Appendiceal goblet cell carcinoma: comparison of classification and staging systems with evaluation of the prognostic role of immunohistochemistry stains

Background: Goblet cell carcinoma (GCC) of the appendix is a unique lesion that exhibits features of both adenocarcinoma and neuroendocrine tumors. Due to the rarity of this cancer, multiple grading (e.g., Tang, Yozu, and Lee) and staging systems (e.g., tumor, lymph nodes, and metastasis [TNM]) have been developed for classification. This study aimed to compare commonly used classification systems and evaluate the prognostic effectiveness immunohistochemical staining may or may not have for appendiceal GCC. Methods: An electronic medical records review of patients who were diagnosed with GCC of the appendix in our hospital system from 2010 to 2020. The data were collected regarding the age at diagnosis, gender, initial diagnosis at presentation, operation(s) performed, final pathology results, current survival status, and year of recurrent disease or death year. Results: Ten patients were evaluated. Seventy percent of the patients were above the age of 50 years at diagnosis. Postdischarge survival ranged from 1 month to 109 months postdiagnosis. Two patients expired from GCC at 13- and 54-months following diagnosis. When comparing the classification systems, Lee categorized more patients as high risk than Tang and Yozu. Immunohistochemical staining was analyzed using four staining methods: Ki67, E-cadherin, Beta-catenin, and p53. Tumor, lymph nodes, and metastasis staging has supportive evidence for worsening prognosis and overall survival secondary to the depth of invasion of the tumor. Conclusion: Tumor, lymph nodes, and metastasis staging may be superior to the other classification systems in predicting overall mortality. Our study demonstrated that immunohistochemistry staining does not appear to have a significant impact in determining the prognosis for GCC of the appendix. (AU)

S100 Staining Adds to the Prognostic Significance of the Combination of Perineural Invasion and Lymphovascular Invasion in Colorectal Cancer.

Studies have suggested that perineural invasion (PNI) and lymphovascular invasion (LVI) serve as independent prognostic factors in colorectal cancer (CRC). Currently, little is known regarding the combination of PNI and LVI as prognostic factors, independent of stage. We hypothesized that this combination was a better prognostic marker than either PNI or LVI alone, and that S100 staining would detect PNI not seen with hematoxylin and eosin (H&E). Surgical pathology slides were retrospectively reviewed for 151 stages I to IV CRC patients who had surgery between January 1, 2008 and December 8, 2008 at 3 Hackensack Meridian Health hospitals in New Jersey. PNI and LVI were detected by H&E staining and a subset of 127 patient samples were additionally examined for PNI by S100 staining. Correlation between staining characteristics and patient outcomes was assessed using the Pearson χ tests and the Fisher exact tests. Survival was analyzed using Kaplan-Meier methods. Of the 151 cases reviewed, 30.5% were positive for PNI and 35.1% were positive for LVI by H&E. The use of S100 staining for PNI enabled its detection in 27 additional cases. Median time from patient diagnosis to death was significantly shorter for patients who were positive for both PNI and LVI (P<0.001). PNI and LVI were individual markers for poor survival in CRC patients and their combined presence had an even worse outcome. Failure to detect PNI on H&E can be overcome by S100 staining.

The Effect of the New Eighth Edition Breast Cancer Staging System on 100 Consecutive Patients.

BACKGROUND: In October 2016 the American Joint Committee on Cancer published the early eighth edition breast cancer prognostic staging system, incorporating biomarkers into previously accepted staging. The updated and current eighth edition became effective nationwide in January 2018 after a large update to its staging guidelines. This study's aim was to compare patients' anatomic seventh edition (anatomic), early eighth (pre-update, prognostic), and current eighth (post-update, prognostic) pathological stages and to assess the utility of recent inclusions to staging criteria. Additionally, we observed how the aforementioned stage changes aligned with breast cancer histologic subtypes. METHODS: An Institutional Review Board (IRB)-approved retrospective chart review was performed. Inclusion criteria included female patients between the ages of 35 to 95 years with a diagnosis of invasive ductal or lobular carcinoma of the breast (n = 100) at three Hackensack Meridian Health hospitals. The study evaluated any trends in patients' stage changes between the seventh edition, early eighth edition, and current eighth edition breast cancer staging guidelines. Breast cancer restaging was performed using a novel staging tool on Microsoft Excel. RESULTS: Only 26% of patients' stages changed when comparing the seventh edition stage vs. current eighth edition prognostic staging, most of which were downstaged. When comparing the seventh with early eighth edition prognostic staging, 38% of the patients' stages changed, with a majority of them being upstaged. Lastly, 95% of total stage changes were downstages between the early eighth and current eighth edition staging guidelines. CONCLUSIONS: When comparing the seventh edition vs. current eighth edition staging, few patients (especially those with early stage cancer) underwent a stage change. However, there were significant changes in stage when comparing early eighth vs. current eighth stages. Considering these changes were mostly downstages and many patients reverted to their original seventh edition stage, the current eighth edition is based on a personalized, less radical staging approach, one that is more synonymous with original seventh edition staging.

Mutational analysis of metastatic lymph nodes from papillary thyroid carcinoma in adult and pediatric patients.

BACKGROUND: Limited data are available on the analysis of somatic mutations in metastatic lymph nodes in adult and pediatric patients with papillary thyroid carcinomas. METHODS: A total of 92, microdissected, formalin-fixed, paraffin-embedded tissue specimens from 39 patients were analyzed for the presence of somatic mutations utilizing the ThyGenX next-generation sequencing test. RESULTS: Somatic mutations were detected in 67% of papillary thyroid carcinoma specimens. The majority of patients with synchronous and all 6 patients with radioactive iodine-resistant (metachronous) metastatic lymph nodes contained BRAF mutations. Four patients had mutations detected in their metastatic lymph nodes that were not detected in their primary tumors. For the most part, BRAF mutations were seen in adults, and RAS mutations were seen in children. CONCLUSION: Findings of different mutations in metastatic lymph nodes compared with the primary papillary thyroid carcinomas are probably the result of tumor heterogeneity. The presence of the BRAF mutation in metastatic lymph nodes might be responsible for the recurrence of papillary thyroid carcinomas and resistance to radioactive iodine therapy. The good prognosis observed in papillary thyroid carcinomas found in pediatric and young adult patients might be explained by the predominance of RAS rather than BRAF mutations.

Confirmation of a potential biomarker for early-stage pancreatic cancer.

INTRODUCTION: Pancreatic cancer has a dismal prognosis because it is often diagnosed at an advanced stage. Therefore, serological biomarkers are eagerly sought for early detection. The digestive enzyme pro-carboxypeptidase A (PCPA) may be able to fill this role. The purpose of this study was to validate and extend previous research done at New York University (NYU), demonstrating that measurement of serum PCPA is a sensitive biomarker for early stage pancreatic cancer. MATERIALS AND METHODS: Samples were collected from 10 early and 16 late stage patients at Jersey Shore University Medical Center (JSUMC) and Robert Wood Johnson Hospital (RWJ) with adenocarcinoma of the head of the pancreas. RESULTS: The percentages of early and late stage cancer patients with PCPA values above the upper limit (2.35 u/L) were 90.0% and 56.0%, respectively. Mean PCPA values for early and late stage cancer were determined to be 22.95 u/L and 3.55 u/L, respectively. In one case, the prospective patient was detected by our assay one month before diagnosis. Additionally, data from an ampullary cancer patient supports the proposed mechanism behind this test. CONCLUSIONS: Combining the JSUMC and NYU results show 94% sensitivity, demonstrating that determining serum PCPA has the requisite sensitivity to detect early stage pancreatic cancer.

CD117, Ki-67, and p53 predict survival in neuroendocrine carcinomas, but not within the subgroup of small cell lung carcinoma.

High-grade neuroendocrine carcinomas (NECs) are aggressive tumors with limited treatment options. Recently, studies have observed that the tyrosine kinase receptor CD117 is often overexpressed in this malignancy. As a result, CD117 has been identified as a target for therapy via the small molecule, tyrosine kinase inhibitor imatinib mesylate. In the present study, 17 low-grade, 4 intermediate-grade, and 76 high-grade NECs were immunostained for CD117, Ki-67, and p53. Overexpression of the three markers was mainly, but not exclusively seen in the high-grade NECs. Patients with overexpression of CD117 and p53 and increased Ki-67 expression showed reduced survival. However, no difference in survival was observed when the same analysis was applied solely to small cell lung cancer patients, the largest subset studied. These findings suggest that overexpression of CD117, p53, and Ki-67 reflects tumor grade and predicts survival in NECs, but fail as prognostic markers in the subset of small cell lung cancer patients.