Adult Type Lipoblastoma With a Predominantly Fibroblastic Morphology and a Novel DLEU2::PLAG1 Gene Rearrangement: Two Cases of a Rare Entity.

Lipoblastoma is a benign adipocytic lesion with embryonal fat cell differentiation. The tumors most commonly occur in children, however, rare cases have been reported to occur in adults and are generally considered to represent "maturing" or long-standing lipoblastomas. Approximately 60%-80% of these tumors harbor a gene fusion involving the PLAG1 gene, which is known to rearrange with numerous unique fusion partners.

TFE3-Altered Perivascular Epithelioid Cell Tumour (PEComa) of the Nasal Cavity With a Novel TRAF3::TFE3 Fusion-A Report of a Case Expanding the Molecular Genetic Spectrum and a Brief Literature Review on PEComas of the Head and Neck Region.

Background: Perivascular epithelioid cell tumours (PEComas) constitute a unique group of neoplasms with a distinctive myomelanocytic immunohistochemical phenotype and uncommonly occur in the head and neck region. We herein report the clinicopathologic features of a case of a sinonasal PEComa occurring in an 18-year-old male with a novel TRAF3::TFE3 fusion.

Case Presentation: The patient presented with an infiltrative nasal cavity tumour.

Angiomatoid fibrous histiocytoma occurring at distal/acral extremity sites: clinicopathological and molecular study of 26 cases highlighting frequent myxoid histology and site-dependent genotypic variation.

Angiomatoid fibrous histiocytoma (AFH) is a rare mesenchymal neoplasm of borderline malignancy (locally recurring, rarely metastasizing), most often involving the limbs, trunk, and head/neck. Rarely, AFH may involve unusual locations. Herein, we characterize the clinicopathologic features of 26 AFH of the distal extremities, including acral sites.

Ossifying Spindled and Epithelioid Tumor: A Novel Soft Tissue Tumor.

This investigation describes the clinicoradiologic, pathologic, and molecular features of a unique soft tissue tumor characterized by a peripheral shell of bone and composed of bland myoid spindle and epithelioid cells that are keratin-positive. Our study cohort consists of 6 men and 6 women, with a mean age of 32 years. The tumors arose in the extremities (n = 9) and proximal limb girdle (n = 3) and were equally distributed between deep and superficial soft tissues.

Deciphering Pseudoendocrine Sarcoma: A Clinicopathological, Molecular, and Epigenetic Study Suggesting Biological Links With Solid Pseudopapillary Neoplasm of the Pancreas.

Pseudoendocrine sarcoma (PS) is a recently described neoplasm of uncertain differentiation, characterized by recurrent CTNNB1 mutations, frequent paravertebral location, and a neuroendocrine-like histomorphology. In this study, we report the clinicopathologic, immunohistochemical, transcriptomic, and epigenetic findings of 12 PS cases. The tumors affected 7 men and 5 women with a median age of 66 years and were located in the paraspinal/paravertebral region (n = 11) and the thigh (n = 1).

Beyond Hybrid Morphology: A Large Series of Fusion-Driven Benign Peripheral Nerve Sheath Tumors Including 5 Tumors With Novel Fusions.

Benign peripheral nerve sheath tumors (PNSTs) represent a heterogeneous group of neoplasms with varying histologic and molecular characteristics. Although traditional classifications categorize these tumors based on predominant cell types, recent advances in molecular pathology have revealed the presence of hybrid tumors featuring elements from at least 2 nerve sheath tumors (hybrid peripheral nerve sheath tumor [hPNST]). We herein studied 20 cases of hPNST involving 15 female and 5 male patients (median age, 29.

MITF Pathway-Activated Cutaneous Neoplasms.

Over the past few years, several fusion genes have been reported in dermal-based tumors, resulting in the activation of the microphthalmia (MITF) signalling pathway and a melanocytic phenotype by immunohistochemistry. The best-studied example of these tumors is clear cell sarcoma, which rarely may present as a primary dermal tumor. These tumors are characterized by EWSR1 gene rearrangements, typically with ATF1 and less commonly CREB1.

Malignant Chondroblastoma: An Epigenetically Distinct Subtype of Chondroblastoma With a Predilection for the Skeletally Mature.

Malignant chondroblastoma is a recently described variant of chondroblastoma showing a distinct age/site distribution and morphology along with the typical H3-3B p.K36M mutation. We sought to further compare conventional and malignant chondroblastoma.

SS18::POU5F1-fused sarcoma of the parotid with divergent ganglioneuromatous differentiation-a novel manifestation of a rare tumor.

SS18::POU5F1-fused sarcomas are rare tumors that show an undifferentiated round cell morphology. We report for the first time a case of SS18::POU5F1-fused sarcoma occurring in the parotid gland, with a highly unusual biphasic morphology comprising of epithelioid/undifferentiated round cell component and a ganglioneuromatous component consistent with divergent differentiation. We illustrate the cytology, histomorphological, immunohistochemical profile of the tumor, and show that both components of the tumor share a common origin.

Utility of Protein Kinase C Beta II Immunohistochemistry in Differential Diagnosis of Ewing Sarcoma.

The diagnosis of Ewing sarcoma can be challenging, particularly when the tumor is present in an atypical location and resembles histologic mimics. The hallmark feature of Ewing sarcoma is chromosomal translocation, t(11;22)(q24;q12), involving EWSR1 and ETS gene family members. For decades, fluorescence in situ hybridization with a break-apart EWSR1 probe has been the diagnostic gold standard.

Integrating clinicopathological and molecular data to assess the biological behavior of uterine inflammatory myofibroblastic tumors.

Assessing the biological behavior of uterine inflammatory myofibroblastic tumors (IMTs) remains challenging. This study evaluated previously proposed risk schemes and features in 9 IMTs (6 indolent, 3 aggressive) by integrating clinicopathological features, immunohistochemistry, and next-generation sequencing (NGS). High-risk features (necrosis, infiltrative growth, nuclear atypia) were present in both groups, with LVSI in 1/3 of aggressive IMTs.

Blastemal predominant WT1 negative Wilms tumour of the young adult: a unique case report and review of the literature.

Wilms tumour is a common juvenile cancer of the kidney, and its occurrence in adolescence or adulthood is extremely rare, accounting for around 1% of all adult kidney malignancies. Histopathologically, three tissue patterns can be identified, including blastemal, epithelial, and stromal components, while the overall microscopic appearance of an adult-type tumour does not differ from that of its juvenile counterpart. The blastemal predominant Wilms tumours are the most aggressive and have the worst prognosis.

Dermatofibrosarcoma protuberans with PDGFD rearrangements: a case series featuring a novel EMILIN1::PDGFD fusion and comprehensive literature review.

Dermatofibrosarcoma protuberans (DFSP) is a locally infiltrative mesenchymal neoplasm usually characterized by a COL1A1::PDGFB fusion. A minority of DFSPs have recently been shown to harbor alternative fusions, involving the PDGFD gene. The aim of this case series and literature review is to highlight the clinicopathologic and molecular features of PDGFD-rearranged DFSPs.

Cutaneous Hemangioma With Epithelioid Features Harboring TPM3/4::ALK Fusions : A Distinct Entity or a Molecular Variant of Epithelioid Hemangioma?

Vascular neoplasms with epithelioid cytomorphology encompass a wide spectrum of benign and malignant lesions, including epithelioid hemangioma (EH), cutaneous epithelioid angiomatous nodule (CEAN), epithelioid hemangioendothelioma (EHE), and epithelioid angiosarcoma (EAS). Recently, the first case of a cutaneous hemangioma with epithelioid features harboring a TPM3::ALK fusion was reported. Herein, we report 4 additional cases, including 1 case with an alternate TPM4::ALK fusion, and expand on the clinicopathologic and molecular genetic features of these unusual vascular lesions.

Nodular fasciitis: a case series unveiling novel and rare gene fusions, including two cases with aggressive clinical behavior.

Nodular fasciitis is a benign myofibroblastic tumor characterized by rapid growth and spontaneous regression. While nodular fasciitis is typically an indolent process, rare cases with benign morphologic features have developed metastases. Conversely, nodular fasciitis with malignant histologic features and benign clinical course have also been reported.

Renal Juxtaglomerular Cell Tumors Exhibit Distinct Genomic and Epigenomic Features and Lack Recurrent Gene Fusions: Comprehensive Molecular Analysis of a Multi-institutional Series.

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent.

GLI1::FOXO4-rearranged kidney tumors: a potentially distinct renal subtype within the spectrum of GLI1-altered tumors?

Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology.

Next-generation sequencing in the molecular classification of endometrial carcinomas: Experience with 270 cases suggesting a potentially more aggressive clinical behavior of multiple classifier endometrial carcinomas.

Molecular classification of endometrial carcinomas (EC) divides these neoplasms into four distinct subgroups based on their molecular background. Given its clinical significance, genetic examination is becoming integral to the diagnostic process. This study aims to share our experience with the molecular classification of EC using immunohistochemistry (IHC) and next-generation sequencing (NGS).

TFE3 -rearranged Head and Neck Neoplasms : Twenty-two Cases Spanning the Morphologic Continuum Between Alveolar Soft Part Sarcoma and PEComa and Highlighting Genotypic Diversity.

TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3 -related neoplasms are rare in the head and neck and may pose diagnostic challenges.

Malignant Esophageal Glomus Tumor With Fusion: An Additional Tumor Underscoring the Frequent Tendency of Esophageal Glomus Tumors for Aggressive Behavior.

Malignant glomus tumors are rare tumors of pericytic origin with a propensity to develop in the upper gastrointestinal tract. Hereby we demonstrate a tumor of a 20-year-old man, who presented with dysphagia and an exophytic esophageal mass. Histologic examination of the resected mass revealed a multinodular tumor in the esophageal wall composed of epithelioid cells showing nesting and monomorphic atypia, staghorn vessels and scanty stroma.

S100 and CD34 positive spindle cell tumors of the uterine cervix with EGFR mutation: a hitherto unrecognized neoplasm phenotypically and epigenetically overlapping with "NTRK-rearranged spindle cell neoplasms" of the uterus.

NTRK-rearranged spindle cell neoplasm represents an emerging entity included in the latest 5th edition of WHO classification of both soft tissue and female genital tumors. By immunohistochemistry, they are commonly positive for CD34, S100 protein, and CD30 and typically harbor fusions of kinase genes such as NTRK1/2/3, RET, and BRAF. In the gynecological tract, they typically affect the uterine cervix or uterine body.