Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity.

Multicentric reticulohistiocytosis (MRH) is a rare systemic disease of non-Langerhans cell histiocytosis. A number of studies in the literature have documented that it can coexist with malignancy or autoimmune disease, making it difficult to determine the most appropriate therapy. Here, we present a case study of MRH associated with posterior mediastinal adenosquamous carcinoma along with antinuclear antibody positivity and lupus anticoagulant positivity. The patient experienced 6 months of clinical benefit after surgical resection and chemoradiotherapy of the mediastinal malignancy. This case adds to the available literature on multicentric reticulohistiocytosis associated with different types of malignancy and provides supplementary clinical data on the coexistence of this syndrome with malignancy and immune system abnormalities. To the best of our knowledge, this is the first case study describing MRH accompanied by posterior mediastinal adenosquamous carcinoma and lupus anticoagulant positivity. The unknown aetiology and polymorphic clinical presentation of MRH warrants further investigation.

Two siblings with PRKDC defect who presented with cutaneous granulomas and review of the literature.

V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.

Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease: An Observational Case Report Study.

Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.

Caso para diagnóstico / Case for diagnosis

Relatamos um caso de histiocitose cefálica benigna em uma criança do sexo masculino, de um ano e três meses de idade que desenvolveu múltiplas pápulas na região malar bilateralmente, sem outros comemorativos associados. A histopatologia caracterizou-se pelo padrão derme papilar, com imuno-histoquímica negativa para S100 e CD1a, e positiva para CD68, ficando assim estabelecido o diagnóstico desta histiocitose não- Langerhans, baseado nos aspectos clínicos, histopatológicos e imuno-histoquímicos característicos.

The present paper reports a case of benign cephalic histiocytosis in a 15-month baby boy, who developed multiple papules bilaterally in the malar region with no other associated manifestations. Histopathology revealed a papillary dermal pattern, while immunohistochemistry was negative for S100 and CD1a and positive for CD68. Therefore, diagnosis was established as non-Langerhans cell histiocytosis, based on the clinical, histopathological and immunohistochemical features present.

Multicentric reticulohistiocytosis with elevated cytokine serum levels.

Multicentric reticulohistiocytosis (MRH) is an uncommon non-Langerhans cell histiocytosis of unknown etiology. It is a multisystem disorder characterised by a papulonodular skin eruption, mainly in the extensor surfaces, and destructive polyarthritis. Histologically, either cutaneous lesions or the synovium show a dense dermal infiltrate of histiocytes and multinucleated giant cells with an eosinophilic granular material in the cytoplasm. In the immunohistochemical analysis these cells stain positively with monocyte/macrophage markers (CD68 and CD45), as well as with certain cytokines (tumor necrosis factor-α, interleukin 1ß and interleukin 6). Moreover, recent reports suggest an osteoclastic nature of the infiltrating cells, as they stain strongly with osteoclast tissue lytic markers including tartrate-resistant acid phosphatase and cathepsin K. We report a case of MRH presenting with clinical features of dermatomyositis. Furthermore, the patient showed elevated cytokine serum levels that lowered after therapy.

Case for diagnosis. Benign cephalic histiocytosis.

The present paper reports a case of benign cephalic histiocytosis in a 15-month baby boy, who developed multiple papules bilaterally in the malar region with no other associated manifestations. Histopathology revealed a papillary dermal pattern, while immunohistochemistry was negative for S100 and CD1a and positive for CD68. Therefore, diagnosis was established as non-Langerhans cell histiocytosis, based on the clinical, histopathological and immunohistochemical features present.

Multicentric reticulohistiocytosis: an autoimmune systemic disease? Case report of an association with erosive rheumatoid arthritis and systemic Sjogren syndrome.

Multicentric reticulohistiocytosis is a rare, systemic, reactive histiocytic disease of unknown aetiology. Autoimmune diseases have previously been reported in association with multicentric reticulohistiocytosis, but whether this is a true association or mere coincidence is not known. Here, we report the case of a 50-year-old woman who had been diagnosed as suffering from rheumatoid arthritis (RA), four years ago with positive rheumatoid serology was evaluated for multiple asymptotic papulonodules eruption. Histopathologic examination was suggestive of multicentric reticulohistiocytosis. She developed concomitantly Sjogren syndrome with systemic manifestations. Multicentric reticulohistiocytosis may be misdiagnosed as RA, but evaluation of the time course of specific symptoms can greatly help in the correct diagnosis. The possibility of commune etiopathogeny of these affections is discussed.

Multicentric reticulohistiocytosis with S100 protein positive staining: a case report.

Multicentric reticulohistiocytosis is a very rare systemic disease that affects skin, mucosa and joints. We reported a case of a woman with multicentric reticulohistiocytosis who presented typical skin syndromes and arthralgia. Immunohistochemical analysis showed positive staining for S100 protein, which was reported negative in the majority of previously presented cases. Other immunohistochemical markers (CD68(+), CD1a(-), lagerin (-) and complete histologic and clinical picture were specific enough to make the definitive diagnosis of multicentric reticulohistiocytosis. The patient was administered prednisone just when arthritis appeared and we believe that this therapy protected her from the development of destructive arthritis. No autoimmune disease or internal malignancy was observed during 12-month follow up.

[Characteristics of chronic active Epstein-Barr virus infection-associated hematological disorders in children].

The aim of this study was to analyze characteristics of chronic active Epstein-Barr virus (CAEBV) infection associated hematological disorders in children. Clinical characteristics were summarized; the morphology of hematopoietic cells in bone marrow was observed by microscopy; the lymphocyte subpopulations were analyzed by flow cytometry; the immunophenotype of liver biopsies was assayed by immunohistochemistry; EBV-related antibodies were measured by ELISA; serum EBV-DNA loads were detected by real-time quantitative PCR; EBV-encoded small RNA 1-positive cells in peripheral blood mononuclear cells were identified by in situ hybridization. The results indicated that the clinical manifestations in patients included persistent or recurrent fever, hepatosplenomegaly, liver dysfunction, anemia, thrombocytopenia, systemic inflammatory reaction. Bone marrow presented as hypocellularity, dysmaturation, myelodysplasia and hemophagocytosis. CD8(+) cell high counts were demonstrated in all 4 patients, one of them developed into a T cell lymphoma. Serum EBV-DNA load was 3.26 x 10(3) copies/ml in one patient, EBER1(+) cells were detected at a frequency of 1.7% in PBMNCs from another patient; the titers of IgG to EBV-VCA were >or= 1:5120 in the rest 2 patients. All 4 patients described above were diagnosed as CAEBV infection. In conclusion, the immune-related cytopenia, macrophage activation syndrome and lymphoproliferative disorders are characteristics of CAEBV infection associated hematological disorders in these 4 children patients.

A case of generalized eruptive histiocytosis.

Histiocytoses are a heterogeneous group of diseases, characterized by the accumulation of reactive or neoplastic histiocytes in various tissues. Generalized eruptive histiocytosis belongs to cutaneous non-Langerhans' cell histiocytoses and is a rare, generalized, self-healing disorder that usually follows a benign clinical course. Herein, we report a case of generalized eruptive histiocytosis in a 41-year-old woman with peculiar clinical and histological features. Clinically, the papules showed a marked distribution into the seborrhoeic areas of the trunk, with a great tendency to coalesce. Furthermore, immunohistochemical labelling demonstrated that the histiocytes were positive for CD68, but negative for CD34, S100, CD1a and XIIIa factor. This is the second report of generalized eruptive histiocytosis with a negative XIIIa factor. We discuss the differential diagnoses of the clinical picture and emphasize that this benign cutaneous disorder should be subjected to close follow-up, owing to the possibility of evolution to a more severe type of histiocytosis or the association with underlying diseases. Spontaneous regression was observed in this actual case.

Multicentric reticulohistiocytosis with positive anticyclic citrullinated antibodies.

This is a case report of a woman with multicentric reticulohistiocytosis with positive anticyclic citrullinated antibodies. This patient had been misdiagnosed with rheumatoid arthritis for many years. Recently, she presented with symmetric distal interphalangeal joint destruction and papules along her nail beds. Her clinical presentation, laboratory data, radiographic and histologic findings were all consistent with multicentric reticulohistiocytosis, not rheumatoid arthritis. This is the first case report of a patient with multicentric reticulohistiocytosis that tested positive for anticyclic citrullinated antibodies.

Multicentric reticulohistiocytosis.

Multicentric reticulohistiocytosis is a rare granulomatous disease of unknown etiology, characterized by cutaneous nodules and destructive arthritis. Skin lesions can cause significant deformity, and approximately half of affected patients develop a severe disabling arthritis. The disease is often associated with malignancy; however, the paraneoplastic nature of multicentric reticulohistiocytosis is not established. The diagnosis is confirmed by the presence of oncocytic ("ground-glass") histiocytes and multinucleated giant cells on histopathology of the cutaneous nodules and the synovial membrane.