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.     

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.     

Search for Kaposi's sarcoma-associated virus DNA in hemangioproliferative disorders and cutaneous malignant lymphoma

Recently, a Kaposi's sarcoma-associated herpesvirus (KSHV) was discovered. We evaluated by PCR 14 paraffin-embedded specimens with the histological diagnosis of endemic, classic and HFV-associated Kaposi's sarcoma (KS) for the presence of the KSHV DNA sequence. In addition, biopsies of adjacent, histologically unaffected skin, peripheral-blood mononuclear cells (PBMCs) of HIV-infected KS patients, PBMCs of one classic KS patient, and specimens of patients with hemangioproliferative disorders other than KS as well as samples of cutaneous T-and B-cell lymphoma were analyzed for KSHV. In all cases of KS, independent of the KS subtype, KSHV was detected in lesional skin. No KSHV was found in biopsies of the adjacent unaffected skin or PBMCs of HFV-infected KS patients. We found KSHV in the PBMCs of a patient with classical KS. All specimens of cutaneous T-and B-cell lymphomas or lymphomatoid papulosis were negative for KSHV. In addition, the samples with hemangioproliferative disorders other than KS were negative for KSHV. There was one borderline case of KS or acroangiodermatitis that was positive for KSHV. Additional histological sections and clinical evaluation confirmed the diagnosis of classic KS. In summary, the data indicate that PCR for KSHV should be a useful diagnostic tool in cases of hemangioproliferative disorders.     

Cutaneous Manifestations of Internal Malignancy

An association between systemic malignancy and cutaneous manifestations has long been recognized. The cutaneous features that can occur are numerous and heterogeneous, and many different etiologic mechanisms are represented - from direct tumor invasion of skin or distant metastases to a wide variety of inflammatory dermatoses that may occur as paraneoplastic phenomena. In addition, there are a number of inherited syndromes that carry an increased risk of cutaneous as well as internal malignancies. While some of these inherited syndromes and paraneoplastic phenomena are exceedingly rare, all clinicians will be aware of the common cutaneous manifestations of advanced malignant disease such as generalized xerosis and pruritus. This review classifies these wide-ranging cutaneous manifestations of internal malignancy into five basic groups and provides practical advice regarding diagnosis and screening of patients who initially present with a cutaneous complaint. Also included is up-to-date information on two rapidly expanding and exciting areas of research that are likely to have far-reaching clinical implications: (i) clarification of underlying humoral mechanisms, for example, in the malignant carcinoid syndrome; and (ii) identification of an increasing number of specific genetic defects that confer a susceptibility to malignancy.Increased clinician awareness regarding the associations between these lesions and internal malignancy or inherited syndromes will facilitate screening and early diagnosis.     

Cutaneous lymphoma. Understanding the new classification schemes.

Both the REAL and EORTC classification schemes classify lymphomas according to their cell of origin. These schemata also incorporate clinical features that allow for the distinction of some of these disorders. The EORTC classification scheme for primary cutaneous tumors uses terminology similar to that of the REAL classification and should allow for the recognition of teleologically similar tumors in cutaneous and extracutaneous sites. Future investigations will no doubt yield information regarding the true nature of the low-grade B-cell lymphomas of the skin and sort out the ever-increasing number of tumors found to express CD30. Most important, the continued expansion of knowledge regarding cutaneous lymphomas should enhance the ability of physicians to predict prognosis and to arrive at the most effective therapy for patients with these diseases.     

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.     

Paraneoplastic cutaneous manifestations: concepts and updates

The skin often signals systemic changes. Some neoplastic diseases that affect internal organs may trigger several cutaneous manifestations. Although these dermatoses are relatively unusual, the recognition of some typical paraneoplastic dermatoses may lead to the early diagnosis of a neoplasm and determine a better prognosis. In this review article, we discuss the paraneoplastic cutaneous manifestations strongly associated with neoplasms, which include acanthosis nigricans maligna, tripe palms, erythema gyratum repens, Bazex syndrome, acquired hypertrichosis lanuginosa, necrolytic migratory erythema, Leser-Trélat sign and paraneoplastic pemphigus. We also review the clinical manifestations of each condition and include updated knowledge on disease pathogenesis.     

Initial cutaneous manifestation of lymphomas in children

Cutaneous lymphomas comprise a heterogeneous group of lymphoproliferative disorders with skin involvement and are classified as a subgroup of non-Hodgkin lymphomas. From 1981 to 2007, 100 children with non-Hodgkin lymphomas were admitted to the Hematology Unit of the Federal University of Minas Gerais Teaching Hospital. In nine of these children, the skin was involved at the onset of the disease. Three patients were classified as having primary cutaneous lymphoma, while in six the disease was systemic with cutaneous involvement. In seven patients, the immunophenotype was T-cell, in one it was B-cell, and in the remaining case the immunophenotype was indefinable. No deaths occurred in any of the children with primary cutaneous lymphoma.     

Dystrophic xanthomatosis in primary CD30-positive cutaneous T-cell lymphoma. Report of two cases and review of the literature

The development of xanthomatous changes in lesions of primary cutaneous T-cell lymphomas (CTCL) is a rare event. It is usually observed in regressing skin tumours or plaques spontaneously or after a specific treatment. The pathogenetic mechanisms implicated in these changes are poorly understood. We are reporting 2 cases of extensive dystrophic xanthomatous changes, developing in regressing lesions of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Previously reported cases of primary CTCL developing secondary (dystrophic) xanthomata are reviewed.     

Primary cutaneous lymphoma, with the exception of mycosis fungoides]

Cutaneous lymphomas other than mycosis fungoides (MF) form a rare and heterogeneous group. Their clinical behavior remains largely unknown. In this study, the clinical, immunohistological characteristics and follow-up data of 27 well-documented cases of primary cutaneous lymphomas other than MF, limited to the skin (stage IE) were reviewed. The tumors were divided into large-cell lymphomas (LCL) (21/27 = 77 p. 100) and small-cell lymphomas (SML) (6/27 = 23 p. 100). A B-cell phenotype was most often expressed by cutaneous lymphomas (23/27 = 85 p. 100). The clinical course of cutaneous lymphoma was closely dependent upon the histological subtype. Fourteen patients with LCL were treated by radiotherapy alone. Nine patients (64 p. 100) relapsed within two years post-treatment. Seven of them relapsed in the skin outside the initial site, suggesting that radiotherapy alone is not an adequate treatment for these patients. The preliminary results concerning 7 other patients with LCL treated with an initial third generation polychemotherapy regimen are presented.     

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.     

Dermatologic conditions reported in patients with rheumatoid arthritis

Dermatologists, while becoming increasingly involved in the diagnosis and management of patients with connective tissue diseases, have left rheumatoid arthritis relatively unexplored. An increased awareness of possible pathomechanisms of rheumatoid arthritis may allow for generalizations that lead to increased understanding of other connective tissue disorders. The types of cutaneous disorders that occur in association with rheumatoid arthritis include: vasoreactive dermatoses (e.g., various forms of vasculitis), which may occur secondary to the circulating immune complexes present in rheumatoid arthritis; autoimmune bullous disorders, which may occur in the setting of a suppressor T cell defect in rheumatoid arthritis; and various miscellaneous cutaneous associations. Hopefully, this review will lead to an increased understanding of both rheumatoid arthritis and the wide array of cutaneous associations of rheumatoid arthritis.     

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.     

Demonstration of clonal immunoglobulin gene rearrangements in cutaneous B-cell lymphomas and pseudo-B-cell lymphomas: differential diagnostic and pathogenetic aspects.

Twenty-five patients with a benign or malignant cutaneous B-cell lymphoproliferative disease, including seven cutaneous pseudo-B-cell lymphomas, eight primary cutaneous B-cell lymphomas (CBCL), and 10 secondary cutaneous B-cell lymphomas, were investigated for the presence of clonal immunoglobulin (Ig) gene rearrangements using Southern blot hybridization analysis. The selection of pseudo-B-cell lymphomas was based on the presence of polyclonal light-chain expression with immunohistochemical analysis. All cases of CBCL demonstrated monotypic light-chain expression or absence of detectable Ig on CD20+ B cells. Clonal rearrangements of one or more Ig genes were demonstrated in four of seven cases of cutaneous pseudo-B-cell lymphomas, six of eight cases of primary CBCL, and in all cases of secondary CBCL. The observation that cutaneous pseudo-B-cell lymphomas as defined by immunohistochemical criteria often contain occult monoclonal B-cell populations implies that differentiating between pseudo-B-cell lymphomas and CBCL is not always possible by means of gene-rearrangement analysis. These findings may support the concept that cutaneous pseudo-B-cell lymphomas and primary CBCL are part of a continuous and progressive spectrum of B-cell lymphoproliferative skin disorders.     

Primary cutaneous B cell lymphoma: Clinical features,diagnosis and treatment

Primary cutaneous B cell lymphoma(PCBCL) is defined as B cell lymphomas that presents in the skin without any evidence of extra-cutaneous involvement at diagnosis. They are the second most common type of primary cutaneous lymphomas accounting for 25%-30%. Since the prognosis and treatment differ from systemic lymphomas involving the skin, differential diagnosis is very important. PCBCL is a heterogeneous group of disease comprising different B cell lymphomas with distinct treatment and prognosis. PCBCL is divided into 5 subclasses according to World Health Organization and European Organization of Research and Treatment of Cancer classification. Primary cutaneous marginal zone lymphoma and primary cutaneous follicle centerlymphoma are indolent forms and often confined to skin at presentation and during the course of the disease. But primary cutaneous diffuse large B cell lymphoma, leg type and intravascular large B cell lymphoma are more aggressive forms that may disseminate to extra-cutaneous tissues. There is not a treatment consensus since they are rare entities. Local therapies like radiotherapy, surgery or intralesional steroids are options for localized disease in indolent forms. More disseminated disease may be treated with a systemic therapy like single agent rituximab. However combination chemotherapies which are used in systemic lymphomas are also required for aggressive PCBCL. Although indolent forms have relatively better prognosis, early relapses and disseminated diseases are mostly observed in aggressive form with a consequent poor prognosis.     

Hypersensitivity Reaction as a Harbinger of Acute Myeloid Leukemia: A Case Report and Review of the Literature

Cutaneous paraneoplastic syndromes comprise a broad spectrum of cutaneous reactions to an underlying malignancy. These dermatoses are not the result of metastatic spread to the skin, but rather a reaction to the presence of malignancy. Cutaneous paraneoplastic syndromes often precede the identification of a malignancy. We describe the case of a 79-year-old man with a six-month history of recalcitrant treatment- resistant dermatitis. A complete blood count test performed at the time of initial presentation was normal. The patient ultimately presented with erythroderma and was diagnosed with acute myeloid leukemia (AML). The evolution of the dermatitis to erythroderma coincided with the clinical presentation of AML, and was therefore considered to be a paraneoplastic syndrome. The patient decided against therapy and died seven weeks after diagnosis. Physicians should consider a cutaneous paraneoplastic syndrome when faced with dynamic recalcitrant dermatoses that are difficult to treat and decide on laboratory testing accordingly. Patients should be evaluated regularly for two to three years after initial diagnosis with a physical exam and review of systems to monitor for signs and symptoms of malignancy.     

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 B-cell lymphoma leg type: good response with the RADHAP 21 protocol

Primary cutaneous lymphomas are defined as the ones that exclusively affect the skin for up to 6 months after the diagnosis. B-cell lymphomas represent 20-25% of primary cutaneous lymphomas and have, among its subtypes, the leg type, which represents 10 to 20% of cutaneous B-cell lymphomas, generally affecting elderly people and with an intermediate prognosis. This is the report of a rare case of a leg-type B-cell lymphoma with an exuberant clinical presentation affecting a young male patient.     

Cutaneous manifestations of internal malignancy

Skin lesions associated with internal malignancy may present as cutaneous metastases or as typical lesions occurring in the context of certain cancer‐associated genetic syndromes. Paraneoplastic syndromes, on the other hand, are only indirectly associated with an underlying malignancy and are not malignant per se. Historically, a distinction has been made between “obligate” and “facultative” paraneoplastic disorders, depending on the likelihood with which they are potentially associated with malignancy. In addition, there are nonspecific cutaneous manifestations that are only rarely associated with an underlying malignancy. Another possible classification is based on the pathophysiological mechanisms underlying the cutaneous lesions. In everyday practice, it is essential that dermatologists recognize potentially cancer‐associated dermatoses, as this will frequently contribute to the initial diagnosis of an underlying neoplasm.     

Co-expression of CD56 and CD30 in lymphomas with primary presentation in the skin: clinicopathologic, immunohistochemical and molecular analyses of seven cases

BACKGROUND: Natural killer and natural killer-like T-cell lymphomas presenting in the skin usually demonstrate aggressive behavior, an angiocentric distribution and a characteristic immunophenotype. In contrast, primary cutaneous CD30+ lymphoproliferative disorders form a heterogeneous spectrum including anaplastic large cell lymphomas, the majority of which display a good prognosis. Lymphomas with co-expression of CD56 and CD30 are extremely rare and the significance of this co-expression is unknown. METHODS: Seven retrospectively identified cases of lymphomas with co-expression of CD56 and CD30 presenting in the skin comprise this study. Immunohistochemistry, in situ hybridization for Epstein-Barr virus and T-cell receptor gene rearrangement studies were performed on paraffin sections. RESULTS: This subset of cutaneous lymphomas showed a variable clinical course that ranged from resolution without treatment, treatment-failure and recurrence, to death from disease. Histologic, immunophenotypic and molecular studies were of limited utility in predicting prognosis. CONCLUSIONS: Cutaneous lymphomas co-expressing CD56 and CD30 share many clinicopathologic features with natural killer and natural killer-like T-cell lymphomas or anaplastic large cell lymphomas, two entities with widely disparate clinical behavior. It is important to recognize that these lymphomas may behave more aggressively than primary cutaneous anaplastic large cell lymphomas do. Longer follow-up and further investigations on larger numbers of cases are necessary to fully characterize this rare subset of cutaneous lymphomas.