Pediatric and Developmental Pathology最新文献

Pulmonary cystic lesions in infants are uncommon and can present diagnostic challenges due to overlapping radiologic features with other cystic lung conditions. We present 2 cases of left lung cystic lesions in infants. Initial high-resolution computed tomography (HRCT) suggested differential diagnoses, including pneumatocele, type I congenital pulmonary airway malformation (CPAM), or a solitary cystic lymphangioma. Definitive diagnosis was achieved through histopathological examination after left lower lobectomy and resection of the lesion. These cases highlight the challenges in accurately diagnosing pulmonary cystic lesions, given the limitations of imaging alone.

Background: Chorionic histiocytic hyperplasia (CHH) is a chronic inflammatory lesion (CIL) with a linear infiltrate of fetal histiocytes in the base of fetal or membranous chorion. We performed a retrospective study of placentas diagnosed since our last study period in order to analyze the strength of the association of CHH with other CIL.

Methods: Third trimester placentas diagnosed with CHH were identified in our LIS. Comparisons of incidence of associated lesions, including chronic villitis (CV), chronic deciduitis (CD), chronic chorioamnionitis (CC), eosinophilic/T-cell chorionic vasculitis (ETCV), and maternal and fetal acute inflammatory responses, between the prior and current studies were evaluated using the chi square statistic.

Results: CHH was present in 2.2% of placentas, significantly higher than 1.3% in the prior study period. A majority of CHH cases had accompanying CV (82.3%). CD was more often associated with CHH in the current study than in the prior study (49.1% vs 40.0%).

Conclusions: The greater incidence of CHH in third trimester placentas diagnosed in the past 7.5 years may be due to greater recognition of the lesion by our pathologists. This study demonstrated the need for more research of CIL.

Campomelic dysplasia (CD) is a rare skeletal dysplasia typically associated with a high neonatal mortality rate due to respiratory insufficiency. The condition is due to mutations in the SOX9 gene, which affects skeletal and sexual development. Mutations further away from this gene result in a milder condition, and thus some of those affected live into adulthood. Due to SOX9's effect on sexual development, there is sex reversal in approximately 75% of genotypic males (46XY). This report presents a unique case of a 1-year-old phenotypic female with a 46XY karyotype, diagnosed with CD, gonadal dysgenesis, and bilateral gonadoblastoma. The patient exhibited non-ambiguous female genitalia and a uterus but had undescended streak gonads. The streak gonads were surgically removed due to the increased risk of malignancy. Histological analysis revealed a right-sided streak gonad with multiple foci of dissecting gonadoblastoma and a left-sided streak gonad with classic gonadoblastoma. While the patients' gene break point lies at the 17q23.1 locus, outside of the widely accepted SOX9 region, there may be reason to believe her mutation is affecting the SOX9 gene. This case shows the importance of early diagnosis and intervention with gonadectomy in patients with campomelic dysplasia or other sex reversal disorders.

Teratocarcinosarcoma is rare malignant sinonasal neoplasm with immature and malignant endodermal, mesodermal, and neuroepithelial elements resembling immature teratoma, commonly with SMARCA4 loss or activating CTNNB1 mutation. The carcinoma component may be either squamous or adenocarcinoma and the mesenchymal component may be composed of spindle cells, cartilage, bone, smooth muscle, or skeletal muscle. Due to the uncommon nature of this malignancy, there are frequently diagnostic difficulties that result in management problems. Herein we report a teratocarcinosarcoma arising in the nasal cavity of a 13-year-old boy with CTNNB1 activating mutation and copy number variations by next-generation sequencing along with an abnormal karyotype. This tumor must be included in the differential of neoplasms with immature elements, more likely seen in pediatric patients.

Pediatric pancreatic acinar cell carcinoma (PACC) is a rare malignancy, comprising 5-15% of pediatric pancreatic tumors. BRAF rearrangement is found in 20%-30% of PACC cases. We report a case of PACC with a novel GLCCI1::BRAF fusion and independent amplifications in MYC and MYCN. A 10-year-old male presented with 6 months of weight loss, back pain, and loose stools. Imaging demonstrated concentric soft tissue thickening around the superior mesenteric artery, prompting biopsy of a periaortic lymph node showing metastatic PACC. Pancreaticoduodenectomy revealed PACC and metastatic deposits in multiple lymph nodes and retroperitoneal soft tissue. Fluorescence in situ hybridization of both the periaortic lymph node and pancreaticoduodenectomy specimens demonstrated BRAF gene rearrangement, with the partner identified as GLCCI1 by next generation sequencing and fusion assays. Chromosomal microarray analysis demonstrated amplification of MYC in the periaortic lymph node biopsy and amplification of MYCN in the resection specimen. The patient was treated with neoadjuvant chemotherapy, radiation, and a pan-RAF inhibitor, but developed new widespread metastasis and was deceased 22 months after presentation. The combination of the primary GLCCI1::BRAF fusion with secondary amplification of MYC and MYCN is likely to drive the aggressive behavior and metastasis in this case of PACC.

Hirschsprung disease (HD) is a disorder caused by the failed migration of neural crest cells, resulting in abnormal innervation of the colon. Histologic hallmarks include the absence of ganglion cells and the presence of hypertrophic nerve fibers. At present, an immunostain for calretinin is the most used ancillary study. The supportive staining pattern for HD is the absence of immunoreactive ganglion cells and mucosal nerve fibers (neurites). While studying a patient with mantle cell lymphoma involving the colon, we observed a similar immunoreactive pattern for ganglion cells and neurites with anti-BCL-1 and hypothesize that this immunostain might complement calretinin staining. To test this hypothesis, we prospectively collected biopsy and resection specimens from patients clinically suspected of having HD. BCL-1 immunoreactive ganglion cells and/or mucosal neurites were observed in 10 biopsy specimens of patients without HD while these elements were absent in biopsy and affected areas of resection specimens in 12 patients with HD. The staining of ganglion cells and neurites dependent of the source of the antibody used. The parallel negative staining of neural elements with 2 unrelated antibodies provides credence to the absence of immunoreactivity for calretinin in the diagnostic workup of patients suspected of having HD.

Acute respiratory distress in a neonate is a potentially critical condition with multiple possible causes. Developmental etiologies are particularly problematic by virtue of being refractory to routine modalities for enhancing ventilation and oxygen exchange. Some genetic causes of neonatal respiratory distress, such as surfactant protein deficiencies and alveolar capillary dysplasia with misalignment of pulmonary veins, are well known, and sequencing panels have been formulated to detect them. We present a case of fatal neonatal respiratory insufficiency in which the autopsy showed primary pulmonary hypoplasia and congenital alveolar dysplasia. A sequencing panel of genes associated with heritable pulmonary disorders gave a normal result; however, a chromosomal microarray identified a heterozygous deletion encompassing the TBX4 gene on chromosome 17. Haploinsufficiency for TBX4 is a known cause of disturbed pulmonary development. This case illustrates why work-up of pulmonary developmental disorders must look beyond standard sequencing panels in some instances, if rare causes of pulmonary maldevelopment such as deletions causing haploinsufficiency are not to be missed.

Osteopetrosis is a rare metabolic bone disease that can lead to progressive bone marrow failure if left untreated. Resulting cytopenia and extramedullary hematopoiesis are frequently encountered in autosomal recessive form of the disease (ARO) and may result in death. Recurrent bone fractures and skeletal deformities are mostly seen in autosomal dominant form osteopetrosis (ADO) and cause significant morbidity. In this report, clinical, laboratory, and radiological findings of 5 patients with osteopetrosis were presented. Three had cytopenias, typical peripheral smear, and bone marrow aspiration findings regarding bone marrow failure as well as extensively increased bone density which was a classical radiological appearance. Two of them had TCIRG1 mutations associated with ARO, died because of severe infections. One with certain findings of ARO without genetic analysis is alive after hematopoietic stem cell transplantation. Two siblings had novel variants of CLCN7 (NM_001114331) p.Val755Serfs*4 (c.2263del) heterozygocity, associated with ADO and severe skeletal problems. One had been followed up also for nephrotic syndrome. Detection of genetic abnormalities is important as well as typical physical examination findings and, presence of hematological or radiological indicators in definitive diagnosis of the disease. Although osteopetrosis is rare, it is a potentially fatal disease that should be considered in the differential diagnosis.

NUT carcinoma is challenging to diagnose and may mimic a germ cell tumor (GCT) due to raised serum alpha-fetoprotein (AFP). A 15-year-old patient presented with back pain and cough. Investigation revealed a mediastinal mass and multiple bone metastases. Serum AFP was highly elevated, consistent with a metastatic malignant nonseminomatous GCT. Aggressive chemotherapy was initiated with initial response, unfortunately not sustained. Diagnostic biopsy showed undifferentiated tumor cells with weak GCT immunophenotype but was ultimately non-diagnostic. Serum miR-371a-3p levels, highly sensitive/specific for malignant GCTs, were negative casting diagnostic suspicion. Routine use of agnostic molecular investigations, including whole genome sequencing, identified a chromosome 15:19 translocation, with BRD4::NUTM1 gene fusion on RNA sequencing, confirming NUT carcinoma. Subsequent NUTM1 immunohistochemistry was positive. A high index of clinical suspicion is required for non-pathologically/molecularly confirmed diagnoses. Serum miR-371a-3p quantification ruled out malignant GCT and routine agnostic molecular studies identified the correct diagnosis; a low threshold for NUTM1 immunohistochemistry is thus recommended.