Cutaneous CD4+/CD56+ hematodermic neoplasm

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is a rare and aggressive neoplasm with a high incidence of cutaneous involvement, risk of leukemic dissemination and poor prognosis. The characteristic features are expression of the T helper inducer cell marker CD4 and the NK-cell marker CD56 in the absence of other T cell or NKcell specific markers. Because of the rarity of this disease, we describe a 48 year old woman suffering from CD4+/CD56+ hematodermic neoplasm on her cheek without leukemic infiltration.     

Agranular CD4+ CD56+ hematodermic neoplasm: a new case report

BACKGROUND: "Agranular CD4+ CD56+ hematodermic neoplasm" are rare hematologic neoplasms which were recently shown to correspond to the plasmocytoid dendritic cells. CASE REPORT: A 83-year-old presented isolated skin lesions purple, infiltrating the dermis. The biopsy has shown a dense dermal infiltration with malignant cells CD4+ CD56+ CD43+. There were no bone marrow involvement and no circulating blood cells. A chemotherapy permitted a clinical remission after six courses. Unfortunately, skin and blood relapses appear four months later. After a short success of chemotherapy by DHAP, the patient died three month later. DISCUSSION: "Agranular CD4+ CD56+ hematodermic neoplasm" is a distinct entity from the cutaneous primary lymphomas. Recently plasmocytoid monocyte cells have been identified as the precursor of the malignant population with the high expression of CD123, IL3 receptor. It is a distinct clinicopathologic entity by its clinical presentation with skin tropism, bone marrow involvement with or without leukemic phase and poor prognosis independent of the kind of treatment and its particular phenotype CD4+ CD56+ CD43+. It would be interesting to use antibodies linked to CD123 in therapeutic because any treatment have efficacity in this disease.     

CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that frequently first presents in the skin

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is an aggressive and rare preculsor hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to affect elderly patients, who usually present with skin lesions but often have a disseminated disease, including bone marrow involvement. Although the lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a relationship to plasmacytoid dendritic cells. Because of the rarity of this disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.     

CD4-negative variant of CD4+/CD56+ hematodermic neoplasm: description of three cases

Background: CD4+/CD56+ hematodermic neoplasm (HN) (blastic natural killer (NK)‐cell lymphoma) is a rare entity characterized by dense, monomorphous infiltrates of medium‐sized cells with blastic appearance and a characteristic immunophenotype (positivity for CD4, CD56 and CD123). The combination of CD4 and CD56 positivity is thought to be so striking that it has been used to name this entity. Methods: Three cases of HN with ambiguous phenotypic profile were included in this study. In all cases, phenotypic, molecular and in situ hybridization studies were carried out. Results: All three cases showed an aberrant phenotype with negativity for CD4. Conclusions: CD4‐negative or CD56‐negative cases of HN have been rarely reported in the literature and represent a diagnostic problem. Our three cases confirm that CD4 is not always expressed in these neoplasms. The term ‘CD4+/CD56+ hematodermic neoplasm’ adopted in the World Health Organization–European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas may be misleading and should probably be revised in the light of all data published in the literature.     

CD4+/CD56+ hematodermic neoplasm: report of a rare variant with a T-cell receptor gene rearrangement

CD4+/CD56+ hematodermic neoplasm (HN), formerly known as a blastic natural killer (NK) cell lymphoma, is a rare subtype of a cutaneous dendritic cell neoplasm notable for highly aggressive behavior. The characteristic features are: expression of the T-helper/inducer cell marker CD4 and the NK-cell marker CD56 in the absence of other T cell or NK-cell specific markers. In particular, CD3 (surface or cytoplasmic) and CD2 are not expressed. Although T-cell receptor (TCR) genes are generally reported to be in a germline configuration, we present an unusual variant of a CD4+/CD56+ HN with a clonal rearrangement of TCR genes. This feature of a CD4+/CD56+ HN has been only rarely reported. Recognition of the presence of clonal TCR gene rearrangements in a small subset of CD4+/CD56+ HN is important to avoid misdiagnosis of this entity as an unusual variant of a cutaneous T-cell lymphoma.     

Agranular CD4+ CD56+ CD123+ hematodermic neoplasm (blastic NK-cell lymphoma) revealed by cutaneous localization: 2 cases

BACKGROUND: Agranular CD4+ CD56+ hematodermic neoplasm (blastic NK-cell lymphoma) has been recently described. The skin is often the first organ involved. OBSERVATIONS: Two old men of respectively 70 and 77 years consulted for infiltrated cutaneous lesions. Preliminary histological examination of cutaneous biopsy taken in both patients showed a malignant proliferation suggesting a cutaneous lymphoma, and the patients were referred. Histological examination of new biopsies showed a very similar proliferation in the 2 cases of monotonous medium-sized mononuclear cells without expression of the common antigens CD3 and CD20 and the expression of CD4, CD56, and CD123. No rearrangement of the T-cell receptor gene or the immunoglobulin heavy chain gene were evidenced. No extracutaneous involvement was initially detected in the first patient. Thrombocytopenia associated with the abnormal presence of 15 p. 100 of circulating CD4+ CD56+ cells was initially found in the second patient. The first patient was treated with chemotherapy, with complete remission. A cutaneous relapse promptly occurred, followed by bone and cerebral localizations. The patient died one year after the diagnosis of the disease, in spite of intensification of the treatment. Treatment is still ongoing in the second patient. COMMENTS: The histological presentation of these two patients was very similar with an unusual phenotype of tumor cells expressing CD4, CD56, CD123, but not expressing CD3 and CD20. Some cases have been published under the "term of blastic NK lymphoma" which is the actual term for the disease in the WHO classification. However, the tumor cells derive from the dendritic plasmacytoid cells, also called type 2 dendritic cells, and perhaps from a common precursor to lymphocyte T and dendritic plasmacytoid cells. In spite of complete cutaneous response in the 2 cases presented, as in other reports, extra-cutaneous involvement occurs quickly. Overall survival is usually poor since nearly all the patients died in less than 3 years. This justifies attempting aggressive protocols, with bone marrow allograft in the younger patients.     

CD4+ CD56+ hematodermic neoplasm and plasmacytoid dendritic cell tumor: case report and review of the literature

CD4+ CD56+ hematodermic neoplasm (HN) is a rare and aggressive neoplasm that has raised controversy regarding its etiology. CD4+ CD56+ HN is thought to be derived from plasmacytoid dendritic cells (pDCs) and most commonly stains with CD4, CD56, CD123, and T-cell leukemia/lymphoma 1 (TCL1). Skin manifestations usually are the presenting signs and vary in appearance. Lymph node involvement also is common at the time of presentation, and the natural course of the disease is a progression to leukemia. Treatment of CD4+CD56+ HN focuses on multiple chemotherapeutic regimens but none have been proven to successfully impact overall survival.     

Skin manifestations in CD4+, CD56+ malignancies

CD4+ CD56+ hematologic neoplasms were recently individualized. We report three cases of CD4+ CD56+ malignancies with cutaneous lesions in three cases and also bone marrow involvement in two cases. Two patients relapsed 2 and 3 months after polychemotherapy. Two patients died within 3-10 months. A constant immunophenotype was observed with the co-expression of CD4 and CD56, the absence of B and T-cell markers. The salient fact of this report is the presence of T-cell clonal rearrangement. The clinical and pathological features closely resemble the specific cutaneous manifestations in acute leukemia with monocytic differentiation, especially the granulocytic sarcoma. Because of the positivity of the CD56, natural killer cell proliferations were discussed. Since 1994, 50 cases of CD4+, CD56+ cutaneous neoplasms have been reported with specific clinical, cytologic and immunohistochemical features. The diagnosis is more difficult when the cutaneous location is exclusive; on the contrary, the cytological features of the blood and medullar cells with cytoplasmic vacuoles and pseudopodia are characteristic of this hematologic neoplasm. The presence of CD123 antigen in most of the cases is an argument for a plasmacytoid dendritic cell proliferation and it is also a good marker for primary cutaneous lesions.     

CD4+ CD56+ hematodermic/plasmacytoid dendritic cell tumor with response to pralatrexate

The CD4(+) CD56(+) hematodermic/plasmacytoid dendritic cell tumor is a rare, highly aggressive, systemic neoplasm for which effective therapies have not yet been established. These tumors express CD4, CD56, CD123, and T-cell leukemia/lymphoma (TCL)-1 and are clinically characterized by cutaneous involvement with spread to bone marrow and blood, and poor prognosis with current chemotherapy regimens. We describe a Caucasian woman who presented with plasmacytoid dendritic cell tumor, but an absence of systemic symptoms. Clinically, multiple cutaneous lesions were brown to violaceous firm nodules on the face, arms, and trunk. The patient underwent two courses of cyclophosphamide, Adriamycin, vincristine, and prednisone chemotherapy but relapsed quickly. The investigational agent, pralatrexate (30 mg/m(2)) was given weekly with vitamin B12 and folic acid and resulted in remarkable clinical response with regression of skin tumors. Our observation highlights pralatrexate as a promising therapeutic option for hematodermic/plasmacytoid dendritic cell lymphoma/leukemias.     

CD2- CD4+ CD56+ hematodermic/hematolymphoid malignancy

BACKGROUND: CD2- CD4+ CD56+ lymphoid malignancy has been only rarely reported the last 5 years. It is characterized by a high incidence of cutaneous involvement, cytologically agranular cells, aggressive clinical course, and negative Epstein-Barr virus (EBV) involvement. OBSERVATION: We describe a Japanese patient with a unique hematolymphoid malignancy characterized by an involvement of skin, nasopharyngeal region, bone marrow, lymph node, and a CD4+ CD43+ CD56+ CD2- CD3- CD8- and terminal deoxynucleotidyl transferase phenotype. Clinically, the cutaneous eruptions were purplish, hard, multiple nodules. Histologically, a massive proliferation of atypical pleomorphic cells with medium-sized nuclei were observed throughout the dermis. No clonal rearrangement of T-cell receptor (TCR)-beta gene or immunoglobulin heavy chain J gene was found, and no positive identification of EBV by in situ hybridization for EBV-encoded small nuclear RNA was found. The patient underwent high-dose chemotherapy with autografting of peripheral blood stem cells; however, the tumors quickly relapsed. CONCLUSION: We gathered data from 17 cases of lymphoid malignancy from the literature sharing immunophenotypic and genotypic features similar to those of our case, including CD2- CD4+ CD56+ and germline rearrangement of TCR. Although the cellular origin could not be decided, this malignancy was found to have 100% affinity for skin, a short course, and poor prognosis.     

Pathogenesis and therapy of cutaneous lymphomas – Progress or impasse?

The cutaneous environment hosts a number of hematopoietic neoplasms that are dominated by primary cutaneous (PC) T-cell lymphomas. Recent progress in molecular biology and immunology has provided tools to investigate the pathogenesis and the biology of these neoplasms. This review highlights newest findings concerning the immune biology of CD4+ CD56+ hematodermic neoplasms, and PC T-cell and B-cell lymphomas, speculating how these can be translated into more sophisticated, biology-based treatment approaches in the near future.     

Childhood mycosis fungoides with a CD8+ CD56+ cytotoxic immunophenotype

Primary cutaneous T‐cell lymphomas mostly occur in patients of middle and higher age. Their rarity and an oftentimes atypical clinical presentation in childhood as well as the reluctance of taking biopsies in children are reasons for a delayed diagnosis. We report the case of an 11‐year‐old boy with a 7‐year history of slowly progressive CD8+CD56+ mycosis fungoides of the cytotoxic immunophenotype. His trunk and extremities were affected by extensive pale‐erythematous patches and plaques with fine scaling. In addition, several poikilodermatous lesions were present on his thighs. Improvement was achieved by topical mometasone furoate treatment. On the basis of our observation, a brief review on cutaneous T‐cell lymphomas in childhood and on CD8+ subtypes in particular is given. Clinicopathological correlation is crucial for establishing the correct diagnosis and for estimation of the prognosis.     

Primary cutaneous non T non B CD4+ CD56+ leukemia (2 cases): an original anatomoclinical syndrome

INTRODUCTION: Non T non B CD4+ CD56+ leukemia is often revealed by cutaneous lesions. We report 2 patients with this disorder who had characteristic anatomoclinical findings. CASE REPORTS: An 81 year-old female and a 75 year-old man presented with erythematous macules which increased in number and progressed to infiltrated plaques and nodules. The lesions became ecchymotic, but the patients remained in good general condition and blood count as well as bone marrow examination were unremarkable. A cutaneous biopsy revealed a lymphomatous mononuclear cell infiltrate. The cells expressed CD4 and CD56, but not CD3. The cutaneous lesions preceded for 10 and 9 months respectively the appearance of overt leukemia and medullar involvement. At this stage, the patients deceased rapidly from their leukemia. DISCUSSION: This is an original anatomoclinical syndrome. The histopathologist must pay attention to the unusual CD4+ and CD3- immunophenotype and search for CD56 expression. The malignant cell responsible for this type of leukemia is now individualized and corresponds to a type II dendritic cell precursor.     

An Unusual Hematologic Malignancy Derived from Plasmacytoid Dendritic Cells

Recently reported cases of CD4+ CD56+ hematologic malignancies with a strong predilection for the skin correspond to the neoplastic counterpart of plasmacytoid dendritic cells. This rare, aggressive malignancy lacks pan‐myeloid and pan‐lymphoid markers and often presents with cutaneous lesions, splenomegaly, and involvement of lymph nodes and bone marrow. It has a poor prognosis, and many patients progress to acute myeloid leukemia. The proposed cellular origin is a CD56+ precursor cell related to plasmacytoid monocytes, which strongly expresses CD123 (IL‐3Ra). We describe a 70 year‐old man who presented with gray‐brown truncal nodules and plaques, lymphadenopathy, and splenomegaly. His bone marrow demonstrated malignant CD4+ CD56+ mononuclear cells. Histologic sections of skin lesions showed an atypical infiltrate extending into the deep reticular dermis. Immunohistochemical staining of these cells for CD4 was diffusely positive. Moreover, the infiltrate strongly expressed CD56 and CD123 but showed only patchy or negative staining for other T and B cell markers. The combination of the patient's clinical presentation and biopsy results best fits the diagnosis of this newly characterized, distinct clinicopathologic entity described in recent literature as agranular CD4+ CD56+ hematodermic neoplasm, plasmacytoid dendritic cell acute leukemia, and tumor‐forming accumulations of plasmacytoid monocytes associated with myeloid disorders.     

Poikilodermatous mycosis fungoides with a CD8+ CD56+ immunophenotype: a case report and literature review

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. MF shows varieties in both its clinical presentation and immunophenotype. We herein report one case of poikilodermatous MF with a CD8+ CD56+ immunophenotype and present a literature review. A 20‐year‐old Japanese woman presented with a 10‐year history of multiple poikilodermatous and reddish or brownish patches with mild pruritus on the chest, abdomen, back, buttock and thighs. Histopathologically, small‐ to medium‐sized atypical lymphocytes infiltrated into the epidermis, indicating epidermotropism, along the basal layer, and distributed in band‐like appearance in the papillary dermis. Immunohistochemically, atypical lymphocytes expressed CD3, CD8, CD56, T‐cell intracellular antigen (TIA)‐1, granzyme B and beta F1 but lacked expression of CD4, CD20, CD30 and Epstein‐Barr virus (EBV) latent membrane protein 1. An EBV‐encoded small non‐polyadenylated RNA‐1 (EBER‐1) signal was not detected. On the basis of these findings, the diagnosis of CD8+ CD56+ MF was established. Poikilodermatous MF with a CD8+ CD56+ immunophenotype, as presented herein, is extremely rare. Although further investigation is needed to fully clarify the nature of this aberrant phenotype of MF, we stress that it is important to recognize this rare immunophenotype of MF to distinguish it from aggressive cytotoxic cutaneous lymphomas.     

CD4-/CD56+/CD123+ Hematodermic Neoplasm Showing Early Liver Metastasis

Hematodermic neoplasm (HN) is a clinically aggressive neoplasm with a high incidence of cutaneous involvement and a risk of leukemic dissemination. In the recent WHO-EORTC classification, the term blastic natural killer cell lymphoma has been replaced with CD4+/CD56+ HN because of its derivation from a plasmacytoid dendritic cell precursor. Cases of HN that completely lack CD4 or CD56 expression, therefore represents a diagnostic problem. A 68-year-old Korean male was diagnosed with CD4-/CD56+ HN and treated with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) at initial treatment, and then switched to high dose methotrexate/cytarabine. His disease relapsed and resulted in death from bone and brain disease 6 months after complete clinical remission, despite diagnostic workups, including a radioisotope liver scan and ultrasound-guided fine needle aspiration biopsy. Further cytogenetic studies such as comparative genomic hybridization could elucidate the genetic mechanisms in the development and progression of lymphomas. We report an unusual case of ''CD4-/CD56+/CD123+ HN'' showing early liver metastasis.     

Cutaneous tumors as the initial presentation of non-T, non-B, nonmyeloid CD4+ CD56+ hematolymphoid malignancy in an adolescent boy

We describe a 14-year-old Hispanic boy who presented with a 2-month history of enlarging plum-colored cutaneous tumors on his face, trunk, and proximal extremities. Histopathologic examination showed nodular infiltrates of malignant mononuclear cells extending from the superficial dermis to the deep subcutis. Immunohistochemical staining of the biopsy specimen and flow cytometry studies on a bone marrow aspirate revealed a CD4+, CD56+ hematolymphoid tumor that was negative for all other myeloid and lymphoid markers. Based on this information, the patient was diagnosed with the recently described, rare non-T, non-B, nonmyeloid CD4+ CD56+ hematolymphoid malignancy. To our knowledge, this is the youngest patient reported in the literature.     

CD56 expression in a case of primary cutaneous CD30+ anaplastic large cell lymphoma

We describe clinicopathological features of an unusual case of CD30+/CD56+ T-cell lymphoma in a 58-year-old Korean man who presented with disseminated nodules, papules and hyperpigmented patches. Coexpression of CD30 and CD56 in T-cell lymphoma is very rare. Our patient did not respond to an intensive chemotherapy regimen, in contrast to the previously reported cases of primary cutaneous CD30+ anaplastic large cell lymphoma. Coexpression of CD56 might therefore identify a subset of CD30+ lymphomas with more aggressive features.     

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.     

原发性皮肤CD4+多形性小/中T细胞淋巴瘤一例

报告1例原发性皮肤CD4+多形性小/中T细胞淋巴瘤.患者男,19岁.全身多发暗红色斑块和小结节2年.皮损组织病理检查示,真皮内血管及附属器周围有致密小到中等大,胞质空亮,核扭曲的淋巴样细胞浸润,可见核分裂像.未见亲表皮性,但有浸润毛囊现象.免疫组化检查显示,CD3阳性、CD4阳性、CD8阴性、CD30阴性和CD20阴性,Ki-67阳性率约为25%.诊断:原发性皮肤CD4+多形性小/中T细胞淋巴瘤.