Exploring the molecular landscape of cutaneous mixed tumors characterized by TRPS1::PLAG1 gene fusion DOI Creative Commons
Ziyad Alsugair, Marie Donzel, Nicolas Macagno

et al.

The Journal of Pathology, Journal Year: 2024, Volume and Issue: 264(4), P. 448 - 456

Published: Oct. 29, 2024

The histological similarities between pleomorphic adenomas (PAs) and cutaneous mixed tumors (CMTs) found in certain facial regions can create a diagnostic challenge. Molecular findings reveal common genetic profiles, particularly PLAG1 rearrangements both PA CMT. Although molecular distinctions have received limited attention, our observations indicate multiple cases of CMTs carrying the TRPS1::PLAG1 fusion. This clinical experience has driven investigation into potential utility fusions for determining tumor origin. Two cohorts consisting 46 CMT 45 salivary glands were obtained from French institutions reviewed by specialists each subspecialty. RNA sequencing analysis was conducted to identify features harboring PLAG1. Clinical, pathological, data collected. In this study, exhibited recurrent gene fusions, primarily (74%). These shared characteristic features, including tubuloductal differentiation 55% squamous metaplasia varying proportions. contrast, had involving with various partners, only one case which identified. disparity also observed at transcriptomic level other tumors. However, TRPS1 immunostaining did not correlate conclusion, we report that fusion exhibit similar is associated around half cases. Detection could be valuable correctly identifying origin these © 2024 Pathological Society Great Britain Ireland.

Language: Английский

Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases DOI Creative Commons
Thibault Kervarrec,

Danna Westphal,

Daniel Pissaloux

et al.

Histopathology, Journal Year: 2024, Volume and Issue: 85(4), P. 566 - 578

Published: May 24, 2024

Aims Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of duct and may arise from transformation preexisting benign poroma. In 2019, Sekine et al. demonstrated presence YAP1::MAML2 YAP1::NUTM1 fusions in most poromas porocarcinomas. Recently, our group identified PAK2‐ subset poromas. Herein we report series 12 porocarcinoma cases harbouring PAK1/2/3 fusions. Methods Results Five patients were male median age was 79 years (ranges: 59–95). Tumours located on trunk ( n = 7), thigh 3), neck 1), or groin area 1). Four developed distant metastases. Microscopically, seven harboured poroma component invasive part. Ductal formations observed all, while infundibular/horn cysts cells with vacuolated cytoplasm detected six tumours, respectively. three cases, consisted proliferation elongated cells, some which formed pseudovascular spaces, whereas others predominant solid trabecular growth pattern. Immunohistochemical staining for CEA EMA confirmed ducts. Focal androgen receptor expression specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 2), ZDHHC5::PAK1 DLG1::PAK2 , CTDSP1::PAK1 CTNND1::PAK1 SSR1::PAK3 CTNNA1::PAK2 RNF13::PAK2 ROBO1::PAK2, CD47::PAK2 . Activating mutation HRAS (G13V, 3, G13R, 1, Q61L, 2) present cases. Conclusion Our study suggests that oncogenic driver porocarcinomas lacking YAP1 rearrangement.

Language: Английский

Citations

8
PLAG1-Rearranged Uterine Sarcomas: A Study of 11 Cases Showing a Wide Phenotypical Spectrum Not Limited to Myxoid Leiomyosarcoma-Like Morphology DOI
Michael Michal, Abbas Agaimy, Sabrina Croce

et al.

Modern Pathology, Journal Year: 2024, Volume and Issue: 37(9), P. 100552 - 100552

Published: June 26, 2024

Language: Английский

Citations

4
Gene Fusion-Driven Cutaneous Adnexal Neoplasms: An Updated Review Emphasizing Molecular Characteristics DOI
Gerardo Cazzato, Maged Daruish, Francesco Fortarezza

et al.

American Journal of Dermatopathology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract: Gene rearrangements or fusions have emerged as critical oncogenic drivers in various cutaneous adnexal neoplasms. This review offers a comprehensive overview of both established and recently identified molecular alterations, with specific focus on gene fusions. Key alterations discussed include YAP1 rearrangements, CRTC1::MAML2 fusions, BRD3 MYB::NFIB ETV6::NTRK3 PLAG1 alongside rarer fusion transcripts, such MEF2C::SS18 , FOXK1::GRHL1/2 GPS2::GRHL RARA::NPEPPS . The article highlights the significance these genetic changes tumor biology their potential therapeutic implications for locally advanced metastatic skin tumors. It also addresses diagnostic challenges distinctions, providing updated insights into tumors driven by

Language: Английский

Citations

0
Primary cutaneous NUT adnexal carcinoma: morphologic, genetic and methylation analysis of seven new cases with comparison to extracutaneous NUT carcinoma and NUTM1‐rearranged porocarcinoma DOI Creative Commons
Mélanie Legrand, Baptiste Louveau,

Amélie Osio

et al.

Histopathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

NUT carcinoma is a rare malignant neoplasm characterised by recurrent NUTM1 rearrangements, initially reported in the midline. Recently, 10 cases of cutaneous with adnexal differentiation harbouring BRD3::NUTM1, NSD3::NUTM1, BRD4::NUTM1 or BRD3::NUTM2B fusions have been reported. Accordingly, 'NUT carcinoma' (NAC) has introduced as provisional tumour entity to fifth edition WHO Classification Skin Tumours. We report histopathological, molecular genetic and epigenetic features seven additional NAC. The cohort consisted four female three male patients median age 58 years. Follow-up was available for six cases, documented diffuse metastatic spreading leading death at 18 months after diagnosis one case. Histopathological examination all revealed dermal/subcutaneous neoplasms composed poorly differentiated cells large irregular vesicular nuclei least focally prominent nucleoli. All showed areas duct/gland formation. Using immunohistochemistry, tumours expression co-expression SOX10 five cases. P63 P40 were diffusely positive case confined periphery nests Molecular analysis (n = 3), BRD3::NUTM1 3) NSD3::NUTM1 1). Although being close this latter group, methylation transcriptional that NAC formed unique cluster distinct from extracutaneous NUTM1-rearranged porocarcinoma. Our results further support existence primary suggest it may represent an carcinoma.

Language: Английский

Citations

0
In‐frame insertions of SOX10 are highly enriched and characterize a distinct transcriptomic profile in gastrointestinal schwannomas DOI
Pei‐Hang Lee, Shih‐Chiang Huang, Jen‐Chieh Lee

et al.

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Gastrointestinal schwannomas are molecularly and histologically distinct from their non‐gastrointestinal counterparts, lacking NF2 alterations, although the primary drivers of these tumors barely understood. A recent study has identified SOX10 in‐frame insertions in schwannomas, particularly intracranial non‐vestibular lesions, whereas role gastrointestinal remains unexplored. Whole exome sequencing 15 two revealed recurrent 14 cases (93%) without other nerve sheath tumor‐related such as mutations or SH3PXD2A :: HTRA1 fusions (~14% cases). The prevalence, mutation spectrum, specificity were validated using Sanger a large cohort comprising 61 98 well 110 non‐schwannomatous mesenchymal melanocytic neoplasms. insertions, occurring within near high mobility group box domain, significantly enriched (91.8%) compared with (5.1%). most common insertion, p.Y173_Q174insKY, was present 86.9% but absent cases. Another p.P175_R176insKYQP, rare exclusively found (3/98), while all controls ‐normal. ‐inserted exhibited histologic features characteristic including microtrabecular arrangement Schwann cells, peripheral lymphoid cuffs, lack encapsulation. Both ‐normal demonstrated diffuse immunoreactivity. associated locations ( p < 0.001), older patients fusion negativity larger tumor size = 0.013). Gene expression profiling 44 transcriptomic profiles between primarily groups, latter being classifiable into fusion‐poor fusion‐enriched sub‐clusters. This highlights genetic heterogeneity suggests that play pivotal tumorigenesis distinctly separating them counterparts contributing to unique molecular profile. © 2025 Pathological Society Great Britain Ireland.

Language: Английский

Citations

0
Microcystic Adnexal Carcinoma (MAC) and Eccrine Cutaneous Mixed Tumor (ECMT): 2 Cases of Rare HPV-independent Vulvar Cutaneous Adnexal Tumors DOI

Margarita Consing Gangelhoff,

Josephine Harter,

Virginia Kurth

et al.

International Journal of Gynecological Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Microcystic adnexal carcinoma (MAC) and eccrine cutaneous mixed tumor (ECMT) are both tumors that may occur in the vulvar region, but very rare at this site. Consequently, they not enter differential diagnosis of lesions for gynecologic pathologists a subspecialized practice setting. Here we report case MAC ECMT recently diagnosed our institution underscore key histologic immunophenotypic features each lesion can assist their correct identification. Both have tubular to corded pattern lesional cells within desmoplastic chondromyxoid stroma. However, shows true sweat duct differentiation, characterized by 2 SOX10 negative cell layers, including an outer p63+/p40+/EMA− basal layer inner p63−/p40−/EMA+ ductal layer. The main diagnostic considerations include other with namely syringoma squamoid (SEDC). Conversely, is single SOX10+ population without immunoreactivity p63 or p40. apocrine variant (ACMT)—the analog salivary gland pleomorphic adenoma—and gland-type neoplasms. Unlike described HPV-associated multiphenotypic sinonasal carcinoma, neither nor therefore p16 negative. In summary, one discuss ancillary testing results help differentiate these from morphologic mimics.

Language: Английский

Citations

0
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 DOI
Boulos Mansour, Michele Donati, Tamás Pancsa

et al.

Virchows Archiv, Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Language: Английский

Citations

2
Tumeurs annexielles cutanées : mise au point et synthèse des gènes de fusion à connaître pour le diagnostic DOI
Thibault Kervarrec, Maxime Battistella, Nicolas Macagno

et al.

Annales de Pathologie, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Citations

1
Reappraisal of Oncocytic Adenocarcinoma DOI Creative Commons

Lucas Vial,

Françoise Descôtes,

Jonathan Lopez

et al.

The American Journal of Surgical Pathology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS emerging entities" in 2022 WHO classification head neck tumors. The lack specific molecular alterations its potential affiliation with other gland carcinomas, such oncocytic mucoepidermoid carcinomas (OMEC) or subtype duct (OSDC) justified this reclassification. becoming essential to clarify complex spectrum diagnoses surrounding objective study explore histologic features, well immunohistochemical profiles, cases previously diagnosed OC OMEC glands. This involved 28 predominantly component. sex distribution equal. median age 59 years (range 10 89). Most these originated from parotid (25/28). mean tumor size 2.4 cm 0.5 6.5). Primary immuno-morphological mutation/gene fusion profiles mainly (64.3%, 18/28). them were descending order OSDC (8/18), (5/18), (2/18). But 3 remained unclassified (3/18). transcriptomic analysis found proximity their profile group distance OSDCs. These findings imply that not distinct but represents variants carcinomas. underscores importance thorough morphologic, immunohistochemical, examinations accurately diagnose predominant components

Language: Английский

Citations

1
Calcifying Spindle Cell Soft Tissue Tumor With SOX10::PLAG1 Fusion: A Case Report of a Morphologically Distinctive and Potentially Novel Soft Tissue Tumor DOI
Kemal Kösemehmetoğlu,

Elaheh Mosaieby,

Petr Šteiner

et al.

Genes Chromosomes and Cancer, Journal Year: 2024, Volume and Issue: 63(6)

Published: June 1, 2024

ABSTRACT The widespread use of advanced molecular techniques has led to the identification several tumor types with PLAG1 gene fusions some which also affect skin and soft tissues. Herein, we present a 38‐year‐old female subcutaneous affecting her forearm, does not seem fit into any currently recognized entity. It was well‐circumscribed measuring 6 × 4,5 4 cm. had thick capsule composed bland spindle cells forming palisades Verocay body‐like structures within myxocollagenous background. Scattered calcifications were dispersed throughout lesion. No cytological atypia, mitotic activity, or necrosis present. Targeted NGS revealed SOX10::PLAG1 fusion fluorescent in situ hybridization confirmed presence rearrangement. neoplastic showed diffuse immunohistochemical expression S100, SOX10, PLAG1, as well patchy desmin CD34 positivity. methylation profile this did match other entity covered by DKFZ sarcoma classifier apart from gain chromosome 12, copy number normal. completely excised, patient been free disease for years since excision. While more cases are needed confirm distinct entity, propose provisional name “ ‐rearranged calcifying cell tumor.”

Language: Английский

Citations

0