Pancreatic metastases of renal cell carcinomas - evaluation of the contrast behavior at echo-enhanced power-Doppler sonography in comparison to primary pancreatic tumors

BACKGROUND: Renal cell carcinomas are the most common primary tumors leading to pancreatic metastases. The differentiation of metastases from primary pancreatic tumors is important for the prognosis. Echo-enhanced power-Doppler sonography may be used for the differential diagnosis of tumors. In this study, the contrast behavior of metastases of renal cell carcinomas was evaluated in comparison to primary pancreatic tumors.PATIENTS AND METHODS: Each 5 patients with pancreatic metastases of a renal cell carcinoma, a ductal carcinoma, a neuroendocrine tumor and a pancreatitis-associated mass were investigated by B-mode sonography, fundamental and echo-enhanced power-Doppler sonography.RESULTS: Similar to neuroendocrine tumors, metastases of renal cell carcinomas were found to be hypervascularized. In contrast, ductal carcinomas are hypovascularized compared to the surrounding tissue. Tumors associated with pancreatitis show different vascularization pattern depending on inflammation and necrosis.CONCLUSIONS: Metastases of renal cell carcinomas and ductal carcinomas show different vascularization pattern at echo-enhanced power-Doppler sonography. Renal cell metastases and neuroendocrine tumors have similar contrast behaviors, therefore, clinical symptoms should be referred for their differentiation. However, histology is the standard of reference for the differential diagnosis of pancreatic tumors.     

L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma

AIM:To determine the expression of L1 in pancreaticneuroendocrine tumor and to correlate it with WHO clas-sification of this tumor.METHODS:We retrospectively analyzed L1 expres-sion in 63 cases of pancreatic neuroendocrine tumor byimmunohistochemistry on paraffin sections of primarytumors or metastases.Staining was performed by per-oxidase technique with monoclonal antibody UJ127.11against human L1,All tumors were classified accordingto WHO classification as well-differentiated neuroendo-crine tumors and carcinomas or poorly-differentiatedneuroendocrine carcinomas.RESULTS:L1 was detected in 5 (7.9%) of 63 pancre-atic neuroendocrine tumors.Four (44.4%) of 9 poorly-differentiated carcinomas expressed L1,In contrast,only1 (1.9%) of 54 well-differentiated tumors or carcinomaswas positive for L1.No expression was found in Langer-hans islet cells of normal pancreatic tissue.Cross tableanalysis showed a significant association between L1 ex-pression and classification of neuroendocrine tumors ofthe pancreas(P<0,01).CONCLUSION:L1 is specifically expressed in poorly-differentiated pancreatic neuroendocrine carcinomasthat are known to have the worst prognosis.L1 might bea marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.     

Tumeur neuroendocrine de la vésicule biliaire avec métastases hépatiques et pulmonaires: à propos d’un cas

Neuroendocrine tumours of the gallbladder are rare. They have been classified as carcinoide tumor and endocrine cell carcinoma. The primary treatment of neuroendocrine carcinoma of gallbladder remains surgery. They are aggressive tumours with poor prognosis. We report the case of a 54-year-old woman with a gallbladder mass with pulmonary and liver metastases. Fine needle biopsy of these revealed neuroendocrine carcinoma. There was no evidence of any other primary site. The patient was treated symptomatically; she died within two months of discharge fromthe hospital.     

Neuroendocrine Carcinomas of the Colon and Rectum

PURPOSE: This study was designed to review experience with neuroendocrine carcinomas of the colon and rectum at a single institution, with emphasis on the pathology and clinical characteristics of this uncommon malignancy. METHODS: A study group of patients was identified from a prospective colorectal service database. Pathology was reviewed and neuroendocrine tumors were classified by a single pathologist. Medical records were retrospectively reviewed. RESULTS: From March 1975 to September 1998, 38 patients with neuroendocrine carcinomas were identified from the colorectal service database comprising 6495 patients (0.6 percent). These neuroendocrine carcinomas did not include carcinoid tumors. Average patient age was 57 years (range, 29–86 years). There were 17 males (44.7 percent) and 21 females (55.3 percent). Tumors were located as follows: 17 colon, 14 rectum, 6 anal canal, and 1 appendix. The diagnosis of neuroendocrine carcinoma was suggested preoperatively from tissue biopsy in 59.3 percent (16/27) of patients evaluable. Pathology was reviewed and tumors were categorized as small cell carcinoma (n = 22) or large cell neuroendocrine carcinoma (n = 16). Most tumors (20/25 evaluable, 80 percent) stained positive by means of immunohistochemistry for neuroendocrine markers, including chromogranin (18/19), synaptophysin (10/15), and/or neuron-specific enolase (14/15). Metastatic disease was detected at the time of diagnosis in 69.4 percent of the patients (25/36). Tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer (AJCC) Stage I (n = 6), Stage III (n = 7), and Stage IV (n = 25) tumors. As a group, these tumors had a poor prognosis, with a median survival of 10.4 months. One-year, two-year, and three-year survival was 46 percent, 26 percent, and 13 percent, respectively. There was no significant difference in survival based on pathologic subtypes. Median follow-up time was 9.4 months (range, 0.6–263.7 months). CONCLUSIONS: Neuroendocrine carcinomas of the colon and rectum are uncommon, comprising less than 1 percent of colon and rectal cancers. Pathologically, these tumors are poorly differentiated carcinomas with distinctive cytoarchitectural features and are often immunoreactive for markers of neuroendocrine differentiation. The prognosis for highgrade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.     

Unusual Case of Small Cell Gastric Carcinoma: Case Report and Literature Review

Background  

Small cell carcinomas are among the most aggressive, poorly differentiated, and highly malignant of the neuroendocrine tumors (NETs). Of which, small cell gastric carcinoma is a rare small cell neuroendocrine tumor. The purpose of our study was to present this case and perform a comprehensive literature review.     

Lung and digestive neuroendocrine neoplasms. From WHO classification to biomarker screening: Which perspectives?

The recent classifications of lung and digestive neuroendocrine neoplasms (NENs) make a fundamental distinction between well- and poorly-differentiated neoplasms. Well-differentiated NENs are termed carcinoids in the lung and neuroendocrine tumors in the gastroenteropancreatic sphere; their risk of malignancy is highly variable; histological grading is used to stratify patients into prognostically significant groups. Poorly-differentiated NENs are termed neuroendocrine carcinoma in both the lung and the digestive sphere; they constantly are of high grade of malignancy; two types are recognized on the basis of tumor cell morphology, the small cell and the large cell types. Recent studies have largely uncovered the genetic landscape of several subsets of well-differentiated NENs (lung, pancreas, small intestine) and of poorly-differentiated NENs. Some molecular markers may help to the differential diagnosis between highly proliferative neuroendocrine tumors and neuroendocrine carcinomas, especially in the pancreas. In well-differentiated tumors, MGMT status is proposed as a predictive marker of the response to temozolomide, but remains to be validated. In poorly-differentiated neoplasms, large cell neuroendocrine carcinoma has been shown to be a heterogeneous category, with some cases presenting the same molecular signature than small cell carcinoma and others the same signature than adenocarcinomas of the same body site. Rb protein has been recently shown to be a potential marker of response to platinum salts in neuroendocrine carcinoma. Much remains to be done to translate the rapid progress in the molecular understanding of NENS into diagnostic, prognostic or predictive markers.     

肝脏神经内分泌肿瘤报道1例并文献回顾

背景肝脏可疑恶性肿瘤行手术切除后病理诊断肝脏神经内分泌肿瘤(hepatic neuroendocrin neoplasmas,HNENs)病例,此病例易与肝癌混淆,了解转移性和原发性HNENs的特性,对临床治疗手段有很好的指导意义.病例简介一名56岁男性患者体检发现肝脏占位性病变复查腹部增强CT提示肝脏转移性恶性肿瘤可能;胃部包块考虑良性.手术切除胃部包块并行术中冰冻病理检查提示梭形细胞肿瘤;完整切除肝脏包块术后石蜡病理检查结果提示NENs(G2),患者术后恢复佳.结论本文报道了一例HNENs,考虑转移性.术前诊断不能排除肝脏转移性恶性肿瘤可能.通过对患者病情的详细分析,最终行手术切除治疗并行病理检查确诊.同时我们对HNENs相关文献进行了分析,进一步了解原发和转移性HNENs的临床特征、治疗方案以及预后,以期对此类疾病有更深入的了解,对临床治疗方案决策做证据支撑作用.     

Carcinoid of the ampulla of Vater

Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.     

Primary hepatic neuroendocrine tumor: Five cases with different preoperative diagnoses

Neuroendocrine tumors, also known as carcinoid tumors, behave like benign tumors; however, they show the characteristics of carcinoma. While more than 80% of the neuroendocrine tumors found in the liver are metastatic, primary hepatic neuroendocrine tumors are very rare. Five patients with hepatic mass who admitted to our clinic between August 2003 and July 2007 were treated surgically. Ultrasonography, computerized tomography and magnetic resonance imaging were performed in all patients. Endoscopy and colonoscopy were conducted to exclude malignancy of other sites. Hepatectomy was carried out in all patients. Diagnosis was confirmed with immunohistochemical examination. The five patients treated surgically were diagnosed as primary hepatic neuroendocrine tumor histopathologically. Abdominal pain was the most common complaint of all patients. Hepatectomy was conducted in all patients due to tumors originating from the liver lobes. Only one patient (Case 2) underwent transarterial chemoembolization before hepatectomy to reduce tumor bleeding. Owing to tumor recurrence on the left lobe of the liver in Case 2, transarterial chemoembolization was performed four years after hepatectomy. R0 resection was achieved in two patients (Cases 1 and 3). In conclusion, primary hepatic neuroendocrine tumors are very rare and asymptomatic tumors. Thus, high-sensitive laboratory and imaging examinations are required. At present, hepatectomy remains the main treatment for primary hepatic neuroendocrine tumor.     

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.     

Partial hepatic resection for liver metastases of non-colorectal origin, is it justified?

BACKGROUND/AIMS: The liver is a common site of metastases for many solid tumors. Resection of noncolorectal liver metastases is controversial. The aim of this retrospective study is to evaluate partial liver resection as a treatment option for non-colorectal liver metastases. METHODOLOGY: During a 20-year period, 480 patients underwent partial liver resection. Thirty-two patients (17 male, 15 female, median age 55 years) who received partial liver resection for noncolorectal liver metastases were identified. A detailed analysis of these patients was conducted. RESULTS: Primary tumors were: medullary thyroid cancer (n=3), Grawitz tumor (n=2), breast carcinoma (n=2), stomach carcinoma (n=2), neuroendocrine carcinoma (n=10), unknown primary origin (n=9) and various other carcinomas (n=4). Operative morbidity and mortality for partial liver resection were 28 and 6%, respectively. The median overall survival time was 37 months, with an actuarial 5-year survival of 42%. Actuarial 5-year survival rates for patients with neuroendocrine and the non-neuroendocrine carcinomas were 22 and 52% respectively (NS). Median survival for patients with carcinoma of unknown primary origin was 43 months with an actual 5-year survival of 44%. CONCLUSIONS: Partial liver resection for liver metastases of non-colorectal primaries can be performed safely and has survival rates comparable to that of colorectal metastases in carefully selected cases and should therefore be considered.     

Large lymph node metastasis gives hint to a glicentin positive small endocrine rectal carcinoma

In a patient with a small endocrine carcinoma of the rectum, an unusually large lymph node metastasis was the only preoperative clinical finding. Low anterior rectal resection with total mesorectal excision and lymph node dissection was performed. The tumor demonstrated some highly unusual characteristics: it was classified as a small, low-grade neuroendocrine rectal carcinoma of L-cell type with three large lymph node metastases and morphological consistency with an endocrine tumor and focal positivity of glicentin, demonstrating a proliferation of smooth muscle cells. The established Capella classification of endocrine tumors of the rectum by morphological findings would have characterized this primary tumor as benign. In this case, however, clinical and histopathological findings more accurately reflected its malignant potential.     

Neuroendocrine liver metastases: contributions of endoscopy and surgery to primary tumor search

Neuroendocrine tumors (NETs) are diagnosed with increasing frequency and patients often present with liver metastases at the time of diagnosis. Apart from treatment of the metastases, resection of the primary tumor at an early phase is recommended to prevent complications, although it may be difficult to locate, especially in patients with functionally inactive NETs. Small and multifocal tumors in the jejunum and ileum represent a particular challenge. Primary hepatic neuroendocrine carcinoma is extremely rare and is diagnosed only after exclusion of other primary tumors. Therefore, some uncertainty may remain, as small non-hepatic primary tumors may escape detection. Diagnostic work-up in these patients includes biochemical assays and imaging modalities (also comprising specific techniques of scintigraphy and positron emission tomography). This editorial highlights the contributions of endoscopy and operative exploration to the search for the primary tumor. Besides esophago-gastro-duodenoscopy, endoscopic ultrasonography, colonoscopy and bronchoscopy, special endoscopic techniques such as balloon enteroscopy or capsule endoscopy are used with growing experience. Compared with balloon enteroscopy, capsule endoscopy is non-invasive and better tolerated, but it cannot localize a lesion precisely and does not allow biopsy or removal of lesions. Before proceeding to surgery, a discussion of the findings by a tumor board should be a standard procedure. Improvements in diagnostic tools have created new perspectives for the detection of obscure primary tumors in patients with neuroendocrine liver metastases, and these searches are best coordinated by a multidisciplinary team.     

The value of fine needle aspiration biopsy in the diagnosis of metastatic liver tumours.

BACKGROUND/AIMS: Fine needle aspiration biopsy is a useful tool in the diagnosis of primary malignancies and metastatic lesions of the liver. The aim of this study was to determine the types and features of tumors diagnosed by this method and the difficulties in differential diagnosis. METHODS: Fine needle aspiration biopsy smears from 704 patients with metastatic liver lesions were reviewed. RESULTS: Among the metastastatic carcinomas in which their primary origin was identified, pulmonary carcinomas were the largest group. While colon adenocarcinoma was most prevalent (21.65%) where the primary origin of metastatic tumors was identified, followed by breast carcinoma (20.10%) and gastric adenocarcinoma (19.59%). The cases which cannot be differentiated from hepatocellular carcinoma in cytologic examination are invasive ductal carcinoma, renal cell carcinoma and squamous cell carcinoma. CONCLUSIONS: Pulmonary and colon carcinomas are the common metastatic tumors of the liver.     

Clinical features and outcomes of primary hepatic neuroendocrine carcinomas

Background and Aim: Primary hepatic neuroendocrine carcinomas (PHNECs) are extremely rare, with only about 150 cases having been reported in the English‐language literature. Because of the rarity of PHNECs, its clinical features and treatment outcomes are not well understood. Here, we report our experiences with PHNECs. Methods: We identified patients diagnosed with PHNEC and analyzed their demographics, baseline laboratory data, tumor characteristics, treatment modalities and outcomes. Results: A total of 218 consecutive patients were identified with pathologically confirmed neuroendocrine carcinoma. Of these, 12 patients were diagnosed with PHNECs; the median age was 66.5 years (range, 37 to 80 years), and seven patients (58.3%) were male. Two patients who each had a single hepatic mass underwent curative surgical resection. One patient who was of inoperable status at the initial diagnosis because of multiple intrahepatic metastases showed a partial response after the ninth round of systemic chemotherapy and then underwent surgical resection. The median overall survival in the 12 patients was 16.5 months (range, 0.7 to 41.7 months). Three patients who underwent surgical treatment are alive without recurrence for 15.2 months, 18.0 months, and 36.9 months, respectively. Conclusions: Primary hepatic neuroendocrine carcinoma should be considered as a possible differential diagnosis in the management of hepatic tumors. The liver can be the primary origin of neuroendocrine tumors, and if the tumors are diagnosed as primary hepatic neuroendocrine tumors, surgical resection must be considered for curative treatment.     

Anorectal neuroendocrine carcinoma and small cell carcinoma. Report of two cases

INTRODUCTION: Anorectal neuroendocrine small cell carcinomas are rare and frequently difficult to treat. EXEGESIS: Two women presented with a fungating tumor located on the upper part of the anal canal. Histology displayed neuron-specific enolase and chromogranin A immunoreactive small cell tumors. A plasmatic neuron-specific enolase secretion was noticed in one case. Tumors were poorly reactive to chemotherapy and irradiation, less than in usual epidermoid anal canal cancer. Evolution was quickly leading to hepatic and pulmonary metastases in both cases. CONCLUSION: Anorectal neuroendocrine small cell carcinomas are rare but need to be individualized from epidermoid anal canal tumors owing to their poor prognosis with a frequent occurrence of hepatic and pulmonary metastasis.     

Prostatic metastasis of large cell neuroendocrine carcinoma of the lung

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive tumour with a poor prognosis. Lung cancer metastases to the prostate are also uncommon, and are usually found incidentally during autopsy. Most reported primary lung cancers with prostatic metastases are small cell carcinomas, and prostatic metastases from LCNEC of the lung have not been reported previously. This case report describes a 70-year-old man with LCNEC of the lung and metastases in the prostate, brain, bone, liver and lymph nodes.     

Surgical resection and adjuvant chemotherapy for small cell carcinoma

Poor long-term results following the surgical management of small cell carcinoma have contributed to the opinion that small cell carcinoma is a non-surgical disease; polychemotherapy is generally given preference. As nowadays adequate therapy (chemotherapy) achieves control of local tumor growth as well as of extended metastases, surgical resections should be discussed from a different viewpoint: "Does surgery profit from modern chemotherapy?" In our clinic, 1332 patients have been operated on for bronchogenic carcinoma from 1973 to 1983: 170 (12.8%) suffered from small cell carcinoma. The indications for surgery were either non-histologically classified tumors (e.g. peripheral coin lesions) or small cell carcinomas stage I, and only in rare cases for palliative reasons. Lobectomy, including bronchoplastic and arterioplastic resections (n = 108), was the most common procedure. The postoperative mortality was 15%, the average survival 341 days, the latter having improved significantly since 1979 when a postoperative polychemotherapy (ACO) was instigated. Recent results of surgical resection after primary chemotherapy are encouraging. Nevertheless, this new concept is reserved for the few cases of strictly limited disease and must be controlled by future studies.     

Neuroendocrine gastric carcinoma expressing somatostatin： A highly malignant, rare tumor

Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.