https://www.pathologica.it/issue/feedPathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology2025-10-17T08:02:17+00:00Mattia Barbareschipathologica@pacinieditore.itOpen Journal SystemsPathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, Italian Division of the International Academy of Pathologyhttps://www.pathologica.it/article/view/1295Trends in Thyroid Fine-Needle Aspiration Cytology - Results from the Italian Cytopathology Committee National Practice Survey2025-05-07T12:11:01+00:00Gennaro AcanforaGennaro.acanfora95@gmail.comMariantonia Nacchionacchiomariantonia92@gmail.comCarla Baronchellicarla.baronchelli@gmail.comAmedeo Boscainointab@libero.itCarolina Burianic.buriani@ospfe.itElisabetta Caricoelisabetta.carico@uniroma1.itAndrea Cavazzanaandrea.cavazzana@uslnordovest.toscana.itAnna Maria Cesinarocesinaro.annamaria@aou.mo.itDoglione Claudiodoglioni.claudio@hsr.itImmacolata Cozzolinocoimma73@gmail.comAnna Crescenzia.crescenzi@policlinicocampus.itStefania Damianistefania.damiani@unibo.itGiovanni De Chiaraendocrinologiadechiara@gmail.comGiselle de Rezendegisele.derezende@ospedaleniguarda.itLudovica De VincentiisLudovicadevincentiis@gmail.comGuido Faddaguido.fadda@unime.itGerardo Ferraragerardo.ferrara@istitutotumori.na.itFlavio Pironiflavio.pironi@auslromagna.itGiacomo Gazzanog.gazzano@auxologico.itAnnarita Gencarelliannarita.gencarelli@gmail.comLeo Guidobaldileo.guidobaldi@aslroma2.itMaria Letizia Laimarialetizialai@yahoo.itGaetano Magrog.magro@unict.itGrazie Marangigrazia.marangi@gmail.comFabio Pagnifabio.pagni@unimib.itGianmaria Pennelligianmaria.pennelli@unipd.itSimonetta Pianasimonetta.piana@ausl.re.itMichele Pirellimichele.pirrelli@asl.taranto.itStefano Pizzolittostefano.pizzolitto@asufc.sanita.fvg.itGiuseppina Renzullirenzullipina@gmail.comEsther Diana Rossiesther.rossi@policlinicogemelli.itSilvia Taccognastaccogna@reginaapostolorum.itSilvia Uccellasilvia.uccella@hunimed.euClara Ugolini clara.ugolini@unipi.itAndrea VecchioneAndrea.Vecchione@uniroma1.itElena Vigliarelena.vigliar@unina.itMarco VolanteAndrea.Vecchione@uniroma1.itRoberta Zappacostazappacosta2@hotmail.comFrancesco Alfredo Zitofazito@libero.itGiovanni Tallinigiovanni.tallini@ausl.bologna.itGiancarlo Tronconegitronco@unina.itClaudio Bellevicineclaudio.bellevicine@unina.it<p class="p1">Objective. To understand the state of the art of Italian thyroid cytopathology practice, a survey was sent by the Italian Committee of cytopathology to the 846 registered emails of the Italian society of pathology and cytology (SIAPEC) members.</p> <p class="p1">Methods. A survey divided in 4 sections (geographic distribution, pre-analytics, diagnostic work up, molecular testing) was sent to SIAPEC members in April 2023. An additional set of questions regarding molecular analysis was sent to first round participants.</p> <p class="p1">Results. A total of 104/846 (12.2%) SIAPEC members replied to the survey. Non-pathologist physicians performed FNA in the majority of cases (78/104, 75%). The Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) system is adopted by most centers (94/104 90,38%), although in 32.6% it was used along with other classifications systems. Only 44/104 (42.2%) of the participants performed molecular tests on thyroid FNA, mostly upon requests from the caring physician (25/41, 61.1%).</p> <p class="p1">Conclusion. This survey offers a snapshot of the current Italian thyroid FNA practice. The volume of thyroid FNA performed is similar to the pre-Covid workload and the ICCRTC is the most frequently adopted classification system. Molecular tests are performed by a significant minority of participants, with different testing modalities and clinical-pathological indications.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/866Public health impact of a diagnostic improvement intervention supported by Rapid On-Site Evaluation (ROSE) in thoracic CT-guided biopsies: a pre-post study2024-12-16T15:51:15+00:00Francesca Ambrosifrancesca.ambrosi@ausl.bologna.itMatteo Riccimatteo.ricci18@studio.unibo.itJonathan Beonijonathan.beoni@ausl.bologna.itStefano Guicciardistefano.guicciardi@ausl.bologna.itNazarena Nannininazarena.nannini@ausl.bologna.itElena Mengozzielena.mengozzi@ausl.bologna.itMichele Imbrianimichele.imbriani@ausl.bologna.itClaudio Lazzaric.lazzari@ausl.bologna.itMichelangelo FIORENTINOmichelangelo.fiorentino@unibo.it<p class="p1">Background. Lung cancer is the leading cause of cancer death worldwide and was the most commonly diagnosed cancer in 2022. The Rapid On-Site Evaluation (ROSE) technique allows immediate evaluation of samples collected during needle aspiration and needle biopsy procedures, improving diagnostic accuracy and reducing the need for repeated procedures.</p> <p class="p1">Study <strong>Design</strong>. A pre-post study evaluated the health benefits for patients and improved healthcare costs with ROSE diagnostic support from a public health perspective.</p> <p class="p1">Methods. We compared two groups of patients who underwent TC-guided transthoracic needle aspiration/biopsy from March 2017 to March 2022. In the first group (pre-ROSE) the procedures were performed without the support of ROSE, while in the second group (post-ROSE) the pathologist assisted the radiologist in all cases. The diagnostic advantages, the economic-organizational impact of the procedure, and the related benefits for patients were analyzed.</p> <p class="p1">Results. The pre-ROSE group comprised 97 patients, and the post-ROSE group comprised 67. In the group receiving ROSE diagnostic support, the rate of inadequate diagnostic tests requiring repetition decreased from 29.9% to 9.0% (p<strong> = </strong>0.001). This saved time for the radiologist, pathologist, nurse, radiology technician, laboratory technician, and support staff, freeing up diagnostic slots that could be used to reduce waiting lists and improve the quality of patient service.</p> <p class="p1">Conclusions. ROSE support has improved diagnostic efficacy and sample quality, reducing repeat testing and associated costs. This leads to better management of healthcare resources, reduced waiting times, and more accurate diagnoses, improving the quality of patient care and bringing public health benefits.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/953Clinical autopsy: methodological applications and scientific perspectives in post-mortem diagnostics2025-01-08T21:03:05+00:00Martina Padovanomartina.padovano@uniroma1.itMatteo Scopettimatteo.scopetti@uniroma1.itFederico Manettifederico.manetti@uniroma1.itDonato Morenadonato.morena@uniroma1.itGianluca Pirasgianluca.piras@uniroma1.itVittorio Gattovitt8812@gmail.comAlessandro Santurroasanturro@unisa.itVittorio Fineschivittorio.fineschi@uniroma1.it<p class="p1">Objective. To analyze mortality from natural causes in hospital and out-of-hospital settings using clinical autopsy, emphasizing its methodological rigor and scientific contributions.</p> <p class="p1">Methods. The present retrospective study included 1,340 autopsies conducted at the Umberto I General Hospital (2017-2023). Standardized protocols were applied, including complete autopsies, ancillary investigations (histopathology, imaging, microbiology, genetics), and systematic data collection.</p> <p class="p1">Results. Out of 912 natural deaths, cardiac pathologies were the leading terminal cause (70.3%), followed by vascular (10.4%) and respiratory disorders (7.0%). Males (71%) predominated, with peak mortality between 55-74 years. Ancillary methods were crucial in identifying causes, particularly in individuals < 30 years where macroscopic findings were absent. Genetic studies helped identify hereditary cardiac conditions, enabling preventive family screening.</p> <p class="p1">Conclusions. Clinical autopsy remains indispensable for determining the cause of death and improving diagnostic accuracy. A rigorous, standardized approach with ancillary methods enhances scientific understanding and public health interventions. Expanding post-mortem diagnostics and promoting centralized facilities is vital for quality mortality assessments.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/979SPOP and MMR/MSI alterations in prostate cancer: relationship with PD-L1, TILs and AR expression2025-02-18T20:52:02+00:00Vincenzo Fiorentinovincenzo.fiorentino@unime.itEmanuela Germanàemanuelagermana@hotmail.itGabriele Ricciardigricciardi1998@gmail.comSara Capodimontisaracapodimonti@libero.itTonia Cencitonia.cenci@gmail.comAugusto Orlandiorlandi@uniroma2.itValeria Zuccalàvaleria.zuccala@unime.itEugenia Guidaeugenia.guida@uniroma2.itVincenzo Ficarravincenzo.ficarra@unime.itCristina Pizzimenticristinapizzimenti86@gmail.comAngelo Totaroangelo.totaro@policlinicogemelli.itGuido Faddaguido.fadda@unime.itSusanna Dolcidolci@uniroma2.itFrancesco Piercontifrancesco.pierconti@unicatt.itMaurizio Martinimaurizio.martini@unime.it<p class="p1">bjective. Despite the promising introduction of anti-PD-L1 therapy for advanced stage of prostate cancer (PCa), recent studies have demonstrated limited success, suggesting the need to improve patient selection.</p> <p class="p1">Methods. We retrospectively selected 153 PCa patients. We performed SPOP mutational analysis and evaluated PD-L1 expression, MMR/MSI status, TIL (as CD4/CD8 ratio), and the mRNA expression of AR and CD274. Using SPOP interfering-RNA in two PCa cell lines (LNCaP, PC3) and western-blot analysis, we examined the role of SPOP silencing on CD274 expression.</p> <p class="p1">Results. Functionally altered SPOP mutations (14 out of 153 samples, 9.15%) and MMR/MSI status (3.3%) were associated with higher PD-L1 expression (both p < 0.0001), lower TIL (p < 0.0001 and p = 0.0004), and higher Gleason scores (both p < 0.05). SPOP-mutated patients exhibited significantly higher CD274, and AR mRNA expression compared to those without mutations (p = 0.0006 and p = 0.0148). Reducing SPOP expression in cancer cell lines resulted in a significant upregulation of PD-L1 expression.</p> <p class="p1"><span class="s1">Conclusions. Our analysis identifies SPOP mutations and MMR/MSI status as cofactors in high PD-L1 expression and CD8/TIL presence in PCa, representing potential markers for selecting patients who are more likely to respond immunotherapy or to combined treatment.</span></p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/981HER2-positive neuroendocrine breast carcinoma: a case study uncovers CCND1, FGF19, and IGF1R amplifications as new molecular drivers2025-03-05T17:01:01+00:00Margherita Zordanmargheritazor@gmail.comElena Fiorioelena.fiorio@aovr.veneto.itValeria Maffeisvaleria.maffeis@aovr.veneto.itAndrea Mafficiniandra.mafficini@univr.itGiulia Querzoligiulia.querzoli@aosp.bo.itBianca Bariogliobianca.barioglio@gmail.comPamela Biondanipamela.biondani@aovr.veneto.itMatteo Brunellimatteo.brunelli@univr.itAlessandra Inventoalessandra.invento@aovr.veneto.itFrancesca Pellinifrancesca.pellini@aovr.veneto.itClaudio Luchiniclaudio.luchini@univr.itAldo Scarpaaldo.scarpa@univr.itAlessia Nottegaralessia.nottegar@univr.it<p class="p1">Primary neuroendocrine carcinoma of the breast (NEBC) is a rare entity among breast malignancies, and is usually associated with a more aggressive clinical course compared to other types of invasive breast cancer. Although some studies have characterized the molecular profile of NEBCs using targeted sequencing, these tumors are often treated similarly to other primary breast carcinomas despite their unique morpho-phenotypic characteristics.</p> <p class="p1">In this study, we present the case of a woman with HER2-positive primary large cell NEBC with homolateral axillary nodal metastases. After neoadjuvant therapy, the patient underwent surgical resection of the breast, showing a partial pathological response. Next-generation sequencing was performed on pre- and post-treatment samples using a 174-genes panel. Both samples exhibited a similar molecular profile, including a somatic mutation in <em>GATA3</em> and amplifications of <em>CCND1</em>, <em>FGF19</em>, and <em>IGF1R</em>. <em>ERBB2</em> amplification was identified in the pre-operative biopsy but was lacking in the post-treatment surgical specimen.</p> <p class="p1">This study represents the first report of <em>CCND1</em>, <em>FGF19</em>, and <em>IGF1R</em> gene amplification in a breast neuroendocrine carcinoma. These findings provide new insights into the molecular profile of this entity and may contribute to future studies on precision oncology.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1059Data-driven insights into post-autopsy consultations: causes of perinatal mortality and parental outcomes2025-05-06T19:55:27+00:00Rosario Barrancorosario.barranco@unige.itMatteo Lorenzonilorenzonimatteo94@gmail.comFrancesco Ausaniafrancesco.ausania@univr.itFrancesco Venturafrancesco.ventura@unige.itRiccardo Guglielmoriccardo.guglielmo@unige.itMaria Teresa Diviziamariateresadivizia@gaslini.orgSimone Ferrerosimone.ferrero@unige.itPierangela De Biasiopierangela.debiaisio@hsanmartino.itCesare Arionicesare.arioni@hsanmartino.itChiara Maria Biattachiara.biatta@gmail.comGabriele Gaggerogabrielegaggero@gaslini.orgmichele paudicemichele.paudice@unige.itValerio Vellonevalerio.vellone@unige.it<p class="p1">Objective. Perinatal mortality deeply affects parents and healthcare providers. Post-autopsy consultations (PACs) help parents understand the causes of fetal death and offer emotional support. This study evaluates their effectiveness in emotional healing, preventing medico-legal disputes, and identifying key death causes.</p> <p class="p1">Methods. This retrospective study analyzes 360 fetal autopsies at San Martino Hospital, Genoa (2013-2021). Among them, 120 parents sought PACs. Causes of fetal death were classified using the relevant condition at death (ReCoDe) system, and parental emotional outcomes were evaluated based on consultation timing.</p> <p class="p1">Results. Fetal causes, mainly congenital anomalies, accounted for 52.5% of deaths, while placental causes were 46.7%. PACs performed within 5 months of loss led to better emotional outcomes, whereas delayed PACs were linked to ongoing distress. Parents who attended with partners reported greater emotional stability. Additionally, PACs helped reduce medico-legal disputes by clarifying causes of death.</p> <p class="p1">Conclusions. PACs are crucial for helping parents cope with fetal loss, offering emotional closure and reducing legal disputes. A multidisciplinary approach with clear communication from healthcare professionals addresses both the medical and emotional aspects of perinatal mortality. Tailored follow-up care is essential for supporting grieving parents and managing future pregnancies<em>.</em></p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1281Current approaches, barriers, and future directions in pleural mesothelioma diagnostics: results from an Italian National Survey2025-07-03T10:56:33+00:00Federica Pezzutofederica.pezzuto@unipd.itGianluca Lopezgianluca.lopez@unimi.itFrancesca Barbisanfrancesca.barbisan@ospedaliriuniti.marche.itLorenzo Rossolorenzo.rosso@unimi.itGiuseppe Pelosigiuseppe.pelosi@unimi.itMauro Papottimauro.papotti@unito.itLuisella Righiluisella.righi@unito.itFiorella Calabresefiorella.calabrese@unipd.it<p class="p1">Objective. This nationwide survey aimed to assess current diagnostic practices, adherence to international guidelines, and challenges encountered by Italian pathologists in the diagnosis of diffuse pleural mesothelioma (PM).</p> <p class="p1">Methods. A structured questionnaire with 38 items was distributed electronically via Google Forms to Italian pathologists involved in mesothelioma diagnosis. Questions covered demographics, biopsy practices, pathology report, immunohistochemistry, molecular diagnostics, educational needs, and barriers to collaborative research.</p> <p class="p1">Results. Participants represented diverse experience levels and institutional affiliations, primarily academic medical centers. Significant variability was found in tissue sampling and biobanking practices. Major diagnostic challenges included identifying sarcomatoid/desmoplastic patterns and inadequate adipose tissue in biopsies. Most pathologists managed inconclusive cases via multidisciplinary discussions and molecular analyses (BAP1, MTAP). Barriers identified included inadequate digital pathology infrastructure and limited standardized protocols for tissue collection. Participants strongly favored enhanced molecular resources, standardized histopathological protocols, and national collaborative initiatives.</p> <p class="p1">Conclusions. Improved diagnostic accuracy requires targeted training, standardized protocols, enhanced molecular diagnostic capabilities, and structured national collaborations.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1139Oncotype DX in clinical practice: impact on treatment decisions and healthcare system economy2025-05-06T19:27:28+00:00Alessia Capozzialessia.capozzi@unicampus.itSilvia Maria Rossisilviamaria.rossi@unicampus.itGiovanna Sabareseg.sabarese@policlinicocampus.itMarco Germanim.germani@policlinicocampus.itGabriella Gullottag.gullotta@policlinicocampus.itStefania Sfregolas.sfregola@policlinicocampus.itGiuseppe Perroneg.perrone@policlinicocampus.it<p class="p1">Objective. The aim of this study is to assess the impact of Oncotype DX on treatment decisions and healthcare economy.</p> <p class="p1">Methods. Data were retrospectively collected from Fondazione Policlinico Universitario Campus Bio-Medico of Rome. 313 female patients with HR-positive, HER2-negative breast cancer underwent Oncotype DX between August 2020 and January 2024. Recurrence score, recurrence risk and chemotherapy benefit were collected from Oncotype DX report. Clinical and pathological data were collected. To objectify the oncological prescription based on clinicopathological variables, we used PREDICT 2.2 algorithm. Reimbursements, hospital accesses and number of health services in one-year follow-up were also collected.</p> <p class="p1">Results. Oncotype DX did not indicate chemotherapy in 223/313 (71.2%) patients. In the PREDICT 2.2 scenario, 147/313 (47%) patients were not indicated chemotherapy. Thus, genomic test approach led to a decrease of 24.2% in chemotherapy prescription. Patients receiving chemotherapy had 21 (+91.3%) more hospital accesses, 115 (+101.8%) more health services and a reimbursement of €2811 (+31.5%) higher than patients not receiving chemotherapy (median values).</p> <p class="p1">Conclusions. Oncotype DX results in lower rates of chemotherapy prescription and in possible healthcare cost savings.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1518TFE3-rearranged and TFEB-altered renal cell carcinoma: from classification to real-life. Insights from a national Italian survey2025-08-13T08:16:23+00:00Stefano Marlettastefano.marletta92@gmail.comAnna Caliòanna.calio@univr.itGiuseppe Nicolò Fanellinicolo.fanelli@unipi.itPaola Biancopaolabianco83@gmail.comAngelo Giovanni Bonadioabonadio@aslal.itClaudia Covellicla.covelli85@gmail.comSimona Francesconis.francesconi@aospterni.itMariia Ivanovamariia.ivanova@ieo.itDaniele Lisciadanyliscia@gmail.comAlessia Moroalessia.moro@asst-santipaolocarlo.itDaniela Onnisdanielaonnis@aob.itMaria Rosaria Raspollinimariarosaria.raspollini@gmail.comCostantino Riccicostantino.ricci4@unibo.itSteno Sentinellisteno8@virgilio.itMarina Valerimarinavaleri22@gmail.comGuido Martignoniguido.martignoni@univr.it<p class="p1">Objective. Ongoing discoveries in cancer research keep expanding the landscape of renal cell carcinoma classification, particularly for “molecularly-defined” tumors like TFE3-rearranged and TFEB-altered renal cell carcinoma. However, scientific updates often do not align with pathologists’ daily practice and resources. Herein, we present the results from a national Italian survey assessing physicians’ personal experience on TFE3-rearranged and TFEB-altered renal cell carcinomas.</p> <p class="p1">Methods. An online questionnaire encompassing 26 questions was delivered to the Italian Study Group of Uropathology (GIUP) members, addressing critical concerns on their routine approach to these tumors. The answers were collected and further analyzed.</p> <p class="p1"><span class="s1">Results. Thirteen pathologists with varying uropathological experience responded to the survey. Data confirmed the rarity of these neoplasms, with 69% of participants experiencing fewer than five or none at all. Despite this, aggressive behavior was documented by half of the respondents. Unusual morphology (62%) and young age (38%) were identified as the most relevant clues for suspecting TFE3-rearranged and TFEB-altered renal cell carcinoma. However, variability was observed in the specific histological features and the age threshold. The majority of the participants (54%) agreed on the need for ancillary molecular techniques for diagnostic purposes. Regarding immunohistochemistry, all professionals relied on multiple assays, attributing a primary role to a panel including cathepsin K, melanocytic markers (HMB45 and melan-A), PAX8, cytokeratin 7, and CA9. Additionally, most (58%) reported routine TFE3 immunohistochemical staining, although generally considering it reliable as long as diffuse and intense (58%) or requiring FISH confirmation in every positive case (25%). As for this latter, variability was recorded regarding split-signals positivity cut-off.</span></p> <p class="p1"><span class="s1">Conclusions. The continuous evolution of renal cell carcinoma classification significantly impacts the pathologists’ routine approach. Our survey underscores the importance of ongoing knowledge sharing and heightened awareness for accurately identifying TFE3-rearranged and TFEB-altered renal cell carcinoma and providing further insights on still unsolved issues.</span></p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/774Mesonephric-like metaplasia of the endometrium in a woman treated with letrozole: morphological, immunohistochemical and molecular analysis2024-11-12T15:59:07+00:00Antonio Travaglinoantonio.travaglino.ap@gmail.comAngela Santoroangela.santoro@policlinicogemelli.itDamiano Arciuolodamiano.arciuolo@policlinicogemelli.itAntonio Raffoneanton.raffone@gmail.comGiuseppe Angelicogiuangel86@hotmail.itJvan Casarinjvan.casarin@uninsubria.itSusanna Ronchisusanna.ronchi@asst-settelaghi.itNicoletta D'Alessandrisnicoletta.dalessandris@policlinicogemelli.itGiulia Scaglionegiulia.scaglione@policlinicogemelli.itMichele Valentedr.valente.m@gmail.comBelen Padial Urtuetabelen.padialurtueta@policlinicogemelli.itFrancesca Addantefrancesca.addante@policlinicogemelli.itNadine Narduccinadine.narducci@policlinicogemelli.itAlessia Piermatteialessia.piermattei@policlinicogemelli.itThomas Rossithomas.ross@asst-settelaghi.itFederica Cianfrinifederica.cianfrini@policlinicogemelli.itGian Franco Zannonigianfranco.zannoni@unicatt.itStefano La Rosastefano.larosa@uninsubria.it<p class="p1">Endometrial mesonephric-like adenocarcinoma (MLA) is thought to arise from endometrial epithelium through a Müllerian-to-mesonephric transdifferentiation. However, no benign or precancerous mesonephric-like endometrial lesions have been reported so far. Herein, we describe the first case of endometrial mesonephric-like metaplasia.</p> <p class="p1">A 61-year-old woman who was treated with letrozole for 5 years underwent removal of an endometrial polyp. Histological examination highlighted an area of small round glands resembling mesonephric remnants, with no cytological atypia and no mitotic activity. Immunohistochemistry showed positivity for PAX8, estrogen receptor and GATA3, patchy p16 expression, wild-type p53 pattern, low Ki-67 expression, and negativity for progesterone receptor, TTF1 and CD10. Next-generation sequencing analysis of 17 genes (<em>KRAS, NRAS, HRAS, BRAF, EGFR, ERBB2, FGFR3, IDH1, IDH2, KIT, MET, PDGFRA, PIK3CA, RET, ROS1</em>) showed no pathogenetic mutations.</p> <p class="p1">These features appear consistent with a benign endometrial mesonephric-like metaplasia. Its relationships with hormone treatment and with MLA carcinogenesis remain to be defined.</p>2024-12-28T00:00:00+00:00Copyright (c) 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/831Lung and nodal hairy cell leukemia with concurrent infectious granulomatosis: a mimic of metastatic lung epithelial neoplasia 2025-01-16T13:52:54+00:00Massimiliano Mancinimamancini@ospedalesantandrea.itGiulio Maurizigiulio.maurizi@uniroma1.itEvelina Roggesevelina.rogges@uniroma1.itStefania Scarpinostefania.scarpino@uniroma1.itDavide Vaccadavide.vacca@unipa.itKatia Paciaronikatia.paciaroni@aslroma1.itAndrea Vecchioneandrea.vecchione@uniroma1.itArianna Di Napoliarianna.dinapoli@uniroma1.it<p class="p1">Hairy cell leukemia (HCL) is a rare, indolent B-cell neoplasm, typically involving bone marrow, spleen, and peripheral blood, with extranodal sites rarely affected. Herein, we present the unique case of a 52-year-old man with lung and lymph node involvement by HCL concurrently with atypical mycobacteriosis. Initial imaging showed mediastinal lymphadenopathy and a pulmonary nodule, which raised suspicion for lung neoplasia. A minimally invasive biopsy of the mediastinal nodes and hilar lesion revealed a lymphoid proliferation mixed with necrotizing granulomatous inflammation, with an immunophenotype consistent with HCL and BRAF V600E mutation, confirmed by digital PCR. Notably, molecular analyses detected atypical mycobacteria in lymph nodes. This unusual co-occurrence of HCL with atypical mycobacterial infection in the lung and lymph nodes poses a complex diagnostic and therapeutic challenge, highlighting the importance of recognizing such presentations to optimize patient management.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/896A tough NUT carcinoma to crack2024-12-16T09:06:25+00:00Alessandra Celialed.celi1@gmail.comRossella Brunorossobruno.2112@gmail.comPaola Vignalipaola.vignali@med.unipi.itIacopo Petriniiacopo.petrini@unipi.itAngelo Valettoa.valetto@ao-pisa.toscana.itVeronica Bertiniv.bertini@ao-pisa.toscana.itOlivia Fanucchio.fanucchi@ao-pisa.toscana.itAntonio Chellaanto.kell@tiscali.itGreta Alìgreta.ali@unipi.it<p class="p1"><span class="s1">We describe the case of a NUT carcinoma of the thorax in a 27-year-old male, non-smoker, presenting a voluminous neoformation in the hilum and the left side of the mediastinum infiltrating heart and great vessels. The biopsy revealed a poorly differentiated cancer with focal crush artifact consisting of undifferentiated small to medium-size cells, with minimal indistinct to clear cytoplasm, round or oval nuclei, nuclear molding and brisk mitotic activity. Suggestive morphological features often associated with NUT carcinoma, for example abrupt foci of keratinization, were not seen. Moreover, immunohistochemical (IHC) analysis showed negativity for epithelial markers, such as Cytokeratin AE1/AE3, CK7, CK-CAM5.2, CK5/6, p40 and TTF1; therefore, further immunohistochemical markers were evaluated, and the conclusive diagnosis was based on a diffuse speckled nuclear positivity for NUT1 (clone C52B1). Considering the unusual morphological and IHC findings, a comprehensive genome profiling, by FoundationOne®CDx Next Generation Sequencing (NGS), was performed on DNA from the transbronchial needle aspiration formalin-fixed and paraffin-embedded cell block. Neither <em>NUTM1</em> gene fusions nor other pathogenic gene variants were detected. However, focal and segmental copy number variations (CNV) were seen in chromosome 19, in the middle of the <em>BRD4</em> gene, the most common <em>NUTM1 </em>fusion partner. In addition, an array CGH (aCGH) analysis was performed: this analysis revealed different CNV, including a 2.7Mb deletion and a 14.4Mb duplication in chromosome regions were <em>NUTM1</em> and <em>BRD4</em> are respectively located. Finally, an RNA-based NGS confirmed the presence of a <em>BDR4-NUTM1</em> fusion transcript, supporting IHC findings. IHC and molecular results all together are suggestive for a likely non-canonical <em>BRD4</em>-<em>NUTM1 </em>fusion. Our case showed unusual features both from a morphological and a molecular point of view: the diagnosis was driven by NUT1 positive immunohistochemistry, thus underlining the crucial role of this test.</span></p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/961Lymphoepithelioma-like carcinoma of urinary bladder - a rare subtype of urothelial carcinoma: a series of 12 cases2025-01-10T20:48:59+00:00Rutvij Khedkarrutvijkhedkar@gmail.comRamandeep Kaurdrjohal18@gmail.comSwapnil Raneraneswapnil82@gmail.comGagan Prakashgagan2311@gmail.comMahendra PalMahen1197@gmail.comAmandeep Aroraamanarora12389@gmail.comAmit Joshidramitjoshi74@gmail.comPriyamvada Maitrepriyamvadamaitre@gmail.comSangeeta Desaisangeetabdesai@gmail.comSantosh Menonmensantosh@gmail.com<p class="p1">Lymphoepithelioma-like carcinoma (LELCa) is a rare and aggressive subtype of urothelial carcinoma. This study presents a series of 12 cases of LELCa of the urinary bladder, highlighting its clinical and pathological features with treatment related details. The majority of cases presented with advanced-stage disease, often mixed with conventional urothelial carcinoma. Histologically, LELCa is characterized by sheets of undifferentiated tumor cells with prominent nucleoli in a syncytial growth pattern, accompanied by a dense lymphocytic infiltrate. Immunohistochemistry aids in confirming the epithelial nature of the tumor cells. Treatment strategies for LELCa are evolving. While radical cystectomy remains the standard treatment for advanced-stage disease, a multimodal approach, including chemotherapy and radiation therapy, may be considered, especially in cases with pure or predominant LELCa histology.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1033When scars tell a story: cases of scar sarcoidosis preceding or following diagnosis of systemic disease 2025-02-16T18:05:04+00:00Francesco Fortarezzafrancescofortarezza.md@gmail.comChristian Ciolfichriciolfi96@gmail.comJacopo Tartagliajacopo.tartaglia@studenti.unipd.itAnna Poputchikovaanna.poputchikova@studenti.unipd.itGerardo Cazzatogerardo.cazzato@uniba.itMauro Alaibacmauro.alaibac@unipd.itAngelo Paolo Dei Tosangelo.deitos@unipd.it<p class="p1"><span class="s1">Sarcoidosis is a systemic granulomatous disease of unknown etiology, characterized by the formation of non-necrotizing granulomas in various organs, with the lungs and mediastinal lymph nodes being the most commonly affected sites. “Scar sarcoidosis” refers to the rare phenomenon in which sarcoid granulomas develop in pre-existing scars, such as surgical scars, tattoos, or sites of previous skin trauma. We report two cases of patients who presented with sarcoid granulomas developing in previous scar sites. The first case involved a 37-year-old man with a prior diagnosis of stage II pulmonary sarcoidosis who later developed erythematous plaques over scarred areas. A skin biopsy confirmed non-necrotizing granulomas. The second case describes a 45-year-old woman who presented with erythematous-violaceous plaques over previous traumatic scars, with subsequent tests revealing systemic sarcoidosis. Scar sarcoidosis highlights the diverse clinical presentations of sarcoidosis, emphasizing the need for clinicians to be vigilant of new or unusual manifestations. Recognizing this form of sarcoidosis can facilitate early systemic diagnosis and impact patient management. These cases underscore the importance of a multidisciplinary approach in diagnosing and managing sarcoidosis, given its dynamic and unpredictable nature.</span></p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1157A novel germline NF1 splicing variant drives the onset of an anorectal mucosal melanoma in a patient with a stable and durable nivolumab response2025-03-19T14:09:46+00:00Enrico Berrinoenrico.berrino@ircc.itSara Erika Bellomosaraerika.bellomo@ircc.itLuca Mastorinoluca.mastorino@unito.itValeria Morbidonivaleria.morbidoni@gmail.comNicola Crosettonicola.crosetto@ircc.itAnna Sapinoanna.sapino@ircc.itIvana Sarottoivana.sarotto@ircc.itAnita Chestaanita.chesta@ircc.itGianluca Avallonegianluca.avallone2@gmail.comPietro Quaglinopietro.quaglino@unito.itDaniela Zampieridaniela.zampieri@ircc.itRebecca Senettarebecca.senetta@unito.itEva Trevissoneva.trevisson@unipd.itCaterina Marchiòcaterina.marchio@ircc.itSimone Riberosimone.ribero@unito.it<p class="p1">Objective. Neurofibromatosis type-1 (NF1) patients rarely develop mucosal melanomas. We report a rare form of anorectal mucosal melanoma (ARMM) in an NF1 syndromic patient profiled for genomics and transcriptomics to assess the determinants of the response to nivolumab.</p> <p class="p1">Methods. Primary melanoma and metastases were analyzed with targeted sequencing and gene expression profile (tGEP). We applied <em>in silico</em> (cBioPortal and predictor tools) and <em>in vitro</em> (hybrid minigene) approaches to confirm the variant pathogenicity.</p> <p class="p1">Results. We detected the novel c.4269+2_4269+3delTG germline splicing variant in <em>NF1</em>, which proved to be pathogenic by the minigene assay showing an aberrant splicing. The tumor showed a copy-number (CN) neutral loss of heterozygosity for the WT allele, and both ARMM and metastases carried several CN gains associated with <em>NF1</em>-driven carcinogenesis and very low mutation burden. The tGEP analysis unveiled a macrophagic infiltration, with a pro-inflammatory M1-type polarization, in the context of lack of PD-L1 expression.</p> <p class="p1">Conclusions. The response to nivolumab in a germline NF1-driven ARMM case seems independent from levels of TMB and PD-L1 expression and may be mediated by inflammatory response induced by M1-polarized macrophages.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/818Spinal drop metastases of choroid plexus papilloma: a brief report and updated literature review2025-01-30T19:54:15+00:00Filippo Nozzolifilippo.nozzoli@unifi.itAgnese Pedoneagnese.pedone@unifi.itElena Nuccielena.nucci@unifi.itManuel Cameliamanuel.camelia@unifi.itGiovanni Muscasmuscasgi@aou-careggi.toscana.itTommaso Cassericasserit@aou-careggi.toscana.itFrancesca Di Pasqualefrancesca.dipasquale@unifi.itIsacco Desideriisacco.desideri@unifi.itEnrico Fainardienrico.fainardi@unifi.itLorenzo Livilorenzo.livi@unifi.itAlessandro Della Puppaalessandro.dellapuppa@unifi.it<p class="p1">Choroid plexus papillomas (CPPs) are rare central nervous system benign tumours and spinal metastases are even less frequent. Herein, we describe a case of a 51-year-old man with several episodes of loss of consciousness. Brain magnetic resonance imaging (MRI) displayed a fourth ventricle contrast-enhancing lesion that was totally resected, and histopathological findings showed a papillary neoplasm derived from choroid plexus epithelium, with mild pleomorphism and absence of mitotic activity, consistent with CPP. Two months after the first operation, multiple spinal drop metastases at L4, L5 and S1-S2 were revealed through spine MRI. Histological examination of the spinal lesions fulfilled as well the diagnostic criteria for CPP. Radiological and histological findings are presented, and the relevant literature of spinal spreading of CPPs is discussed. This special case, together with the literature review, helps expanding the spectrum of knowledge on benign CPPs, their potential for disease spread and progression and highlights the need to identify biomarkers that correlate with clinical behaviour.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/904A lung nodule showing both adenocarcinoma and diffuse large lymphoma: a pathological anatomy surprise2024-12-16T10:49:18+00:00Carolina Sassorossisassorossi.caro@gmail.comQianqian Zhangqianqian.zhang@policlinicogemelli.itAlessandra Cancellierialessandra.cancellieri@policlinicogemelli.itElena MaioloElena.maiolo@policlinicogemelli.itMarco Chiappettamarcokiaps@hotmail.it<p class="p1">Dear Editor,</p> <p class="p2">it is with a great pleasure that we want to submit this very interesting case about the unique coexistence of a lung adenocarcinoma and diffuse large lymphoma in the same lung nodule. The nodule was found accidentally, and the patient was asymptomatic for both the oncological pathologies. At anatomo-pathological analysis the histological features of both lesions were identified. To the best of our knowledge, this is the first case in which the two tumors are together in the very same nodule.</p> <p class="p2">A lung nodule in the right upper lobe was occasionally detected in a 74-year-old man.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/994Early gestational choriocarcinoma: report of two cases and review of the literature2025-07-16T18:52:05+00:00Angela Guerrieroangela.guerriero@aopd.veneto.itLara Alessandrinilara.alessandrini@aopd.veneto.itLuisa Santoroluisa.santoro@aopd.veneto.itKathrin Ludwigkathrin.ludwig@aopd.veneto.itVennus Shafieivennus.shafiei@aulss5.veneto.itPietro Gogliapietro.goglia@studenti.unipd.itPava Srsenpava.srsen@studenti.unipd.itGiulia Tascagiulia.tasca@iov.veneto.itAngelo Paolo Dei Tosangelo.deitos@unipd.it<p class="p1">Gestational choriocarcinoma (GCC) is a malignant and aggressive tumor composed of neoplastic trophoblasts rarely arising months after a normal gestation or after an hydatidiform mole (HM). Histologically, its main diagnostic features are a trimorphic population of trophoblast cells and an absence of chorionic villi. Recently, extremely rare cases of GCC diagnosed in molar and in placenta specimens have been described and accepted as early forms of GCC. We report two cases of GCC diagnosed in a term placenta and in a complete HM (CHM) and underline the importance of recognizing such a rare early form of GCC.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1071Myxoid glioneuronal tumor with PDGFRA p.K385 mutation in the periventricular white matter: a rare case and literature insights2025-08-04T16:09:05+00:00Serena Salzanosere.salzano@gmail.comMichele Massiminomichedot@yahoo.itRosario Caltabianorosario.caltabiano@unict.itTindaro Buzzancabutin94@tiscali.itFrancesco Certocicciocerto@yahoo.itGiuseppe Barbagallogbarbagallo@unict.itPaolo Vignerivigneripaolo@gmail.comGiuseppe Broggigiuseppe.broggi@gmail.com<p class="p1">Dear Editor,</p> <p class="p2">We report the case of a 29-year-old man who presented with severe headache. MRI revealed an oval, well-defined lesion (12×18 mm) in the left periventricular white matter, hyperintense on T2-weighted imaging without contrast enhancement or edema. Gross total resection was performed.</p> <p class="p2">Brain and brainstem MRI revealed, in the left frontal region, an ovoid-shaped lesion measuring approximately 12×18 mm in axial dimensions, exhibiting a ‘target-like’ appearance. On FLAIR sequences, the lesion showed peripheral hyperintensity with a centrally hypointense area. The lesion margins appeared well-defined, and the core demonstrated high signal intensity on T2-weighted images (Fig. 1A) and hypointensity on FLAIR sequences.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1172Interventional pathologists: a new challenge for pathologists in the modern era2025-03-25T20:55:27+00:00Sofia Asiolisofia.asioli3@unibo.itMaria Berezinamari.berezina@gmail.comGiulia Querzoligiulia.querzoli2@unibo.itMaria Pia Foschinimariapia.foschini@unibo.it<p class="p1">This letter highlights the growing importance of Interventional Pathologists (IP) in modern diagnostic practice. Building on the established role of Interventional Cytopathologists, the integration of In-Vivo and Ex-Vivo Confocal Microscopy (CFM) into surgical and outpatient settings enables real-time histological evaluation. These technologies allow for rapid and accurate diagnosis, reduce procedural repetition, and shorten time to treatment. Clinical applications—including in neurosurgery, dermatology, and breast pathology—demonstrate high diagnostic concordance with standard histology. The authors advocate for the formal recognition and training of Interventional Pathologists to meet the evolving demands of precision medicine.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1156The Shrinking Workforce of Pathologists: Implications for Healthcare and Possible Solutions2025-03-19T07:45:10+00:00Francesco Giuseppe CarboneFrancescogiuseppe.Carbone@apss.tn.it<p class="p1">Dear Editor,</p> <p class="p2">I would like to draw your attention to a pressing issue that threatens the sustainability and effectiveness of pathological diagnostics in Italy: the alarming shortage of pathologists and the increasing workload imposed on the remaining specialists, which significantly affects diagnostic turnaround times, a critical aspect of patient care. This situation could compromise service efficiency and raise concerns about diagnostic accuracy and patient safety.</p> <p class="p2">Recent projections indicate a growing deficit of medical specialists across various disciplines, with pathology being one of the most affected. According to workforce planning data, the number of active pathologists in Italy is expected to decline significantly by 2025 due to an aging workforce and an insufficient number of newly trained specialists <sup>1</sup>. Moreover, many residency scholarships remain unfilled each year, as pathology remains an unpopular choice among medical graduates. For example, in 2024 alone, 110 out of 180 (52%) residency positions in pathology were left unassigned <sup>2</sup>. While this high percentage may be partially attributed to a general shortage of new medical graduates, it also suggests a declining interest in pathology as a career choice, with many students preferring other disciplines.</p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathologyhttps://www.pathologica.it/article/view/1613Shortage of Pathologists: a candid narrative2025-08-21T08:01:25+00:00Massimo Barberismassimo.barberis@ieo.it<p class="p1">Dear Editor,</p> <p class="p2"><span class="s1">after a long, distinguished and lucky career as a Pathologist I think back to my first experiences and to the reasons of this professional choice. After graduation in the 1970s, I was looking for a graduate school. I was attracted by the classic fields like Internal Medicine, Pneumology or Infectious Diseases. While I was looking around, I had the opportunity to be introduced to the Director of the Department of Pathology of the largest General Hospital, in Milan. After some weeks the unique cultural atmosphere inside the laboratories and the wonderful travels at the microscope won me over. No anxiety, no fears, no concerns about earnings. I loved Herasmus of Rotterdam. In its “Praise of Folly” he wrote “The only certain fact is that without the seasoning of madness, pleasure cannot exist” <sup>1</sup>. The choice was made. And Pathology proved itself a fiery and ever-changing lover. Probably no other specialties have the two-fold characteristics of being the most ancient and the most modern discipline in the same time. In the Pandora’s jar of Pathology, you can find a world of sub-fields, a world of techniques such as electron microscopy, histochemistry, immunohistochemistry, molecular pathology and new cutting-edge sciences based on artificial intelligence (AI). Now I put aside the superfluous memories of an old man and I get to the point. Why is this evergreen discipline underappreciated by recent graduates? A number of vacant positions in medical residency programs are the sad constant in many schools in spite of the efforts of some enlightened spirits who try in vain to highlight the positive aspects of this profession during the degree course. </span></p>2025-10-17T00:00:00+00:00Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology