Telomerase activity in small cell esophageal carcinoma

Small cell carcinoma of the esophagus is a rare and aggressive malignant tumor. Telomerase activation is common in human cancers. There is a lack of data on telomerase activity in esophageal small cell cancers. The present report studied the role of telomerase activity in esophageal small cell carcinoma. The clinicopathologic data of five patients with small cell carcinoma of the esophagus who underwent primary surgical treatment between 1991 and 2000 were studied. Telomeric repeat amplification protocol assays were used to investigate telomerase activity in these tumors. The proliferative activity (MIB-1) and p53 expression of these tumors were also studied using immunohistochemistry and correlated with the telomerase activity. All five small cell carcinomas showed detectable telomerase activity in the primary tumor. Two out of the five morphologically normal esophageal mucosae adjacent to the primary tumor had detectable telomerase activity. There was no correlation between the p53 expression, tumor stage, survival of patients, and the presence of telomerase activity. High MIB-1 expression in esophageal small cell carcinomas was associated with high telomerase activity. Telomerase activation is common in small cell carcinoma of the esophagus. This fact may find application in anti-telomerase treatment for this aggressive tumor.     

老年人原发性食管小细胞未分化癌（附12例报告）

目的探讨老年人原发性食管小细胞未分化癌的发病情况、临床病理特征及治疗方法。方法分析１９８７～１９９４年我院收治的１２例老年人原发性食管小细胞未分化癌，单纯手术４例，手术结合化疗２例，单纯放疗６例。结果平均生存期：手术治疗组６个月，放疗组５个月。治疗失败的主要原因是远处转移。结论单纯手术、化疗、放疗的疗效较差，综合治疗是提高该病疗效的研究方向。     

Carcinosarcoma of the esophagus producing granulocyte-colony stimulating factor: report of a case

A 51-year-old man was admitted to the hospital for dysphagia, pyrexia, and leukocytosis. The serum level of granulocyte-colony stimulating factor (G-CSF) was elevated. Barium esophagography and endoscopy revealed a polypoid tumor in the middle portion of the esophagus. After an esophagectomy, the leukocyte count and serum G-CSF level normalized. The pathological diagnosis was carcinosarcoma of the esophagus with two components: namely, squamous cell carcinoma and sarcoma. Moreover, cancer cells were positive for G-CSF antibody. These findings confirmed that the esophageal carcinosarcoma in this case was a G-CSF-producing tumor. Although a G-CSF-producing esophageal carcinosarcoma is very rare, this disease should be considered when a patient has symptoms such as leukocytosis and pyrexia without an associated infection.     

The radiological features of primary small-cell carcinoma of the esophagus

Primary small cell carcinoma of the esophagus is a rare neoplasm. The incidence was 2% in our series. A primary lung tumor must be excluded before the diagnosis can be made. Two cases of primary small-cell carcinoma of the esophagus are presented. The radiological features of this tumor are nonspecific. Its unusual histological appearance is described. One patient had received radiotherapy for breast carcinoma 21 years earlier and the possible relationship of this type of cancer to radiotherapy has not been previously described in the literature. Each patient had a short-term response to therapy.     

Effective treatment with chemotherapy and surgical resection for small cell carcinoma of the esophagus: report of a case.

We report on a patient with small cell carcinoma of the esophagus treated with effective combination chemotherapy followed by surgical resection. A 69 year-old male had an ulcerated tumor in the middle part of the esophagus, which was microscopically diagnosed as small cell carcinoma of the esophagus. After combination chemotherapy, endoscopy showed that the esophageal tumor had changed into a shallow ulcer. No cancer cell was found in the biopsy specimen of the ulcer. A subtotal esophagectomy with regional lymph node dissection was performed. Histological examination showed that a few cancer cells remained in a microvessel of the submucosal layer in the removed esophagus and no cancerous lesion was found in regional lymph nodes. The patient was well and was able to remain at home. However, he eventually died 21 months after first detection of the carcinoma due to progression of multiple lung and mediastinal lymph node metastases. After complete or partial remission is achieved by the combination chemotherapy, surgical resection may be recommended as the second therapy that occasionally produces long-term remission and possibly long-term survival for patients with small cell carcinoma of the esophagus, such as the present case.     

Intraoperative endoscopy in obstructive hypopharyngeal carcinoma

AIM: To demonstrate the necessity of intraoperative endoscopy in the diagnosis of secondary primary tumors of the upper digestive tract in patients with obstructive hypopharyngeal carcinoma. METHODS: Thirty-one patients with hypopharyngeal squamous cell carcinoma had been operated, with radical intent, at our Institution in the period between 1978 and 2004. Due to obstructive tumor mass, in 7 (22.6%) patients, preoperative endoscopic evaluation of the esophagus and stomach could not be performed. In those patients, intraoperative endoscopy, made through an incision in the cervical esophagus, was standard diagnostic method for examination of the esophagus and stomach. RESULTS: We found synchronous foregut carcinomas in 3 patients (9.7%). In two patients, synchronous carcinomas had been detected during preoperative endoscopic evaluation, and in one (with obstructive carcinoma) using intraoperative endoscopy. In this case, preoperative barium swallow and CT scan did not reveal the existence of second primary tumor within esophagus, despite the fact that small, but T2 carcinoma, was present. CONCLUSION: It is reasonable to use intraoperative endoscopy as a selective screening test in patients with obstructive hypopharyngeal carcinoma.     

Small cell carcinoma in the esophagus rapidly developing multiple fistulae

This case report describes a small cell carcinoma in the esophagus with a squamous cell carcinoma that developed multiple fistulae. Autopsy findings demonstrated that both the primary tumor and the metastatic lymph nodes became necrotic and caused an abscess cavity spreading into the mediastinal, retroperitoneal, and subcutaneous spaces. An esophageal stent was effective for palliation.     

Small cell carcinoma of the esophagus with metastasis to the brain: a case report

Small cell carcinoma of the esophagus is a rare disease with early systemic metastasis, and the prognosis remains poor. This present case (a 60-year-old Japanese man) was a small cell carcinoma at the lower third of the esophagus complicated by multiple liver and brain metastases. After the first chemotherapy, endoscopic study showed significant shrinkage of the primary esophageal tumor. About 4 months later, however, a primary tumor formed a deep ulceration, and a CT scan of the abdomen also showed further progression of the liver metastases. One year after starting the therapy, a disturbance in the patient’s right eyesight and awkward movement of his right hand occurred. Brain magnetic resonance imaging revealed several high-density areas compatible with metastasis. Gamma knife radiosurgery for metastatic brain tumors was carried out, and all tumors had shrunk. Unfortunately, the patient’s liver function deteriorated gradually because of the aggravation of liver metastases, and the patient died 1 year and 5 months from the time of diagnosis.     

Small cell carcinoma of the esophagus: a case report.

Primary small cell carcinoma of the esophagus, which is similar in appearance and behavior to its counterpart of the lung, is a rare tumor. We describe a 77 year-old woman whose esophagram revealed a well-defined mass in the lower third of the thoracic esophagus. A biopsy specimen showed an infiltration of small malignant cells. The individual cells were oval- or spindle-shaped with hyperchromatic nuclei and scant cytoplasm. Synaptophysin staining was positive. The mass was diagnosed as a small cell carcinoma of the esophagus. She underwent an esophagectomy with esophagogastric anastomosis. We discuss the treatment of small cell carcinoma of the esophagus.     

Primary small cell carcinoma of esophagus： Report of 9 cases and review of literature

AIM: To analyze the clinical manifestations, pathological features and treatment of primary small cell carcinoma (SCC) of the esophagus and to review the literature on this entity.METHODS: The records of 9 patients with primary esophageal small cell carcinoma were examined and the demographic data, presenting symptoms, methods of tumor diagnosis, and types of treatment given, response to treatment, pathologic findings, and clinical outcome were reviewed. Features of mixed patterns of histological differentiation and lymph node metastases were specifically sought.RESULTS: All the patients reported dysphagia, weight loss and chest pain as the initial symptoms. In 5 cases the tumors were located in the mid-esophagus, 3 cases in the lower third of the esophagus and 1 case in the upper third.The average length of esophageal involvement was 5 cm.They underwent radical resection, regional lymph node clearance and esophageal-stomach anastomosis in thorax or at neck. Two patients had a stage Ⅱa disease, five had a stage Ⅱb disease, and the other two had a stage Ⅲ disease of International Union Contrele Cancer (UICC). All of them were histologically and immunohistochemically confirmed SCC of esophagus. Immunohistochemical staining for neuron-specific enolase (NSE), synaptophsin (Syn) and chromogranin A exhibited strong immunoreactivity in all specimens. Three of the nine resected specimens showed foci of squamous cell carcinoma in situ. Metastasis was present in 7 of 9 adjacent lymph nodes. All the patients survived the operations and made an uneventful postoperative recovery. They received adjuvant systemic chemotherapy and local radiation therapy after discharge. During followup, three patients developed multiple liver, brain, lung and bone metastases and died between 5 and 18 mo after the diagnosis. Three patients developed widespread metastasis disease and died between 18 and 37 mo after the diagnosis.There was no local tumor recurrence in these 6 patients.The other three patients were lost during follow-up.CONCLUSION: Primary small cell carcinoma of the esophagus is a rare but very malignant tumor. Radical resection combined with chemotherapy and radiotherapy is helpful in limited stage cases.     

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     

Double primary cancer of the esophagus consisting of ectopic gastric mucosa-derived adenocarcinoma and squamous cell carcinoma: a first case report

Most esophageal cancers are either squamous cell carcinomas or Barrett??s mucosa-derived adenocarcinomas. A 64-year-old man with a long history of alcohol drinking and smoking was found to have a tumor in the cervical esophagus on screening esophagography. Subsequent work-up revealed double primary cancer of the esophagus consisting of adenocarcinoma arising from ectopic gastric mucosa in the cervical esophagus and squamous cell carcinoma in the abdominal esophagus. He underwent subtotal esophagectomy. On microscopic examination of the resected specimen, the Ip tumor in the cervical esophagus was confirmed to be an adenocarcinoma derived from ectopic gastric mucosa that had invaded the muscularis mucosa, and the 0-IIb tumor located near the esophagogastric junction was confirmed to be a squamous cell carcinoma that had invaded the proper mucosal layer. No lymph node metastases were noted. Adenocarcinoma from ectopic gastric mucosa is rare, and its coexistence with squamous cell carcinoma is extremely rare.     

Submucosal tumor (SMT)-like esophageal squamous cell carcinoma with gastric metastasis

We present here a case of submucosal tumor-like esophageal cancer with metastasis to the stomach. A 60-year-old man, whose ability to swallow was impaired, was admitted to Kyorin University School of Medicine Hospital. Gastrointestinal endoscopy demonstrated a small bulging mass in the lower esophagus and a large submucosal mass in the gastric cardia. The gastric lesion was growing rapidly and becoming easily hemorrhagic. It appeared rich in blood flow by angiography. Surgical treatment was adopted after a diagnosis of esophageal cancer and a gastric submucosal tumor was made. However, in the end, the gastric mass was identified as a metastasis from the esophageal squamous cell carcinoma. Moreover, the primary esophageal lesion displayed quite a special type of histology, a so-called submucosal tumor-like pattern, which was covered by normal epithelium and grew mainly in the submucosal layer of the esophagus. Gastric metastasis from esophageal cancer is relatively rare, and it is quite rare that an esophageal squamous cell carcinoma grows as a submucosal tumor. Finally, the patient died of pneumonia and metastasis to the liver on the 110th day of hospitalization. Intramural metastasis to the stomach from esophageal cancer should be treated in its advanced stage, and poor prognosis can be expected from aggressive treatment. It is necessary to recognize this complication so that appropriate therapy can be carried out on patients with esophageal cancer, and the situation needs to be carefully evaluated, including the stomach, both before and after treatment.     

Esophageal combined carcinomas: Immunohoistochemical and molecular genetic studies

Primary esophageal combined carcinoma is very rare. The authors herein report 2 cases. Case 1 was a combined squamous cell carcinoma and small cell carcinoma, and case 2 was a combined squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. Case 1 was a 67-year-old man with complaints of dysphagia. Endoscopic examination revealed an ulcerated tumor in the middle esophagus, and 6 biopsies were obtained. All 6 biopsies revealed a mixture of squamous cell carcinoma and small cell carcinoma. Both elements were positive for cytokeratin, epithelial membrane antigen, and p53 protein, and had high Ki-67 labeling. The small cell carcinoma element was positive for synaptophysin, CD56, KIT, and platelet-derived growth factor-α (PDGFRA), while the squamous cell carcinoma element was not. Genetically, no mutations of KIT and PDGFRA were recognized. The patient died of systemic carcinomatosis 15 mo after presentation. Case 2 was a 74-year-old man presenting with dysplasia. Endoscopy revealed a polypoid tumor in the distal esophagus. Seven biopsies were taken, and 6 showed a mixture of squamous cell carcinoma, small cell carcinoma, and adenocarcinoma. The 3 elements were positive for cytokeratins, epithelial membrane antigen, and p53 protein, and had high Ki-67 labeling. The adenocarcinoma element was positive for mucins. The small cell carcinoma element was positive for CD56, synaptophysin, KIT, and PDGFRA, but the other elements were not. Mutations of KIT and PDGFRA were not recognized. The patient died of systemic carcinomatosis 7 mo after presentation. These combined carcinomas may arise from enterochromaffin cells or totipotential stem cell in the esophagus or transdifferentiation of one element to another. A review of the literature was performed.     

An esophageal squamous cell carcinoma patient with high serum granulocyte-colony stimulating factor level: report of a case

We present herein a case of a patient who was clinically diagnosed as having a granulocyte-colony stimulating factor (G-CSF)-producing tumor on the basis of the close correlation of the hematological parameters with the tumor status and his high serum G-CSF level. A 76-year-old male patient underwent transthoracic radical esophagectomy for advanced carcinoma of the lower esophagus. His leukocyte count and serum G-CSF level were markedly high at 24 260/μl and 134 pg/ml, respectively, before the operation. By immunohistochemical staining of the resected tumor, focal but obvious expression of G-CSF was demonstrated in the cytoplasm of cancer cells, and neutrophilic infiltration was histologically observed in adjacent struma of the tumor invasion front. After surgery, the leukocyte count decreased to a nearly normal level but increased again when the disease recurred in the pleura and lymph nodes 5 months later. Although palliative chemoradiotherapy decreased the leukocyte count to a normal level transiently, leukocyte count again markedly increased when metastatic disease occurred. The leukocyte count reached 78 060/μl the day before the patient died.     

Early-stage primary malignant melanoma of the esophagus detected simultaneously with esophageal squamous cell carcinoma

Primary malignant melanoma of the esophagus is a rare disease. The majority of patients are diagnosed at an advanced stage, and only a few are detected at an early stage. We herein describe a case of early-stage primary malignant melanoma of the esophagus that was detected simultaneously with early-stage primary esophageal squamous cell carcinoma. Both tumors were detected during esophagogastroduodenoscopy for heartburn. The malignant melanoma tumor was a nevus-like flat-type lesion in the upper thoracic esophagus, and the squamous cell carcinoma was a slightly depressed lesion in the abdominal esophagus. The tumor was resected by thoracoscopic esophagectomy. Histologically, the invasion of both tumors was limited to the mucosal layer, and no lymph node metastasis was detected. Immunohistochemically, the malignant melanoma cells were strongly positive for HMB-45, melan-A, and S-100 protein. The patient has survived without recurrence for 17?months after the operation.     

Granulocyte colony-stimulating factor producing lung large cell carcinoma with sarcomatous transformation]

We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung large cell carcinoma with sarcomatous transformation. A 57-year-old man was admitted for evaluation of an abnormal shadow near the right pulmonary hilus on chest X-ray film. Brush cytology specimen from right B6 disclosed large cell carcinoma. His clinical stage was already IIIB (T3N3M0) on admission, so we immediately administered chemotherapy and radiation therapy. However, the patient's condition gradually deteriorated and he died of respiratory failure. Although there was no evidence of infection throughout his clinical course, his peripheral white blood cell count gradually increased and reached 47,000/mm3 (neutrophils 96%) before death. Histological study of the autopsy specimen revealed that the primary tumor was composed of two different elements (large cell carcinoma and spindle cell sarcomatoid element). The spindle cell sarcomatoid element appeared to have arisen from sarcomatous transformation of carcinoma cells, because the transition margin of the carcinoma to the sarcomatoid element was smooth, and special and immunohistochemical staining of both elements showed the same properties. Moreover, immunohistochemical study with monoclonal antibody to human G-CSF, 4A6 clearly demonstrated granular staining of G-CSF in the cytoplasm of tumor cells.     

Primary composite tumor with bipartite differentiation of the esophagogastric junction

We describe a rare case of primary composite tumor with bipartite differentiation of the esophagogastric junction. An 88‐year‐old Japanese man with a history of distal subtotal gastrectomy was admitted to Harima Hospital of Ishikawajima‐harima Heavy Industries with dysphagia of 2 months duration. Endoscopy showed a round, sharply demarcated lesion with a smooth surface in the lower esophagus. Distally, the lesion was irregular and elevated with a deep central depression. The gastric cardia was slightly elevated with a granular mucosa. After surgical resection, histological and histochemical findings showed a primary composite tumor with bipartite differentiation of the esophagogastric junction. There is no evidence of recurrence for 21 months after surgery without adjuvant chemotherapy. The present case indicates the necessity for a careful evaluation for accessory lesions in composite tumors containing small cell carcinoma of the esophagogastric junction, and that resectional surgery might not only be the treatment of choice, but also important in the evaluation of immature composite tumor without distant metastases.     

Superficial undifferentiated small cell carcinoma of the esophagus showing an interesting growing pattern in histology

We report a case of superficial undifferentiated small cell carcinoma of the esophagus. The histology of the tumor was interesting; there was squamous cell differentiation within the epithelial layer and undifferentiated small cells growing within the submucosal layer. The tumor had a negative Grimelius reaction, suggesting no differentiation into a hormone-producing carcinoma known as an apudoma (Amine Precursor Uptake and Decarboxylation (APUD)). The serum levels of ACTH and calcitonin were within normal limits. As the patient was elderly and had a history of pleural tuberculosis causing poor pulmonary function, and owing to the fulminant nature of this carcinoma, he underwent blunt dissection of the esophagus by posterior mediastinal gastric pull-up. The patient recovered quickly and was able to be discharged with a good quality of life until the tumor recurred as a liver metastasis 6 months later.