Pathology最新文献

Ovarian sex cord-stromal tumours (SCSTs) present diagnostic difficulties during frozen section (FS) consultations due to their diverse morphology. This study aimed to evaluate the accuracy of FS evaluation of SCSTs in our institution, as well as to examine the reasons leading to incorrect FS diagnosis. Cases mimicking SCSTs and diagnosed as such during FS were also highlighted.

We analysed 121 ovarian SCST cases and their mimics which underwent FS consultations over a 10-year period, to evaluate FS accuracy, reasons for deferrals and discrepancies. FS diagnoses were concordant, deferred and discrepant compared to the final diagnosis in 50 (41.3%), 39 (32.2%) and 32 (26.5%) cases, respectively. Major discrepancies (9/121, 7.4%) were mostly related to the diagnosis of adult granulosa cell tumour (AGCT). A fibromatous AGCT was misinterpreted as fibroma on FS, while a cystic AGCT was called a benign cyst. Conversely, a mesonephric-like adenocarcinoma, a sertoliform endometrioid carcinoma and a thecoma were misinterpreted as AGCT on FS. Another discrepant case was a Krukenberg tumour with prominent fibromatous stroma in which malignant signet ring cells were overlooked and misinterpreted as fibroma. Minor discrepancies were primarily associated with fibroma (21/23, 91.3%), wherein minor but potentially impactful details such as cellular fibroma and mitotically active cellular fibroma were missed due to sampling issues and misinterpretation as leiomyoma. FS evaluation for ovarian SCSTs demonstrated an overall accuracy of 78.5%, 81.0% and 81.8% for benign, uncertain/low malignant potential and malignant categories, respectively. There was no FS-related adverse clinical impact in all cases with available follow-up information (120/121 cases).

Intraoperative FS evaluation of ovarian SCSTs is challenging. A small number of cases were misinterpreted, with AGCTs being the primary group where errors occur. Awareness of common diagnostic pitfalls and difficulties, alongside application of a stepwise approach, including (1) obtaining comprehensive clinical information, (2) thorough macroscopic examination and directed sampling, (3) meticulous microscopic examination with consideration of pitfalls and mimics, (4) effective communication with surgeons in difficult cases, and (5) consultation of subspecialty colleagues in challenging cases, will enhance pathologists' reporting accuracy and management of such cases in the future.

Histone H1 (H.H1) is involved in chromatin organisation and gene regulation and is overexpressed in many malignant tumours, including breast cancer (BC). This study proposed and evaluated the prognostic role of H.H1 expression in BC.

H.H1 mRNA expression was evaluated in publicly available BC dataset bc-GenExMiner database (n=4421). H.H1 protein expression was assessed immunohistochemically in a well-characterised early-stage BC cohort (n=1311), and associations with clinicopathological data and survival outcomes were evaluated.

At the mRNA level, there was a significant association between high H.H1 mRNA and basal-like BC subtype and with poor outcome. The association with shorter survival was observed in the whole cohort and in the basal-like class. H.H1 protein expression was detected in both tumour cells and surrounding stroma. Total expression was detected in 72% of the cases, including 28% in tumour cell nuclei and 44% in the stroma. There was strong association between high tumour H.H1 expression and triple-negative BC (TNBC) subtype (p=0.007) and with shorter survival (p=0.019), independent of other variables including tumour size, histologic tumour grade, and lymph node status.

H.H1 expression is associated with poor prognosis in BC. Given poor prognostic role of H.H1 in TNBC, it may represent a potential therapeutic target for patients with this aggressive disease.

Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed.

From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features.

Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant.

KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

Cytokeratin 15 (CK15) has been described as a stem cell marker in human organs and its expression is seen in breast tissue. CK15 expression is associated with aggressive features in endometrial and oesophageal cancers, but data on the breast are lacking. This study aims to investigate the clinicopathological associations and prognostic significance of CK15 in breast carcinomas.

A multi-institute cohort of breast carcinomas were retrieved. Clinicopathological and outcome data were obtained and compared with immunohistochemical expression CK15 and a panel of biomarkers.

In total, 1,476 cases were included, with an expression rate of 3.5%, preferentially expressed in luminal subtypes (p=0.024), with luminal B carcinomas being the highest (4.7%), as opposed to basal-like (1%) and HER2-overexpressed carcinomas (0%). Except for nodal stage (p=0.013) and nodal metastasis (p=0.048), oestrogen (p=0.035) and progesterone receptor (p=0.001) positivity, there were no associations with other clinicopathological parameters. A trend was observed with shorter breast cancer specific survival (BCSS) in CK15-positive luminal B carcinomas (p=0.062). On further subgroup multivariate analysis of luminal B HER2-negative carcinomas, CK15 expression exhibited robust correlation with shorter BCSS (HR=9.004, p=0.001) and disease-free survival (HR=7.085, p<0.001).

Restricted to luminal breast carcinomas, specifically luminal B HER2-negative, CK15 is demonstrated to be a robust independent predictor of higher risk of recurrence and shorter survival, with potential as a clinical prognostic marker and an exclusive stem cell marker for this subgroup of carcinomas.

Deaths from non-melanoma skin cancers (NMSCs) have almost doubled in Australia in recent years. Cutaneous squamous cell carcinoma (cSCC) constitutes approximately 20% of NMSCs, but is responsible for most of the deaths. Most skin cancers are easy to diagnose and treat and therefore cSCC are often trivialised; however, there is a high-risk subgroup of cSCC (HRcSCC) that is associated with a high risk of metastasis and death. The definition of early HRcSCC and our ability to identify them is evolving. Many significant prognostic factors have been identified, but a universally accepted prognostic index does not exist. Guidelines for workup, treatment, and follow-up leave many important decisions open to broad interpretation by the treating physician or multidisciplinary team. Some of the treatments used for metastatic cSCC are not supported by robust evidence and the prognosis of metastatic cSCC is guarded. In this review, we highlight the rapid rise in NMSC deaths and discuss some of the deficiencies in our knowledge of how to define, diagnose, stage, and manage HRcSCC.