A Case of Familial Adenomatous Polyposis Complicated by Thyroid Carcinoma, Carcinoma of the Ampulla of Vater and Adrenocortical Adenoma
Chihiro ONO, Takeo IWAMA and Yoshio MISHIMA
ABSTRACT: A 63 year old female with familial adenomatous polyposis (FAP) complicated by carcinoma of the thyroid and ampulla of Vater and a nonfunctioning adrenocortical adenoma is reported herein. We reviewed 23 cases of duodenal or periampullary carcinoma, 10 cases of thyroid carcinoma and 4 cases of adrenal neoplasm presented in the Japanese literature. From studying these cases, we identified that FAP patients had a high risk of developing periampullary carcinoma and consequently, it is very important to periodically examine the ampulla of Vater. Thyroid carcinomas in patients with FAP were well differentiated carcinomas and occurred earlier than in the general population. The use of medical imaging equipment with mean that insidious abdominal tumors in cases of FAP will be detected more frequently in the future and as patients with FAP have a high risk of developing malignancies, surgery should be indicated for incidentally found adrenal tumors.
KEY WORDS: familial adenomatous polyposis, carcinoma of the ampulla of Vater, thyroid carcinoma, adrenocortical adenoma
INTRODUCTION
Patients with familial adenomatous polypo- sis (FAP) reportedly have a high risk of developing even extra-colonic malignancies. We experienced a patient with FAP who developed three different extra-colonic neo- plasms, namely; thyroid carcinoma, carci- noma of the ampulla of Vater and a non- functioning adrenocortical adenoma. We present this case in conjunction with a review
of the Japanese literature.
CASE REPORT
A 63 year old female was first referred to our hospital in May 1976, at the age of 50 years, for evaluation after her younger brother was diagnosed as having FAP and colonic carcinoma. She was also diagnosed as having FAP, as was her mother, 2 brothers, a daughter, a grandchild, a nephew and two nieces. Her daughter also had thyroid car- cinoma and her nephew had undergone surgery for a Wilms’ tumor. Her past medical history was notable only for an appendec- tomy and a hysterectomy for myoma of the uterus. Physical examination showed a tumor of about 1.0 cm in diameter in the right thyroid lobe. Laboratory tests showed no abnormalities except for a slight elevation in
The Second Department of Surgery and the Research Center for Polyposis and Intestinal Disease, Tokyo Medical and Dental University, Tokyo, Japan
Reprint requests to: Takeo Iwama, MD, The Re- search Center for Polyposis and Intestinal Disease, the Second Department of Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan
| Volume | 21 |
| Number | 2 |
| Blood | Serological findings | ||
|---|---|---|---|
| RBC | 451×104/uL | CRP | 6++* |
| Hb | 14.8 g/dL | Endocrinological findings | |
| Hct | 45.6% | s-T4 | 14.8 ug/dL* |
| WBC | 5500/uL | s-free T4 | 1.5.ng/dL |
| Plt | 22.6×104/uL | s-T3 | 130 ng/dL |
| Biochemical findings | TSH | 4 uU/mL | |
| T. protein | 6.8 g/dL | s-Cortisol | 17.6 ug/dl |
| Alb. | 3.7 g/dL ** | s-110HCS | 24.7 ug/dl |
| BUN | 15 mg/dL | u-17OHCS | 3.0 mg/dL |
| Cre | 0.8 mg/dL | u-17KS | 1.5 mg/dL ** |
| Na | 141 mEq/L | u-Catecholamine | 68 ug/day |
| K | 3.7 mEq/L | u-VMA | 3.4 mg/day |
| LDH | 445 U/L* | u-HVA | 3.4 mg/day |
| GOT | 202 U/L* | u-5-HIAA | 3.4 mg/day |
| GPT | 252 U/L* | Tumor marker | |
| r-GPT | 1123 U/L* | CEA | 5.7 ng/mL* |
| ALP | 1174 U/L* | AFP | <1 ng/ml |
| T. Bil | 1.5 mg/dL* | Ferritin | 440 ng/dL* |
| D. Bil | 0.7 mg/dL* | CA19-9 | <6 ng/ml |
| T. Cholesterol | 288 mg/dL* | Du-Pan II | 1190 U/mL* |
| TG | 113 mg/dL* | Feces | |
| Lipoprotein | 351 mg/dL* | Occult blood | (-) |
| LAP | 379 U/L* | ||
| Amylase | 971 U/L* | ||
*, increased; ** , decreased; s-, serum; u-, urinary
serum thyroxine level, and normal levels of serum free thyroxine and thyroid stimulating hormone. A barium enema and colonoscopy revealed many polyps throughout the entire colon. A total colectomy with ileo-rectal anastomosis and a hemithyroidectomy were performed which revealed 775 polyps but no malignancies. The thyroid tumor was a well encapsulated follicular carcinoma without lymphatic or distant metastasis. The remain- ing rectum, thyroid, stomach and duodenum were periodically examined and she was again hospitalized in June 1989, at the age of 63, for back and right upper quadrant ab- dominal pain. Although jaundice was not observed, the gallbladder was tender on palpation. Laboratory data showed hepatic cellular damage with cholestasis and slightly elevated serum carcinoembryonic antigen and ferritin (Table 1). CT examination re- vealed a 3.0 cm tumor at the right adrenal
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gland which had clear margins with slight contrast enhancement (Fig. 1). Endocrino- logic examination demonstrated no abnor-
malities except for decreased urinary 17- ketosteroids. No polyps were found in the stomach or duodenum. Although the am- pulla of Vater showed no specific findings, endoscopic retrograde cholangiography re- vealed a dilated common bile duct measur- ing 2.2 cm in diameter with stenosis at the ampulla of Vater. An adrenalectomy and cholecyctectomy with transduodenal sphinc- terotomy were performed, and a small tumor diagnosed as a moderately differentiated villous adenocarcinoma was observed inside the ampulla of Vater. A pancreaticoduode- nectomy was then carried out and no duo- denal or pancreatic infiltration or regional lymphnode involvement observed (Fig. 2). The adrenal tumor was an adrenocortical adenoma, 4.0 × 3.0 × 1.6 cm in size, which consisted of clear cells and compact cells, and was encapsulated in tissue. After the adrenalectomy, there were no symptoms of adrenal insufficiency, such as hypotension or hyponatremia. The adrenal tumor was diag- nosed as being non-functional and the pa- tient recovered uneventfully and was dis- charged in a satisfactory condition.
DISCUSSION
A review of the Japanese literature re- vealed, including our case, 23 cases of duo- denal or periampullary carcinoma,1-20 10
cases of thyroid carcinoma21-28 and 4 cases of adrenal neoplasm24,27,29 associated with FAP. The first case of FAP being associated with periampullary carcinoma was reported by Cabot30 in 1935, and in Japan, 23 cases of FAP with periampullary or duodenal car- cinoma have been reported (Table 2) com- prising 12 males and 11 females with a mean age of 42 years, ranging from 19 to 63 years. Considering that the average age when duo- denal or periampullary carcinoma develops in the general Japanese population is re- ported to be from 5431-93 to 60 years of age, patients with FAP tend to develop periampul- lary carcinoma about 13 years earlier. The interval between colo-rectal carcinoma and the occurrence of periampullary carcinoma varied. In 2 cases, periampullary carcinoma occurred earlier than colonic carcinoma, while in 5 cases, they were detected at the same time, and in 7 cases, colo-rectal car- cinoma was diagnosed first, from 22 months to 25 years earlier. In 7 cases, colorectal surgery for FAP had been performed before the development of colorectal carcinoma and in the remaining 2 cases, the interval was obscure. This relationship suggests that colo-rectal carcinoma usually occurs earlier than periampullary carcinoma, but the age distribution of both tumors overlaps in a wide range. Eighteen of the 23 tumors (78 per cent) were located at the ampulla or periampullar region, 6 of which (Cases 3, 7, 9, 19, 20, 23) were very small and situated just at the ampulla of Vater. In one case (Case 23), the carcinoma was not exposed to duo- denal mucosa and 8 cases had no duodenal polyps. The duodenal polyps seen appeared to be benign, and not the origin of the carcinoma, suggesting that examination of the biliary tract, including the ampulla of Vater, and gastroduodenoscopy are impor- tant in the follow up of FAP patients.
There were 10 cases, including our own, of thyroid carcinoma, 4 of which were males and 6 females, (Table 3) and 4 cases, 1 male and 3 females of adrenal neoplasm (Table 4). Eight (80 per cent) of the thyroid car-
| Case | Age | Sex | Site /Operation | Colo- rectal Cancer | Interval from Colo- rectal Ca. | Duodenal Polyp | Gastric Polyp | Author |
|---|---|---|---|---|---|---|---|---|
| 1 | 19 | F | inf. flexure | |||||
| / autopsy | + | + | - | Iida1 "78 | ||||
| 2 | 29 | F | 4th/GJ | - | * | ? | + | Obata2 "78 |
| 3 | 36 | M | PA/PD | - | - | - | Kimura3 '82 | |
| 4 | 45 | M | PA/PD | + | 0 | - | - | Takano4 '82 |
| 5 | 46 | M | 2nd/PD | + | 17 years | 256 | + | Sugihara5 '82 |
| 6 | 31 | F | duodenum | |||||
| / autopsy | - | 100 | + | Ogawa6 '83 | ||||
| 7 | 46 | M | PA/PD | - | - | + | Yosimi? '84 | |
| 8 | 47 | F | 1st/PD | + | 22 months | 10 | - | Iida8 '84 |
| 9 | 41' | M | PA/PD | + | 4 years | 29 | - | Hishiki9 '84 |
| 10 | 46 | M | 2nd/PD | + | 6 years | + | + | Egawa1º '85 |
| 11 | 51 | M | 2nd/PD | + | 0 | ? | ? | Kajihara '86 |
| 12 | 43 | M | PA/PD | + | 3 years | ? | ? | Tada12 '86 |
| 13 | 44 | M | PA/PD | ? | + | - | Aioi18 '87 | |
| 14 | 40 | F | PA/LE | + | 0 | + | + | Masaki14 '87 |
| 15 | 47 | M | PA/LE | + | 0 | - | - | Shimoda15 '87 |
| 16 | 48 | F | PA/PD | - | - | - | Suzuki16 '87 | |
| 17 | 41 | F | PA/PD | + | 12 years | 5 | ca | Yamanaka '88 |
| 18 | 45 | M | PA/Autopsy | + | 3 years | - | - | Hirokawa '88 |
| 19 | 32 | F | PA/PD | - | - | - | Hohjyo19 '89 | |
| 20 | 49 | F | PA/PD | + | 25 years | + | ca | Kataoka20 '89 |
| 21 | 36 | M | PA/PD | - | + | + | ** '85 | |
| 22 | 43 | F. | PA/PD | + | 12 years | + | + | ** '86 |
| 23 | 63 | F | PA/PD | - | - | - | ** |
PA, Periampullary carcinoma; GJ, Gastro-jejkunostomy; PD, Pancreatico-duodenectomy; LE, Local excision; Ca., carcinoma; 1st, first portion; 2nd, second portion; 4th, fourth portion.
*, There was no colonic carcinoma when reported; ** , our experiences.
| Case | Age | Sex | Histological Diagnosis | Colo-rectal Ca. | Author |
|---|---|---|---|---|---|
| 1 | 31 | M | adenocarcinoma | + | Ogata21 '64 |
| 2 | 58 | M | papillary carcinoma | + | Takahashi22 "76 |
| 3 | 26 | M | carcinoma | + | Iida23 '77 |
| 4 | 26 | F | carcinoma | + | Iida23 "77 |
| 5 | 27 | M | carcinoma | + | Ushio24 "77 |
| 6 | 22 | F | papillary carcinoma | - | Harada25 "77 |
| 7 | 29 | F | papillary carcinoma | + | Okamura26 "79 |
| 8 | 27 | F | papillary carcinoma | + | Miura27 '80 |
| 9 | 26 | F | papillary carcinoma | + | Masuyama28 '86 |
| 10 | 50 | F | follicular carcinoma | - | ** |
carcinoma. the only case reported as thyroid carcinoma; Ca., carcinoma.
** , our own experience.
| Case | Age | Sex | Histological Diagnosis | Colo-rectal Ca. | Author |
|---|---|---|---|---|---|
| 1 | 48 | F | adenoma | + | Ushio24 "77 |
| 2 | 27 | F | nodular hyperplasia | - | Miura27 '80 |
| 3 | 18 | (adrenocortical adenoma) | |||
| M | adrenocortical adenoma (adrenal carcinoma) | - | Furuya19 '89 | ||
| 4 | 63 | F | adrenocortical adenoma | - | ** |
Ca., carcinoma.
** , our own experience.
cinoma cases occurred in patients in their twenties or thirties. Thyroid carcinoma also occurred earlier than in the general popula- tion. Six cases with known histology had well differentiated carcinoma, 5 being papillary carcinomas and 1 follicular carcinoma. Since most cancers associated with FAP are well differentiated with a good prognosis and as the thyroid gland is a superficial organ, we can expect curative treatment for thyroid carcinoma in FAP patients if it is found in the early stages.
Owing to the improvement in medical imaging with equipment such as X-ray CT and ultrasonography, an increasing number of adrenal tumors or so-called adrenal inci- dentalomas, are expected to be discovered. Bitter et al34 reviewed many reports of the surgical indications for such adrenal inci- dentalomas. The critical size for carcinoma varied from 3.5 cm to 6.0 cm, but most authors recommend removing the tumors if the possibility of malignancy cannot be ex- cluded. As FAP has a high potential of developing malignancies, surgery should be more often performed for adrenal inci- dentalomas in FAP cases than sporadic cases. It is noteworthy that one of the four cases of adrenal neoplasms associated with FAP was first diagnosed as an adrenal adenoma, which recurred after removal as an adrenal carcinoma.
It is also well known that FAP patients are more prone to develop colorectal carcinoma, so if it is prevented, an improved prognosis
for FAP depends largely upon the early discovery of extra-colonic malignancies.
(Received for publication on Dec. 28, 1989)
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