymphomatoid papulosis, 2 CD30+ anaplastic large-cell lymphomas, 1 NK/T-cell lymphoma, and 6 peripheral T-cell lymphomas, unspecified. Of the 6 "unspecified" T-cell lymphomas, 3 were CD4+ small/medium-sized pleomorphic T-cell lymphoma, which is considered currently a provisional entity under the unspecified T-cell category. The remaining 3 cases could not be classified beyond the unspecified T-cell category, of which 2 cases had an aggressive course. The new WHO-EORTC classification is applicable to most non-mycosis fungoides/Sezary syndrome PCL cases, especially the B-cell lymphomas. However, there is still a substantial subset of T-cell PCLs which cannot be classified beyond the unspecified peripheral T-cell category, some of which may have an aggressive course.     

The spectrum of cutaneous lymphomas in patients less than 20 years of age

Cutaneous lymphomas are rare in young patients and are mostly represented by mycosis fungoides and its variants and CD30+ lymphoproliferative disorders (lymphomatoid papulosis [LYP] and anaplastic large T-cell lymphoma). We report our observations in a series of 69 patients less than 20 years of age who presented either with primary cutaneous lymphoma (n = 62) or with secondary manifestations of extracutaneous disease (n = 7). Clinicopathologic features permitted classification of the cases into the following diagnostic categories: mycosis fungoides (n = 24, all primary cutaneous), anaplastic large T-cell lymphoma (n = 13, all primary cutaneous), LYP (n = 11, all primary cutaneous), subcutaneous "panniculitis-like" T-cell lymphoma (n = 1, primary cutaneous), small-medium pleomorphic T-cell lymphoma (n = 2, all primary cutaneous), natural killer (NK)/T-cell lymphoma, nasal-type (n = 1, secondary cutaneous), follicle center cell lymphoma (n = 1, primary cutaneous), marginal zone B-cell lymphoma (n = 7, all primary cutaneous), B-lymphoblastic lymphomas (n = 6, 3 primary and 3 secondary cutaneous), specific cutaneous manifestations of Hodgkin disease (n = 1, secondary cutaneous), and acute myeloid leukemia (n = 2, both secondary cutaneous). Cutaneous lymphoma in children should be differentiated from benign skin disorders that may simulate them. In particular, mycosis fungoides and LYP in this age group may present with clinicopathologic features reminiscent of inflammatory disorders such as pityriasis alba, vitiligo, pityriasis rosea, and pityriasis lichenoides et varioliformis acuta. Even in secondary cutaneous lymphomas, skin manifestations may be the first sign of the systemic disease, and a diagnosis may be achieved on examination of histopathologic specimens of a cutaneous lesion. Our study illustrates the wide spectrum of cutaneous lymphomas and leukemias in patients less than 20 years of age and underlines the need for proper interpretation of these lesions by dermatologists and dermatopathologists.     

Characteristics of cutaneous lymphomas in Korea

The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the WHO classification in Korean cases of cutaneous lymphoma. The Korean Dermatopathology Research Group conducted a clinicopathologic review of a nationwide collection of 80 cutaneous lymphomas, diagnosed at 23 institutes over a recent 3-year period. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 80 patients with malignant lymphomas of the skin were reviewed. In our study, the most frequent cutaneous lymphoma was mycosis fungoides. Compared with Western countries, Korea had higher rates of NK/T cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma and a much lower rate of B-cell lymphoma. The occurrence rates for various subtypes of malignant lymphoma in Korea are distinct from those in Western countries. The EORTC classification is not fully appropriate in dealing with Korean cases of cutaneous lymphoma, because NK/T cell lymphoma is not included in the EORTC classification for cutaneous lymphoma.     

CD30-positive cutaneous T-cell lymphoma with concurrent solid tumour

Extranodal CD30+ T-cell lymphomas seldom carry classical t(2;5) translocation and are usually anaplastic large cell lymphoma kinase protein negative. They cover a wide spectrum of histological and clinical behaviour. The prognosis of CD30+ cutaneous T-cell lymphoma (CTCL) is good in the absence of nodal primary or disseminated disease. These lesions can undergo spontaneous regression, and overlap with the group of lesions of lymphomatoid papulosis. Although an increased incidence of solid tumours has been reported in patients with CD30+ non-Hodgkin lymphoma of the skin, reports of concurrent malignancies are rare in CD30+ CTCL. We report two patients with CD30+ CTCL who, respectively, had concurrent disseminated gastric carcinoma and bilateral ovarian teratoma. Despite an aggressive clinical and histological appearance, both cases ran favourable clinical courses. The CTCL responded completely to chemotherapy in one patient, who eventually succumbed to gastric cancer. In the other patient, lesions regressed spontaneously after bilateral oophorectomy. A possible relationship between the lymphoma and the solid tumours is discussed.     

Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-Cell lymphomas suggesting impaired cell cycle control in disease pathogenesis

Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However, little is known about the abnormalities of CCND1 and its regulator RB1 in primary cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and Affymetrix expression microarray. FISH revealed loss of CCND1/BCL1 in five of nine Sézary syndrome (SS) cases but gain in two cases, and RB1 loss in four of seven SS cases. IHC showed absent CCND1/BCL1 expression in 18 of 30 SS, 10 of 23 mycosis fungoides (MF), and three of 10 primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL). Increased CCND1/BCL1 expression was seen in nine MF, seven C-ALCL, and six SS cases. Absent RB1 expression was detected in 8 of 12 MF and 7 of 9 SS cases, and raised RB1 expression in 7 of 8 C-ALCL. Affymetrix revealed increased gene expression of CCND2 in four of eight CTCL cases, CCND3 in three cases, and CDKN2C in two cases with a normal expression of CCND1 and RB1. These findings suggest heterogeneous abnormalities of CCND and RB in CTCL, in which dysregulated CCND and RB1 may lead to impaired cell cycle control.     

Pseudoepitheliomatous hyperplasia in cutaneous T-cell lymphoma. A clinical, histopathological and immunohistochemical study with particular interest in epithelial growth factor expression. The French Study Group on Cutaneous Lymphoma

Pseudoepitheliomatous hyperplasia has occasionally been reported in cutaneous T-cell lymphoma (CTCL). This association raises the question of the relationship between epidermal hyperplasia and the lymphomatous infiltrate. Because epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) have been demonstrated to be involved in epidermal proliferation through binding to EGF receptor (EGFr), we tested the hypothesis that these cytokines could be secreted by lymphomatous cells, and induce the overlying pseudoepitheliomatous hyperplasia. The purposes of this study were: (i) to describe the clinical and immunohistological features of pseudoepitheliomatous hyperplasia; (ii) to determine its frequency in a large series of CTCLs; and (iii) to evaluate the expression of EGF, TGF-alpha and EGFr in CTCL with or without pseudoepitheliomatous hyperplasia. Eleven cases of CTCL with pseudoepitheliomatous hyperplasia were collected from a series of 353 cases of cutaneous lymphoma registered from 1990 to 1996. They consisted of eight of 28 (28.5%) CD30+ large T-cell lymphomas and three of 148 (2%) cases of mycosis fungoides. Epidermal expression of EGF, EGFr and TGF-alpha was stronger in CTCL than in control normal human skin. Lymphomatous T cells expressed EGF and TGF-alpha whereas no expression of these cytokines could be detected in cutaneous and nodal B-cell lymphomas, nor in a normal lymph node. In addition, epidermal expression of EGFr was stronger in CTCL with pseudoepitheliomatous hyperplasia than in control cases of CTCL without pseudoepitheliomatous hyperplasia, suggesting that these cytokines, in association with other factors, are probably involved in the epidermal hyperplasia observed in some cases of CTCL.     

Phenotypic heterogeneity of lymphoma of the skin

We studied surface markers present in 56 cases of lymphoma of the skin by immunohistochemical staining, using the ABC (avidin-biotin-peroxidase complex) and PAP (peroxidase-antiperoxidase complex) methods. Of these cases, 49 were T-cell lymphoma and 7 were B-cell lymphoma. Ten of the 49 cases of T-cell lymphoma were adult T-cell leukemia/lymphoma (ATL). Twenty-five of 31 cases of T-cell lymphoma except ATL analyzed by the ABC method showed a helper/inducer phenotype (Leu2a-,Leu3a+), two cases showed a suppressor/cytotoxic phenotype (Leu2a+, Leu3a-), one case showed Leu2a+Leu3a+, one case showed an inducer phenotype (Leu2a-, Leu3a+, Leu9+), and one case showed OKT11+, Leu2a-, Leu3a-, Leu1-, Leu9+, CD25+, Leu10+, CD30+. One CD8+ lymphoma was Pagetoid reticulosis, and a CD4+, CD8+ lymphoma was lymphomatoid papulosis with erythematous plaque. Cutaneous T-cell lymphoma (CTCL), previously described by Edelson et al., is defined as a helper T-cell lymphoma with marked affinity for the skin. In our study, 5 cases of T-cell lymphoma of the skin were not CTCL as described by Edelson et al. These results show that T-cell lymphoma of the skin is heterogeneous in nature. In other words, CTCL is one type but represents a major proportion of T-cell lymphomas of the skin.     

Diagnostic principles and new developments in primary cutaneous B-cell lymphomas

The most common subtypes of primary cutaneous B-cell lymphomas are marginal zone B-cell lymphoma/immunocytoma, follicle center cell lymphoma, and large B-cell lymphoma of the leg. Precise classification (European Organization for Research and Treatment of Cancer (EORTC) scheme) can be achieved only after a complete synthesis of clinical, histopathological, immunophenotypic, and molecular features. It is extremely important to emphasize that primary cutaneous B-cell lymphomas differ significantly from their nodal counterparts and are frequently characterized by an excellent prognosis. Awareness of this special clinical behavior should prevent the application of unnecessarily aggressive treatment protocols. Future definitions of primary cutaneous B-cell lymphomas will be based on their etiology and pathogenesis and especially on their molecular features. Some important areas are presented where exciting findings have been detected.     

Non‐mycosis fungoides cutaneous T‐cell lymphoma: reclassification according to the WHO‐EORTC classification

Background: Non‐mycosis fungoides (non‐MF) primary cutaneous T‐cell lymphomas (PCTCL) are heterogeneous and divided into subgroups by the World Health Organization‐European Organization for Research and Treatment of Cancer (WHO‐EORTC) classification of cutaneous lymphomas. We report the first North American series to examine the applicability of the classification, compare our findings with the predominant European literature and confirm the significance of separation into the indolent and aggressive groups. Methods: Forty‐four non‐MF PCTCL cases with available tissue for phenotyping, adequate clinical staging information and follow‐up were reclassified according to the WHO‐EORTC classification. Results: Non‐MF PCTCL had a longer overall survival (OS) (13.8 years) compared with secondary cutaneous T‐cell lymphoma (SC‐TCL) (2.5 years). Primary cutaneous anaplastic large cell lymphoma (PC‐ALCL) had the most favorable outcome (OS 14.1 years), whereas secondary and primary peripheral T‐cell lymphoma, unspecified had the shortest OS (2.5 and 2.4 years, respectively). Primary cutaneous CD4+ small/medium‐sized pleomorphic T‐cell lymphoma (CTLCD4) appeared to have a favorable course. Conclusions: Most non‐MF PCTCL can be classified according to the WHO‐EORTC classification. The relative frequencies are similar to European experience. Non‐MF PCTCL is a heterogeneous group with a favorable outcome compared to SC‐TCL, especially PC‐ALCL and CTLCD4. Separation of non‐MF PCTCL into indolent and aggressive groups appears clinically significant and may provide direction for therapeutic decisions. Weaver J, Mahindra AK, Pohlman B, Jin T, His ED. Non‐mycosis fungoides cutaneous T‐cell lymphoma: reclassification according to the WHO‐EORTC classification.     

Primary cutaneous diffuse large B-cell lymphoma of the leg according to the new WHO-EORTC classification. Two cases

Primary cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders characterized by skin involvement with no evidence of systemic disease at the time of diagnosis. Their clinical behavior is generally indolent, and only occasionally is the development of extracutaneous disease observed. Since the 1980s, primary cutaneous B-cell lymphomas have been considered a specific group of lymphomas, differentiated from both T-cell lymphomas and from secondary cutaneous B-cell lymphomas. Both the EORTC and the WHO have proposed alternative classifications for these entities, with significant discrepancies that were finally resolved through the development of a new classification (WHO-EORTC classification for cutaneous lymphomas), which standardizes criteria that had previously been different. We present two new cases of primary cutaneous diffuse large B-cell lymphoma of the leg according to the new classification.