A case of subcutaneous panniculitis-like T-cell lymphoma with haemophagocytosis developing secondary to chemotherapy

A 45-year-old woman presented with fever, generalized skin lesions and multiple lymphadenopathies. In her past history she had had six courses of cyclophosphamide and cisplatin combination chemotherapy 7 years ago because of an ovarian carcinoma. We found pancytopenia in the peripheral blood examination. Skin biopsy showed diffuse subcutaneous infiltration reminiscent of panniculitis but composed of malignant lymphoid cells that were of T lineage. Bone marrow biopsy showed normocellular myeloid tissue with abundant haemophagocytic macrophages. Subcutaneous panniculitis-like T-cell lymphoma with haemophagocytic syndrome was diagnosed. This is the first case reported of subcutaneous panniculitis-like lymphoma occurring secondary to chemotherapy.     

Virus-associated haemophagocytic syndrome caused by rubella in an adult

Haemophagocytic syndrome is a systemic clinicopathological entity characterized by systemic proliferation of benign haemophagocytic histiocytes, fever, cytopenia, abnormal liver function and, frequently, coagulopathy and hepatosplenomegaly. Its occurrence has been documented in association with viral, bacterial, fungal and parasitic infections, a wide spectrum of malignant neoplasms, autoimmune diseases and drugs. We report a case of rubella virus-associated haemophagocytic syndrome in a previously healthy 29-year-old woman. Blood tests showed cytopenia, especially severe thrombocytopenia, liver dysfunction, hyperferritinaemia and hypercytokinaemia. Bone marrow examination showed many mature histiocytes with active haemophagocytosis. A skin biopsy from the rash revealed perivascular lymphohistiocytic infiltrates with haemophagocytic histiocytes in the upper and mid-dermis. The patient was treated with antibiotics and immunoglobulin, and by supportive measures including platelet transfusion, and recovered completely.     

A Rare Case of Cutaneous T-Cell Lymphoma Accompanied by Acute Monoblastic Leukemia and Diffuse Large B-Cell Lymphoma

A 70-year-old female was referred for brown-to-gray colored papules and nodules on her lower legs. She had been diagnosed with diffuse large B-cell lymphoma (DLBCL) in her stomach, and myelodysplastic syndrome (MDS) by bone marrow biopsy. Three years after complete remission of DLBCL, she experienced DLBCL recurrence in her small bowel and was hospitalized. MDS had been stationary, but during the treatment of DLBCL, her laboratory findings suggested signs of leukemia. Bone marrow biopsy was done, and acute monoblastic leukemia (AMoL) was diagnosed. After 1 cycle of chemotherapy for AMoL, skin lesions developed, and her skin biopsy showed cutaneous T-cell lymphoma (CTCL). Terminal deoxynucleotidyl transferase staining and CD123 staining were negative, and bone marrow re-biopsy conducted after the skin lesion developed still showed monoblastic proliferation. Whether the CTCL represented with an AMoL lineage switch could not be completely proved due to the absence of molecular or clonal marker evaluations, but the possibility of coexistence of three different malignancies was higher. During treatment, a neutropenic fever developed, and the patient died due to sepsis. We herein report a rare case of CTCL accompanied by AmoL and DLBCL.     

Sézary syndrome presenting with 'leonine facies'

A 71-year-old man presented with erythroderma and multiple nodular skin lesions over the face, scalp, upper limbs and trunk. The facial skin was thickened, producing the rare 'leonine facies' appearance. Investigations revealed the presence of atypical lymphoid cells in the peripheral blood, bone marrow and skin. The atypical lymphoid cells in the peripheral blood and bone marrow were positive for helper T-cell antigens (CD4, CD2, CD5 and CD7) on immunophenotyping by flow cytometry. The histopathology of skin showed dermal infiltration by atypical small lymphocytes with epidermotropism. These cells were positive for helper T-lymphocyte antigens on immunohistochemistry. A diagnosis of Sézary syndrome was made based on clinical, peripheral blood and immunophenotypical findings.     

Human herpesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome

Viral infections are thought to play a part in some cutaneous drug reactions. Human herpesvirus 6 (HHV6), which is the agent of exanthema subitum (sixth disease), has never been implicated in a drug reaction. We report a patient with severe phenobarbital-induced anticonvulsant hypersensitivity syndrome in whom a fulminant haemophagocytic syndrome was associated with HHV6 infection. We discuss the possible role of HHV6 in this reactive condition.     

Leukemia cutis in a patient with acute monocytic leukemia presenting as unique facial erythema

A 67‐year‐old woman was referred to our department with a 1‐month history of facial exanthemas. She had been diagnosed as having acute monocytic leukemia (French–American–British classification, M5b) based on the histological findings of bone marrow. Physical examination revealed diffuse edematous erythema on her cheeks, eyelids and glabella with scattered reddish papules. Histological examination demonstrated dense infiltration of atypical mononuclear cells in the dermis. Specific cutaneous lesions could occur in acute monocytic leukemia more frequently than in other types of leukemia, but rarely show symmetrical edematous erythema limited to the face.     

Epidermodysplasia verruciformis in a Setting of Common Variable Immunodeficiency

A 14-year-old native American female with common variable immunodeficiency was admitted for bone marrow transplantation. Preoperative evaluation showed a generalized lichenoid papular eruption present for several years. Light microscopy revealed expansion of the epidermis by atypical keratinocytes; electron microscopy showed intranuclear papillomavirus inclusions within the granular keratinocytes; DNA hybridization revealed a type 5-related human papilloma virus homology. Four days after bone marrow transplantation the lichenoid papules blackened and began to disappear. Within 30 days after bone marrow transplantation the distribution and appearance of the papules was similar to that of the pretransplantation evaluation. One year after transplantation the patient showed evidence of a successful T lymphocyte graft. No transformation to squamous cell carcinoma had occurred. Epidermodysplasia verruciformis has been associated with deficient cell-mediated immunity, the varying severity of which does not predict the tendency to neoplasm formation (2, 5). Several distinct human papillomavirus genomes have been recovered with DNA hybridization techniques in these patients. It is hoped that the bone marrow transplantation might be associated with diminished transformation to squamous cell carcinoma.     

Immature myeloid precursors in chronic neutrophilic dermatosis associated with myelodysplastic syndrome

Sweet syndrome (SS) associated with myeloproliferative disorders has been considered an inflammatory process mediated by neutrophils in which immunologic mechanisms are operative. The authors report the case of a 68-year-old man suffering from a myelodysplastic syndrome, who presented with a relapsing skin eruption resembling SS. Histopathologically, the skin infiltrates showed prominent neutrophilic features masking the underlying malignant process. Extensive immunophenotypic studies of skin revealed the presence of a few immature myeloid cells intermingled with an overwhelming infiltrate of neutrophils. The atypical cells in the skin had a phenotype identical to that of leukemic cells in the peripheral blood and bone marrow. Whether or not immature myeloid cell precursors constitute a specific infiltrate of leukemia cutis or are a result of recruitment of circulating leukemic cells to this area of inflammation is discussed.     

Disseminated hyperkeratotic and granulomatous nodules in a child with fatal Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis is a rare and potentially fatal syndrome associated with a variety of genetic, malignant, autoimmune, or infectious conditions. The importance of cutaneous presentations of this syndrome has only recently been brought forward. We report the first case of Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis presenting with papulonodular and granulomatous skin lesions. A girl of African origin developed several umbilicated papules on her extremities and face at the age of 18 months. She was born in Germany, had never visited Africa, and was otherwise healthy. Over the next 5 months the lesions progressed in size and number and became hyperkeratotic. Histopathologic analysis of early lesions revealed a superficial lympho- and plasmacellular dermatitis with some features of panniculitis. Later biopsy specimens from nodular lesions showed the formation of tuberculoid granulomas in the deep dermis. At the age of 23 months she became severely ill, rapidly developing high fever, hepatosplenomegaly, icterus, pancytopenia, and ascites. On the basis of bone marrow and lymph node biopsies, the diagnosis of hemophagocytic lymphohistiocytosis was established. However, this phenomenon could not be detected in any of the skin specimens. An active Epstein-Barr virus infection was diagnosed by polymerase chain reaction in blood, lymphoid tissue, and skin. Despite chemotherapy with etoposide and cortisone, the girl expired 14 days after clinical onset of her systemic disease.     

Chronic recurrent lymphocytic Sweet syndrome as a predictive marker of myelodysplasia: a report of 9 cases

BACKGROUND: Sweet syndrome is an acute neutrophilic dermatosis that occurs with malignant diseases, mainly myeloid hemopathies, in about 20% of cases. When associated with myelodysplasia, Sweet syndrome may be clinically atypical. It can be histologically unusual. Concomitant infiltration of mature neutrophils and immature myeloid cells has been reported, and its significance is still debated. In few patients, lymphocytic infiltrates are the presenting feature of Sweet syndrome with myelodysplasia. OBSERVATIONS: We present 9 male adult patients with chronic Sweet syndrome, all with recurrent eruptions of erythematous and annular plaques that were associated with relapsing polychondritis in 4 of the 9 patients. Results from sequential biopsies showed that infiltrates were initially composed of lymphocytes and that neutrophilic dermal infiltration typical of Sweet syndrome occurred 24 to 96 months later, except in 2 cases. Moreover, atypical mononuclear cells were present on all initial biopsy specimens and strongly reacted to CD68 and myeloperoxidase, indicating a myeloid origin. Myelodysplastic syndrome occurred in all 9 patients, concomitantly with the neutrophilic infiltrate in 4 cases. CONCLUSIONS: Lymphocytic infiltrates with a clinical aspect of Sweet syndrome might represent the initial stage of a cutaneous dysgranulopoiesis syndrome and should lead to the research of atypical myeloid cells in skin infiltrate, blood, and bone marrow for the early detection of an associated myelodysplastic syndrome.     

Cutaneous Presentation of Juvenile Chronic Myelogenous Leukemia: A Diagnostic and Therapeutic Dilemma

Abstract: Annular, erythematous, circinate plaques were the first manifestation of juvenile chronic myelogenous leukemia (JCML) in an otherwise healthy 2.5-year-old boy who had had these lesions since 6 months of age. The lesions showed an atypical hematopoietic infiltrate on biopsy. Biopsy of a bone marrow specimen and peripheral blood smear were normal six months before leukemic transformation. At 3 years of age the boy developed splenomegaly, thrombocytopenia, and petechiae, and a bone marrow aspirate and cell marker studies were regarded as consistent with, if not diagnostic of, JCML. Four previous cases of cutaneous leukemic infiltrate associated with JCML have been published. Our patient had recurring urticarial-like plaques for two years before the initial bone marrow finding of JCML. Given the poor prognosis and progressively evolving course of JCML, it may be appropriate to consider therapy before bone marrow changes, based on the presence of the cutaneous eruption with the appropriate findings on skin biopsy and an elevated fetal hemoglobin.     

银屑病合并急性髓细胞白血病一例的治疗观察

目的 报告继发急性髓细胞白血病(M4EO型)的慢性斑块状银屑病1例临床研究及骨髓移植治疗.方法采用临床资料收集,组织病理检查,骨髓和外周血涂片检查,利用流式细胞仪进行细胞免疫分型,用骨髓细胞体外培养做染色体检查及G显带分析.结果患者女,33岁,有寻常性银屑病史20余年,反复出现红斑鳞屑,皮损以斑块为主,有家族史,用多种方法治疗(以中药为主).近来不明原因肌肉酸痛,牙龈出血,发热伴胸骨叩痛.骨髓检查发现异常幼稚单核细胞及早幼粒细胞,并见含有粗大嗜碱颗粒的嗜酸粒细胞,确诊为急性髓细胞白血病M4EO型,经骨髓细胞免疫分型检查符合诊断.骨髓细胞体外培养做染色体检查,+G-显带发现inv(16)的克隆异常和+8克隆异常,染色体核型为46,XX,inv(16)/47,XX,inv(16),+8(2/22).经异基因骨髓移植治疗,银屑病皮损完全消退,急性髓性白血病症状缓解,骨髓异常幼稚细胞减少,病情得到有效控制.结论为国内首例寻常性银屑病(斑块状)继发急性髓细胞白血病M4EO型的临床研究及骨髓移植治疗     

T cells in cutaneous lesions of Sézary syndrome and T-cell leukemia. Characterization by monoclonal antibodies

Anti-T-cell monoclonal antibodies (LEU series) immunoperoxidase technique study for the presence of T cells in cutaneous lesions from four patients with Sézary syndrome and one patient with chronic T-cell leukemia showed that most dermal-lymphoid cells from three patients with Sézary syndrome were reactive with monoclonal antibodies to anti-pan T-cell (LEU-1) and helper T-cell (LEU-3a) subsets but not with those to suppressor-cytotoxic T-cell (LEU-2a) subsets. One patient with progressive disease had atypical dermal-lymphoid cells positive for pan T-cell (LEU-1). Epidermotropic cells were reactive to LEU-1 in all four patients, LEU-2a in one patient, and LEU-3a in one patient. Neoplastic cells in skin lesions of chronic T-cell leukemia showed strong positive staining with LEU-1, but were reactive with both anti-T-cell subset, monoclonal antibodies. The atypical, dermal-lymphoid cells in Sézary syndrome represent mature, helper T cells in most cases. The absence of T-cell subset antigens in one patient with fulminant Sézary syndrome and the finding of both T-cell subset antigens on T-cell leukemia cells suggest the presence of actively proliferating, immature T cells in those cases.     

Acute myelomonocytic leukemia presenting as a benign-appearing cutaneous eruption

Aleukemic leukemia cutis is a rare condition in which patients have skin lesions containing leukemic cells before evidence of leukemia can be detected in the peripheral blood. There are only 23 cases of this phenomenon documented in the English literature. We describe a 62-year-old woman who developed a diffuse, clinically benign-appearing cutaneous eruption, which histologically showed an atypical infiltrate of cells, 4 months before leukemic cells were found in her peripheral blood and the diagnosis of acute myelomonocytic leukemia was made by bone marrow aspiration. This case illustrates the difficulty in diagnosing leukemia cutis from examination of routine histologic sections and the importance of specialized marker studies in determining the cause of an atypical cellular infiltrate of the skin. It also illustrates how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption in a seemingly healthy patient with normal blood parameters.     

Atypical fibroxanthoma in a young female patient with systemic lupus erythematosus: A case report and literature review

A 23-year-old woman presented with an asymptomatic erythematous subcutaneous nodule on her right shin that had been present for the preceding 6 months. She had been diagnosed with systemic lupus erythematosus (SLE) and Sjogren's syndrome 6 years ago and was controlled with prednisolone and hydroxychloroquine. The nodule was excised and the pathologic diagnosis was atypical fibroxanthoma. This case is reported because this tumor occurred in an atypical site in a young female patient with SLE. The occurrence of this unusual atypical fibroxanthoma is believed to be related to altered immunity.     

Acquired erythropoietic protoporphyria as a result of myelodysplasia causing loss of chromosome 18

We report a patient aged 73 years, who developed erythropoietic protoporphyria with typical photosensitivity, at the same time as she was diagnosed as having myelodysplastic syndrome. The myelodysplastic clone in her bone marrow completely lacked one of the two copies of chromosome 18. As chromosome 18 is the locus of the ferrochelatase gene, we postulate that this chromosomal deletion led to reduced synthesis of the enzyme in the bone marrow clone, so causing the porphyria. The nature of the remaining ferrochelatase allele was examined by polymorphism analysis and we discuss the insights that this patient's genotype may reveal about the pathogenesis of porphyria in myelodysplasia.     

Cytotoxic γ/δ subcutaneous panniculitis-like T-cell lymphoma: report of a case with pulmonary involvement unresponsive to therapy

Peripheral subcutaneous panniculitis-like T-cell lymphoma (PSPTCL) is a rare form of cutaneous lymphoma recently proposed as a distinct clinicopathological entity. It usually presents with multiple indurated subcutaneous plaques or tumours, most commonly located on the extremities and trunk and clinically mimicking lobular panniculitis. Associated constitutional symptoms due to haemophagocytic syndrome may advance or, more often, complicate the clinical course in about 40-70% of cases. Finding of TIA-1+ and perforin + cytolytic granules in atypical pleomorphic lymphocytes suggests PSPTCL origin from granular cells of T-cell or natural killer cell phenotype. Cells have a CD3+ CD4+ CD8- or CD3+ CD4- CD8+ T-cell phenotype. Moreover, these lymphomas can express natural killer cell associated antigens, such as CD56, especially in gamma/delta variants. PSPTCL following an indolent clinical course with recurrent self-healing lesions have been described. The prognosis of most PSPTCL is poor even when treated with aggressive chemotherapy. This paper reports a case of PCTCL in a young woman with T-cytotoxic differentiation, with rapid progression unresponsive to several treatments.     

Specific cutaneous lesions of the scalp in myelodysplastic syndrome with deletion of 20q.

We reported a specific skin lesion on the scalp in a patient with myelodysplastic syndrome (MDS), treated as refractory anemia with excess of blasts (RAEB). Histologically, a specimen from a nodule of the scalp consisted of a diffuse infiltration of atypical cells in the dermis and subcutaneous tissue. The patient died of acute leukemia 3 months later. Chromosomal examination of bone marrow cells revealed deletion of 20q and 21 trisomy. The specific cutaneous lesions in this patient were associated with acute transformation. The deletion of 20q and specific cutaneous lesions are regarded as signs of poor prognosis.     

Cutaneous Verrucous Xanthoma in a Bone Marrow Transplant Recipient with Recessive Dystrophic Epidermolysis Bullosa

Verrucous xanthomas (VXs) typically arise on the oral mucosa but have been reported on glabrous skin in patients with graft‐versus‐host disease or recessive dystrophic epidermolysis bullosa (RDEB). The inciting cause of these tumors is unclear but may result from cutaneous inflammation and trauma. We describe a patient with RDEB who had previously undergone a bone marrow transplant for her condition and subsequently developed an VX on her neck.     

Atypical generalized eruptive histiocytosis clonally related to chronic myelomonocytic leukemia with loss of Y chromosome

Generalized eruptive histiocytosis, described in 1963 by Winklemann and Muller, is a reactive, self‐healing form of non‐Langerhans histiocytosis. Rare cases of atypical generalized eruptive histiocytosis have been reported in patients with hematopoietic malignancy, but the biological relationship between the two disorders is not known. We report an 84‐year‐old man with chronic myelomonocytic leukemia who presented with coalescing erythematous papules and plaques on the posterior neck, ear and lower lip, followed by development of blast crisis. Skin biopsy revealed a thick band‐like dermal infiltrate of cells that exhibited morphologic features of macrophages or histiocytes and prominent elastolytic phagocytosis. These cells demonstrated a mature immunophenotype, expressing CD14 and CD68, with partial expression of CD13 but not CD1a, CD43, CD56, CD123, Langerin, or S‐100 protein. Karyotype and fluorescence in situ hybridization analyses showed loss of the Y chromosome in bone marrow and skin specimens, providing evidence of a clonal relationship between the cutaneous eruption and the underlying chronic myelomonocytic leukemia. The presence of the same clone in skin and bone marrow specimens from our patient supports the possibility that atypical generalized eruptive histiocytosis is a marker for underlying hematopoietic malignancy. Discovery of additional cases may shed further light on the pathogenesis of this rare entity.