Among thyroid neoplasms, Hurthle cell tumors (HCTs) have traditionally been a distinct diagnostic category. Hurthle cell adenomas are encapsulated follicular lesions with benign behavior. Hurthle cell carcinomas exhibit unequivocal capsular and/or vascular invasion; they are aggressive tumors with a poor prognosis. Recently, Hurthle cell papillary thyroid carcinomas (PTCs) have been identified on morphological grounds. We hypothesize that a subset of HCTs represent PTC with clinical, histological, and immunohistochemical features based on specific molecular events. ret/PTC gene rearrangements give rise to novel oncogenes that are unique to PTC. We studied a group (n = 50) of HCTs for ret/PTC gene rearrangements. Tumors were examined for papillary differentiation by light microscopic evaluation of nuclear features, by RT-PCR for ret/PTC gene rearrangements, and by immunohistochemistry for ret. Among 24 noninvasive tumors, 13 contained ribonucleic acid for ret/PTC-1, -2, or –3, and 9 of these were immunoreactive for ret. Among 19 Hurthle cell carcinomas, 15 had focal nuclear hypochromasia with grooves and/or inclusions; expressed transcripts of ret/PTC-1, -2, or –3; and exhibited ret positivity. Tumors with ret/PTC gene rearrangements tended to have lymph node metastases rather than hematogenous spread. Our results indicate that a subset of HCTs exhibit features of PTC that are attributable to specific gene rearrangements, resulting in expression of ret/PTC oncogenes. These data support subclassification of HCTs into three groups: Hurthle cell adenomas, Hurthle cell carcinomas, and Hurthle cell PTC.

In advanced non-small cell lung cancer (NSCLC), patients with actionable genomic alterations may derive additional clinical benefit from targeted treatment compared to cytotoxic chemotherapy. Current guidelines recommend extensive testing with next generation sequencing (NGS) panels. We investigated the impact of using a targeted NGS panel (TruSight Tumor 15, Illumina) as reflex testing for NSCLC samples at a single institution. Molecular analysis examined 15 genes for hotspot mutation variants, including AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53 genes. Between February 2017 and October 2020, 1460 samples from 1395 patients were analyzed. 1201 patients (86.1%) had at least one variant identified, most frequently TP53 (47.5%), KRAS (32.2%) or EGFR (24.2%). Among these, 994 patients (71.3%) had clinically relevant variants eligible for treatment with approved therapies or clinical trial enrollment. The incremental cost of NGS beyond single gene testing (EGFR, ALK) was CAD $233 per case. Reflex upfront NGS identified at least one actionable variant in more than 70% of patients with NSCLC, with minimal increase in testing cost. Implementation of NGS panels remains essential as treatment paradigms continue to evolve.

Human tissue is excised for either medical care or research. Demand for excised human tissue is increasing because of the realization of personalized medicine, which relies on excised human tissue to develop innovative tests for application in patient care. However, because excised human tissue is a

Aims Low-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT) are recently described emerging entities, which demonstrate distinct features but are not yet recognised as separate neoplasms in the fifth WHO classification. Published series to date have been largely multi-institutional and based on surgically resected tumours. This study aims to determine the frequency, clinicopathologic features and outcome of LOT and EVT in a single institutional series of oncocytic/eosinophilic renal neoplasms, including patients managed with active surveillance and non-surgical intervention. Methods and results Cases were identified from a consecutive institutional series of in-house renal tumours diagnosed on biopsy and/or nephrectomy (2003–2023). Tumours with a diagnosis or differential diagnosis of oncocytoma, chromophobe renal cell carcinoma or oncocytic neoplasm not otherwise specified (including LOT, EVT and tumours with overlapping hybrid features) were retrospectively reviewed and classified/reclassified. In total, 605 oncocytic/eosinophilic renal neoplasms were reviewed, among which 33 LOT (5.5%) and 5 EVT (0.8%) were identified. LOT were CK7+, CD117− and GATA3+ (94%). EVT were CD117+, CK7 focal+ (80%) and cathepsin K+ (80%). At the median follow-up of 34 months (range 2–253) and 56 months (range 8–90) for LOT and EVT, respectively, there was no evidence of recurrence following ablation/surgical resection, metastasis or death from disease for all patients, including the 22 managed with active surveillance (20 LOT and 2 EVT). Conclusions LOT and EVT comprised a minority of oncocytic renal neoplasms in this series. We report a large institutional series including patients managed non-surgically, with no adverse outcome, adding to the existing literature indicating a benign outcome.

Aims Renal tumour biopsy (RTB) is increasingly recognised as a useful diagnostic tool in the management of small renal masses, particularly those that are incidentally found. Intratumoural heterogeneity with respect to morphology, grade and molecular features represents a frequently identified limitation to the use of RTB. While previous studies have evaluated pathological correlation between RTB and nephrectomy, no studies to date have focused specifically on the role of RTB for the diagnosis of papillary renal cell carcinoma (PRCC) and its further subclassification into clinically relevant subtypes. Methods This single-institution study evaluated 60 cases of PRCC for concordance between RTB and nephrectomy with respect to diagnosis, grading and subtyping (type 1/type 2). Results We observed 93% concordance (55 of 59 evaluable cases) between RTB and nephrectomy for the diagnosis of PRCC, although seven tumours (12%) were undergraded on RTB. Subtyping of PRCC on RTB was concordant with nephrectomy in 89% of cases reported as type 1 PRCC on RTB (31/35), but only 40% of cases reported as type 2 PRCC on RTB (4/10). Morphological misclassification of PRCC on RTB was most likely to occur in tumours showing a solid growth pattern. Discordant PRCC subtyping most often occurred in tumours with eosinophilia/oncocytic change. Conclusion There was good concordance between RTB and nephrectomy for the primary diagnosis of PRCC. Although further subtyping of PRCC can aid therapeutic stratification, this can be challenging on RTB and tumours with overlapping or ambiguous features are best reported as PRCC not otherwise specified pending development of more robust methods to facilitate definitive subclassification.

Gastric cancer is common globally and has a generally poor prognosis with a low 5-year survival rate. Targeted therapies and immunotherapies have improved the treatment landscape, providing more options for efficacious treatment. The use of these therapies requires predictive biomarker testing to identify patients who can benefit from their use. New therapies on the horizon, such as CLDN18.2 monoclonal antibody therapy, require laboratories to implement new biomarker tests. A multidisciplinary pan-Canadian expert working group was convened to develop guidance for pathologists and oncologists on the implementation of CLDN18.2 IHC testing for gastric and gastroesophageal junction (G/GEJ) adenocarcinoma in Canada, as well as general recommendations to optimize predictive biomarker testing in G/GEJ adenocarcinoma. The expert working group recommendations highlight the importance of reflex testing for HER2, MMR and/or MSI, CLDN18, and PD-L1 in all patients at first diagnosis of G/GEJ adenocarcinoma. Testing for NTRK fusions may also be included in reflex testing or requested by the treating clinician when third-line therapy is being considered. The expert working group also made recommendations for pre-analytic, analytic, and post-analytic considerations for predictive biomarker testing in G/GEJ adenocarcinoma. Implementation of these recommendations will provide medical oncologists with accurate, timely biomarker results to use for treatment decision-making.