Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature.

Five cases of goblet cell carcinoid tumor of the appendix showed characteristic histologic features that justified classification of these lesions as mucinous variants of carcinoid tumor. The tumor has low-grade malignancy, and metastases are uncommon. Resemblance to mucinous adenocarcinoma of the appendix is striking, and the features that help to differentiate the two lesions are delineated.     

Goblet Cell Carcinoid of the Vermiform Appendix with Ovarian Metastasis Mimicking Mucinous Cystadenocarcinoma

We describe a case of goblet cell carcinoid of the vermiform appendix, which metastasized to the bilateral ovaries, uterus, vagina and peritoneum three years and four months after appendectomy. The appendiceal tumor showed transmural infiltration of carcinoembryonic antigen-positive goblet cell-type tumor cells, intermingled with a small number of argyrophilic cells immunoreactive for serotonin and chromogranin A. The presence of neurosecretory-type granules was confirmed ultrastructurally in some mucin negative tumor cells. The pattern of proliferation was typical of carcinoid tumor originating from the lowermost part of the mucosa, and showed lymphatic permeation. The metastatic lesions in the pelvic organs showed either diffuse infiltration of goblet cell-type tumor cells or mucinous cystadenocarcinoma like features, the latter being evident in the right ovary. No neuroendocrine component was identified in the metastatic deposits. The kinship of appendiceal goblet cell carcinoid to adenocarcinoma is discussed. Acta Pathol Jpn 41: 455–460,1991.     

Goblet cell carcinoid of the vermiform appendix with ovarian metastasis mimicking mucinous cystadenocarcinoma

We describe a case of goblet cell carcinoid of the vermiform appendix, which metastasized to the bilateral ovaries, uterus, vagina and peritoneum three years and four months after appendectomy. The appendiceal tumor showed transmural infiltration of carcinoembryonic antigen-positive goblet cell-type tumor cells, intermingled with a small number of argyrophilic cells immunoreactive for serotonin and chromogranin A. The presence of neurosecretory-type granules was confirmed ultrastructurally in some mucin-negative tumor cells. The pattern of proliferation was typical of carcinoid tumor originating from the lower-most part of the mucosa, and showed lymphatic permeation. The metastatic lesions in the pelvic organs showed either diffuse infiltration of goblet cell-type tumor cells or mucinous cystadenocarcinoma-like features, the latter being evident in the right ovary. No neuroendocrine component was identified in the metastatic deposits. The kinship of appendiceal goblet cell carcinoid to adenocarcinoma is discussed.     

Combined goblet cell carcinoid and mucinous cystadenoma of the appendix.

Two cases of combined goblet cell carcinoid and mucinous cystadenoma occurring in the appendix are reported. The histogenesis of the goblet cell carcinoid remains one of its most controversial aspects and the occurrence of both of these relatively uncommon tumours in the same organ may lend support to the unitary stem cell hypothesis on the origin of this tumour. Alternatively, this occurrence may represent an example of the adenoma/carcinoma sequence.     

Revisiting the necessity for routine appendectomies in mucinous neoplasms of the ovary: An evaluation of 460 mucinous ovarian tumors

Appendectomies are not uncommonly performed following an intraoperative diagnosis of a mucinous ovarian neoplasm, although the evidentiary basis for the practice is relatively limited. The current study is a contemporary re-examination of the issue, based on an analysis of a large single institutional cohort. We assessed whether there are any composite of factors that may be associated with the finding of significant disease in the appendix in this setting following intraoperative consultation (IOC) diagnosis of a mucinous neoplasm on an ovary-based mass. Records for 460 consecutive patients whose ovarian tumors were classified as “mucinous” on IOC (n = 246) and/or permanents (n = 214) were reviewed. The distribution of IOC diagnoses on the 246 tumors were as follows: cystadenoma (114), borderline (55), carcinoma (21), mucinous neoplasm or tumor without definitive classification (53), and probable metastases (3). Appendectomies were performed on 82 (33%) of the 246 cases. In 30 (36%) of these 82 cases, the appendix was grossly normal, the ovarian tumor was unilateral, and there was no intraabdominal/peritoneal disease. Microscopic examination of the appendices in these 30 cases showed no mucinous neoplasms therein, but one case had a grossly inapparent, 4 mm well-differentiated carcinoid. In contrast, among the remaining 52 cases (i.e. those with at least one of the “key abnormal features”: intra-abddominal/peritoneal disease and/or appendiceal gross abnormality and/or ovarian tumor bilaterality), 12 neoplasms (23%) were microscopically identified in the appendix (4 adenocarcinomas; 7 LAMN; 1 carcinoid) [p = 0.0256]. Of these 12, a grossly abnormal appendix, intraabdominal/peritoneal disease, and ovarian tumor bilaterality was the sole key abnormal feature in 10, 8 and 4 cases respectively, meaning that requiring that any one feature be present to justify the appendectomy would have missed 17%, 33% and 67% of cases respectively. Only 33% (3/12) cases had all 3 features. Our findings support the emerging body of work that indicates that appendectomies should not be routinely performed during the primary surgery for suspected or confirmed mucinous tumors that involve the ovary, unless there is a specific indication. In our cohort, all identified mucinous appendiceal neoplasms were associated with at least one key abnormal feature (gross abnormalities of the appendix, intraabdominal/peritoneal disease, ovarian tumor bilaterality), which suggests that only in patients that meet these criteria would appendectomies most likely be beneficial.     

Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms

The varied aspects of spread of appendiceal neoplasms are reviewed with emphasis on the often clinically dramatic phenomenon known as pseudomyxoma peritonei, a term mostly used to describe grossly evident mucin within the peritoneal cavity. The majority of cases of pseudomyxoma peritonei result from tumors primary in the appendix, which are usually low-grade. On microscopic examination pseudomyxoma peritonei is typically characterized by large aggregates of mucin which may be relatively acellular or cellular containing strips of mucinous epithelium, mucinous epithelium encircling glands and cysts, or aggregates of mucinous epithelium lying within mucin pools. High-grade adenocarcinoma of the appendix may spread to the omentum and peritoneal surfaces without grossly striking mucin deposition and resemble spread of other high-grade gastrointestinal adenocarcinomas. In many cases of pseudomyxoma peritonei in females there is involvement of one, or more often, both ovaries. The size of the ovarian neoplasms characteristically dwarfs the often relatively unremarkable appearing appendix in these cases. The ovaries are typically multilocular, although one locule may dominate, and in cases in which the primary is a low-grade appendiceal mucinous neoplasm often have a "jelly-like" consistency. In cases of spread of frank adenocarcinomas the ovarian metastases typically have a more solid, albeit still somewhat gelatinous consistency. Microscopic examination of the ovaries typically shows surface involvement, a characteristic of spread to the ovaries in general, and the glands and cysts that replace most or all of the parenchyma are typically lined by tall mucin-rich cells with, in many cases, relatively bland microscopic features. In cases of frank adenocarcinoma, the tumors may mimic closely a primary mucinous adenocarcinoma of the ovary. Spread to the ovaries may also be seen in cases of frank intestinal-type adenocarcinoma primary in the appendix and the uncommon signet ring cell carcinoma of the appendix, the latter being one cause of the Krukenberg tumor. Occasional cases are reported in the literature of ovarian spread of goblet cell carcinoid tumor of the appendix, but in our opinion most of the primary tumors in those cases are better classified as adenocarcinomas, usually dominantly of signet-ring cell type, albeit sometimes with focal neuroendocrine differentiation. Other interesting aspects of spread of appendiceal neoplasms include to the lining of the uterus and the fallopian tube. In yet other cases the tumors may present clinically as incidentally discovered mucinous aggregates within hernia sac specimens or as a scrotal mass.     

Mucinous carcinoid tumor of the appendix presenting as bilateral ovarian tumors

Mucinous carcinoid tumor of the vermiform appendix, an uncommon variant of appendiceal carcinoid, may present clinically with ovarian metastases. We studied a tumor by immunohistochemistry and electron microscopy and reviewed eight similar cases from the literature. The primary and metastatic tumors in our case were composed of mucin-producing cells and small argyrophilic cells arranged in cords and acini. Tumor cells in both primary and metastatic sites exhibited identical patterns of immunoreactivity for epithelial antigens (epithelial membrane antigen, carcinoembryonic antigen) and neuroendocrine antigens (serotonin, vasoactive intestinal polypeptide, adrenocorticotropic hormone). Ultrastructurally, the cells contained either mucin vacuoles or dense-core neurosecretory granules; rare individual cells contained both types of inclusions. When bilateral solid mucinous ovarian tumors are discovered at laparotomy, diagnostic appendectomy is indicated if no obvious extraovarian primary tumor can be found.     

Subepithelial neuroendocrine cells and carcinoid tumours of the human small intestine and appendix. A comparative immunohistochemical study with regard to serotonin, neuron-specific enolase and S-100 protein reactivity

A comparative immunocytochemical study was performed of subepithelial neuroendocrine cells of the human small intestine and appendix and carcinoid tumours of these sites, using a monoclonal antibody to serotonin and polyclonal antisera against neuron-specific enolase (NSE) and S-100 protein. Subepithelial neuroendocrine cells were easily identified in the lamina propria of the appendix. These cells, which sometimes occurred in aggregates, displayed serotonin and NSE immunoreactivity and were surrounded by S-100 protein immunoreactive cells, presumably of Schwann cell origin. In the appendix scattered cells with corresponding morphological features and immunoreactivity were also observed deep in the submucosa. In addition, subepithelial neuroendocrine cells were sparsely present in the lamina propria of the small intestine, occurring only as single cells in the deeper part of the mucosa below or between the epithelial crypts. Most appendiceal carcinoid tumours (11 of 12 examined cases) were biphasic and consisted of neuroendocrine tumour cells with intermingled S-100 protein immunoreactive cells (Schwann cells) with long cytoplasmic extensions. However, small intestinal (11 cases) and caecal (10 cases) carcinoids lacked S-100 protein immunoreactive cells as an integral component. The results indicate that the appendiceal carcinoids are mostly closely related structurally to the subepithelial neuroendocrine and Schwann cell aggregates of the lamina propria and are thus presumed to be histogenetically related to this cell system, while the histogenesis of small-intestinal and caecal carcinoids remains less clear.     

Goblet cell carcinoid of the appendix: a specific type of carcinoma

AIMS: Goblet cell carcinoid is a poorly understood tumour of the appendix. The aim of this study was to determine whether it should be regarded as a separate entity or as a variant of classical carcinoid. METHODS AND RESULTS: The immunohistochemical expression pattern of 21 markers and the mutation status of KRas codon 12 were determined in 16 goblet cell carcinoids and compared with 14 classical carcinoids, 19 colonic adenocarcinomas and 10 appendiceal mucinous cystadeno (carcino)mas. The results were subjected to a stepwise linear discriminant analysis. Goblet cell carcinoids were significantly different from the control groups. The most important markers for discriminating between the groups were CEA (classical carcinoid versus all others), KRas mutation (present in all mucinous cystadeno (carcino)mas), beta-catenin (goblet cell carcinoid versus left sided colonic adenocarcinoma) and chromogranin (goblet cell carcinoid versus right sided colonic adenocarcinoma). Expression of Math1 and HD5 was similar in goblet cell carcinoid and colonic adenocarcinoma but absent in classical carcinoid. CONCLUSION: The results suggest that goblet cell carcinoids should be regarded as a separate entity. The formerly used term 'crypt cell carcinoma' may be more appropriate because it reflects the more aggressive clinical behaviour of these tumours as well as their greater similarity to adenocarcinomas rather than to carcinoids.     

Goblet cell carcinoids and related tumors of the vermiform appendix

Appendiceal carcinoids with glandular differentiation pose difficulties in classification and prediction of clinical behavior. Sixty-four such cases were divided into three histologic groups on the basis of routine and immunohistochemical stains: (1) Tubular carcinoids were small and confined to the appendix, had small amounts of intraluminal mucin with few or no goblet cells, were nonargentaffin, lacked serotonin, and were diffusely positive for glucagon. All ten with follow-up (mean, 17 months) were without metastasis. (2) Goblet cell carcinoids were confined to the appendix and mesoappendix, circumferentially surrounded the appendiceal lumen, and were often not suspected grossly. Histologically, they were often mixed with small crypt-like glands and were serotonin positive. All 22 with follow-up (mean, 19 months) were without metastasis whether or not right hemicolectomy was performed. (3) Mixed carcinoid-adenocarcinomas showed spread into the cecum or adjacent viscera at the time of diagnosis and had a large carcinomatous pattern with areas of mucinous, signet-ring, or single-file structure, in addition to goblet cell or insular carcinoid. All patients had right hemicolectomies, and all but two with follow-up died of the disease (mean, 16 months). Although a histologic spectrum exists among carcinoid tumors and certain adenocarcinomas of the appendix, it is possible to delineate three biologically distinct groups. Surgical margins should be taken of all appendices because these tumors often do not form discrete masses.     

Development of dysplastic mucinous epithelium from endometriosis of the appendix

AIM: We report an unusual case of mucinous metaplasia and epithelial dysplasia occurring in endometriotic epithelium in the appendix. METHODS AND RESULTS: A 39-year-old woman developed an appendiceal endometriosis in which the endometrial glands displayed extensive areas consisting of mucinous epithelium and Paneth cells. Focally the mucinous epithelium showed low-grade epithelial dysplasia. These changes occurred in portions of the endometriotic tissue closest to the appendiceal lumen. Both the intestinal and endometrial epithelial components were surrounded by typical endometrial-type stroma showing positive reactivity for oestrogen receptor. CONCLUSIONS: Formation of the mucinous epithelium most likely represents a metaplastic process of the endometrial epithelium rather than a result of a simple 'collision' of the appendiceal and endometrial epithelium. Further support for this being a metaplastic process was the presence of glandular structures containing a mixture of mucinous cells, goblet cells, Paneth cells, ciliated and nonciliated endometrial cells, and ciliated and nonciliated mucinous cells, all showing the same positive reactivity for oestrogen receptor. The disposition of mucinous epithelium in the foci of endometriosis in this case suggests that the appendiceal mucosa or extracellular mucin may play a role as an inducer of mucinous cell metaplasia in endometriotic epithelium.     

Mucinous epithelial cysts of the spleen associated with pseudomyxoma peritonei

AIMS: We report two rare cases of neoplastic pseudomyxoma peritonei associated with splenic mucinous epithelial cysts and review previously reported cases of splenic mucinous lesions in order to investigate the extent and implications of such an association. METHODS AND RESULTS: The majority of mucinous lesions of the spleen appear to be associated with pseudomyxoma peritonei. The clinicopathological profile of these cases conforms to that of neoplastic pseudomyxoma peritonei, showing a similar age of onset, outcome and histological features. Most of the cases were associated with a confirmed or suspected appendiceal primary. The immunophenotype (cytokeratin 7 negative; cytokeratin 20 and CEA positive) of the lesions of both our cases, including those in the ovary, was suggestive of a gastrointestinal origin. CONCLUSIONS: Splenomegaly due to cystic intrasplenic mucinous epithelial lesions may occasionally be the presenting feature of pseudomyxoma peritonei or herald tumour recurrence. Mucinous epithelial cysts of the spleen may also precede the development of pseudomyxoma peritonei. All cases of pseudomyxoma peritonei should be investigated for splenic involvement and, conversely, a primary mucinous neoplasm sought elsewhere in the abdomen in all cases of splenic mucinous cysts.     

The demonstration of a subset of carcinoid tumours of the appendix by in situ hybridization using synthetic probes to proglucagon mRNA.

Previous studies using immunohistochemistry have shown variable hormone production by carcinoid tumours of the appendix. In order to confirm the existence of a specific subset of these tumours, in situ hybridization using synthetic oligonucleotide probes to detect pre-proglucagon and pre-proinsulin mRNA was performed in formalin-fixed, paraffin-embedded material from eight tubular carcinoids, 12 insulin carcinoids, and two mucinous carcinoids. The results were correlated with standard silver and mucin stains. All tubular carcinoids but none of the insular or mucinous carcinoids contained proglucagon mRNA. Proinsulin mRNA was not detected in any of the tumours. Tubular carcinoids of the appendix constitute a definable subset of appendiceal carcinoids which have a similar distribution and prognosis to typical insular carcinoids and can be diagnosed on haematoxylin and eosin-stained sections confirmed by routine special stains. The main need for recognition is to avoid confusion with mucinous carcinoids, which have a worse prognosis and may require more aggressive treatment.     

以阑尾炎起病的阑尾上皮性肿瘤15例临床病理分析

目的:探讨以阑尾炎起病的阑尾上皮性肿瘤的临床病理学特征.方法:对15例以阑尾炎起病的阑尾上皮性肿瘤的临床病理资料进行回顾性分析.结果:15例以阑尾炎起病的阑尾上皮性肿瘤中,6例为低级别阑尾黏液性肿瘤(low-grade appendiceal mucinous neoplasm,LAMN),其余9例为前驱病变,包括8例锯齿状病变及1例绒毛状-管状腺瘤,其中锯齿状病变为6例无蒂锯齿状腺瘤/息肉(sessile serrated adenoma/polyp,SSA/P)及2例传统型锯齿状腺瘤(traditional serrated adenoma,TSA).14例以"急性阑尾炎"起病,1例以"慢性阑尾炎"起病.SSA/P镜下见锯齿状结构、隐窝扩张呈L或倒T形;TSA见显著的锯齿状轮廓和异位隐窝,具有细胞异型性;锯齿状病变的黏膜肌层完整.LAMN内衬轻度异性的黏液性上皮,管壁纤维化或破裂,管壁内及浆膜见无细胞性黏液池.9例获得随访包括5例前驱病变及4例LAMN,随访时间1.0~81.5个月,患者均无病生存.结论:阑尾锯齿状病变及LAMN均可因急性阑尾炎起病,锯齿状病变大多数为镜下偶然发现.外科医生应提高对这些病变的认识,以避免医源性穿孔导致的腹膜假黏液瘤.病理医生应将该类阑尾病变标本全部取材以便于鉴别诊断,报告阑尾切缘情况.     

Composite glandular-endocrine cell carcinoma of the stomach. Report of two cases with goblet cell carcinoid component

Composite glandular-endocrine cell carcinoma (CGECC) is recognized as a special type of gastric tumor composed of ordinary adenocarcinoma and neuroendocrine tumors. Goblet cell carcinoid (GCC) is a well-established type of appendiceal carcinoid, but the GCC component has not been well delineated in CGECC of the stomach. We report on two gastric CGECCs with a GCC component, analyzing the histologic components by immunohistochemistry. On initial biopsy, both cases were diagnosed as signet-ring cell carcinoma. However, the resected tumors consisted of three components: signet-ring cell carcinoma, GCC, and glandular adenocarcinoma. Although some signet-ring carcinoma cells and goblet carcinoid cells were indistinguishable by hematoxylin and eosin staining, E-cadherin immunostaining disclosed a definitive difference regarding the staining pattern in these cells. Both patients are well, with no recurrent tumor for about 10 years of follow-up. CGECC with a GCC component may have been confused with conventional adenocarcinoma with signet-ring cells. In cases of advanced signet-ring cell carcinoma with good prognosis, the possibility of such CGECC has to be considered.     

Non-carcinoid epithelial tumours of the appendix--a proposed classification

Examination of 33 cases of non-carcinoid epithelial tumours of the appendix and a review of the previous literature has led us to propose a new classification of these lesions. It is based on nomenclature currently used for similar mucosal proliferations in the colon, facilitating communication between pathologists and clinicians with respect to their nature and possible behaviour. The use of the term "mucocele" to describe any lesion in which there is mucinous distension of the appendiceal lumen, irrespective of the type of underlying mucosal pathology, is now largely discredited. Yet, although a resemblance of some appendiceal lesions to similar lesions in the colon has been recognized, current terminology is still confused by the use of "cystadenoma". We have been able to place all of the known non-carcinoid appendiceal mucosal tumours into 4 main diagnostic categories, these being--adenoma, hyperplasia, mixed adenoma/hyperplasia and adenocarcinoma, and propose these terms as the basis for a new classification.     

Benign epithelial neoplasms of the appendix: classification and clinical associations

The nomenclature of non-carcinoid epithelial proliferations of the appendix is confused and many of the terms used have no histogenetic basis. A classification based on the well-established diagnostic categories of colonic epithelial polyps has been proposed recently. We have applied this classification to 42 benign epithelial lesions of the appendix in order to determine its suitability for routine diagnostic use, and in order to determine the prognosis of patients with these lesions. All lesions could be classified as either hyperplastic, adenomatous, mixed hyperplastic/adenomatous or dilated appendices. Six cases were associated with a synchronous carcinoma of the colon with all types of appendiceal histology being represented. Follow-up of the remainder of the patients revealed two subsequent colonic carcinomas, at 3 and 6 years post-appendicectomy respectively. In both of these patients, the appendix had shown adenomatous epithelium. We suggest that adenomas of the appendix may have a similar prognostic significance to adenomas elsewhere in the large bowel.     

Primary thymic epithelial tumours of the pleura mimicking malignant mesothelioma

AIMS: To illustrate the macroscopic, light microscopic and immunophenotypic similarities that exist between primary pleural thymic epithelial tumours and diffuse malignant mesothelioma. To investigate the expression of the mesothelial markers, cytokeratin (CK) 5/6, calretinin and thrombomodulin in a series of mediastinal thymic epithelial tumours. METHODS AND RESULTS: Over a 10-year period, 64 diffuse pleural tumours of non-mesothelial histogenesis were identified in the files of referrals to the South Wales regional thoracic centre (Llandough Hospital, Cardiff). Of these, five pleural tumours were diagnosed as primary pleural thymic epithelial neoplasms. From the files of the Mesopath group, Caen, three additional cases of thymic epithelial tumours with pleural involvement were identified. The study group comprised eight cases (four males, four females) with median age at presentation of 56 years (range 19-75 years). In one case there was a history of asbestos exposure. Macroscopically, seven tumours formed diffuse pleural masses. No mediastinal abnormality or intraparenchymal lesions were seen in five cases. By light microscopy, seven thymic epithelial neoplasms showed a lobulated architecture, one appeared extensively cystic. The tumours were of varied morphological subtypes: one medullary (WHO Type A), two mixed (WHO Type AB), three predominantly cortical (WHO Type B1) and two cortical (WHO Type B1). The subtypes morphologically mimicked sarcomatoid, biphasic, lymphohistiocytoid variant and epithelioid mesothelioma. The pleural thymic epithelial tumours showed immunoreactivity with broad spectrum cytokeratin AE1/AE3 (8/8; 100%), CK5/6 (8/8; 100%), and 1/8 (13%) expressed thrombomodulin. Calretinin showed variable nuclear and cytoplasmic expression in all cases, but equivocally in the thymic epithelial cell component. In 7/8 (88%) the thymic epithelial cells exhibited focal aberrant expression of CD20. Epithelial membrane antigen (EMA) showed focal expression in the perivascular and organoid areas in 6/8 (75%) cases. Carcinoembryonic antigen (CEA) and CD34 were uniformly negative. In 4/8 (50%) cases the lymphoid cell component was of immature phenotype expressing CD99, terminal deoxynucleotidyl transferase (TdT) and lymphoid precursors had a high proliferation fraction with Ki67. In the series of 20 primary mediastinal thymic epithelial tumours tested, mesothelial marker expression revealed CK5/6 (20/20), thrombomodulin (3/20; 15%) and calretinin (0/20; 0%). Varying amounts of calretinin-positive stromal cells were present. CONCLUSION: Primary pleural thymic epithelial tumours are rare but may mimic malignant mesothelioma by forming diffuse serosal-based masses. In addition, both tumours may show morphological diversity (with epithelial, spindled and mixed components present). An awareness that thymic epithelial tumours may variably express the mesothelial markers CK5/6, calretinin and thrombomodulin prevents misdiagnosis. In the distinction from malignant mesothelioma a lobulated architecture and organoid features favour a thymic epithelial neoplasm. The presence of aberrant CD20 expression in a cytokeratin-positive epithelial neoplasm and/or the presence of an immature lymphoid population (by demonstration of CD1a, CD2, CD99 and TdT) indicates a thymic epithelial neoplasm. In contrast, nuclear calretinin expression favours malignant mesothelioma.     

Neuroendocrine tumors of the appendix

The vast majority of neuroendocrine neoplasms of the appendix are carcinoid tumors. Most are of enterochromaffin (EC) cell type, although rare examples are of L cell type. EC cell carcinoids of the appendix differ from those encountered elsewhere in the gastrointestinal system. For example, they are remarkably common given the small size of the appendix, are usually benign, occur in younger patients, and typically contain sustentacular cells that express S-100. Origin from subepithelial neuroendocrine cells could explain these characteristics. It has also been suggested that most appendiceal carcinoids are hyperplastic rather than neoplastic, although this hypothesis requires further study. Nevertheless, truly neoplastic EC cell carcinoids of the appendix undoubtedly occur, and those greater than 2 cm in diameter have a significant risk of producing distant metastases. Carcinoid syndrome is a very rare presentation. Tubular carcinoids are unusual benign neoplasms; it has been proposed that they represent L cell carcinoids with a predominant tubular pattern of growth. Goblet cell carcinoids tend not to produce a grossly visible tumor mass but diffusely infiltrate the wall. They typically exhibit tight clusters of goblet cells, usually with scattered neuroendocrine cells and sometimes with Paneth cells, sometimes surrounding a small lumen. They may behave as a low-grade malignancy. The distinction between goblet cell carcinoid and other types of tumor is of great importance because of the implications for treatment and prognosis. Frank adenocarcinoma can arise from goblet cell carcinoids, and tumors with both components are classified as mixed goblet cell carcinoid-adenocarcinoma. The carcinoma component of the latter determines their prognosis, which would be worse than for a goblet cell carcinoid alone.     

Expression and mutational analysis of c-kit in ovarian surface epithelial tumors

Coexpression of Kit ligand and c-kit has been reported in some gynecologic tumors. To determine whether imatinib mesylate is useful in ovarian epithelial tumors, we performed immunohistochemical and mutational analysis. The cases consisted of 33 cases, which included 13 serous cystadenocarcinomas, 1 borderline serous tumor, 8 mucinous cystadenocarcinomas, 6 borderline mucinous tumors and 5 clear cell carcinomas. Five cases of serous cystadenoma and 5 cases of mucinous cystadenoma were also included. In the immunohistochemical study, 3 cases (3/6, 50%) of borderline mucinous cystic tumor and two cases (2/8, 25%) of mucinous cystadenocarcinoma show positive staining for KIT protein. Only one case (1/13, 7.7%) of serous cystadenocarcinoma had positive staining. On mutational analysis, no mutation was identified at exon 11. However, two cases of borderline mucinous tumors and one case of mucinous cystadenocarcinoma had mutations at exon 17. In these cases, the immunohistochemistry also shows focal positive staining at epithelial component. Although, KIT protein expression showed higher incidence in mucinous tumors than serous tumors, they lack KIT-activating mutations in exon 11. Thus, ovarian surface epithelial tumors are unlikely to respond to imatinib mesylate.