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Simple Summary: In this study, scientists investigated how pathologists test for a protein called HER2 in a type of cancer called endometrial cancer (EC). They checked samples from 180 patients tested over the first two years following approval of the test in the clinic. They found that 28% of the samples had HER2 overexpression, which makes them eligible for HER2-targeted therapies. They also noticed that in some cases, the test results were different depending on the method used. This study shows that there are challenges in testing for HER2 in endometrial cancer and suggests that we need standardized guidelines to help doctors make better decisions about endometrial cancer treatment. HER2-targeted therapies have transformed the management of advanced or recurrent serous endometrial cancer (EC), leading to an increased clinical demand for HER2 testing. Despite its adoption in select academic centers, the global extent of such tumor testing is unclear. In this study, we report on the initial two-year experience of HER2 testing at a major academic center with a reference gynecologic oncology service and biomarker reference laboratory. All patients who underwent HER2 testing based on physician discretion, reflex HER2 testing, and reference laboratory requests were included. From February 2021 to October 2023, HER2 testing was performed on 192 tumor tissue samples from 180 EC patients. Serous carcinoma constituted 52% of samples, reflecting diagnostic challenges and limited therapeutic options for advanced EC. HER2 positivity was found in 28% of all cases and 30% of p53-aberrant cases. An immunohistochemistry (IHC) score of 3+ was found in 15% of samples, while IHC 2+ was found in 45% (13% IHC 2+/ISH+ and 32% IHC 2+/ISH−). The newly identified 'HER2-low' category comprised 46% of the samples. Heterogeneity was noted in 42% of HER2-positive cases, with complex patterns in 3%. NGS and HER2 IHC-FISH showed a 24% discordance, attributed to intratumoral heterogeneity, tumor cellularity, a small number of amplified cells, and the HER2/CEP17 ratio near the cut-off. This study offers real-world insights into HER2 testing in EC, highlighting the challenges and underscoring the need for standardized guidelines in specimen handling, proficiency testing, and scoring criteria to enhance patient management and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Benign epithelial inclusions are rarely found in peripancreatic lymph nodes and have not been studied by up-to-date immunohistochemistry. Here, we describe 2 cases of benign epithelial inclusions in the peripancreatic lymph nodes with discussion of differential diagnosis. The first case was a 2.2 cm lymph node from a 61-year-old woman with pancreatic ductal adenocarcinoma. The second case was a 4.3 cm lymph node from a 28-year-old man with distal common bile duct cholangiocarcioma. The epithelial inclusions in the first case consisted of several small squamous cell nests with central duct-like lumina. The lymph node from the second case showed convoluted cystic inclusions lined by a single layer of bland cuboidal epithelium with scattered mucin-producing cells. We also conducted literature review on similar lesions and found that some lesions were associated with pancreatic hetertopia. It is imperative in clinical practice to distinguish these epithelial inclusions in the lymph nodes from tumor metastasis. A hypothetic connection of these benign epithelial inclusions in the peripancreatic lymph nodes to the enigmatic pancreatic lymphoepithelial cysts is suggested. [ABSTRACT FROM AUTHOR]

Summary: The relationship between higher total lymph node resection number in colorectal cancer resection specimens and improved overall survival is well known. Recent studies describe an association between a high rate of microsatellite instability and a high total lymph node count in colorectal cancer. Higher lymph node retrieval may potentially explain the improved survival seen in cancers with microsatellite instability. We investigate whether these associations can be validated in a cohort of American Joint Committee on Cancer stage III colon cancers. Medical records from 200 cases of stage III colon cancer resection specimens were reviewed, and sufficient tissue was available for 168. Expression of DNA mismatch repair proteins was determined by immunohistochemistry, and microsatellite status, by polymerase chain reaction. The mean total lymph node count in cases with microsatellite instability versus microsatellite stable tumors (15.9 versus 16.9; P = .664) and the mean number of negative lymph nodes in each respective category (12.2 versus 13.6; P = .522) were not significantly different. There was no difference between microsatellite stable cases and cases with microsatellite instability when total lymph node counts (P = .953) or negative lymph node counts (P = .381) were analyzed with respect to percentage of cases above and below the medians. This cohort of stage III colon cancers does not support a significant relationship between microsatellite status and a higher retrieval of total or negative lymph nodes. Although microsatellite instability is associated with improved overall survival in our cohort (P = .026), the reason for this does not appear to be related to higher numbers of retrieved lymph nodes. [ABSTRACT FROM AUTHOR]