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.     

Cutaneous natural killer/T-cell lymphoma

Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.     

Subcutaneous T-cell lymphoma: A clinical, histopathologic, and immunohistochemical study of six cases

Recently, T-cell lymphoma localized to the subcutaneous tissue has been reported. We report the clinical, histolpgic, immunohistochemical, and molecular genetic findings in 6 patients who we believe had this peculiar T-cell lymphoma with its unique morphologic and clinical features. All patients presented with deep-seated nodules, most frequently on the extremities, and with systemic complaints of low-grade fever, fatigue, myalgias, and weight loss. In all cases, the neoplastic lymphocytic infiltrate was confined to the subcutaneous tissue, predominantly in a lobular pattern. Hemorrhage, necrosis, and rare erythrophagocytosis were also seen. Immunohistochemical staining was predominantly T-cell reactive (CD43, CD3, and CD45RO). Clonal rearrangements of the β and γ chains of the T-cell antigen receptor genes were found in 1 case. Three of the 6 patients died within 22 months of the diagnosis of lymphoma. We believe that subcutaneous T-cell lymphomas are a distinctive group of peripheral T-cell lymphomas with unusual clinical and morphologic features and that they should be distinguished from other types of lymphoma.     

Cutaneous CD8+ squamous T-cell bullous lymphoma

INTRODUCTION: Bullous forms of cutaneous T-cell lymphomas are rare. A new group of cutaneous T-cell lymphomas has recently been identified as a distinct clinicopathological and immunophenotype entity. These cutaneous T-cell lymphomas express a CD8+ phenotype, rarely expressed in other cutaneous T-cell lymphomas. CASE REPORT: We describe a cutaneous CD8+ squamous T-cell lymphoma with polymorphic clinical features, strongly epidermotropic lymphoid infiltrate and spongiosis, classical for this type of lymphoma. DISCUSSION: Bullous lesions in cutaneous T-cell lymphoma should evoke the possibility of a cutaneous CD8+ T-cell lymphoma, once other bullous diseases have been excluded. Spongiosis, rare in other types of T-cell lymphoma, and strongly epidermotropic pleomorphic lymphoid infiltrate are classical histological features. The association of polymorphic lesions, bullas and atypical CD8+ epidermotropic phenotype should evoke this diagnosis even at the early stage. Treatment is difficult and classical chemotherapy often fails. Prognosis is poor with a mean overall survival of 32 months.     

Peripheral T-cell lymphoma involving subcutaneous tissue

The peripheral T-cell lymphomas, presumably derived from various immunocompetent peripheral T-cell system components, form a heterogeneous group of non-Hodgkin's lymphomas. We describe two patients with peripheral T-cell lymphoma primarily involving subcutaneous tissue. They presented with multiple subcutaneous nodules. Skin biopsy specimens in both patients demonstrated a lobular subcutaneous infiltrate. The infiltrate consisted of small and medium-sized atypical lymphoid cells. Both patients had a protracted clinical course before they were diagnosed as having malignant lymphoma. We detected latent Epstein-Barr virus infection in the skin lesions of case 2. Latent Epstein-Barr virus infection might be related to the development of this variant of peripheral T-cell lymphoma.     

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.     

Extranodal NK / T-cell lymphoma with cutaneous involvement: 'nasal' vs. 'nasal-type' subgroups— a retrospective study of 18 patients

Background  Extranodal natural killer T (NK/T) cell lymphoma is subcategorized into 'nasal' and 'nasal-type' NK/T-cell lymphomas according to the primary sites of anatomical involvement.
Objectives  The aim of this study was to characterize the cutaneous manifestations of the skin involving extranodal NK/T-cell lymphoma and to define the distinctive features of 'nasal' and 'nasal-type'. In addition, the prognostic factors that affect overall survival were investigated.
Methods  A retrospective case study of 18 patients with extranodal NK/T-cell lymphoma with cutaneous involvement was performed.
Results  The NK/T-cell lymphomas usually occurred in middle-aged, male patients. Most of the patients presented with either cellulitis or ulcer. A facial predilection for the location of the lesion was noted. The characteristic features of the 'nasal-type' compared with the 'nasal' were a localized involvement of the skin, less aggressive clinical course and better survival outcome.
Conclusions  Extranodal NK/T-cell lymphomas are extremely aggressive regardless of their subgroup. However, the 'nasal-type' NK/T-cell lymphoma was clinically less aggressive, more localized and had a better outcome compared with the other type. Cellulitis and ulcer were the major cutaneous manifestations.     

Aggressive B-cell lymphoma induced by Epstein-Barr virus infection in erythrodermic cutaneous T-cell lymphoma

The coexistence of two cutaneous non-Hodgkin's lymphomas of different lineage is rare. We report a patient with an indolent erythrodermic cutaneous T-cell lymphoma followed by an aggressive B-cell lymphoma. To our best knowledge, this is the first report describing Epstein-Barr virus-associated B-cell lymphoma in a patient with cutaneous T-cell lymphoma. We suggest that the long-standing cutaneous T-cell lymphoma, as well as the long-term chemotherapy, suppressed host immunity and caused reactivation of latent Epstein-Barr virus.     

Subcutaneous panniculitic-like T-cell lymphoma and other primary cutaneous lymphomas with prominent subcutaneous tissue involvement

The concept of subcutaneous T-cell lymphoma defines a reduced group of primary cutaneous lymphomas characterized morphologically by a prominent or exclusive subcutaneous tissue involvement. Subcutaneous panniculitic-like T-cell lymphoma is a rare subtype of primary cutaneous T-cell lymphoma clinically mimicking panniculitis. The clinical course is usually protracted with recurrent cutaneous lesions but rarely with early extracutaneous dissemination. The clinical, histopathologic, immunophenotypic, and evolutive features of this heterogeneous and rare group of primary cutaneous lymphomas are reviewed.     

Malignant lymphoma and leukemia with prominent ulceration: clinicopathologic correlation of 33 cases.

BACKGROUND: The clinical and pathologic findings in patients with malignant lymphomas who presented with prominent cutaneous ulcers are described. OBJECTIVE: Our purpose was to determine the histologic findings, type, and prognosis of lymphomas with cutaneous ulcers. METHODS: Thirty-three patients (20 with cutaneous T-cell lymphomas, 10 with other non-Hodgkin's lymphomas, and 3 with leukemia) were retrospectively studied. RESULTS: All patients had a poor prognosis; 23 died within 9 months after the onset of the ulcers. Patients with non-Hodgkin's lymphoma had a worse prognosis, had a higher incidence of systemic involvement, and more often had ulcers as an initial manifestation of lymphoma than did the patients with cutaneous T-cell lymphoma. The histopathologic findings ranged from a nonspecific inflammatory infiltrate to ulcers with marked adjacent epidermal epidermotropism to ulcers with an angiocentric infiltrate. CONCLUSION: A variety of lymphomas may cause cutaneous ulceration. Adequate sampling of these ulcers is necessary for diagnosis. The average life expectancy after ulcer formation is 21 months.     

Cutaneous lymphoma

Cutaneous lymphomas are uncommon. They must be distinguished from secondary skin manifestations of primary nodal lymphomas. Primary cutaneous lymphomas are divided into B-cell- and T-cell cutaneous lymphoma and commonly have good prognosis. Therapy is based on the stage of the disease. Since cure is not possible, the aim of treatment is to control the disease and reduce symptoms. A variety of new and promising therapeutic modalities have been introduced in recent years.     

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.     

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.     

CD56+ lymphoma with skin involvement: clinicopathologic features and classification

BACKGROUND: Extranodal lymphomas expressing CD56 (neuronal cell adhesion molecule) are characterized by a high incidence of cutaneous involvement and a very aggressive clinical course. Knowledge about the prognosis and clinicopathologic features of CD56(+) lymphomas with skin involvement is very limited. OBJECTIVES: To determine survival and prognostic factors for extranodal CD56(+) lymphomas with skin involvement and to describe their clinicopathologic features. DESIGN: Retrospective literature survey and case studies. PATIENTS: A total of 181 patients with CD56(+) lymphoma involving the skin: 177 cases from the literature and 4 new cases. MAIN OUTCOME MEASURE: Survival and its dependence on the following putative prognostic factors: staging, histopathologic findings, lymphocyte markers, T-cell receptor gene rearrangement, Epstein-Barr virus infection, treatment modality. RESULTS: Three major subtypes of CD56(+) lymphoma in the skin were distinguished: blastic lymphoma, nasal-type natural killer-cell/T-cell lymphoma, and subcutaneous panniculitislike lymphoma. The disease disseminated readily, mainly to lymph nodes, bone marrow, the central nervous system, and the liver, but 45% of patients had a purely cutaneous disease at presentation. All subtypes had a very aggressive course with a median survival of 14 months. The main risk factors were age older than 55 years (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.8-3.2), systemic dissemination at presentation (HR, 2.0; 95% CI, 1.5-3.3), and lack of CD30 (HR, 3.8; 95% CI, 1.4-4.9) or CD4 expression (HR, 1.56; 95% CI, 1.06-2.57). The different treatment modalities did not improve survival. CONCLUSIONS: CD56(+) lymphomas involving the skin are rare and extremely aggressive regardless of their histologic presentation and the extent of skin involvement. No effective treatment is available. The risk of death is particularly increased in older patients with CD30(-)CD4(-) lymphomas.     

Primary cutaneous CD20-positive T-cell lymphoma

CD20 is a transmembrane protein that is expressed by B cells during their development and is, therefore, commonly used to label cells of B lineage in lymphoid infiltrates. CD20-positive T-cell lymphoma is infrequent but well recognized. Cases reported in the literature show a variety of clinical and histoimmunochemical profiles. Primary cutaneous CD20-positive T-cell lymphoma is vanishingly rare; only eight cases have been previously reported. We present two new cases of this entity and describe their clinical, histological and immunohistochemical features. CD20 is a highly specific B-cell marker. However, it has been reported in a subset of normal T-cells in peripheral blood and bone marrow of healthy individuals. This subset of T-cells also expresses more often CD8 and g/d than the CD20-negative T-cells. Two main theories have been postulated to explain the expression of CD20 by neoplastic T-cells. The first possibility is that these lymphomas develop from the CD20-positive subset of normal T-cells. The second theory regards CD20 as an activation marker. Prognostic implications and therapeutic options of T-cell lymphomas with positivity for CD20 remain to be elucidated.     

Cutaneous anaplastic T-cell lymphoma in a patient with human immunodeficiency virus infection: detection of Epstein–Barr virus DNA

Summary The Epstein–Barr virus (EBV) genome exists in tumour cells of T-cell lymphomas in nonimmunosuppressed patients. We identified EBV-DNA by in situ hybridization in a case of anaplastic T-cell lymphoma associated with acquired immunodeficiency syndrome (AIDS). EBV-DNA has been reported in AIDS-related Hodgkin's disease or B-cell lymphoma, but never in T-cell lymphoma. Although our results suggest that EBV could play a role in the development of these anaplastic T-cell lymphomas, the mechanism of EBV penetration into T-cells remains uncertain.     

T-cell lymphoma of the skin--clinicopathological relationships, therapy and survival

We investigated the pretreatment characteristics and prognosis of T-cell lymphomas, including mycosis fungoides (MF), T-cell lymphoma of the skin other than MF (CTL), adult T-cell leukemia/lymphoma (ATL), immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma and angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), as well as B-cell lymphoma of the skin (CBL) and analyzed the prognostic factors for skin T-cell lymphoma when the skin was the organ initially or predoienantly involved. Twenty-eight cases of erythematous-stage MF, ten cases of plaque-stage MF, eleven cases of tumor-stage MF, twelve cases of ATL, eleven cases of IBL-like T-cell lymphoma/AILD, and eight cases of CBL were studied. CTCL patients were treated by photochemotherapy with topical 8-methoxypsoralen (8-MOP) followed by VUA irradiation, electron-beam irradiation, or systemic chemotherapy. Complete remission (CR) was obtained with all of these therapies. However induction of CR was not a major prognostic factor in skin T-cell lymphoma, and the clinical stage was more valuable in this respect. No cases of death occurred among erythematous-stage MF patients, but eight out of 11 patients with tumor-stage MF died (mean survival rate, 38 months). The prognosis for tumor-stage MF was better than that of ATL (19 months) or IBL-like T cell lymphoma/AILD (28 months), but worse than those of erythematous-a plaque-stage MF. TNM staging of CTCL was also a useful factor for prognosis.     

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.