OBJECTIVETo investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.

METHODSClinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.

RESULTSThe expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.

CONCLUSIONNeuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.

Adenocarcinoma ; diagnosis ; pathology ; Biomarkers, Tumor ; metabolism ; Chromogranin A ; metabolism ; Disease Progression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Secretagogins ; metabolism ; Stomach Neoplasms ; diagnosis ; pathology ; Synaptophysin ; metabolism

OBJECTIVETo study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC).

METHODSImmunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC. The diagnostic value of these markers was evaluated.

RESULTSThe expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied. Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity (P < 0.01). On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8% (170/275), 85.5% (242/283) and 89.2% (248/278), respectively. The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 (P < 0.01). TTF1 was expressed in 77.2% (217/281).

CONCLUSIONSp63 and p40 are expressed in a subset of SCLC. In contrast, CK5/6 is rarely positive in SCLC. An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.

CD56 Antigen ; genetics ; metabolism ; Chromogranin A ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Diagnosis, Differential ; Humans ; Keratin-5 ; genetics ; metabolism ; Keratin-6 ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; Small Cell Lung Carcinoma ; genetics ; metabolism ; Synaptophysin ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo analyze the clinicopathological features of pancreatic neuroendocrine neoplasms (P-NENs).

METHODSFrom January 2006 to December 2010, 64 patients with P-NENs were diagnosed in the Department of Pathology, West China Hospital, Sichuan University. Immunohistochemical staining of neuroendocrine markers, synaptophysin (Syn) and chromogranin A (CgA), were first made to determine whether the tumor had neuroendocrine properties, then the P-NENs were classified as neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC, G3) according to the morphological changes and proliferative activity (Ki 67 expression).

RESULTSOf all the 64 cases detected, 60 were NETs and four were NEC. Most of the tumors were single solitary masses, and more than half of the tumors arose in the head of the pancreas, while about one third in the tail. The positive rates of CgA and Syn immunostaining were 96.9% and 95.3%, respectively. The tumor stages of the 64 patients were as follows: stage I, 44 cases; stage II, 11 cases; stage III, one case; and stage IV, 8 cases. The median age of patients in the study was 45.56 years. Of all the P-NENs, 38 cases were functional ones, presenting with characteristic clinical syndrome owing to hormone hypersecretion, while 26 cases were nonfunctional ones with no distinct clinical syndrome. 58 patients underwent surgical operation. The 5-year progression-free survival rate was 91.4%.

CONCLUSIONSP-NENs may occur anywhere in the pancreas, and the clinical manifestations may not be easy to distinguish from other diseases. Diagnosis depends on pathological examination. Surgery is the major approach option, and the clinical prognosis is rather good. The tumor histological grade and distant metastasis are independent prognostic factors in P-NENs.

Adult ; Aged ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; secondary ; surgery ; therapy ; Chemoembolization, Therapeutic ; Chromogranin A ; metabolism ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neuroendocrine Tumors ; metabolism ; pathology ; secondary ; surgery ; therapy ; Pancreatic Neoplasms ; metabolism ; pathology ; surgery ; therapy ; Retrospective Studies ; Survival Rate ; Synaptophysin ; metabolism ; Young Adult

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

Gangliocytic paraganglioma (GP) is a rare, benign tumor which is usually found in the duodenum. We here report four recent cases of GP, with successful endoscopic resection in three cases, including a lesion on the ampulla of Vater. In all cases, each lesion had a stalk that facilitated removal using an endoscopic approach. Endoscopic mucosal resection is a feasible and safe treatment if the location, depth, and lymph node status are all favorable and is also helpful for definite diagnosis of unknown duodenal mass. To avoid morbidity resulting from open surgical resection, careful inspection for the peduncle of the GP will help determine the feasibility of endoscopic resection.
Aged ; Ampulla of Vater/pathology ; Chromogranin A/metabolism ; Colonoscopy ; Duodenal Neoplasms/pathology/*surgery ; Endoscopy, Gastrointestinal ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa/pathology/surgery ; Male ; Middle Aged ; Neuroendocrine Tumors/pathology/surgery ; Paraganglioma/pathology/*surgery ; S100 Proteins/metabolism ; Synaptophysin/metabolism ; 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 clinicopathologic characteristics of parathyroid carcinoma (PTC).

METHODSEleven cases of PTC encountered during the period from 1994 to 2012 were enrolled into the study. Forty cases of parathyroid adenoma (PA) were also retrieved for comparison. The clinical manifestations, laboratory results and pathologic features were analyzed, with literature review.

RESULTSThe main clinical manifestations of PTC included neck mass (11/11), hypercalcemia (11/11) and hyperparathyroidism (11/11). Most patients also had osteoporosis (10/11). In contrast, PA often manifested as hypercalcemia (40/40) and hyperparathyroidism (40/40). Histologic examination of PTC showed that the tumor cells contained clear to eosinophilic cytoplasm and separated by dense bands of fibrosis. The tumor mass was surrounded by thick fibrous capsule. Foci of capsular invasion and vascular permeation were identified at the tumor periphery in all cases. Cellular atypia was not conspicuous but mitotic figures and coagulative necrosis were easily identified. On the other hand, PA were composed of tumor cells with clear to eosinophilic cytoplasm, forming glands, trabeculae or nests. Most of them (35/40) had intact fibrous capsule. Mitotic figures were rarely encountered and tumor necrosis was absent. Immunohistochemical study showed that the tumor cells in PTC were positive for CK19 (11/11), chromogranin A (9/11), synaptophysin (7/11) and parathyroid hormone (11/11). They were negative for thyroglobulin, TTF-1 and calcitonin. The Ki-67 index was less than 10% (range = 2% to 9%). In contrast, the tumor cells in PA were positive (40/40) for CK19, chromogranin A, synaptophysin and parathyroid hormone. They were negative for thyroglobulin, TTF-1 and calcitonin. The Ki-67 index was less than 3%. Follow up-data were available in 9 cases of PTC (duration of follow up = 11 months to 224 months) and 7 of the patients were still alive. Follow up of all PA cases showed no evidence of recurrence.

CONCLUSIONSPTC is a rare malignant endocrine tumor presenting as neck mass. Histologic features suggestive of malignant behavior include presence of coagulative tumor necrosis and capsular/vascular invasion. It needs to be distinguished from other entities such as parathyroid adenoma, papillary thyroid carcinoma and medullary thyroid carcinoma.

Adenoma ; metabolism ; pathology ; Adult ; Carcinoma ; metabolism ; pathology ; Carcinoma, Neuroendocrine ; Carcinoma, Papillary ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hypercalcemia ; etiology ; Hyperparathyroidism ; etiology ; Immunohistochemistry ; Keratin-19 ; metabolism ; Male ; Middle Aged ; Osteoporosis ; etiology ; Parathyroid Hormone ; metabolism ; Parathyroid Neoplasms ; complications ; metabolism ; pathology ; surgery ; Synaptophysin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

Adult ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; surgery ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Female ; Humans ; Keratin-7 ; metabolism ; Keratin-8 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Liver Neoplasms ; secondary ; Mixed Tumor, Malignant ; metabolism ; pathology ; surgery ; Nephrectomy ; Neprilysin ; metabolism ; Synaptophysin ; metabolism ; Vimentin ; metabolism

OBJECTIVEThe aim of this study was to investigate the clinicopathological features of different histological types of primary gastric neuroendocrine neoplasms (including the esophagogastric junction), and to analyze the characteristics and difficulties in diagnosis of all the subtypes of this disease.

METHODS75 cases of primary gastric neuroendocrine neoplasms (including the esophagogastric junction) were included in this study. The expressions of several markers including somatostatin, synaptophysin, chromogranin A, CD56, S-100, neuron-specific enolase and CD57 were assayed in all the specimens by immunohistochemical staining, and their significance in the diagnosis and prognosis of gastric neuroendocrine neoplasms were assessed. In addition, the relationship between various clinical parameters such as tumor location, histological types, depth of invasion and metastasis was also analyzed.

RESULTSThe incidence of gastric neuroendocrine neoplasms accounted for 1.5% of gastric cancer in the same period, and the proportion of each subtype was 53.3% (40/75) in G3, 29.3% (22/75) in MANEC, 16.0% in G1(12/75), and 1.3% (1/75) in G2, respectively. 41.7% (5/12) of the G1 showed multifocal lesions, accompanyied with neuroendocrine cell hyperplasia in the gastric mucosa. 54.67% (41/75) of the NEN located in the esophagogastric junction. The lymph node metastasis of MANEC is unique. The coincidence rate in diagnosis of preoperative biopsies and postoperative specimen was 75.0% (9/12) in G1, 72.7% (16/22) in MANEC, and 25.0% (10/40) in G3, respectively.

CONCLUSIONSGastric neuroendocrine neoplasms occur mainly in the esophagogastric junction, and most of them were highly malignant. The coincidence rate of preoperative and postoperative pathological diagnosis for primary gastric neuroendocrine neoplasms is low. Therefore, it should be very cautious when diagnosis of this disease is made in a preoperative biopsy.

Chromogranin A ; metabolism ; Esophagogastric Junction ; metabolism ; Gastric Mucosa ; metabolism ; pathology ; Humans ; Lymphatic Metastasis ; pathology ; Neuroendocrine Tumors ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Prognosis ; Stomach Neoplasms ; pathology ; Synaptophysin ; metabolism

Adult ; Breast Neoplasms ; metabolism ; pathology ; secondary ; Carcinoid Tumor ; metabolism ; pathology ; surgery ; Carcinoma, Adenoid Cystic ; pathology ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hysterectomy ; Keratins ; metabolism ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Ovarian Neoplasms ; metabolism ; pathology ; Sex Cord-Gonadal Stromal Tumors ; metabolism ; pathology ; Synaptophysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery