Graft Versus Host Disease with Mixed Chimerism

We report a patient with graft versus host disease (GVHD) with mixed chimerism (MC). The patient had chronic myelogenous leukemia and received bone marrow transplantation (BMT) from his elder sister. Eighty days after BMT, erythematous lesions appeared on his chest. Histological examination from the skin lesion revealed lymphocytic infiltration into the upper dermis. Eosinophilic necrotic keratinocytes were scattered through the epidermis. Liquefaction degeneration was also recognized. Sicca syndrome appeared from 110 days after BMT. Detection of host origin Y-chromosome-specific DNA by polymerase chain reaction (PCR) method in bone marrow and peripheral blood showed that all bone marrow samples obtained 6 months from BMT were positive for Y-specific DNA, while peripheral blood became positive in the 60th month after BMT. The host origin normal karyotype (46,XY) in the bone marrow samples was identified for the first time in the 60th month after BMT. These results indicate that host-origin hematopoietic cells survived after BMT.     

Atypical pachydermatous cutaneous course of mastocytosis

We describe the case of a 75-year-old man first seen in our department 32 years ago for generalized yellowish erythematous papular lesions along with an attack of pruritus, tachycardia, and flushing. A diagnosis of urticaria pigmentosa was proposed on the basis of these symptoms and the results of skin biopsy. Periodic follow-up in the intervening years included serial laboratory analyses, skin biopsy, radiological studies, bone scintigraphy, and ultrasound of the liver and spleen, with no remarkable findings. The symptoms caused by release of mediators decreased progressively. In one of the most recent visits, bone marrow aspirate and biopsy were performed, revealing multifocal infiltrates of typical CD117+ mast cells. Consequently, the hematology department diagnosed indolent systemic mastocytosis. A number of marked cutaneous changes were observed during the follow-up period: the skin currently appears thickened, indurated, redundant, and grayish, with a pachydermatous appearance. This represents an extremely rare form of cutaneous involvement in mastocytosis and only 1 case has been described in the literature.     

Lymphomatoid papulosis in a patient with Waldenström's macroglobulinemia

Lymphomatoid papulosis (LyP) is a rare skin disease with a benign course but a malignant histologic appearance based on atypical lymphocytes. Waldenström's macroglobulinemia (WM) is a diffuse infiltration of the bone marrow by cells that synthesize IgM immunoglobulins. A 46‐year‐old female presented with a two year history of weakness, fatigue, anemia, and recurring multiple erythematous papules and nodules in the skin. The skin biopsy showed pleomorphic lymphoid cells with atypical mitoses permeated by a diffuse dermal infiltrate of normal appearing lymphocytes. The neoplastic cells were positive for CD30, CD3, and CD5 but negative for CD20 and EMA. The bone marrow was hypercellular due to a diffuse infiltration by lymphocytes, plasma cells, and plasmacytoid lymphocytes. LyP is a lymphoproliferative disorder of CD30‐positive T cells that may be associated with other lymphoid malignancies, particularly Hodgkin's disease, mycosis fungoides, and anaplastic T cell lymphomas. To our knowledge, this is the first report of a LyP appearing in a patient with WM.     

Leucemia cutánea aleucémica: presentación de un caso

—The term aleukemic leukemia cutis describes the invasion of the skin by leukemic cells in the absence of peripheral blood and/or bone marrow involvement. Although the pathogenic mechanisms of this disease are still unknown, it is widely recognized its poor prognosis. Most of the reported patients completely developed the hematologic disease (the majority acute granulocytic or monocytic leukemias) in 10-14 months after diagnosis of aleukemic leukemia cutis, and they had a median survival of 22 months.We report on a case of a 77-year-old man with aleukemic leukemia cutis who presented with numerous erythematous to violaceous papulonodular lesions, mainly located on the trunk and head, lack of peripheal blood involvement and very early alterations in the bone marrow aspirate. Inmunohistochemical stains of skin and bone marrow biopsies revealed the infiltration of both tissues by blast cells of monocyte-histiocytic lineage. Our patient presented spontaneous resolution of skin lesions and his hematological disease showed no progression during 9 months after diagnosis, although he did not undergo any treatment.We emphasize the low incidence of association between myelodysplastic syndromes and aleukemic leukemia cutis as well as the surprising spontaneous remission of cutaneous lesions in our patient.     

急性髓细胞性白血病(M4型)

报告1例急性髓细胞性皮肤白血病(M4型).患者女,48岁.全身出现丘疹、红色结节14d,伴剧烈瘙痒.体格检查:全身泛发大小不等的红色丘疹、结节,质韧,无压痛.皮损组织病理检查:真皮内弥漫淋巴样细胞浸润,有明显异形及较多核分裂象.免疫组化组织病理检查:CD68阳性(灶性),MPO阳性(少量).骨髓穿刺:白血病细胞大量增生,免疫标记:CD68、CD11b、MPO及HLA-DR均阳性.诊断:急性髓细胞性白血病(M4型).患者经过2次DA(伊达比星、阿糖胞苷)方案化疗后,再次行骨髓穿刺示缓解,但皮损仍有复发.     

Aleukemic leukemia cutis presenting as benign-appearing exanthema.

Aleukemic leukemia cutis is a rare condition characterized by the infiltration of the skin by leukemic cells before their appearance in the peripheral blood or bone marrow. We report here a 62-year-old seemingly healthy patient who presented with disseminated erythematous maculae. A skin biopsy showed leukemia cutis of monocytic type. No involvement of bone marrow or peripheral blood was found. The patient developed acute monocytic leukemia 7 months later. We present this case to illustrate how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption without leukemic changes in blood or bone marrow. To confirm the diagnosis of aleukemic leukemia cutis, immunohistochemistry of the skin lesions as well as a complete staging procedure is necessary.     

Zosteriform B-cell chronic lymphocytic leukemia infiltration

Cutaneous infiltration by leukemic cells is uncommon and may be associated with progression of disease. The authors present the case of a 77-year-old female patient, referred to the dermatology clinic for red, erythematous, pruritic papules, which had suddenly appeared on her left hemithorax, along the C6 dermatome, with a 4-week duration. She had already been medicated with Valacyclovir and Acyclovir for 4 weeks, without clinical improvement. She also had a diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), type 2 diabetes mellitus, and multinodular goiter. Tzanck smear showed no multinucleated giant cells,and PCR testing for Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV) on skin biopsy was negative. Histopathology showed a typical B-CLL infiltrate (CD3+, CD20+) and cytogetic analysis was compatible with alterations seen in the bone marrow, confirming the diagnosis of cutaneous infiltration by B-CLL. The patient began chemotherapy with chlorambucil and intravenous human immunoglobulin, which resulted in total regression of the lesions as well as the pruritus. Even though lymphocytic infiltration of Herpes Simplex or Herpes Zoster scars is well documented, cutaneous infiltration with a zosteriform distribution without a previous episode of herpes is very rare. The therapeutic target should be the leukemia itself.     

Dual presentation of extranodal marginal B-cell lymphoma involving the skin, viscera and bones

A 65-year-old man presented with an erythematous indurated plaque on the scalp and forehead. A low-grade marginal-zone B-cell lymphoma with small cells and kappa-chain monoclonality was diagnosed. Radiotherapy was initiated. He soon developed abdominal pain and hematemesis. A high-grade marginal-zone B-cell lymphoma with large cells and lambda-chain predominance was disclosed infiltrating the stomach and lungs. Bone localizations were also found. There was no evidence for lymph node and bone marrow involvement. The distinct cytological and immunophenotypic presentations in the skin and viscera are a puzzling finding.     

Cutaneous presentation of aleukemic monoblastic leukemia cutis - a case report and review of literature with focus on immunohistochemistry

Aleukemic monoblastic leukemia cutis is a rare cutaneous manifestation of a systemic hematological disorder associated with dermal infiltration of monoblasts preceding bone marrow or peripheral blood involvement. We report a case of a 75-year-old woman who presented with an erythematous maculopapular rash, which was clinically diagnosed as viral exanthema. Microscopy of the skin biopsy showed features of monoblastic leukemia. Her general physical condition rapidly deteriorated and she died 4 weeks later. We present this case to alert dermatologists of innocuous erythematous skin lesions clinically resembling a viral exanthema, which, in rare instances, may be a presenting feature of an aleukemic monoblastic leukemia cutis. This entity poses problems for dermatopathologists even on immunohistochemistry as monoblasts are negative for hemopoietic precursor cell antigens like CD34, Terminal deoxynncleotidy1 transferase (TdT) and CD117.     

Kikuchi's disease and the skin: case report and review of the literature

We report scattered indurated erythematous lesions that presented in an 18-year-old Japanese man with Kikuchi's disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well-documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.     

Leucemia cutánea en un paciente con leucemia mieloide aguda M2

—The leukemia cutis is the cutaneous infiltration by leukemics cells. Patients with acute myelogenous leukemia (AML) present specific cutaneous involvement in approximately 10% of the cases.We report the case of a leukemia cutis in a 73-year-old male with AML-M2. The patient presented with a one-week history of general malaise, asthenia, cough, dysnea and fever. Physical examination revealed and indurated red-brown plaque on his back of two moths duration, which was pruritic. Concomitance blood and bone marrow findings were diagnostic of AML-M2. A cutaneous biopsy was consistent with leukemia cutis. A CT and a bronchial biopsy showed pulmonary involvement. Since starting chemotherapy the patient had complete remission and the cutaneous lesion cleared, but 15 days later the skin lesion reappeared. A new bone marrow examination revealed recurrent leukemia. He died one month later.     

CD30 positive pilotropic lymphoma]

BACKGROUND: We report an unusual case of cutaneous CD30-positive lymphoma with pilar tropism and circulating Sezary cells which had a rapidly fatal course. CASE REPORT: A 78-year-old man presented erythematous infiltration of the face, a pruriginous eruption on the trunk and proximal portions of the limbs with small erythematopurpuric follicular papulae, and node enlargement in the inguinal and axillary areas. The rest of the clinical examination was normal. Circulating Sezary cells were found in significant numbers on two different blood smears. Histologic and immunohistochemistry examination of a skin biopsy evidenced medium to large sized lymphoid cell infiltration in a perifollicular localization. A few small cells penetrated the pilar apparatus. There was no follicular mucinosis. The tumoral cells expressed CD2, CD3, CD4 and 75 p. 100 were positive for CD30. Node aspiration showed lymphomatous cells and CD3+ and CD30+ lymphomatous infiltration was found on marrow smears. A T clone was evidenced both in blood and bone marrow leading to the diagnosis of pilotropic CD30-positive lymphoma. Chlorambucil and prednisone were given. The patient died 5 months later. DISCUSSION: The cytology findings suggest medium to large cell pleomorphic lymphoma. The circulating Sezary cells, the pilotropic eruption, and the rapidly fatal outcome suggest transformation of a Sezary syndrome into CD30-positive large cell lymphoma which has been described in fungoid mycosis.     

Case of follicular mucinosis: Nestin-expression in mucin-producing cells

A 29-year-old Japanese man had an asymptomatic, solitary, indurated, erythematous plaque measuring 30 mm × 30 mm on his jaw that had been present for a month. The skin lesion had follicular hyperkeratosis, and lacked hair. A skin biopsy specimen showed a dense perifollicular infiltration composed of lymphocytes, with an admixture of eosinophils in the full thickness of the dermis. The hair follicles and sebaceous glands had reticular epithelial degeneration by mucoid material of the outer root sheath and sebaceous epithelium. The mucoid material stained with Alcian blue at pH 2.5. The clinical and histological features were consistent with the diagnosis of follicular mucinosis. On immunohistochemistry, the outer root sheath cells with reticular epithelial degeneration were nestin-positive and keratin 15-negative. These results suggest that the outer root sheath cells with reticular epithelial degeneration come from the nestin-positive, multipotent, hair follicle stem cells.     

皮肤淋巴细胞浸润症

报告1例皮肤淋巴细胞浸润症.患者女,41岁.因左鼻翼皮肤红色斑疹半年来我院门诊就诊,既往曾多次被诊断为"毛囊炎"、"痤疮"等,但治疗效果欠佳.皮损组织病理检查:真皮中、深层血管及皮肤附属器周围可见以淋巴细胞为主的带状浸润.免疫组化染色:CD68(+)、CD3(+++)、CD45RO(+++)、CD20(+)及CD79a(-).根据临床表现及组织病理检查结果,诊断为皮肤淋巴细胞浸润症.     

Neurofibromatosis Type 1 Diagnosed in a Child Based on Multiple Juvenile Xanthogranulomas and Juvenile Myelomonocytic Leukemia

An association between juvenile xanthogranuloma (JXG), neurofibromatosis type 1 (NF1), and juvenile myelomonocytic leukemia (JMML) has been described in the literature but has only been documented in approximately 20 cases. We diagnosed a patient with NF1 at 25 months of age, before any cutaneous stigmata of this disease had appeared, because we decided to screen for the NF1 gene mutation because of his presentation with multiple JXGs and moderate macrocephaly (2.5 standard deviations) at 9 months of age and JMML diagnosed at 20 months of age. The child is well today after treatment with chemotherapy and allogenic bone marrow transplantation. With increased awareness, patients with JXG and NF1 who develop symptoms possibly related to JMML, such as paleness, skin bleeding, cough, unexplained fever, and hepatosplenomegaly, should be further evaluated. We also emphasize that multiple JXG lesions can be an early marker of NF1.     

Posttransplantation lymphoproliferative disease with features of lymphomatoid granulomatosis in a lung transplant patient

A 58-year-old lung transplant patient developed worsening shortness of breath and indurated erythematous plaques on the lower left leg. A skin biopsy specimen revealed a dense angiocentric and angioinvasive infiltrate in the mid to reticular dermis and panniculus containing large, atypical lymphocytes with convoluted nuclei and prominent nucleoli. Immunohistochemical stains showed that the atypical cells were of B-cell origin, and that Epstein-Barr virus was present. Molecular studies demonstrated B-cell clonality. The patient was successfully treated with rituximab. The clinical and pathologic features in this case represent posttransplantation lymphoproliferative disease with features of lymphomatoid granulomatosis. The case also highlights the importance of clinical and pathologic examination of cutaneous lesions in the evaluation of lymphoproliferative disorders for patients undergoing transplantation.     

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.     

A Case of Chronic GVHD Following Bone Marrow Transplantation from a Phenotypically HLA-Matched Unrelated Donor

A 45-year-old male with chronic myelocytic leukemia who received a bone marrow transplantation from a phenotypically HLA-matched unrelated donor developed chronic GVHD on day 100 post transplantation. He developed a slight fever, malaise, hepatic dysfunction and extensive itchy erythema with scaling over his entire body. The inflammatory skin lesion developed into erythroderma in about two weeks. H&E staining of a skin biopsy revealed eosinophilic bodies and a lymphocytic infiltration in the dermis and epidermis, which were compatible with the early phases of chronic GVHD. Immunohistochemistry revealed that keratinocytes expressed dense HLA-DR and ICAM-1 epitopes. Langerhans cells (CD1a⁺ cells) had disappeared from the epidermis. Many T cells (CD3⁺ cells) had migrated into the epidermis as well as into the reticular dermis. The majority of the T cells in the epidermis were CD8⁺ cells, while almost all the T cells in the dermis were CD4⁺ cells. These immunohistochemical features were similar to those previously reported for acute cutaneous GVHD. Despite the corticosteroid therapy, the eruptions did not disappear. The patient was then treated with whole body bath-methoxsalen (Oxsoralen®) plus ultraviolet A (UVA). The bath-psoralen plus UVA therapy was effective in this patient.     

MYD88 L265P mutation in cutaneous involvement by Waldenström macroglobulinemia

Cutaneous manifestations of Waldenström macroglobulinemia (WM) may occur because of several mechanisms, the least common being direct skin infiltration by neoplastic cells. We report a case of patient that after 4‐year history of indolent WM developed skin infiltration by lymphoplasmacytoid cells in the form of a small, mildly indurated plaque on the anterior chest. MYD88 L265P mutation was detected both in the previous bone marrow biopsy and in the cutaneous lesion. We review the impact of this new genetic tool in the diagnosis and treatment of lymphoplasmacytic proliferations.     

线状苔藓伴皮肤钙沉着症并表皮囊肿一例

患者女,14岁。11年前右下肢内侧出现一线状排列的淡红色扁平丘疹,上覆少许鳞屑,逐渐向两端扩展,未予治疗。5年前原发皮损处开始出现坚实的皮下结节。就诊前10d局部皮损出现溃破,并有红肿痛,异物排出,一直未予处理。皮肤科检查：右下肢内侧及腹部可见线状排列萎缩性暗红斑,其下可触及深在结节状物质,活动度尚可,有粘连,触之硬,压之疼痛。局部隆起于皮面,溃破处有块状、质硬、白色物质排出。组织病理检查：右大腿内侧皮损：表皮角化过度伴灶性角化不全,灶性基底细胞液化变性,真皮浅层较多的淋巴细胞浸润,真皮浅中层见深蓝色的无定形物质。右小腿内侧皮损：表皮灶性角化不全,灶性基底细胞液化变性,真皮乳头及真皮中深部血管及附属器周围淋巴细胞呈片状及团块状浸润,真皮深部及皮下脂肪层可见块状及细碎状的深蓝色钙沉积。右股（大腿）内侧皮损表现为线状苔藓伴皮肤钙沉积症,右小腿内侧皮损表现为线状苔藓伴皮肤钙沉着症并表皮囊肿。结合临床与病史,诊断为线状苔藓伴皮肤钙沉着症并表皮囊肿。治疗：先后分2次予以手术全部切除。