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.

Malignant Bone-Forming Neoplasm With NIPBL::BEND2 Fusion.

Conventional high-grade osteosarcomas are characterized by aggressive radiologic features, cytologic pleomorphism, and complex genomics. However, rare examples of osteosarcomas remain challenging due to unusual histology, such as sclerosing or osteoblastoma-like features, which may require molecular confirmation of their complex genetic alterations. We have encountered such a case in a 17-year-old man, who presented with a third metatarsal sclerotic bone lesion, found incidentally in the work-up of a foot trauma.

An Inflammatory Myofibroblastic Tumor With a Novel ALK Mutation Leading to Acquired Resistance to Tyrosine Kinase Inhibitors.

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that can locally recur and potentially metastasize. Approximately 50% of IMTs harbor rearrangements in the gene encoding anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase that can be therapeutically targeted with tyrosine kinase inhibitors (TKIs). With successful application of TKI in ALK-positive nonsmall cell carcinoma (NSCLC), ALK inhibitors are often first-line treatments for patients with unresectable or metastatic IMTs.

DICER1-sarcomas of GYN tract: Expanding on an emerging entity.

Tumors with pathogenic DICER1 mutation are rare and encompass sporadic or hereditary benign, intermediate and malignant tumors. DICER1-associated sarcomas are heterogeneous; however, the prototypical ones in the GYN-tract include embryonal rhabdomyosarcoma, adenosarcoma and moderately to poorly differentiated Sertoli-Leydig tumor. In this report, we present three unique uterine sarcomas with DICER1 mutation and remarkable diffuse round/spindle cell morphology.

A Comprehensive Clinicopathologic and Molecular Reappraisal of GLI1 -altered Mesenchymal Tumors with Pooled Outcome Analysis Showing Poor Survival in GLI1 - amplified Versus GLI1- rearranged Tumors.

GLI1 -altered mesenchymal tumor is a recently described distinct pathologic entity with an established risk of malignancy, being defined molecularly by either GLI1 gene fusions or amplifications. The clinicopathologic overlap of tumors driven by the 2 seemingly distinct mechanisms of GLI1 activation is still emerging. Herein, we report the largest series of molecularly confirmed GLI1 -altered mesenchymal neoplasms to date, including 23 GLI1- amplified and 15 GLI1 -rearranged new cases, and perform a comparative clinicopathologic, genomic, and survival investigation.

Back to the future! Selected bone and soft tissue neoplasms with shared genetic alterations but differing morphological and immunohistochemical phenotypes.

Bone and soft tissue tumors (BST) are a highly heterogeneous group largely classified by their line of differentiation, based on their resemblance to their normal counterpart in adult tissue. Yet, rendering a specific diagnosis can be challenging, primarily due to their rarity and overlapping histopathologic features or clinical presentations. Over the past few decades, seemingly histogenetic-specific gene fusions/translocations and amplifications have been discovered, aiding in a more nuanced classification, leading to well-established objective diagnostic criteria and the development of specific surrogate ancillary tests targeting these genetic aberrations (e.

Vascular Neoplasms With NFATC1/C2 Gene Alterations : Expanding the Clinicopathologic and Molecular Characteristics of a Distinct Entity.

Despite significant advances in their molecular pathogenesis, skeletal vascular tumors remain diagnostically challenging due to their aggressive radiologic appearance and significant morphologic overlap. Within the epithelioid category and at the benign end of the spectrum, recurrent FOS/FOSB fusions have defined most epithelioid hemangiomas, distinguishing them from epithelioid hemangioendothelioma and angiosarcoma. More recently, the presence of EWSR1/FUS :: NFATC1/2 fusions emerged as the genetic hallmark of a novel group of unusual vascular proliferations, often displaying epithelioid morphology, with alternating vasoformative and solid growth, variable atypia, reminiscent of composite hemangioendothelioma.

Amplification Status in a Cohort of Well-Characterized Myxofibrosarcoma: A Clinicopathologic Analysis of 22 Tumors.

Myxofibrosarcomas (MFS) present as slowly enlarging superficial masses in elderly patients. Even though these tumors fail to exhibit a distinct immunophenotype, diagnosis is straightforward when they present in subcutaneous tissue. Intramuscular MFS, however, are more challenging to diagnose as the differential also includes dedifferentiated liposarcoma with myxoid features.

Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes PRC2 and NuA4/TIP60 as alternative fusion partners.

Endometrial stromal sarcomas (ESS) are morphologically and molecularly heterogeneous. We report novel gene fusions (EPC1::EED, EPC1::EZH2, ING3::PHF1) identified by targeted RNA sequencing in five cases. The ING3::PHF1-fusion positive ESS presented in a 58-year-old female as extrauterine mesocolonic, ovarian masses, and displayed large, monomorphic ovoid-to-epithelioid cells arranged in solid sheets.

Prognostic factors for pleomorphic dermal sarcoma: analysis of 1911 cases from the SEER database.

Prognostic factors for pleomorphic dermal sarcoma, a rare undifferentiated neoplasm of the skin, are poorly defined, and typical staging systems do not appear to be appropriate for these neoplasms. We; therefore, sought to identify prognostic factors for disease-specific survival and predictors of metastasis.Pleomorphic dermal sarcomas were identified in the Surveillance, Epidemiology and End Results database (N=1911).

Plexiform fibrohistiocytic tumor: a clinicopathological and immunohistochemical study of 39 tumors, with evidence for a CSF1-producing "null cell" population.

Plexiform fibrohistiocytic tumor (PFHT) is a mesenchymal tumor of intermediate malignancy, typically occurring in the superficial soft tissues of young patients and displaying a biphasic pattern, with nodules of histiocytoid cells surrounded by fascicles of myofibroblastic spindled cells. The pathogenesis of PHFT is unknown. We comprehensively studied 39 PFHT, occurring in 25 females (66%) and 13 males (34%), ranging from 2 to 55 years of age (median 21 years).

A novel WWTR1::AFF2 fusion in an intra-abdominal soft tissue sarcoma with associated endometriosis.

Application of molecular testing in clinical practice has led to significant advances in the classification of soft tissue sarcomas. Despite remarkable progress, there are still challenging cases that remain unclassified. In this study, we present an unusual spindle cell sarcoma arising in the abdominal cavity of a 37-year-old female.

A proposed risk assessment score for gastrointestinal stromal tumors based on evaluation of 19,030 cases from the National Cancer Database.

Background: Standard risk assessment algorithms for gastrointestinal stromal tumor (GIST) are based on anatomic and histopathological variables with arbitrarily defined subcategories. Our goal was to improve risk assessment for GIST through retrospective analysis of patient data.

Methods: The National Cancer Database (NCDB) was queried for patients with GIST; the final cohort consisted of 19,030 cases.

A unique epithelioid vascular neoplasm of bone characterized by EWSR1/FUS-NFATC1/2 fusions.

An increasing number of epithelioid vascular lesions, in particular tumors from the benign and low-grade end of the spectrum, have been characterized by recurrent gene fusions. As a result, the detection of these molecular markers have improved the classification of diagnostically challenging cases. However, despite the significant progress, there are occasional lesions that do not fit in known histologic or molecular groups.

Risk Assessment of Visceral Sarcomas: A Comparative Study of 2698 Cases from the SEER Database.

Soft tissue sarcomas arising in visceral organs are rare and lack validated tumor-staging protocols. Clinicopathologic features and clinical outcomes of 2698 visceral sarcomas identified in the Surveillance, Epidemiology, and End Results Program (SEER) database were compared with sarcomas arising in the extremities/trunk (n = 10,237) or retroperitoneum (n = 1067) using standard statistical techniques. Important prognostic criteria for visceral sarcomas, as in other anatomic sites, included tumor size, histologic grade, and presence of metastatic disease.

A Proposed Staging System for Improved Prognostication of MDM2-amplified Liposarcoma.

Despite the release of anatomic site-specific staging systems for soft tissue sarcomas in the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, the algorithms for sarcomas arising in the extremities/trunk and retroperitoneum differ only in the staging of lymph node metastasis. The retroperitoneum not only provides a larger potential space for tumor growth before the clinical presentation, but its anatomic complexities complicate surgical resection and adversely affect disease-free survival. Here, we propose a new staging system for MDM2-amplified liposarcomas (well-differentiated and dedifferentiated subtypes) that properly emphasizes retroperitoneal localization, degree of differentiation (histologic subtype), and presence of distant metastasis.

Diagnoses and Difficulties in Mesenteric Pathology.

Mesenteric diseases are broadly separated into 2 groups: non-neoplastic and neoplastic. Common non-neoplastic mesenteric diseases include those involving the mesenteric vasculature and those of inflammatory processes. Mesenteric inflammatory processes can mimic a neoplastic process.

Leiomyoma with KAT6B-KANSL1 fusion: case report of a rapidly enlarging uterine mass in a postmenopausal woman.

Background: Uterine leiomyomas, in contrast to sarcomas, tend to cease growth following menopause. In the setting of a rapidly enlarging uterine mass in a postmenopausal patient, clinical distinction of uterine leiomyoma from sarcoma is difficult and requires pathologic examination.

Case Presentation: A 74-year-old woman presented with postmenopausal bleeding and acute blood loss requiring transfusion.

Perinephric myxoid pseudotumor of fat: a distinctive pseudoneoplasm most often associated with non-neoplastic renal disease.

In 2009, Tanas et al reported unusual changes in the perinephric fat, mimicking well-differentiated liposarcoma. We report 11 perinephric masses showing similar changes but chiefly arising in patients with non-neoplastic renal disease. Tissue from 11 perinephric masses was retrieved, and immunohistochemistry for IgG/IgG4 and fluorescence in situ hybridization (FISH) for MDM2 amplification was performed.