Schwannomas in the colon and rectum: a clinicopathologic and immunohistochemical study of 20 cases.

Schwannomas of the colon and rectum are uncommon and incompletely characterized tumors, and only a small number of cases have been reported. This study was undertaken to determine the clinicopathologic profile of such tumors. A total of 20 colorectal schwannomas were identified and analyzed in a review of 600 mesenchymal tumors of the colon and rectum from the files of the Armed Forces Institute of Pathology. The schwannomas occurred equally in men (n = 9) and women (n = 11) in a wide age range (18-87 years; median age 65 years). The most common location was cecum (n = 7), followed by sigmoid and rectosigmoid (n = 6), transverse colon (n = 3), descending colon (n = 2), and rectum (n = 1); the location of one tumor had not been specified. The tumors commonly presented as polypoid intraluminal lesions, often with mucosal ulceration. Rectal bleeding, colonic obstruction, and abdominal pain were the most common presenting symptoms. The most common histologic variant (n = 15) was a spindle cell schwannoma with a trabecular pattern and vague or no Verocay bodies. These tumors ranged from 0.5 to 5.5 cm in diameter. A lymphoid cuff with germinal centers typically surrounded these tumors and focal nuclear atypia was often present, but mitotic activity never exceeded 5 per 50 HPF. All four epithelioid schwannomas occurred in the descending colon or sigmoid, three of them as small submucosal tumors. There was one plexiform schwannoma in the sigmoid composed of multiple nodules of prominently palisading schwann cells similar to those seen in conventional soft tissue schwannomas. All tumors studied were strongly positive for S-100 protein and also for low affinity nerve growth factor receptor (p75), collagen IV, and GFAP. Three tumors had CD34-positive cells, but all were negative for CD117 (KIT), neurofilament proteins, smooth muscle actin, and desmin. The percentage of MIB-1-positive cells was usually less than 1% and never higher than 3%. Colorectal schwannomas behaved in a benign fashion with no evidence of aggressive behavior or connection with neurofibromatosis 1 or 2, based on follow-up information on 18 patients.

MIC2 detection in tumors of bone and adjacent soft tissues.

The diagnosis of Ewing's sarcoma has been based classically in large part on the exclusion of other similar small round-cell tumors by light microscopic and histochemical criteria. This study was undertaken to explore the use of a recently developed immunohistochemical stain directed against the glycoprotein p30/32MIC2 antigen (the gene product of MIC2), as a diagnostic tool and as a probe for the examination of potential interrelationships among the putative members of the family of peripheral primitive neuroectodermal tumors. Fifty-six small round-cell tumors of bone were selected for study from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital; all tissues had been formalin fixed and paraffin embedded. Nine of 10 Ewing's sarcomas were MIC2 positive, as were 2 of 3 atypical Ewing's sarcomas (small round-cell tumors that diverged from the classic pattern of Ewing's sarcoma by exhibiting a greater degree of cytologic atypia and pleomorphism), and 7 of 8 Askin tumors of the thoracopulmonary region. Ten of 11 mesenchymal chondrosarcomas, 1 primitive neuroectodermal tumor of bone, 10 small cell osteosarcomas, 10 malignant lymphomas, and 3 sarcomas of bone (not additionally subclassified) were negative. The finding of MIC2 positivity in the majority of Ewing's sarcomas and Askin tumors provides additional support for earlier proposals (based on a shared cytogenetic abnormality, among other criteria) that these lesions be considered members of the same family, the peripheral primitive neuroectodermal tumors. The present study, drawing on archival and current case material (including decalcified and undecalcified specimens), indicates that neither the specimen age nor the application of any of a variety of decalcification solutions appears to adversely influence MIC2 staining of paraffin-embedded tissues. This suggests that this antibody has use in retrospective and prospective studies. The rare occurrence of false negative (in the case of Ewing's sarcoma) and positive results in tumors other than peripheral primitive neuroectodermal tumors (as in 1 of the mesenchymal chondrosarcomas) suggests that MIC2 staining should not be relied on as the sole criterion for identification or exclusion of Ewing's sarcomas and related tumors.

Ganglioneuromas of the gastrointestinal tract. Relation to Von Recklinghausen disease and other multiple tumor syndromes.

We studied 43 patients with ganglioneuromas of the gastrointestinal tract accessioned at the Armed Forces Institute of Pathology (AFIP) from 1940 to 1990 in order to determine their relation to von Recklinghausen's disease and other multiple tumor syndromes. They fell into three groups: polypoid ganglioneuroma (28 patients); ganglioneuromatous polyposis (7 patients); and diffuse ganglioneuromatosis (8 patients). Follow-up (1-24 years, average 8 years) for 16 of 28 patients with polypoid ganglioneuroma showed that none of these patients developed von Recklinghausen's disease or evidence or multiple tumor syndromes. Three of seven patients with ganglioneuromatous polyposis were alive and well but were reported to have multiple cutaneous lipomas and one reported a family history of multiple intestinal polyps. For seven of eight patients, diffuse ganglioneuromatosis was associated with other tumors, namely multiple endocrine neoplasia type IIb, multiple ganglioneuromas and neurofibromas limited to the gastrointestinal tract, von Recklinghausen's disease and neurogenic sarcoma. We conclude that the solitary polypoid ganglioneuroma of the gastrointestinal tract is not associated with the subsequent development of von Recklinghausen's disease or multiple endocrine neoplasia. All three forms of gastrointestinal ganglioneuromatous disease appear to be largely centered in the colon and rectum, unlike neurofibromas and neurofibromatosis, which, in our experience, occur more commonly in the small intestine and stomach.

Inflammatory fibroid polyps of the gastrointestinal tract: radiologic evaluation.

Inflammatory fibroid polyps (IFPs) are uncommon lesions of the gastrointestinal tract. Only scattered case reports have appeared in the radiology literature. The authors reviewed the cases of 33 patients (20 women and 13 men; average age, 45 years) to determine if these polyps had any distinctive diagnostic radiologic features. The IFPs were located in the stomach (n = 16), small bowel (n = 13), and colon (n = 4). The lesions originated in the submucosa and were composed of fibroblasts, inflammatory cells, and a network of blood vessels. Gastric IFPs were most often located in the antrum and were usually ulcerated. Most of the patients presented with clinical evidence of gastrointestinal blood loss. Small bowel polyps were usually located in the ileum, and patients were typically older women with intestinal obstruction due to intussusception. Most of the lesions appeared as large, intramural masses at radiologic examination. Some of the lesions were pedunculated, and all were solitary. There were no distinctive features to differentiate IFPs from other mural or intraluminal lesions of the gastrointestinal tract.

Peritoneal mesothelioma. Radiologic appearances correlated with histology.

Previous imaging reports of peritoneal mesothelioma have described a variety of radiologic appearances, but have not included its pathologic classification. We retrospectively reviewed 10 cases of peritoneal mesothelioma representing the following histologic categories: 7 epithelial, 2 sarcomatoid, and one biphasic. By imaging, epithelial mesotheliomas demonstrated diffuse thickening of the peritoneum and mesentery and/or multiple small nodules. The sarcomatoid-type appeared as a mass and the biphasic-type had radiologic and gross pathologic features of both sarcomatoid and epithelial types. We conclude that peritoneal mesothelioma presents with a wide spectrum of radiographic appearances and should therefore be included in the differential diagnoses of diffuse as well as localized peritoneal processes.

Dysplasia of the stomach and Barrett esophagus: a follow-up study.

Seventy-seven patients with biopsy-proven glandular dysplasia of the esophagus (39 patients) or stomach (38 patients) were followed for a mean of 44 mo or until resection. Of 34 patients with low-grade dysplasia at initial biopsy, 29 had no evidence of high-grade dysplasia or carcinoma on follow-up, three died of other causes, and two had severe dysplasia diagnosed on subsequent biopsy. Of 43 patients with high-grade dysplasia, 28 had no evidence of dysplasia on follow-up (four died of unrelated causes and two of postoperative complications). Fifteen were shown to have invasive carcinoma. Thirteen of the 15 diagnoses of invasive carcinoma were made within 12 mo of original endoscopy. Ulcerated high-grade dysplasias were more likely associated with carcinoma than were nonulcerated high-grade dysplasias (P = 0.001). The presence of ulceration and short time interval to the progression of carcinoma suggest that carcinoma may have been present at the time of initial biopsy in many cases. The frequency of adenocarcinoma's arising in severe dysplasia was slightly less in the stomach (29%) than in the esophagus (41%). We conclude that low-grade dysplasia is often indolent and that ulcerated high-grade dysplasia is often a marker for adjacent invasion.

Deceptive bizarre stromal cells in polyps and ulcers of the gastrointestinal tract.

The clinical and pathologic features of 33 pseudomalignant lesions of the gastrointestinal tract with bizarre stromal cells are reported. Deceptive histologic changes were identified in ulcers of seven patients and in inflammatory polyps of 26. A misdiagnosis of malignant neoplasm was made in six of the 33 patients (three polyps and three ulcers). A history of gastrointestinal bleeding and/or inflammatory bowel disease was common. The bizarre stromal cells were usually distributed beneath the ulcerated mucosa or within granulation tissue. They stained strongly for vimentin in 20 of 23 cases. Some of the bizarre cells also stained for muscle specific actin (seven of 23 cases). The cells appear to be reactive fibroblasts or myofibroblasts. Follow-up information obtained on 24 of the 33 patients (including four of the six cases initially diagnosed as malignant) revealed 22 patients to be alive without evidence of a malignant neoplasm (average follow-up, 13 months). Two patients died of other causes. Correct recognition of these bizarre stromal cells in gastrointestinal ulcers and inflammatory polyps will prevent a potentially serious diagnostic pitfall.

Small cell carcinomas of the large intestine.

The authors studied the clinical and pathologic features of 38 small cell carcinomas of the large intestine. Most were located in the right colon. Overlying adenomas were present in 45% and squamous differentiation in 21% of tumors. Endocrine differentiation was present in all tumors by at least one method; neuron-specific enolase, dense-core granules, and synaptophysin were present in most cases. Seventy-one percent of tumors metastasized to the liver; 64% of patients were dead at five months follow-up. Twenty-one poorly differentiated adenocarcinomas and undifferentiated carcinomas of the large intestine accessioned during the same period showed less endocrine (7 of 21) and squamous differentiation (1 of 15) and fewer liver metastases (4 of 15) than did small cell carcinomas. Among all 59 tumors studied, small cell histologic characteristics correlated better with liver involvement than did endocrine markers or other histologic features. Small cell carcinomas of the large intestine are aggressive tumors with a propensity for early liver involvement. Although there is a spectrum of squamous, endocrine, and glandular features in large bowel tumors of low degrees of differentiation, the identification of a small cell component appears to be most clinically relevant.

Carcinoembryonic antigen and carcinoids of the gastrointestinal tract.

We studied the prognostic significance of immunohistochemically localized carcinoembryonic antigen in 131 nonmetastasizing and 35 metastasizing gastrointestinal carcinoid tumors. The rate of positivity was lower with preabsorbed versus nonabsorbed polyclonal antiserum. Compared with generally used prognostic features (depth of invasion, tumor size, and mitotic rate) positivity for absorbed anticarcinoembryonic antigen was the most specific feature for metastatic tumors but was least sensitive. Although our results demonstrate that anticarcinoembryonic antigen, particularly when absorbed, is highly associated with metastatic disease, depth of invasion and tumor size are better predictors of behavior.

Mesenteric fibromatosis. A follow-up study.

Eighty-two fibromatoses of the mesentery and other peritoneal sites were studied, with emphasis on features associated with recurrence. Twelve patients had Gardner's syndrome. Seventy-two tumors were completely excised at the time of surgery; 56 patients had no evidence of tumor recurrence (mean, 91 months), and in 16 patients tumors recurred (mean, 117 months of follow-up). Patients with Gardner's syndrome had a much higher risk of recurrence and death related to fibromatosis or surgery for fibromatosis than sporadic cases. There was a weaker association between recurrence and multiplicity. A history of trauma or estrogen exposure, size, mitotic activity, gross circumscription, and histologic features did not correlate with recurrence. Biopsies or partial resections were performed on 10 tumors (8 in patients without Gardner's syndrome and 2 in patients with Gardner's syndrome). The patients without Gardner's syndrome did well: 7 are alive without evidence of disease (mean, 72 months) and 1 died of lung carcinoma at 108 months. The 2 patients with Gardner's syndrome have persistent fibromatosis: 1 patient had recurrence in the abdominal wall at 103 months and 1 is alive at 72 months with intra-abdominal masses. We conclude that mesenteric fibromatosis is much more aggressive in patients with Gardner's syndrome than in patients without Gardner's syndrome, that pathologic features are not good predictors of aggressive behavior, and that complete surgical excision may not always be necessary.

Carcinoid tumors of the duodenum. A clinicopathologic study of 99 cases.

Ninety-nine carcinoid tumors of the duodenum were studied. Seventy-seven patients were followed up for a mean period of 65 months, 20 tumors were autopsy findings, and two patients were unavailable for follow-up. Sixteen tumors (21%) produced metastases, all discovered initially; 3 patients (4%) died from metastatic disease (mean survival, 37 months postoperatively). Features associated with metastatic risk were involvement of muscularis propria, size greater than 2 cm, and the presence of mitotic figures. For 51 tumors, there was no correlation between immunohistochemical somatostatin and history of diarrhea, cholelithiasis, or diabetes mellitus (somatostatin syndrome). Five tumors were associated with Zollinger-Ellison syndrome and had immunohistochemical gastrin, but in the others there was no correlation between ulcer disease and gastrin positivity. Duodenal carcinoids are indolent, especially when small and localized to the submucosa. Immunohistochemical identification of somatostatin and gastrin has little clinical relevance.

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.

Correlation of nucleolar organizer regions and glandular dysplasia of the stomach and esophagus.

Forty-seven biopsies of gastric mucosa and Barrett esophagus from 32 patients were studied with the argyrophilic nucleolar organizer region method. Twenty-two biopsies were gastric and 25 esophageal. Four showed normal noninflamed mucosa, 14 reactive glandular changes, eight intestinal metaplasia without dysplasia, ten low grade dysplasia with intestinal metaplasia, and 11 high grade dysplasia. The mean number of nucleolar organizer regions was 14.9 for high grade dysplasia, 10.9 for low grade dysplasia, 8.5 for intestinal metaplasia without dysplasia, 6.7 for reactive changes, and 3.9 for normal mucosa. The difference between high grade dysplasia and the other groups was significant (P = 0.004). However, the difference between high and low grade dysplasia was not significant (P = 0.06), and there was an overlap between reactive and high grade dysplastic lesions. We conclude that although nucleolar organizer counts correlate with the degree of dysplasia, the technique is of limited practical use.

Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction.

Epstein-Barr virus DNA was detected by polymerase chain reaction in a paraffin-embedded block of an undifferentiated lymphoepithelial gastric carcinoma but was absent in a poorly differentiated gastric adenocarcinoma which also had pronounced lymphoid stroma. This is the first report, to our knowledge, of a lymphoepithelial carcinoma of the stomach. The association with Epstein-Barr virus and the distinctive histologic appearance justify the separate classification of undifferentiated lymphoepithelial carcinomas of the stomach similar to those of the nasopharynx from adenocarcinomas with lymphoid stroma.

Intra-abdominal fibromatosis. A pathologic analysis of 130 tumors with comparison of clinical subgroups.

We studied the clinical, gross, and histologic findings of 130 fibromatoses of the mesentery and other peritoneal sites. Seventeen patients had Gardner syndrome, 12 had prior abdominal surgery, and six had apparent estrogen elevation, including five pregnant or postpartum women and an alcoholic male with gynecomastia. The tumors were usually large and grossly circumscribed. Most often, they were located in the mesentery of the small bowel. They were multiple in 18 cases. Typical histologic features included a dense, collagenous stroma; prominent, dilated, thin-walled vessels; muscular hyperplasia of small arteries; keloidal change; myxoid change; and fibrous tissue insinuation into the muscularis propria of the bowel. Although mitoses were noted in many tumors, they were usually few in number. The gross and histologic features were similar in the clinical subgroups; however, keloidal change was seen less often in female patients. Less than half of the cases were initially correctly diagnosed. Most patients without Gardner syndrome were without recurrence at follow-up, even when the lesions had been incompletely excised.

Somatostatin-producing duodenal carcinoids in patients with von Recklinghausen's neurofibromatosis. A predilection for black patients.

Eight patients with von Recklinghausen's disease (VRD) and duodenal carcinoids are presented. Seven patients were black, and one white. Six of the eight were women. The presenting symptom was either jaundice or abdominal pain. All tumors were located in the second portion of the duodenum, and three were multiple. Associated tumors other than neurofibromas included multiple leiomyomas, meningioma, neurofibrosarcoma, and prostatic sarcoma. Seven tumors had psammoma bodies, and in three they were numerous. Somatostatin-positive cells were demonstrated in all cases. Two tumors had spread to regional lymph nodes at the time of surgery. There appears to be a predilection for black patients among those with VRD and duodenal carcinoids.

Rectal and colonic carcinoids. A clinicopathologic study of 84 cases.

Eighty-four carcinoids of the colon and rectum were studied with emphasis on prognostic features, immunohistochemical characteristics, and pitfalls in diagnosis. Follow-up data were available on 35 patients. Tumors with adenocarcinomatous components, or those resembling small cell carcinomas of the lung, were excluded. Eighty-one tumors were in the rectum and three tumors were in the distal sigmoid colon. Neuron-specific enolase, chromogranin, and Leu-7 were positive in 87%, 58%, and 53% of the tumors, respectively. Hormones were positive in the following percentages: serotonin, 45%; pancreatic polypeptide, 46%; glucagon, 10%; gastrin, 3%; somatostatin, 3%; adrenocorticotrophic hormone, 1%; cholecystokinin, 0%; calcitonin, 0%; and insulin, 0%. Many tumors elaborated more than one hormone. Fifty-five percent of the tumors were argyrophil and 28% were argentaffin. Carcinoembryonic antigen was present in 24% of the tumors; 82% of the tumors contained prostatic acid phosphatase. Three patients had liver metastases; their tumors ulcerated, invaded muscularis propria, and had more than 2 mitoses per 10 high-power fields (HPF). One patient with a 2.5-cm tumor without mitoses had regional lymph node metastases. All non-metastasizing tumors had less than one mitosis in 10 HPF. We conclude that large bowel carcinoid tumors are essentially limited to the rectum and sigmoid, that they are indolent if mitotically inactive and smaller than 2 cm, and that most show production of a selected group of endocrine markers.

Appendiceal carcinoids: correlation of histology and immunohistochemistry.

In order to compare histologic subtypes and endocrine profiles, immunohistochemical and silver stains were performed on 120 appendiceal carcinoids. Forty-three were predominantly insular; 21 were mixed insular, glandular, and trabecular; 33 were goblet cell; 17 were tubular; and five were clear cell carcinoids. Insular, mixed, and clear cell carcinoids were generally diffusely argentaffin and positive for chromogranin, neuron-specific enolase (NSE), and serotonin. Occasional tumors of insular or mixed patterns had scattered cells that stained weakly for glucagon, calcitonin, adrenocorticotrophic hormone (ACTH), somatostatin, cholecystokinin (CCK), human pancreatic polypeptide (HPP), or gastrin. Most had S-100-positive sustentacular cells. Less than half were positive for carcinoembryonic antigen (CEA). Many were cytokeratin-positive, but often focally. Goblet cell carcinoids contained few endocrine cells, but these were strongly argentaffin and positive for serotonin in nearly all, and positive for HPP in almost a third. Tubular carcinoids lacked argentaffinity and serotonin but were diffusely and strongly positive for glucagon. All goblet cell and tubular carcinoids were diffusely positive for CEA and cytokeratin. Somatostatin stained strongly in a single tumor, which had psammoma bodies and was in a patient with neurofibromatosis. In all groups, argentaffinity correlated with serotonin positivity, and argyrophilia with chromogranin positivity, although the latter was somewhat more sensitive. We conclude that among appendiceal carcinoids, the endocrine content varies according to histologic subtype.

Carcinoids of the duodenum. A histologic and immunohistochemical study of 65 tumors.

The light-microscopic and immunohistochemical characteristics of 65 duodenal carcinoids are presented. Most tumors showed a mixture of cribriform, insular, glandular, solid, and trabecular growth patterns. Eighty-five percent of the tumors were argyrophil and 15% argentaffin. The nonspecific neuroendocrine markers chromogranin, Leu-7, and neuron-specific enolase were positive in 97, 91, and 83% of tumors, respectively. Immunoreactivity for specific hormones/amines were as follows (percent positive tumors): somatostatin, 47%; N-gastrin, 56%; serotonin, 39%; calcitonin, 19%; insulin, 5%; pancreatic polypeptide, 3%; adrenal corticotropic hormone, 0%; glucagon, 0%. Sixty-eight percent had gastrin/cholecystokinin-like reactivity. Ten psammomatous tumors were located near the ampulla; eight were somatostatin positive, including two in patients with neurofibromatosis. One additional tumor in a patient with neurofibromatosis lacked psammoma bodies but elaborated somatostatin. Eight additional tumors in nonneurofibromatosis patients produced solely somatostatin. Duodenal carcinoids often elaborate more than one polypeptide hormone; those in the ampulla often elaborate somatostatin and have psammoma bodies.