Updates on lung neuroendocrine neoplasm classification.

Lung neuroendocrine neoplasms (NENs) are a heterogeneous group of pulmonary neoplasms showing different morphological patterns and clinical and biological characteristics. The World Health Organisation (WHO) classification of lung NENs has been recently updated as part of the broader attempt to uniform the classification of NENs. This much-needed update has come at a time when insights from seminal molecular characterisation studies revolutionised our understanding of the biological and pathological architecture of lung NENs, paving the way for the development of novel diagnostic techniques, prognostic factors and therapeutic approaches. In this challenging and rapidly evolving landscape, the relevance of the 2021 WHO classification has been recently questioned, particularly in terms of its morphology-orientated approach and its prognostic implications. Here, we provide a state-of-the-art review on the contemporary understanding of pulmonary NEN morphology and the potential contribution of artificial intelligence, the advances in NEN molecular profiling with their impact on the classification system and, finally, the key current and upcoming prognostic factors.

Combined transarterial chemoembolization and thermal ablation in candidates to liver transplantation with hepatocellular carcinoma: pathological findings and post-transplant outcome.

OBJECTIVES: Evaluating the pathological response and the survival outcomes of combined thermal ablation (TA) and transarterial chemoembolization (TACE) as a bridge or downstaging for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) > 3 cm. MATERIALS AND METHODS: A retrospective review encompassed 36 consecutive patients who underwent combined TA-TACE as bridging or downstaging before LT. Primary objectives included necrosis of the target lesion at explant pathology, post-LT overall survival (OS) and post-LT recurrence-free survival (RFS). For OS and RFS, a comparison with 170 patients subjected to TA alone for nodules <3 cm in size was also made. RESULTS: Out of the 36 patients, 63.9% underwent TA-TACE as bridging, while 36.1% required downstaging. The average node size was 4.25 cm. All cases were discussed in a multidisciplinary tumor board to assess the best treatment for each patient. Half received radiofrequency (RF), and the other half underwent microwave (MW). All nodes underwent drug-eluting beads (DEB) TACE with epirubicin. The mean necrosis percentage was 65.9% in the RF+TACE group and 83.3% in the MW+TACE group (p-value = 0.099). OS was 100% at 1 year, 100% at 3 years and 94.7% at 5 years. RFS was 97.2% at 1 year, 94.4% at 3 years and 90% at 5 years. Despite the different sizes of the lesions, OS and RFS did not show significant differences with the cohort of patients subjected to TA alone. CONCLUSIONS: The study highlights the effectiveness of combined TA-TACE for HCC>3 cm, particularly for bridging and downstaging to LT, achieving OS and RFS rates significantly exceeding 80% at 1, 3 and 5 years.

Low PD-L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment.

AIMS: The current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD-L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal. METHODS AND RESULTS: Histopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non-metastatic cases were assessed. PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and impact upon patients' surgical management were determined. PD-L1 expression in terms of CPS and ICS independently correlated with lymph node metastasis (PD-L1CPS : OR = -2.5, 95% CI = -4.11 to -0.97, P = 0.008 and PD-L1ICS : OR = -1.85, 95% CI = -2.90 to -0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non-metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1CPS = 43.2; PD-L1ICS = 51.9%). Ultimately, PD-L1 evaluation showed good interpathologist concordance in absolute terms [PD-L1CPS interclass correlation coefficient (ICC) = 0.91; PD-L1ICS ICC = 0.793] and using the identified cut-off values (PD-L1CPS ICC = 0.848; PD-L1ICS ICC = 0.756). CONCLUSIONS: Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.

Changes in categorization or nomenclature within neuroendocrine tumors.

Abstract: The 5th edition of the World Health Organization (WHO) classification of neuroendocrine neoplasms (NENs) is built to achieve a uniform terminology and to define a similar diagnostic scheme across different anatomic locations. Since the 4th edition, a chapter discussing NENs in nonneuroendocrine organs has been introduced, which proposes a binary system for classification segregating well-differentiated neoplasms, termed neuroendocrine tumors (NETs), and poorly differentiated neoplasms, termed neuroendocrine carcinomas (NECs). A grading system for NETs is based on mitotic index and/or Ki-67 index and/or necrosis, depending on the different locations. Although this approach has been already well established in the digestive system, it modifies and homogenizes the classification of NENs in the urinary tract, in female genital organs, and in the male genital system. In the lung and thymus, the double terminology of carcinoid/NET, already introduced in the 5th edition of the WHO classification of thoracic tumors, is endorsed. This approach undoubtedly helps the multidisciplinary approach for the diagnosis and clinical management of patients affected by these neoplasms, without losing site-specific characteristics that influence the clinical and biological behavior of tumors in different anatomical sites. Other major advances of the new WHO scheme are the homogenization of epidemiological data and the correct integration of data from prospective future studies aimed at the definition of molecular profiles and at the identification of tumor type-specific and patient-specific therapeutic approaches.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.