Pediatric and Developmental Pathology最新文献

Background: Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date.

Methods: Multicenter retrospective study of pediatric GIT GCT.

Results: A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease.

Conclusion: We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.

A 1-week-old girl died suddenly and unexpectedly. At autopsy the major finding was of a right dominant coronary artery circulation with an inapparent left coronary artery ostium. After careful examination, an anomalous origin of the left coronary artery was found with the ostium located in the non-coronary cusp immediately adjacent to the commissure of the non- and left coronary cusps. The ostium was of small caliber with an obliquely oriented artery (<45°) with no ostial ridges. The artery coursed anteriorly past the left coronary cusp between the aorta and the left atrial appendage to then follow its usual course inferiorly along the anterior aspect of the left ventricle. The reminder of the autopsy was unremarkable. Death was, therefore, attributed to an anomalous and hypoplastic left coronary artery (and ostium) with an acute angle of take-off. Tracing coronary arteries in the very young may be technically difficult due to their small size, thus identifying the location of ostia is important. This may be difficult when the ostium was located close to a commissure.

Acinar dysplasia (AcDys) of the lung is a rare lethal developmental disorder in neonates characterized by severe respiratory failure and pulmonary arterial hypertension refractory to treatment. Recently, abnormalities of TBX4-FGF10-FGFR2-TMEM100 signaling regulating lung development have been reported in patients with AcDys due to heterozygous single-nucleotide variants or copy-number variant deletions involving TBX4, FGF10, or FGFR2. Here, we describe a female neonate who died at 4 hours of life due to severe respiratory distress related to AcDys diagnosed by postmortem histopathologic evaluation. Genomic analyses revealed a novel deleterious heterozygous missense variant c.728A>C (p.Asn243Thr) in TBX4 that arose de novo on paternal chromosome 17. We also identified 6 candidate hypomorphic rare variants in the TBX4 enhancer in trans to TBX4 coding variant. Gene expression analyses of proband's lung tissue showed a significant reduction of TMEM100 expression with near absence of TMEM100 within the endothelium of arteries and capillaries by immunohistochemistry. These results support the pathogenicity of the detected TBX4 variant and provide further evidence that disrupted signaling between TBX4 and TMEM100 may contribute to severe lung phenotypes in humans, including AcDys.

Background: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago.

Methods: Single-center retrospective study of GPLB.

Results: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum.

Conclusion: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.

A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging (MRI) revealed bilateral multicystic uterine adnexa. Exploratory laparotomy was performed at 17 weeks of gestation and bilateral serous ovarian adenocarcinoma FIGO stage IIIC was diagnosed. Complete cytoreductive surgery (CRS) was not feasible at that moment. Nine days after the exploratory laparotomy, immature rupture of membranes and contractions occurred and she delivered a premature boy after 19 weeks of gestation. Pathological examination of the placenta revealed that her ovarian cancer metastasized to the membranes. We describe the first case of ovarian cancer metastasized to the decidua of the placental membranes with histological, immunohistochemical, and molecular confirmation. This case highlights the importance of conscientious evaluation of placenta and membranes in pregnant women with ovarian cancer.

Background: The unexpected observation of calretinin immunoreactivity in smooth muscle cells in the muscularis propria of the cecum led to a more detailed examination of calretinin expression and its possible relationship to propulsive contractile activity around the vermiform appendix.

Methods: Immunohistochemistry and RNA in situ hybridization were performed to analyze calretinin expression in intestinal samples from 33 patients at ages ranging from mid-gestation fetuses to adults, as well as in some potentially relevant animal models. Dual immunolabeling was done to compare calretinin localization with markers of smooth muscle and interstitial cells of Cajal.

Results: Calretinin expression was observed consistently in the innermost smooth muscle layers of the muscularis interna in the human cecum, appendiceal base, and proximal ascending colon, but not elsewhere in the intestinal tract. Calretinin-positive smooth muscle cells did not co-express markers located in adjacent interstitial cells of Cajal. Muscular calretinin immunoreactivity was not detected in the ceca of mice or macaques, species which lack appendices, nor in the rabbit cecum or appendix.

Conclusions: Localized expression of calretinin in cecal smooth muscle cells may reduce the likelihood of retrograde, calcium-mediated propulsive contractions from the proximal colon and suppress pro-inflammatory fecal stasis in the appendix.

Introduction: Blue rubber bleb nevus syndrome (BRBNS) is an uncommon vascular anomaly characterized by multifocal cutaneous, visceral, and other soft tissue or solid organ venous malformations. We observed that BRBNS lesions express immunohistochemical markers of lymphatic differentiation.

Methods: BRBNS histopathologic specimens assessed at our institution during the past 27 years were reviewed. Slides from 19 BRBNS lesions were selected from 14 patients (9 cutaneous, 9 gastrointestinal, and 1 hepatic). We recorded the involved anatomical compartments and presence/absence of thrombi or vascular smooth muscle. Immunohistochemical endothelial expression of PROX1 (nuclear) and D2-40 (membranous/cytoplasmic) was evaluated semi-quantitatively.

Results: Endothelial PROX1 immunopositivity was noted in all specimens; the majority (89.5%) demonstrated staining in more than 10% of cells. D2-40 immunopositivity was present in one-third (33%) of cutaneous lesions and only 1 gastrointestinal lesion.

Conclusion: Endothelial cells in BRBNS almost always express 1 or more immunohistochemical markers of lymphatic differentiation.

Objectives and methods: We analyzed upper endoscopic and histological findings in 3 cohorts of children undergoing upper gastrointestinal endoscopy over a 10-year period. Five hundred seventy-nine patients were identified, with 244 (42%), 199 (35%), and 136 (23%) in the 2011, 2015, and 2019 cohorts, respectively. The most common symptoms and signs were abdominal pain, vomiting, failure to thrive, and diarrhea.

Results: The number of patients who had histological evidence of chronic gastritis increased from 2011 (n = 70, 29%) to 2015 (n = 106, 53%) and 2019 (n = 92, 68%; P < .001). The prevalence of "normal" endoscopic gastric findings was higher in controls (n = 247, 90%) compared to cases (n = 201, 76%; P < .001). There was a small but statistically significant difference in endoscopic esophageal grading (P = .008) over time, with lower grades being more prevalent in 2011 compared to 2015 (P = .026) and 2019 (P = .001). Crude comparisons of the predictors (sex, weight percentile, payor type, month of endoscopy, symptom duration, PPI exposure, and endoscopic stomach findings) yielded no difference between cases and controls.

Conclusions: There has been a significant rise in the prevalence of mild chronic gastritis or non-specific gastritis over the last decade in our population.