Publications by authors named "Sara O Vargas"

150 Publications

Secondary Pulmonary Vein Stenosis Due to Total Anomalous Pulmonary Venous Connection Repair in Children: Extravascular MDCT Findings.

Children (Basel) 2021 Aug 25;8(9). Epub 2021 Aug 25.

Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Purpose: To evaluate extravascular findings on thoracic MDCT angiography in secondary pulmonary vein stenosis (PVS) due to total anomalous pulmonary venous connection (TAPVC) repair in children.

Materials And Methods: All patients aged ≤18 years with a known diagnosis of secondary PVS after TAPVC repair, confirmed by echocardiography, conventional angiography, and/or surgery, who underwent thoracic MDCT angiography studies between July 2008 and April 2021 were included. Two pediatric radiologists independently examined MDCT angiography studies for the presence of extravascular thoracic abnormalities in the lung, pleura, and mediastinum. The location and distribution of each abnormality (in relation to the location of PVS) were also evaluated. Interobserver agreement between the two independent pediatric radiology reviewers was studied using kappa statistics.

Results: The study group consisted of 20 consecutive pediatric patients (17 males, 3 females) with secondary PVS due to TAPVC repair. Age ranged from 2 months to 8 years (mean, 16.1 months). In children with secondary PVS due to TAPVC repair, the characteristic extravascular thoracic MDCT angiography findings were ground-glass opacity (19/20; 95%), septal thickening (7/20; 35%), pleural thickening (17/20; 85%), and a poorly defined, mildly heterogeneously enhancing, non-calcified soft tissue mass (17/20; 85%) which followed the contours of affected pulmonary veins outside the lung. There was excellent interobserver kappa agreement between two independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (k = 0.99).

Conclusion: Our study characterizes the extravascular thoracic MDCT angiography findings in secondary pediatric PVS due to TAPVC repair. In the lungs and pleura, ground-glass opacity, interlobular septal thickening, and pleural thickening are common findings. Importantly, the presence of a mildly heterogeneously enhancing, non-calcified mediastinal soft tissue mass in the distribution of the PVS is a novel characteristic thoracic MDCT angiography finding seen in pediatric secondary PVS due to TAPVC repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/children8090726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468419PMC
August 2021

Extravascular MDCT Findings of Pulmonary Vein Stenosis in Children with Cardiac Septal Defect.

Children (Basel) 2021 Jul 30;8(8). Epub 2021 Jul 30.

Department of Radiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

: To retrospectively investigate the extravascular thoracic MDCT angiography findings of pulmonary vein stenosis (PVS) in children with a cardiac septal defect. Pediatric patients (age ≤ 18 years) with cardiac septal defect and PVS, confirmed by echocardiogram and/or conventional angiography, who underwent thoracic MDCT angiography studies from April 2009 to April 2021 were included. Two pediatric radiologists independently evaluated thoracic MDCT angiography studies for the presence of extravascular thoracic abnormalities in: (1) lung and airway (ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, septal thickening, fibrosis, and bronchiectasis); (2) pleura (pleural thickening, pleural effusion, and pneumothorax); and (3) mediastinum (mass and lymphadenopathy). Interobserver agreement between the two independent pediatric radiology reviewers was evaluated with kappa statistics. The final study group consisted of 20 thoracic MDCT angiography studies from 20 consecutive individual pediatric patients (13 males (65%) and 7 females (35%); mean age: 7.5 months; SD: 12.7; range: 2 days to 7 months) with cardiac septal defect and PVS. The characteristic extravascular thoracic MDCT angiography findings were GGO (18/20; 90%), septal thickening (9/20; 45%), pleural thickening (16/20; 80%), and ill-defined, mildly heterogeneously enhancing, non-calcified soft tissue mass (9/20; 45%) following the contours of PVS in the mediastinum. There was a high interobserver kappa agreement between two independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (k = 0.99). PVS in children with a cardiac septal defect has a characteristic extravascular thoracic MDCT angiography finding. In the lungs and pleura, GGO, septal thickening, and pleural thickening are frequently seen in children with cardiac septal defect and PVS. In the mediastinum, a mildly heterogeneously enhancing, non-calcified soft tissue mass in the distribution of PVS in the mediastinum is seen in close to half of the pediatric patients with cardiac septal defect and PVS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/children8080667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394993PMC
July 2021

Thoracic Multidetector Computed Tomography Findings of Dedicator of Cytokinesis 8 Deficiency in Children.

J Thorac Imaging 2021 Sep;36(5):304-309

Department of Radiology.

Purpose: To investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of dedicator of cytokinesis 8 (DOCK8) deficiency, a rare autosomal recessive form of hyperimmunoglobulin E syndrome, in children.

Materials And Methods: All pediatric patients (age 18 y and below) with a known diagnosis of DOCK8 deficiency based on genetic testing who underwent thoracic MDCT studies from November 2004 to November 2020 were included. Two pediatric radiologists independently evaluated MDCT studies for the presence of thoracic abnormalities in the lung [ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, and bronchiectasis], pleura (pleural effusion and pneumothorax), and mediastinum (lymphadenopathy). When a lung abnormality was present, laterality, distribution (upper, middle, and lower lung zone), and extent were also evaluated. When a pleural abnormality was identified, laterality and size of the abnormality were also assessed. When mediastinal lymphadenopathy was present, its location and size were also evaluated. Interobserver agreement between two independent reviewers was evaluated with κ statistics.

Results: In all, 17 thoracic MDCT studies from 17 individual pediatric patients [5 males (29%) and 12 females (71%); mean age: 7.4 y; SD: 3.7; range: 1 to 13 y] comprised the final study population. Among 17 thoracic MDCT studies, 11 studies (65%) were performed with intravenous contrast (IV) and the remaining 6 MDCT studies (35%) were obtained without IV contrast. Bilateral bronchiectasis (11/17; 65%) with a middle lung zone predominance (8/11; 73%) was the most frequently detected lung abnormality, followed by GGO in 9/17 patients (53%). Among 11 contrast-enhanced MDCT studies, the majority (9 patients, 82%) had mediastinal lymphadenopathy. There was excellent interobserver κ agreement between 2 independent reviewers for detecting abnormalities on thoracic MDCT studies (κ>0.90).

Conclusion: Children with DOCK8 deficiency have characteristic thoracic MDCT findings, including bilateral bronchiectasis with a middle lung zone predominance, GGO, and mediastinal lymphadenopathy. When these characteristic thoracic MDCT findings are detected, although rare, DOCK8 deficiency should be considered as a possible underlying diagnosis in the pediatric population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RTI.0000000000000587DOI Listing
September 2021

A homozygous stop-gain variant in ARHGAP42 is associated with childhood interstitial lung disease, systemic hypertension, and immunological findings.

PLoS Genet 2021 07 7;17(7):e1009639. Epub 2021 Jul 7.

Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

ARHGAP42 encodes Rho GTPase activating protein 42 that belongs to a member of the GTPase Regulator Associated with Focal Adhesion Kinase (GRAF) family. ARHGAP42 is involved in blood pressure control by regulating vascular tone. Despite these findings, disorders of human variants in the coding part of ARHGAP42 have not been reported. Here, we describe an 8-year-old girl with childhood interstitial lung disease (chILD), systemic hypertension, and immunological findings who carries a homozygous stop-gain variant (c.469G>T, p.(Glu157Ter)) in the ARHGAP42 gene. The family history is notable for both parents with hypertension. Histopathological examination of the proband lung biopsy showed increased mural smooth muscle in small airways and alveolar septa, and concentric medial hypertrophy in pulmonary arteries. ARHGAP42 stop-gain variant in the proband leads to exon 5 skipping, and reduced ARHGAP42 levels, which was associated with enhanced RhoA and Cdc42 expression. This is the first report linking a homozygous stop-gain variant in ARHGAP42 with a chILD disorder, systemic hypertension, and immunological findings in human patient. Evidence of smooth muscle hypertrophy on lung biopsy and an increase in RhoA/ROCK signaling in patient cells suggests the potential mechanistic link between ARHGAP42 deficiency and the development of chILD disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289122PMC
July 2021

Thoracic MDCT findings of a combined congenital lung lesion: Bronchial atresia associated with congenital pulmonary airway malformation.

Pediatr Pulmonol 2021 Sep 21;56(9):2903-2910. Epub 2021 Jul 21.

Department of Radiology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA.

Purpose: To investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of pathologically proven combined congenital lung lesion consisting of bronchial atresia (BA) and congenital pulmonary airway malformation (CPAM) in children.

Materials And Methods: All pediatric patients (age ≤ 18 years) with a known pathological diagnosis of a combined BA-CPAM congenital lung lesion, who underwent thoracic MDCT studies from January 2011 to January 2021 were included. Two pediatric radiologists independently evaluated thoracic MDCT studies for the presence of abnormalities in the lung, including nodule, mass, cyst, ground-glass opacity, and consolidation. When a lung abnormality was present, the number, size, composition (solid, cystic, or combination of both), borders (well-circumscribed vs. ill-defined), contrast enhancement pattern (nonenhancement vs. enhancement), and location (laterality, and lobar distribution) were also evaluated. Interobserver agreement between two independent reviewers was evaluated with κ statistics.

Results: Eighteen contrast-enhanced thoracic MDCT studies from 18 individual pediatric patients (8 males (44%) and 10 females (56%); mean age: 4.9 months; SD: 2.6; range: 1-10 months) with a pathological diagnosis of combined BA-CPAM congenital lung lesion comprised the final study population. The most frequent MDCT finding of combined BA-CPAM congenital lung lesion in children was a solitary (18/18; 100%), well-circumscribed (18/18; 100%), both solid and cystic (17/18; 94%) lesion with nonenhancing (17/17; 100%) nodule, reflecting the underlying BA component, adjacent to a well-circumscribed multicystic mass (18/18; 100%), representing the underlying CPAM component. This combined congenital lung lesion occurred in all lobes with similar frequency. There was almost perfect interobserver κ agreement between the two independent reviewers for detecting abnormalities on thoracic MDCT studies (k = 0.98).

Conclusion: The characteristic thoracic MDCT findings of a combined BA-CPAM congenital lung lesion are a solitary, well-circumscribed solid and multicystic mass, with a nonenhancing nodule, reflecting the BA component, adjacent to a cystic mass, representing the CPAM component. Accurate recognition of these characteristic MDCT findings of combined BA-CPAM congenital lung lesion has great potential to help differentiate this combined congenital lung lesion from other thoracic pathology in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.25556DOI Listing
September 2021

Thoracic Multidetector Computed Tomography Angiography of Primary Pulmonary Vein Stenosis in Children: Evaluation of Characteristic Extravascular Findings.

J Thorac Imaging 2021 Sep;36(5):318-325

Departments of Radiology.

Purpose: The purpose of this study was to investigate the extravascular thoracic multidetector computed tomography (MDCT) angiography findings of pediatric primary pulmonary vein stenosis (PVS) by comparing extravascular thoracic MDCT angiography findings in children with and without PVS.

Materials And Methods: All pediatric patients (age 18 y and below) with a known diagnosis of primary PVS, confirmed by echocardiogram and/or conventional angiography, who underwent thoracic MDCT angiography studies from July 2006 to December 2020 were included. A comparison group, comprised of age-matched and sex-matched pediatric patients without PVS who underwent thoracic MDCT angiography studies during the same study period, was also generated. Two pediatric radiologists independently evaluated thoracic MDCT angiography studies for the presence of extravascular thoracic abnormalities in the lung (ground-glass opacity [GGO], consolidation, pulmonary nodule, mass, cyst, septal thickening, fibrosis, and bronchiectasis), pleura (pleural thickening, pleural effusion and pneumothorax), and mediastinum (lymphadenopathy and mass). When a thoracic abnormality was identified, the location and distribution of the abnormality (in relation to the location of PVS) were also evaluated. Extravascular thoracic MDCT angiography findings of pediatric patients with and without primary PVS were compared. Interobserver agreement between the 2 independent reviewers was evaluated with κ statistics.

Results: The study group consisted of 15 thoracic MDCT angiography studies from 15 individual pediatric patients with primary PVS (8 males [53%] and 7 females [47%]; mean age: 10.9 mo; SD: 11.7 mo; range: 1 to 48 mo). The comparison group consisted of 15 thoracic MDCT angiography studies from 15 individual pediatric patients without PVS (8 males [53%] and 7 females [47%]; mean age: 10.2 mo; SD: 11.5 mo; range: 1 to 48 mo). In children with primary PVS, the characteristic extravascular thoracic MDCT angiography findings were GGO (14/15; 93%), septal thickening (5/15; 33%), pleural thickening (14/15; 93%), and ill-defined, mildly heterogeneously enhancing, noncalcified soft tissue mass (14/15; 93%) following the contours of PVS in the mediastinum. There was excellent interobserver κ agreement between 2 independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (κ=0.99 for the study group and κ=0.98 for the comparison group).

Conclusions: Children with primary PVS have characteristic extravascular thoracic MDCT angiography findings. In the lungs and pleura, GGO, septal thickening, and pleural thickening are common findings. Importantly, in the mediastinum, the presence of a mildly heterogeneously enhancing, noncalcified soft tissue mass in the distribution of PVS is a novel characteristic thoracic MDCT angiography finding unique to pediatric primary PVS. When this constellation of extravascular thoracic MDCT angiography findings is detected, although rare, primary PVS should be considered as a possible underlying diagnosis, especially in symptomatic children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RTI.0000000000000590DOI Listing
September 2021

Airway basal stem cells generate distinct subpopulations of PNECs.

Cell Rep 2021 Apr;35(3):109011

Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:

Pulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.109011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140387PMC
April 2021

Thoracic Multidetector Computed Tomography Evaluation of Inflammatory Myofibroblastic Tumor of the Lung in Pediatric Patients in the Era of Modern Diagnosis.

J Thorac Imaging 2021 Sep;36(5):310-317

Departments of Radiology.

Purpose: The purpose of this study was to investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of pathologically proven inflammatory myofibroblastic tumor (IMT) of the lung in children in the era of modern understanding based on refined pathologic diagnosis.

Materials And Methods: All pediatric patients (age 18 y and above) with a known pathologic diagnosis of IMT of the lung who underwent thoracic MDCT studies from May 2008 to December 2020 were included. Two pediatric radiologists independently evaluated thoracic MDCT studies for the presence of abnormalities in the lung (nodule, mass, cyst, ground-glass opacity, consolidation), pleura (pleural effusion, pneumothorax), and mediastinum and hilum (lymphadenopathy). When a lung abnormality was present, the number, size, composition (solid, cystic, or combination of both), location (laterality, lobar distribution, and intraparenchymal vs. pleural-based), borders (well-circumscribed vs. ill-defined), the presence and type of associated calcification (punctate, dense, curvilinear, or flocculent), the presence of associated cavitation, contrast enhancement pattern (homogeneous, heterogenous, central, or peripheral), and other associated findings (neural foramen involvement, anomalous vessels, mass effect, and invasion of adjacent thoracic structures) were also evaluated. Interobserver agreement between 2 independent reviewers was evaluated with κ statistics.

Results: In all, 12 thoracic MDCT studies from 12 individual pediatric patients (5 males [42%] and 7 females [58%]; mean age: 9.9 y; SD: 4.4 y; range: 2 to 16 y) comprised the final study population. All 12 thoracic MDCT studies (100%) were performed with intravenous contrast. The most frequent MDCT finding of IMT of the lung in children is a solitary (92%), pleural-based (83%), well-circumscribed (100%), solid (92%) mass with heterogenous contrast enhancement (100%), often with dense calcification (50%), which occurred in both lungs and all lobes with similar frequency. No pleural abnormality (pleural effusion, pneumothorax) or mediastinal abnormality (lymphadenopathy) was detected. In addition, although mass effect on adjacent thoracic structures was frequently seen (42%), no invasion, neural foramen involvement, or associated anomalous vessels was identified. There was excellent interobserver κ agreement between 2 independent reviewers for detecting abnormalities on thoracic MDCT studies (κ>0.95).

Conclusions: IMT of the lung in children typically presents as a solitary, pleural-based, well-circumscribed, solid mass with heterogenous contrast enhancement, often with dense calcification, without significant laterality or lobar preference. In addition, pleural or mediastinal abnormalities are characteristically absent. These notable MDCT attributes of IMT of the lung are an important and novel finding, with great potential to help differentiate pediatric IMT of the lung from other thoracic masses in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RTI.0000000000000589DOI Listing
September 2021

Correlation of Intravascular Ultrasound with Histology in Pediatric Pulmonary Vein Stenosis.

Children (Basel) 2021 Mar 4;8(3). Epub 2021 Mar 4.

Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Preliminary intravascular ultrasound (IVUS) images of suspected pediatric intraluminal pulmonary vein stenosis (PVS) demonstrate wall thickening. It is unclear how the IVUS-delineated constituents of wall thickening correlate with the histology. We analyzed six postmortem formalin-fixed heart/lung specimens and four live patients with PVS as well as control pulmonary veins using IVUS and light microscopic examination. In PVS veins, IVUS demonstrated wall thickening with up to two layers of variable echogenicity, often with indistinct borders. Histologically, the veins showed fibroblastic proliferation with areas rich in myxoid matrix as well as areas with abundant collagen and elastic fibers. Discrete vein layers were obscured by scarring and elastic degeneration. A lower reflective periluminal layer by IVUS corresponded with hyperplasia of myofibroblast-like cells in abundant myxoid matrix. The hyper-reflective layer by IVUS extended to the outer edge of the vessel and corresponded to a less myxoid area with more collagen, smooth muscle and elastic fibers. The outer less reflective edge of the IVUS image correlated with a gradual transition into adventitia. Normal veins had a thin wall, correlating with histologically normal cellular and extracellular components, without intimal proliferation. IVUS may provide further understanding of the anatomy and mechanisms of pediatric pulmonary vein obstruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/children8030193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999454PMC
March 2021

Liver Pathology, Including MOC31 Immunohistochemistry, in Congenital Tufting Enteropathy.

Am J Surg Pathol 2021 08;45(8):1091-1097

Departments of Pathology.

Congenital tufting enteropathy (CTE) is a rare heritable cause of intractable diarrhea due to EPCAM mutation. Pathologic findings include intestinal villous atrophy, tufted discohesive tear-drop-shaped epithelium, and a normal brush border. In affected patients, absent intestinal epithelial cell adhesion molecule (EpCAM) expression results in loss of MOC31 immunostaining. CTE liver pathology has not yet been described. We identified CTE patients with liver biopsies and reviewed clinicopathologic material including MOC31 immunohistochemistry. Three CTE patients had 4 liver core biopsies (at ages 1, 5, 7, and 16 y), 2 for preintestinal transplant evaluation, and 2 (from a single patient) for pretreatment assessment of chronic hepatitis C; all had received parenteral nutrition (PN). All samples showed loss of biliary epithelial polarization and mild portal and lobular inflammation. Only the hepatitis C patient demonstrated fibrosis. One patient each had lobular neutrophilic microabscesses and macrovesicular steatosis. Proliferative ductular reactions were absent in CTE patients but present in all controls on PN for other reasons. MOC31 was absent in biliary epithelium and hepatocytes of all CTE patients; controls showed consistent strong membranous biliary epithelial and patchy membranous periportal hepatocyte staining. Our data show that, histologically, hepatopathy in CTE can be difficult to separate from comorbid disease including PN effect; however, the absent ductular reaction may be characteristic. MOC31 localization in the biliary epithelium and zone 1 hepatocytes of controls suggests these compartments of the liver might be most susceptible to effects of EpCAM deficiency. In addition, we validate the liver as suitable tissue for CTE diagnosis using MOC31 immunohistochemistry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001710DOI Listing
August 2021

CT Features of Benign Intrapulmonary Lymph Nodes in Pediatric Patients With Known Extrapulmonary Solid Malignancy.

AJR Am J Roentgenol 2021 05 17;216(5):1357-1362. Epub 2021 Mar 17.

Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, MA.

The purpose of our study was to determine the CT features of benign intrapulmonary lymph nodes in pediatric patients with known extrapulmonary solid malignancy. A retrospective review of surgical pathology archives was performed to identify consecutive chest CT studies of pediatric patients (≤ 18 years) with extrapulmonary solid malignancy and histologically confirmed benign intrapulmonary lymph nodes between January 1, 2004, and March 15, 2020. CT features of intrapulmonary lymph nodes-including size, shape, margin, type, associated calcification or fat, and location-were independently evaluated by two pediatric radiologist reviewers. The CT features of benign intrapulmonary lymph nodes in pediatric patients were analyzed using summary statistics. Interobserver agreement was measured with the kappa coefficient. There were 36 pathology-confirmed benign intrapulmonary lymph nodes in 27 pediatric patients (18 boys and nine girls; mean age, 12 years; age range, 1-18.2 years). Twenty-three (63.9%) of the benign intrapulmonary lymph nodes were biopsied from the right lung and 13 (36.1%) from the left lung ( = .03). The mean size, determined from CT studies, of benign intrapulmonary lymph nodes was 3.6 mm (SD, 1.4 mm; range, 1.3-7.8 mm). Triangular shape (25/36, 69.4%) was the most common shape of the benign intrapulmonary lymph nodes. Less commonly seen shapes of benign intrapulmonary lymph nodes were oval (6/36, 16.7%), round (3/36, 8.3%), and trapezoidal (2/36, 5.6%). All benign intrapulmonary lymph nodes were smoothly marginated and solid without associated calcification or fat. Of the 36 benign intrapulmonary lymph nodes, 15 (41.7%) were pleura-based; 11 (30.6%), perifissural; and 10 (27.8%), parenchymal. The kappa value for interobserver agreement between the two reviewers was 0.917 (95% CI, 0.825-1.000; standard error, 0.047), which corresponds to near-perfect agreement. In pediatric patients with known extrapulmonary solid malignancy, benign intrapulmonary lymph nodes are subcentimeter (mean size, 3.6 mm), smoothly marginated, and solid without containing calcification or fat on CT. In particular, triangular shape was the most commonly encountered shape of a benign intrapulmonary lymph node.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.20.23363DOI Listing
May 2021

Restrictive allograft syndrome after lung transplantation.

Pediatr Transplant 2021 May 17;25(3):e14000. Epub 2021 Mar 17.

Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Despite recent advances over the past decade in lung transplantation including improved surgical technique and immunotherapy, the diagnosis and treatment of chronic lung allograft dysfunction remains a significant barrier to recipient survival. Aside from bronchiolitis obliterans syndrome, a restrictive phenotype called restrictive allograft syndrome has recently been recognized and affects up to 35% of all patients with CLAD. The main characteristics of RAS include a persistent and unexplained decline in lung function compared to baseline and persistent parenchymal infiltrates on imaging. The median survival after diagnosis of RAS is 6 to 18 months, significantly shorter than other forms of CLAD. Treatment options are limited, as therapies used for BOS are typically ineffective at halting disease progression. Specific medications such as fibrinolytics are lacking large, multicenter prospective studies. In this manuscript, we discuss the definition, mechanism, and characteristics of RAS while highlighting the similarities and differences between other forms of CLAD. We also review the diagnoses along with current and potential treatment options that are available for patients. Finally, we discuss the existing knowledge gaps and areas for future research to improve patient outcomes and understanding of RAS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.14000DOI Listing
May 2021

Pulmonary manifestations of immune dysregulation in CTLA-4 haploinsufficiency and LRBA deficiency.

Pediatr Pulmonol 2021 07 23;56(7):2232-2241. Epub 2021 Mar 23.

Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objective: The primary immunodeficiency syndromes of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency and lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency present with multisystem immune dysregulation. The aim of this study was to characterize and compare the pulmonary manifestations of these two diseases.

Methods: We retrospectively analyzed the pulmonary clinical, radiologic, and histopathologic characteristics of six patients with CTLA-4 haploinsufficiency and four patients with LRBA deficiency with pulmonary involvement followed at a large tertiary care center.

Results: Chronic respiratory symptoms were more frequent in patients with LRBA deficiency versus CTLA-4 haploinsufficiency (3/4 vs. 1/6). Cough was the most common respiratory symptom. Abnormalities in pulmonary exam and pulmonary function testing were more frequent in LRBA deficiency (4/4, 2/4) compared to CTLA-4 haploinsufficiency (1/6, 2/6). Chest computed tomography (CT) findings included mediastinal lymphadenopathy (4/4 in LRBA deficiency vs. 1/4 in CTLA-4 haploinsufficiency), pulmonary nodules (4/4, 3/4), ground-glass opacification (4/4, 3/4), and bronchiectasis (3/4, 1/4). Lymphocytic inflammation, concentrated bronchovasculocentrically and paraseptally, was the predominant pathologic finding and was observed in all patients who had lung biopsies (N = 3 with LRBA deficiency; N = 3 with CTLA-4 haploinsufficiency).

Conclusion: Despite phenotypic overlap amongst these diseases, LRBA deficiency demonstrated greater severity of pulmonary disease, indicated by respiratory symptoms, pulmonary exam, and intrathoracic radiologic findings. Chest CT was the most sensitive indicator of pulmonary involvement in both disorders. Lymphocytic inflammation is the key histologic feature of both disorders. Pediatric pulmonologists should consider these disorders of immune dysregulation in the relevant clinical context to provide earlier diagnosis, comprehensive pulmonary evaluation and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.25373DOI Listing
July 2021

Heterotopic Liver Nodule Compressing a Two-Vessel Umbilical Cord: An Unusual Cause of Intrauterine Fetal Demise.

Pediatr Dev Pathol 2021 May-Jun;24(3):241-245. Epub 2021 Feb 16.

Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Heterotopic liver tissue in the umbilical cord is rare, and the outcome is quite unpredictable based on the few reported cases. We present a case of heterotopic liver nodule in the umbilical cord of a midtrimester fetus who died in utero. Although such association has only been reported once, heterotopic nodular tissue in the umbilical cord must be regarded as a potential cause of fetal demise by a mechanism analogous to the more common umbilical cord abnormalities resulting in umbilical vessel compromise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1093526621993330DOI Listing
February 2021

NEDD9 Is a Novel and Modifiable Mediator of Platelet-Endothelial Adhesion in the Pulmonary Circulation.

Am J Respir Crit Care Med 2021 06;203(12):1533-1545

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. To identify a hypoxia-sensitive, modifiable mediator of platelet-pulmonary artery endothelial cell adhesion and thrombotic remodeling. Network medicine was used to profile protein-protein interactions in hypoxia-treated human pulmonary artery endothelial cells. Data from liquid chromatography-mass spectrometry and microscale thermophoresis informed the development of a novel antibody (Ab) to inhibit platelet-endothelial adhesion, which was tested in cells from patients with chronic thromboembolic pulmonary hypertension (CTEPH) and three animal models . The protein NEDD9 was identified in the hypoxia thrombosome network . Compared with normoxia, hypoxia (0.2% O) for 24 hours increased HIF-1α (hypoxia-inducible factor-1α)-dependent NEDD9 upregulation . Increased NEDD9 was localized to the plasma-membrane surface of cells from control donors and patients with CTEPH. In endarterectomy specimens, NEDD9 colocalized with the platelet surface adhesion molecule P-selectin. Our custom-made anti-NEDD9 Ab targeted the NEDD9-P-selectin interaction and inhibited the adhesion of activated platelets to pulmonary artery endothelial cells from control donors and from patients with CTEPH . Compared with control mice, platelet-pulmonary endothelial aggregates and pulmonary hypertension induced by ADP were decreased in NEDD9 mice or wild-type mice treated with the anti-NEDD9 Ab, which also decreased chronic pulmonary thromboembolic remodeling . The NEDD9-P-selectin protein-protein interaction is a modifiable target with which to inhibit platelet-pulmonary endothelial adhesion and thromboembolic vascular remodeling, with potential therapeutic implications for patients with disorders of increased hypoxia signaling pathways, including CTEPH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202003-0719OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483217PMC
June 2021

A case of metastatic adenocarcinoma of unknown primary in a pediatric patient: Opportunities for precision medicine.

Pediatr Blood Cancer 2021 04 12;68(4):e28780. Epub 2020 Dec 12.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28780DOI Listing
April 2021

Role of Surgery in Rhabdomyosarcoma of the Head and Neck in Children.

Laryngoscope 2021 03 20;131(3):E984-E992. Epub 2020 Jul 20.

Department of Otolaryngology & Communication Enhancement, Boston Children's Hospital, Boston, Massachusetts, U.S.A.

Objectives: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The goal of this research is to analyze the role of surgery in the management of pediatric parameningeal (PM) and non-PM head and neck RMS (HNRMS).

Study Design: Retrospective review.

Methods: Retrospective chart review of patients <20 years of age treated for HNRMS between 1970 and 2015. Clinical presentation, tumor characteristics, treatment, recurrence, follow-up, and outcome data were collected.

Results: Of 97 patients with HNRMS, 56% were male. Overall median (IQR: interquartile range) age at diagnosis was 5.8 (3.3-9.8) years. Sixty-five patients (67%) had PM tumors. Of 75 patients with histologic subtype identified, 51 (53%) had embryonal and 20 (21%) alveolar RMS. Almost all patients received chemotherapy (99%) and radiotherapy (95%). Forty-four patients (45%) underwent surgery. Surgery was more likely to be conducted in patients with lesions of a non-PM site. Median follow-up time was 3.4 years (IQR: 1.1-10.8). In 5 years of follow-up, 20% (17 of 85) died and 29% (20 of 70) had recurrence. The estimated 5-year survival rate was 72% (95% CI, 57.8, 81.5%). Surgery was associated with a reduced risk of mortality after accounting for TNM stage 4 and tumor site (adjusted HR 0.24; 95% CI, 0.07, 0.79; P = .02). The association between surgery and risk of mortality was similar in PM and non-PM tumors.

Conclusion: A multimodal protocol for treatment including chemotherapy, surgery, and radiotherapy is the mainstay for management of children with HNRMS. While surgery is more commonly used to treat non-PM HNRMS, patients who are able to undergo surgery have significantly higher 5-year survival.

Level Of Evidence: 4 Laryngoscope, 131:E984-E992, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.28785DOI Listing
March 2021

A serous borderline ovarian tumour in a transgender male adolescent.

Br J Cancer 2021 02 27;124(3):567-569. Epub 2020 Oct 27.

Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA, USA.

Here we present a transgender male adolescent with an androgen receptor-positive serous borderline ovarian tumour in the setting of testosterone treatment for medical gender transition. To our knowledge, this is the second report of borderline tumour in a transgender individual and the first in an adolescent, an age group in which borderline tumours are extremely rare. We discuss the specific considerations of treating ovarian tumours in the transgender male population, the incompletely understood role of androgens in the genesis of ovarian epithelial neoplasia, and an emphasis on assessing cancer risk in transgender patients based on patient anatomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-020-01129-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851115PMC
February 2021

Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant.

Histopathology 2021 Jan 9;78(2):265-275. Epub 2020 Nov 9.

Department of Pathology, Boston Children's Hospital, Boston, MA, USA.

Aims: Primary intracranial sarcoma, DICER1-mutant is a recently described central nervous system tumour with specific genomic and DNA-methylation profiles. Although some of its histological features (focal spindle-cell morphology, intracytoplasmic eosinophilic granules, and focal heterologous differentiation) are common across most reported cases, the presence of significant histological variability and the lack of differentiation pose diagnostic challenges. We aim to further define the immunoprofile of this tumor.

Methods And Results: We reviewed the clinical history and performed immunohistochemistry for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, SOX2, SOX10, S100, histone H3 trimethylated on lysine 27 (H3K27me3), desmin, myogenin, CD99, epithelial membrane antigen (EMA) and transducin-like enhancer of split 1 (TLE1) on six primary intracranial sarcomas, DICER1-mutant, with appropriate controls. Targeted exome sequencing was performed on all cases. The sarcomas showed diffuse (n = 4), mosaic (n = 1) or minimal (≤5%, n = 1) loss of H3K27 trimethylation and nuclear TLE1 expression (n = 6). Four had immunohistochemical evidence of myogenic differentiation. SOX2, SOX10, S100 and EMA were negative; CD99 expression ranged from focal cytoplasmic (n = 4) to crisp diffuse membranous (n = 2). One tumour had focal cartilaginous differentiation. Similar immunohistochemical findings were observed in a pleuropulmonary blastoma (albeit with focal TLE1 expression), a DICER1-related pineoblastoma, and an embryonal tumour with a multilayered rosette-like DICER1-related cerebellar tumour. Targeted exome sequencing confirmed the presence of pathogenic biallelic DICER1 mutations in all tumours included in this study.

Conclusion: We conclude that H3K27me3 and TLE1 immunostains, when utilised in combination, can be helpful diagnostic markers for primary intracranial sarcoma, DICER1-mutant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14217DOI Listing
January 2021

Making the most of small samples: Optimization of tissue allocation of pediatric solid tumors for clinical and research use.

Pediatr Blood Cancer 2020 09 15;67(9):e28326. Epub 2020 Jul 15.

Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.

Introduction: Tissue from pediatric solid tumors is in high demand for use in high-impact research studies, making the allocation of tissue from an anatomic pathology laboratory challenging. We designed, implemented, and assessed an interdepartmental process to optimize tissue allocation of pediatric solid tumors for both clinical care and research.

Methods: Oncologists, pathologists, surgeons, interventional radiologists, pathology technical staff, and clinical research coordinators participated in the workflow design. Procedures were created to address patient identification and consent, prioritization of protocols, electronic communication of requests, tissue preparation, and distribution. Pathologists were surveyed about the value of the new workflow.

Results: Over a 5-year period, 644 pediatric solid tumor patients consented to one or more studies requesting archival or fresh tissue. Patients had a variety of tumor types, with many rare and singular diagnoses. Sixty-seven percent of 1768 research requests were fulfilled. Requests for archival tissue were fulfilled at a significantly higher rate than those for fresh tissue (P > .001), and requests from resection specimens were fulfilled at a significantly higher rate than those from biopsies (P > .0001). In an anonymous survey, seven of seven pathologists reported that the process had improved since the introduction of the electronic communication model.

Conclusions: A collaborative and informed model for tissue allocation is successful in distributing archival and fresh tissue for clinical research studies. Our workflows and policies have gained pathologists' approval and streamlined our processes. As clinical and research programs evolve, a thoughtful tissue allocation process will facilitate ongoing research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28326DOI Listing
September 2020

DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor.

Mod Pathol 2020 10 14;33(10):1910-1921. Epub 2020 Apr 14.

Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

The spectrum of neoplasms associated with DICER1 variants continues to expand, with the recent addition of primary "DICER1-associated central nervous system sarcoma" (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. Six pediatric DCS were identified through a combination of clinical diagnostic studies, archival inquiry, and interinstitutional collaboration. Clinical, histologic, immunohistologic, and molecular features were examined. Genomic findings in the 6 DCS were compared with those in 14 additional DICER1-associated tumors sequenced with the same assay. The six patients presented at ages 3-15 years with CNS tumors located in the temporal (n = 2), parietal (n = 1), fronto-parietal (n = 1), and frontal (n = 2) lobes. All underwent surgical resection. Histologic examination demonstrated high-grade malignant spindle cell tumors with pleuropulmonary blastoma-like embryonic "organoid" features and focal rhabdomyoblastic differentiation; immature cartilage was seen in one case. Immunohistochemically, there was patchy desmin and myogenin staining, and patchy loss of H3K27me3, and within eosinophilic cytoplasmic globules, alfa-fetoprotein staining. Biallelic DICER1 variants were identified in all cases, with germline variants in two of five patients tested. DCS demonstrated genomic alterations enriched for Ras pathway activation and TP53 inactivation. Tumor mutational burden was significantly higher in the 6 DCS tumors than in 14 other DICER1-associated tumors examined (mean 12.9 vs. 6.8 mutations/Mb, p = 0.035). Postoperative care included radiation (n = 5) and chemotherapy (n = 3); at the last follow-up, three patients were alive without DCS, and three had died of disease. Our analysis expands the clinical, histologic, immunohistological, and molecular spectrum of DCS, identifying distinctive features that can aid in the diagnosis, multidisciplinary evaluation, and treatment of DCS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-0516-1DOI Listing
October 2020

Prostatic Metaplasia of the Vagina and Uterine Cervix: An Androgen-associated Glandular Lesion of Surface Squamous Epithelium.

Am J Surg Pathol 2020 08;44(8):1040-1049

Departments of Pathology.

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation "androgen-associated prostatic metaplasia" for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001486DOI Listing
August 2020

An Unusual Cause of Mosaic Attenuation.

Am J Respir Crit Care Med 2020 07;202(1):128-129

Division of Pulmonary and Critical Care Medicine and.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201908-1618IMDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328322PMC
July 2020

Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms.

Histopathology 2020 Jun 15;76(7):1032-1041. Epub 2020 May 15.

Department of Pathology, Boston Children's Hospital, Boston, MA, USA.

Aims: The classification of paediatric spindle mesenchymal tumours is evolving, and the spectrum of so-called 'infantile fibrosarcoma' has expanded to include tumours with NTRK, BRAF and MET gene fusions. RET-rearranged paediatric spindle cell neoplasms are an emerging group; there is sparse literature on their clinical, pathological and genetic features, and their nosological place in the canon of soft tissue tumours is uncertain. In this study, we report five RET-rearranged paediatric spindle cell tumours with fusion partners MYH10, KIAA1217 and CLIP2.

Methods And Results: The tumours occurred in the pelvic region, paraspinal region, kidney and subcutaneous tissue of hand and abdomen. The patients' ages ranged from 6 months to 13 years (median 1 year). The tumours were composed of monomorphic spindle cells arranged in a fascicular pattern. Lesional cells had minimally atypical ovoid or tapered nuclei and pale cytoplasm with indistinct borders. Necrosis was not identified. Mitoses numbered three to 12 per 10 high-power field. Cases showed inconsistent and variable expression of S100, CD34 and SMA. Clinical behaviour ranged from small lesions potentially cured by simple resection to large lesions exhibiting metastasis, but responsive to kinase inhibitor therapy.

Conclusions: Our findings help to define RET-rearranged spindle cell tumours. Although it is likely that these tumours comprise part of the morphological and clinical spectrum of infantile fibrosarcoma (IFS), identification of RET gene alteration is important for its unique therapeutic implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14082DOI Listing
June 2020

CORR® Tumor Board: Is the Width of a Surgical Margin Associated with the Outcome of Disease in Patients with Peripheral Chondrosarcoma of the Pelvis? A Multicenter Study.

Clin Orthop Relat Res 2019 11;477(11):2429-2431

M. E. Anderson, Orthopaedic Oncology Surgeon, Beth Israel Deaconess Medical Center and Boston Children's Hospital, Boston, MA, USA J. S. Wu, Musculoskeletal Radiologist, Beth Israel Deaconess Medical Center, Boston, MA, USA S. O Vargas, Staff Pathologist, Boston Children's Hospital, Boston, MA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CORR.0000000000000983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903844PMC
November 2019

Emergent high fatality lung disease in systemic juvenile arthritis.

Ann Rheum Dis 2019 12 27;78(12):1722-1731. Epub 2019 Sep 27.

Pediatrics, Prince of Wales Hospital, New Territories, Hong Kong.

Objective: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).

Methods: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.

Results: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.

Conclusions: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-216040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065839PMC
December 2019

Congenital Epidermoid Cyst of the Liver: A Rare Entity Characterized by Antenatal Onset, Slow Postnatal Growth, and Consistent Histologic and Immunohistologic Features.

Pediatr Dev Pathol 2020 May-Jun;23(3):181-188. Epub 2019 Sep 11.

Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.

Background: There are only 15 reported hepatic epidermoid cysts; they include patients presenting congenitally through adulthood, with varied speculations about pathogenesis. Aside from recently reported pancytokeratin staining, no other descriptions have included immunohistochemistry. Splenic epidermoid cysts were recently characterized as positive for HBME-1, p63, CEA, CK7 (luminal), and CK19. We interrogate 2 hepatic epidermoid cysts with a broad panel of immunohistochemistry, with the aim of elucidating histogenesis.

Methods: Archives were searched for "liver," "hepatic," and "cyst." Hepatic cysts lined by squamous epithelium were included. Clinical records, macroscopic findings, and hematoxylin and eosin and immunohistochemically stained slides were reviewed.

Results: We identified 2 patients with epidermoid cysts of the liver, first detected on antenatal ultrasound. Both were females and asymptomatic; neither had other congenital abnormalities. Cysts enlarged slowly after birth. Resection was at ages 2 and 6 months, done to avoid potentially more difficult surgery in the future. Cysts were unilocular (4.8 cm) and multilocular (7.0 cm). Both were lined by stratified nonkeratinizing squamous to focally transitional-like epithelium and surrounded by paucicellular fibrous stroma. In the multilocular cyst, hepatocytes and fibrous stroma populated septa. Epithelium was positive for HBME-1, p63, CK19, CEA, Cam5.2, and CK7, negative for EMA, D2-40, WT-1, calretinin, and Ca19-9. Cytogenetic analysis of one showed a normal female karyotype. During the study period, 22 other pediatric liver cysts were diagnosed.

Conclusion: Hepatic epidermoid cyst is a distinct entity, rare but nevertheless constituting 8% of pediatric hepatic cysts at our institution. It is characterized by intrauterine onset and growth roughly commensurate with that of the fetus/infant; it is apparently unsyndromic. It may be unilocular or multilocular. It stains for an array of epithelial markers as well as HBME-1. Strong immunohistochemical overlap with splenic epidermoid cyst points to a shared pathogenesis and detracts from hypotheses that hepatic epidermoid cysts derive from hepatic elements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1093526619875237DOI Listing
March 2021

Mesenchymal Hamartoma of the Liver and DICER1 Syndrome.

N Engl J Med 2019 08;381(6):586-587

Boston Children's Hospital, Boston, MA

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMc1907523DOI Listing
August 2019
-->