Histone H3 trimethylation on lysine 27 immunostaining pattern in DICER1-associated tumors.

Background: DICER1-associated tumors are heterogeneous and affect several organs. DICER1-associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27 (H3K27me3) loss in nucleus by immunohistochemistry. Methods: We explored the H3K27me3 immunostaining pattern in other DICER1-associated tumors. Twelve tumors from eleven patients with confirmed DICER1 mutations (sporadic and germline) data from a pancancer next-generation sequencing panel, and four tumors of pleuropulmonary blastoma (PPB) were retrieved from our database and stained with anti-H3K27me3 antibody. Results: The H3K27me3 expression in the nucleus showed heterogeneous mosaic loss in neoplastic Sertoli cell components in three of the five cases of moderately to poorly differentiated Sertoli-Leydig cell tumors. Among two tumors of DICER1-associated primary intracranial sarcoma, one showed complete loss of H3K27me3 in all neoplastic cells, whereas the other showed mosaic loss in the sarcomatous spindle cells. One DICER1-associated tumor with epithelial and mesenchymal differentiation, including pulmonary blastoma and PPB, showed mosaic loss of glandular epithelial and mesenchymal components. Four cases of type II PPB and a single case of type III PPB showed a similar mosaic loss of H3K27me3 staining restricted to large spindle cell components. All other components in all tumors-including Leydig cells; the areas of epithelial, cartilaginous, and rhabdomyomatous differentiation; and all cells of the remaining three cases (one papillary thyroid carcinoma and two cases of PPB type I)-demonstrated retained H3K27me3 staining. Conclusions: H3K27me3 expression is not universally lost in DICER1-associated tumors and thus is not predictive of DICER1 mutation status. The mosaic regional loss of H3K27me3 immunostaining is consistent in PPB type II and III, which can be a helpful diagnostic marker for these tumors and suggests a similarity to DICER1-associated intracranial sarcoma.

Comparative Clinicopathologic and Genomic Analysis of Hepatocellular Neoplasm, Not Otherwise Specified, and Hepatoblastoma.

Accurate diagnosis and treatment of hepatocellular neoplasm, not otherwise specified (HCN-NOS), poses significant challenges. Our study aimed to investigate the clinicopathologic and genomic similarities and differences between HCN-NOS and hepatoblastoma (HB) to guide diagnostic and treatment strategies. The clinicopathologic characteristics of 16 patients with HCN-NOS and 23 patients with HB were compared. Molecular studies, including the OncoKids DNA- and RNA-based next-generation sequencing panel, chromosomal microarray, and targeted Sanger sequencing analyses of CTNNB1 and TERT promoters, were employed. We found that patients with HCN-NOS were older (P < .001) and more frequently classified as high risk (P < .01), yet they showed no significant differences in alpha fetoprotein levels or survival outcomes compared with those with HB. HCN-NOS and HB had a comparable frequency of sequence variants, with CTNNB1 mutations being predominant in both groups. Notably, TERT promoter mutations (37.5%) and rare clinically significant variants (BRAF, NRAS, and KMT2D) were exclusive to HCN-NOS. HCN-NOS demonstrated a higher prevalence of gains in 1q, encompassing the MDM4 locus (17/17 vs 11/24; P < .001), as well as loss/loss of heterozygosity (LOH) of 1p (11/17 vs 6/24; P < .05) and chromosome 11 (7/17 vs 1/24; P < .01) when compared with HB. Furthermore, the recurrent loss/LOH of chromosomes 3, 4p, 9, 15q, and Y was only observed in HCN-NOS. However, no significant differences were noted in gains of chromosomes 2, 8, and 20, or loss/LOH of 4q and 11p between the 2 groups. Notably, no clinically significant gene fusions were detected in either group. In conclusion, our study reveals that HCN-NOS exhibits high-risk clinicopathologic features and greater structural complexity compared with HB. However, patients with HCN-NOS exhibit comparable alpha fetoprotein levels at diagnosis, CTNNB1 mutation rates, and survival outcomes when subjected to aggressive treatment, as compared with those with HB. These findings have the potential to enhance diagnostic accuracy and inform more effective treatments for HCN-NOS.

Pediatric Sertoli-Leydig Cell Tumors of the Ovary: An Integrated Study of Clinicopathological Features, Pan-cancer-Targeted Next-generation Sequencing and Chromosomal Microarray Analysis From a Single Institution.

Sertoli-Leydig cell tumors (SLCTs) are currently classified into 3 molecular subtypes: DICER1 -mutant (younger patient age), FOXL2 -mutant, and DICER1/FOXL2 -wildtype. However, it is not clear whether all pediatric SLCTs are DICER1 -mutant molecular subtypes and whether other molecular genetic aberrations besides DICER1 are involved in the pathogenesis and prognosis of these tumors. We studied comprehensive data for 8 cases of pediatric SLCTs, including clinicopathological features, pan-cancer-targeted next-generation sequencing/OncoKids panel, and chromosomal microarray analysis, to further analyze the correlation among clinicopathological features, molecular genetic aberrations, and prognosis. The ages of the patients ranged from 4 to 16 years (median, 14 y). Seven cases were moderately differentiated, and one was poorly differentiated with heterologous mesenchymal elements. Two cases had heterologous epithelium or retiform elements. Follow-up was available for all 8 patients (median, 49.5 mo). Seven patients were alive without evidence of recurrence or metastasis, and only case 5 developed metastases (synchronous bilateral pulmonary tumors with rhabdomyosarcomatous differentiation). All 8 tumors were found to harbor somatic hotspot DICER1 mutations, and 5 patients carried germline DICER1 mutations (2 of them had the phenotype of DICER1 syndrome). Together with recent studies, the DICER1 mutation frequency is 100% in pediatric SLCTs (n=27, age≤16 y). Copy number alterations were detected in 3 tumors; the only recurrent copy number alterations was the gain of whole chromosome 6 in case 5 and case 8. This is the first report describing clinicopathological features and molecular alterations in pediatric SLCTs. Our results demonstrate that all pediatric SLCTs belong to the DICER1 -mutant molecular subtype, highlighting that somatic hotspot DICER1 mutation detection has high sensitivity (100%) for the auxiliary diagnosis of pediatric SLCTs (age ≤16 y). Some pediatric SLCTs harbor molecular genetic aberrations other than DICER1 mutation, and their significance needs further study.

A Diagnostic Conundrum: A Case of Pediatric Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is rare cause of abdominal pain in children who often present with obstructive jaundice, mimicking malignancy. An investigation of clinical symptoms, serology, imaging, and histopathology is necessary for diagnosis. We report a 10-year-old female presenting with abdominal pain and jaundice, ultimately found to have AIP after confirmation with tissue pathology. Our patient's prompt response to corticosteroid initiation is characteristic of this disease state. AIP has 2 subtypes, the second of which is more frequently found in children. Our patient's pathology did not fit perfectly with either subtype, but had features found in each one. While diagnostic criteria for AIP have not established in pediatrics, our case highlights the combination of clinical symptoms, imaging, and histopathology that children classically present with. While rare, the diagnosis of AIP is associated with comorbidities and must be considered in any child presenting with a pancreatic mass or biliary stricture.

Malignancy Rates by Bethesda Subcategory in the Pediatric Population.

INTRODUCTION: While the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the most widely used method for categorizing thyroid nodules, its applicability to children is often debated. We describe our institution's experience utilizing the TBSRTC and examine the rates of malignancy in our population. METHODS: We conducted a retrospective chart review of eligible patients undergoing primary thyroidectomy at a high-volume tertiary care pediatric hospital. All patients had pre-operative fine needle aspiration. RESULTS: Of the 112 patients in our cohort, 85 (76%) were female. The median age was 15.1 years. The patients were divided into groups based on the Bethesda categorization of the fine needle aspirations of their nodules. The percentages of patients whose resection specimens showed evidence of malignancy on the surgical pathology reports were recorded as follows: category I (n = 5): 20%, category II (n = 11): 0%, category III (n = 30): 17%, category IV (n = 13): 31%, category V (n = 17): 94% and category VI (n = 36): 100%. CONCLUSION: Our findings indicate that the malignancy rates at our institution are comparable to those reported by other high-volume studies. When compared with the 2017 TBSRTC data, we found that our results were similar in many categories, with the exception of categories I and V.

VITREOUS HEMORRHAGE IN TYPE 3 GAUCHER DISEASE: AN ANGIOGRAPHIC AND PATHOLOGIC ANALYSIS.

PURPOSE: To describe the case of a 12-year-old woman with vitreoretinal manifestations of Type 3 Gaucher disease. METHODS: A retrospective case report including multimodal imaging and histologic examination of the vitreous. RESULTS: A 12-year-old woman with a history of Gaucher disease Type 3 was referred to the ophthalmology service for evaluation of vitreous deposits in both eyes. Funduscopic examination was notable for white vitreous opacities in both eyes. Ultra-widefield fluorescein angiography demonstrated areas of blockage associated with the deposits and focal areas of leakage. Optical coherence tomography angiography showed shadow artifact without intrinsic flow at these sites. Three years after presentation, she developed a right hemorrhagic posterior vitreous detachment, requiring pars plana vitrectomy with scleral buckle. A vitreous sample was sent to pathology, which demonstrated Gaucher cells. CONCLUSION: Gaucher disease is a rare metabolic condition caused by an autosomal recessive deficiency of glucocerebrosidase. To the best of our knowledge, this is the first report of hemorrhagic posterior vitreous detachment in Type 3 Gaucher disease, including ultra-widefield imaging, optical coherence tomography angiography, and histopathology.

Non-invasive biomarkers of Fontan-associated liver disease.

BACKGROUND & AIMS: Fontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored. METHODS: A retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed. RESULTS: Among 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m2, with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/µl for congestive hepatic fibrosis score [CHFS] 0-2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005). CONCLUSIONS: In this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population. LAY SUMMARY: In this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population.

Post-infectious inflammatory syndrome associated with SARS-CoV-2 in a paediatric patient with Down syndrome.

Neurological complications of SARS-CoV-2 continue to be recognised. In children, neurological phenomenon has been reported generally in the acute infectious period. It is possible that SARS-CoV-2 could trigger an immune-mediated post-infectious phenomenon. Here, we present a unique case of post-infectious marantic cardiac lesion causing cerebrovascular accident in a patient with Down syndrome.

Primary Knee Intra-articular Synovial Sarcoma in Pediatric and Adolescent Patients.

Synovial sarcoma (SS) arising within a knee joint is extremely rare, with 10 reported cases in pediatric and adolescent patients in English literature. Its rarity and nonspecific clinical and radiological features pose a diagnostic challenge. We present two cases of primary intra-articular SS of left knee to enhance awareness of this entity. One patient is a 17-year-old male complained of left knee pain and gait abnormality for 9 years. The other one is a 13-year-old female presented with left knee pain for one year. Both cases were clinically diagnosed as benign joint lesion and underwent biopsies. Histological examination, immunohistochemical staining and molecular study confirmed that both patients had primary intra-articular SS, monophasic spindle cell type. Intraarticular SS should be considered as a potential diagnosis with unexplained long-standing knee pain.

Clinicopathologic Characteristics of Late Acute Antibody-mediated Rejection in Pediatric Liver Transplantation.

BACKGROUND: An early and accurate diagnosis of liver antibody-mediated rejection (AMR) followed by timely intervention is important for clinical management but remains challenging. The aim of this study was to assess the clinicopathologic characteristics and outcomes of late acute AMR in pediatric liver transplantation recipients. METHODS: We performed a retrospective review of 739 ABO-identical/compatible allograft liver biopsies from 199 pediatric transplantation recipients. RESULTS: Based on Banff 2016 AMR criteria, 3 recipients fulfilled the criteria for definite for late acute AMR, 2 met the criteria for suspicious for AMR, and 2 were indeterminate for AMR. We further assessed the clinicopathologic characteristics of these 7 patients. All 7 patients had at least 1 biopsy with a histopathologic pattern compatible with acute AMR. Additionally, we observed accompanied moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury in all 7 patients; periportal/perivenular hepatocyte necrosis was seen in 6 of 7 patients; and arteritis was seen in 3 of 7 patients. In each case, microvascular C4d deposition was present in at least 1 biopsy. Posttransplant donor specific anti-HLA antibodies were detected in 5 patients. Two of 7 patients were retransplanted, and 2 died after developing refractory AMR. The remaining 5 patients were alive with stable graft function at a median follow-up of 4.1 years. CONCLUSIONS: Our data suggest that acute AMR in pediatric liver grafts is rare, can develop late, and may be associated with graft loss or patient death. The recurrent histopathologic findings of moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury are features that appear unique to pediatric acute AMR of liver grafts.

Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease.

BACKGROUND: It can be challenging to recognize undifferentiated/immature ganglion cells, especially single forms. Ganglion cells and glia are derived from enteric neural crest cells (ENCCs), a group of autonomic nervous system (ANS)-lineage neural crest progenitors that PHOX2B regulates. Phox2b is an excellent marker for neoplastic and non-neoplastic ANS cells (eg, peripheral neuroblastic tumors [pNTs]). We hypothesized that Phox2b immunohistochemical staining (IHC) would also be useful for detecting ENCCs. METHODS: Hematoxylin and eosin, calretinin IHC, and Phox2b IHC were reviewed on 21 pull-through specimens and on a cohort of 12 rectal biopsies. RESULTS: Phox2b IHC demonstrated nuclear positivity in all of the ganglion cells across the different phases of differentiation without background staining. The Phox2b result correlated with the morphological findings, calretinin IHC results, and diagnoses based on the routine diagnostic method. The intensity was uniformly strong in the undifferentiated/immature forms and became variable in the mature forms; this pattern was similar to that seen in pNTs. CONCLUSION: Phox2b IHC was highly sensitive and specific for detecting ganglion cells. It worked especially well for immature ganglion cells, seen in premature neonates, and scattered single forms in transition zones. In basic research settings, Phox2b can be a useful marker for early differentiation of ENCCs.

The Effect of Gross Total Resection on Patients with Pleuropulmonary Blastoma.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common primary lung cancer in children. While rare, these tumors are highly aggressive. Tumor recurrence and overall survival are dependent on histologic grade and extent of surgical resection. We sought to examine our institutional experience with PPB to determine the effect of gross total resection (GTR) on recurrence and patient outcomes. MATERIALS AND METHODS: After IRB approval, a retrospective chart review from 1998 to 2018 was performed. Cases were confirmed by histology and Dehner Grade (I to III). Data collection included demographics, treatment, extent of surgical resection, and patient outcomes. RESULTS: Eight patients with nine procedures were identified. Histologically, three cases were type 1, 2 type 2, and four poor prognosis type 3. Three patients received neoadjuvant chemotherapy to facilitate surgical resection. The operative goal was to achieve GTR (>95%), and to this end, three partial lobectomies, five lobectomies, and one pneumonectomy were performed. All nine cases achieved GTR, of which eight had negative microscopic margins. Two patients with type III disease recurred (one locally, one distant) and died. One type 3 patient had a positive microscopic hilar margin not amenable to further resection. The patient recurred (distant) but is in remission. With respect to patient outcomes, the event-free survival was 2.3 y with an overall survival of 3.3 y. CONCLUSIONS: From our experience, GTR of PPB is associated with minimal surgical morbidity and good overall survival. Multi-institutional studies are needed to determine if positive surgical margins affect outcomes given the morbidity of mediastinal dissection.

Autoimmune Gastritis in Pediatrics: A Review of 3 Cases.

OBJECTIVES: To bring heightened awareness to a condition, autoimmune gastritis (AIG), which is a well-established entity in adults; however, rarely described in pediatrics. Currently, the literature describes AIG in pediatric patients who also suffer from other autoimmune disorders, which precedes the diagnosis of AIG, and often presents with unexplained anemia. Additionally, there have been case reports describing patients with immunodeficiencies and AIG, which progress to gastric adenocarcinoma. AIG is a histopathologic diagnosis, demonstrating chronic inflammatory process with loss of parietal cells with or without intestinal metaplasia and enterochromaffin-like cell hyperplasia. Management of these patients includes nutritional replacement as well as routine surveillance endoscopy with biopsy in search of metaplastic and dysplastic changes. METHODS: We queried the pathology database at Children's Hospital Los Angeles (CHLA) for cases with a final diagnosis of AIG and for those with a differential diagnosis that includes AIG in the diagnostic comment. All cases that were identified were selected as long as they did not only meet the histopathologic criteria, but also the biochemical criteria for this condition. RESULTS: Of the 3 patients, 2 were referred to gastroenterology for the evaluation of iron-deficiency anemia in the context of diabetes mellitus and Addison's disease; and diabetes mellitus and Hashimoto's thyroiditis. AIG was confirmed on the biopsies, which showed a reduction in parietal cell mass, pseudopyloric metaplasia and enterochromafin-like cell hyperplasia. Both patients were treated with iron replacement therapy. The third patient presented with symptomatic anemia and diagnosed with pernicious anemia without other autoimmune disorders. She was successfully treated with oral vitamin supplementation. In this case, serial gastric biopsies demonstrated stable intestinal metaplasia without evidence of dysplasia. CONCLUSION: Although AIG is rare in children, pediatric gastroenterologists and pathologists should have a heightened suspicion for this entity in those patients with a history of autoimmune disorders and/or pernicious anemia.

Routine Surveillance Catheterization is Useful in Guiding Management of Stable Fontan Patients.

We developed a Fontan surveillance catheterization protocol as part of routine assessment of stable patients 10 years after Fontan completion. The surveillance catherization includes hemodynamic assessment with inhaled nitric oxide, angiography, liver biopsy, and transcatheter intervention if indicated. We aimed to describe hemodynamic and liver biopsy findings, response to pulmonary vasoreactivity testing, rates of transcatheter intervention, and changes in medical therapy following surveillance catheterization in stable Fontan patients. A single-center retrospective review of Fontan patients undergoing surveillance catheterization between November 2014 and May 2019 was performed. Liver biopsies were independently scored by two pathologists. Sixty-three patients underwent surveillance catheterization (mean age 14.6 ± 3.0 years). The mean Fontan pressure was 11.8 ± 2.1 mmHg. The mean cardiac index was 2.9 ± 0.6 L/min/m2. In the 51 patients who underwent pulmonary vasoreactivity testing, there was a significant decrease in median pulmonary vascular resistance (1.8 [range 0.8-4.1] vs 1.4 [range 0.7-3.0] Wood units × m2; p < 0.001). The mean cardiac index increased (3.0 ± 0.6 vs 3.2 ± 0.7 L/min/m2, p = 0.009). The Fontan pressure did not change significantly. Fifty-seven patients underwent liver biopsy, and all but one showed fibrosis. Nineteen patients (33.3%) demonstrated bridging fibrosis or cirrhosis. Twenty-five patients underwent 34 transcatheter interventions. Pulmonary artery or Fontan stent placement was performed in 19 patients. Phosphodiesterase type 5 inhibitors were initiated in nine patients following surveillance catheterization. Routine surveillance catheterization with liver biopsy in adolescent Fontan patients reveals information that can guide interventional and medical management. Further long-term follow-up and assessment are indicated to assess the benefit of these interventions.

Primary Epithelioid Sarcoma of the Zygomatic Bone.

Primary epithelioid sarcoma (ES) of bone is extremely rare with only 2 reported cases in the English literature. A previously healthy 18-year-old man presented with a 6-month history of right facial numbness and tingling and right eye diplopia. A computerized tomography scan revealed an ill-defined mass with dense osseous matrix centered in the right zygomatic bone. An outside biopsy was read as osteosarcoma. The resection specimen revealed large epithelioid and spindle cells embedded in a prominent hyalinized matrix with focal metaplastic bone formation. The tumor cells were strongly and diffusely positive for AE1/AE3 and epithelial membrane antigen, but a definitive diagnosis of ES was not immediately reached due to the presence of dense hyalinized matrix and weak expression of SAT2B by tumor cells. Deficient INI1 protein expression by immunohistochemistry and homozygous loss of the SMARCB1 gene by chromosomal microarray analysis ultimately justified this tumor's designation as ES.

Bronchial Mucoepidermoid Carcinoma With the Classic MAML2 Gene Rearrangement in a 2-year-old Boy.

Pulmonary mucoepidermoid carcinoma (PMEC) is rare. To date, primary PMEC has not been reported in a child younger than 3 years of age. We report a case of a 2-year-old boy who presented with 3 episodes of wheezing, cough, and fever over a period of 1 month. Radiologic findings were consistent with foreign body aspiration with consequent bronchial obstruction. Bronchoscopy was performed and attempts to retrieve the foreign body resulted in a biopsy of a fleshy lesion. By histology, the lesion was an epithelial neoplasm comprising cells arranged in a nested pattern. The neoplastic cells were round with round nuclei and amphophilic, vacuolated cytoplasm. Our diagnosis was low-grade salivary gland-type carcinoma of the bronchus. The pneumonectomy specimen showed a well-circumscribed, polypoid intrabronchial mass measuring 2.1 cm in greatest dimension. Histologic examination of the tumor showed an admixture of intermediate cells which were predominant, a small number of mucus cells and rare foci of squamous cells. The final diagnosis rendered was a low-grade mucoepidermoid carcinoma of the bronchus. Accurate diagnosis of PMEC can be challenging on limited biopsy material as seen in the case reported here. The use of molecular studies such as MAML2 gene rearrangement may facilitate diagnosis in difficult cases. Increased awareness of this entity and further molecular studies are needed for a better understanding of the pathogenesis of PMEC. To date, the reported age range for primary bronchial mucoepidermoid carcinoma is between 3 years and 78 years. This case represents the youngest patient reported in the English literature.

Restricted Range of Motion and a Cold Upper Extremity in a Two-Year-Old Boy: Kaposiform Hemangioendothelioma of the Bone and the Brachial Plexus: A Case Report.

CASE: We report a case of kaposiform hemangioendothelioma (KHE) of the scapula in a 2-year-old boy with motor and sensory abnormalities of the left upper extremity, suggesting brachial plexus involvement. The locally invasive nature prevented resection; sirolimus therapy resulted in improvement of the motor and sensory impairment, as well as decreased tumor size on imaging. CONCLUSION: Osseous infiltration of KHE is known to occur, but its primary presentation in bone without skin involvement is rare and diagnostically challenging. Awareness of rare presentations of KHE, along with accurate histopathologic interpretation, is important to achieve a diagnosis and to differentiate KHE from more common vascular lesions (e.g., infantile hemangioma). Sirolimus therapy is emerging as a promising treatment for unresectable KHE.

Melanotic Neuroectodermal Tumor of Infancy Presenting With Fast-Growing Scrotal Swelling: A Case Report and Literature Review.

Testicular melanotic neuroectodermal tumor of infancy (MNTI) is extremely rare, with 2 cases reported in the literature. Its rarity and rapid and infiltrative growth pattern pose a diagnostic challenge. A previously healthy 3-month-old male, presented with a history of worsening left hemiscrotal swelling for 1 week. An outside ultrasound was suggestive of testicular torsion. Left orchiectomy demonstrated a mass occupying almost entire testicle with a variegated cut surface, with areas of pigmentation, necrosis, and hemorrhage. Histological examination confirmed MNTI of the testis and epididymis. MNTI should be included in differential diagnosis in infants presenting with fast-growing scrotal swelling.