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.

Update on cutaneous mesenchymal tumors in the 5th edition of WHO classification of skin tumors with an emphasis on new fusion-associated neoplasms.

The section on mesenchymal tumors in the 5th edition of WHO classification of skin tumors has undergone several changes, the most important of which is the inclusion of newly identified tumor entities, which will be the main focus of this review article. These specifically include three novel cutaneous mesenchymal tumors with melanocytic differentiation, and rearrangements of the CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM genes as well as EWSR1::SMAD3-rearranged fibroblastic tumors, superficial CD34-positive fibroblastic tumors, and NTRK-rearranged spindle cell neoplasms. Some of the other most important changes will be briefly mentioned as well.

Using Copy Number Variation Data and Neural Networks to Predict Cancer Metastasis Origin Achieves High Area under the Curve Value with a Trade-Off in Precision.

The accurate identification of the primary tumor origin in metastatic cancer cases is crucial for guiding treatment decisions and improving patient outcomes. Copy number alterations (CNAs) and copy number variation (CNV) have emerged as valuable genomic markers for predicting the origin of metastases. However, current models that predict cancer type based on CNV or CNA suffer from low AUC values.

Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.

ALK -rearranged Mesenchymal Neoplasms With Prominent Foamy/Pseudolipogenic Cell Morphology : Expanding the Phenotypic Spectrum of ALK Fusion Neoplasms and Report of Novel Fusion Partners.

The category of ALK -rearranged mesenchymal neoplasms has been evolving rapidly, with reports of morphologically diverse lesions of cutaneous, soft tissue, and visceral origin. While some of these represent morphologically defined entities harboring recurrent ALK fusions (inflammatory myofibroblastic tumor and epithelioid fibrous histiocytoma), others are unclassified by morphology with variable overlap with the tyrosine kinase family of neoplasia and their underlying ALK fusions cannot be suspected based on morphology. We herein report 3 cases that expand the anatomic, morphologic, and genotypic spectrum of ALK -rearranged unclassified neoplasms.

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.

Novel CRTC1::MRTFB(MKL2) Gene Fusion Detected in Myxoid Mesenchymal Neoplasms With Myogenic Differentiation Involving Bone and Soft Tissues.

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78).

Molecular analysis of apocrine mixed tumors and cutaneous myoepitheliomas: a comparative study confirming a continuous spectrum of one entity with near-ubiquitous PLAG1 and rare mutually exclusive HMGA2 gene rearrangements.

Myoepithelial neoplasms of the skin and soft tissue still represent a confusing and somewhat controversial field in pathology as it appears that this category includes several different entities. However, recent studies have suggested that both apocrine mixed tumors (AMT) and cutaneous myoepitheliomas (CM) harbor identical chromosomal rearrangements involving the PLAG1 gene and hence may represent a morphological spectrum. The aim of the present study was to share our institutional experience with these tumors and specifically focus on studying their immunohistochemical and molecular features to further assess their relatedness.

Mesenchymal skin tumors - Novel entities in the 5th edition of WHO classification of skin tumors.

The section on mesenchymal tumors in 5th edition of WHO classification of skin tumors has undergone several changes, the most important of which, as usual, is the inclusion of newly identified tumor entities, which will be the main focus of this review article. These specifically include three novel cutaneous mesenchymal tumors with melanocytic differentiation, and rearrangements of the CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM genes. In addition, EWSR1::SMAD3-rearranged fibroblastic tumors, superficial CD34-positive fibroblastic tumors, and NTRK-rearranged spindle cell neoplasms were newly included.

Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review.

A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes.

Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations.

Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity 'NTRK-rearranged spindle cell neoplasms' included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months).

Inflammatory Rhabdomyoblastic Tumor: From a Nebulous Smooth Muscle Neoplasm to a Novel Skeletal Muscle Tumor Subtype.

Inflammatory rhabdomyoblastic tumor is a recently introduced name for neoplasms currently included in the World Health Organization classification of soft tissue tumors under the rubric inflammatory leiomyosarcoma. Inflammatory rhabdomyoblastic tumor is an excellent example of how surgical pathologists working in conjunction with tumor biologists can greatly improve tumor classification to the benefit of patients. Over the last 28 years, understanding of this entity has undergone a fascinating evolution.

Molecular pathology in diagnosis and prognostication of head and neck tumors.

Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal tract, oropharynx, nasopharynx, and soft tissue. Availability of new molecular techniques allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, the expanding spectrum of immunohistochemical markers facilitates a rapid identification of diagnostic molecular abnormalities.