PATHOLOGICA最新文献

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.

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.

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.

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.

Objective: To analyze mortality from natural causes in hospital and out-of-hospital settings using clinical autopsy, emphasizing its methodological rigor and scientific contributions.

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.

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.

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.

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.

Methods: Primary melanoma and metastases were analyzed with targeted sequencing and gene expression profile (tGEP). We applied in silico (cBioPortal and predictor tools) and in vitro (hybrid minigene) approaches to confirm the variant pathogenicity.

Results: We detected the novel c.4269+2_4269+3delTG germline splicing variant in NF1, 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 NF1-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.

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.

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.

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.

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%).

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.

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.

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.

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).

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.

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.

Conclusions: Improved diagnostic accuracy requires targeted training, standardized protocols, enhanced molecular diagnostic capabilities, and structured national collaborations.

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.

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.

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 (KRAS, NRAS, HRAS, BRAF, EGFR, ERBB2, FGFR3, IDH1, IDH2, KIT, MET, PDGFRA, PIK3CA, RET, ROS1) showed no pathogenetic mutations.

These features appear consistent with a benign endometrial mesonephric-like metaplasia. Its relationships with hormone treatment and with MLA carcinogenesis remain to be defined.

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.

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 GATA3 and amplifications of CCND1, FGF19, and IGF1R. ERBB2 amplification was identified in the pre-operative biopsy but was lacking in the post-treatment surgical specimen.

This study represents the first report of CCND1, FGF19, and IGF1R 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.