Diagnosis Of Histiocytosis Research Articles

OCT2 expression in histiocytoses.

Diagnosis of histiocytosis can be difficult and one of the biggest challenges is to distinguish between reactive and neoplastic histiocytes on histology alone. Recently, OCT2 nuclear expression was reported in Rosai-Dorfman disease (RDD). Our purpose was to expand the testing of OCT2 on a broader variety of sporadic or H syndrome-related histiocytoses. Cases of histiocytoses were retrieved from the files of Ambroise Paré Pathology Department. All slides and molecular analyses were reviewed, and staining was completed with immunohistochemistry for OCT2. A total of 156 samples from different localizations were tested. Among sporadic cases, 52 patients had RDD, and 10 patients had mixed histiocytosis combining RDD with Erdheim Chester disease (ECD, n = 8), Langerhans cell histiocytosis (LCH, n = 2) or juvenile xanthogranuloma (JXG, n = 1). All these patients were positive for OCT2 in RDD characteristic histiocytes. Twenty-three patients had ECD and all but two (91% - 21/23) were negative for OCT2. By contrast, OCT2 was positive in 11/27 (41%) LCH and 6/16 (38%) JXG. Among the 10 samples of H syndrome-associated histiocytosis, 3 had typical RDD histology, 6 had unclassified histiocytosis, and one had mixed RDD-LCH; all were positive for OCT2. On 16 samples of granulomatous lymphadenitis, OCT2 was negative in epithelioid histiocytes. Our study shows that OCT2 has a sensitivity of 100% for RDD cases and mixed histiocytoses with an RDD component. It is negative in 92% of ECD but expressed in at least 38% of LCH, JXG, and C group histiocytoses. Finally, OCT2 is positive in all H syndrome-related histiocytoses, independent of their histology.

C46 A RARE CASE OF LANGERHANS CELLS HISTIOCYTOSIS CARDIO–VASCULAR INVOLVMENT

Abstract A 54–year–old woman presented at our department for clinical follow–up. She was affected by hypertension, hypercholesterolemia, diabetes insipidus and autoimmune hypotiroidism in substitutive therapy. She had chronic coronary syndrome treated by medical therapy after unsuccessfull left anterior descending artery percutaneous revascularization and underwent to left common iliac artery stenting. The echo–doppler study showed a thickening of both common and internal carotid. Moreover, the patients underwent a skin biopsy of nodular, purple lesions which showed a xanthomatous infiltration suggestive of Langherans cell histiocytosis (CD1A+ e S100+). A subsequent PET–TC total body demonstrated a FDG uptake tissue around the great vessels and a focal increased uptake in the proximal thirds of the left tibia and in the distal thirds of fibula. The patient underwent to a new skin biopsy which confirmed histiocytosis (S100+, langherin+, CD1a+, BRAFV600E negative) and to a negative bone biopsy. Since the diagnosis of histiocytosis was confirmed the association of mercaptopurine and steroid therapy was started. In our department we performed a follow–up echocardiography which showed normal left and right ventricle dimensions and a good bi–ventricular function (LVEF according to Simpson 55% and FAC 50%) and surprisingly a focal right atrial wall thinckening of 3 mm. Therefore, the cardiac MRI showed no oedema in triple T2, no late gadolinium enhancement inIR–GRE T1 and at the posteriori wall of the right ventricle a focal thickening of 2.3 x 2.4 cm of increased intensity and a disomogenous enhancement after contrast agent administration (Figure 1); the same non stenotic tissue was showed along the aortic arch and the discending aorta (Figure 2). The MRI characteristic of these cardio–vascular lesions are consistent with the diagnosis of Langeran’s cells histiocytosis.

From classical Langerhans cell histiocytosis to Erdheim-Chester disease: different sides of the same coin?

Objective. Analysis of the clinical course of classical histiocytosis (LCH) in children and clinical differences, diagnostic difficulties and a different therapeutic strategy in a child with a rare variant of LCH in the form of Erdheim-Chester syndrome (ECD). Patients and methods. Retrospective single-center analysis of the clinical course of classic LCH in 54 children who were diagnosed with the disease in the last 40 years and the differences shown in a patient with diagnosed EDC. The clinical response was assessed according to the LCH programs valid at the time for the classic form of LCH and in the child with ECD. Results. The multi-system form of LCH was diagnosed more often than the single-system form. The skull bones were the most common localization of LCH in both forms of the disease. Recurrence of the disease occurred in about 5% of patients, death in one (1.9%) patient. The course of the child with ECD was more turbulent, with rapid progression, involvement of critical organs, no response to standard chemotherapy according to the LCH 2009 protocol. After the molecular diagnosis was specified, therapy with vemurafenib, a BRAF-V600E kinase inhibitor, followed by transplantation of hematopoietic stem cells (allo-HCT) was applied. Basic disease was in remission and lasts for 12 months. Conclusions. The lack of an expected response to LCH therapy should indicate the possibility of rare forms of histiocytic hyperplasia. Molecular tests are an important element in the diagnosis of histiocytosis and allow to precisely select the most appropriate, targeted therapy. BRAF-V600E kinase inhibitors are highly safe and effective in the treatment of LCH and ECD with a confirmed BRAF-V600E mutation, however allo-HCT should be considered in selected cases.

Peritoneal or mesenteric tumours revealing histiocytosis

ObjectivePeritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead...

HISTIOCYTOSIS: CASE REPORT

Histiocytosis is part of histiocyte-related proliferative diseases. The term histiocyte involves all types of macrophages and other dendritic cells (antigen-presenting cells: dermal dendrocytes, Langerhans cells (CL), and indeterminate cells). An 11-year-old male patient presented with an initial complaint of dental pain. Intraoral examination revealed exophytic and ulcerated lesions associated with the left maxillary first and second premolar and with left mandibular first and second molar with a time-course evolution of 2 months. An incisional biopsy was performed, and histopathologic examination revealed the presence of histiocytes with nuclei shaped like kidney beans, permeated by eosinophils. There also were lymphocytes and giant cells. Immunohistochemistry was positive for S-100, concluding the diagnosis of histiocytosis. The patient underwent chemotherapy, and there has been no recurrence after 2 years of follow-up.

Histiocytosis: An Uncommon Presentation with Hypopituitarism

Langerhans cell histiocytosis is a multi system disorder with a certain predilection for involving hypothalamic pituitary axis. We hereby report a 7 year old girl presenting with polyuria, polydipsia and growth retardation. The girl had a past history of pain in right hip joint and nodular region over chest. Water deprivation test confirmed the diagnosis of central diabetes inspidus. Other investigations revealed Growth hormone deficiency and central hypothyroidism. X-ray and MRI hip revealed absent right inferior pubic ramus with bone marrow biopsy confirming the diagnosis of histiocytosis. Patient was treated with nasal Arginine Vasopressin spray, subcutaneous growth hormone and oral thyroxine. Key words: Histiocytosis; Diabetes inspidus; Growth hormone deficiency; Central hypothyroidism DOI: http://dx.doi.org/10.3126/jnps.v32i1.5343 J. Nepal Paediatr. Soc. Vol.32(1) 2012 81-84

Neurodegeneration in the course of Langerhans cell histiocytosis

Cerebral involvement in the course of Langerhans cell histiocytosis has been described especially in children. It is mainly characterized by hypothalamic-pituitary functional deficit, due to granuloma growth. Here we describe a rare case of adult-onset histiocytosis developing a neurodegenerative disease resembling multiple system atrophy. The patient we describe here started suffering from subtle personality changes which progressed to a severe neurological syndrome 2 years after the diagnosis of histiocytosis. Twenty years before she developed a diabetes insipidus, without any apparent cause. Brain MRI scans at the time of neurodegeneration revealed slight signal alterations at the cerebellum, especially involving the dentate nuclei and the white matter. Despite being rare, histiocytosis should be considered in adult patients with cerebellar abnormalities and/or with unexplained diabetes insipidus to rapidly discern and treat histiocytosis before the onset of its neurodegenerative, untreatable phase.

A rare case of infantile myofibromatosis and review of literature

Infantile myofibromatosis is a rare benign tumor-disease (1/400,000). Four different types have been reported in literature. The most commonly affected body areas are the head, the neck, and the trunk. We would like to present a rare case of a multicentric type with singular visceral involvement and a literature review of all case series with more than five patients. A 9-month-old boy presented with a swelling on the medial side of his proximal left tibia. The lesion which was present since birth, was well palpable, indolent, hard, and mobile in relation to the surrounding tissue. Radiographic films and ultrasound examination presented a pretibial soft-tissue tumor mass with calcifications and two osteolytic lesions with a sclerotic rim. A skeletal survey showed more osteolytic lesions, but the magnetic resonance imaging showed no more soft-tissue lesions. The rapid frozen section biopsy hinted at the diagnosis of histiocytosis X. The definitive histological result 6 days later was infantile myofibromatosis. As therapy, we determined a wait-and-see policy with controls all 3 months. At 20 months follow-up, the boy showed beginning of regression of all lesions. Infantile myofibromatosis is a very rare benign tumor-disease. Radiologically often soft-tissue masses with calcifications and osteolytic lesions with sclerotic rims are described. These findings also can be interpreted as histiocytosis X, which is a potential differential diagnosis. Histopathologically, cells characteristically appear as spindle-shaped fibroblast cells with pale pink cytoplasm and elongated nuclei and the immunophenotype is defined with a positive reaction on smooth-muscle antigen vimentin and the muscle-specific antigen HHF-35. The data of the literature review underline that a wait-and-see-policy should be considered as the first treatment of choice as in most instances the bony lesions regress spontaneously. However, a thorough examination has to be carried out to exclude lesion in other organs like gastro-intestinal or cardio-pulmonary nodular tumor masses. In conclusion, the present case report and the literature review support the notion that infantile myofibromatosis should be considered as a possible differential diagnosis for soft tissue expansions and/or osteolytic lesions in a newborn.

La gammagrafía ósea demuestra ser útil para el diagnóstico de extensión en un caso de histiocitosis X del hueso temporal

We present the case of a 43-year-old man diagnosed of insipid diabetes and hypogonadotropic hypogonadism in whom a right temporal bone lesion was observed in the control MRI, thus leading to his admission. A bone scintigraphy with 99mTc-HMDP showed increased uptake in the right temporal region with sphenoidal extension, coinciding with the MRI. In addition, increased uptake having less intensity and size was observed in the left temporal region. A biopsy on the newly appearing mouth ulcers in the jugal mucous was performed and showed Langerhan's cells, the diagnosis of histiocytosis X being confirmed. Six months later a new MRI indicated disease progression with bilateral temporal involvement. The bone scan findings in this case provided a more exact extension diagnosis of the disease than the MRI.

Histiocitose x (síndrome de hand-schuller-christian): relato de caso

Os autores relatam o caso de uma criança do sexo feminino, quatro anos de idade, que apresentava cefaléia, irritabilidade, otorréia e exoftalmia unilateral. No estudo tomográfico e na radiologia convencional encontraram-se grandes áreas líticas no crânio e na sua base. O restante do esqueleto não evidenciou anormalidades. O diagnóstico de histiocitose X (síndrome de Hand-Schuller-Christian) foi confirmado pelo mielograma. Este estudo mostra achados radiológicos e citológicos, além de apresentar uma revisão da literatura sobre o caso.

下顎に発生した単核食細胞系組織球症の１例

A case of mononuclear phagocyte system (MPS) histiocytosis in the mandible of a 26-year-old woman is reported. Although she had no complaints, orthopantomography showed a honeycomb appearance in the right mandible.A diagnosis of histiocytosis was made on biopsy. The tissue was consisted of large numbers of histiocytes rich in foamy cytoplasm. Immunohistochemical examinations revealed that these cells were S-100 protein (-), α 1-antitrypsin (+), α 1-antichymotrypsin (+), and CD68 (+). The lesion was considered to represent histiocytosis derived from MPS histiocytes. Enucleation was done, and there have been no radiographic signs of remodeling and no clinical evidence of progression as 7 years after the operation.

Histiocytosis X presenting as prolonged cholestatic jaundice in childhood

Objective To report the case histories of two children in whom cholestatic liver disease preceded other manifestations of histiocytosis X. To discuss the possible relevance of the timing and nature of liver involvement in the immunologie pathogenesis of this disease. Outcome In both patients, the diagnosis of histiocytosis X was made only upon the appearance of extrahepatic manifestations of the disease. A review of the initial liver biopsy specimens failed to reveal any evidence of histiocytic involvement. Conclusion In children with cholestatic jaundice simulating sclerosing cholangitis, a diagnosis of histiocytosis X should be considered and extrahepatic histiocytic involvement actively sought.

How useful are Birbeck granules in the diagnosis of histiocytosis

How useful are Birbeck granules in the diagnosis of histiocytosis

Production of anti-B monoclonal antibodies (DBB.42, DBA.44, DNA.7, and DND.53) reactive on paraffin-embedded tissues with a new B-lymphoma cell line grafted into athymic nude mice

A new B-lymphoma cell line (DEAU-cell line) was established from a diffuse large-cell lymphoma (centroblastic type) and was successfully grafted in athymic nude mice. Monoclonal antibodies (MoAbs) were generated using splenocytes of DEAU-tumor bearing mice. Before the fusion experiments, cellular immunity of the mice bearing growing DEAU tumors was restored by injection of spleen cells from conventional Balb/C mice. Spleen cells from conventional Balb/C mice immunized with DEAU-cell line were also used for the generation of MoAbs. Four MoAbs (DBB.42 and DBA.44 from normal Balb/C mice, and DNA.7 and DND.53 from athymic nude mice) were investigated because they identified B-cell- associated antigens not destroyed by fixatives. DBB.42 recognized a pan- B cell-associated antigen (molecular weight (mol wt) = 45 Kd). DBA.44 detected a B-cell antigen (mol wt not determined) expressed on a subpopulation of B lymphocytes in the mantle zone of lymphoid follicles. DNA.7 also defined a B-cell antigen (43 Kd) mainly expressed on germinal center cells. Similarly, DND.53 recognized a B-cell antigen (two bands of mol wt 20 Kd and 35 Kd, respectively) mainly expressed on germinal center cells and mantle zone lymphocytes and interdigitating reticulum cells in the paracortical area. Major differences were found in the reactivities of these MoAbs on malignant lymphomas. DBB.42 was positive with almost all B-cell lymphomas and some T-cell lymphomas. Within the group of low-grade B-cell lymphomas, DBA.44 reacted principally with hairy-cell leukemia. DNA.7 reacted mainly with high- grade B-cell lymphomas with a weak positivity in low-grade B-cell lymphomas. DND.53 reacted with all but one B-cell lymphoma, cells of histiocytosis X, and Reed-Sternberg cells. These findings indicate that new MoAbs can be generated by using spleen cells from athymic mice bearing human tumors as well as by new lymphoid cell lines. The MoAbs so generated, as in the present study, are deemed potentially useful for the recognition of B-cell lymphomas in routine diagnostic histopathology. In addition, DND.53 could be of value for the diagnosis of histiocytosis X and the detection of Reed-Sternberg cells in Hodgkin's disease.

The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis.

Diabetes insipidus is a well-recognized complication of Langerhans-cell histiocytosis (histiocytosis X), but its frequency and natural history are not well defined. Of 52 children with histiocytosis whom we studied, 12 (23 percent) had diabetes insipidus. Only two children had diabetes insipidus at presentation with histiocytosis, but the cumulative risk that it would develop during the first four years after the presentation and diagnosis of histiocytosis was found to be 42 percent. Diabetes insipidus occurred most often among children with multisystem disease and those with proptosis. To determine the natural history of diabetes insipidus in children with histiocytosis, we measured the response of urinary arginine vasopressin to water deprivation every six months in 21 children who did not have diabetes insipidus and who had had histiocytosis for less than four years. Five of the 21 children (24 percent) had subnormal responses during the initial test. One subsequently had spontaneous improvement in the functioning of the posterior pituitary, and diabetes insipidus subsequently developed in two, as it did in one of the children who initially had normal function of the posterior pituitary. Two of the children received irradiation to the pituitary within two to four weeks after diabetes insipidus developed, but they had no improvement in pituitary function. However, diabetes insipidus improved transiently during prednisolone therapy in one of these children and improved permanently after etoposide therapy in another child. We conclude that prospective study with the use of a simple water-deprivation test will allow partial defects of posterior-pituitary function to be detected in patients with histiocytosis and will permit a more appropriate evaluation of the effects of therapeutic intervention.

Expression of sialylated Leu-M1 antigen in histiocytosis X.

The purpose of this study is to determine the versatility of the monoclonal antibody anti-Leu-M1 in histiocytosis X diagnosis. This antibody recognizes an unsialylated lacto-N-fucopentaose III (hapen X) carbohydrate moiety that is linked to the cell membrane protein in interdigitating reticulum cells and Langerhans' cells. Previously, the authors have shown that anti-Leu-M1 can be used to stain Reed-Sternberg cells, which are likely related to interdigitating reticulum cells. In this study, the authors tested the usefulness of anti-Leu-M1 in staining formalin-fixed and paraffin-embedded tissue sections from eight patients with histiocytosis X. For staining of histiocytosis X cells, unlike Reed-Sternberg cells in Hodgkin's disease, neuraminidase treatment was required for removal of sialic acid residues from the Leu-M1 antigen. The staining characteristics of anti-Leu-M1 in histiocytosis X cells resembled those of normal Langerhans' cells and lymphocyte and histiocyte variants (L & H cells) in the lymphocyte-predominant type of Hodgkin's disease. The significance of sialylation of Leu-M1 antigen in histiocytosis X cells has yet to be determined in order to correlate the prognosis of the disease. The authors suggest that anti-Leu-M1 used together with neuraminidase treatment is a valuable tool in the diagnosis of histiocytosis X when electron microscopy or frozen sections for OKT6 immunostaining are not available.

Colonic Ulceration in Histiocytosis X

Gastrointestinal symptoms in histiocytosis X are distinctly unusual. This report describes a 5-month-old infant with a prolonged history of lower gastrointestinal bleeding which was found to be caused by diffuse histiocytic infiltration of the colon. Immunopathologic and electron microscopic studies confirmed the diagnosis of histiocytosis X. The differential diagnosis of lower gastrointestinal bleeding in young children should include histiocytosis X.

CELL SUBPOPULATIONS IN HISTIOCYTOSIS X

Histiocytosis X (HX) is currently believed to be a Langerhans' cell neoplasm. Cell subpopulations in 5 biopsies from 3 cases of HX were scrutinized using an indirect immunoperoxidase technique and 21 McAbs. The following McAbs were used: Leu l(pan T), Leu 3A (Helper T, macrophages), Leu 2A (suppressor T), OKT 3 (pan T), OKT 6 (cortical thymocyte, Langerhans'), HLADR (macrophages, activated T,B), R423 (dendritic reticulum cell), My 3 (monocyte), Leu M1 (myelomonocytic), Leu M3 (monocyte), OKT 9 (transferrin receptor), OKT 10 (prothymocyte, bone marrow progenitor), B1 (B cells), B2 (B subset), T 11 (E receptor), HNK 1 (K/NK), My 10-13 (immature myeloid), J5 (C.A.L.A.). The tumor phenotype was OKT 6+ HIADR+ Leu 3A+. However, cells reacting with Leu 1, Leu 2A, OKT 3, My3, Leu M1, Leu M3, 10, 11, 13 were also present. This study indicates considerable heterogeneity of cells in HX and suggests that numerous cell-cell interactions may be occurring. The OKT 6 marker may be a useful adjunct in the diagnosis of Histiocytosis X.

Pleural Effusion in Histiocytosis X

In Reply.— The case reported by Drs Winkler and Yam seems to confirm that pleural involvement may not be uncommon in histiocytosis X. As we stressed in our two cases, the diagnosis of histiocytosis X cannot be excluded in the presence of a pleural effusion. We thank Drs Winkler and Yam for their interesting case record.

Quality of survival in histiocytosis X: a Southwest Oncology Group study.

Sixty children survived for five years after the diagnosis of histiocytosis X. Serious disabilities were seen in 50% of children whose disease involved soft tissue and bone. Late deaths from pulmonary failure were associated with opportunistic infections in two cases. Future treatment approaches must weigh the risks of therapy-related complications against the probability of significant disability if the disease continues for many years.