Cytogenetic signatures of recurrent pregnancy losses.

Objectives: To investigate the incidence of chromosomal abnormalities in the products of conception (POC) of patients with spontaneous miscarriages (SM) and with recurrent pregnancy losses (RPL) and to determine biological mechanisms contributing to RPL.

Methods: During a 20-year period, 12 096 POC samples underwent classical chromosome analysis. Cytogenetic findings were compared between the SM and RPL cohorts.

Proteinaceous Lymphadenopathy in a Young Patient With History of Classical Hodgkin Lymphoma: A Case Report With Literature Review.

Proteinaceous lymphadenopathy (PLD) is a poorly defined, underreported pathological entity of uncertain etiology characterized by massive deposition of amorphous, eosinophilic, and periodic acid-Schiff-positive material involving lymph nodes, which is distinct from amyloid and clonal immunoglobulin deposition. PLD can resemble collagen sclerosis and needs to be differentiated from lymphomas with sclerosis, particularly classical Hodgkin lymphoma, nodular sclerosis type, and therefore is an important pitfall in the diagnosis of lymphoma with sclerosis. We are reporting a young patient with history of classical Hodgkin lymphoma who eventually developed PLD and review the literature on this subject.

Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes within affected tissues. RDD, which now belongs to the R group of the 2016 revised histiocytosis classification, is a widely heterogeneous entity with a range of clinical phenotypes occurring in isolation or in association with autoimmune or malignant diseases. Recent studies have found , , , and mutations in lesional tissues, raising the possibility of a clonal origin in some forms of RDD.

CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions.

Background: Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS-LCH.

Methods: Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in CSF from patients with CNS-LCH lesions compared with patients with brain tumors and other neurodegenerative conditions.

Predicting Cellular Rejection With a Cell-Based Assay: Preclinical Evaluation in Children.

Background: Allospecific CD154+T-cytotoxic memory cells (CD154+TcM) predict acute cellular rejection after liver transplantation (LTx) or intestine transplantation (ITx) in small cohorts of children and can enhance immunosuppression management, but await validation and clinical implementation.

Methods: To establish safety and probable benefit, CD154+TcM were measured in cryopreserved samples from 214 children younger than 21 years (National Clinical Trial 1163578). Training set samples (n = 158) were tested with research-grade reagents and 122 independent validation set samples were tested with current good manufacturing practices-manufactured reagents after assay standardization and reproducibility testing.

Nosology and Pathology of Langerhans Cell Histiocytosis.

The classification of the histiocytoses has evolved based on new understanding of the cell of origin as a bone marrow precursor. Although the pathologic features of the histiocytoses have not changed per se, molecular genetic information now needs to be integrated into the diagnosis. The basic lesions of the most common histiocytoses, their patterns in different sites, and ancillary diagnostics are now just one part of the classification.

Langerhans cell histiocytosis and Erdheim-Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAF(V600E) mutation.

Langerhans cell histocytosis (LCH) and Erdheim-Chester disease are two rare histiocytic disorders. Their occurrence in the same patient is more infrequent, but has been described. We report a case of a 38-year-old woman who presented with a diagnosis of single system cutaneous LCH.

The Role of ARF6 in Biliary Atresia.

Background & Aims: Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA).

Methods: To identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data.

Inflammatory myofibroblastic tumor of the bladder masquerading as eosinophilic cystitis: case report and review of the literature.

A 9-year-old boy presented with gross hematuria of 2 days duration. Cystoscopic evaluation revealed an anterior bladder mass. Pathology was consistent with eosinophilic cystitis, and a steroid regimen was initiated accordingly, but no improvement ensued.

Histologic patterns of thymic involvement in Langerhans cell proliferations: a clinicopathologic study and review of the literature.

Thymic involvement by Langerhans cell histiocytosis (LCH) has been described mainly in isolated case reports. A description of the histopathologic patterns of LCH proliferations in the thymus, together with therapeutic implications, has not, to our knowledge, been previously addressed. The pathology consultation files at Children's Hospital of Pittsburgh of the University of Pennsylvania Medical Center were reviewed for cases of thymic involvement by LCH.

Atypical Hemolytic Uremic Syndrome and Chronic Ulcerative Colitis Treated with Eculizumab.

Background: Hemolytic-uremic syndrome (HUS) presents with hemolytic anemia, thrombocytopenia, and thrombotic microangiopathy of the kidney and usually results from Shiga-toxin induced activation of the alternative complement pathway. Gastroenteritis is a common feature of the Shiga-toxin producing HUS, referred to as STEC-HUS. An inherited or acquired complement dysregulation may lead to HUS referred to as non-STEC or atypical (a)HUS.

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.

Background: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management.

Objectives: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients.

Methods: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness.

Ciliary inclusion disease: report of a new primary ciliary dyskinesia variant.

Biopsies from 6 children with clinical presentations suggestive of primary ciliary dyskinesia (PCD) displayed respiratory epithelial cells with disorganized accumulations of basal bodies within the cytoplasm and large intracytoplasmic vesicles into which projected numerous microvilli and cilia. Microvilli, but few cilia, were present at the cell surface. Ultrastructural study revealed a variety of nonspecific abnormalities but demonstrated the cilia generally to be morphologically normal, suggesting that the cause of cilia malfunction was not any recognized primary cause or secondary effect.

Langerhans cell sarcoma: case report and review of world literature.

Langerhans cell sarcoma is a rare malignancy with only 1 pediatric case (less than 15 y of age) reported. Here, we report the second case of Langerhans cell sarcoma in a child who presented with cord compression. This patient was treated with extensive surgical resection, postoperative chemotherapy, and involved-field radiation therapy.

Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy.

Histiocytic sarcoma (HS) is a malignant tumor composed of proliferating cells of histiocytic origin. True HS is exceedingly rare, particularly in pediatric patients. These tumors are frequently aggressive, and outcome for patients with HS has traditionally been poor.

Bullous Sweet's syndrome after granulocyte colony-stimulating factor therapy in a child with congenital neutropenia.

We present the case of a 20-month-old boy with congenital neutropenia for which he was being treated with granulocyte colony-stimulating factor (G-CSF) who developed bullous Sweet's syndrome. Because of the challenging and extensive differential diagnosis of an acute bullous eruption in an immunocompromised child, we highlight the importance of a prompt and precise diagnosis before initiation of any systemic therapy in children with Sweet's syndrome.

Langerhans Cell Sarcoma Arising from Chronic Lymphocytic Lymphoma/Small Lymphocytic Leukemia: Lineage Analysis and BRAF V600E Mutation Study.

Background: the phenomenon that histiocytic/dendritic cell sarcomas may be transformed from lymphoproliferative diseases is dubbed 'transdifferentiation'. Langerhans cell sarcoma (LCS) transdifferentiated from chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) is extremely rare. The underlying mechanisms of LCS tumorogenesis and its transdifferentiation from CLL/SLL are largely unknown.

Pathology of central nervous system posttransplant lymphoproliferative disorders: lessons from pediatric autopsies.

Posttransplant lymphoproliferative disorders (PTLD) involving the central nervous system (CNS) in children are uncommon and can prove diagnostically challenging. The clinical and imaging characteristics of CNS PTLD can overlap with those of infection, hemorrhage, and primary CNS tumors. Some cases of CNS PTLD remain clinically unsuspected and are diagnosed postmortem.

Optic pathway glioma as part of a constitutional mismatch-repair deficiency syndrome in a patient meeting the criteria for neurofibromatosis type 1.

Patients with constitutional mismatch repair-deficiency (CMMR-D) caused by the biallelic deletions of mismatch repair (MMR) genes have a high likelihood of developing malignancies of the bone marrow, bowel, and brain. Affected individuals often have phenotypic features of neurofibromatosis type 1 (NF-1), including café-au-lait spots. Optic pathway gliomas (OPGs), a common manifestation of NF-1, have not been reported.

A novel TCIRG1 gene mutation leads to severe osteopetrosis with altered content of monocytes/macrophages in several organs.

Osteopetrosis (OP) is a clinically and genetically heterogeneous disease. Defects in the TCIRG1 gene are most frequently implicated in the osteoclast-rich form of OP. Little is known about the content and/or function of monocytes and macrophages of various organs rich in those cells in patients with OP.

Cytomorphology of Erdheim-Chester disease presenting as a retroperitoneal soft tissue lesion.

Erdheim-Chester disease (ECD) is a rare, multisystem disorder of macrophages. Patients manifest with histiocytic infiltrates that lead to xanthogranulomatous lesions in multiple organ systems. The cytologic features of this disorder are not well characterized.

Current status of pediatric intestinal failure, rehabilitation, and transplantation: summary of a colloquium.

An international symposium convened September 9-11, 2010, in Chicago to present the state of the art and science of the multidisciplinary care of intestinal failure in children. Medical and surgical management of the child with intestinal failure was presented with a focus on the importance of multidisciplinary intestinal failure management. Issues of timing of referral and benefit risk analysis for intestine "rehabilitation" and transplant were presented.

Increased expression of peripheral blood leukocyte genes implicate CD14+ tissue macrophages in cellular intestine allograft rejection.

Recurrent rejection shortens graft survival after intestinal transplantation (ITx) in children, most of whom also experience early acute cellular rejection (rejectors). To elucidate mechanisms common to early and recurrent rejection, we used a test cohort of 20 recipients to test the hypothesis that candidate peripheral blood leukocyte genes that trigger rejection episodes would be evident late after ITx during quiescent periods in genome-wide gene expression analysis and would achieve quantitative real-time PCR replication pre-ITx (another quiescent period) and in the early post-ITx period during first rejection episodes. Eight genes were significantly up-regulated among rejectors in the late post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY, SLAMF7, TGFBR3, NKG7, SYNE1, and GK5.