Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants

Eighty-one primary pulmonary neuroendocrine neoplasms were assessed by the classification of Gould and associates. The neuroendocrine features of these tumors were studied by a combination of conventional light microscopy, electron microscopy, and immunohistochemical staining for hormonal substances and neuron-specific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bronchial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only occasionally metastasize late in their course. Well-differentiated neuroendocrine carcinomas are relatively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called "large cell undifferentiated carcinoma." Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of "carcinoids" and their presumed variants.     

Carcinoid tumors of the lung. An analysis of 65 operated cases.

BACKGROUND: The aim of this study was to analyse two groups of patients operated for bronchopulmonary neuroendocrine neoplasms (bronchial carcinoid and well-differentiated neuroendocrine carcinoma) and to investigate their clinico-pathological data and long-term survival. METHODS: From January 1978 to June 1996, 65 patients with bronchial carcinoids underwent operation at our Institution. There were 33 males and 32 females, whose mean age was 49.8 years. Forty-four neoplasms (67.7%) were considered to be central. Histology revealed 54 typical bronchial carcinoids (83%) and 11 well-differentiated neuroendocrine carcinomas (17%). Surgical resection of tumor and complete lymph node dissection was performed in all cases. RESULTS: All patients entered follow-up: 5-year survival was 91% for patients with bronchial carcinoid and 49% for those with well-differentiated neuroendocrine carcinoma (p<0.05). Univariate analysis found that there was a significant decrease in survival also for peripheral location of the tumor, advanced pathologic stage and histologically positive lymph nodes. CONCLUSIONS: These results point out that carcinoid tumors are malignant neoplasms, so they require a complete and radical surgical resection. Most tumors are only locally invasive and show a low aggressive behaviour; therefore, when possible, it is recommended to attempt a limited resection. Frozen sections of bronchial margins and complete lymphadenectomy should be routinely performed. The same criteria should apply to well differentiated neuroendocrine carcinomas, though their behaviour is more aggressive.     

Neuroendocrine secretory protein-55 (NESP-55) expression discriminates pancreatic endocrine tumors and pheochromocytomas from gastrointestinal and pulmonary carcinoids

Neuroendocrine secretory protein-55 (NESP-55), the latest addition to the chromogranin family, is a product of a genomically imprinted gene transcribed exclusively from the maternal allele. Initial studies have shown it to have a less widespread distribution than that of chromogranin A in normal tissues. It has also been suggested that NESP-55 may be a marker of neuroendocrine tumors differentiating toward the adrenal chromaffin and pancreatic islet cells. Metastatic gastrointestinal and pulmonary carcinoids may occasionally be difficult to distinguish from pancreatic endocrine tumors (PETs) and pheochromocytomas on morphologic grounds alone. We studied neuroendocrine tumors from these sites to see if NESP-55 expression could reliably discriminate pulmonary and gastrointestinal carcinoids from neuroendocrine tumors arising in the pancreas or the adrenal medulla. Sixty-three neuroendocrine tumors positive for one or more immunohistochemical marker of neuroendocrine differentiation (chromogranin A, chromogranin B, synaptophysin, secretogranin II, neuron-specific enolase) were selected for the study and consisted of 34 typical carcinoids (15 pulmonary, 11 ileal, 4 gastric, and 4 rectal), 19 PETs, and 10 pheochromocytomas (4 sporadic, 3 MEN-2, 2 neurofibromatosis type 1, and 1 VHL). All cases were stained for NESP-55 after microwave antigen retrieval using a rabbit polyclonal antibody at a dilution of 1:1000. Sections of normal adrenal medulla were used as positive controls for NESP-55 staining. Negative controls consisted of omission of primary antibody and replacement with normal rabbit serum at an equivalent concentration. NESP-55 immunoreactivity was seen as brown finely granular cytoplasmic staining with prominent perinuclear accentuation. All gastric and ileal carcinoids studied were completely negative for NESP-55. One of four rectal and 1 of 15 pulmonary carcinoids showed focal positivity for it in less than 5% of tumor cells. In contrast, all 10 pheochromocytomas and 14 of 19 PETs showed strong immunohistochemical staining in a variable proportion of tumor cells. Diffuse positivity (>75% of tumor cells) was seen in 6 of 14 PETs and 8 of 10 pheochromocytomas. Our results indicate that, in contrast to the other granins, NESP-55 reactivity is restricted to endocrine tumors of the pancreas and the adrenal medulla. Immunohistochemical expression of NESP-55 may thus be useful in assigning a pancreatic or adrenal origin to metastatic endocrine tumors of unknown origin.     

Approach to the diagnosis of neuroendocrine lung neoplasms: variabilities and pitfalls

With the publication of the spectrum of neuroendocrine proliferations and neoplasms and the features and criteria for diagnosing neuroendocrine lung neoplasms, there is more agreement in making a specific pathologic diagnosis of a neuroendocrine lung neoplasm. However, problems exist, especially in diagnosing well-differentiated neuroendocrine carcinomas (atypical carcinoids), large-cell neuroendocrine carcinomas, and even some small-cell lung cancers. Some of this disagreement has to do with a pathologist's perception of sizes and shapes of cells. Nonneuroendocrine small-cell carcinomas exist and include small-cell squamous cell carcinoma, small cell adenocarcinoma, and basaloid carcinoma. Nonneuroendocrine lung cancers, especially large-cell undifferentiated carcinoma and poorly differentiated adenocarcinoma, not infrequently express neuroendocrine markers immunohistochemically.     

Thymic carcinoid associated with multiple endocrine neoplasia type 1

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy.     

Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine neoplasms include well-differentiated pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine carcinomas (NECs) with well-differentiated PanNETs accounting for most cases. Other pancreatic primaries and metastatic carcinomas from other sites can mimic pancreatic neuroendocrine neoplasms. Immunohistochemical studies can be used to aid in the differential diagnosis. However, no specific markers are available to differentiate PanNETs from NETs of other sites. Although NECs are uniformly deadly, PanNETs have variable prognosis. Morphology alone cannot predict the tumor behavior. Although some pathologic features are associated with an aggressive course, Ki67 is the only prognostic molecular marker routinely used in clinical practice.     

Well-differentiated neuroendocrine carcinomas: the spectrum of histologic subtypes and various clinical behaviors

The term "well-differentiated neuroendocrine carcinoma" was coined to describe a variety of demonstrably neuroendocrine tumors which were more aggressive (both with respect to their histologic appearance and their clinical course) than (typical) bronchial carcinoids but were also clearly distinguishable from small cell neuroendocrine carcinomas. This umbrella term encompasses a variety of tumors previously described by a variety of terms including "atypical" carcinoids, "malignant tumorlets," peripheral stage I small-cell carcinoma, as well as neoplasms described simply as "undifferentiated carcinoma" (prior to the recognition of their neuroendocrine properties). As such, this term is a broad term and is not simply synonymous with "atypical carcinoid." Over time, at least 3 subtypes have been identified based upon their histologic appearance and mitotic index, with correspondingly aggressive clinical courses.     

Carcinoids of lungs]

The analysis of the results of the examination and treatment of 29 patients with carcinoids of the lungs has been carried out for 1984-1995. Peripheral carcinoids were detected in 59% of cases, of the tumor in the main and lobar bronchi was revealed in 41% of cases. The analysis showed that there are no symptoms, pathognomonic for carcinoids of the lungs; carcinoid syndrome was not detected in any patient. The examination (roentgenography and CT of the lungs, bronchoscopy) has not provided any objective, differential diagnostic criteria for carcinoids, cancer and benign tumors of the lungs. Morphological examination of the removed tumors allowed all the carcinoids to be divided in two types: typical (benign neuroendocrine tumor) and atypical (well differentiated neuroendocrine carcinoma). The final differentiation is possible only after conduction of thorough histological, electron microscopy and immunohistochemical examination. The principal method of carcinoids treatment is surgical one. The optimal surgical procedure is pneumonectomy or lobectomy with lymphadenectomy. Atypical resection of the lung without lymphadenectomy in peripheral location of the tumor is justified only in early stages of the disease and in cases of morphological verification of benign character of neuroendocrine tumor. Late results were followed up in 27 patients. In the group of patients with atypical carcinoids in terms of 6 to 12 months 3 patients died from progressing of the main disease. There were neither lethal outcomes nor signs of relapse of the disease in the group of patients with typical carcinoid. The terms of follow up were from 1 year to 12 years.     

Small cell carcinoma of the major salivary glands: clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome

Small cell carcinomas arising in salivary glands, extremely rare high-grade malignant tumors, are subclassified into neuroendocrine and ductal types. The neuroendocrine type may be segregated further into Merkel cell and pulmonary varieties according to cytokeratin 20 immunoreactivity. Whether subclassification of this tumor group has any biologic or clinical significance is not known. We examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma of major salivary glands from a single institution and analyzed their clinicopathologic profiles, including immunohistochemical features and prognostic factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive immunostaining, often with a paranuclear dotlike pattern of reactivity. All tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined, and 6 tumors were also positive for neurofilament, with a paranuclear dotlike pattern. Postoperatively, 9 patients developed metastatic disease, and 10 patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By log-rank analysis, overall survival was reduced significantly for patients with a primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for neuroendocrine markers (P = 0.034). These results indicate that small cell carcinoma of major salivary glands is a highly aggressive tumor, although the prognosis may be better than for extrasalivary neoplasms. Our data also suggest that most salivary gland small cell carcinomas exhibit neuroendocrine differentiation. Immunohistochemical expression of cytokeratin 20 can be used to classify salivary small cell carcinomas into Merkel cell and pulmonary types and may have prognostic significance.     

直肠类癌23例临床病理分析

为探讨类癌病理学特点及临床表现．回顾性分析23例直肠类癌活检的病理学特点及临床资料。结果显示。23例直肠类癌位于肛门3～10cm．其中8例内镜下诊断为息肉，8例光镜下诊断为类癌．15例加做神经内分泌标记物诊断为类癌。结果表明，直肠类癌常位于黏膜下，体积小，临床易误诊为息肉。类癌的确诊依赖于常规病理与免疫组化技术，早期结肠镜检查并及时送检有利于提高类癌的确诊率。     

Simultaneous double thymic carcinoids: a rare initial manifestation of multiple endocrine neoplasia type 1

A 53-year-old man was referred to our hospital for treatment of two anterior mediastinal tumors. The anterior mediastinal tumors were resected by thymectomy under the probable diagnosis of double thymomas. The final pathological diagnosis was multiple thymic carcinoids. Although 20%–25% of patients with thymic carcinoid have a family history of multiple endocrine neoplasia type 1 (MEN-1), radiographic screening just after the operation did not detect any endocrine tumors. However, the patient had a urinary calculus 4 months 7 months after the operation. Endocrinological examination then revealed mild hypercalcemia, hypophosphatemia, hyperinsulinemia, and hyperprolactinemia. Radiologically, a parathyroid tumor and a pancreatic tumor were found. The patient was referred to a university hospital and a mutation of MEN-1 gene was detected. The diagnosis of MEN-1 was confirmed about 1 year after the operation.     

Ovarian mucinous carcinoids including some with a carcinomatous component: a report of 17 cases

Only rare primary mucinous (goblet cell) carcinoids of the ovary have been reported, and their clinicopathologic features have not been well delineated. The authors studied 17 examples from patients 14 to 74 years of age. The clinical presentations were similar to those of ovarian neoplasms in general. The tumors ranged from 0.8 to 30 cm in diameter. In six cases the tumor was in the wall of a mature cystic teratoma, appearing grossly as solid nodules or areas of thickening in four of them, six tumors were entirely solid, and five were solid associated with other types of cystic tumor. The tumors were divided into three groups on the basis of their microscopic features. Six neoplasms, designated "well differentiated," were composed of small glands, many of which floated in pools of mucin. The glands were lined by goblet cells and columnar cells, some of which were of neuroendocrine type. Three tumors, designated "atypical," were characterized by crowded glands, some of which were confluent, small islands with a cribriform pattern, and scattered microcystic glands. The glands were lined by cuboidal to columnar cells, some of them neuroendocrine, admixed with goblet cells. Eight tumors, designated "carcinoma arising in mucinous carcinoid," contained islands and larger nodules of tumor cells, or closely packed glands, as well as single cells, mainly of the signet ring cell type. Most of the cells were devoid of mucin and were severely atypical with marked mitotic activity. Necrosis was present in all eight tumors. Seven of the eight tumors with a carcinomatous component contained at least minor foci of well-differentiated mucinous carcinoid; the eighth contained only foci of atypical mucinous carcinoid. The neuroendocrine nature of a variable proportion of the cells in all three groups was demonstrated by staining for neuroendocrine markers. The mucinous nature of other cells was confirmed by mucicarmine or Alcian blue stains. The ovary contained an intrinsic component of trabecular and insular carcinoid, and of strumal carcinoid in one case each, an adjacent mature cystic teratoma in six cases, mucinous cystadenocarcinoma in three cases, and borderline mucinous cystic tumor, borderline Brenner tumor, and epidermoid cyst in one case each. Fifteen tumors were stage I, one was stage II, and one was stage III. The last two tumors had a carcinomatous component. Follow-up data were available for 15 patients; 12 were alive and free of tumor 2.3 to 14 years (average, 4.7 years) after the ovarian tumor was excised. One patient, whose tumor had a carcinomatous component, died 3 years postoperatively of unrelated causes. Two patients, both of whom had a carcinomatous component in their tumor, died 9 and 12 months postoperatively. Primary mucinous carcinoids must be distinguished from metastatic mucinous carcinoid tumors from the appendix or elsewhere. Features supporting an ovarian origin are the additional presence in the specimen of teratoma or an ovarian surface epithelial tumor, an absence of blood vessel or lymphatic space invasion, and confinement to a single ovary. Similar features help to distinguish mucinous carcinoids from Krukenberg tumors. Mucinous carcinoids should also be distinguished from strumal carcinoids, which can contain mucinous glands, and insular carcinoid tumors that arise rarely in the wall of a mucinous cystic neoplasm. Although the number of cases in this series is small, the follow-up data suggest that the degree of differentiation, particularly the presence of frank carcinoma, is an important prognostic factor.     

Carcinoid tumors of the thymus

Carcinoid tumors arising in the thymus are rare. Since Rosai and Higa in 1972 distinguished these neoplasms from thymomas, fewer than 100 cases have been reported in the world literature. In a 38-year review (1950 to 1988) of surgically treated thymic tumors at Henry Ford Hospital, only 7 cases of thymic carcinoids were identified. These 6 men and 1 woman ranged in age from 27 to 70 years (mean, 48 years) at diagnosis. Follow-up was available in all patients with the longest survival being 12 years in 2 patients, and the shortest, 1 year, in 1. Recurrences and/or metastases developed in 4 of 7 patients between 1 and 9 years after initial resection. Recurrences were treated by reexcision in addition to radiation treatment and chemotherapy in 3 patients and reexcision with radiation treatment alone in 1 patient. A review of the literature along with our experience suggests that thymic carcinoids have a biological behavior distinct from thymoma in terms of cell origin, associated syndromes, neoplastic behavior, and prognosis. An aggressive surgical approach with complete initial excision of the tumor and of subsequent recurrences, along with radiation and probably chemotherapy, is the best available treatment today.     

Renal neuroendocrine tumours: a clinicopathological study

OBJECTIVES: To report cases of primary neuroendocrine tumours (NETs) of the kidney, including carcinoid tumour, large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCC), which show a wide range of NE differentiation and biological behaviour, and are exceedingly rare. PATIENTS AND METHODS: The clinicopathological features of all nine renal NETs diagnosed during a 7-year period were reviewed. RESULTS: Six carcinoids, two SCC and one LCNEC were identified from 2780 kidney tumours. No patient had carcinoid syndrome or other NE symptoms. Three of six carcinoids and no SCC/LCNEC arose in horseshoe kidneys. The mean size of the six carcinoids and three SCC/LCNEC was 4.8 cm and 12.2 cm, respectively. No carcinoid had tumour necrosis or mitosis. By contrast, three SCC/LCNEC had extensive tumour necrosis and brisk mitosis. All renal NETs were positive for synaptophysin but were variably positive for chromogranin and CD56. Three of six carcinoid tumours were confined to the kidney, and four of five patients were disease-free at a mean (range) of 26 (6-74) months. One patient with nodal metastases has had no recurrence and another died with liver metastases. Three patients with SCC/LCNEC each presented with locally advanced disease and extensive lymphadenopathy; two of them died from distant metastasis or local tumour progression, and the third is currently alive with disease. CONCLUSIONS: Various NETs can occur in the kidney, but rarely. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. The diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical NE markers.     

Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms

Foxn1 and CD205 (DEC205) are novel thymic epithelial markers that are important for thymic organogenesis and the positive selection process for thymocytes, respectively. These markers were immunohistochemically applied to a total of 77 cases of thymic epithelial neoplasms comprised of 58 cases of thymomas, 17 cases of thymic carcinomas, and 2 cases of thymic neuroendocrine carcinomas. Foxn1 was diffusely expressed in nuclear staining in all cases of type B thymoma and all but 1 case of type A thymoma, whereas the expression was generally focal in thymic carcinoma (76%). The expression was identified in all cases of mixed AB thymoma, with the expression in type A component being more variable than the one in type B component. CD205 cytoplasmic expression in the form of coarse granular staining with membranous accentuation was strong and diffuse in all cases of type B thymoma (100%), and a majority of type A thymoma (89%), and focal with variable intensity in thymic carcinoma (59%). Mixed AB thymoma demonstrated diffuse expression in type B component (100%), and variable expression in type A component (94%). Neither Foxn1 nor CD205 was expressed in 2 cases of thymic neuroendocrine carcinoma. Foxn1 was focally expressed in 13% of cutaneous squamous cell carcinoma and completely negative in cutaneous basal cell carcinoma, whereas it was completely negative in squamous cell carcinoma from head and neck, esophagus and uterine cervix, and normal tissue and malignant neoplasms from all other organs other than thymus. CD205 was expressed in 4% of nonsmall cell carcinomas of lung, 27% of squamous cell carcinoma of head and neck, and 10% of squamous cell carcinoma of esophagus, but the staining pattern was different from that of thymic epithelial neoplasm and was characterized by rather homogeneous and amorphous quality without granularity or membranous reaction. CD205 was expressed in myeloid dendritic cells of various organs and tissues as well. Foxn1 is a sensitive and specific marker for thymoma and thymic carcinoma, and it appears to be superior to CD5 and CD117 for the diagnosis of thymic carcinoma. CD205 is a sensitive and specific marker for thymoma but its sensitivity to thymic carcinoma is lower than CD5 and CD117.     

Neuroendocrine differentiation in the glandular peripheral nerve sheath tumor. Pathologic distinction from the biphasic synovial sarcoma with glands

We studied eight glandular peripheral nerve sheath tumors and seven biphasic synovial sarcomas with glands with the objectives of (a) characterizing the nerve sheath tumors, especially with respect to a possible neuroendocrine differentiation, and (b) identifying features that could be used to distinguish between the two lesions. In a mainly immunohistochemical study, neuroendocrine differentiation of glandular cells was observed in five of eight (62.5%) nerve sheath tumors. The neuroendocrine cell markers found included chromogranin (five of eight cases), serotonin (four of seven cases), pancreatic polypeptide (two of five cases), and gastrin (two of six cases). These findings--together with histological, histochemical, and ultrastructural observations made in this and in other studies--point to a foregut type of intestinal differentiation for the glands in a majority of glandular peripheral nerve sheath tumors. Specific histological and immunohistochemical differences between the nerve sheath tumors and the synovial sarcomas were identified. The main histological differences were a sharp distinction between the spindle and glandular cells of the former but not the latter lesion, and the presence of goblet-type cells only in the glandular peripheral nerve sheath tumors. Major immunohistochemical differences included neuroendocrine differentiation and reactivity for S-100 protein and CEA (seen only or mainly in the nerve sheath tumors), and the reactivity of spindle cells of only the biphasic synovial sarcomas for epithelial membrane antigen.     

A Composite Adenoendocrine Carcinoma of the Stomach Arising from a Neuroendocrine Tumor

Gastric neuroendocrine tumors (carcinoids) are relatively uncommon neoplasms. Some 70 to 80% of these lesions occur in patients with autoimmune body gastritis. This disorder, however, is also a risk factor for the development of conventional gastric adenocarcinomas. We report a case of a patient with autoimmune body gastritis and a well-differentiated neuroendocrine tumor of the stomach, which was removed with endoscopic full-thickness resection in sano upon signs of invasive growth several years after its first diagnosis. Histological examination surprisingly showed a composite glandular-endocrine gastric carcinoma. We discuss the histopathological genesis of the tumor and provide evidence that endoscopic full-thickness resection might be an oncologically appropriate minimally invasive treatment for such gastric lesions.     

Neuroendocrine neoplasms of the lung. A clinicopathologic update

One hundred forty-six cases of pulmonary neuroendocrine tumors are assessed according to the classification of Gould and associates and are evaluated for their clinical presentation and subsequent clinical course. Bronchial carcinoids are characteristically found to be central tumors often occurring in comparatively young patients; surgical resection with minimal but clear margins is usually curative. The long-term prognosis is excellent in the majority of patients, although rarely regional nodal and distant metastases develop. Well-differentiated neuroendocrine carcinomas are most frequently peripheral tumors. In stage I and II disease, surgical resection alone is curative and patients with locally advanced tumors may have a prolonged disease-free interval. The overall prognosis is less favorable than that of bronchial carcinoids but considerably better than that of small cell neuroendocrine carcinomas, with which they are still at times confused. Intermediate-sized cell neuroendocrine carcinomas are often wrongly categorized as large cell undifferentiated carcinoma. They have a distinctly aggressive clinical course comparable with that of small cell neuroendocrine carcinoma and should be treated similarly. Small cell neuroendocrine carcinomas are aggressive, rapidly disseminating neoplasms. Even in clinical stage I tumors, patients must be considered to have disseminated metastases. The role of surgical therapy in these two latter tumor types is adjuvant to aggressive systemic chemotherapy.     

Primary Large Cell Neuroendocrine Carcinoma of the Parotid Gland. Report of a Rare Case

Primary neuroendocrine carcinomas of the salivary glands are very rare neoplasms that present light microscopic, ultrastructural, and immunohistochemical features of neuroendocrine differentiation. Twelve cases have been published in the English language literature. We describe the pathologic features of a case of primary large cell neuroendocrine carcinoma of the parotid gland in a 91-year old male and summarize the immunophenotype of previously reported LCNECs of the major salivary glands. It is concluded that primary LCNEC of the salivary glands presents as a high-grade undifferentiated carcinoma, whose diagnosis may be hindered by its rarity and non-specific light microscopic features. A high level of awareness, immunohistochemical staining for neuroendocrine markers synaptophysin and CD56, and a thorough diagnostic work-up in order to exclude metastasis from a primary neuroendocrine carcinoma will allow its diagnosis.     

Endoscopic treatment of gastric carcinoid. Report of a clinical case

We report on a case of a gastric carcinoid of the sporadic type successfully treated by endoscopic electroresection. From January 1998 to October 2002, 1523 gastroscopies were performed in the Palermo University General Emergency Surgery and Organ Transplant Unit. In a 59-year-old man with a history of dyspepsia, a sessile polypoid gastric lesion was observed in the gastric corpus. Laboratory data were normal. The lesion was successfully treated by electroresection. Histological evaluation revealed an 8-mm-diameter well-differentiated neuroendocrine polypoid tumour infiltrating the muscularis mucosa. According to Rindi et al.'s classification, the polyp was a carcinoid of the sporadic type. A two-year follow-up consisting in gastroscopy every 6 months and evaluation of tumour markers and CT scans once a year has so far shown no recurrence. Surgical treatment is the therapy of choice for gastric carcinoids, but endoscopic resection may be a successful alternative in cases of carcinoids measuring less than 1 cm and presenting multricentric growth. Moreover, endoscopy can also be used in patents at high surgical risk.