Microcystic adenomas (serous cystadenomas) of pancreas. A clinicopathologic investigation of eight cases with immunohistochemical and ultrastructural studies.

Microcystic adenomas are rare tumors, which have only recently been distinguished from other cystic pancreatic lesions. This study details eight cases diagnosed at the Cleveland Clinic. Seven occurred in females. The mean age at diagnosis was 66 years. Abdominal or epigastric pain was the most common symptom. A history of extrapancreatic tumors was frequent, and one patient had a concomitant renal carcinoma with adrenal and renal cysts. The adenomas were multicystic, ranging in size from 2 to 14 cm. Cuboidal epithelial cells with vacuolated or clear cytoplasm containing abundant glycogen lined the cysts. The intervening stromal septa were collagenous and hypocellular. The epithelial cells exhibited strongly positive immunostaining for cytokeratins AE1 and AE3, but did not stain with CEA and Uro-2,3, and 4. Ultrastructurally, the epithelial cells rested on well-formed basal lamina and a delicate subepithelial capillary network. They had blunted apical microvilli and contained glycogen, few lipid droplets, and occasional apical secretory granules. Five adenomas were resected, and three had only a diagnostic biopsy. There were no metastases, but one patient died of postoperative complications following local excision. Elderly or high-risk patients may benefit more from biopsy alone than from attempts at total surgical resection of these benign tumors.

A clinicopathologic study of 42 patients with granulomatous gastritis. Is there really an "idiopathic" granulomatous gastritis?

Idiopathic granulomatous gastritis (IGG) is a diagnosis made only by excluding other causes of granulomatous gastritis, such as infection, foreign bodies, and systemic granulomatous diseases. Recently, several investigators have questioned the existence of IGG. We reviewed the slides and clinical data of all cases of granulomatous gastritis seen at the Cleveland Clinic between 1975 and 1994. In addition to routine hematoxylin and eosin stains, slides from all cases were stained with Ziehl-Neelsen, Gomori's methenamine silver, and Giemsa stains. Clinical information and follow-up were available for 42 patients. The clinicopathologic diagnoses of the 42 patients with granulomatous gastritis were as follows: Crohn's disease (n = 23), three of whom had concomitant chronic active gastritis with Helicobacter pylori infection; sarcoidosis (n = 9), four of whom had concomitant chronic active gastritis with H. pylori infection; chronic active gastritis with H. pylori infection and no other systemic illness (n = 2); distal esophageal adenocarcinoma and chronic active gastritis (n = 2); mucosa-associated lymphoid tissue (MALT) lymphoma with chronic active gastritis and presumed H. pylori infection (n = 2); peptic ulcer complications (n = 2); hypertrophic gastropathy with chronic active gastritis (n = 1); and possible Crohn's disease (n = 1). We conclude that (a) in most cases of granulomatous gastritis, a diagnosis of Crohn's disease or sarcoidosis could be established; (b) the background inflammatory pattern was helpful in suggesting a diagnostic category for granulomatous gastritis; (c) granulomatous gastritis is not associated with H. pylori per se; however, if known cases of Crohn's disease and sarcoidosis are excluded, an association between H. pylori and granulomatous gastritis cannot be ruled out; and (d) IGG, if it exists, is extremely rare.

Pseudomyxoma peritonei. A clinicopathologic study of 19 cases with emphasis on site of origin and nature of associated ovarian tumors.

Nineteen patients (10 men, 9 women) with pseudomyxoma peritonei were studied to determine the site of origin of the disease and the nature of associated ovarian tumors. A primary appendiceal mucinous neoplasm was found in 16 of the 17 patients with an evaluable appendix. One woman's appendix had intramural and serosal mucinous deposits without neoplastic epithelial cells. The appendiceal tumors were classified as mucin-producing adenoma ("mucinous cystadenoma") in 13 patients (seven women, six men), intramucosal adenocarcinoma associated with mucin-producing adenoma in one man, and invasive adenocarcinoma associated with mucin-producing adenoma in one man and one woman. Five of the nine women had cystic mucinous ovarian neoplasms; each also had an appendiceal mucinous neoplasm (adenoma in four, invasive adenocarcinoma with adenoma in one). The ovarian neoplasms had histologic features resembling a borderline (low malignant potential) mucinous tumor in four and a mucinous cystadenoma in one; all five ovarian tumors also had features of pseudomyxoma ovarii. Mucinous implants were also on the ovarian surface of the contralateral ovary in four of the five women with ovarian tumors and in the other four women without ovarian tumors. The intraperitoneal mucus deposits contained neoplastic mucinous epithelial cells in 16 patients (eight men, eight women) and were acellular in three (two women, one man). Of 17 patients with more than 6 months of follow-up, 12 (seven women, five men) were alive after postoperative intervals of 7 to 147 months, including three with known residual disease. Five (three men, two women) died of disease 16 to 60 months after initial operation, including two patients with appendiceal carcinoma. Acellular intraperitoneal mucus appeared to be a favorable prognostic feature. We conclude that (a) the appendix is the primary site of origin of pseudomyxoma in the vast majority of cases in both men and women, and (b) the associated mucinous ovarian tumors are most likely secondary neoplasms resulting from incorporation of implanted mucus and neoplastic mucinous epithelial cells of the pseudomyxoma peritonei.

Gastric antral vascular ectasia. A histologic and morphometric study of "the watermelon stomach".

Gastric antral vascular ectasia (GAVE) is an uncommon but important cause of gastrointestinal blood loss and iron deficiency anemia that is characterized by a distinctive endoscopic appearance consisting of parallel erythematous folds traversing the gastric antrum. In order to clarify the histologic features of this lesion, nine antral biopsy specimens from seven patients with the clinical and endoscopic diagnosis of GAVE were reviewed and compared with specimens from normal controls and patients with other common antral lesions. Specimens obtained using standard endoscopic biopsy forceps were evaluated for mucosal vascularity, presence of intravascular fibrin thrombi, and the following histologic changes: mucosal inflammation, fibromuscular hyperplasia of lamina propria, epithelial regeneration, and mucosal architectural distortion. Mucosal vascularity was determined by counting the absolute number of vascular lumina per slide, measuring the mean cross-sectional area of each vessel lumen, and determining the percentage of each specimen occupied by vessels. Histologic changes were graded as absent to minimal, moderate, or marked. Significant differences (p less than 0.05) between GAVE and control groups were mean vessel cross-sectional area, percentage of area occupied by vessels, presence of intravascular fibrin thrombi, and fibromuscular hyperplasia. GAVE appears to demonstrate sufficiently distinctive histopathologic features to allow its recognition in antral biopsy specimens obtained by endoscopy.

Colonic epithelial lymphocytosis associated with an epidemic of chronic diarrhea.

The term Brainerd diarrhea has been applied to outbreaks of chronic watery diarrhea of unknown etiology characterized by acute onset and prolonged duration. Our aim was to describe the histologic changes in gastrointestinal biopsy specimens from patients with Brainerd diarrhea. We examined 52 colonic and 12 small bowel biopsy specimens from 22 patients who were involved in an outbreak of Brainerd diarrhea that was linked to the water supply of a cruise ship visiting the Galapagos Islands. Small bowel biopsy specimens from seven patients were histologically normal. One patient had a duodenal biopsy specimen that resembled celiac sprue. Colonic biopsy specimens from 20 patients revealed surface epithelial lymphocytosis without distortion of mucosal architecture, surface degenerative changes, or thickened subepithelial collagen plates. The degree of surface epithelial lymphocytosis was greater than that seen in control groups of persons with normal colons, acute colitis, and ulcerative colitis (p < 0.001), similar to that seen with collagenous colitis, and less than that seen with lymphocytic colitis (p < 0.001). Three patients showed focal active colitis similar to that described in acute infectious-type colitis in addition to the epithelial lymphocytosis. Two patients had colonic biopsy specimens that were histologically normal. In summary, histologic abnormalities in the small bowel are generally absent in Brainerd diarrhea. Colonic biopsy specimens in Brainerd diarrhea frequently show epithelial lymphocytosis similar to that seen in collagenous and lymphocytic colitis. Although currently Brainerd diarrhea can be diagnosed only with epidemiologic data indicating an epidemic and a point source, the lack of surface degenerative changes and the relatively lower lymphocyte counts seen in our cases of Brainerd diarrhea may serve to distinguish it from lymphocytic colitis, and the lack of a thickened subepithelial collagen plate distinguishes it from collagenous colitis.

Colonic epithelial lymphocytosis without a thickened subepithelial collagen table: a clinicopathologic study of 40 cases supporting a heterogeneous entity.

Lymphocytic colitis (LC) is classically described as a triad of chronic nonbloody, watery diarrhea, normal or nearly normal endoscopy findings, and colonic epithelial lymphocytosis without a thickened subepithelial collagen table (SECT). It is unknown how often patients with colonic epithelial lymphocytosis without a thickened SECT actually present with this classic triad. Cases diagnosed histologically as lymphocytic or microscopic colitis were reviewed. Criteria for inclusion were the presence of at least 15 surface lymphocytes per 100 epithelial cells and the absence of a thickened SECT (<12 microm). Clinical features and course were recorded by chart review and telephone follow-up. Forty patients met the inclusion criteria, including 25 women and 15 men with a mean age of 63.2 years (range, 25-83 years). Twenty-eight patients had the classic triad and were designated as having classic LC. The other 12 patients fulfilled the histologic criteria but not the clinical or endoscopic criteria for classic LC and were classified as having atypical LC (constipation, five patients; macroscopic colitis at endoscopy, five patients; hematochezia, one patient; and incidental finding, one patient). Clinically, patients with classic LC were predominantly women and had a higher incidence of autoimmune disease (p = 0.03) than did those with atypical LC. Histologically, surface eosinophilia was significantly greater in patients with classic LC (p = 0.04). Twenty patients were using nonsteroidal antiinflammatory drugs at the time of their colonic biopsy. Surface epithelial lymphocyte counts were higher in these patients, particularly in the distal sigmoid colon (p = 0.02). Fourteen patients had associated autoimmune disease, including three patients with sprue diagnosed by small bowel biopsy, all of whom responded to gluten withdrawal. Diarrhea present in 25 patients, without documented evidence of celiac sprue, was self-limited in five, resolved with treatment in three, required intermittent treatment in eight, daily treatment in five, and was refractory to treatment in four. All eight patients who experienced spontaneous or treatment-related symptom resolution had classic LC. No histologic feature correlated with clinical course. In conclusion, our study shows that colonic epithelial lymphocytosis without a thickened SECT is a histologic finding seen in a heterogeneous group of patients. Within this heterogeneous group is a distinct subset of patients who have the classic clinicopathologic triad of LC. This subset of patients has striking similarities to patients with collagenous colitis, lending further support to a close relationship between these two entities. Atypical LC comprises a heterogeneous group and includes patients with idiopathic constipation, coexisting LC and inflammatory bowel disease, and possibly infectious colitides. Because of the clinical heterogeneity among our study population, the descriptive term colonic epithelial lymphocytosis may be a more prudent diagnosis than lymphocytic colitis in the absence of adequate clinical information.

Intestinal adenocarcinoma in Crohn's disease: a report of 30 cases with a focus on coexisting dysplasia.

There are relatively few reports that detail the types of intestinal adenocarcinoma complicating Crohn's disease and examine associated epithelial dysplasia. We determined the prevalence, grade, and type of dysplasia found adjacent to and distant from Crohn's-related adenocarcinomas. Thirty cases of resected Crohn's-related adenocarcinoma were reviewed, and histologic type, degree of differentiation, TNM stage, and the presence or absence, grade, and location of dysplasia were recorded. Most of the patients were male (70%). The median ages at diagnosis of Crohn's disease and adenocarcinoma were 34 and 49 years, respectively. The extent of Crohn's disease included ileocolitis in 21 patients, only colonic disease in six, and only small bowel disease in three. In most cases (67%), carcinoma was found incidentally at surgery. All carcinomas arose in areas involved by Crohn's disease. Eight (27%) adenocarcinomas arose in the small bowel, and 22 (73%) arose in the colon, including two in out-of-circuit rectums. Most carcinomas (63%) were poorly differentiated. Dysplasia was found adjacent to the carcinoma in 26 (87%) cases. Of the colorectal carcinomas, 19 (86%) had adjacent dysplasia, and nine (41%) had distant dysplasia. In conclusion, most cases of Crohn's-related intestinal adenocarcinoma have dysplasia in adjacent mucosa, and 41% of those arising in the colorectum have distant dysplasia, supporting a dysplasia-carcinoma sequence in Crohn's disease.

Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature.

Solitary endobronchial papillomas in adults are rare neoplasms. Only sporadic cases have been documented. The histologic classification of these tumors remains problematic, and little is known about their clinical behavior. The clinical and pathologic features of 13 endobronchial papillomas and a single endobronchiolar papilloma were reviewed. In situ hybridization for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/51 was performed on seven cases. Twenty-seven additional well-documented cases were identified in a literature review. Human papillomavirus studies were performed in four of the previously reported cases. The 41 neoplasms combined from the Armed Forces Institute of Pathology and literature review were divided into three groups according to their histologic features. Thirty-one of 41 (76%) patients were men. The ages of the patients ranged from 26 to 74 years (median, 57 years). Three morphologically distinct histologic types were recognized; 27 squamous cell papillomas, 7 glandular papillomas, and 7 mixed squamous and glandular papillomas. Squamous papillomas: 23 of 27 (85%) patients were men, and the median age was 54 years. Six of eleven (55%) of these patients smoked. Twenty-six lesions were exophytic and a single lesion had an inverted pattern. Seven of 24 (29%) lesions featured cytologic atypia and 5 of 24 (14%) had viral cytopathic effect. Five of seven (71%) cases examined for HPV DNA were positive. Three of 18 (17%) recurred. Glandular papillomas: Four of seven (57%) patients were women. The mean age was 67 years. One of five (20%) patients smoked. Five lesions were central, and two were peripheral. Four lesions had columnar epithelium, and three had ciliated epithelium. One of six (17%) lesions recurred. Mixed papillomas: five of seven (71%) patients were men. The median age was 64 years. Three of five (60%) patients smoked. Three of seven (43%) lesions featured cytologic atypia. Four of five lesions were examined for HPV DNA and all were negative. No lesions recurred. This study demonstrates that solitary endobronchial papillomas can be separated into three distinct morphologic categories. Squamous cell and mixed papillomas are predominantly lesions of male smokers in their 6th decade. Although cytologic atypia is observed in many cases, the rarity of these tumors and difficulty in separating papillomas from endobronchial papillary squamous carcinomas make generalizations regarding the risk of progression to carcinoma tenuous at best. Human papillomavirus appears to play a pathogenetic role in some squamous cell papillomas, but not in mixed papillomas, yet its presence in the squamous lesions does not correlate with recurrence or malignancy. The first report of an inverted squamous cell papilloma indicates clinical features similar to the more common exophytic squamous cell papillomas. Glandular papillomas, the rarest of all endobronchial papillomas, are found in an older age group than squamous and mixed papillomas, and most-patients are nonsmokers. Based on these findings, all endobronchial papillomas should be completely excised.

Short- and long-term follow-up of treatment for lymphocytic and collagenous colitis.

Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies. Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less. Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids. Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.

Pulmonary lymphoid neoplasms. Role of immunohistology in the study of cellular immunotypes and in differential diagnosis.

Seven cases of lymphoid neoplasms presenting in the lung were evaluated by immunohistology for T and B cell antigens and immunoglobulin light chains in frozen tissue sections. Although follow-up was short or inconclusive in some patients with lymphoma and pseudolymphoma, it was concluded that evaluation of T and B cell antigens and immunoglobulin light chains in frozen tissue is helpful in classifying lymphocytic neoplasms, especially in cases without definite cytologic evidence of malignancy. As demonstrated in two additional cases, lymphocyte/leukocyte markers in paraffin-embedded tissue are important in the differential diagnosis of lesions with cytologic features of malignancy.

Diagnostic yield and therapeutic impact of flexible bronchoscopy in lung transplant recipients.

BACKGROUND: Bronchoalveolar lavage and transbronchial biopsy are often used for definitive diagnosis of lung rejection and infection in lung transplant recipients. Although protected specimen brushing is of value in nosocomial bacterial pneumonia, its role in lung transplant recipients had not been widely reported. The aim of the study is to review the diagnostic yield and therapeutic impact of flexible bronchoscopy with the use of a combination of bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy in lung transplant recipients. METHODS: We reviewed flexible bronchoscopy data in 83 transplant recipients between February 1990 and March 1995. Only those with bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy were included in the analysis. There were 282 bronchoscopies performed for clinically suspected lung rejection or infection (clinical bronchoscopy) and 38 bronchoscopies for follow-up of a previously detected histologic abnormality (follow-up bronchoscopy). RESULTS: The total yields for rejection and infection for clinical and follow-up bronchoscopies were 67.4% and 58.9%, respectively. Acute rejection was detected with transbronchial biopsy in 26.2% and 34.2% of clinical and follow-up bronchoscopies, respectively. Cytomegalovirus pneumonitis was detected with transbronchial biopsy in 4.0% and 11.4% of clinical and follow-up bronchoscopies, respectively. Overall, bacteria was the most common cause of lower respiratory tract infection. When used together, protected specimen brushing and bronchoalveolar lavage were complementary techniques for detection of bacterial lower respiratory tract infection with a significantly higher proportion detected with protected specimen brushing ( > or = 10(3) colony forming units/ml) compared with bronchoalveolar lavage ( > or = 10(5) colony forming units/ml) (p < 0.001). Complications were hemorrhage (1.9%), pneumothorax (2.5%) and transient hypoxemia (10.5%). The results had an impact on management of rejection and infection in 57.8% of clinical and 39.5% of follow-up bronchoscopies. CONCLUSIONS: We conclude that bronchoscopy, with the use of a combination of bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy, is safe with a high diagnostic yield and therapeutic impact for treating lung transplant recipients.

Deoxyribonucleic acid ploidy and cell cycle analysis of colorectal carcinoma by flow cytometry. A prospective study of 137 cases using fresh whole cell suspensions.

Several retrospective studies suggest that abnormal deoxyribonucleic acid (DNA) content in colorectal carcinoma correlates with adverse clinical outcome. Many of these studies have used naked nuclei retrieved from formalin-fixed, paraffin-embedded tissues for flow cytometry. The purpose of this study was to prospectively analyze 137 colorectal carcinomas using fresh whole-cell suspensions for flow cytometry and to determine whether abnormal DNA content (DNA aneuploidy or tumors with high proliferative activity) correlates with Dukes' stage, histologic grade, lymphocytic infiltration of the tumor, tumor fibrosis, extramural venous spread, or tumor size. Cell suspensions for flow cytometry were prepared by enzyme disaggregation with collagenase XI, DNase, and trypsin. Satisfactory DNA histograms were obtained from 132 of the 137 samples. The mean coefficients of variance for the G1/G0 of the external 2C control, internal 2C populations, and aneuploid populations were 2.5, 3.5, and 3.5, respectively. The mean percentage of viable cells was 97%. Of 132 cases, 102 (77%) demonstrated abnormal DNA histograms, of which 77 (58%) showed DNA aneuploidy. Abnormal DNA histograms of DNA aneuploidy did not correlate with Dukes' stage. Tumors of higher histologic grade were more likely to demonstrate DNA aneuploidy, however, these differences did not reach statistical significance. The authors conclude that (1) satisfactory DNA histograms can be obtained with the use of a fresh, whole-cell technique; (2) abnormal DNA histograms did not statistically correlate with standard clinical, grading, or staging parameters; and (3) carcinomas of high histologic grade showed an increased proportion of aneuploid DNA histograms, but this trend did not reach statistical significance.

Papillary cystic epithelial neoplasms of the pancreas. A clinical study of four cases.

We treated four cases of papillary cystic epithelial neoplasm of the pancreas. This neoplasm typically presents in young female patients as a slowly growing mass that may attain large size. It is of low malignant potential, and surgical resection will be curative in almost all cases. One patient presented with a liver metastasis from the pancreatic tumor; both lesions were successfully resected. Papillary cystic epithelial neoplasm should be considered in the differential diagnosis of any cystic pancreatic neoplasm.

Brugia infection in Northern Ohio.

A new case of infection with Brugia sp. is recorded from Northern Ohio, increasing the geographical range of this zoonosis, known previously in New England, New York and New Jersey. The patient, a 53-year-old man, had a 7-year history of malignant fibrous histiocytoma of the spermatic cord, for which he received intense chemo- and radiotherapy. The worm found was alive at the time of fixation, allowing a description of the parasite in cross sections.

Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms.

Histologic differential diagnosis of acinar cell carcinoma (ACC), mixed acinar-endocrine cell carcinoma (MAEC), and pancreatic endocrine tumors (PET) can be difficult but is important because of differences in their clinical behavior. This study investigates the utility of immunohistochemistry (IHC) in this differential diagnosis using immunohistochemical stains that are available in most laboratories. IHC was performed on paraffin-embedded tissue in ACC (n = 6), MAEC (n = 2), and PET (n = 13), using synaptophysin (SYN), chromogranin (CHR), chymotrypsin (CHY), and alpha-1-antitrypsin (AAT). Electron microscopy (EM) was performed in all cases to confirm the diagnosis. Long-term follow-up and death of disease (DOD) was known in all patients. The ACCs stained as follows: CHY (4/6), AAT (3/6), SYN (4/6); CHR was negative in all cases. Both cases of MAEC stained with CHY, AAT, and SYN (2/2); CHR was negative. PET stained as follows: SYN (13/13), CHR (8/13), CHY (4/13), AAT (5/13). In the ACC/ MAEC group, six of eight patients were DOD at mean follow-up of 11 months. Among the PET, two of 16 patients were DOD at mean follow-up of 37 months. Considerable immunophenotypic overlap exists between ACC, MAEC, and PET. Consequently, one can neither confirm nor rule out a diagnosis of ACC or MAEC using generally available immunohistochemical stains alone. These findings support a role for EM in the evaluation of exocrine and endocrine pancreatic neoplasms.

Spectroscopic diagnosis of colonic dysplasia.

We have developed a method for defining diagnostic algorithms for pathologic conditions based on fluorescence spectroscopy. We apply this method to human colon tissue and show that fluorescence can be used to diagnose the presence or absence of colonic adenoma. This method uses fluorescence excitation-emission matrices (EEM) to identify optimal excitation regions for obtaining fluorescence emission spectra which can be used to differentiate normal and pathologic tissues. In the case of normal and adenomatous colon tissue, these were found to be: 330, 370, and 430 nm +/- 10 nm. At these excitation wavelengths, emission wavelengths for use in diagnostic algorithms are identified from average difference and ratio of the spectra from normal and pathologic tissues. In colon tissue, at 370 nm excitation, 404, 480, and 680 nm were found to be useful emission wavelengths for diagnosing the presence of adenoma in vitro. The basis of colon tissue autofluorescence was investigated using EEM of pure molecules and relevant excitation-emission maxima in the literature.

Villous and tubulovillous adenomas of the colon and rectum. A retrospective review, 1964-1985.

The records of 1,040 patients with 1,440 villous and tubulovillous adenomas of the colon and rectum treated at the Cleveland Clinic over a 21 year period were reviewed. The incidence of invasive adenocarcinoma was higher in patients with multiple adenomas at the time of presentation, in patients with a family history of colorectal cancer, and in those with adenomas greater than 4 cm in diameter. Eighty percent of the adenocarcinomas were Dukes' A or B, 15 percent were Dukes' C, and 5 percent presented with distant metastases. Clinical impression on examination was more accurate than biopsy in assessing the presence of malignancy in these tumors. Recurrence after local treatment of both benign and malignant tumors was high. Recurrence was significantly related to the size of the adenoma (more common when the tumor was more than 4 cm in diameter), location (more common when it was located in the rectum), and the type of treatment. Only 4 percent of the patients had died from colorectal cancer at the time of follow-up. The overall 5 year actuarial survival rate was 85 percent.

Duodenal microgastrinoma producing the Zollinger-Ellison syndrome.

A 1.5-mm gastrinoma of the duodenal wall was discovered during dissection of a duodenal ulcer in a patient in whom the Zollinger-Ellison (ZE) syndrome was later suspected due to gross autopsy findings. Multiple duodenal ulcers and gastric rugal hypertrophy were noted, and hyperplasia of the parietal cells associated with a duodenal gastrinoma was confirmed by immunohistochemical studies. In many cases of ZE syndrome, a primary neoplasm cannot be localized by angiography, computed tomography, ultrasound, or palpation at exploratory laparotomy. If a neoplasm cannot be identified, many cases will be attributed to islet cell hyperplasia, or antropyloric gastrin cell (G cell) hyperplasia. This case confirms that the primary neoplasm may be grossly undetectable and still produce the clinicomorphologic manifestations of this syndrome.

Strumal carcinoids of the ovary. An immunohistologic and ultrastructural study.

A series of six ovarian strumal carcinoids was examined. The presence of thyroid follicular epithelium was conclusively proved by the presence of follicular cells immunohistochemically positive for thyroglobulin, and by the ultrastructural identification of non-neuroendocrine cells with features of thyroid epithelium lining the follicles. Progressive replacement of thyroid epithelial cells by carcinoid cells accounts for the predominance of neuroendocrine granule-containing cells and the scarcity of thyroid epithelial cells lining many of the follicles. A variety of neuroendocrine hormones and other immunoreactive substances was demonstrated within carcinoid cells, including somatostatin (five cases), chromogranin (five cases), serotonin (five cases), glucagon (four cases), insulin (two cases), and gastrin (one case). Only one case contained calcitonin-positive cells. None were carcinoembryonic antigen-positive or had amyloid deposits. The carcinoid element in five cases stained positively for prostatic acid phosphatase. While strumal carcinoid shares some features with medullary carcinoma of the thyroid gland, it has sufficient differences to warrant a separate designation.

Bizarre atypia in gastric brushings associated with hepatic arterial infusion chemotherapy.

Hepatic arterial infusion chemotherapy (HAIC) for unresectable hepatic neoplasms has been associated with gastric ulcers and epithelial atypia that may be misinterpreted as carcinoma. Gastric brushings were reviewed from six patients who developed gastric ulcers with histologically proven atypia following HAIC. Marked cytologic atypia, reminiscent of a pronounced radiation effect, was present in gastric epithelial cells in five patients. The atypical cells occurred singly or in small sheets. They were markedly enlarged but a low nuclear-cytoplasmic ratio was preserved. The abundant cytoplasm was vacuolated or foamy. Binucleation and multinucleation were common, and massive nucleoli were characteristic. The brushings also contained the reparative, inflammatory and necrotic changes associated with usual benign gastric ulcers. The bizarre atypia associated with HAIC can be a source of misdiagnosis of cancer in cytologic as well as in histologic specimens.