Gastric adenomyoma (GA) is a rare submucosal benign neoplasm that occurs mostly in the gastric antrum and is often misdiagnosed. No standard treatment has been established for this disease in cases of malignancy.

A 75-year-old woman with a 10-year history of hypertension was admitted to the Emergency Department of our hospital complaining of paroxysmal exacerbation of acute abdominal pain for 1 d with no apparent cause. Enhanced computed tomography and magnetic resonance imaging indicated a mass in the caudal pancreas, cholecystitis, and cholecystic polypus. Gastrointestinal endoscopy showed a mass arising from the gastric antrum. Due to the imaging findings, pancreatic cancer (PC), gastric lesion, cholecystitis, and cholecystic polypus were our primary consideration. Radical pancreatectomy, splenectomy, and cholecystectomy were performed successfully, and the gastric tumor was locally resected. Postoperative paraffin specimens confirmed the diagnosis of caudal PC, GA, and heterotopic pancreas (HP). Unfortunately, the patient died 13 mo later due to PC metastases to the liver, lung, and adrenal glands.

GA is a rare benign disease, especially when occurring with HP. It may stem from the same origin as HP. This is the first case report to date of a patient suffering from the simultaneous occurrence of GA, HP, and PC. GA is a lesion that can mimic other benign or malignant gastrointestinal diseases; thus, a definitive diagnosis depends on postoperative pathological biopsy. Although GA and HP are both benign lesions, they should be resected because there is a chance of malignancy. Additional research should be conducted to better understand these submucosal lesions.

We report an unusual case of adenomyoma of the common hepatic duct mimicking bile duct cancer. A 50-year-old woman was referred to our hospital for the investigation of general fatigue. Laboratory data showed abnormal liver test results and computed tomography showed a mass lesion in the hepatic hilum and dilatation of the intrahepatic bile ducts. These findings led to a preoperative diagnosis of hilar bile duct carcinoma, and we performed a left lobectomy with resection of the extrahepatic bile duct. Macroscopically, an elevated lesion was found in the common hepatic duct, which was confirmed histologically to be an adenomyoma. Bile duct strictures are rarely caused by benign tumors of the biliary tract, such as adenomyoma. Surgical resection of the bile duct should be considered for all bile duct strictures because it is often difficult to differentiate malignant from benign lesions in this location preoperatively, and malignant cells may be present in the lesion.

A very rare case of adenomyoma of the common hepatic duct is described. A 54-year-old woman was admitted with impending obstructive jaundice secondary to adenomyoma of the common hepatic duct. Our impression, formulated from her clinical presentation, endoscopic investigations, and biochemical and radiological findings, was a cancer of the proximal common hepatic duct. The patient was treated successfully by combination surgical resection and hepaticojejunostomy. Despite our obtaining an intraoperative frozen section, final histological examination was required to confirm the diagnosis. The patient remains well 16 months postoperatively. A survey of the world literature revealed that this is the second report of adenomyoma occurring in the common hepatic duct.

Thyroid carcinoma has been described as occurring more frequently than expected in association with familial adenomatous polyposis. The histology of these cases has not been described in detail, although the reported cases were usually diagnosed as papillary carcinoma. We now report the pathological features of four cases of thyroid carcinoma associated with familial adenomatous polyposis, and review the findings in the literature. The tumours in these four cases were all of follicular cell origin as shown by thyroglobulin immunohistochemistry. In three they were multifocal. The tumours showed some features of papillary carcinoma--grooved nuclei and papillary architecture, but these were not consistent. They also showed features that were unusual for papillary carcinoma--a cribriform pattern and solid areas with spindle cell component. Commonly the tumours combined both patterns. A review of the reported cases of thyroid cancer associated with familial adenomatous polyposis showed that they also were commonly multifocal and occurred predominantly in young women. When the histology was adequately reported or illustrated it was, in most instances, consistent with the findings in our own cases. We therefore suggest that these thyroid tumours form a distinct type with some unusual features. Clearly it is likely that the APC gene is associated with their pathogenesis, and that other factors contribute to the predominantly female incidence in this as in sporadic tumours. Six of 63 reported cases showed metastasis or died from thyroid carcinoma. In a number of cases the tumours presented before the familial adenomatous polyposis was recognized. The findings of these unusual histological features in a thyroid tumour, and particularly of multicentricity, should alert the pathologist to the possibility of familial adenomatous polyposis with its implications for family screening. The tumours are often well demarcated but, because of the multicentricity, total thyroidectomy should be advocated.

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma.

A patient known to be suffering from Gardner's syndrome who developed carcinoma of the thyroid gland is presented. A review of the literature reveals that this relationship is not fortuitous and that it has the following characteristics: female predominance (89%), youth (< 30 years in 78%), papillary form (88%), multicentricity (70%) and thyroid carcinoma preceding diagnosis of hereditary polyposis in 30%. Hereditary polyposis patients affected by familial polyposis coli are at significant risk of developing extracolonic malignant tumours, and require life-long surveillance. Palpation of the thyroid gland and possibly ultrasound examination of the neck should be part of the routine follow up of these patients.

The case history of a 24-year-old woman with Gardner's syndrome [familial adenomatous polyposis (FAP)] and papillary thyroid carcinoma is presented, representing the 37th report of this association. Although FAP is transmitted as an autosomal dominant trait with similar penetrance in both sexes, thyroid carcinoma has been found almost exclusively in women (94.3%). The majority have been papillary carcinomas (88.5%), which have become apparent during the third decade (average 23.6, range 16-40 years). Most (55.5%) thyroid carcinomas have been discovered 1-17 years after FAP was identified, although some have been found before (29.6%), or at the same time (14.8%) FAP was diagnosed. Multicentric papillary carcinomas have been reported in 64% (14 of 22) of FAP patients, a frequency at least twofold greater than usual. Although papillary carcinoma found before age 30 (as it was in most patients with FAP) typically has an excellent prognosis, one patient with FAP developed distant metastases from thyroid carcinoma and a 28-year-old woman's death was attributed to papillary carcinoma. The high frequency of multicentric papillary thyroid carcinoma in young patients with FAP and the potential for metastases and death due to thyroid carcinoma warrant aggressive diagnostic screening at regular intervals with neck palpation, ultrasonography, and if necessary, fine-needle aspiration biopsy. When thyroid carcinoma is found, total or near-total thyroidectomy should be considered because of the tumor's high likelihood of being multifocal.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial polyposis coli (FPC) is hereditary condition that conveys a virtual 100% risk for the development of colon cancer in the untreated patient. A total of 56 patients with FPC underwent complete ophthalmic examination. Highly pleomorphic pigmented retinal lesions were identified bilaterally in 52% (n = 29) and unilaterally in 14% (n = 8) of our subjects. In all, 33 patients had one or more extracolonic expressions associated with FPC, including desmoids, osteomas, epidermoid cysts, lipomas, fibromas, and upper gastrointestinal tract polyps. In 15 patients, pigmented fundus lesions were the only extracolonic manifestations. No significant association between eye findings and other extracolonic manifestations could be established. The presence or absence of pigmented fundus lesions was found to cluster within families. Pigmented fundus lesions are probably a variably penetrant expression of the polyposis gene and do not appear to be specifically associated with subgroups of inherited polyposis syndromes such as Gardner's syndrome.

In view of the rarity of small-bowel epithelial neoplasms as compared with the case for the large bowel, evidence for an adenoma-carcinoma sequence in the small bowel was studied based on a search for data in the medical literature for the years 1927 through 1986. Sufficiently defined data were found for comparison of 185 benign adenomas, 76 adenoma-with-carcinomas, and 1333 carcinomas in patients without familial polyposis disease and for 63, five, and 30, respectively, in patients with disease. For patients without polyposis, it was found that (1) 29.8% of all small-bowel adenomas (33.6% if those at Vater's ampulla are excluded) showed malignancy; (2) the mean and median ages were lower for benign adenoma than for adenoma-with-carcinoma and carcinoma, although the ratios by sex were the same; (3) there is a nearly identical spatial distribution of the three types of epithelial neoplasms within the small bowel; and (4) both the frequency of finding adenomatous residues existing in continuity with carcinoma and the life history of the adenoma-carcinoma sequence are similar in the small bowel as in the large. In comparing these results with those from patients with familial polyposis disease, it was particularly noted that (1) the only difference was that adenomas in familial polyposis occurred earlier and multiply, and (2) the spatial distributions of adenomas and carcinomas for both cases were closely similar. It is therefore postulated that the adenoma-carcinoma sequence is as significant in the small bowels as in the large. A hypothesis regarding the relationship of epithelial neoplasms in people with and without familial polyposis disease is suggested.

The authors report two patients with familial adenomatous polyposis and thyroiditis. One patient was discovered at autopsy to have in addition, a follicular carcinoma of the thyroid and focal nodular hyperplasia of the liver. The other patient had a sister with familial adenomatous polyposis and a papillary carcinoma of the thyroid. The association between familial adenomatous polyposis and thyroiditis has not been previously reported.

Ophthalmic examinations were performed on 56 patients with validated familial adenomatous polyposis (FAP) for hyperpigmented defects of the retinal pigment epithelium. Such lesions were seen bilaterally in 29 patients (52%) and unilaterally in 8 patients (14%). Of the 56 patients, 33 had one or more of the extracolonic expressions associated with Gardner syndrome. We found retinal lesions in 8 patients without any of the expressions of Gardner syndrome. No association was found between Gardner syndrome and the retinal lesions when these patients were compared to patients without any stigmata of Gardner syndrome, nor was any significant association found when each of the expressions was compared individually with the presence of the pigmented retinal lesions. The presence or absence of eye findings were seen to cluster within families. There was no association with sex. Fundus lesions are apparently a variable expression of the FAP gene and are not specifically associated with Gardner syndrome.

A review of the St Mark's Hospital Polyposis Registry has revealed an association between adenomatous polyposis (familial polyposis coli) and thyroid carcinoma. Even though full clinical information was unavailable on all patients in the registry, it is evident that young women (below 35 years of age) are at particular risk of developing thyroid cancer, mainly of a papillary type, their chances of being affected being approximately 160 times that of normal individuals. All patients with adenomatous polyposis should thus have regular thyroid examination.

We examined 134 members of 16 families with Gardner's syndrome for pigmented ocular fundus lesions. Of 41 patients with documented Gardner's syndrome, 37 (90.2 percent) had such lesions. The lesions were bilateral in 32 of the patients (78.1 percent) and in 2 of 42 controls (4.8 percent). Twenty (46.5 percent) of 43 first-degree relatives at 50 percent risk for Gardner's syndrome had bilateral pigmented fundus lesions, indicating that they had probably inherited the abnormal gene. The presence of bilateral lesions, multiple lesions (more than four), or both appeared to be a specific (specificity, 0.952) and sensitive (sensitivity, 0.780) clinical marker for Gardner's syndrome. The lesions are probably congenital; they were observed in a three-month-old baby at risk. The multiplicity of the pigmented fundus lesions and their association with diffuse disturbances of the retinal pigment epithelium in the same eye suggest a widespread expression of the abnormal gene in the retinal pigment epithelial cells.

Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.

HLA typing was performed in 51 patients to analyse the pathogenetic background of differentiated and medullary thyroid carcinomas. A higher incidence of Bw62 and DR5 was observed in patients with papillary carcinoma (n = 24), DRw6 antigen in follicular carcinoma (n = 13), and DR3 antigen in patients with medullary carcinoma (n = 11). The DR3 antigen was present in one of two patients with a familial history of medullary thyroid carcinoma. Therefore, HLA typing is not suitable as a screening method for the detection of early thyroid carcinoma.

This report describes three patients with both multiple intestinal polyps and tumors of neural crest origin. This combination of findings may represent a new clinical syndrome. The embryologic relationships between tumors derived from endoderm and tumors derived from neurocrest are described. An inherent defect in tissue proliferation or repair is postulated to explain the abnormal growth in these two different cell lines.

Gardner syndrome is a dominantly inherited familial cancer syndrome characterized by intestinal polyposis, bony hamartomata, and various soft tissue tumors. The risk of malignancy during adult life is essentially 100%, but as yet no phenotypic marker nor biochemical or serological linkage have been useful to identify the presence of the gene in early life. We studied three families in which multiple and bilateral patches of congenital hypertrophy of the retinal pigment epithelium are related uniquely to other phenotypic features of the Gardner gene. This readily identifiable characteristic may be useful to identify early in life individuals at risk for malignancy. We also suggest that the Gardner syndrome may be genetically heterogeneous.

A case of malignant polyposis coli, occurring in a 71-year-old man in association with a primary invasive adenocarcinoma of the gallbladder is presented. The eventuality that the carcinoma of the gallbladder could be a metastasis from the colonic neoplasia was excluded due to the observation in the mucosa of the gallbladder of changes corresponding to carcinoma in situ. This is the fourth case reported of polyposis coli coexisting with a carcinoma of the biliary tract.

A 22-year-old white woman in whom multicentric papillary carcinoma of the thyroid developed two years after prophylactic colectomy for intestinal polyposis is reported. This association has been observed by others. Patients with familial polyposis coli are at risk for a variety of malignancies other than colonic, and careful life-long surveillance is necessary.

Two hundred and twelve papillary and 40 follicular carcinomas were found in 3002 thyroid glands examined from 1931 to 1975 in four Laboratories of Pathology that fairly cover northern Portugal. There was a striking preponderance of women both in papillary (female:male = 6.9:1) and follicular carcinoma (5.7:1). Sex-specific frequency of malignancy was significantly greater in men (13.3%) than in women (8.8%). The overall papillary/follicular ratio was 5.3:1 and did not significantly change throughout the study period. Papillary/follicular ratio was not significantly greater in litoral (5.5:1) than in regions with a low iodine intake and a relatively high prevalence of goiter (3.5:1). It is advanced that this high relative frequency of papillary carcinoma in northern Portugal, even in goiter areas, may reflect the existence of a racial factor since there is not enough evidence to support the influence of dietary iodine, previous irradiation and concurrent thyroiditis.

Endocrine neoplasms have occasionally been noted in patients with Gardner's syndrome and other polyposis coli (PC) syndromes; 15 such cases were found in a survey of the English literature. This article reports four additional patients with PC in whom occult endocrine neoplasms were found at autopsy. Four sets of 100 consecutive autopsy reports, each bracketing but excluding one of the above cases, were reviewed. The incidence of endocrine neoplasia in patients with non-PC-colorectal cancer (2/18) was similar to that in the entire sample (32/400), while four of five PC patients had such tumors. These data suggest that endocrine neoplasia is significantly more frequent in PC than in other cancer patients, and a more frequent part of the PC syndromes than generally recognized. The relevance of these data to the issue of the genetics of the PC syndromes is discussed.

A 48-year-old man with Gardner's syndrome, who had abdominoperineal resection for rectal carcinoma in 1962, was found to have an ulcerating growth of the duodenum, and pancreaticoduodenectomy was performed in 1979. Histologic examination by complete step-serial sectioning disclosed a well-differentiated adenocarcinoma with adenomatous remnants, a large adenoma with focal carcinoma, 256 adenomas of the duodenum, and 91 adenomas of the gastric antrum. The world medical literature was reviewed, and 29 cases of periampullary carcinoma and 12 cases of gastric carcinoma complicating familial polyposis coli or Gardner's syndrome were analyzed.

A patient with adenomatous polyposis coli (APC) without extraintestinal lesions is presented. The clinical course was complicated by rectal adenocarcinoma following subtotal colectomy. A primary adenocarcinoma arising in a villous adenoma within the ileostomy stoma developed seven years later. The varied pathology of gastric and small intestinal involvement in APC/Gardner's syndrome is reviewed. Greater awareness of these lesions has implications for further management.

The authors studied 51 patients who had small bowel tumors that contained adenomatous epithelium. These rare lesions were identified among 392,000 surgical pathology cases seen during a 62-year period. Grossly and histologically, adenomas arising in the mucosa of the small intestine are similar to the adenomas found in the colon. Of the 51 patients, 18 had adenomas, and 33 had tumors that contained both adenoma and carcinoma in the same lesion, including five intramucosal and 28 invasive carcinomas. The location of the tumor usually determined which clinical problems were produced. The data indicate that adenomas originating in the small bowel mucosa probably are premalignant lesions and that many primary adenocarcinomas of the small intestine arise in adenomas. Of the authors' 130 apparently primary small bowel carcinomas (including the papilla of Vater), 33 (25%) histologically demonstrated adenomatous epithelium in the same lesion. Factors associated with an increased chance of finding carcinoma in an adenoma include adenoma type, size of lesion, location, and multicentricity. Carcinomas appear to develop more frequently in papillary (villous) adenomas than in ordinary adenomas. The larger the lesion is, the more likely carcinoma will be identified. Adenomas involving the ampulla contain carcinoma more often than do lesions found elsewhere in the duodenum and small intestine. Three patients had multiple adenomatous polyps of the small bowel; two of these individuals also had duodenal carcinomas. Various problems in pathologic diagnosis and clinical management are discussed.

Gardner's syndrome is an autosomal dominant condition characterized by multiple colorectal polyposis, associated with various soft- and hard-tissue tumors. The occurrence of adrenal adenomas in patients with the syndrome has not been fully appreciated. The following is a report of a member of the original Utah kindred #109, first described in the early 1950's who was found at autopsy to have bilateral adrenal adenomas. A review of the literature resulted in the identification of six cases with adrenal adenomas and one with a primary adrenal carcinoma. The association with the syndrome of these adrenal tumors, as well as other endocrine tumors, especially thyroid tumors, is discussed.

In recent years, a number of comprehensive reviews have been written on inherited intestinal polyposis syndromes (1-7), but none has dealt specifically with Gardner's syndrome and none has focused on basic research being carried out in an attempt to understand this syndrome and to improve the medical management of affected patients. A better understanding of this rare genetic disorder is essential for surgeons, gastroenterologists, cancer researchers, and geneticists alike. To the clinician, it poses difficult challenges in management; to the cancer researcher, it presents a rare opportunity to study very early premalignant transformations; and to the geneticist, it poses exciting questions at the cellular, chromosomal, and molecular levels.

In a family with colonic polyposis and the typical associated findings of Gardner syndrome (osteomas and soft-tissue tumors), two and possibly four of the affected members developed periampullary malignancy. A review indicates that individuals with Gardner syndrome may have a 100- to 200-fold increased risk of developing periampullary carcinoma when compared to the general population. While certain families and certain individuals (those with other duodenal involvement, males and those with all of the characteristics of Gardner syndrome expressed) may be most susceptible, all patients with Gardner syndrome should be periodically endoscopically evaluated for the presence of upper gastrointestinal tract disease.