Relapsing lymphomatoid papulosis after allogenic bone‐marrow transplant

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder in children, which can rarely be associated with a cutaneous or systemic lymphoma. We report a 13‐year‐old girl who presented with typical LyP and pathological features of subtype A. Six months later, the patient presented with rapidly progressive peripheral and systemic lymphadenopathy. On examination of a lymph‐node biopsy, a lymphoid infiltrate negative for anaplastic lymphoma kinase (ALK) and positive for CD30 was found, suggestive of systemic anaplastic large T‐cell lymphoma (S‐ALCL). The patient was treated with chemotherapy, followed by allogeneic bone‐marrow transplant (BMT). Over the following 6 years, she presented with biopsy‐confirmed LyP relapses with complete cutaneous, peripheral‐blood and bone‐marrow chimerism. This is only the third reported paediatric association of S‐ALCL with LyP to our knowledge, and seems to be the first paediatric case of recurrent relapses of LyP after bone‐marrow allograft for S‐ALCL with total (100%) cutaneous and bone‐marrow chimerism. LyP occurring after allogenic BMT does not appear to be donor‐derived.     

BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection

Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.     

乙型肝炎肝硬化与酒精性肝硬化患者骨髓细胞学检查结果分析

目的探讨乙肝肝硬化和酒精性肝硬化患者骨髓象变化不同特点和意义。方法对本院近5年明确诊断为慢性HBV感染的肝硬化和酒精性肝硬化且临床表现为三系减低患者的骨穿结果进行回顾性分析。结果两种不同诱因的肝硬化均可导致患者造血系统发生改变。慢性HBV感染的肝硬化患者的骨髓增生程度高于酒精性肝硬化患者;两组肝硬化患者粒、红两系不同阶段细胞存在病态造血率,中途凋亡比例增加,乙型肝炎肝炎后肝硬化组病态造血率高于酒精性肝硬化组;两组肝硬化患者巨核系统均明显存在成熟障碍。结论慢性HBV感染对骨髓造血细胞的成熟过程存在影响。酒精性肝硬化对骨髓造血细胞增殖、分化存在影响。     

Mouse bone marrow‐derived dendritic cells can phagocytize the Sporothrix schenckii,and mature and activate the immune response by secreting interleukin‐12 and presenting antigens to T lymphocytes

In sporotrichosis, dermal dendritic cells were considered to participate in induction of the immune responses against Sporothrix schenckii infection. However, it is still unclear whether and how dermal dendritic cells were involved in the progress. To clarify the pathogenic role of dermal dendritic cells (DC) in sporotrichosis, we examined the phagocytosis, maturation stages, cytokine production and antigen‐presenting ability of mouse bone marrow‐derived DC after stimulation with S. schenckii. By analysis of flow cytometry, electron microscope and confocal microscope, mouse bone marrow‐derived DC were proved to be able to phagocytize the S. schenckii. The increased expression of CD40, CD80 and CD86 on the surface of S. schenckii‐pulsed mouse bone marrow‐derived DC was detected by flow cytometer, indicating that the S. schenckii‐pulsed mouse bone marrow‐derived DC underwent the maturation program. The secretory enhancement of interleukin (IL)‐12, but not IL‐4, was found in S. schenckii‐pulsed mouse bone marrow‐derived DC, suggesting the possible activation of T‐helper 1 prone immune responses. Furthermore, S. schenckii‐pulsed mouse bone marrow‐derived DC were demonstrated to be capable of inducing the proliferation of T lymphocytes from BALB/c mice that were pre‐sensitized with S. schenckii. Together, all the results implied that dermal DC may participate in the induction of immune responses against S. schenckii infection in sporotrichosis.     

Disseminated histoplasmosis in an AIDS patient treated with itraconazole.

A patient with AIDS presented with a fever, shortness of breath and a productive cough. A provisional diagnosis of Pneumocystis carinii pneumonia was made; however, blood cultures and bone marrow examination revealed disseminated infection with Histoplasmosis capsulatum. This was treated by itraconazole with initial success, but the patient relapsed while on maintenance therapy.     

Self‐renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft

Abstract: Epidermal Langerhans cells (LC) are dendritic, antigen‐presenting cells residing within mammalian epidermis and mucosal epithelia. When massively depleted, they are replaced by cells of bone‐marrow origin. However, their renewal within normal skin under steady‐state conditions is not precisely known. We observed that epidermal LC within a human hand allograft remain stable in the long term (10 years) and are not replaced by cells of recipient’s origin; furthermore, we observed a Langerhans cell in mitosis within the epidermis 8 years postgraft. These results show that under almost physiological conditions, human LC renew in the epidermis by local mitoses of preexisting cells.     

Urinary N-methylhistamine as an indicator of bone marrow involvement in mastocytosis

Thirty-seven patients with mastocytosis and unexplained elevated levels of urinary N-methylhistamine who were undergoing bone marrow biopsy were studied with respect to the diagnosis of mastocytosis and the manifestations of the disease. These patients were from a group of 66 patients from whom a bone marrow biopsy was obtained and urinary N-methylhistamine levels were measured in the period 1990-1998. In seven (19%) of the 37 patients, mastocytosis was limited to the skin. Five (14%) of the 37 patients showed accumulation of mast cells in the bone marrow without characteristic skin lesions, whereas seven (19%) of the 37 patients showed increased numbers of mast cells both in the skin and the bone marrow. Eighteen (49%) of the 37 patients with elevated N-methylhistamine did not have mast cell accumulation in either the skin or the bone marrow biopsy. The median level of N-methylhistamine in the urine of patients with mastocytosis limited to the skin was 245 micro mol/mol creatinine. The average level of N-methylhistamine was 509 micro mol/mol creatinine in patients with mast cell accumulation in the bone marrow and cutaneous mastocytosis. There was a significant difference in the levels of N-methylhistamine in patients with mast cell accumulation in the bone marrow biopsy compared with those without. The likelihood of mastocytosis with mast cell accumulation in the bone marrow biopsy at a given level of N-methylhistamine was calculated. It was established that an N-methylhistamine level of 297 micro mol/mol creatinine or higher may be considered as a threshold indicator for obtaining a bone marrow biopsy in patients suspected of mastocytosis with mast cell accumulation in the bone marrow. For practical purposes, we propose to consider the cut-off level of approximately 300 micro mol/mol N-methylhistamine creatinine for this assay.     

Persistent Erythema Infectiosum-Like Rash as a Prodrome of Acute Lymphocytic Leukemia

Abstract: A 7-year-old boy had erythema infectiosum with typical manifestations. over more than 40 days, these lesions showed no sign of regression, and chronic anemia became progressively more severe.Electron microscopic examination performed 20days after onset showed abnormal Sezary-like lymphocytes. Bone marrow biopsy, which was performed to evaluate the anemia, was consistent with acute lymphocytic leukemia. Persistent parvovirus B 19 infection may be connected with immunosuppression. Therefore, early electron microscopic study and bone marrow biopsy may be helpful for early diagnosis of hematologic malignancies.     

Disseminated Fusarium solani Infection With Cutaneous Nodules in a Bone Marrow Transplant Patient

Fusarium is a ubiquitous fungus that commonly colonizes ulcerated, burned, or traumatized skin and may cause keratitis and onychomycosis in healthy hosts. Serious disseminated infection due to Fusarium has been reported with increasing frequency in immunocompromised patients. We describe a bone marrow transplant patient who developed fungal septicemia and disseminated skin nodules due to Fusarium solani. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients.     

银屑病患者骨髓基质细胞分泌TNF-α,LIF和HGF的分析

目的通过比较银屑病患者与对照组骨髓基质细胞分泌肿瘤坏死因子-α(TNF-α)、白血病抑制因子(LIF)和肝细胞生长因子(HGF)水平的差异,揭示银屑病患者骨髓造血微环境的异常。方法采用密度梯度离心法分离患者与对照组骨髓单一核细胞,通过贴壁法培养骨髓基质细胞,收集传代3次后又培养72h的骨髓基质细胞及培养上清,用流式细胞仪鉴定细胞表面标志并用ELISA法检测上清液中TNF-α,LIF和HGF的水平。结果90%以上细胞表面抗原高表达CD29,而CD34,CD45及HLA-DR表达阴性,即骨髓基质细胞纯度在90%以上;患者组骨髓基质细胞分泌TNF-α,LIF和HGF均显著低于对照组(P<0.05)。结论银屑病患者骨髓基质细胞分泌的某些细胞因子存在异常,表明患者骨髓造血微环境可能存在异常。     

Primary human parvovirus B19 infection in an HIV infected patient on highly active antiretroviral therapy

Adults developing primary human parvovirus B19 (B19) infection may present with arthralgia, fever, and maculopapular rash. Recovery is linked to the development of specific neutralising antibodies. In immunosuppressed patients, including those with HIV infection, such humoral responses are impaired and severe chronic bone marrow suppression and arthritis may occur.     

No correlation of tyrosinase mRNA in bone marrow with prognosis of metastatic melanoma

BACKGROUND: Recent publications suggest that tyrosinase mRNA in blood as well as in bone marrow is detectable only in a subgroup of patients with metastatic melanoma. OBJECTIVE: We addressed the question, whether patients with metastatic melanoma and with RT-PCR-detectable tyrosinase mRNA in blood or bone marrow have a different prognosis compared to tyrosinase mRNA-negative patients. METHODS: 20 melanoma patients with widespread clinical metastases were enrolled and the survival time after first diagnosis of visceral metastases was correlated to tyrosinase mRNA presence in blood and bone marrow samples. RESULTS: The time of survival of 8 patients with metastatic melanoma and detectable tyrosinase mRNA in either blood or bone marrow was not different from the prognosis of 12 patients without detectable tyrosinase mRNA in either blood or bone marrow. CONCLUSION: Although based on a limited number of patients our results suggest that detection of tyrosinase mRNA in blood or bone marrow samples of melanoma patients with advanced disease seems to have no substantial relevance for survival time and outcome of disease. For this purpose, detection of tyrosinase mRNA by RT-PCR is not a valid tumor marker. Nevertheless, tyrosinase positivity in bone marrow in earlier tumor stages might indicate increased risk for the development of distant metastases. This should be addressed in further studies.     

Limitations of the immunocytochemical detection of isolated tumor cells in frozen samples of bone marrow obtained from melanoma patients

We report on a case of a 70-year-old woman with an ocular melanoma, which was diagnosed and treated 14 years ago. The patient was referred to the hospital with a suspected lymphoma. Cytological examination of bone marrow proved a marked infiltration with melanoma cells. Because detection of isolated tumor cells in the bone marrow of patients with various types of tumors was shown to be of prognostic significance and since current tumor-staging techniques are unable to detect single disseminated tumor cells or small aggregates of tumor cells, which might be the seed for subsequent metastatic relapse, we therefore evaluated the feasibility of immunocytochemical screening of bone marrow aspirates of 36 melanoma patients in different clinical stages using three monoclonal antibodies against melanoma-associated antigens in comparison with 43 non-melanoma control patients. Two of these antibodies (HMB45 and NKI-beteb) are directed against the melanoma antigen gp100/pmel17, whereas the third one (TA99) recognizes gp75/Tyrosinase-related protein 1 (TRP-1). None of the patients demonstrated a macroscopic bone marrow infiltration as was present in our patient with metastatic ocular melanoma. Seven (20.6%) of the 34 eligible melanoma patients presented with cells in the bone marrow positive for one or more of the above-mentioned melanosomal markers. Four of the positive patients were clinically free of tumors by the time of puncture, whereas the remaining 3 patients showed overt metastases in the subcutaneous fat (2 patients) and the brain (1 patient). On the other hand, 20 (66%) of the 29 patients with negative bone marrow findings also presented with clinical advanced disease with overt metastasis in the skin, lymph node, spleen, liver, lung, bone and brain. In conclusion, immunocytochemical screening of bone marrow samples is a feasible procedure that allows the detection of micrometastatic tumor cells in a subset of melanoma patients. Massive invasion of bone marrow with melanoma cells is a rare event even in far-advanced metastatic stages and no clear correlation between tumor load and bone marrow infiltration could be established.     

Morphological and functional findings of fixed phagocytes in psoriatics

Twenty-one psoriatics as well as 24 normal healthy adults were studied by functional bone marrow scintigraphy using Tc-99m-labeled human serum albumin millimicrospheres (Tc-99m-HSA-MM). Functional bone marrow scintigraphy is an in vivo test system for the assessment of various functional properties of fixed phagocytes. Of psoriatics who had no systemic drug treatment, 59% demonstrated peripheral extension of the bone marrow space, indicating hyperplasia of bone marrow phagocytes. This phenomenon could be observed only in one normal subject who was a high-performance sportsman. Of psoriatics treated with aromatic retinoid, 83% (n = 6) demonstrated bone marrow extension, as did 100% (n = 3) of psoriatics with cirrhosis of liver. The "capacity' of bone marrow phagocytes to engulf Tc-99m-HSA-MM ("uptake ratio') was diminished in 34% of nontreated as well as 66% of psoriatics treated with aromatic retinoid. The phagocytic and proteolytic turnover of Tc-99m-HSA-MM in the bone marrow, spleen, and liver was found to e accelerated in 66% of nontreated psoriatics, normal (83%) or accelerated (17%) in psoriatics treated with aromatic retinoid, and considerably delayed in all of the psoriatics with cirrhosis of liver. Functional bone marrow scintigraphy proved to be an appropriate in vivo test system for revealing abnormalities of fixed phagocytes in psoriatics. Furthermore, therapeutic effects as well as the influences of preexisting disorders on different phagocyte populations can be assessed.     

The bone marrow in urticaria pigmentosa and systemic mastocytosis. Cell composition and mast cell density in relation to urinary excretion of tele-methylimidazoleacetic acid

The bone marrow sections from five normal subjects and 18 patients with mastocytosis were examined to establish criteria to distinguish urticaria pigmentosa from systemic mastocytosis. Nine patients had increased numbers of mast cells in bone marrow sections stained with a long toluidine blue staining technique specific for mast cells, whereas five patients exhibited increased numbers of mast cells on May-Grünwald-Giemsa-stained smears of bone marrow. A positive correlation between the number of mast cells in sections of the bone marrow and the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid was found. In ten of the examined bone marrow specimens, focal lesions containing mast cells, lymphocytes, and eosinophils appeared. The presence of these focal lesions together with either an increased number of mast cells in bone marrow sections and/or increased urinary excretion of telemethylimidazoleacetic acid is considered diagnostic of systemic mastocytosis. No patient exhibited myeloproliferative condition or other major hematologic abnormality.     

Crusted (Norwegian) scabies. Occurrence in a child undergoing a bone marrow transplant

A case of crusted (Norwegian) scabies is reported in a child who was a recipient of a bone marrow transplant. The infestation is presumed to have predated the bone marrow transplant and continued asymptomatically during chemotherapy and total body x-irradiation in preparation for transplant. The child was asymptomatic until 23 days after transplantation, when bone marrow engraftment was attained. The altered host-parasite relationship is emphasized by the observation that the onset of symptomatic pruritus coincided with successful engraftment.     

Bone marrow examination has limited value in the staging of patients with an anaplastic large cell lymphoma first presenting in the skin. Retrospective analysis of 107 patients

Background According to criteria of the World Health Organization–European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas a diagnosis of primary cutaneous CD30‐positive anaplastic large cell lymphoma (C‐ALCL) should be made only when systemic localizations have been excluded by adequate staging procedures, including a bone marrow biopsy. It has recently been questioned whether or not bone marrow examination should be performed routinely in indolent cutaneous lymphomas such as C‐ALCL. Studies addressing this issue have never been performed. Objectives To determine the incidence of bone marrow involvement in patients with an ALCL first presenting in the skin to find out if the current policy to advise bone marrow examination should be maintained or whether a bone marrow biopsy should be performed only in selected cases. Methods All patients presenting with skin lesions with histological and immunophenotypical features of an ALCL were retrieved from the database of the Dutch Cutaneous Lymphoma Group. Patients with a history of systemic ALCL and patients without bone marrow examination were excluded from the study. The final study group included 107 patients with an ALCL first presenting in the skin, who had been staged completely. Results Staging procedures showed the presence of extracutaneous disease in 20 patients, but bone marrow involvement was not detected in any of the 107 patients. Moreover, only one patient developed bone marrow involvement during follow up (median follow‐up period 69 months). Conclusions Bone marrow examination has limited value in the staging of patients with an ALCL first presenting in the skin, and should be performed only in selected cases.     

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     

Eosinophilic folliculitis: a self-limiting illness in patients being treated for haematological malignancy

Summary Eosinophilic folliculitis is a recognized skin manifestation of human immunodeficiency virus (HIV) disease. Five cases of eosinophilic folliculitis occurring in HIV-negative patients treated for haematological malignancy are reported. In four cases this self-limiting, pruritic eruption, affecting the head and upper trunk, occurred 3 months after bone marrow transplantation, and the fifth case was a patient undergoing chemotherapy for Waldenström's macroglobulinaemia. This suggests that eosinophilic folliculitis is a consequence of disturbances of immune function, and is not specific for HIV infection.