Individual DNA bands obtained by RAPD analysis of canine genomic DNA often contain multiple DNA sequences

We present a case of Langerhans' cell histiocytosis (LCH) of the liver and spleen in an adult. The imaging features are different from those in the few previously reported cases of individual organ involvement by LCH.     

Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone

BACKGROUND: The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. OBJECTIVE: To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. MATERIALS AND METHODS: Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). RESULTS: Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/ RBS+ abnormalities (n = 10) were most frequently insignificant. CONCLUSION: In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.     

Cathepsin D and E co-expression in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and Langerhans' cell histiocytosis: further evidences of a phenotypic overlap between these histiocytic disorders

Nosological classification of sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) is difficult, and the normal cellular counterpart of Rosai-Dorfman (RD) cells is uncharacterised. The peculiar S-100+ phenotype of RD cells suggests a relationship with the dendritic cell family. Recent investigations have revealed cathepsin E to be selectively concentrated in antigen-presenting cells, whereas cathepsin D was found to be expressed in cells of macrophage lineage. Cathepsin D and E distribution was investigated by immunohistochemistry in a series of SHML biopsies and in two types of dendritic cell proliferative lesions: dermatopathic lymphadenitis (DL) and Langerhans' cell histiocytosis (LCH). In SHML biopsies, RD cells and monocyte-related elements of the sinuses and pulp coexpressed cathepsin D and E. LCH cells also stained for both these aspartic proteinases. Conversely, in DL cathepsin E and D were localised to separate cells that resembled Langerhans' cells (LC) or macrophages, respectively, in morphology and distribution. Our data outline the peculiar immunophenotype of RD and LCH cells and suggest that caution should be exercised in the identification of their normal cellular counterpart. The common expression of cathepsin D and E and of S-100 protein suggests some phenotypic overlap between SHML and LCH cells, despite their striking morphological divergence.     

Effect of contrast concentration on abdominal enhancement in the rabbit: spiral computed tomography evaluation

BACKGROUND: Langerhans' cell histiocytosis (LCH) is an uncommon, poorly understood granulomatous disease, characterized by the idiopathic proliferation of Langerhan's cells or their marrow precursors. In 1985, the Philadelphia Work-shop adopted the term "Langerhans' cell histiocytosis" (LCH) to differentiate it from reactive and neoplastic causes of histiocytosis. METHODS: This study includes 73 pediatric patients diagnosed with this condition in Dublin, Ireland, and Nottingham, England, during a 34-year period (1959 to 1993). These patients are reviewed with respect to clinical presentation, difficulty with making a histological diagnosis, their management, and outcome. RESULTS: A total of 49 patients (67%) had head and neck involvement. Bony involvement was the most frequent sign, most frequently located in the skull. There were 11 deaths (15%) in this series, all associated with multisystem disease, and nine of these deaths were in children younger than 2 years of age. CONCLUSIONS: The role of otolaryngologists is important in the early and accurate evaluation, staging, and diagnosis of LCH. It may mimic more common diseases, such as otitis externa, acute mastoiditis, skin rash, gingivitis, or cervical lymphadenopathy. Patients with multisystem disease may be so ill at presentation that the head and neck lesions may be overlooked. The current management of LCH has become increasingly conservative, and in the 1990s, fewer cases are given chemotherapy or radiotherapy. The prognosis is very good for single-system disease and poor for multisystem disseminated disease with early onset.     

Detection of GM-CSF in the sera of children with Langerhans' cell histiocytosis

GM-CSF induces proliferation and activation of Langerhans' cells in vitro. The density of Langerhans' cells in human tumours is correlated to the in situ density of GM-CSF, and intradermal injection of GM-CSF induces local accumulation of Langerhans' cells. Therefore, we investigated the presence of GM-CSF in the sera of children with Langerhans' cell histiocytosis (LCH). We detected GM-CSF in the sera of all children with disseminated and active LCH, but not in the sera of patients with localized (i.e. bone) LCH. These results suggest that GM-CSF level is related to extent and the activity of LCH.     

Diabetes insipidus for five years preceding the diagnosis of hypothalamic Langerhans cell histiocytosis

We report a case of an adult male with Langerhans cell histiocytosis (LCH), in which the hypothalamic involvement went undetected by radiology and who was diagnosed as having central diabetes insipidus for 5 years before the skin lesions and the hypothalamic mass became evident on a CT scan. The skin lesions spontaneously disappeared but relapsed 12 months later. The hypothalamic mass disappeared six months after low dose radiotherapy with persistence of diabetes insipidus and loss of thirst sensation. We did not observe relapse of the hypothalamic mass within the five years of post-radiotherapy follow-up. Despite the fact that patients with LCH may experience spontaneous remissions and exacerbations in their clinical manifestations, the patient's long-term evolution suggested the mass was cured. We would like to draw the attention of clinicians to the necessity of long-term follow-up in patients initially diagnosed of idiopathic central diabetes insipidus. Furthermore, low dose radiotherapy is a successful treatment for LCH-dependent masses in the hypothalamus; however, normalization or regression of CT abnormalities after radiotherapy did not affect the clinical diabetes insipidus status.     

Central nervous system disease in Langerhans cell histiocytosis

Central nervous system (CNS) disease in Langerhans cell histiocytosis (LCH) is a poorly understood complication of yet unknown frequency. By far the most common manifestation is in the hypothalamic-pituitary system with diabetes insipidus as the leading sign, followed by other endocrinopathies and hypothalamic dysfunction. However, essentially all other parts of the CNS may be involved. On the one hand, space-occupying histiocytic infiltrates may lead to size- and site-depending symptoms, extending from adjacent bone lesions or arising from the meninges or choroid plexus. On the other hand, a progressive neurological deterioration can occur with mainly cerebellar-pontine symptoms. In this article, these clinical patterns are described in correlation with the morphology on MR imaging and histopathology. Further, the therapeutic strategies are reviewed critically, and guidelines for the management of patients with LCH-related CNS disease are presented.     

CNS sequelae in Langerhans cell histiocytosis: progressive spinocerebellar degeneration as a late manifestation of the disease

Central nervous system involvement in Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is manifested mainly by diabetes insipidus reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalamus. We describe two patients with progressive spinocerebellar degeneration appearing 4 and 6 years after the initial diagnosis of LCH. No correlation was found between the clinical course of the disease or its treatment and the neurological impairment. An extensive search for metabolic, toxic, neoplastic, and hereditary etiologies for progressive cerebellar degeneration was negative.     

Production of endothelin-1 by cultured human synoviocytes

Langerhans-cell histiocytosis (LCH) is a rare condition with a wide clinical spectrum and variable prognosis. Patients with multisystem LCH have been treated with a variety of agents but may develop resistant and progressive disease. Based on a preliminary encouraging report on the activity of 2 chlorodoxyadenosine in this disease, we administered this agent to a patient with LCH which was resistant to corticosteroids and etoposide. After 4 courses of treatment the patient achieved a complete remission which is currently ongoing for 12 months. 2 CdA appears to be effective in patients with resistant LCH and warrants investigation in previously untreated patients with poor risk disease.     

Langerhans cell histiocytosis of the skin

Cutaneous involvement in Langerhans cell histiocytosis (LCH) occurs in 50% of cases and may be the presenting feature. It is, therefore, important to recognize the wide spectrum of clinical disease that this disorder may adopt in the skin. Cutaneous involvement is not necessarily a benign feature and many patients progress to multi-system disease. There are a number of treatments available for cutaneous LCH. The rationale is to start with the simplest treatment and progress to systemic or interventional therapy as needed.     

A rapid microbiological method for enumerating Escherichia coli from broiler chicken carcasses

We treated a 46-year-old Japanese man with Langerhans cell histiocytosis (LCH) localized to the eyelid alone. He was cured successfully by local and complete resection. Results of pathological examinations of the excised tumor demonstrated diffuse infiltration by atypical histiocytic cells with eosinophilic cytoplasm and convoluted nuclei, S100 immunoreactivity, and tennis-racket-shaped Birbeck granules. Based on these pathological findings, we diagnosed LCH. Clinical examination revealed no LCH involvement in other parts of the body. To our knowledge, there has been only one report of LCH occurring as an isolated tumor in the eyelid. Generally LCH has been reported in children or young people. This is an unusual case of LCH isolated to the eyelid of an older patient.     

Controversies and new approaches to treatment of Langerhans cell histiocytosis

There continues to be genuine ambivalence as to whether Langerhans cell histiocytosis (LCH) is a primary neoplastic or immuno-dysregulatory disorder. Treatment strategies have moved from one camp to the other depending upon the most current alleged successes or failures. This has been particularly true for patients who fall outside of the sphere where treatment is minimal or where known treatment approaches are clearly beneficial. However, there is growing evidence that LCH is both the result of clonal proliferation of Langerhans cells and the immunologic consequence of increased cellular activation. This new knowledge should be the basis for the development of new therapeutic approaches for patients with LCH and its complications.     

Association of malignancy and Langerhans' cell histiocytosis: report of three cases

Among 44 children with Langerhans' cell histiocytosis (LCH) seen at the Pediatric Department of the A.C. Camargo Hospital, S?o Paulo, Brazil, three developed malignancy, two before and one after the diagnosis of LCH. Malignancy could be attributed to treatment in one of the three children. Whether the cancer in the other two children represents a chance association of the two processes or is treatment-related, is unknown.     

The Stomatology Information Retrieval (Reference) System]

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by monoclonal proliferation of activated Langerhans cells. Neither etiology nor pathomechanism of this disorder is presently known. However, despite monoclonality LCH might represent a reactive clonal disorder induced by immune dysfunction rather than a malignant process. To investigate a putative cytokine dysregulation in the pathogenesis of this disorder and searching for parameters of both disease activity and prognosis, serum concentrations of proinflammatory and T-cell derived cytokines were evaluated in LCH patients. MATERIALS AND METHODS: Serum levels of IL-1 beta, IL-2, sIL-2R and TNF-alpha were determined by ELISA in seven children with different types of LCH: Three children (aged 6, 10 and 14 years, respectively) with single system/single bone disease; one child (11 years) with recurrent single system/multiple bone disease and three children (1, 2 and 2 years, respectively) with multisystem disease. RESULTS: sIL-2R was elevated at diagnosis in seven children as compared to healthy adults (mean +/- SEM: 5,256 +/- 3,751 U/ml vs. 73 +/- 5.5 U/ml; P < 0.005) or healthy children (mean +/- SEM: 10,195 +/- 2,798 pg/ml vs. 2,638 +/- 156 pg/ml; P < 0.01). A positive correlation between serum levels of sIL-2R and extent of the disease could be observed. During remission, sIL-2R levels declined. IL-1 beta, IL-2, and TNF-alpha remained within the normal range during the study period. CONCLUSIONS: Elevated sIL-2R levels seem to correlate positively with both extent and activity of LCH, thus indicating a pathological T-cell activation as a pathogenetic factor. sIL-2R level is a promising parameter to monitor disease activity in LCH and may also be of prognostic relevance.     

Differences between platelet phosphoinositide metabolism stimulated by thrombin or SFLLRN are not accounted for by interaction of thrombin with glycoprotein Ib

Tissues from 95 bottlenose dolphins (Tursiops truncatus) that died during the 1987-1988 US Atlantic coast epizootic and 11 bottlenose dolphins that died along the Atlantic coast prior to 1987 were examined histologically and immunohistochemically. Polymerase chain reaction (PCR) testing was performed on 36 of the epizootic and all of the pre-1987 cases. Epizootic cases had syncytia and rare intranuclear and intracytoplasmic inclusion bodies within lung, lymph node, and spleen. Lymphoid depletion was present in lymph node, spleen, and gut-associated lymphoid tissue of epizootic cases. Pre-1987 cases did not have these pulmonary and lymphoid lesions. A larger percentage of epizootic than pre-1987 cases had bacterial and/or fungal infections (primarily pneumonias), pulmonary and lymphoid tissue histiocytosis, mucocutaneous ulcers, and evidence of negative energy balance. Immunohistochemically, 49/95 (52%) epizootic dolphins were positive for morbilliviral antigen. Morbilliviral antigen was detected in lung, lymph node, spleen, thymus, skin, tongue, esophagus, liver, pancreas, gastrointestinal tract, urinary bladder, oviduct, and mammary gland by immunohistochemistry. PCR testing identified morbilliviral RNA in 35/36 (97%) epizootic cases tested. Neither morbilliviral antigen nor morbilliviral RNA were detected in pre-1987 cases. Histologic, immunohistochemical, and PCR results provide strong evidence that morbillivirus infection was the primary cause of the 1987-1988 bottlenose dolphin epizootic.     

Malignant histiocytosis: complete remission with combination chemotherapy

A case of a 16-year-old girl with malignant histiocytosis involving the lymph nodes, bone marrow, peripheral blood, liver, and spleen is described. This patient achieved a complete remission with cyclic quadruple chemotherapy consisting of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). She is alive and free of disease more than 4 years after the completion of COPP and after having had maintenance treatment with a small dose of cyclophosphamide for 2 3/4 years. Such good results with the COPP regimen in malignant histiocytosis have not been reported previously, and it is suggested that this modality of treatment warrants further trial.     

Endocrinological aspects of Langerhans cell histiocytosis complicated with diabetes insipidus

Langerhans cell histiocytosis (LCH) is a rare disorder and may be complicated with hypopituitarism and diabetes insipidus (DI) due to invasion of the hypothalamic-pituitary area. In this study, 10 patients with complete (4) and partial (6) type central DI were found among 125 LCH patients in our hospital records. The water deprivation test, followed by the pitressin test, was performed to confirm DI. Hypothalamic-pituitary endocrine function tests were carried out on these 10 patients at the initial diagnosis and during follow-up. All patients revealed growth hormone insufficiency in the insulin hypoglycemic tolerance test. Four patients had impairment of cortisol secretion, demonstrated by insulin hypoglycemic stimulating test results. Two patients had poor response in the thyrotropin releasing hormone stimulating test. Two patients had only partial responses in the luteinizing hormone releasing hormone test. Four patients had hyperprolactinemia. All patients underwent surgical treatment followed by chemotherapy and/or radiotherapy. One patient completely recovered from the endocrine disorder, 3 patients required smaller doses of desmopressin, and one patient had normal adrenal, thyroid, and gonadal function. Hypothalamic-pituitary disorders in LCH should not be neglected. Treatment of LCH can partially or completely reverse associated endocrine disorders. Therefore, endocrine studies and hormone replacement should be mandatory for patients with LCH.     

Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: a report of five cases and review of the literature

Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly, haemophagocytosis and abnormal laboratory data, without lymphadenopathy or skin lesions. Interestingly, most cases have been reported in Asian patients, and it is unclear whether MH-like BCL is biologically distinct from conventional large B-cell lymphomas. We report five Japanese patients with MH-like BCL. Biopsied specimens of bone marrow, liver and/or spleen showed infiltration of neoplastic B cells accompanied by haemophagocytosing histiocytes. Lymphoma cells were positive for CD19, CD20 and HLA-DR surface antigens, and negative for CD5 and CD10. In four cases elevated serum levels of interleukin (IL)-6 and the soluble IL-2 receptor isoform were noted, but not IL-1beta, IL-2 or tumour necrosis factor-alpha. Autopsies of two cases were pathologically diagnosed as intravascular lymphomatosis (IVL). Based on these observations, the current and nine previous cases reported as MH-like BCL in Japan were re-evaluated. They appear to form a peculiar variant of IVL, characterized by bone marrow involvement at presentation, haemophagocytic syndrome, and a rapidly aggressive clinical course, but rarely neurological complications or skin lesions. This variant may merit separate consideration because of the problems posed in the initial diagnosis and therapeutic approaches.     

Localized eosinophilic granuloma (Langerhans' cell histiocytosis) of the orbital frontal bone

Four patients (aged 5, 8, 14, and 51 years at initial manifestation) with isolated eosinophilic granulomas of the orbital frontal bone displayed short symptomatic periods (two weeks to three months) and some combination of erythema of the lids, a soft, palpable anterior orbital mass, periorbital pain, and osteolytic bone lesions on roentgenography. The bone lesions roentgenographically exhibited irregular, serrated, and sclerotic margins, distinguishing them from the more oval appearance of dermoid cysts. Electron microscopy performed in one case disclosed the presence of Langerhans' granules in the cytoplasm of the histiocytes, indicating that the orbital disease is a mild form of "histiocytosis X" and a benign proliferation of a specific kind of histiocyte--the Langerhans' cell. On follow-up (two to 20 years), after incomplete curettage of two lesions coupled with low doses of postoperative radiotherapy, there was reconstitution of the bone defects, whereas more extensive surgery performed on the other two patients resulted in permanent but subclinical bone defects.     

Cutaneous Langerhans cell histiocytosis of the genitalia in the elderly: a report of three cases

Langerhans cell histiocytosis (LCH) is a disease with a broad spectrum of clinical presentations. All of the variants have in common the proliferation of cells which are morphologically, biochemically, and immunophenotypically indistinguishable from Langerhans cells. A retrospective study of three elderly patients revealed the unique presentation of cutaneous Langerhans cell histiocytosis limited to the genitalia. These cases produced a diagnostic challenge because of their unusual clinical presentation and their morphological similarity to certain other entities, including extramammary Paget's disease and malignant melanoma, which may also show S-100-positive atypical cells. All three cases showed infiltrates of histiocytic-appearing cells with folded nuclei and moderate amounts of cytoplasm which involved the epidermis, dermis, or both. Immunoperoxidase studies using antibody to S-100, CD1a and CD68 in each case showed positive staining.