Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology

Multifocal calcifying fibrous tumor mimicking peritoneal carcinomatosis

Michele Paudice — 2026-11-09

Calcifying fibrous tumor (CFT) is a rare benign mesenchymal lesion that may exceptionally present as multifocal peritoneal disease, mimicking peritoneal carcinomatosis. We describe a 56-year-old woman presenting with abdominal pain and imaging findings highly suggestive of peritoneal malignancy. However, histological and immunophenotypic evaluation of omental biopsies obtained by diagnostic laparoscopy revealed a multifocal CFT. This case highlights that multifocal calcifying fibrous tumor should be considered in the differential diagnosis of suspected peritoneal carcinomatosis, as recognition of this rare benign entity may prevent misdiagnosis and unnecessary aggressive management.

When one tumor isn’t one: a case of dual driver lung adenocarcinoma

Lorenzo Nibid — 2026-11-09

Lung cancer may exhibit marked morphological and molecular heterogeneity, posing relevant diagnostic and therapeutic challenges. We present a case of lung adenocarcinoma that raises important questions regarding the distinction between collision tumors, intratumoral molecular heterogeneity, subclonal alterations, and aberrant mutation profiles. A 76-year-old man was diagnosed with a lung lesion composed of two spatially distinct adenocarcinomas in the same mass, one harboring the EGFR L858R mutation and the other showing the ALK rearrangement. Integrated gross, histopathological, and molecular assessment was essential to establish the diagnosis of a dual-driver collision tumor. This case highlights the need for careful pathological-molecular correlation and emphasizes the role of MTB in managing complex presentations in lung cancer.

Epithelioid cell myofibroblastoma of the breast: Diagnostic role of FISH analysis

Giuseppe Broggi — 2026-11-09

Myofibroblastoma (MFB) is a rare benign breast tumor, predominantly diagnosed in older men and postmenopausal women. The epithelioid cell subtype, although less common, may represent a diagnostic challenge of malignancy. This paper presents an unusual case of epithelioid cell MFB in a 38-year-old woman and explores the role of molecular cytogenetic analysis in confirming the diagnosis in ambiguous cases. A 38-year-old woman presented with a palpable left breast mass, noticed two months prior. Mammography and ultrasound revealed a mass in the retroareolar region. Ultrasound-guided core biopsy indicated a bland-looking epithelioid cell lesion (diagnostic category: B3). Histological examination of surgical specimen showed an epithelioid cell neoplasm raising differential diagnosis between an epithelioid cell leiomyoma and MFB. Fluorescence in situ hybridization (FISH) revealed mono-allelic deletions in the FOXO1, RB1, and D13S319 loci, which were found in 33%, 43% and 48% of analyzed nuclei, respectively. The case herein presented emphasizes the diagnostic utility of FISH in diagnosing rare mesenchymal breast tumors.

Artificial Intelligence in Pathology. Explanations, Limitations, and Directions

Salvatore Lorenzo Renne — 2026-11-09

Artificial Intelligence (AI) is rapidly transforming the landscape of pathology, promising enhanced diagnostic accuracy, efficiency, and reproducibility. This article provides a pathologist centric overview of AI, offering clear definitions, practical examples, and critical insights into its capabilities and limitations. It addresses the current state of AI integration into digital pathology workflows, including image analysis, pattern recognition, and decision support. Importantly, the discussion highlights key challenges such as algorithmic bias, data dependency, and interpretability-factors essential for safe and effective clinical adoption. The paper also reflects on common misconceptions and the human-AI partnership, urging pathologists to engage with these technologies thoughtfully. Ultimately, it offers guidance on how to critically assess, adopt, and contribute to the responsible use of AI in diagnostic practice.

Turnaround time in surgical pathology: influencing factors and process improvement strategies

Diana Patrícia Gonçalves Ferreira — 2026-11-09

Turnaround time (TaT) is a key performance indicator for surgical pathology quality and efficiency. Identifying factors that influence TaT is crucial to achieve high-quality and resource-efficient performance. The implementation of process management methodologies such as Lean and Six Sigma in surgical pathology laboratories is expanding, improving quality and productivity, reducing TaT, and leading to greater satisfaction and reduced costs. This systematic review aimed to summarize the literature on factors that influence TaT and estimate how process improvement methodologies can be used to decrease it in the pathology laboratory setting. Findings demonstrate that prolonged TaT arises from intrinsic specimen characteristics and suboptimal process management, including workflow inefficiencies and resource constraints. Given that intrinsic specimen characteristics are difficult to modify, emphasis should be placed on process optimization. Lean and Six Sigma methodologies have been successfully implemented to optimize workflows, eliminate waste, standardize processes, and ultimately decrease TaT. In conclusion, TaT remains a cornerstone key performance indicator and an essential measure of quality in surgical pathology laboratories. Its optimization improves patient satisfaction, enhances treatment effectiveness, and reduces costs.

SIAPeC RARE-TARGET – VITA Project: A Large Nationwide Study on Immunophenotypic and Genomic Profiling of Rare Biomarkers in Solid Tumors: Cumulative and Preliminary Data

Antonio Marchetti — 2026-11-09

Background. Targeted therapies, based on the identification of actionable biomarkers, have revolutionized oncology. Agnostic strategies have further expanded treatment options by enabling targeted therapies irrespective of tumor site and histotype. However, the implementation of biomarker screening across diverse neoplasms, including rare tumors or tumors with rare mutations, is often limited by technical barriers. Against this background, the SIAPeC RARE-TARGET study aimed to evaluate the feasibility and clinical relevance of a low-cost, tissue microarray–based screening strategy for immunophenotypic and genomic profiling of rare targets within a nationwide project in Italy.

Methods.Tumor specimens from 9,826 patients, collected between 2015 and 2019 in 18 Italian centers, were processed and analyzed during 2020-2021. Samples included: 1) 1258 special-type tumors, 2) 1691 sarcomatous neoplasms, and 3) 6877 early-onset tumors (age ≤50 years). Tissue microarrays (TMAs) were constructed to enable high-throughput immunohistochemistry (IHC) screening for TRK, ALK, ROS1, BRAF V600E, and mismatch repair (MMR) proteins. Positive cases were validated using orthogonal next-generation sequencing (NGS) targeting gene mutations or fusions.

Results. Of the 9,826 tumors analyzed, 686 (7%) were found to be positive by IHC for at least one biomarker: TRK (1.9%), ALK (1.6%), ROS1 (0.8%), BRAF V600E (1.5%), and MMR deficiency (1.6%). The distribution of biomarker alterations differed significantly across the three major tumor groups analyzed. NGS analysis was feasible in 76% of screened-positive cases, with DNA quality issues accounting for the remainder. Significant inter-center variability in sequencing coverage and success rates highlighted technical challenges related to tissue preservation and pre-analytical conditions.

Conclusion.The SIAPeC RARE-TARGET study demonstrates the feasibility and potential clinical utility of combining TMA-based IHC screening with NGS validation for the identification of rare biomarkers in a nationwide setting. The results underscore the importance of histology-agnostic testing approaches in diverse tumors and the urgent need for standardized pre-analytical protocols. Further detailed analyses of molecular data, along with comparative immunohistochemical evaluations across histotypes for the different biomarkers, will be presented in subsequent publications, providing insights to refine biomarker-driven strategies in pathology practice.

Non-Hodgkin B-cell lymphomas with significant proliferation of T follicular helper T cell: a diagnostic pitfall

Xuan Wang — 2026-11-09

Objective. In B-cell lymphomas, the presence of abundant T-follicular helper (TFH) cells is rarely reported but can pose significant diagnostic challenges, potentially leading to misdiagnosis. The limited literature underscores the importance of detailed characterization of this phenomenon. This study presents the largest series of non-Hodgkin B-cell lymphomas with notable TFH cell hyperplasia, broadening the recognized spectrum of lymphomas associated with abundant TFH cells hyperplasia, and aims to enhance awareness and understanding of this phenomenon.

Methods. We investigated 15 cases of non-Hodgkin B-cell lymphomas with notable TFH cell hyperplasia, analyzing clinical information, morphology, immunophenotypic findings, PCR-based clonality, and next-generation sequencing (NGS) results.

Results. Among these, follicular lymphoma was the most common type (n = 7), followed by diffuse large B-cell lymphoma (n = 5), and rare types such as pediatric-type follicular lymphoma (n = 1), small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 1), and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 1). Shared features across these lymphoma subtypes included significant proliferation of TFH cells, and frequently accompanied by prominent paracortical vascularity, with occasional cases exhibiting eosinophilia. However, the absence of concomitant expansion of follicular dendritic cell (FDC) meshworks and EBER negativity argued against a diagnosis of nodal TFH cell lymphoma, angioimmunoblastic type (nTFHL-AI).

Conclusions. TFH cell hyperplasia can occur in various types of non-Hodgkin B-cell lymphomas, making it crucial for pathologists to recognize reactive TFH cells. This study emphasizes the importance of integrating morphological, immunohistochemical, and molecular findings for accurate diagnosis in these cases.

Performance evaluation of a new EDTA-based CE-IVD decalcifying agent on predictive markers for precision medicine

Lorenzo Nibid — 2026-11-09

In bone biopsy specimens decalcification is a mandatory practice before tissue processing. In the era of precision medicine, the available decalcification reagents often affect nucleic acids, compromising molecular characterizations required in case of bone metastasis. Moreover, decalcification lacks homogenized and standardized protocols, leading to a complex management and high inter- and intra-laboratory variability. These issues represent a main challenge for molecular profiling because testing failure may deny access to personalized therapies. The objective of this study was to compare the effect of a new ready-to-use EDTA-based CE-IVD decalcification agent (Microdec®) with other available decalcification reagents on histomolecular analyses. Interestingly, we found that Microdec® outperforms other evaluated agents and tissues treated with Microdec® are comparable with non-decalcified formalin fixed ones in terms of nucleic acid (DNA and RNA) concentration and fragmentation index allowing optimal results for molecular analyses. In addition, we explored the impact of Microdec® on immunohistochemistry demonstrating that it does not significantly affect protein characterization for diagnostics and predictive purposes. Overall, the carful choice of decalcification agents allows the eligibility of bone biopsy for molecular and predictive pathology without affecting morphology.

Diagnostic Concordance Assessment for gene fusion identification: a multi-institutional experience

Simonetta Buglioni — 2026-11-09

Background. Molecular profiling is essential for the therapeutic management of advanced NSCLC; however, the detection of gene fusions involving ALK, ROS1, RET and NTRK, as well as MET exon 14 skipping events, is technically and interpretatively more challenging than routine sequence variant testing. Heterogeneous diagnostic workflows across laboratories may affect result comparability and reporting consistency. This study aimed to evaluate inter-laboratory concordance for these alterations and to develop a harmonized molecular reporting format within the Lazio Region.

Materials and Methods. Eleven molecular pathology laboratories analyzed nine FFPE NSCLC samples, previously selected and validated by three coordinating institutions. Samples were processed according to local workflows using RT-qPCR and/or NGS, with IHC or FISH when applicable. Inter-laboratory concordance and reporting practices were assessed.

Results. Overall, 81.8% of laboratories correctly identified all expected alterations. Two Institutions each missed a single gene fusion event, mainly due to poor RNA quality or prolonged FFPE storage. Challenges were observed in NTRK1 fusion detection and in samples showing 3′/5′ imbalance. Marked heterogeneity in molecular reporting prompted the development and unanimous adoption of a unified regional template.

Conclusions. High diagnostic concordance was achieved despite methodological heterogeneity. Standardized molecular reporting represents a key step toward harmonizing predictive diagnostics and ensuring equitable access to precision oncology across the regional network.

Professional trajectories of pathologist’s assistants in Italy: a descriptive cross-sectional observational study

Beatrice Gessi — 2026-11-09

Objective. To analyze the professional trajectories, scope of practice, and perceived impact of pathologist’s assistants (PAs) trained in Italy, within a context of emerging and not yet fully institutionalised roles.

Methods. A descriptive cross-sectional study was conducted using a structured, anonymous questionnaire administered to professionals who completed an advanced training for PAs at the Universities of Modena and Reggio Emilia and Padua (2017–2024).

Results. Among 31 respondents, only 55% reported actively performing PA-related grossing activities, with variable frequency and with a high autonomy for low-complexity specimens. Participants reported substantial improvements in technical competencies and professional growth; however, satisfaction was polarized, with high personal satisfaction (68%) but low economic satisfaction (74% dissatisfied). Qualitative findings highlighted the need for practice-oriented training, continuous supervision, and stronger institutional recognition.

Conclusions. The PA role in Italy is characterized by partial integration, with a gap between formal training and clinical implementation. While PAs contribute to workflow optimization and professional development, their consolidation is limited by organisational variability and lack of formal recognition.