查看更多>>摘要：Background Granulomatous lymphocytic interstitial lung disease (GLILD) has been increasingly recognized in children affected with primary immunodeficiencies (PIDs). In this study, we aimed to better characterize the spectrum of pediatric PIDs coexisting with GLILD including clinical and immunological predictors, thoracic imaging findings, and histopathologic features. Methods We respectively reviewed records of six representative cases of children, three of them affected with common variable immunodeficiency (CVID) and three with syndromic immunodeficiencies, in whom a diagnosis of GLILD was established based on clinical, radiological, and histopathologic findings. Clinical and immunological predictors for GLILD were also analyzed in the patients studied. Results All the children with GLILD had a history of autoimmune phenomena, organ-specific immunopathology, and immune dysregulation. Defective B-cell maturation and deficiency of memory B cells were found in all the children with GLILD. The radiological and histopathological features consistent with the diagnosis of GLILD, granulomatous disease, and lymphoid hyperplasia, were accompanied by chronic airway disease with bronchiectasis in children with CVID and syndromic PIDs. Conclusions Our study shows that both CVID and syndromic PIDs may be complicated with GLILD. Further studies are required to understand the predictive value of coexisting autoimmunity and immune dysregulation in the recognition of GLILD in children with PIDs.
Hasan, Shaina H.Taylor, SteveGarg, ShipraBuras, Matthew R....
10页
查看更多>>摘要：Background Diagnosis of non-esophageal eosinophilic gastrointestinal disorders requires quantification of tissue eosinophils. Our objective was to evaluate eosinophil peroxidase (EPX) immunohistochemistry (IHC) as a method for histologic diagnosis of eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD). Methods We performed a retrospective analysis of biopsies from pediatric EG/EoD cases and controls. Subjects with EG or EoD had >= 30 eosinophils per high power field (eos/hpf) in >= 5 hpf in the stomach and/or >= 3 hpf in the duodenum, respectively. Controls had no histopathologic diagnosis recorded. Tissue eosinophil counts were assessed by hematoxylin & eosin stains. EPX stains were assessed using a unique histopathologic scoring system. Slides were digitized and EPX+ staining area/mm(2) was quantified by image analysis. Results Twenty-six EG/EoD cases and 40 controls were analyzed. EPX scores and EPX/mm(2) levels were markedly elevated in EG/EoD (p <= 0.0001). Eosinophil density (eos/mm(2)) correlated strongly with EPX scores and EPX/mm(2) levels in the stomach (r >= 0.77) and moderately with EPX scores and EPX/mm(2) levels in the duodenum (r >= 0.52); (p < 0.0001). EPX quantification identified EG/EoD subjects with high diagnostic accuracy (EPX score: AUC = 1 for EG and EoD; EPX/mm(2): AUC = 0.98 (95%CI 0.96-1) for EG, AUC = 0.91 (95%CI 0.81-1) for EoD). Conclusion EPX-based assessment of eosinophilic inflammation may facilitate automated histologic diagnosis.
Alipour, ZahraSchultz, Kris Ann P.Chen, LingHarris, Anne K....
8页
查看更多>>摘要：Introduction Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic DICER1 variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB. Material and Methods Cases were collected from departmental archives and the International PPB/DICER1 Registry. Immunohistochemistry (IHC) for PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) genes were performed. In addition, normal-tumor paired whole exome sequencing (WES) was performed in two cases. Results Twenty-five PPB cases were studied, consisting of Type I (n = 8, including 2 Ir), Type II (n = 8) and Type III (n = 9). PD-L1 combined positive score (CPS) of 1, 4 and 80 was seen in three (3/25, 12.0%) cases of Type II PPB with negative staining in the remaining cases. PD-1 and CD8 stains demonstrated positive correlation (P < .05). The density of PD1 and CD8 in the interface area was higher than within tumor (P < .05). The MMR proteins were retained. TMB was 0.65 mutations/Mb in type II PPB with high expression of PD-L1, and 0.94 mutations/Mb in one negative PD-L1 case with metastatic tumor. Conclusion A small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.
查看更多>>摘要：Introduction Gastroschisis is a congenital malformation characterized by intestinal herniation through an abdominal wall defect. Despite its unknown pathogenesis, known risk factors include maternal smoking, alcohol use, and young maternal age. Previous work has shown that gastroschisis is associated with placental delayed villous maturation, and the goal of this study was to assess for additional associated placental pathologies that may help clarify the pathogenesis of gastroschisis. Methods We conducted a retrospective slide review of 29 placentas of neonates with gastroschisis. Additionally, we reviewed pathology reports from one control group of 30 placentas with other congenital malformations. Gross and histological data were collected based on a standardized rubric. Results Gastroschisis was associated with increased placental fetal vascular malperfusion (FVM) in 62% of cases (versus 0% of controls, p < 0.0001). It was also associated with increased placental villous maldevelopment in 76% of cases (versus 3% of controls, p < 0.0001). Conclusion Our study demonstrates an association between gastroschisis and FVM. While FVM could be the consequence of vascular disruption due to the ventral location of gastroschisis, it could also reflect estrogen-induced thrombosis in early pregnancy. Further research is needed to separate these possibilities and determine the cause of the placental FVM observed in gastroschisis.
Rytting, HeatherDureau, Zachary J.Vega, Jose VelazquezRogers, Beverly B....
9页
查看更多>>摘要：Background Absent submucosal ganglion cells in biopsies 1-3 cm above the pectinate line establishes the pathologic diagnosis of Hirschsprung Disease (HD). Calretinin stains both ganglion cells and their mucosal neurites and has gained importance in HD diagnosis. Absent calretinin positive mucosal neurites in biopsies at the appropriate level above the pectinate line is highly specific for HD. Whether this applies to lower biopsies is uncertain. To address this, we studied anorectal canal autopsy specimens from infants. Methods We performed an autopsy study of infant anorectal canal specimens to describe calretinin staining in this region. Calretinin staining was correlated with histologic and gross landmarks. Results In all 15 non-HD specimens, calretinin positive mucosal neurites were present in glandular mucosa up to the anorectal line where neurites rapidly diminished. Age range was preterm 26 weeks to 3 months. Conclusions Calretinin positive mucosal neurites are present in glandular mucosa up to the anorectal line in young infants. This is potentially important regarding neonatal HD biopsy level and diagnosis. Positive calretinin staining at the anorectal line favors normal innervation making HD unlikely. Absent calretinin positive neurites in glandular mucosa is worrisome for HD in young infants, regardless of location.
De Guzman, John KemuelYu, Weimingde Koning, LawrenceHorn, Christopher...
3页
查看更多>>摘要：Background 4-11% of umbilical cords contain vitelline vessel remnants (VVRs). A recent study has described neutrophilic inflammation arising from VVRs and suggested an association with amniotic fluid infection (AFI). Methods During routine placental pathology sign-out over a six month period, we identified 70 cords with VVRs. HE-stained sections were re-examined for "VVR-derived funisitis," which was classified as low or high grade/stage based upon whether neutrophils were present only in Wharton's jelly near the VVRs or whether neutrophils were also present near the cord's amniotic surface. The same placentas were also examined for histologic evidence of AFI (maternal response = acute chorionitis or chorioamnionitis vs. fetal response = chorionic vasculitis, umbilical vasculitis, or funisitis vs. both). Results Neutrophilic inflammation arising from VVRs was present in 54.3% (38/70); 15 and 23 lesions were low and high grade/stage, respectively. "VVR-derived funisitis" was strongly associated with histological evidence of AFI elsewhere in the placenta. Its overall sensitivity and specificity were 0.94 and 0.88; when VVR-derived funisitis was high grade/stage or diagnosed in the third trimester, specificity rose to 1.0. Conclusion "VVR-derived funisitis" has a strong association with histological evidence of AFI.
Hughes, Caitlin E.Correa, HernanBenedetti, Daniel J.Smith, Brianna...
5页
查看更多>>摘要：Infantile/congenital fibrosarcoma (IFS) is the most common soft tissue tumor in children less than one year of age. The most common anatomic site of IFS is in the extremities or trunk, and rarely in the abdomen or retroperitoneum. Approximately 70-90% of cases are characterized by a distinct t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. As such, TRK inhibitors are considered frontline therapy in TRK-fusion positive IFS. The ETV6-NTRK3 fusion is also detected in congenital mesoblastic nephroma (CMN) and less frequently in myeloid leukemias, secretory breast carcinoma, and mammary-type secretory carcinoma of the skin and salivary glands. Infrequently, cases of tumors with IFS-like morphology without the characteristic ETV6-NTRK3 gene fusion have been identified. Herein, an ETV6-NTRK3 fusion negative spindle cell sarcoma with IFS-like morphology subjected to genomic profiling revealed a PDE10A-BRAF fusion, a fusion event that has been detected previously in an isolated case of undifferentiated infantile sarcoma.
查看更多>>摘要：Chagas disease, once confined to rural Latin America is an increasing public health concern in non-endemic countries due to population movements. Here we present an unexpected finding of a placenta infected with T. cruzi from a Brazilian woman residing in Ireland. Histology of the placenta showed a lymphocytic chorioamnionitis with multinucleated giant cells (MNGCs) as well as cord vasculitis and funisitis. Amastigotes of trypanosomiasis were found in both cord and membranes. The placenta parenchyma, however, had no villitis or amastigotes and maturation was appropriate for gestation. To date, there have been few reported cases of vertical transmission in non-endemic countries. We discuss the histological findings and review the literature on potential modes of transmission from mother to fetus.
Papke, David J., Jr.Fisch, Adam S.Ranganathan, SarangarajanO'Neill, Allison...
6页
查看更多>>摘要：Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive neoplasm that occurs predominantly in children. Like mesenchymal hamartoma of the liver (MHL), UESL harbors recurrent rearrangements involving 19q13.3 and 19q13.4, a region of the genome that contains a primate-specific cluster of micro-RNAs. Here, we present a case of a high-grade neoplasm that arose in the left hepatic lobe of a 5-year-old male and gave rise to widespread lymph node, visceral, and soft tissue metastases. The tumor was composed of sheets, tubules, and papillae of epithelioid cells with rhabdoid morphology. INI1 and BRG1 expression were retained. Tumor cells diffusely expressed epithelial markers, including multiple keratins. While the morphologic and immunophenotypic features were suggestive of poorly differentiated carcinoma with rhabdoid features, the tumor was found to harbor the t(11;19)(q13;q13.3) translocation characteristic of UESL, as well as a TP53 mutation. Given the clinical presentation, imaging, clinical course, the tumor was classified as UESL with unusual, carcinoma-like histopathologic features. In the context of an unclassified high-grade hepatic tumor in a young child, molecular or cytogenetic testing for chromosome 19q13 alterations should be considered.
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