Pancreatoblastoma is a rare malignancy that primarily affects children and involves abnormalities in the WNT/β-catenin signaling pathway. It demonstrates diverse differentiation mimicking fetal pancreatic development res...Pancreatoblastoma is a rare malignancy that primarily affects children and involves abnormalities in the WNT/β-catenin signaling pathway. It demonstrates diverse differentiation mimicking fetal pancreatic development resulting in different histologic patterns including variable acini, ducts, and neuroendocrine cells, often with distinct squamoid nests. We present a notable case of pancreatoblastoma in a 5-year-old girl, who was found to have a large solid mass in her pancreatic tail with elevated blood AFP levels. Histologically, the tumor showed primitive epithelial cells with partial endocrine differentiation and focal squamoid features. Molecular testing detected and mutations, along with numerous copy number alterations. mutations have never been reported in pancreatoblastoma to our best knowledge. The case expands the genetic landscape of pancreatoblastoma and may be helpful for identification of a targeted therapy in the future.
Däniker M, Baleydier F, Rock NM
… +4 more, Menzinger S, Wildhaber BE, McLin VA, Rougemont AL
Pediatr Dev Pathol
· 2026 · PMID 41170802
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Liver involvement by histiocytic and dendritic cell neoplasms signals high-risk disease, often necessitating closer monitoring and aggressive management. Severe cases may progress to liver failure, requiring transplantat...Liver involvement by histiocytic and dendritic cell neoplasms signals high-risk disease, often necessitating closer monitoring and aggressive management. Severe cases may progress to liver failure, requiring transplantation. Liver involvement occurs in about one-third of patients with systemic juvenile xanthogranuloma (JXG) and 20% to 60% of pediatric patients with Langerhans cell histiocytosis (LCH), particularly in multiorgan disease. Tyrosine kinase inhibitors show promise in LCH treatment, but optimal timing for treatment cessation remains uncertain. We present 2 pediatric cases, 1 with LCH, and the other with disseminated JXG, along with a literature review emphasizing liver histopathology and transplant considerations. These cases highlight distinct histological patterns. In LCH, progressive bile duct destruction led to ductopenic cholestatic cirrhosis and secondary sclerosing cholangitis. In contrast, in the case of JXG, bile ducts remained intact despite being surrounded by histiocytes. In both, disease localization to larger, segmental portal tracts may reduce liver biopsy sensitivity. In LCH, BRAF inhibitor therapy triggered a granulomatous reaction that could mimic disease recurrence in the liver graft. Other histiocytoses typically spare the bile ducts and do not cause biliary cirrhosis. Recognizing these distinct infiltration patterns can aid diagnosis and management.
Nevus lipomatosus superficialis (NLS) is an uncommon benign skin lesion and characterized by aggregates of mature adipose tissue ectopically among the collagen bundles of the dermis. The precise etiology of NLS remains p...Nevus lipomatosus superficialis (NLS) is an uncommon benign skin lesion and characterized by aggregates of mature adipose tissue ectopically among the collagen bundles of the dermis. The precise etiology of NLS remains poorly understood, and it is classified as a cutaneous hamartoma in the WHO Classification of Skin Tumors, 5th edition. This is a case report of recurrent classical Hoffmann-Zurhelle form of NLS on a 3-year-old male child's hand. Immunohistochemical stains revealed diffusely PLAG1 positive expression in the lesional stellate stromal cells and adipocytes. Ancillary molecular testing by RNA fusion panel showed COL3A1::PLAG1 rearrangement. These findings suggest that some cases of NLS may share genetic alterations with neoplastic processes involving PLAG1 rearrangements.
INTRODUCTION: Triplet pregnancies have risen in recent decades due to assisted reproductive technology (ART) and are considered high-risk. Placental evaluation is crucial to understanding their outcomes, yet pathological...INTRODUCTION: Triplet pregnancies have risen in recent decades due to assisted reproductive technology (ART) and are considered high-risk. Placental evaluation is crucial to understanding their outcomes, yet pathological findings in triplet placentas remain poorly described. DESIGN: Retrospective observational study including all triplet pregnancies followed at a tertiary referral hospital from January 2000 to December 2024, whose placentas were submitted for pathological analysis. Gross and microscopic findings were reviewed. RESULTS: We analyzed 111 triplet pregnancies (333 fetuses). Fetal loss (miscarriage or stillbirth) occurred in 7.5%. ART accounted for 70.3% of conceptions. Median gestational age at delivery was 32 weeks (P25 = 30; P75 = 34), with 50.4% being trichorionic triamniotic. Mean placental weight was 869 ± 243 g, and median size was 22.5 cm (P25 = 18; P75 = 30). Abnormal umbilical cord insertion was found in 52.2% of cases. Central or peripheral infarcts were present in 43.8% of placentas. The most common histological findings were accelerated villous maturation (65.1%), chorangiosis (53.7%), intervillous fibrin deposits (29.4%), and villous edema (24.3%). Chronic villitis of unknown etiology was the most frequent inflammatory lesion (9.3%). CONCLUSIONS: Triplet placentas exhibit high rates of pathological abnormalities, which may contribute to adverse outcomes. Future studies should explore associations with ART and chorionicity.
Tulonen N, Tallus J, Kaprio H
… +4 more, Laine J, Mattila M, Haanpää M, Keskinen S
Pediatr Dev Pathol
· 2026 · PMID 41099604
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Congenital diaphragmatic hernia is a genetically heterogeneous condition with a developmental defect in the diaphragm. The gene is essential for fetal heart development, and pathogenic variants are a known cause of str...Congenital diaphragmatic hernia is a genetically heterogeneous condition with a developmental defect in the diaphragm. The gene is essential for fetal heart development, and pathogenic variants are a known cause of structural congenital heart diseases. Haploinsufficiency of GATA4 is also associated with diaphragmatic hernia. Pathogenic sequence variants with isolated diaphragmatic hernia in the absence of congenital heart defects are extremely rare. Our report expands the phenotypic spectrum related to .We report a fetus with a prenatal isolated diaphragmatic hernia detected during a routine screening ultrasound. An autopsy of the fetus confirmed a large isolated posterolateral hernia, which affected the left lung volume significantly. Clinical exome sequencing revealed a novel heterozygous nonsense variant c.826C>T,p.(Gln276*) in the gene, which was predicted to cause haploinsufficiency. The variant occurred and was classified as pathogenic.The report presents a detailed clinical description of the fetus with ultrasound, MRI, and post-mortem pictures of a rare prenatal isolated diaphragmatic hernia related to a novel pathogenic sequence variant. Prenatal ultrasound screening with further investigation by MRI and a comprehensive gene panel holds a key role in determining the prognosis of a fetus with a diaphragmatic hernia.
Although liver metastases from solid tumors are common and typically present as discrete masses, a sinusoidal pattern of hepatic involvement is rare, especially in sarcomas. We report a case of -mutated urethral sarcoma...Although liver metastases from solid tumors are common and typically present as discrete masses, a sinusoidal pattern of hepatic involvement is rare, especially in sarcomas. We report a case of -mutated urethral sarcoma exhibiting this unusual metastatic pattern, with features mimicking hepatocellular carcinoma (HCC). Immunohistochemical analysis revealed focal nodular hyperplasia-like changes rather than HCC, attributed to tumor cell infiltration of hepatic sinusoids and consequent alterations in blood flow. Recognizing this distinct metastatic pattern is essential, as it can be overlooked on both imaging and histologic evaluation.
Multicystic adenomatoid pancreatic hamartoma (MAPH) is a rare lesion of the pancreas, particularly in the pediatric age group with only a few cases reported in the literature. We report an unusual cystic lesion diagnosed...Multicystic adenomatoid pancreatic hamartoma (MAPH) is a rare lesion of the pancreas, particularly in the pediatric age group with only a few cases reported in the literature. We report an unusual cystic lesion diagnosed MAPH in a 26-month-old boy who presented with abdominal swelling on the right side for a period of 1 week, accompanied by icterus and itching. Magnetic resonance imaging (MRI) revealed a giant multicystic intra-abdominal mass with pressure-induced cholestasis. The large retroperitoneal lesion was completely resected. Histologically, the lesion consisted of multilocular micro- and macrocysts lined by flat, cuboidal, and columnar epithelium without atypia. The cyst walls contained notably well-formed pancreatic acini, and partially dilated ducts, and inflammatory cells, hemorrhage, edema, fibrosis with reactive fibroblasts.
Left pulmonary artery (LPA) sling is a rare congenital anomaly in which the LPA abnormally originates from the right pulmonary artery (RPA) and courses between the trachea and esophagus to reach the left pulmonary hilum....Left pulmonary artery (LPA) sling is a rare congenital anomaly in which the LPA abnormally originates from the right pulmonary artery (RPA) and courses between the trachea and esophagus to reach the left pulmonary hilum. This anomaly is frequently associated with tracheobronchial and other cardiovascular anomalies and patients may manifest with varying airway and cardiovascular symptoms. Surgical repair is often required for symptomatic patients. Clinical outcomes largely depend on the extent and severity of coexisting anomalies, particularly tracheobronchial abnormalities. We report 2 autopsy cases of LPA sling, 1 pre- and 1 post-surgical repair. Comprehensive autopsy examination was crucial for confirmation of the clinical diagnoses and identification of a rare surgical complication.
PRRX1-rearranged mesenchymal/fibroblastic tumor is a recently proposed, molecularly defined soft tissue tumor, which has not yet been included in the WHO's most recent edition of soft tissue tumors. This entity has previ...PRRX1-rearranged mesenchymal/fibroblastic tumor is a recently proposed, molecularly defined soft tissue tumor, which has not yet been included in the WHO's most recent edition of soft tissue tumors. This entity has previously been reported in a wide age range (20-76 years). However, we report the first pediatric case in an 11-year-old patient presenting with 5.5 cm mass in the head and neck region. Our case is also the second reported case of a PRRX1 (exon 1)::NCOA1 (exon 15) fusion transcript to date.
A 17-month-old male presented with a 4-week history of cough, and a CT scan revealed a large right intrathoracic mass with metastases to the brain and femur. Tumor biopsy demonstrated a high-grade malignant neoplasm with...A 17-month-old male presented with a 4-week history of cough, and a CT scan revealed a large right intrathoracic mass with metastases to the brain and femur. Tumor biopsy demonstrated a high-grade malignant neoplasm with histological and immunostaining features most suggestive of, but not entirely typical for type III pleuropulmonary blastoma (PPB). Molecular analysis identified a gene fusion and a complex copy number profile, with no mutations in or . The patient initially improved with chemotherapy, but progressive brain metastases led to palliative care, and he passed away 10 months later. This is the first reported case of a fusion in a pleuropulmonary neoplasm.
BACKGROUND: The purpose of this study was to investigate placental pathology and cause of death (COD) in pregnancy losses associated with maternal COVID-19 infection and examine associations with detection of SARS-CoV-2...BACKGROUND: The purpose of this study was to investigate placental pathology and cause of death (COD) in pregnancy losses associated with maternal COVID-19 infection and examine associations with detection of SARS-CoV-2 in placenta and fetal organs. METHODS: Demographics, placental pathology, and COD information was collected from fetal autopsies done at Evanston hospital, IL between 03/1/2020 and 12/31/2022 where maternal history indicated positive SARS-CoV-2 test during pregnancy or SARS-CoV-2 infection was suspected after fetal autopsy. Polymerase chain reaction (PCR) testing for SARS-CoV-2 RNA was performed on placenta, fetal liver, and lung tissue. RESULTS: We identified 13 autopsies and detected SARS-CoV-2 in placentas of 5 cases, all showed chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPVFD). CHI and MPVFD were absent in all the PCR-negative cases ( < .001). Fetal liver was positive for SARS-CoV-2 in 1 case, which was in the group with negative placental SARS-CoV-2 PCR. The lung tissue was negative in all cases. CONCLUSION: We confirm the association between detectable placental SARS-CoV-2 with CHI and MPVFD in placentas from pregnancy losses in mother who had COVID-19 during their pregnancy. Detection of SARS-CoV-2 in fetal liver, despite negative placental tissue, was unexpected and may be important for understanding the impact of maternal COVID infection on neonates.
Glembocki A, Siddaway R, Arnoldo A
… +1 more, Somers GR
Pediatr Dev Pathol
· 2025 · PMID 40923514
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BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. For stratification purposes, rhabdomyosarcoma is classified into fusion-positive RMS (alveolar rhabdomyosarcoma) and fusion-negative...BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. For stratification purposes, rhabdomyosarcoma is classified into fusion-positive RMS (alveolar rhabdomyosarcoma) and fusion-negative RMS (embryonal or spindle cell/sclerosing, FN-RMS) subtypes according to its fusion status. This study aims to highlight the pathologic and molecular characteristics of a cohort of FN-RMS using a targeted NGS RNA-Seq assay. METHODS: Twelve tumors were analyzed through targeted RNA-Seq using the Trusight Pancancer panel from Illumina. Molecular alterations were then correlated with the clinicopathological features. RESULTS: Of the 12 tumors analyzed, we identified 6 embryonal rhabdomyosarcomas (ERMSs) harboring mutations in key signaling molecules (, and ), oncogenic mutations in 2 ERMS, pathogenic and mutations in an ERMS with features of anaplasia, a gene fusion in a congenital spindle cell and sclerosing rhabdomyosarcoma (SSRMS), and a gene fusion in a skull base SSRMS. Only 1 ERMS in the bladder showed no reportable molecular alterations. CONCLUSION: We illustrate case examples demonstrating how a combined morphological and molecular approach with targeted RNA-Seq can aid in diagnosis and identify clinically actionable alterations in pediatric FN-RMS.
INTRODUCTION: Phyllodes tumor (PT) are rarely seen in young population. Some authors believe that PT behave less aggressively in young patients and the need for aggressive management is questioned. OBJECTIVE: We aimed to...INTRODUCTION: Phyllodes tumor (PT) are rarely seen in young population. Some authors believe that PT behave less aggressively in young patients and the need for aggressive management is questioned. OBJECTIVE: We aimed to describe the clinicopathological features of PT in pediatric and adolescent population. METHODOLOGY: We reviewed the reports and microscopy glass slides of PT from 22 pediatric and adolescent patients (≤20 years old), diagnosed between 2010 and 2024. RESULTS: Eighteen cases were malignant PT (MPT), 3 benign PT, and 1 borderline PT. Median patient's age was 17 years (range: 14-20). Median tumor size was 11.25 cm (range: 1.3-22). Tumor margins were either positive or <1 mm away in 10/17 (58.9%) tumor excisions. Follow up information was available for 12 MPT patients with median follow up duration of 26.5 months. Recurrence was observed in 2/10 (20%) primary MPT cases at 2- and 3-months interval. Distant metastasis was observed in 4/12 (33.3%) cases at median interval of 12 months. One of the metastatic cases and another patient without definite treatment, died of disease. CONCLUSION: We observed higher frequency of MPT patients, larger tumor size, and higher rate of mastectomy. MPT behave aggressively as evidenced by recurrence, metastasis, and tumor-related death.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of B-cell lymphoma. NLPHL is usually indolent, involves lymph nodes and shows a favorable prognosis with high overall survival. In a minority of c...Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of B-cell lymphoma. NLPHL is usually indolent, involves lymph nodes and shows a favorable prognosis with high overall survival. In a minority of cases, patients may present and/or progress to advanced disease with involvement of the spleen, liver, and/or bone marrow. While splenic involvement by NLPHL is usually presumed evidence of advanced disease with poor prognosis, here we report to our knowledge, the first case of primary splenic NLPHL occurring in a child who showed no overt nodal disease and is currently free of disease 3 years post-splenectomy without additional treatment.
Persistent Müllerian duct syndrome (PMDS) is a rare disorder of sex development in 46,XY individuals, characterized by the presence of Müllerian duct structures and typically associated with cryptorchidism and an elevate...Persistent Müllerian duct syndrome (PMDS) is a rare disorder of sex development in 46,XY individuals, characterized by the presence of Müllerian duct structures and typically associated with cryptorchidism and an elevated risk of testicular malignancy. Germ cell neoplasia in situ (GCNIS) is a known precursor to testicular germ cell tumors, but the earlier stage of pre-GCNIS remains poorly characterized, particularly in the context of PMDS. We report the first known case of pre-GCNIS identified in a patient with PMDS. A male infant presented with a non-palpable right testis and was found to have intra-abdominal gonads with Müllerian remnants. Histopathology revealed centrally located gonocytes with OCT3/4 expression but without the morphological features of GCNIS, consistent with pre-GCNIS. Management included right orchiectomy and left orchiopexy. This case highlights the underrecognized early stages of germ cell dysregulation in PMDS and raises important considerations about the timing of gonadectomy, fertility preservation, and long-term surveillance. Further research is needed to clarify the malignant potential of pre-GCNIS in DSD populations and to inform individualized, risk-based management strategies.
INTRODUCTION: There is a dearth of information regarding the epidemiology of biliary atresia and Kasai portoenterostomy (KPE) outcomes in the Philippines. Here we describe the histopathologic features of biliary atresia...INTRODUCTION: There is a dearth of information regarding the epidemiology of biliary atresia and Kasai portoenterostomy (KPE) outcomes in the Philippines. Here we describe the histopathologic features of biliary atresia and identify outcome predictors of KPE in a local cohort. MATERIALS AND METHODS: We performed a retrospective review of all KPEs done in our institution from 2013 to 2023, focusing on pertinent clinical and histologic features. Patients were categorized into having favorable or unfavorable outcomes based on a 3-month post-operative serum total bilirubin (≥2 mg/dL) or mortality. RESULTS: Of the 71 patients who underwent KPE during this period, 41 had liver biopsies available for review. Fibrosis, ductular reaction, and portal tract cellular infiltrates were consistently present in all samples examined, with varying degrees of giant cell transformation, portal tract edema, and ductal plate malformation. An elevated AST to Platelet Ratio Index (APRI) was linked to poorer prognosis, while visible bile plugs in biopsies significantly correlated with unfavorable outcomes. CONCLUSIONS: This study demonstrated the extensive variability of clinical and histologic features in biliary atresia. Identifying significant laboratory and histologic predictors of liver survival is essential in management and prognostication, especially in resource-limited settings where liver transplantation is not readily available.