Primary small cell carcinoma of the stomach

We report on an 80-year-old man with primary gastric small cell carcinoma (SmCC). He was admitted to hospital with hematemesis. An upper gastrointestinal examination revealed an irregularly ulcerated tumor, 60 mm in diameter, on the lesser curvature of the stomach body extending to the cardia. An endoscopic biopsy revealed a solid proliferation of intermediate-sized tumor cells with hyperchromatic nuclei and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for neuron-specific enolase and chromogranin A, but negative for carcinoembryonic antigen. No tumor was detected on examination of the chest. Therefore, primary gastric SmCC was diagnosed preoperatively. To date, only 38 cases of primary gastric SmCC, including our case, have been reported. By using endoscopic biopsy, approximately two-thirds of cases have been diagnosed incorrectly. In the reported cases of gastric SmCC, the endoscopic findings frequently indicated a submucosal tumor. Gastric SmCC is clinically aggressive and has an extremely poor prognosis, even when discovered at an early stage. Most patients with gastric SmCC die within 1 year of diagnosis. Although a standard treatment for gastric SmCC has not been established, intensive chemotherapy should be considered to promote long-term survival. We believe that careful examination, including immunohistochemical investigation, is necessary for determining the therapeutic strategy whenever gastric SmCC is suspected during endoscopy.     

Combined choriocarcinoma, neuroendocrine cell carcinoma and tubular adenocarcinoma in the stomach

We described a patient with adenocarcinoma of the stomach combined with choriocarcinoma and neuroendocrine cell carcinoma. An 85-year-old man visited our hospital because of appetite loss. Gastric fiberscopy revealed a large tumor occupying the cardial region and anterior wall of the gastric body. The patient underwent total gastrectomy with lymphnode dissection and partial resection of the liver. Choriocarcinoma, small cell carcinoma and tubular adenocarcinoma existed in the gastric tumor. The choriocarcinomatous foci contained cells positive for beta-subunit of human chorionic gonadotropin （B-hCG） and human placental lactogen mainly in syncytiotrophoblastic cells. The small cell carcinomatous loci contained cells positive for synaptophysin, neuron-specific enolase （NSE）, and chromogranin A. The prognosis for gastric adenocarcinoma with choriocarcinoma and neuroendocrine cell carcinoma is exceedingly poor. This patient died about 2 mo after the first complaint from hepatic failure. This is the first reported case of gastric cancer with these three pathological features.     

Tumor markers in pleural effusion of patients with lung cancer and patients with tuberculous pleurisy]

Carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), NCC-ST-439, carbohydrate antigen 19-9 (CA 19-9), cytokeratin 19 fragment (CYFRA 21-1), sialyl Lewis X-i antigen (SLX), progastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) were evaluated in the pleural effusion of 39 patients with lung cancer (29 adenocarcinomas, seven small-cell carcinomas, three squamous cell carcinomas) and 43 patients with tuberculous pleurisy. The levels of the tumor markers other than SCC and NSE were significantly higher in lung cancer than in tuberculosis. High levels of CYFRA 21-1 and SCC were observed in squamous cell carcinoma and high levels of ProGRP and NSE were observed in small-cell carcinoma. According to the validity score, sensitivity (%) + specificity (%) - 100, the optimal cut-off levels of pleural effusion were 8.1 ng/ml for CEA, 660 U/ml for CA 125, 2.6 U/ml for NCC-ST-439, 10 U/ml for CA 19-9, 65 ng/ml for CYFRA 21-1, 140 U/ml for SLX, 23.2 pg/ml for ProGRP, 0.6 ng/ml for SCC and 5 ng/ml for NSE. By comparison of validity scores for each optimal cut-off level and of receiver operating characteristic (ROC) curves, we suggest that a CEA assay is the most useful for pleural effusion. The combined assay of CEA + ProGRP and CEA + ProGRP + CYFRA 21-1 were considered to be useful.     

CEA-producing mucin-negative gastric signet-ring cell carcinoma with neuroendocrine markers: a case report.

Biopsy and autopsy materials excised from a 69-year-old woman were investigated. Serum carcinoembryonic antigen (CEA) showed a high value of 955 ng/mL. A plateaulike tumor was located in the gastric cardia and fundus to the entire gastric body. It showed severe proliferation and infiltration from the mucosa to the serosa. The tumor was comprised of signet-ring cells and poorly differentiated adenocarcinoma cells, which spread into the submucosa of the pylorus, duodenum, and jejunum. Signet-ring cells had a large, eccentric vesicular nucleus and a pale cytoplasmic inclusion. Poorly differentiated adenocarcinoma cells had a pleomorphic nucleus, small eosinophilic nucleolus, and abundant eosinophilic cytoplasm. Both neoplastic cells were positive for CEA, epithelial membrane antigen, Leu-7 (CD57), and neuron-specific enolase, and were negative for cytokeratin, vimentin, and periodic acid-Schiff, Alcian blue, and mucicarmine stains. Electron microscopy showed endocrine granules with a limiting membrane measuring approximately 238 nm in diameter in the cytoplasm. The authors diagnosed this patient as having mucin-negative gastric signet-ring cell carcinoma with neuroendocrine markers, which is suggested to exist among poorly differentiated adenocarcinoma, undifferentiated carcinoma, and signet-ring cell carcinoma.     

Extrapulmonary small-cell carcinoma of the liver

A 53-year-old man was admitted to our hospital for the evaluation of a mass (13 × 10?cm) in the left lobe of the liver seen by imaging studies. On subsequent biopsy of the mass, the lesion was histologically diagnosed as malignant small round-cell tumor, consistent with metastatic small-cell carcinoma. Segment IV segmentectomy was performed. On pathological examination, the mass showed a yellowish-gray granular appearance with multifocal hemorrhage and necrosis. The phenotypes shown by immunohistochemistry revealed characteristic patterns of small-cell carcinoma (neuron-specific enolase [NSE]+, synaptophysin+, c-Kit+, cluster designation [CD]56+, epithelial membrane antigen [EMA]+, cytokeratin [CK]7?). High resolution-computed tomography (HRCT) revealed inactive pulmonary tuberculosis with small calcified tuberculoma in the right upper lobe. Sputum cytology was negative for malignancy. The postoperative course was uneventful, and platinum-based chemotherapy (cisplatin, etoposide) was initiated.     

Biomarkers in the lung cancer diagnosis: a clinical perspective

The propensity for tumor biomarkers to be detected in serum at an early disease stage has become an area of interest for clinicians. This study aimed to evaluate the efficiency of 7 tumor biomarkers, namely, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA-21-1), alpha-fetoprotein, carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9), and ferritin, independently or in combination for the diagnosis of lung cancer. Electrochemiluminescence immunization was used to determine biomarker levels expressed in 530 patients with pulmonary disease and 229 healthy subjects. The observed levels of CEA, NSE, CYFRA-21-1, CA-125, and CA-19.9 in patients with pathologically confirmed lung cancer were significantly higher than those in patients with benign pulmonary disease or control subjects. Adenocarcinoma, squamous cell carcinoma, and small cell carcinoma of the lung were associated with the highest observed levels of CA-125, CYFRA-21-1, and NSE, respectively. Combining biomarkers successfully led to the diagnosis of lung cancer. CEA + NSE + CA-125 showed the highest sensitivity for small cell carcinoma, at 83.33%, whereas CEA + NSE + CYFRA-21-1 + CA-125 showed 94.11% sensitivity for squamous cell carcinoma. The combination of 6 biomarkers, namely, CEA + NSE + CYFRA-21-1 + CA-125 + ferritin + CA-19.9, showed 80.49% sensitivity for adenocarcinoma. Combining biomarkers significantly aided in the diagnosis of lung cancer. However, this increased sensitivity on combination was accompanied by a decreased specificity for lung cancer subtypes. Combining biomarkers appropriately increases their sensitivity and helps with the diagnosis of lung cancer.     

Carcinoembryonic antigen, neuron-specific enolase and creatine kinase-BB as tumor markers for carcinoma of the lung.

Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and creatine kinase-BB (CK-BB) were estimated in blood serum of 75 patients with primary lung carcinoma and of 20 patients with nonmalignant lung diseases. CEA and NSE were determined by immunoenzymatic method using monoclonal antibodies (Abbott CEA-EIA and Roche NSE-EIA) and CK-BB was assayed using kits supplied by Boehringer-Mannheim (Monotest CK-NAC aktiviert). Enhanced levels of CEA were observed in 64% of patients with lung carcinoma, mainly with adenocarcinoma. Increased activities of NSE and CK-BB were obtained in 47% and 39% of patients, respectively, principally of those with small cell carcinoma. The CEA level was dependent on the stage of advanced NSCLC carcinoma and of NSE and CK-BB on the stage of advanced SCLC carcinoma. The complex analysis of the three markers has given 100% specificity of test.     

Esophageal composite carcinoma with tripartite differentiation: clinicopathological analysis of three cases

We here report on the clinicopathological characteristics of three cases of esophageal composite tumor showing tirpartite differentiation toward distinct squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. All tumors had in situ squamous cell carcinoma components and the deeply invasive parts of adenocarcinoma and small cell carcinoma components, which showed positive immunoreactivity for neuroendocrine markers and intracytoplasmic argyrophil granules. All three patients suffered disseminated tumor recurrence soon after esophagectomy and died of the disease within 14 months after operation. The metastatic tumors were predominantly composed of small cell carcinoma, and serum levels of neuron-specific enolase (NSE) were abnormally elevated at the time of recurrence in all cases. Esophageal composite tumors with tripartite differentiation are extremely aggressive; this aggression is primarily the result of the small cell carcinoma component, indicating the necessity for clinicians to treat such tumors as small cell carcinoma.     

肿瘤标志物动态变化在肺癌疗效判断与随访中的意义

目的探讨癌胚抗原(carcino-embryonic antigen,CEA)、铁蛋白(ferritin,FRT)、糖类抗原125(carbohydrate antigen 125,CA125)、神经元特异性烯醇化酶(neuron specific enolase,NSE)和细胞角蛋19片段(cytokeratin19 fragment,CYFRA21-1)等5种血清学肿瘤标志物(tumor markers,TM)的动态变化在肺癌疗效判断与随访中的意义。方法选择唐都医院呼吸内科经治的170例中晚期肺癌患者,采用电化学发光免疫分析法检测CEA、FRT、CA125、NSE和CYFRA21-1等5种血清学TM,观察不同TM在肺癌治疗过程中的动态变化水平。结果治疗2周期后,CA125在各肺癌组、CYFRA21-1在鳞癌和腺癌及未分类癌、NSE在小细胞癌及神经内分泌癌、CEA在腺癌和未分类癌及神经内分泌癌、FRT在鳞癌治疗中呈下降趋势。结论血清TM水平的动态变化,在一定程度上反映肿瘤的活动情况及疗效,可用于肺癌疗效判断与随访。     

消化系神经内分泌癌及文献分析209例

目的:探讨消化系统神经内分泌癌(NEC)发生部位、临床表现、内镜及影像学特点、病理特征、诊断和鉴别诊断、治疗及预后.方法:将我院2000-2005年收治的7例NEC病例和文献检索的202例病例分为A、B两组,分别探讨消化系统NEC临床特点,治疗和预后.结果:消化系统NEC临床表现多为无功能NEC,以局部占位及消耗症状为主,壶腹周围NEC可以急性胰腺炎发作为首发表现;有功能的NEC例数约占2.4%.大小在0.5-13.0 cm,分为典型类癌、不典型类癌和小细胞癌,确诊需要进行突触素(Syn)、细胞角蛋白(CK)、神经特异性烯醇化酶(NSE)、嗜铬素A(CgA)、上皮膜抗原(EMA)等的免疫组化检查和(或)电镜检查发现神经内分泌颗粒(NSG).以手术治疗为主,辅以化疗、放疗,必要时栓塞化疗,也可以辅以生物治疗.对于有功能的NEC,首先需要控制因激素分泌过多所致的相关类癌综合征.小细胞癌预后最差,不典型类癌次之,类癌预后较好,5 a生存率可达70%.肿瘤的大小、转移与否、手术切除是否彻底等等亦是影响预后的重要因素.结论:消化系统NEC发生部位以胃、胰腺、直肠等部位多见,临床表现多样,少数可有类癌综合征表现,治疗方法以手术为主,辅以放化疗及生物治疗或介入治疗,根据病理类型判断其恶性程度和预后.     

Serum neuron-specific enolase as a marker of small-cell carcinoma of the esophagus

We monitored the changes in serum neuron-specific enolase (NSE) level in two patients with esophageal small-cell carcinoma (SCC) during the course of treatment by chemotherapy or surgery, with radiation. Serum NSE levels at diagnosis were 18.5 and 58.0 ng/ml. In both cases, after treatment the serum NSE level decreased to within normal range (less than 10.0 ng/ml), concurrent with reduction in the size of the tumor. However, with relapse of the disease, the serum NSE increased to 24.3 and 200.0 ng/ml, respectively. One patient died of lung and skin metastases 4 months after surgery; the other, who developed brain metastasis, was treated again with chemotherapy by the same regimen. The serum NSE level decreased to 13.0 ng/ml, and the symptoms improved. These results indicate that there is a correlation between serum NSE level and remission or relapse of the disease after treatment in patients with SCC of the esophagus, as with SCC of the lung.     

Primary small cell carcinoma of the esophagus with achalasia in a patient in whom pro-gastrin-releasing peptide and neuron-specific enolase levels reflected the clinical course during chemotherapy

We report a case of primary small cell carcinoma of the esophagus in a patient with achalasia in whom pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) levels were measured. Although chemotherapy markedly reduced the size of the primary tumor and lymph node metastases, it had no effect on liver metastases. The tumor marker levels decreased after chemotherapy as the primary tumor and lymph node metastases decreased in size, and they increased as the liver metastases enlarged. However, there was a discrepancy between the levels of ProGRP and NSE during the patient's clinical course. We demonstrate the usfulness of measuring ProGRP and NSE levels to assess the effect of chemotherapy in patients with esophageal small cell carcinoma. Received: April 30, 1998/Accepted: November 27, 1998     

Diagnostic utility of endoscopic ultrasound-guided fineneedle aspiration biopsy for glomus tumor of the stomach

A 52-year-old man was referred for further investigation of a gastric submucosal tumor on the greater curvature of the antrum. Endoscopic ultrasonography demonstrated a hypoechoic solid mass, which was primarily connected to the muscular layer of the stomach. We performed endoscopic ultrasoundguided fine-needle aspiration biopsy. The pathological examination showed proliferation of oval-shaped cells with nest formation, which stained strongly positive for muscle actin, and negative for c-kit, CD34, CD56,desmin, S-100, chromogranin, and neuron-specific enolase. Therefore, we performed laparoscopy and endoscopy cooperative surgery based on the preoperative diagnosis of glomus tumor of the stomach. The final histological diagnosis confirmed the preoperative diagnosis. Although preoperative diagnosis of glomus tumor of the stomach is difficult with conventional images and endoscopic biopsy, endoscopic ultrasoundguided fine-needle aspiration biopsy is an essential tool to gain histological evidence of glomus tumor of the stomach for early diagnosis.     

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.     

Measurement of carcinoembryonic antigen, squamous cell carcinoma related antigen and neuron-specific enolase in the bronchoalveolar lavage fluid in patients with peripheral lung cancer

Carcinoembryonic antigen (CEA), squamous cell carcinoma related antigen (SCC) and neuron-specific enolase (NSE) in bronchoalveolar lavage fluid were measured in 30 patients with peripheral lung cancer, 11 patients with benign lung disease and 19 healthy controls. The mean levels and positive rates of lavaged fluid CEA were 128.0 +/- 16.9 ng/mg and 33.3% in patients with lung cancer, 68.1 +/- 25.9 ng/mg and 9.1% in patients with benign lung disease, and 68.3 +/- 11.6 ng/mg and 5.2% in healthy controls, respectively. The mean levels and positive rates of lavaged fluid CEA in patients with lung cancer were significantly higher than those in patients with benign lung disease (p less than 0.05) and those in healthy controls (p less than 0.05). The mean levels of lavaged fluid SCC and NSE showed no significant difference between cases of lung cancer and benign lung disease or healthy controls. No lavaged tumor marker level in patients with lung cancer showed any close correlation with histologic types and serum levels. In conclusion, measurement of lavaged fluid CEA was considered to be useful in the differential diagnosis of peripheral lung cancer.     

Small cell neuroendocrine carcinoma of the ampulla of Vater with foci of squamous differentiation: a case report

A 54-year-old woman with obstructive jaundice was found to have a 4-cm ulcerated, elevated tumor, located at the papilla of Vater by endoscopy and radiographic investigation. Based on a clinical diagnosis of carcinoma of the ampulla of Vater, a pylorus-preserving pancreaticoduodenectomy was performed. The histologic appearance of the lesion was identical to extrapulmonary small cell carcinoma, with diffuse proliferation of small, spindle-shaped, atypical tumor cells with numerous mitoses. Neuroendocrine differentiation was demonstrated by immunoreactivity with neuron-specific enolase (NSE) and Leu-7, and by the presence of dense core granules ultrastructurally. The tumor was composed mainly of small cell neuroendocrine carcinoma, and partially of an area of squamous differentiation, showing transition from one to the other. Histopathologic investigation disclosed direct invasion deep to the lamina propria, and infiltration of the pancreatic parenchyma, duodenum, and bile duct. Lymph node metastases were present in the superior pancreaticoduodenal chain. The patient died of liver metastases 8 months later. As in previously reported cases of small cell neuroendocrine carcinoma of the ampullary region, the present case showed extremely aggressive clinical behavior with early metastases resulting in fatal outcome.     

联合检测血清CYFRA21-1、CA-125、NSE诊断肺癌的价值

目的　探讨联合检测血清中细胞角蛋白 19血清片段 2 1- 1(CYFRA2 1- 1)、糖链抗原 - 12 5 (CA - 12 5 )、神经元特异性烯醇化酶 (NSE)表达水平对肺癌的诊断价值。方法　应用 EL ISA和化学发光法分别检测 74例肺癌患者 (肺癌组 )和 34例肺良性疾病患者 (肺良性疾病组 )及 5 2例正常人 (正常对照组 )血清 CYFRA 2 1- 1、CA- 12 5、NSE水平。结果　肺癌组血清 CYFRA2 1- 1、CA- 12 5、NSE浓度显著高于正常对照组和肺良性疾病组 (P <0 .0 0 1) ,CYFRA2 1- 1在肺鳞癌中表达水平最高 ,CA- 12 5在肺腺癌中表达水平最高 ,NSE在肺小细胞癌中表达水平最高。血清 CYFRA2 1- 1+CA- 12 5 +NSE联合检测肺癌的敏感性为 90 .4 % ,特异性为 81.3%。结论　联合检测血清 CYFRA2 1- 1、CA- 12 5、NSE水平对肺癌的诊断有重要的临床参考价值。     

Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer

OBJECTIVE: To assess the value of Cyfra 21-1, carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) combined, all three together as prognostic factors in advanced stage non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Serum samples from untreated NSCLC patients were prospectively collected. All assays were performed using commercial kits blind to clinical information. Serum levels of CEA, NSE and Cyfra 21-1 higher than 10, 13 and 3.5 ng/ml, respectively, were considered as elevated. RESULTS: 264 patients (men, 87%), with Performans Status (PS) of 0/1 in 80% and stage IV disease in 65% were studied. Cyfra 21-1, CEA and NSE were elevated in 52.5%, 41.8% and 33.2% of patients, respectively. Median survival was 9 months (range, 1-77). Cyfra 21-1, age, PS, stage as well as the combination of the three markers together correlated with prognosis in univariate analysis. Multivariate analysis demonstrated that age > or = 65 years (HR = 1.3 [1.02-1.70], p = 0.03), PS 2 (HR = 4.3 [3.13-6.11], p < 0.0001), Cyfra 21-1 > or = 3.5 ng/ml (HR = 1.3 [1.06-1.78], p = 0.01) and the combination of the three markers (HR = 1.06 [1.009-1.13], p = 0.02) remained prognostic determinants. CONCLUSION: Combining Cyfra 21-1, NSE and CEA correlated with prognosis in a significant and independent manner.     

四种肿瘤标志物血清水平的联合检测对肺癌诊断的临床价值

目的探讨血清肿瘤标志物细胞角蛋白19片段（CYFRA21-1）、神经元特异性烯醇化酶（NSE）、癌胚抗原（CEA）、糖类抗原125（CA125）联合检测对肺癌诊断的临床价值。方法采用瑞士罗氏公司cobas e 411型全自动电化学发光免疫分析系统检测经病理确诊的52例肺癌患者、30例肺部良性疾病患者及35例正常人血清CYFRA21-1、NSE、CEA、CA125水平,并计算阳性率、特异度及准确度。结果肺癌组血清4种肿瘤标志物水平显著高于肺良性疾病及健康对照组。其中单项检测CYFRA21-1阳性率以鳞癌最高（70.8%）,NSE阳性率以小细胞肺癌最高（75.0%）,CEA阳性率以腺癌最高（65.0%）,与其他型肺癌相比差异有统计意义。4种肿瘤标志物联合检测阳性率、特异度及准确度明显高于单项检测结果。结论 4种肿瘤标志物对于肺癌的辅助诊断均具有实用价值,且联合检测有助于提高肺癌诊断的阳性率、特异度及准确度。     

Ossifying gastric carcinoid tumor containing bone morphogenetic protein, osteopontin and osteonectin

We report a case of gastric carcinoid tumor with ossification. A 47-yr-old man complaining of abdominal discomfort underwent gastrointestinal endoscopic examination, which revealed a submucosal tumor in his stomach. The tumor was extirpated by endoscopic enucleation. Histologically, the tumor was widely occupied by mature bone tissues, where scattered carcinoid tumor cell nests surrounded bone tissues or located in stromal areas. Immunohistochemically, the tumor cells were strongly positive for cytokeratin, chromogranin A, synaptophysin, neurofilaments and neuron-specific enolase, underscoring the diagnosis of carcinoid tumor. They also stained positive with markers of bone formation and differentiation, such as bone morphogenetic protein, osteopontin and osteonectin. There are only four cases in the world literature, including a current case of ossifying gastric carcinoid tumor, in which the excessive production of peptides promoting ossification was considered to be implicated in the unusual appearance of the bone.