Characterisation of Kürsteiner canals of parathyroid: imparting relevance to a one-and-a-quarter-century-old concept.

AIMS: Kürsteiner canals (KC) were described at least 125 years ago as pharyngeal pouch embryological remnants of parathyroid and thymic development. While considered precursors for a subset of parathyroid cysts and salivary heterotopias (SH), they remain enigmatic. We now define a comprehensive phenotype of KC remnants and investigate their role in a spectrum of parathyroid lesions. METHODS AND RESULTS: `Sixty-two cystic and 22 non-cystic parathyroid lesions (73 patients) were retrieved from our institutional archive (2011-23) and evaluated for the presence of KC and prevalence of KC phenotype in parathyroid hormone (PTH)-positive and PTH-negative cysts. KC phenotype was defined as: cysts and tubules with surrounding sclerosis; bland, unilayered lining with frequent nuclear indentation of lumina; vesicular chromatin relative to chief cells; attenuated eosinophilic to 'hyper-cleared' cytoplasm; and staining pattern PTH-negative, SOX-10-positive, CK7-positive, GATA-3-positive and PAX-9 dim, a subset with oestrogen/progesterone receptor (ER/PR) positivity. Thirty PTH-negative cysts were identified in the neck/mediastinum; 14 of this group also showed SH. Thirty-two PTH-positive cysts included: 11 cystic parathyroid adenomas, 17 hyperplastic parathyroids, and four carcinomas. KC showed two distinct subtypes and were often found near PTH-negative cysts. PTH-negative cysts were associated with inferior parathyroids, SOX-10 positivity, fibrosclerosis, vesicular nuclei indenting cyst lumina and hyper-cleared or attenuated eosinophilic cytoplasm. CONCLUSIONS: KC are common in parathyroids and show a distinct histological and immunohistochemical profile, with an inferior predilection favouring branchial cleft III distribution. Diagnostically, the high prevalence of this phenotype in PTH-negative cysts and salivary heterotopia supports derivation of non-functioning cysts from KC. Conversely, PTH-positive cysts are more compatible with cystic change within hyperfunctioning glands.

Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer.

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.

Upgrade rates of intraductal papilloma with and without atypia diagnosed on core needle biopsy and clinicopathologic predictors.

Surgical excision of breast intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) is controversial as the risk of upgrade to malignant lesions is not well established. This study investigates upgrade rates of benign and atypical IDP to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) and clinicopathologic predictors. We identified 556 cases of IDP diagnosed on CNB at a single institution from 2010 to 2020 after excluding patients with a history of breast carcinoma, ipsilateral high-risk lesion, radiologic/pathologic discordance, or less than 2 years of follow-up if no excision within 1 year. Of these, 97 biopsies were consistent with atypical IDP and 459 were benign IDP. Surgical excision was performed for 318 (57.2%), and the remaining 238 (42.8%) underwent active monitoring. The upgrade rate for IDP without atypia was 2/225 (0.9%; 1 DCIS and 1 IC). Of 93 surgically excised atypical IDPs, 19 (20.4%) upgraded (14 DCIS and 5 IC). Of 238 nonexcised IDPs followed clinically (range, 24-140 months, mean 60 months), there was no subsequent breast cancer diagnosed at the IDP site on follow-up. Mean age of patients was 56 yr ± 12.6 SD without upgrade, 63 yr ± 10.6 SD (P = .027) with DCIS, and 61 yr ± 10.8 SD (P = .35) with IC. Atypical IDP was more likely to upgrade if biopsied by stereotactic guidance (8/19, 42.1% P = .035). At our institution, we had an exceedingly low upgrade rate for benign IDP. Overall, patients with upgrade to DCIS were older. For atypical IDP, upgrade was seen in higher proportions of stereotactic biopsies.

False-Negative 18F-Fluorodeoxyglucose PET/CT in Malignant Pleural Mesothelioma.

We report a diagnostically challenging case of a 77-year-old man who presented with shortness of breath and was found to have a large right hydropneumothorax with collapse of the right lung. A malignancy was suspected, but pleural fluid cytology and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging were negative. He then underwent video-assisted thoracoscopy with biopsies of the pleura and chest wall which revealed malignant pleural mesothelioma (MPM). Older patients with early stage MPM are more likely to have false-negative FDG PET/CT results. Pleural biopsy is essential when there is clinical suspicion for mesothelioma, even with negative initial FDG PET imaging.