Myoepithelial Tumors of Bone With EWSR1::PBX3 Fusion: A Spectrum From Benign to Malignant.

The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These tumors typically demonstrate benign histology and favorable outcomes. This study examines 6 previously unreported intraosseous METs harboring the EWSR1::PBX3 fusion, focusing on their histopathologic characteristics, immunophenotype, clinical and radiographic profiles, and patient outcomes.

Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review.

Purpose: To assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes.

Methods: We conducted a retrospective analysis of medical records spanning 2009-2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma.

Results: Among the 33 patients, SLNB detected metastasis in 57.

Superficial dedifferentiated liposarcoma: A clinicopathologic study.

Introduction: Dedifferentiation occurs in approximately 10% of atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPS), primarily in retroperitoneal or deep-seated tumors, conferring metastatic potential. Superficial dedifferentiated liposarcoma (sDDLPS) is rare, and its progression and natural history are poorly documented.

Methods: We performed a 15-year retrospective review of our pathology database to identify cases of DDLPS in the skin or subcutaneous tissue.

Myxofibrosarcoma in adolescents and young adults: a clinicopathologic study of 17 cases.

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years.

Cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion: A case report emphasizing early detection.

Rhabdomyosarcoma with TFCP2 rearrangement is a recently identified malignant neoplasm characterized by immunohistochemical evidence of rhabdomyoblastic differentiation, keratin expression, upregulation of ALK, and an aggressive clinical course. This neoplasm has a tendency to affect craniofacial bones, with only a few reported cases of extra-osseous tumors. Here, we present a case of cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion in a 35-year-old female.

Non-cutaneous syncytial myoepitheliomas are identical to cutaneous counterparts: a clinicopathologic study of 24 tumors occurring at diverse locations.

Aims: Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study.

UVEAL MELANOMA PRESENTING AS HEPATIC METASTASIS IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS.

Purpose: To report an atypical case of occult uveal melanoma in a patient with oculodermal melanocytosis that first presented with symptoms of hepatic metastasis.

Methods: A previously healthy 16-year-old boy with noted ocular hyperpigmentation developed abdominal pain and vomiting and was found to have a hepatic mass consistent with a metastatic lesion from an occult uveal melanoma.

Results: On examination, the patient's visual acuity was 20/20, and pupils were reactive without an afferent pupillary defect in both eyes.

Adult-onset Langerhans cell histiocytosis of bone: A case series highlighting a rare entity.

Langerhans cell histiocytosis (LCH) is a neoplastic disorder derived from LCH precursor cells that can manifest as a single-system disease or a multisystem disorder. While extensively studied in children, LCH has received less attention in adult patients. We aimed to investigate the pathology and clinical course of LCH in adults presenting with a bone lesion.

Germline pathogenic variants in neuroblastoma.

Heterozygous germline pathogenic variants (GPVs) in , the gene encoding the ATP-dependent chromatin remodelling protein SMARCA4 (previously known as BRG1), predispose to several rare tumour types, including small cell carcinoma of the ovary, hypercalcaemic type, atypical teratoid and malignant rhabdoid tumour, and uterine sarcoma. The increase in germline testing of in recent years has revealed putative GPVs affecting in patients with other cancer types. Here we describe 11 patients with neuroblastoma (NBL), including 4 previously unreported cases, all of whom were found to harbour heterozygous germline variants in Median age at diagnosis was 5 years (range 2 months-26 years); nine were male; and eight of nine cases had tumour location information in the adrenal gland.

A Contemporary Clinicopathologic Analysis of Primary Sarcomas of the Perinephric Soft Tissue and Hilar Vessels Including a Subset Secondarily Involving the Kidney.

A variety of primary malignant mesenchymal neoplasms can arise from the perinephric soft tissue and hilar vessels and potentially involve the kidney, mimicking primary renal tumors. A search was made at our institution for patients that underwent radical nephrectomy with associated perinephric or hilar sarcomas from 2010 to 2021. Twenty-six patients were identified.

Targeted Long-Read Bisulfite Sequencing Identifies Differences in the Promoter Methylation Profiles between Wild-Type and Mutant Cancer Cells.

Background: TERT promoter methylation, located several hundred base pairs upstream of the transcriptional start site, is cancer specific and correlates with increased TERT mRNA expression and poorer patient outcome. Promoter methylation, however, is not mutually exclusive to TERT activating genetic alterations, as predicted for functionally redundant mechanisms. To annotate the altered patterns of TERT promoter methylation and their relationship with gene expression, we applied a Pacific Biosciences-based, long-read, bisulfite-sequencing technology and compared the differences in the methylation marks between wild-type and mutant cancers in an allele-specific manner.

Pancreatoblastomas and mixed and pure acinar cell carcinomas share epigenetic signatures distinct from other neoplasms of the pancreas.

Pancreatic neoplasms are heterogenous and have traditionally been classified by assessing their lines of cellular differentiation using histopathologic methods, particularly morphologic and immunohistochemical evaluation. These methods frequently identify overlapping differentiation along ductal, acinar, and neuroendocrine lines, raising diagnostic challenges as well as questions regarding the relationship of these neoplasms. Neoplasms with acinar differentiation, in particular, frequently show more than one line of differentiation based on immunolabeling.

Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms.

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features.

SLFN11 is Widely Expressed in Pediatric Sarcoma and Induces Variable Sensitization to Replicative Stress Caused By DNA-Damaging Agents.

Pediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA-damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity to replicative stress and has been implicated as a potential biomarker to predict sensitivity to DNA-damaging agents (DDA). SLFN11 expression was quantified in 220 children with solid tumors using IHC.

YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases.

YAP1-TFE3-fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3-fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3-fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20-78 years old, median 44).

Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing.

Unlabelled: Genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. Here, we used a three-platform sequencing approach, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-seq), to examine tumor and germline genomes from 309 prospectively identified children with newly diagnosed (85%) or relapsed/refractory (15%) cancers, unselected for tumor type. Eighty-six percent of patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or cancer-predisposing (18%) variants.

Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells.

Immune cells regulate tumor growth by mirroring their function as tissue repair organizers in normal tissues. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunologic manipulation with noninvasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4 and myeloid populations colocalized within the tumor parenchyma, while CD8 T cells and B cells were peripherally dispersed.

A prospective, comprehensive registry that integrates the molecular analysis of pediatric and adolescent melanocytic lesions.

Background: Childhood melanocytic tumors represent a diagnostic and therapeutic challenge, and additional research is needed to better define the natural history of these tumors.

Methods: The authors developed a comprehensive, prospective registry called Molecular Analysis of Childhood Melanocytic Tumors for children and adolescents with an atypical Spitz tumor/Spitz melanoma (AST/SM), conventional or adult-type melanoma (CM), melanoma arising in a giant congenital nevus (MCM), or atypical melanocytic proliferation of other types (OT) to better define the clinical behavior of these lesions by incorporating an integrated clinicopathologic and molecular analysis using centralized pathology review and various platforms, including fluorescence in situ hybridization; array comparative genomic hybridization; and whole genome, exome, and capture targeted panels.

Results: From May 2016 to November 2019, 70 children were enrolled with a median age at diagnosis of 9.

High-grade neuroepithelial tumor with medulloepithelioma-like areas out of the central nervous system in an infant with hemihypertrophy: a unique association.

Background: High-grade neuroepithelial tumor with areas resembling medulloepithelioma was diagnosed in an infant with coccygeal and inguinal masses. Hemihypertrophy is associated with Wilms tumor, hepatoblastoma and pancreatic tumors in children.

Case: The authors report on the first case of peripheral HNET associated with hemihypertrophy in an infant, with special discussion on histopathological differential diagnosis and management of this rare and highly malignant tumor.

Lipoblastomas presenting in older children and adults: analysis of 22 cases with identification of novel PLAG1 fusion partners.

Lipoblastomas are benign neoplasms of embryonal white fat that typically present in the first 3 years of life and show a lobular arrangement of maturing adipocytes with variable degrees of myxoid change. We systematically studied the clinicopathologic and genetic features of lipoblastomas arising in older children and adults. Cases with a diagnosis of lipoblastoma or maturing lipoblastoma in patients >3 years of age were retrieved from our archives.