Gaetano Paolino

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

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Claudio Luchini

University of Verona

Aldo Scarpa

University of Verona

Paola Mattiolo

University of Verona

Rita T. Lawlor

University of Verona

Roberto Salvia

University of Verona

Andrea Mafficini

University of Verona

Matteo Brunelli

University of Verona

Maria Liliana Piredda

Ospedale San Bortolo

Ilaria Girolami

Ospedale di Bolzano

Giuseppe Malleo

University of Verona

Cooperative Institutions

University of Verona

112

Azienda Ospedaliera Universitaria Integrata Verona

Istituti di Ricovero e Cura a Carattere Scientifico

University of Brescia

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

University Hospital Foundation

CS Diagnostics

Brescia University

University of Bologna

Università Cattolica del Sacro Cuore

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Author response for "Challenges Facing Pathologists Evaluating PD‐L1 in Head & Neck Squamous Cell Carcinoma"

Ilaria Girolami Liron Pantanowitz Massimo Barberis Gaetano Paolino Matteo Brunelli

10.1111/jop.13220/v2/response1

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Molecular characterization of extrahepatic cholangiocarcinoma: perihilar and distal tumors display divergent genomic and transcriptomic profiles

Figshare (2021)

Michele Simbolo Samantha Bersani Caterina Vicentini Sergio Vincenzo Taormina Chiara Ciaparrone

Extrahepatic cholangiocarcinoma (ECC) is classified into two subtypes based on anatomic origin: distal extrahepatic (DECC) and perihilar (PHCC) cholangiocarcinoma. This study aimed to shed light on its genomic and transcriptomic profiles. The genomic alterations of 99 ECC (47 PHCC and 52 DECC) were investigated by next-generation sequencing of 96 genes. A subgroup of cases, representative of each subtype, was further investigated using transcriptomic analysis. Bioinformatics tools were applied for clustering and pathway analysis and defining the immune composition of the tumor microenvironment. PHCC had more frequent KRAS mutations (p = 0.0047), whereas TP53 mutations were more common in DECC (p = 0.006). Potentially actionable alterations included high-tumor mutational burden and/or microsatellite instability (7.1%), PI3KCA mutations (8.1%), and MYC (10.1%) and ERBB2 amplification (5.1%). The transcriptomic profiles showed the presence of three distinct clusters, which followed the anatomic origin and differed in immune microenvironment. DECC appeared to contain two distinct tumor subgroups, one enriched for druggable alterations and one lacking actionable opportunities. This study provides new insights into the molecular landscape and the actionable alterations of ECC. Our findings represent a step toward improved ECC molecular taxonomy and therapeutic strategies for precision oncology.

10.6084/m9.figshare.17382158

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CD117 Is a Specific Marker of Intraductal Papillary Mucinous Neoplasms (IPMN) of the Pancreas, Oncocytic Subtype

International Journal of Molecular Sciences (2020)

Paola Mattiolo Seung‐Mo Hong Gaetano Paolino Borislav C. Rusev Giovanni Marchegiani

The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN) category. IOPN is composed of oxyphil cells, usually expressing MUC5AC, MUC6, and Hep Par-1, and harboring PRKACA/B fusion genes as their genetic hallmark. Although IOPNs are associated with an infiltrative adenocarcinoma in up to 30% of cases, the survival rate after surgical resection approaches 100%. This highlights the importance of the correct IOPN diagnosis, above all in cases with an associated invasive component. In this study, the immunohistochemical expression of CD117 was investigated in 111 IPMNs, including 17 oncocytic, 45 gastric, 20 pancreatico-biliary, and 29 intestinal IPMNs. We also tested the expression of MUC5AC, MUC6, and Hep Par-1 in the IOPN cohort. CD117 positivity was significantly more frequent in IOPNs compared to the other IPMN subtypes (p < 0.0001). Furthermore, within IOPN, a lower or absent CD117, MUC5AC, MUC6, and Hep Par-1 expression tended to be associated with the presence of an infiltrative component. Our findings shed light into the biology of these complex lesions, which are confirmed to be a distinctive IPMN subtype; notably, CD117 emerged as a potential, additional tool in the differential diagnosis of IPMNs.

CD117

CDX2

10.3390/ijms21165794

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Citations (19)

Value of a Multidisciplinary Approach in Sinonasal Inverted Papilloma with Extensive Ossification

American Journal of Case Reports (2021)

Bianca Barioglio Gaetano Paolino Ilaria Girolami Elena Bariani Nicola Santonicco

BACKGROUND:Inverted papilloma is a benign epithelial lesion of the nasal cavities. Although commonly encountered in clinical practice, it rarely presents with extensive ossification and few cases have been described in the literature. CASE REPORT:Herein, we describe the case of a 51-year-old man who presented to clinical attention for persistent right nasal obstruction. Magnetic resonance imaging (MRI) and computed tomography (CT) scans of the facial bones showed a lobated lesion with ossification occupying most of the right nasal cavity. The lesion was removed by endoscopic sinus surgery, leaving the surrounding bone structures intact. On pathological examination, mature bone tissue was found within an inverted papilloma. The pathologist contacted the surgeon, who confirmed that no healthy bone tissue was removed during the procedure. Therefore, a diagnosis of inverted papilloma with ossification could be made without the use of ancillary techniques. CONCLUSIONS:Inverted papilloma with ossification is a common lesion with a rare feature. Our report investigates the diagnostic difficulties of a paradigmatic case, highlighting the importance of multidisciplinary teamwork in reaching the final diagnosis.

Inverted Papilloma

Sinus (botany)

10.12659/ajcr.934149

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Intraductal tubulopapillary neoplasm (ITPN) of the pancreas: a distinct entity among pancreatic tumors

Histopathology (2022)

Gaetano Paolino Iréne Esposito Seung‐Mo Hong Olca Baştürk Paola Mattiolo

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach.PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence.ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.

GNAS complex locus

Pancreatic Intraepithelial Neoplasia

10.1111/his.14698

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KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities

Journal of Experimental & Clinical Cancer Research (2020)

Claudio Luchini Gaetano Paolino Paola Mattiolo Maria Liliana Piredda Alessandro Cavaliere

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, whose main molecular trait is the MAPK pathway activation due to KRAS mutation, which is present in 90% of cases. The genetic landscape of KRAS wild type PDAC can be divided into three categories. The first is represented by tumors with an activated MAPK pathway due to BRAF mutation that occur in up to 4% of cases. The second includes tumors with microsatellite instability (MSI) due to defective DNA mismatch repair (dMMR), which occurs in about 2% of cases, also featuring a high tumor mutational burden. The third category is represented by tumors with kinase fusion genes, which marks about 4% of cases. While therapeutic molecular targeting of KRAS is an unresolved challenge, KRAS -wild type PDACs have potential options for tailored treatments, including BRAF antagonists and MAPK inhibitors for the first group, immunotherapy with anti-PD-1/PD-L1 agents for the MSI/dMMR group, and kinase inhibitors for the third group. This calls for a complementation of the histological diagnosis of PDAC with a routine determination of KRAS followed by a comprehensive molecular profiling of KRAS -negative cases.

Molecular Pathology

10.1186/s13046-020-01732-6

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Citations (75)

Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review

Modern Pathology (2024)

Gaetano Paolino Olca Baştürk Iréne Esposito Seung‐Mo Hong Lodewijk A Brosens

GNAS complex locus

10.1016/j.modpat.2024.100554

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Citations (1)

From fine‐needle aspiration cytology to fluorescent in‐situ hybridization in an unusual case of pharyngeal synovial sarcoma

Diagnostic Cytopathology (2019)

Gaetano Paolino Ilaria Girolami Riccardo Bernasconi Serena Beccari Daniele Marchioni

Abstract Synovial sarcoma arising in the pharynx is a rare entity, with very few cases described in literature, mainly as surgical‐oriented case reports. We report the case of a healthy 20‐year old man who presented with a painless right neck mass, clinically suspicious for a thyroid nodule. Ultrasound scan and fine‐needle aspiration cytology failed to provide a definitive result, although suggesting a mesenchymal proliferation, in accordance with magnetic resonance imaging findings. Therefore, the lesion was removed with a minimally invasive surgical intervention. Definitive histologic and immunohistochemical examination of the surgical specimen revealed a biphasic synovial sarcoma, further validated by the detection of SS18 gene rearrangement on fluorescent in‐situ hybridization examination. Although rarely, synovial sarcoma may arise in the pharynx. Radiological, cytological, histological and molecular findings are needed along each step of the diagnostic process.

Synovial Sarcoma

Nodule (geology)

10.1002/dc.24274

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Early Postoperative Thrombosis of Transcatheter Aortic Valve-in-Valve Prosthesis

The Annals of Thoracic Surgery (2021)

Alessandra Francica Mikhail Dodonov F Tonelli Gaetano Paolino Gabriele Pesarini

Valve replacement

10.1016/j.athoracsur.2020.10.062

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Citations (1)