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.     

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.     

Genotypic analysis of cutaneous T-cell lymphomas

The gene encoding the beta-chain of the T-cell antigen receptor (TCR) has been analyzed for evidence of rearrangement in skin, blood, and lymph node specimens from 23 cases of known or suspected cutaneous T-cell lymphoma (CTCL). Two cutaneous large cell lymphomas, 4 cases of Sézary syndrome, and 5 cases of advanced (tumor) stages of mycosis fungoides showed clonal rearrangement of the TCR beta-chain gene in all samples, including lymph nodes in which histologic examination revealed only dermatopathic lymphadenitis. These results indicate that DNA analysis provides a valuable means for improving the diagnosis of extracutaneous disease in advanced stages of CTCL. In contrast, the gene was in a germline configuration in all samples from 12 patients with plaque stages of mycosis fungoides or suspected early CTCL, suggesting that in these 2 conditions the T-cell proliferation is either polyclonal or contains very few monoclonal (i.e., neoplastic) cells.     

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.     

Treatment of cutaneous T-cell lymphomas with TP-5. Evaluation of the clinical effect in 8 patients

Eight patients with cutaneous T-cell lymphomas (6 patients with mycosis fungoides, 1 patient with Sézary's syndrome, 1 patient with low-grade malignant lymphoma, unclassified) were treated with TP-5, a synthetic pentapeptide having the same biologic activity as the thymic hormone thymopoietin. TP-5 was administered three times weekly at a dosage of 50 mg subcutaneously in 6 patients, 50 mg intravenously in 1 patient, and 100 mg subcutaneously in 1 patient. Clinical evaluation at the end of the trial disclosed improvement in 4 patients (2 patients with mycosis fungoides, 1 patient with Sézary's syndrome, 1 patient with low-grade malignant lymphoma, unclassified), deterioration in 3 patients with mycosis fungoides and no change in 1 patient with mycosis fungoides. As TP-5 evidently exerts some effect on cutaneous T-cell lymphomas, further investigations of its therapeutic potential in this group of diseases seem worthwhile.     

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.     

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.     

Skin is the frequent site for involvement of peripheral T-cell and natural killer cell lymphomas in Korea

We have studied the clinicopathological features of 19 Korean cases of peripheral T-cell and natural killer (NK) cell lymphomas, not including mycosis fungoides. Primary cutaneous involvement was demonstrated in eight of these 19 cases, and we recognized four clinicopathologic subtypes among these eight patients: nasal type NK/T cell lymphoma, three cases; primary cutaneous CD30 positive anaplastic large cell lymphoma, two cases; subcutaneous panniculitis-like T-cell lymphoma, one case; lymphoma with hydroa vacciniforme-like cutaneous lesions, two cases. We did not, however, encounter any cases of HTLV-associated adult T-cell lymphoma/leukemia, which is common in Taiwan and Japan. EBV-associated lymphoma is the most prominent type of peripheral T-cell and NK cell neoplasm involving the skin in Korea.     

Non-Hodgkin lymphoma of the skin excluding mycosis fungoides and cutaneous involvement of adult T-cell leukemia/lymphoma*

Forty-nine cases of cutaneous malignant lymphoma were reviewed in order to analyze the clinicopathological features of these neoplasms. Excluding 13 cases of mycosis fungoides and 4 cases of cutaneous involvement of proven adult T-cell lymphoma/leukemia, the remaining 32 cases were further classified according to their pathological and clinical features. There were 12 primary cutaneous lymphomas, 15 cases of secondary cutaneous involvement of systemic lymphoma, and 5 cases of concurrent skin and lymph node involvement. Histologically, large cell lymphoma predominated in both primary and secondary cutaneous lymphomas. Immunohistochemical study using monoclonal antibodies reactive with B- and T-cells in paraffin sections revealed the cellular lineage in 30 cases. Nineteen cases were of T-cell origin and 11 cases were of B-cell derivation. The prognosis of these patients was rather poor; 25 patients died within 5 years. The predominance of T-cell lymphoma contrasts with a higher frequency of cutaneous B-cell lymphoma in Western countries. As the clinicopathological features of cutaneous lymphomas are diverse, it is suggested that cutaneous lymphomas should be classified and studied in a similar way to their nodal counterparts.     

Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms?

Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.     

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.     

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.     

Cutaneous T-cell lymphoma bullosa: 2 cases

INTRODUCTION: Since the first case described by Kaposi in 1887, bullous forms of cutaneous T-cell lymphomas are extremely. CASE-REPORT: We describe an unusual case of mycosis fungoides bullosa with palmoplantar dyshidrosis-like eruption and, to our knowledge, the first case of pleomorphic cutaneous T-cell lymphoma bullosa. DISCUSSION: Cutaneous T-cell lymphoma bullosa can be very misleading, particularly when the bullous lesions are inaugural. Differential diagnosis have to be excluded (autoimmune blistering diseases or contact dermatitis during topical treatment of lymphoma or bacterial or viral cutaneous infections) by biopsy, direct immunofluorescence and bacteriological examinations. In these cutaneous lymphoma bullosa, the blisters appear to de due to excessive epidermotropism and/or toxicity of the tumoral infiltrate.     

CD13 and TCR clone: markers of early mycosis fungoides

Making a differential diagnosis between early mycosis fungoides and parapsoriasis is often difficult at the clinical and histological level. The aim of this study was to explore markers that could help in this process. A total of 88 patients were included in 2 categories: large plaque parapsoriasis and digitiform parapsoriasis. A histological examination was performed for each patient, and expression of the antigen My7 (CD13), which is lacking in cutaneous T-lymphomas (but not in inflammatory lesions) and rearrangement of the T-cell receptor gene were analysed. A histological aspect of epidermotropic cutaneous T-cell lymphoma was observed in 23.5% of cases of large plaque parapsoriasis and 15% of cases of digitiform parapsoriasis. A disappearance of My7 antigen was noted in the 2 forms of parapsoriasis, more frequently when there was cutaneous T-cell lymphoma histology. A cutaneous clone was observed in 10.3% of cases of large plaque parapsoriasis, but not of digitiform parapsoriasis. For 3 patients, a cutaneous clone and a disappearance of My7 were associated with a non-specific histology. Considering these histological, immunological and molecular biological data, it appears that My7 antigen combined with T-cell clone may help the dermatologist to confirm the diagnosis of early mycosis fungoides. Moreover, further studies will determine whether CD13 is an early prognostic marker of evolution of a parapsoriasis to mycosis fungoides. Finally, these results demonstrate that digitiform parapsoriasis can be an early stage of MF.     

Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas

We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes.     

Lymphomas.

The diagnosis of lymphoma currently relies on a combination of clinical, routine histopathologic, and immunohistochemical studies, sometimes supplemented by other special techniques such as flow cytometry, DNA analysis, and gene rearrangement study. This review considers the practical diagnosis of cutaneous lymphoma, with particular emphasis on three areas: Hodgkin's disease, non-Hodgkin's lymphomas and their differentiation from lymphocytoma cutis, and mycosis fungoides and other T-cell lymphomas.     

An ultrastructural morphometric and immunohistochemical analysis of cutaneous lymphomas and benign lymphocytic infiltrates of skin. Useful criteria for diagnosis

Our combined ultrastructural, immunohistochemical, histologic, and clinical studies over the past five years have allowed us to compile diagnostic criteria useful in the evaluation of cutaneous lymphomas. As a group, mycosis fungoides (MF) patients could be distinguished from those with benign disorders of skin using ultrastructural morphometry (mean form factor and perimeter values), but with some overlap between groups. Another approach, the ultrastructural histogram method, however, clearly separated MF patients from patients with chronic dermatitis. Immunohistochemistry was useful in distinguishing cases of cutaneous peripheral T-cell lymphoma from MF cases on the basis of the occurrence of "novel phenotypes." Neoplastic T-cell infiltrates of skin can usually be distinguished from benign polyclonal T-cell infiltrates by the presence of one T-cell subset to the exclusion of others. Patients with convoluted B-cell lymphomas could also be distinguished from MF patients using ultrastructural morphometric dual parameter analysis. The diagnostic complexity of several cutaneous T-cell lymphoma cases is illustrated. We have emphasized in this study the strength of combining quantitative electron microscopy, immunohistochemistry, and histology in the diagnostic workup of cutaneous lymphomas. This integrative approach may be necessary to assure a definitive diagnosis in difficult cases.     

Adult T-Cell Leukemia/Lymphoma and Cutaneous T-Cell Lymphoma Are They Related?

Comparative studies were performed on clinical and laboratory features of four patients with different types of T-cell lymphoma of the skin; adult T-cell leukemia/lymphoma (ATLL), Sézary syndrome, mycosis fungoides, and Ki-1-positive lymphoma. All neoplastic cells studied showed a helper-inducer T-cell phenotype. A Ki-1-positive lymphoma is distinct from other types of cutaneous lymphomas because of unique morphologic and phenotypic features. Clonal proliferation of lymphocytes infected by human T-cell lymphotrophic virus (HTLV)-1 distinguishes ATLL from other T-cell lymphomas of the skin, especially in the endemic area of ATLL. From the pathogenic point of view, ATLL should not be included in a group with mycosis fungoides and Sézary syndrome.