Coexistence of CD30-positive anaplastic large cell lymphoma and mycosis fungoides

Primary cutaneous T-cell lymphomas, including lymphomatoid papulosis, mycosis fungoides and CD30+ anaplastic large cell lymphoma (ALCL) overlap clinicopathologically and form part of a spectrum of lymphoproliferative disorders. There have been several case reports of these diseases coexisting. We describe a 59-year-old Korean man who presented with a recurrent, solitary CD30+ ALCL of 25 years' duration as well as patch stage mycosis fungoides of 11 years' duration. Such occurrences may represent different clinical manifestations of the same clonal T-cell abnormality, and provide further insight into the pathogenesis of these related disorders.     

Intraepidermal localization of the clone in cutaneous T-cell lymphoma.

BACKGROUND: No immunohistologic techniques are currently available to demonstrate clonality of T-cell lymphomas. Monoclonal antibodies to the variable region of the T-cell receptor (TCR) have been produced that identify minor populations of normal peripheral blood T lymphocytes. OBJECTIVE: We investigated the expression of TCR V-region genes in cutaneous lymphomas to determine whether immunostaining with these antibodies may be a simple method to detect clonal T-cell proliferations and help to distinguish benign lymphoid infiltrates from malignant lymphoma. METHODS: Cutaneous samples were obtained from 18 cutaneous T-cell lymphomas (14 mycosis fungoides, 1 Sézary syndrome, 2 pleomorphic T-cell lymphoma, and 1 large cell anaplastic lymphoma) and 8 benign lymphoid infiltrates. Frozen sections were incubated with monoclonal antibodies and stained by the alkaline phosphatase-antialkaline phosphatase technique. Staining was performed with a panel of 7 anti-TCR V-region antibodies, 6 T-cell markers, 1 anti-beta chain antibody, and 1 anti-delta chain antibody. RESULTS: Clonality could be demonstrated in 2 of 18 cutaneous lymphomas. We observed the strictly intraepidermal localization of clonal proliferation in one case of early-stage mycosis fungoides. CONCLUSION: Anti-TCR V-region antibodies may identify a strictly epidermotropic clone in early mycosis fungoides. However, the panel of antibodies currently available stains only a minority of cutaneous T-cell lymphomas. The usefulness of these antibodies as a clonotypic marker needs to be reevaluated when a larger panel of antibodies becomes available.     

Mycosis fungoides and chronic lymphocytic leukaemia--composite T-cell and B-cell lymphomas presenting in the skin

Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm.     

Clinical features of cutaneous T-cell lymphoma

The distinctive clinical features and natural history of mycosis fungoides, an epidermotropic variant of cutaneous T-cell lymphoma, are presented. These findings are compared with certain non-mycosis fungoides T-cell lymphomas that occasionally occur in the skin. Clinical staging and evaluation of patients with cutaneous lesions including plaques, tumors, or erythroderma, with or without nodal involvement and disseminated disease, are considered. Associated disorders such as follicular mucinosis, actinic reticuloid, lymphomatoid papulosis, and secondary primary malignancies are also presented.     

CD30-positive lymphoproliferative disorders—An Australian Clinical Practice Statement from the Peter MacCallum Cancer Centre

The CD30-postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.     

Characteristics of cutaneous lymphomas in Osaka, Japan (1988-1999) based on the European Organization for Research and Treatment of Cancer classification

Based on accumulating information, European investigators proposed a new classification for primary cutaneous lymphomas known as the European Organization for Research and Treatment of Cancer (EORTC) classification. The clinical utility of this classification in Japanese cases has not been evaluated. Material from 65 patients with cutaneous lymphomas (48 with primary disease and 17 with secondary disease) who were admitted to Osaka University Hospital during the period 1988 through 1999 was reviewed. Immunohistochemical analysis was performed in all cases. Cutaneous T-cell lymphoma (CTCL) comprised mycosis fungoides (15 cases), Sézary syndrome (1 case), lymphomatoid papulosis (5 cases), large cell CTCL (13 cases), pleomorphic small- or medium-sized CTCL (2 cases), and cutaneous natural killer /T-cell lymphoma (4 cases). B-cell lymphomas comprised 7 cases of follicle center cell lymphoma and 1 case of diffuse large B-cell lymphoma of the leg. Each category of disease in the EORTC scheme showed its characteristic features in our series. Five of 13 large cell CTCL cases were positive for CD30, and 5 were negative. The 5-year survival rate of patients with large cell CTCL CD30+ disease was 100% and that of patients with CD30- disease was 0%. (p > 0.1). Only 1 of 7 CTCL cases expressing CD30 was ALK-1+, and all 7 cases showed a favorable clinical course. The EORTC classification is effective in dealing with Japanese cases of cutaneous lymphomas.     

Rimming of adipocytes by neoplastic lymphocytes: a histopathologic feature not restricted to subcutaneous T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features. Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.     

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.     

Linfomas cutáneos. Parte II: otros linfomas cutáneos

Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30⁺ disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish–violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.     

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.     

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.     

Human T-cell leukemia virus in cutaneous T-cell lymphoma in Denmark. A possible association of HTLV and aneuploidy

Cutaneous T-cell lymphomas (CTCL) are neoplasias of mature T-cells and comprise Sezary syndrome, mycosis fungoides and some cases of lymphomatoid papulosis. Clinically this group of disorders differ from the more aggressive neoplasias of mature T-cells known as adult T-cell leukemia/lymphoma and T-cell lymphosarcoma leukemia which are associated with human T-cell leukemia virus (HTLV). We have found that of 68 patients from Denmark with CTCL ten were positive for HTLV antibodies and that the neoplastic T-cells from skin specimens in seven of eight HTLV-antibody positive patients studied by DNA flow cytometry exhibit DNA aneuploidy. Either one or two hyperdiploid cell clones were present. Aneuploidy was found in two patients with histologically verified mycosis fungoides, in four patients with histological non-diagnostic mycosis fungoides, and in one patient with lymphomatoid papulosis. The present data indicate that further seroepidemiologic survey studies of cutaneous T-cell lymphomas should include the early histological non-diagnostic stages, especially when aneuploidy is present.     

Pleomorphic T-cell lymphoma and large-cell anaplastic lymphoma of the skin. A morphological, immunophenotypical, and ultrastructural study of two typical cases

Pleomorphic T-cell lymphoma and large-cell anaplastic lymphoma are recently defined lymphoma types that both occur in the skin. This report outlines the characteristics of these lymphomas and describes the clinical, histological, immunological, and ultrastructural features as seen in two typical case histories. Cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome are heterogeneous; they deserve further scientific attention to obtain data about their natural history and their response to therapy.     

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 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.     

Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?

About 75% of cutaneous lymphomas belong to the group of T-cell lymphomas. Mycosis fungoides is the most common entity in this group. Granulomatous slack skin is a rare form of cutaneous T-cell lymphoma closely related to mycosis fungoides. We present here a patient with areas of lax skin for several years who developed a generalized erythroderma with associated immunoactivation and a deterioration in his general condition. This report discusses clinically and histologically the differential diagnoses, namely granulomatous slack skin and granulomatous mycosis fungoides, and suggests that these 2 disorders are only variants in the broad spectrum of a single disease.     

T-cell receptor-gamma gene analysis in evolving to advancing cutaneous T-cell lymphoma

The diagnosis of cutaneous T-cell lymphoma is often a challenge for the dermatopathologist. Early stages can mimic inflammatory dermatoses. Our aim was to explore the applicability of a standard T-cell receptor-gamma polymerase chain reaction in various subtypes of cutaneous T-cell lymphomas. Ninety-six biopsy specimens from 38 patients were selected. These included 72 specimens of mycosis fungoides, 12 specimens of non-mycosis fungoides T-cell lymphomas, and 12 specimens in which histology was non-specific or equivocal in patients who were later diagnosed to have lymphoma. T-cell clones were detected in 53 of 72 specimens of mycosis fungoides and eight of 12 specimens of non-mycosis fungoides lymphomas. Of the 72 specimens of mycosis fungoides, T-cell clones were detected in eight of 10 specimens of mycosis fungoides-associated follicular mucinosis and pigmented purpura-like mycosis fungoides. Four specimens from the 12 prediagnostic for cutaneous T-cell lymphomas showed presence of T-cell clones, identical to subsequent clones detected when lymphoma was fully established. In specimens where histology is not diagnostic and T-cell receptor-gamma gene analysis is positive, patients should be followed up closely. T-cell receptor-gamma gene analysis is a useful adjunct to histological diagnosis of early stage and variant types of mycosis fungoides.     

HTLV-1-negative pleomorphic T-cell lymphoma of the skin: the clinicopathological correlations and natural history of 15 patients

The peripheral T-cell lymphomas represent a heterogeneous group and include, besides mycosis fungoides and Sézary syndrome, large-cell anaplastic lymphoma. We report 15 cases from our files that fulfil the histological criteria of pleomorphic T-cell lymphoma with primary skin involvement. Most of the cases were elderly with a male-to-female ratio of 1.5:1. The HTLV-1 serology was negative. The clinical features of these patients differed from those with mycosis fungoides and Sézary syndrome, in that eczematous and precursor lesions such as parapsoriasis en plaque were lacking apart from one exception. All the patients with small-cell pleomorphic T-cell lymphomas were alive, although three of the nine patients with medium-to-large tumour cells have died. Pleomorphic T-cell lymphoma should be regarded as a distinct entity among the lymphoproliferative disorders of the skin.     

Primary cutaneous peripheral T-cell lymphoma,not otherwise specified,associated with lymphomatoid papulosis after a 9-year follow up: A case report

Lymphomatoid papulosis (LyP) is a self-limiting cutaneous T-cell lymphoproliferative disorder that may progress into malignant lymphoma. Most of the previously reported associated lymphomas are primary cutaneous anaplastic large-cell lymphoma and mycosis fungoides with a low mortality rate. We report a case of primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), associated with LyP after long-term follow up. The patient was a 79-year old Japanese man followed up for 9 years. He suddenly developed a 3-cm ulcerated lesion on his forehead, which was diagnosed as an exacerbation of LyP. The lesion regressed after conservative treatment, but the patient soon developed multifocal pcPTCL-NOS. Thereafter, the patient developed pneumonia and cerebral infarction and died within a few months of the onset of malignant lymphoma. Aggressive cutaneous lymphoma may develop in LyP patients. The present case re-emphasizes the need for careful follow up of patients with persistent LyP.