Louis P. Dehner

• Washington University in St. Louis

Background Ovarian juvenile granulosa cell tumors (juvGCT) are rare sex cord‐stromal tumors that occur primarily in children and adolescents. This study summarizes the clinical presentation and outcomes of patients with juvGCT. Methods Patients were enrolled in the International Ovarian and Testicular Stromal Tumor and/or International Pleuropulmo...

PURPOSE Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We analyze the role of germline DICER1 status in outcomes of ovarian SLCT. METHODS Patients with SLCT were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry and/or the International Ovarian and Testicular Str...

Introduction: Yolk sac tumor (YST) is a malignant germ cell tumor with 10-15% arising in extragonadal sites. Methods: A search through our institution's database from January 01, 1990, to December 31, 2020, for "yolk sac tumor" or "endodermal sinus tumor" and "liver". Results: Our search yielded three cases. A 20-month-old girl with a liver mass an...

Purpose DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant....

Background: Pleuropulmonary blastoma (PPB) is a rare but often aggressive tumor seen primarily in infants and young children. Type I PPB is a purely cystic lesion, Type II PPB is cystic and solid and Type III PPB is a purely solid sarcoma. Types II and III PPB are aggressive sarcomas, treated with surgery and intensive, multiagent chemotherapy with...

Background Anaplastic sarcoma of the kidney (ASK) is a DICER1 ‐related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1 ‐related n...

Background Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1 -related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed)...

Background: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography (PET) and bone scintigraphy (bone scans) in diagnostic evaluation and surveillance has not been documented to date. Available PET and bone scan data are presented in t...

Sertoli-Leydig cell tumors (SLCTs) are uncommon ovarian sex cord-stromal neoplasms which are currently classified into well, moderately, and poorly differentiated and retiform types. Well-differentiated SLCT is the least common and typically occurs in pure form, whereas moderately and poorly differentiated and retiform types often comprise a morpho...

Background Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells. Methods Children with...

Introduction The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies. Methods Two pediatric patholo...

PURPOSE Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis. METHODS Patients with known or suspected PPB were enrolled in the International PPB/ DICER1 Registry. Medical records were abstracted with follow-up ascert...

Homer-Wright-like rosettes are a common finding in neural tumors but seldom seen in melanocytic nevi and melanoma. We report a case of a 23-year-old male with a compound melanocytic nevus with such rosette-like structures and summarize the current literature on this histopathological feature in melanocytic neoplasms. A symmetric, well-circumscribed...

Juvenile xanthogranuloma is a group C and L non-Langerhans cell histiocytosis, and its cell of origin is still debatable. The expression of CD11c, a more recently described macrophage marker, and CD4 have not been studied comprehensively. This study aimed to expand immunophenotypic profile and hence our understanding of the origin of these lesions....

Background Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis whose cell of origin, etiology and pathogenesis are not fully understood. We aimed to provide an update on histopathologic and immunophenotypic profile of this well-characterized entity whose relationship to the other histiocytoses has received re...

Background: Regardless of age at presentation, many soft tissue neoplasms have overlapping histopathologic and immunophenotypic features to serve as a diagnostic challenge. Case report: We reported a case of a spindle cell neoplasm in an infant, which was initially considered a vascular anomaly clinically and an eventual biopsy revealed marked i...

Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracra-nial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differen...

This report documents a unique multicystic neoplasm of the liver in an 8-month-old boy with a heterozygous germline pathogenic DICER1 variant. This neoplasm, initially considered most likely a mesenchymal hamartoma based on imaging, demonstrated the characteristic histologic pattern of embryonal rhabdomyosarcoma residing in the subepithelial or cam...

DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) wi...

A 2-year-old boy presented with a large cystic and solid chest mass arising from the lung, radiographically consistent with pleuropulmonary blastoma (PPB). He underwent right lower lobectomy with resection of a well-circumscribed, mixed solid and cystic mass. The solid areas were composed of cords and nests of tumor cells in the myxoid stroma and r...

Introduction Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic DICER1 variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB. Material and Methods Cases were collected from departmental archives and the Intern...

Objective: China’s COVID-19 statistics fall outside of recognized and accepted medical norms. Here we estimated the incidence, death and starting time of the COVID-19 outbreak in Wuhan and China based on cremation related information. Methods: Data sources included literature on COVID-19 in China, official Chinese government figures, and media re...

Context - DICER1-associated sarcomas are rare. These are currently described under a wide variety of appellations; morphologic characterizations in reported cases and sites of occurrence have also been disparate. Design – We aimed to review pediatric sarcomas associated with DICER1-mutation reported at our center, along with literature review, to i...

5547 Background: Sertoli-Leydig cell tumors (SLCT) are rare ovarian sex cord-stromal tumors which occur primarily in adolescents and young adults and are associated with DICER1 pathogenic variants. Methods: Informed consent for participation in the International PPB/ DICER1 or OTST Registry was obtained. When available, pathology was centrally revi...

Background: There is strong evidence of a genetic contribution to Wilms tumor, such as WT1 gene variation or epigenetic changes at chromosome locus 11p15. A previous genome wide association study (GWAS) of Wilms tumor identified other significant association loci including Xp22. Case report: A 4-year-old girl developed a Wilms tumor of the left is...

Introduction: CAP polyposis is a benign colorectal process presenting with multiple colorectal polyps with a "CAP" of inflammatory granulation tissue whose etiology has remained largely unknown. Case: A 24-year-old male presented with a long-standing history of repeated multiple sessile colonic polyps over a period of 17 years. Results: The nu...

Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited da...

Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of intermediate malignancy. Treatment options for unresectable and/or metastatic tumors are very limited. Immunotherapy with PD-1/PD-L1 inhibitors may be worth exploring. The aim of this study was to evaluate the expression of PD-L1 in AFHs. PD-L1 expression was assessed on 36 AFHs from 36 pedi...

Centrilobular injury (CLI) is defined as the presence of a perivenular mononuclear inflammation, drop‐out of hepatocytes, and erythrocyte extravasates. In the pediatric liver allografts, CLI has been associated with advanced fibrosis and chronic rejection (CR). We sought to better characterize the clinicopathologic features of CLI in the setting of...

Background This study aims to investigate whether maternal SARS-CoV-2 status affects placental pathology. Methods: A retrospective case-control study was conducted by reviewing charts and slides of placentas delivered between April 1 to July 24, 2020. Clinical history of “COVID-19” was searched in Pathology Database (CoPath). Controls were matched...

Background: Roberts syndrome is a genetic disorder characterized by tetra-phocomelia with abnormalities of ESCO2. We report a male stillborn with tetra-phocomelia and no ESCO2 mutation. Case report: Pre- and post-natal imaging and autopsy findings included schizencephaly, phocomelia of four limbs, micrognathia, oligodactyly, and cardiopulmonary ma...

The Fontan procedure used for palliation of single ventricle physiology is associated with multisystemic morbidity. With improving survival and increased use of surveillance imaging in this patient population, long-term complications associated with Fontan circuits are commonly encountered by radiologists. One interesting observation is the apparen...

Background: This study aims to investigate whether maternal SARS-CoV-2 status affect placental pathology. Methods: A retrospective case-control study was conducted by reviewing charts and slides of placentas between April 1 to July 24, 2020. Clinical history of COVID-19 were searched in Pathology Database (CoPath). Controls were matched with SARS-C...

Smooth muscle hamartoma (SMH) and striated muscle hamartoma (STH) are anomalous proliferations of smooth muscle or striated muscle in anatomic sites where these tissues are normally present, respectively. To date only limited cases have been reported describing these lesions. In this study, we sought to characterize the clinicopathologic features o...

Background: Wuhan, China was the epicenter of COVID-19 pandemic. The goal of current study is to understand the infection transmission dynamics before intervention measures were taken. Methods: Data and key events were searched through pubmed and internet. Epidemiological data were calculated using data extracted from a variety of data sources. Res...

BACKGROUND Wuhan, China was the original epicenter of COVID-19 pandemic. OBJECTIVE The goal of the current study is to understand the infection transmission dynamics before intervention measures were taken, such as issuing a lockdown for the city and other social distancing policies. METHODS Data and key events were searched through pubmed for me...

Background: Wuhan, China was the original epicenter of COVID-19 pandemic. The goal of the current study is to understand the infection transmission dynamics before intervention measures were taken, such as issuing a lockdown for the city and other social distancing policies. Methods: Data and key events were searched through pubmed for medical lit...

BACKGROUND China’s COVID-19 statistics fall outside of recognized and accepted medical norms. OBJECTIVE Here we estimated the incidence, death and starting time of the COVID-19 outbreak in Wuhan and China based on cremation related information. METHODS Data sources included literature on COVID-19 in China, official Chinese government figures, sta...

Background: Epidemiological data provide important information for decision making. COVID-19 statistics from China fall outside of recognized and accepted medical norms. As the epicenter of the COVID-19 initial outbreak, the epidemiological information from Wuhan affects the response and preparation of other parts of China and rest of the world. He...

Here we estimated the incidence, death and starting time of the COVID-19 outbreak in Wuhan and China based on medical literature from China, official and non-official Chinese data sources. Our estimates are based on investigative media reports of crematory operations in Wuhan, which is considered as a common data end point to life. A range of estim...

6064 Background: Juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors which occur primarily in children and adolescents. Methods: All individuals or proxy caregivers provided informed consent/assent for participation in the International OTST Registry. Clinical data was collected. When available, pathology was centrally reviewed....

Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with anoth...

Synovial sarcoma (SS) is a soft-tissue malignancy that most often affects patients between 15 to 40 years, and the prognosis for patients with metastatic disease is generally poor. This study was performed to evaluate checkpoint blockade immunotherapy markers in SS, including tumor mutational burden (TMB), DNA mismatch repair (MMR) status, PDL-1, P...

Objective: Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord stromal tumors, particularly Sertoli-Leydig cell tumors. The gynecologic and reproductive health of these females has not yet been described. Methods: All female subjects re...

Poorly differentiated thyroid carcinomas (PDTC) in young individuals are rare and their clinical and histopathologic features, genetic mechanisms, and outcomes remain largely unknown. Here, we report a detailed characterization of a series of six PDTC in patients ≤21 years old defined by Turin diagnostic criteria studied for mutations and gene fusi...

Metastatic carcinoma to the skin occurs in only a minority of patients with a visceral or internal malignancy, with breast, lung and colorectum accounting for the majority of cases. We present the case of a 66‐year‐old man with a recent violaceous nodule of the left scalp (1.2 x 1.0 x 0.2 cm) that was a metastatic pancreatic adenosquamous carcinoma...

Background/Objectives: Ewing-like sarcoma (ELS) are within a subset of small round cell tumors (SRCT). The histological diagnosis of SRCT is difficult due to the primitive character of the cells. Design/Methods: Case report. Results: A 5.5-year-old boy was admitted with dyspnea. Chest CT revealed the large tumor mass in the right lung. Soon after p...

We report two malignant sacrococcygeal tumors in infants that were associated with pathogenic DICER1 variation. These tumors were composed of primitive neuroepithelium, embryonal rhabdomyosarcoma, and cartilage and initially diagnosed as immature teratomas. One child developed intracranial metastasis and died. The second child underwent surgery and...

Introduction: Endobronchial granular cell tumors are uncommon in the pediatric population. Case report: A 9-year-old female presented with respiratory failure due to an endobronchial tumor. After debulking and diagnosis, she underwent thoracotomy with right upper lobe resection and bronchoplasty. Pathology demonstrated an endobronchial S-100 negati...

NUT midline carcinoma (NMC) is a rare, aggressive poorly differentiated carcinoma genetically defined by NUTM1 gene rearrangement. The purpose of this study was to determine the tumor mutational burden (TMB) and the expression of immunohistochemical (IHC) markers in NMCs that are generally used to identify patients that might benefit from checkpoin...

Liver NRH is seen in all patients age; however, more frequently in those over the age of 60 years and associated with multiple systemic diseases. In liver allograft recipients, the development of DnNRH has been linked with the use of azathioprine or vascular abnormalities. We present the clinicopathologic characteristics of 17 pediatric patients wh...

Pleuropulmonary blastoma (PPB), the most common primary malignant neoplasm of the lung in childhood, occurs in the same early age group (0-6 years) as the other more common solid tumors such as neuroblastoma and Wilms tumor. The tumor begins as a cystic lung lesion with the potential over a period of 3-5 years to progress to a high grade multipatte...

Introduction: Malignant rhabdoid tumor (MRT) is a rare, aggressive pediatric tumor of nuclear lineage. It is mainly characterized by germline or somatic SMARCB1 (INI1) driver mutations. To characterize the potential for immunotherapy in untreated and treated MRT, current study investigated tumor mutational burden (TMB) and other biomarkers in MRT....

Objectives: Identify and characterize pediatric pulmonary emboli present at autopsy. Design: Retrospective single institution observational study with clinicopathologic correlation. Setting: Tertiary medical center. Patients: All autopsy cases performed at Washington University from 1997 to 2017 in pediatric patients (≤ 18 yr old). Main res...

We report a detailed phenotypic, cytogenetic and molecular characterization of a patient prenatally diagnosed with Turner syndrome (TS). In addition to having typical TS clinical characteristics including webbed neck, high arched palate and coarctation of the aorta, the patient had features less frequently seen in TS. These included recurrent parat...

Purpose: DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard rates, and the probability of neoplasm incidence accounting for competing risks ("cumulative incidence") of neoplasms (benign and malignant) and standardized incidence rat...

Background: Omphalocele is a rare congenital abdominal wall defect. It is frequently associated with genetic abnormality and other congenital anomalies, although isolated omphalocele cases do exist. Data have shown that omphalocele with co-occurring genetic abnormality has worse prognosis than isolated omphalocele. Chromosomal analysis by a conven...

Background/Objectives: Pleuropulmonary blastoma (PPB) is a rare malignancy, which may occur sporadically or in the context of a pathogenic variant in the DICER1 gene. Pathogenic variants in DICER1 increase the risk of PPB, ovarian, renal, thyroid and brain tumors, intestinal polyps and lung cysts. Design/Methods: We report the case of a patient dia...

We present a 3-year-old boy with Langerhans cell histiocytosis who developed granulomatous dermatitis while taking vemurafenib. Vemurafenib currently has Food and Drug Administration approval for the treatment of BRAF V600E+ metastatic melanoma in adults, but recent discoveries of BRAF V600E in more than half of tested Langerhans cell histiocytosis...

Background The DICER1 syndrome is a tumor-predisposition disorder caused by germline pathogenic variation in DICER1 and is associated with cystic nephroma and other renal neoplasms. Dicer1 mouse and rare human DICER1 syndrome case reports describe structural kidney and collecting system anomalies. We investigated renal function and the frequency of...

Infantile hemangioma (IH) is one of the most common vascular anomalies of early childhood and is usually recognized in the first few weeks to months of life as a solitary cutaneous lesion. This report documents our experience with a GLUT-1 positive IH presenting as the pathologic lead point in a colocolic intussusception in a 10-week-old infant who...

We report a detailed phenotypic, cytogenetic, and molecular characterization of a patient diagnosed prenatally with Turner syndrome (TS). In addition to having typical TS clinical characteristics such as a webbed neck, high arched palate, and coarctation of the aorta, the patient had features less frequently seen in TS, including recurrent parathyr...

The acquired melanocytic nevus is the most common lesion encountered by pediatric pathologists and dermatopathologists in their daily practice. In most cases, there are few difficulties in histopathologic diagnosis. However, it is the acquired melanocytic lesion known as the Spitz nevus, with its intrinsic atypical features which becomes the challe...

This overview of mesenchymal tumors presenting in the skin and/or subcutis in children brings together the range of neoplasms and hamartomas which are seen in this age-group. It is not surprising from the perspective of the pediatric or general surgical pathologist that vascular anomalies, including true neoplasms and vascular malformations, are th...

This article focuses on cutaneous hematopoietic neoplasms that are more likely to be encountered in the pediatric age-group and includes both lymphoproliferative and histiocytic disorders. The cutaneous hematologic disorders in children have a different epidemiologic profile to what is seen during adulthood. Although mycosis fungoides is the most f...

Introduction: Clear cell sarcoma of the kidney (CCSK) is childhood neoplasm with its own distinctive pattern of metastasis and may appear after a disease free interval of 5 years or more. Materials and methods: Histopathology and immunohistochemistry were available from the radical nephrectomy and the later partial cystectomy, which was performe...

Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord–stromal tumors, particularly Sertoli–Leydig cell tumor, individuals with pathogenic germline DICER1 variants may also develop...

Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typic...

p>Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of dedifferentiated renal cell carcinoma. We report a 62-yearold man who presented with respiratory symptoms and a lung mass on chest computed tomography (CT). The patient underwent positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorodeoxyglucose (...

Evans syndrome (ES) is a rare autoimmune disorder whose exact pathophysiology is unknown. It is characterized by the simultaneous or subsequent development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Intravascular hemolysis, with hemoglobinemia, is known to produce acute kidney injury; however, the development of intrat...

Background: Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinic...

Extrarenal malignant rhabdoid tumors (MRT) have a poor prognosis despite aggressive therapy. Adding high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) as consolidative therapy for MRT is controversial. We describe 2 patients, age 13 years and 19 months, with unresectable neck MRT. After chemotherapy and radiotherapy, both underwent...

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal malignancy after Wilms tumor. CCSK has the potential to metastasize to distant sites and was historically known as the bone metastasizing renal tumor. We report an exceedingly rare case of a bladder recurrence of CCSK. Our patient presented with gross hematuria 7 year...

The most common malignant pulmonary neoplasms in children are metastases from other primary tumors, whereas primary pulmonary malignancies in children are rare. This chapter describes diverse neoplasms that originate from intrathoracic organs or structures or the chest wall, that have been described in children. Most of these neoplasms are malignan...

Bladder tumours in early-onset patients are rare and seem to exhibit unique clinicopathological features. Only few studies have investigated somatic alterations in this specific age of onset group and evidence is accumulating of a distinct molecular behaviour of early-onset bladder tumours. We collected the largest cohort of early-onset tumours of...

Supplementary figure 1 and table 1.

Context: The risk of thyroid cancer and multinodular goiter (MNG) in the DICER1 syndrome, a rare tumor-predisposition disorder, is unknown. Objective: To quantify the risk of thyroid cancer and MNG in individuals with the DICER1 syndrome. Design: Family-based cohort study. Setting: National Institutes of Health (NIH) Clinical Center (CC). P...

Received: May 25, 2016 Accepted: June 27, 2016 Published online: August 26, 2016 Issue release date: December 2016

Omenn syndrome is an autosomal recessive form of “leaky” severe combined immune deficiency resulting in distinct phenotypic features. The patient described herein had an atypical presentation of Omenn syndrome, with conspicuous erythroderma and extreme lymphocytosis at birth, in contrast to the typical evolution of rash seen during the first few we...

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Ovarian sex cord-stromal tumors are clinically significant heterogeneous tumors that include several pathologic types. These tumors are often found in adolescents and young adults and can present with hormonal manifestations as well as signs and symptoms of a pelvic mass. Serum tumor markers may assist in preoperative diagnosis and surveillance. Se...

Purpose: Germ-line mutations in DICER1 increase the risk of various tumors, including pleuropulmonary blastoma. Macrocephaly and symmetric overgrowth have been reported in some, but not all, patients with mosaic DICER1 RNase IIIb mutations. The prevalence of these features in individuals with constitutional germ-line DICER1 mutations is unknown....

Aberrant right subclavian artery (ARSA), the most common aortic arch abnormality, occurs in approximately 0.5 to 1.8% of the general population, with prevalence of up to 25% in those with esophageal atresia. Although ARSA is often asymptomatic, a fistulous tract into esophagus may develop with prolonged nasogastric tube placement or endotracheal in...