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

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Adenocarcinoma ; Chromogranin A ; Classification ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Neural Cell Adhesion Molecules ; Prognosis ; Stomach ; Stomach Neoplasms ; Synaptophysin

PURPOSE: To determine the origin of epiretinal proliferation (EP), a condition that is occasionally observed in lamellar hole and macular hole cases, and EP outcomes after vitrectomy. METHODS: This is a retrospective observational case review of 17 eyes with EP that underwent vitrectomy, EP dissection, and internal limiting membrane peeling between January 2013 and December 2016. Surgical specimens of EP tissue were successfully obtained from 5 cases and they were analyzed after immunohistochemical staining. Postoperative outcomes, including best-corrected visual acuity (BCVA) and macular configuration in spectral domain-optical coherence tomography, were reviewed. RESULTS: Mean BCVA improved from 0.54 ± 0.36 logarithms of the minimum angle of resolution preoperatively to 0.32 ± 0.38 logarithms of the minimum angle of resolution postoperatively (p = 0.002). BCVA improved in 13 eyes and remained unchanged in four eyes. No cases experienced vision decline after surgery. All 17 patients' lamellar hole or macular hole were successfully closed. Despite hole closure, ellipsoid zone defects were not corrected in 11 of the 17 patients. In immunohistochemical analyses, anti-glial fibrillary acidic protein and pan-keratin (AE1/AE3) were positive, but synaptophysin, anti-α-smooth muscle actin, and anti-CD68 were negative. CONCLUSIONS: The epiretinal proliferative membrane seems to originate from Müller cells, not from the vitreous. It is unclear whether retinal pigment epithelia also contribute to EP formation. Gentle handling and preservation of the epiretinal proliferative tissue is crucial for successful surgical outcomes.
Actins ; Humans ; Membranes ; Prognosis ; Retinal Perforations ; Retinaldehyde ; Retrospective Studies ; Synaptophysin ; Visual Acuity ; Vitrectomy

PURPOSE: Primary hepatic neuroendocrine tumor (PHNET) is a very rare neoplasm, requiring strict exclusion of metastasis from possible extrahepatic primary sites for its diagnosis. METHODS: We reviewed our clinical experience of 13 patients with primary hepatic NET who underwent liver resection from January 1997 to December 2015. RESULTS: The mean age of the 13 patients (8 males and 5 females) was 51.1 ± 12.8 years; the most common clinical manifestation was vague, nonspecific abdominal pain (n = 9). Of them, 11 patients underwent preoperative liver biopsy, 7 of which correctly diagnosed as neuroendocrine tumor (NET). Ten patients underwent R0 resection, and 3 underwent R1 resection. Diagnosis of PHNET was confirmed both immunohistochemically and by absence of extrahepatic primary sites. All tumors were single lesions, with a mean size of 9.6 ± 7.6 cm and a median size of 4.3 cm; all showed positive staining for synaptophysin and chromogranin. During a mean follow-up period of 95.1 ± 86.6 months, 7 patients died from tumor recurrence, whereas the other 6 remain alive to date, making the 5-year tumor recurrence rate 56.0% and the 5-year patient survival rate 61.5%. When confined to R0 resection, 5-year recurrence and survival rates were 42.9% and 70.0%, respectively. Univariate analysis showed that Ki-67 proliferative index was the only risk factor for tumor recurrence. CONCLUSION: PHNET is a very rare tumor with no specific clinical features, and its final diagnosis depends primarily on pathology, immunohistochemistry, and exclusion of metastasis from other sites. Aggressive surgical treatment is highly recommended for PHNET because of acceptably favorable postresection outcomes.
Abdominal Pain ; Biopsy ; Carcinoid Tumor ; Diagnosis ; Follow-Up Studies ; Hepatectomy ; Humans ; Immunohistochemistry ; Liver ; Male ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pathology ; Prognosis ; Recurrence ; Risk Factors ; Survival Rate ; Synaptophysin

As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.
Aged ; Alzheimer Disease ; Animals ; Cognition ; Colloids ; Curcumin ; Glutathione ; Humans ; Malondialdehyde ; Mice ; Microglia ; Neurons ; Oxidative Stress ; Post-Synaptic Density ; Spatial Memory ; Superoxide Dismutase ; Synaptophysin

The liver is one of the most common sites to which malignancies preferentially metastasize. Although a substantial number of liver malignancies are primary tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the metastasis of carcinomas to the liver is relatively common and frequently encountered in clinical settings. Representative carcinomas that frequently metastasize to the liver include colorectal carcinoma, breast carcinoma, neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic confirmation of suspected metastatic lesions in the liver is generally achieved through a histopathologic examination of biopsy tissues. Although morphology is the most important feature for a pathologic differential diagnosis of metastatic carcinomas, immunohistochemical studies facilitate the differentiation of metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin, etc.). Here, we provide a brief review about the pathologic differential diagnosis of major metastatic carcinomas in the liver.
Biopsy ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Colorectal Neoplasms ; Diagnosis, Differential ; Immunohistochemistry ; Keratins ; Liver Neoplasms ; Liver ; Lung ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pathology ; Synaptophysin

Colorectal large-cell neuroendocrine carcinomas (NECs) are extremely rare and have very poor prognosis compared to adenocarcinomas. A 74-year-old man presented with abdominal pain, diarrhea and hematochezia. The histopathologic report of colonoscopic biopsy performed at a local clinic was a poorly differentiated carcinoma. An abdominopelvic computed scan revealed irregularly enhanced wall thickening at the sigmoid colon with regional fat stranding and lymphnode enlargement. He underwent a laparoscopic high anterior resection with selective peritonectomy for peritoneal carcinomatosis, intraoperative peritoneal irrigation chemotherapy, and early postoperative intraperitoneal chemotherapy for 5 days. The tumor had a high proliferation rate (mitotic count > 50/10 HPFs and 90% of the Ki-67 index) and lymph-node metastases had occurred. On immunohistochemistry, the tumor cells expressed CD56 and synaptophysin. Large-cell NEC was confirmed. Systemic chemotherapy with cisplatin/etoposide was done. The patient is still alive after 3 years with no evidence of recurrence.
Abdominal Pain ; Adenocarcinoma ; Aged ; Biopsy ; Carcinoma* ; Carcinoma, Neuroendocrine* ; Colon* ; Colon, Sigmoid ; Diarrhea ; Drug Therapy ; Gastrointestinal Hemorrhage ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Peritoneal Lavage ; Prognosis ; Recurrence ; Synaptophysin

We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.
Actins ; Adrenal Rest Tumor ; Adrenocortical Carcinoma ; Back Pain ; Carbonic Anhydrases ; Carcinoma, Renal Cell ; Chromogranin A ; Desmin ; Humans ; Integrases ; Keratin-7 ; Lymphoma ; MART-1 Antigen ; Melanoma ; Middle Aged ; Mitosis ; Mucin-1 ; Muscle, Smooth ; Neoplasm Metastasis ; Nephrectomy ; Phosphotransferases ; Prognosis ; Recurrence ; Synaptophysin ; Transcription Factors ; Vimentin

We report a case of acute pancreatitis secondary to pancreatic neuroendocrine tumor. A 46-year old man presented with upper abdominal pain. The serum amylase and lipase were elevated. Abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a 1.7 cm sized mass at the pancreas body with a dilatation of the upstream pancreatic duct and mild infiltrations of peripancreatic fat. An endoscopic ultrasound-guided fine needle biopsy was performed for the pancreatic mass, but only necrotic tissue was observed on the pathologic examination. A chest and neck CT scan revealed anterior mediastinal, paratracheal, and cervical lymph node enlargement, which were indicative of metastasis. An ultrasound-guided core needle biopsy was performed for the enlarged neck lymph node, and pathologic examination revealed a metastatic poorly differentiated carcinoma. Immunohistochemical analysis showed positive staining for synaptophysin, chromogranin A, and CD 56, indicative of a neuroendocrine carcinoma.
Abdominal Pain ; Amylases ; Biopsy, Fine-Needle ; Biopsy, Large-Core Needle ; Carcinoma, Neuroendocrine ; Cholangiopancreatography, Magnetic Resonance ; Chromogranin A ; Dilatation ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Lipase ; Lymph Nodes ; Neck ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pancreas ; Pancreatic Ducts ; Pancreatitis ; Synaptophysin ; Thorax ; Tomography, X-Ray Computed

Primary neuroendocrine tumors originating from the extrahepatic bile duct are rare. Among these tumors, large cell neuroendocrine carcinomas (NECs) are extremely rare. A 59-year-old man was admitted to Sanggye Paik Hospital with jaundice that started 10 days previously. He had a history of laparoscopic cholecystectomy, which he had undergone 12 years previously due to chronic calculous cholecystitis. Laboratory data showed abnormally elevated levels of total bilirubin 15.3 mg/dL (normal 0.2–1.2 mg/dL), AST 200 IU (normal 0–40 IU), ALT 390 IU (normal 0–40 IU), and gamma-glutamyl transferase 1,288 U/L (normal 0–60 U/L). Serum CEA was normal, but CA 19-9 was elevated 5,863 U/mL (normal 0–37 U/mL). Abdominal CT revealed a 4.5 cm sized mass involving the common bile duct and liver hilum and dilatation of both intrahepatic ducts. Percutaneous transhepatic drainage in the left hepatic duct was performed for preoperative biliary drainage. The patient underwent radical common bile duct and Roux-en-Y hepaticojejunostomy for histopathological diagnosis and surgical excision. On histopathological examination, the tumor exhibited large cell NEC (mitotic index >20/10 high-power field, Ki-67 index >20%, CD56 [+], synaptophysin [+], chromogranin [+]). Adjuvant concurrent chemotherapy and radiotherapy were started because the tumor had invaded the proximal resection margin. No recurrence was detected at 10 months by follow-up CT.
Bile Duct Neoplasms ; Bile Ducts, Extrahepatic* ; Bilirubin ; Carcinoma, Neuroendocrine* ; Cholecystectomy, Laparoscopic ; Cholecystitis ; Common Bile Duct ; Diagnosis ; Dilatation ; Drainage ; Drug Therapy ; Follow-Up Studies ; Hepatic Duct, Common ; Humans ; Jaundice ; Liver ; Middle Aged ; Neuroendocrine Tumors ; Radiotherapy ; Recurrence ; Synaptophysin ; Tomography, X-Ray Computed ; Transferases