Objective: To investigate the clinical features, morphological characteristics, immunophenotype, and differential diagnosis of goblet cell adenocarcinoma (GCA) in the digestive system. Methods: The clinicopathological data, morphological characteristics, immunophenotypes of 22 cases of GCA in the digestive system diagnosed from January 2010 to January 2021 were collected. Meanwhile, 25 cases of neuroendocrine neoplasm (NEN) and 24 cases of adenocarcinoma were used as controls. Relevant literature was also reviewed. Results: There were 16 males and 6 females, aged from 36 to 79 years with an average of 56 years. The anatomical sites of the 22 GCA were mostly appendix (17 cases) and occasionally extra-appendix (5 cases), including 3 cases in stomach, 1 case in duodenum and 1 case in anal. All 17 cases of appendiceal GCA were pure GCA. Among the 5 cases of extra-appendiceal GCA, One case of gastric GCA was pure, two cases of gastric GCA with NEN or adenocarcinoma, duodenal GCA with NEN and adenocarcinoma, anal GCA with NEN.Low-grade GCAs were composed of goblet, Paneth and neuroendocrine cells, which were arranged in intestinal crypt tubular or cluster structures and distributed in the wall of digestive system. The tubular and cluster structures lacked adhesion. Goblet cells were columnar, located in the base, with clear cytoplasm, small nuclei, inconspicuous atypia, and uncommon mitoses. Extracellular mucus and signet-ring cells with nuclear variations could be seen in some cases. Nerve fiber bundle invasion and tumor thrombus in vessels were often present. High-grade GCAs lacked tubular and cluster structures, and their histological structures were more complex. Tumor cells expressed mixed neuroendocrine and glandular epithelial markers. Similar to the expression patterns of synaptophysin and chromogranin A, CD200 and INSM1 were also dot-like or patch-positive in GCA. Conclusions: GCA is an infrequent tumor of the digestive system and shows the bi-directional differentiation characteristics of neuroendocrine and glandular epithelium. Accurate diagnosis and staging are related to its prognosis.
Adenocarcinoma/pathology* ; Appendiceal Neoplasms/surgery* ; Carcinoid Tumor/surgery* ; Chromogranin A ; Female ; Goblet Cells/pathology* ; Humans ; Male ; Neuroendocrine Tumors/pathology* ; Repressor Proteins ; Synaptophysin

Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.
Cell Differentiation/genetics* ; Disease Progression ; Humans ; Male ; Neoplasm Metastasis ; Neovascularization, Pathologic/pathology* ; Neuroendocrine Cells/pathology* ; Prostatic Neoplasms/pathology* ; Receptors, Adrenergic, beta ; Signal Transduction

Prostate cancer (PCa) is a major health risk for older men worldwide. Existing systemic therapies mostly target androgen receptor (AR). Although treatments are initially effective, the disease always recurs. A potential mechanism for the treatment failure is that PCa contains, in addition to the AR-positive luminal type tumor cells, a small component of neuroendocrine (NE) cells. The function of NE cells in PCa remains poorly understood, and one important characteristic of these cells is their lack of expression of AR and resistance to hormonal therapy. In addition, many patients develop the more aggressive small-cell neuroendocrine carcinoma (SCNC) after hormonal therapy. Although this clinical phenomenon of disease transformation from adenocarcinoma to SCNC is well established, the cell of origin for SCNC remains unclear. Recently, loss of function of Rb and TP53 and amplification and overexpression of MYCN and Aurora A kinase have been identified as important biomarkers and potential disease drivers. In this article, we systematically review the histology of normal prostate and prostate cancer including the main histologic types: adenocarcinoma and SCNC. We also review the findings from many studies using cellular and animal models as well as human specimens that attempt to understand the molecular mechanisms of treatment failure, disease progression, and tumor transformation from adenocarcinoma to SCNC.
Adenocarcinoma/pathology* ; Carcinoma, Small Cell/pathology* ; Humans ; Male ; Neuroendocrine Cells/pathology* ; Prostatic Neoplasms/pathology*

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin initially believed to arise from the Merkel cells. In the community setting a general radiation oncologist may only encounter this pathology in a handful of cases over the course of their career. Due to the low incidence of this malignancy, few prospective randomized controlled trials have ever been conducted and therefore guidelines are based on relatively lower levels of evidence upon which the clinical recommendations are made. We discuss the case of a female in her 90s presenting with a classic MCC primary lesion, as well as satellite lesions proximal to both the primary and the draining regional lymph nodes with no evidence of nodal involvement. Here we discuss the presentation, management, treatment planning, underlying pathology, results and sequelae of treatment. We also review new treatment modalities, and the most current staging systems and guidelines.
Carcinoma, Merkel Cell ; Female ; Hand ; Humans ; Incidence ; Lymph Nodes ; Merkel Cells ; Neuroendocrine Tumors ; Pathology ; Prospective Studies ; Skin

BACKGROUND/AIMS: Neuroendocrine tumors (NETs) may originate from heterogeneous neuroendocrine cells. The incidence is increasing worldwide, and World Health Organization (WHO) updated its classification in 2010. We investigated clinical characteristics of gastroenteropancreatic NETs in a single center. METHODS: Clinicopathologic characteristics of patients with pathologically confirmed gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August 2011 were retrospectively analyzed. The grade and stage were determined according to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th ed., 2010) of American Joint Committee on Cancer. RESULTS: One hundred and twenty-five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a functional NET. The rectum (n = 99, 79.8%) was most common primary site and found in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8% stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7% grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic grade (Spearman’s rank correlation coefficient, 0.644). CONCLUSIONS: Wide range of clinicopathological features of Korean gastroenteropancreatic NETs were demonstrated using WHO 2010 classification. Rectal NET was most frequent and found in early stage.
Classification ; Epidemiology ; Humans ; Incidence* ; Joints ; Korea* ; Male ; Neoplasm Staging ; Neuroendocrine Cells ; Neuroendocrine Tumors* ; Pathology ; Prevalence ; Rectum ; Retrospective Studies ; Seoul ; World Health Organization

BACKGROUND/AIMS: Neuroendocrine tumors (NETs) may originate from heterogeneous neuroendocrine cells. The incidence is increasing worldwide, and World Health Organization (WHO) updated its classification in 2010. We investigated clinical characteristics of gastroenteropancreatic NETs in a single center. METHODS: Clinicopathologic characteristics of patients with pathologically confirmed gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August 2011 were retrospectively analyzed. The grade and stage were determined according to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th ed., 2010) of American Joint Committee on Cancer. RESULTS: One hundred and twenty-five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a functional NET. The rectum (n = 99, 79.8%) was most common primary site and found in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8% stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7% grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic grade (Spearman’s rank correlation coefficient, 0.644). CONCLUSIONS: Wide range of clinicopathological features of Korean gastroenteropancreatic NETs were demonstrated using WHO 2010 classification. Rectal NET was most frequent and found in early stage.
Classification ; Epidemiology ; Humans ; Incidence* ; Joints ; Korea* ; Male ; Neoplasm Staging ; Neuroendocrine Cells ; Neuroendocrine Tumors* ; Pathology ; Prevalence ; Rectum ; Retrospective Studies ; Seoul ; World Health Organization

Autoimmune Diseases ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Female ; Gastrectomy ; Gastric Mucosa ; pathology ; Gastrin-Secreting Cells ; metabolism ; pathology ; Gastrins ; metabolism ; Gastritis, Atrophic ; metabolism ; pathology ; surgery ; Humans ; Hyperplasia ; Middle Aged ; Mucin-6 ; metabolism ; Neuroendocrine Tumors ; metabolism ; pathology ; surgery ; Stomach ; pathology ; surgery ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; Synaptophysin ; metabolism

Acetates ; therapeutic use ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hyperplasia ; Infant ; Lung ; diagnostic imaging ; pathology ; physiopathology ; Lung Diseases, Interstitial ; diagnosis ; drug therapy ; physiopathology ; Methylprednisolone ; therapeutic use ; Neuroendocrine Cells ; pathology ; Quinolines ; therapeutic use ; Tomography, X-Ray Computed

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.
Adult ; Chromogranin A/blood ; Female ; Glucagon/*metabolism ; Glucagon-Secreting Cells/metabolism ; Humans ; Hyperplasia/complications/*diagnosis ; Islets of Langerhans/metabolism/ultrasonography ; Nesidioblastosis/complications/*diagnosis ; Neuroendocrine Tumors/complications/*diagnosis/pathology ; Pancreas/*pathology ; Tomography, X-Ray Computed

OBJECTIVETo study the possible clonal origin of neuroendocrine cells in colorectal adenocarcinoma.

METHODSTwenty-six microsatellite loci were screened using laser capture microdissection, DNA extraction and whole genome amplification. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in adenocarcinoma cells and neuroendocrine cells amongst 30 cases of colorectal carcinoma with neuroendocrine differentiation were detected using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-silver staining. The mutation status of p53 was evaluated by PCR-sequencing. The clonal origin of neuroendocrine cells in colorectal adenocarcinoma was determined.

RESULTSAmongst the 30 cases studied, the prevalence of MSI was 16.9% while that of LOH was 8.5%. The rate showed no statistically significant difference between adenocarcinoma cells and neuroendocrine cells. In 6 cases, the microsatellite alteration was entirely consistent. In 23 cases, the rate of microsatellite alteration consistency was greater than that of inconsistency. In 1 case, the consistency and inconsistency rates were identical. There was statistically significant difference between consistency and inconsistency of microsatellite alteration. The prevalence of p53 mutation was 16.7% which was the same for both adenocarcinoma cells and neuroendocrine cells.

CONCLUSIONSAdenocarcinoma cells and neuroendocrine cells in colorectal adenocarcinoma with neuroendocrine differentiation have similar biologic changes. It is likely that they are of identical origin.

Adenocarcinoma ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; DNA Mutational Analysis ; Humans ; Laser Capture Microdissection ; Loss of Heterozygosity ; Microsatellite Instability ; Neuroendocrine Cells ; pathology ; Tumor Suppressor Protein p53 ; genetics