Pediatric and Developmental Pathology最新文献

Background: Colonic graft-versus-host disease (GVHD) is rare in children. The goal of this study was to evaluate the Lerner and the Farooq grade in pediatric patients.

Methods: Retrospective multicenter study including all biopsies with a diagnosis of GVHD.

Results: 101 patients were included (median age: 8.9 years) with a male predominance (59%). 71% of patients had extracolonic GVHD. 98% and 54% of cases had apoptotic bodies and >6 apoptotic bodies, respectively. Crypt dropout was seen in 53% of cases and ulceration in 19%. Using the Lerner grade, 47% of cases were grade 1, 13% grade 2, 20% grade 3 and 20% grade 4; and using the Farooq grade, 35% were indeterminate for GVHD, 25% low, 27% intermediate and 14% high grade. There was moderate agreement (K = 0.47) between the system. 67% of the Lerner grade 1 cases were considered indeterminate for GVHD using the Farooq grade. No difference was seen with GVHD-related death and the grading systems. GVHD-related death was associated with extraintestinal involvement (P = .04), and with treatment response (P < .01).

Conclusions: Although neither system was associated with GVHD-related death, given the more comprehensive approach, the authors suggest utilizing the Farooq grading system.

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated disease in children that could progress rapidly, and lead to significant morbidity or mortality. ANE's diagnostic challenges render it difficult to recognize and treat in a timely and effective manner. Although infantile-onset cases have been reported, the presentation of ANE in preterm neonates has not been described. Herein, we report a case of a preterm newborn who had a relatively stable clinical course in the first week of life, after which the neonate exhibited sudden deterioration due to progressive encephalopathy with refractory status epilepticus. Despite aggressive management of seizures and sepsis, the patient succumbed. Whole-exome sequencing analyses of the patient and parents were negative. Viral and metabolic testing were non-contributory. An autopsy showed evidence of acute to subacute fulminant liquefactive necrosis with extensive hemorrhage diffusely in the cortex with relative sparing of the cerebellum and the brainstem. A major consideration highlighted by this case is that the adaptive immune response to the immune-mediated or cytokine storm-related proposed etiology of acute necrotizing encephalopathy may differ in preterm compared with full-term infants due to properties dictated by their innate immune responses. Clinical suspicion of ANE should be heightened whenever preterm neonates with early sepsis continue to deteriorate despite aggressive management.

DICER1 syndrome is a heterogeneous cancer predisposition syndrome, characterized by a large variety of benign and malignant tumor types, and caused by germline heterozygous pathogenic variants in the DICER1 gene, which is essential in miRNA processing and RNA interference. The clinical manifestations are diverse, with pleuropulmonary blastoma, Sertoli-Leydig cell tumor, cystic nephroma, uterine cervical embryonal rhabdomyosarcoma, and thyroid follicular nodular disease being the most prevalent tumor types. Since these neoplasms are rare and particularly occur in the pediatric population, pathologists should be aware of the potential relationship of these tumors with an underlying DICER1 syndrome in order to perform or suggest additional molecular pathologic analysis and refer patients and their parents for genetic counseling and testing. This review describes the various DICER1-related tumor types with emphasis on the histological features, reflects on the molecular pathogenesis of DICER1, and aims to raise awareness of this syndrome to facilitate earlier diagnosis.

Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder characterized by deficiency of branched-chain α-keto acid dehydrogenase complex. The affected patients can experience severe metabolic intoxication and encephalopathy in the first few years of life. Liver transplantation is an effective long-term treatment. There has been a lack of histologic description of explanted livers from MSUD patients in the literature.

Methods: A search of the medical record system was performed for cases carrying a diagnosis of MSUD between January 2003 and May 2024. Eight patients who underwent liver transplantation were identified. Their explanted livers were evaluated and their medical records were extensively reviewed.

Results: The weights of explanted livers were within normal range for patients' age. Histologic examination demonstrated features of nodular regenerative hyperplasia (NRH) in 5 (62.5%) liver explants. Other histologic findings included minimal to mild lymphocytic portal inflammation seen in 6 cases and mild steatosis in 2 cases. A detailed review of clinical histories revealed no signs of portal hypertension or specific underlying conditions conducive to NRH development.

Conclusion: NRH is a frequent histologic finding in explanted livers from MSUD patients, although the underlying etiopathogenesis and clinical implication remain to be elucidated.

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Association of CD and aplastic anemia (AA) has been reported in the literature, yet this association remains rare in children. The authors report a case of a previously healthy 4-year-old boy with 1-month history of diarrhea, asthenia, loss of appetite, and weight loss. Laboratory evaluation showed bicytopenia with very severe aregenerative anemia and neutropenia. Bone marrow aspirate and biopsy were performed with findings suggestive of bone marrow aplasia. Further etiological research showed IgA deficiency and increased plasma concentrations of anti-tissue transglutaminase IgG antibodies (anti-tTG IgG 336 U/mL). Patient underwent upper digestive endoscopy confirming diagnosis of CD. The child started a gluten-free diet (GFD) with subsequent clinical and serological improvement. At 12-month post-hospitalization follow-up, the child was asymptomatic, with normal growth rate, resolution of bicytopenia, and anti-tTG IgG lower but still positive (151 U/ml) due to partial adhesion to GFD. To the best of author's knowledge, this is the eighth published pediatric case describing the association of CD with AA. The pathogenesis of this association is not yet fully understood. The authors suggest that CD screening should be considered in patients with unexplained hematological abnormalities.

We report a teenage patient with a delayed diagnosis of compound heterozygous POLG pathogenic variants [(POLG c. 1943 C>G, p.P648R) and (POLG c. 679 C>T, p.R227W)] who presented with fatigue and neuropathy, as well as long standing malnutrition and cachexia, erroneously attributed to an eating disorder. She experienced multiple bowel perforations and pathologic examination revealed jejunal diverticula and features of visceral neuromyopathy. In addition to ganglion cell mega-mitochondrial inclusions, there were multiple foci of interrupted muscularis mucosae, an alteration not previously recognized in the intestines of patients with primary mitochondrial disorders. We provide a detailed account of the gastrointestinal pathologic findings in this patient and compare with prior cases of Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) phenotypes.

Mowat-Wilson Syndrome is an autosomal dominant disorder caused by de novo heterozygous mutations of ZEB2 on 2q22. It is characterized by developmental delay, Hirschsprung's disease, seizures, and a wide variety of malformations affecting the neurologic, cardiac, and genitourinary systems. Reports describing the findings of Mowat-Wilson Syndrome at autopsy are sparse. Case reports of suprasellar spindle cell lipomas are even rarer, a circumstance that contributes to uncertainty regarding their etiology as true neoplasms rather than congenital malformations. Here we report the gross, histopathologic, and molecular findings of a 4-year-old female with Mowat-Wilson Syndrome presenting with sepsis in the setting of otitis media and incidentally found to have a rare suprasellar spindle cell lipoma demonstrating loss of RB1 by immunohistochemistry, suggestive of a neoplastic etiology.

Expression of glypican-3 is seen in a variety of malignant liver neoplasms, such as hepatoblastoma and hepatocellular carcinoma. It is generally not expressed in benign neoplasms and is therefore used as a reliable immunohistochemical marker for distinguishing benign from malignant liver neoplasms. Its expression can also be seen normally in the liver during embryonic development. It has not been described in non-neoplastic liver outside of embryonic development. We present 2 cases of glypican-3 positivity in the background non-neoplastic liver parenchyma of 2 pediatric patients with liver masses.

Introduction: We describe placental findings associated with SARS-CoV-2 infection in pregnancy and any differences between trimester of infection.

Methods: We included 314 pregnant patients who tested positive for SARS-CoV-2 during pregnancy and had their placenta submitted for pathology examination. Trimester of infection was based on the gestational age at the time of infection. Placental pathology was categorized into acute inflammation (AI), chronic inflammation (CI), maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), and divided into none, low-grade, and high-grade. RT-PCR for SARS-CoV-2 was performed on placenta tissue in 238/314 (75%) cases.

Results: The prevalence of AI, CI, FVM, and MVM did not differ by trimester of infection. However, high-grade inflammatory and/or vascular pathology were more prevalent with earlier infection in pregnancy (1st trimester (27/40, 67.5%), 2nd trimester (37/67, 55.2%), and 3rd trimester (82/207, 39.6%, P < .01). Third trimester infection ≤10 days before delivery was associated with a higher prevalence of FVM compared to infection more remote from delivery (46/134, 34.3% vs 14/73, 19.2%; P < .02). We detected SARS-CoV-2 RNA in placenta, in 8/238 (3.4%) of cases.

Conclusion: High-grade inflammatory and/or vascular placental pathology are more prevalent with earlier SARS-CoV-2 infection in pregnancy.

Indian childhood cirrhosis is a chronic liver disease in infants and children. Indian childhood cirrhosis is unique to the Indian subcontinent and occurs from 6 months to 5 years of age. We report 2 cases in a period of 5 years, including 1 male and 1 female. Both children were less than 3 years of age. Presenting complaints were jaundice and hepatosplenomegaly. The clinical diagnosis was metabolic liver disease. Histological findings included diffuse hepatocellular ballooning degeneration, prominent Mallory Denk bodies, diffuse pericellular fibrosis, and marked copper/copper-associated protein deposits, along with the absence of steatosis and glycogenated nuclei. Mettalothionein immunohistochemistry was performed in 1 case and showed strong positivity. The first child developed liver failure and died. The second child was started on oral penicillamine therapy and is alive on the most recent follow-up. Whole-exome studies of both patients showed no significant findings. None of the children had exposure to excess dietary copper. Sporadic cases of Indian childhood cirrhosis continue to occur. There should be greater awareness among pediatricians and pathologists of the disease to enable earlier diagnosis. Awareness of metallothionein expression in biopsies of patients with Indian childhood cirrhosis is important to prevent misdiagnosis of Wilson disease.