Heterotopic salivary glandular tissue within the rectum is exceptionally rare. To date, only 4 cases have been reported in literature and all in adult patients. Here we report a case of ectopic salivary glandular tissue...Heterotopic salivary glandular tissue within the rectum is exceptionally rare. To date, only 4 cases have been reported in literature and all in adult patients. Here we report a case of ectopic salivary glandular tissue in the rectum in a 12-year-old girl who also had a lumbosacral lipomeningocele. The coexistence of these 2 developmental anomalies; 1 endodermal and 1 neuroectodermal, has not been reported previously. The case is discussed with emphasis on embryologic correlation, review of literature, and a summary of prior published cases.
PURPOSE: This review is intended to provide practical guidance to those who examine the tissues of fetuses and infants under the microscope. We focus on what is normal at various stages of development, and try to point o...PURPOSE: This review is intended to provide practical guidance to those who examine the tissues of fetuses and infants under the microscope. We focus on what is normal at various stages of development, and try to point out when caution should be used in interpreting histologic findings. CONTENT: We present descriptions and images of normal developmental histology and its variations in the major human organs during fetal and neonatal life. The organs reviewed include the cardiovascular system, lungs, liver, pancreas, tubular gastrointestinal tract, kidneys, thymus, adrenal glands, gonads, thyroid gland, spleen, brain, bone, and skeletal muscle.
PURPOSE: The purpose of this article is to highlight the unique aspects of the perinatal autopsy, compared to the autopsy of patients outside the perinatal period. This article focuses on what would be useful to general...PURPOSE: The purpose of this article is to highlight the unique aspects of the perinatal autopsy, compared to the autopsy of patients outside the perinatal period. This article focuses on what would be useful to general pathologists who perform autopsies as a small portion of their practice. We will also discuss in some detail the autopsy of the macerated fetus and determining time of death prior to delivery. BACKGROUND: General pathologists performing perinatal autopsies commonly lack specific training in perinatal autopsy techniques, where interpretation of detailed measurements and dissections are essential. Macerated fetuses provide an additional challenge, as planes of dissection are hard to see and microscopic examinations require interpretation of degenerated tissue. CONTENT: This article describes the basic steps to perform a perinatal autopsy including tips to streamline dissections, which are useful for the general pathologist. It includes how to recognize features of maceration to provide an accurate time of death prior to delivery and information about the classification of the cause of death in stillbirth.
PURPOSE: To provide information for the general pathologist about what is considered normal in the placenta and to differentiate findings that are abnormal or pathologic. BACKGROUND: The literature about the placenta is...PURPOSE: To provide information for the general pathologist about what is considered normal in the placenta and to differentiate findings that are abnormal or pathologic. BACKGROUND: The literature about the placenta is confusing. It can be opinionated, and terminology varies among authors. Even what is expected to be seen, which we refer to as normal, is not consistent among experts. RESULTS: This article focuses on what the general pathologist should know about normal macroscopic and histologic features of the placenta throughout gestation, as well as alterations that are controversial related to whether they are normal or not. Normal findings are differentiated from pathology when the morphology is confusing or overlaps. We further guide the reader to selected literature that describes pathology in clear, understandable terms. This is not a consensus document but does represent agreement among the authors and, when agreement isn't reached, differing opinions are noted. CONCLUSION: This article is a report of normal features in the placenta based on distillation of evidence from the literature and personal experience in areas where the literature fails to provide clarity.
Pediatr Dev Pathol
· 2026 · PMID 42394239
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PURPOSE: This article describes how techniques such as advanced imaging, nucleic acid evaluation, integrated approaches, and data collection systems can facilitate the examination of a stillbirth or newborn, particularly...PURPOSE: This article describes how techniques such as advanced imaging, nucleic acid evaluation, integrated approaches, and data collection systems can facilitate the examination of a stillbirth or newborn, particularly when an autopsy is not possible. CONTENT: The traditional autopsy remains the gold standard for investigating stillbirth and neonatal death. However, declining rates due to parental refusal, financial constraints, and cultural barriers highlight the need to widely adopt modern alternatives. This review examines emerging ancillary and advanced diagnostic techniques necessary to maximize diagnostic yield and ensure equitable access to comprehensive postmortem evaluations. Since imaging alone often misses critical microscopic pathologies, hybrid methods like Minimally Invasive Autopsy with Laparoscopically Assisted Sampling (MinImAL) are essential. MinImAL combines Postmortem Magnetic Resonance Imaging (PMMR) with image-guided tissue sampling to acquire specimens for histological and microbiological analysis. Complementary molecular techniques aid in identifying underlying genetic causes and informing recurrence risk. The success of these tests relies on optimized tissue selection. Systemic improvements include adopting standardized protocols, establishing Stillbirth Centers of Excellence, and using Artificial Intelligence (AI) for risk prediction. Importantly, integrating these advanced, less invasive methods is vital for addressing financial and racial health disparities, especially given the lack of Medicaid coverage for autopsy, thereby ensuring all bereaved families receive accurate and necessary diagnostic information.
Words are our primary means of communication as practitioners of perinatal pathology and so we must focus on detail, accuracy, and clarity. This aim of this article is to provide a glossary of common terms in order to im...Words are our primary means of communication as practitioners of perinatal pathology and so we must focus on detail, accuracy, and clarity. This aim of this article is to provide a glossary of common terms in order to improve clarity when writing or speaking about the infant, fetus, pregnancy, and the placenta. We address terminology used in perinatal pathology when performing an autopsy or examining products of conception or a placenta that can be confusing or unclear. The purpose is to convey meanings of commonly used terms, keeping to the subject of the normal, uncomplicated examination as much as possible. Additional articles in this Perspectives issue focused on fetal growth and development as well as the perinatal autopsy expand on many of the definitions below.
Pediatr Dev Pathol
· 2026 · PMID 42394236
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PURPOSE: This manuscript examines the role of postmortem conference in supporting families in their grief and enhancing care following perinatal loss. It synthesizes current knowledge, highlights challenges in recognitio...PURPOSE: This manuscript examines the role of postmortem conference in supporting families in their grief and enhancing care following perinatal loss. It synthesizes current knowledge, highlights challenges in recognition and support, and recommends evidence-based approaches for healthcare professionals to better address the needs of grieving families. CONTENT: Perinatal loss, encompassing miscarriage, stillbirth, and neonatal death, is profoundly distressing, affecting individuals, couples, and families. This manuscript explores the complex nature of grief following perinatal loss, emphasizing the psychological, emotional, and social challenges bereaved parents may face. It synthesizes recent literature focused on grief and bereavement. The disenfranchised nature of perinatal grief, the insufficient recognition and support from social networks and healthcare providers, and implications for long-term mental health are discussed. Evidence-based interventions and supportive approaches include compassionate communication, memory-making practices, and psychological therapies tailored for perinatal loss. Best practices for healthcare professionals and recommendations for institutional policies that foster a supportive environment for grieving families are highlighted. The manuscript addresses the need for increased education, resources, and research to improve care outcomes. By recognizing the legitimacy and depth of perinatal grief, and addressing it through holistic, responsive care, both immediate suffering and long-term complications for parents and families can be mitigated.
PURPOSE: To explain which growth and development parameters are most useful when faced with a perinatal autopsy and identify factors complicating the use of these parameters. BACKGROUND: Growth and development charts see...PURPOSE: To explain which growth and development parameters are most useful when faced with a perinatal autopsy and identify factors complicating the use of these parameters. BACKGROUND: Growth and development charts seem to be straightforward, but when faced with a perinatal autopsy, they may be confusing or misleading. Autopsy weight and measurement charts are based on much smaller groups of individuals than clinical charts. Perinatal postmortem growth charts are confounded by maceration, the small numbers of subjects to define normal, and population differences. Interpretation of growth and development parameters when performing a perinatal autopsy is complicated by the interpretation of deviations from expected or "normal" as defined by the charts. RESULTS: This article provides an analysis of growth and development charts used in perinatal examinations and gives guidance about which charts are the most robust. Weights, measurements, and aspects of development will be described and distilled into those most relevant to the general pathologist. CONCLUSION: Growth and development charts are important when performing a perinatal autopsy to define what is normal versus pathologic, and a distillation of the key points with review of the literature is central to using them.
Pediatr Dev Pathol
· 2026 Jun · PMID 42333635
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BACKGROUND: Erythropoietic Protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by pathogenic variants in FECH. Although most patients present with cutaneous photosensitivity in childhood, clinic...BACKGROUND: Erythropoietic Protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by pathogenic variants in FECH. Although most patients present with cutaneous photosensitivity in childhood, clinically significant liver disease is uncommon, and severe fibrosis in early childhood is rarely reported. CASE: A 2-year-old girl presented with recurrent photosensitivity and erythematous swelling after sun exposure. Laboratory evaluation revealed markedly elevated erythrocyte protoporphyrin (2406 µg/dL) and elevated plasma protoporphyrin. Genetic testing identified compound heterozygous FECH variants: c.901_902del (p.Trp301Alafs*23) and c.801G>A (p.Met267Ile). Liver enzymes were significantly elevated. Following liver biopsy demonstrated stage 3 bridging fibrosis with crystalline deposits in hepatocytes consistent with protoporphyric hepatopathy. The patient subsequently underwent hematopoietic stem cell transplantation with improvement of protoporphyrin levels and liver enzymes. However, the post-transplant course was complicated by severe infections, acute respiratory distress syndrome, and multiorgan failure, resulting in death. CONCLUSION: This case highlights rapidly progressive liver fibrosis in a toddler with EPP and emphasizes the importance of early hepatic monitoring in pediatric patients with markedly elevated protoporphyrin levels and rare FECH variants.
Pediatr Dev Pathol
· 2026 Jun · PMID 42311008
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Fetiform teratoma (FT) and fetus-in-fetu (FIF) represent a spectrum of rare retroperitoneal masses containing organoid structures. While FIF is classically defined by the presence of a vertebral axis, FT lacks this organ...Fetiform teratoma (FT) and fetus-in-fetu (FIF) represent a spectrum of rare retroperitoneal masses containing organoid structures. While FIF is classically defined by the presence of a vertebral axis, FT lacks this organized skeletal development. Distinguishing between these entities is critical given the malignant potential associated with FT, estimated at approximately 10%. We report a case of a 5-month-old male presenting with a large (12 cm) retroperitoneal mass and elevated alpha-fetoprotein (AFP 56.8 IU/mL; age-matched reference <7 IU/mL). Macroscopically, the resected tumor featured a distinct rudimentary digitiform projection with a nail bed. Histopathology demonstrated extensive organoid differentiation, including gastrointestinal loops with muscular layers, respiratory epithelium, and well-formed pancreatic parenchyma and adrenal cortex. Despite the complex organogenesis and limb-like morphology, the absence of a vertebral column or ossified long bones supported a diagnosis of mature cystic teratoma with fetiform features (FT) over FIF. This report highlights the diagnostic ambiguity within the "gray zone" of these lesions and emphasizes the role of axial skeletal organization and serum AFP levels as complementary tools for classification and oncologic surveillance.
Pediatr Dev Pathol
· 2026 Jun · PMID 42304547
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BACKGROUND: Fetal hemorrhage (FH) is an important and difficult cause of death to recognize at perinatal autopsy. Existing literature is restricted to case reports and small case series, and none comprehensively describe...BACKGROUND: Fetal hemorrhage (FH) is an important and difficult cause of death to recognize at perinatal autopsy. Existing literature is restricted to case reports and small case series, and none comprehensively describe both placental and autopsy findings. We sought to characterize fetal and placenta findings where the ultimate cause of death was determined to be FH to aid in the identification of these cases. MATERIALS AND METHODS: This is an autopsy series of perinatal deaths with fetomaternal hemorrhage (FMH) and FH into the amnionic sac. We included singleton pregnancies with Kleihauer Betke (KB) testing, and divided cases into 3 groups: FMH with ≥40% of fetal blood volume, FMH ≤39%, and suspected FH into the amnionic sac with negative KB test. RESULTS: We identified 20 cases from 691 perinatal autopsies, 10 with FMH ≥40%, 5 with FMH ≤39%, and 5 suspected FH into the amnionic sac. Cases with FMH≥40% were likely to have a normal placental weight, villous edema, and fetal hydrops. While FH into the amnionic sac was more likely to have a small placenta with disruption/defect of fetal vessels, and less likely to have fetal hydrops. CONCLUSION: This study describes the differences and similarities between cases with FMH and FH in to the amnionic sac, and highlights the need for careful placenta and fetal autopsy examinations.
Biswas D, Mitra S, Lal R
… +6 more, Babbar A, Thunga C, Bansal D, Kakkar N, Lal S, Dey P
Pediatr Dev Pathol
· 2026 Jun · PMID 42299105
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BACKGROUND AND AIMS: Langerhans cell histiocytosis (LCH) commonly affects children. The histological distinction of hepatic LCH from its mimickers is challenging and often requires judicious use of immunohistochemistry i...BACKGROUND AND AIMS: Langerhans cell histiocytosis (LCH) commonly affects children. The histological distinction of hepatic LCH from its mimickers is challenging and often requires judicious use of immunohistochemistry in the correct clinical and radiological context. We described the patterns of hepatic LCH and applied an ensemble transfer-learning model to predict and distinguish hepatic Langerhans cell infiltration from histological mimics. MATERIALS AND METHODS: Clinical, histological, and immunophenotypic data from 6 pediatric LCH cases with liver biopsies were retrieved from the archives. The histological patterns were reviewed. Histological images were obtained from all cases of hepatic LCH with histologically overt Langerhans cell infiltration, as well as from cases with histological mimickers. A soft-voting-based ensemble transfer learning model was applied to the images after splitting them into training, validation, and test sets. The performance metrics were evaluated. RESULTS: All cases were multisystem LCH (MS-LCH). The hepatic histomorphology showed sclerosing cholangiopathy with/without Langerhans cell infiltration as the most common pattern. Bile extravasation and cystic dilatation were noted in a single case. Eosinophilic microabscesses, cholangiopathy, and portal-based aggregates are the important histological clues. The ensemble learning model had an area under the curve (receiver operating characteristic) of 0.99, with sensitivities, specificities, and accuracies of 33.3%, 100%, and 75%, respectively. CONCLUSION: Sclerosing cholangiopathy with or without Langerhans cells is the most common pattern of hepatic LCH. An ensemble transfer learning model can serve as a valuable screening tool for histopathologists to predict and diagnose hepatic LCH.
Pediatr Dev Pathol
· 2026 Jun · PMID 42262030
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Drug-induced liver injury (DILI) in children remains a diagnostic challenge due to its broad clinical and histologic spectrum. Based on pathogenesis, DILI is classified as idiosyncratic, intrinsic (direct), or indirect....Drug-induced liver injury (DILI) in children remains a diagnostic challenge due to its broad clinical and histologic spectrum. Based on pathogenesis, DILI is classified as idiosyncratic, intrinsic (direct), or indirect. In the United States, antimicrobials and antiepileptic medications are the most commonly implicated agents. Because histologic features are often nonspecific, diagnosis and assessment of causality rely on clinicopathologic correlation. Although not always required, liver biopsy can aid in characterizing injury patterns, assessing severity, and excluding mimickers. This review highlights the major morphologic patterns of pediatric DILI, associated agents, and practical considerations for biopsy interpretation in routine practice.
Carreon CK, Sanders SP, Blume ED
… +2 more, Smoot L, Perez-Atayde AR
Pediatr Dev Pathol
· 2026 Jun · PMID 42240283
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BACKGROUND: Desmin-related cardiomyopathy is a rare disorder caused by pathogenic variants in desmin and associated protein genes. We aimed to describe the clinical, histopathological, immunohistochemical, ultrastructura...BACKGROUND: Desmin-related cardiomyopathy is a rare disorder caused by pathogenic variants in desmin and associated protein genes. We aimed to describe the clinical, histopathological, immunohistochemical, ultrastructural, and molecular features in a pediatric cohort. METHODS: This retrospective descriptive study reviewed pediatric cases diagnosed over a 30-year period. Clinical data were extracted from electronic medical records. Archived histologic slides (H&E, desmin immunostains, and special stains) and electron photomicrographs were re-evaluated. Key features were documented and summarized. RESULTS: Four pediatric patients (3 males and 1 female) presented between ages 2 and 14 years with restrictive cardiomyopathy and conduction abnormalities. Endomyocardial biopsies and/or explanted heart specimens showed eosinophilic cytoplasmic inclusions that were desmin-immunoreactive, PAS-negative, and highlighted by toluidine blue. Electron microscopy revealed dense cytoplasmic granulofilamentous aggregates that were frequently continuous with the sarcoplasmic membrane, Z-bands, and intercalated discs. Two patients harbored the same pathogenic variant: DES c.1360T>C (p.Arg454Trp). CONCLUSION: Desmin-related cardiomyopathy should be considered in any child presenting with restrictive cardiomyopathy and/or rhythm disturbances. Distinctive light microscopic and ultrastructural features can aid in confirming the diagnosis. Certain pathogenic variants are increasingly linked to more severe phenotypes, highlighting the importance of genetic evaluation and its implications for family counseling.
Guest R, Van Arnam J, Kinnear D
… +5 more, El-Dana F, Hummel K, Lafreniere A, Castro E, Blessing M
Pediatr Dev Pathol
· 2026 May · PMID 42218607
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DICER1 syndrome is a rare autosomal dominant cancer predisposition syndrome caused by germline mutations in the gene and several associated benign and malignant entities. This case describes a premature 8-day old neonat...DICER1 syndrome is a rare autosomal dominant cancer predisposition syndrome caused by germline mutations in the gene and several associated benign and malignant entities. This case describes a premature 8-day old neonate prenatally diagnosed with renal and cystic lung abnormalities who died from severe respiratory dysfunction. Autopsy additionally revealed ETMR and genitourinary abnormalities, leading to the diagnosis of probable DICER1 syndrome. While the family declined postmortem genetic testing, detailed postmortem examination led to important diagnoses capable of guiding clinical follow-up and future family planning.
S Akkelle B, Celik E, Dirimtekin E
… +4 more, Bagci İ, Turkmen AD, Celikel C, Ertem D
Pediatr Dev Pathol
· 2026 May · PMID 42218606
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Persistent diarrhea that occurs in the first weeks of life and is caused by monogenic defects are defined as congenital diarrhea and enteropathies (CoDEs). The PERCC1 (proline and glutamate-rich protein with coiled-coil...Persistent diarrhea that occurs in the first weeks of life and is caused by monogenic defects are defined as congenital diarrhea and enteropathies (CoDEs). The PERCC1 (proline and glutamate-rich protein with coiled-coil domain 1) gene which has a role in development of enteroendocrine cells, was recently found to be associated with CoDEs. We report the clinical, laboratory, and histopathologic findings of CoDE caused by a novel, homozygous variant (c.337 del) in the second exon of PERCC1 gene in an infant diagnosed at 2 months postnatally. The unique findings in our case were the location and/or distribution abnormality of enteroendocrine cells and exocrine pancreatic insufficiency. We can conclude that these distinctive features may expand the spectrum of PERCC1-associated CoDE.
Pediatr Dev Pathol
· 2026 May · PMID 42212859
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Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma with a high risk of local recurrence, of which the congenital atrophic variant is exceptionally rare and prone to misdiagnosis. We report a case o...Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma with a high risk of local recurrence, of which the congenital atrophic variant is exceptionally rare and prone to misdiagnosis. We report a case of a 10-month-old male infant with a rapidly enlarging, tender nodule arising within a congenital atrophic plaque on the left lower leg, which histopathologically demonstrated a CD34-positive spindle cell tumor featuring storiform architecture and deep honeycomb infiltration. Notably, fluorescence in situ hybridization (FISH) analysis revealed no evidence of the characteristic gene rearrangement, consistent with a molecularly unconfirmed DFSP. This case highlights the critical importance of including DFSP in the differential diagnosis of progressive congenital plaques, supports the biphasic growth model, and underscores the necessity of integrating histopathology with advanced molecular techniques for accurate diagnosis and management, even in the absence of classic molecular markers.
Manukyan I, Rossi CT, Vaidyanathan P
… +2 more, Mudd PA, Sirotnikov S
Pediatr Dev Pathol
· 2026 May · PMID 42210516
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Most thyroid nodules encountered in clinical endocrinology are epithelial in origin. In contrast, primary thyroid mesenchymal tumors are exceedingly rare but increasingly recognized with advances in immunohistochemistry...Most thyroid nodules encountered in clinical endocrinology are epithelial in origin. In contrast, primary thyroid mesenchymal tumors are exceedingly rare but increasingly recognized with advances in immunohistochemistry and molecular diagnostics. Thyroid myofibroma is an exceptionally uncommon benign fibroblastic-myofibroblastic neoplasm, with only a limited number of cases reported to date. We report a 9-year-old girl with Turner syndrome (TS) and a prior myofibroblastic proliferation of the parotid gland 5 years earlier, who presented with a solitary thyroid nodule. Fine-needle aspiration (FNA) demonstrated a spindle-cell proliferation suspicious for an extrafollicular process. Lobectomy revealed a well-circumscribed, unencapsulated spindle-cell tumor composed of bland myofibroblastic cells arranged in fascicles within a collagenous stroma. The immunophenotype supported myofibroma. Targeted molecular testing identified a pathogenic variant and a novel variant of uncertain significance, confirming the diagnosis. No prior reports have described thyroid myofibroma associated with TS or a preceding salivary gland myofibromatous lesion, making this case unique and diagnostically and pathogenetically significant. Awareness of this entity is critical to avoid misclassification as other spindle-cell thyroid lesions on FNA. Integrated cytomorphology, immunophenotyping, and PDGFRB-focused molecular analysis provide a robust diagnostic approach and may offer insight into shared pathogenetic mechanisms linking TS and myofibroblastic proliferations.