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

Rediscovering neuroblastoma pathology from the perspective of digital pathology and AI: Current challenges and future implications

2026-04-24T07:06:35+00:00

Neuroblastoma is the most common extracranial solid malignancy of childhood and demonstrates marked clinical and biologic heterogeneity. Histopathologic evaluation, particularly through the International Neuroblastoma Pathology Classification system, remains central to risk stratification by integrating patient age, degree of neuroblastic differentiation, Schwannian stromal development, and the mitosis–karyorrhexis index. However, diagnostic interpretation is challenged by intratumoral heterogeneity, sampling bias, interobserver variability, and the subjective assessment of subtle morphologic thresholds. These limitations directly influence prognostic categorization and subsequent clinical management.

Digital pathology, through whole-slide imaging, provides a platform for standardized visualization and quantitative analysis of entire tumor sections. Recent computational and artificial intelligence–assisted approaches have demonstrated feasibility in tumor category classification, assessment of differentiation, automated mitosis–karyorrhexis index quantification, prognostic stratification, and prediction of molecular features such as MYCN amplification. While reported performance metrics are promising, most studies remain retrospective, single-institution studies, and limited by small pediatric datasets.

Significant barriers to clinical translation persist, including the need for multi-institutional validation, workflow standardization, quality assurance frameworks, regulatory governance, and mitigation of algorithmic bias. Current evidence supports the role of digital and artificial intelligence tools as complementary aids rather than replacements for expert pathologist interpretation. Coordinated efforts addressing validation, infrastructure readiness, and ethical considerations will be essential for responsible integration of computational methods into neuroblastoma histopathology.

SMARCB1/INI1-deficient tumour of the thorax: a differential diagnosis to be included in thoracic basaloid tumours with ambiguous differentiation and review of the literature

2026-05-06T02:33:02+00:00

Loss of switch/sucrose non-fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), also known as integrase interactor 1 (INI1), has been observed in various malignancies, including malignant rhabdoid tumour, atypical teratoid/rhabdoid tumour, epithelioid sarcoma, renal medullary carcinoma, myoepithelial carcinoma, and SMARCB1-deficient sinonasal carcinoma. Recently, rare cases of primary thoracic SMARCB1/INI1-deficient tumours have been reported and reviewed. Here, we report a case of primary lung SMARCB1/INI1-deficient tumour that fits the category of “thoracic SMARCB1/INI1-deficient undifferentiated tumour”. SMARCB1/INI1 immunohistochemistry should be performed in basaloid tumours with ambiguous differentiation in primary lung malignancy for accurate diagnosis.

Cytopathologist-Performed Thyroid Fine-Needle Aspiration: An Integrated Single-Institution Experience in Verona

2026-04-24T15:04:21+00:00

This letter contributes to the ongoing discussion on thyroid fine-needle aspiration (FNA) practices in Italy by presenting a single-institution experience in which cytopathologists directly perform FNAs within an integrated, multidisciplinary setting. Our model ensures close correlation between sampling and diagnosis, maintains high diagnostic standards, and enables rapid, patient-centered clinical decision-making. Additionally, it highlights the educational value of involving pathology residents and supports the role of the interventional pathologist to meet the evolving demands of precision medicine.

Plexiform neuroblastoma-like cutaneous schwannoma: report of a rare morphological variant

2026-06-08T19:29:17+00:00

Dear Editor,

Schwannomas are benign nerve sheath tumours composed of neoplastic cells with schwannian differentiation, of which several morphological variants have been described. Neuroblastoma-like schwannoma is an exceptionally rare subtype defined by the presence of rosette-like structures composed of neoplastic Schwann cells surrounding a collagenous core. We describe a case of neuroblastoma-like schwannoma (schwannoma with rosette-like structures) also exhibiting a plexiform growth pattern; such combined features have been rarely reported so far.

The IL-1β signaling axis as a prognostic determinant in early-stage breast cancer: integrated analysis of tumor and circulating biomarkers

2026-02-12T13:11:31+00:00

Background. Chronic inflammation contributes to breast cancer progression, yet the prognostic relevance of inflammatory signaling pathways in early-stage disease remains incompletely defined. Interleukin-1β (IL-1β) is a key pro-inflammatory cytokine regulated by inflammasome activation and receptor-mediated signaling. This study evaluated the clinical and prognostic significance of major IL-1β pathway components in early-stage invasive breast cancer.

Methods. A retrospective cohort of 562 patients with early-stage invasive breast cancer treated between 2018 and 2025 was analyzed. Tissue microarrays were constructed, and immunohistochemistry was used to assess intratumoral expression of caspase-1, IL-1 receptor type I (IL-1R I), IL-1 receptor type II (IL-1R II), IL-1 receptor accessory protein (IL-1RacP), and IL-1 receptor antagonist (IL-1RA). Protein expression was quantified using H-scores and dichotomized by survival-based cut-offs. Circulating IL-1β levels were measured by ELISA in a subset of patients (n = 66). Associations with clinicopathological features, disease-free survival (DFS), and breast cancer-specific survival (BCSS) were evaluated.

Results. High intratumoral caspase-1 expression was associated with favorable tumor characteristics, reduced recurrence and metastasis, and improved DFS and BCSS. In contrast, elevated IL-1R II expression correlated with disease recurrence and shorter DFS. IL-1β expression alone showed no independent prognostic significance. Combined analyses demonstrated improved outcomes in tumors with preserved caspase-1 and IL-1β expression. Circulating IL-1β levels were higher in basal-type tumors but showed limited prognostic value.

Conclusions. Prognostic effects of IL-1β signaling in early-stage breast cancer depend on inflammasome integrity and receptor regulation rather than cytokine abundance alone. Integrated pathway profiling may improve biologically meaningful prognostic stratification.

The role of transbronchial cryobiopsy in DIPNECH diagnosis

2026-06-09T17:58:44+00:00

Objective
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare condition for which the diagnostic role of transbronchial lung cryobiopsy (TBLC) remains incompletely investigated. This study compared histological samples obtained by transbronchial lung cryobiopsy (TBLC) with those obtained by surgical lung biopsy (SLB).

Methods
This is an observational retrospective study enrolling adult patients with final diagnosis of DIPNECH histologically proved by TBLC and/or SLB, from 2011 to 2025. Clinical data, pulmonary function tests, BAL findings, CT features, and histology were compared between groups.

Results
Fourteen women with a final biopsy-proven diagnosis of DIPNECH were included: 8 diagnosed by TBLC and 6 by SLB. Median age was 64 years (IQR 59-67). Pulmonary function tests showed airflow obstruction and air trapping, with median FEV1 71.4% predicted (IQR 49.8-90.0), FEV1/FVC 0.67 (IQR 0.57-0.75), and RV/TLC 47.3% (IQR 42.4-53.5). Clinical and radiological features were similar across groups. BAL showed lymphocytosis in 6/9 patients (67%). Histology showed a nonsignificant trend toward more frequent detection of constrictive bronchiolitis in SLB specimens than in TBLC specimens (66% vs 13%; p = 0.09), whereas no significant differences were observed for the other histological features. In the TBLC group, pneumothorax occurred in two cases, neither requiring drainage.

Conclusion
The study suggests that TBLC can represent a valid diagnostic alternative to SLB for DIPNECH, capturing key histological features, though apparently less sensitive for constrictive bronchiolitis. Moreover, a lymphocytic BAL pattern may be observed in DIPNECH and, if confirmed in larger cohorts, could support the diagnostic workup.

Custom Next-Generation Sequencing panel for cholangiocarcinoma diagnostic profiling

2025-11-20T18:43:49+00:00

Objective. Cholangiocarcinoma (CCA) is an aggressive malignancy with limited therapeutic options and poor prognosis. Advances in next-generation sequencing (NGS) revealed distinct molecular profiles between intrahepatic (iCCA) and extrahepatic (eCCA) subtypes, identifying recurrent mutations with diagnostic and therapeutic significance. We evaluated the performance of a laboratory-developed NGS panel designed for the integrated diagnostic and predictive profiling of CCA.

Methods and Results. In this multicentric retrospective study, 50 biopsies were analyzed, achieving 92% success rate. Pathogenic variants were identified in 58.7% of samples, with TP53 (26.1%) and KRAS (21.7%) as the most frequently mutated genes. Multiple mutations were observed in 14 cases, the most frequent co-mutation being KRAS plus TP53 (6 cases). Non-druggable but diagnostically relevant genes (e.g., ARID1A, BAP1) were added to enhance classification accuracy.

Conclusions. Despite limitations such as inability to detect gene fusions (e.g., FGFR2), the panel demonstrated strong analytical feasibility and clinical utility. Integrating DNA/RNA sequencing, optimized pre-analytical workflows, and multidisciplinary interpretation will refine precision oncology approaches for CCA management in the future.

The Digital Pathology Perspective in Forensic Assessment of Medical Liability Cases

2026-04-13T07:05:09+00:00

In forensic evaluations of alleged medical malpractice, histopathology has historically offered a robust basis for expert opinion. Tissue sections examined microscopically can assist in establishing causal relationships between clinical interventions and adverse outcomes, frequently guiding the course of civil or criminal proceedings ^1,2,3. In cases of supposed malpractice, the collaborative dialogue between forensic and clinical pathologists, despite their differing perspectives, where the former primarily focuses on reconstructing causal links in death investigations and the latter on disease classification and patient care, can enhance the depth and reliability of medico-legal evaluations regarding micromorphological features. This teamwork may help reduce interpretive bias, encourage consistency, and strengthen the robustness of expert opinions ⁴. In this article, we outline the opportunities, challenges, and medico-legal implications of implementing digital pathology and Whole-Slide Imaging (WSI) in the forensic assessment of alleged medical liability cases.

In this context, the digital transformation permeating the field of medicine is now extending to forensic practice. WSI and digital pathology have evolved from theoretical concepts to validated realities, driven by rigorous technical advancements and an expanding body of evidence.