A young Female Patient with Gardner Syndrome: a case report

中華放射醫誌 Chin J Radiol 2008; 33: 5-56 5 A young Female Patient with Gardner Syndrome: a case report Yu-Kun Tsui Reng-Hong Wu Ching-Cherng Tzeng 2 Te-Chang Wu Tai-Yuan Chen Tai-Ching Wu Wen-Sheng Tzeng Department of Radiology, Department of Pathology 2, Chi Mei Medical Center Gardner syndrome is a variant of the familial adenomatous polyposis syndrome. We describe a case of Gardner syndrome with clinical manifestations including colonic and gastric polyposis, colon adenocarcinoma, abdominal desmoid tumor, and skull osteomas. A 37-year-old woman suffered from intermittent epigastric dull and cramping pain for one week. Moreover, poor appetite and vomiting after medication and no stool passage were also noted. An abdominal computed tomography (CT) revealed infiltrative tumor at hepatic flexure of colon and two tumor masses at abdominal wall. Colonoscopy showed polyposis and the biopsy showed tubular adenoma. The patient underwent surgical intervention. Colon adenocarcinoma, adenomatous polyposis of colon, and abdominal wall desmoid tumors were diagnosed. Three months later, the patient suffered from upper gastrointestinal (UGI) bleeding and conscious change. UGI endoscope study revealed gastric polyposis and a brain CT survey showed multiple osteomas. The diagnosis of Gardner syndrome was made according to these clinical manifestations. Physicians should be aware of this diagnosis and further evaluation is needed if any of the clinical manifestations of Gardner syndrome is found. Gardner syndrome is a variant of the familial Reprint requests to: Dr. Wen-Sheng Tzeng Department of Radiology, Chi Mei Medical Center No. 90, Chung Hwa Road, Yung Kang, Tainan 70, Taiwan, R.O.C. adenomatous polyposis syndrome []. This disease is characterized by the presence of familial adenomatous polyposis, benign osteomas, and skin and soft tissue tumors [, 2]. We describe a case of Gardner syndrome with clinical manifestations including colonic and gastric polyposis, colon adenocarcinoma, abdominal desmoid tumor, and skull osteomas. CASE REPORT A 37-year-old female patient suffered from intermittent epigastric dull and cramping pain for one week. She had visited local medical department, while the symptoms could not be resolved after medication. Moreover, poor appetite and vomiting after medication and no stool passage were noted. Because of the persistent symptoms, she was referred to our emergency department for help. She did not have any major disease before, except underwent tubal ligation years ago. At ER, abdominal CT was performed and revealed tumor infiltration at hepatic flexure of colon with marked dilatation of proximal intestinal loops and collapse of the distal colon (Fig. a). The diagnosis of colon cancer was made according to CT images. Additionally, there were two well enhanced abdominal wall masses measuring about 6.5 4.4 cm and 2.7.8 cm in size at right lower quadrant of abdomen (Fig. b). After admission, colonoscopy was performed first up to 90 cm from the anal verge, but the procedure was stopped due to intolerance of this patient. Colonoscopy showed colonic polyposis (Fig. 2). Biopsy of one polyp showed tubular adenoma. Surgical resection including radical right hemicolectomy, colostomy, and partial excision of abdominal wall tumor was performed two days later. Pathology of the resected colon showed adenocarcinoma and polyposis. There was no evidence of mesenteric metastatic lymphadenopathy (Fig. 3). The pathology of the abdominal wall tumor revealed desmoid tumor (Fig. 4). After post-operative wound care, she was discharged with the diagnosis of polyp-

52 Gardner syndrome a Figure. a. Contrast-enhanced CT scan shows tumor infiltration at hepatic flexure of colon (black arrow). There is no enlarged lymph node nearby the colon tumor mass. b. Contrast-enhanced CT scan shows one of the abdominal wall masses with well enhancement at RLQ of abdomen (white arrow). Marked dilatation of proximal intestinal loops and collapse of the distal colon are also depicted. b Figure 2. Colonoscopy shows many polyps in the colon. Figure 3. Histological photomicrography reveals welldifferentiated adenocarcinoma with tumor invasion into pericolonic connective tissue ( H & E stain, 00 original magnification ). osis syndrome with colon cancer. Adjuvant chemotherapy was given weekly in out-patient department. Unfortunately, three months later, the women suffered from progressive weakness for several days. There were vomiting and tarry stool passage from colostomy. She was brought to our ER for help. Neutropenia and hyponatremia were noted. She was admitted under the impression of shock and upper gastrointestinal (UGI) bleeding. UGI endoscopy was arranged for UGI bleeding survey, which revealed diffuse esophagitis with ulcers, multiple polypoid lesions in gastric body and fundus (Fig. 5). Biopsy of one of the polyps revealed fundic gland polyp. During hospitalization, confusion state was noted and brain CT scan showed no evidence of intracranial abnormality, while multiple well-circumscribed cortical nodules and hyperdensity at ethmoid sinus as well as outer table of skull were found incidentally, sugges-

Gardner syndrome 53 tive of multiple osteomas (Fig. 6). Gardner syndrome was considered according to the aforementioned clinical manifestations. After appropriate treatment including supportive treatment, antibiotics and proton pump inhibitor agent, the patient was discharged in stable condition and follow-up at OPD. DISCUSSION Gardner syndrome, which was first described in 953 by Gardner and Richard, is a disease characterized by gastrointestinal polyps that develop in the colon as well as in the stomach and upper intestine, multiple osteomas, and skin and soft tissue tumors [2]. Gardner syndrome is an autosomal dominant disorder genetically associated with chromosome 5-q2, the adenomatous polyposis coli locus [3]. However, approximately 20% of patients demonstrate new mutations and have a negative family history [4]. Most authors believe that Gardner syndrome is a Figure 4. Histological photomicrography shows the tumor composed of bland spindled or stellate fibroblastic cells embedded in a collagenous stroma, (H & E stain, 00 original magnification). Figure 5. UGI endoscopy shows diffuse nodular mucosa and multiple polypoid nodules at gastric body and fundus. Hemorrhagic surface is noted in some of the lesions. Figure 6. Precontrast CT scan of brain shows several well-circumscribed lesions with high density at ethmoid sinus and skull outer table (arrows).

54 Gardner syndrome variant of familial polyposis due to the wider spectrum of abnormalities []. One person per million is diagnosed with Gardner syndrome in United State [3]. Most patients manifest clinical symptoms and are diagnosed by 20 years of age. However, symptoms may occur anytime between 2 months to 70 years. The clinical signs and symptoms of Gardner syndrome include rectal bleeding, cramping abdominal pain, weight loss, diarrhea, and small bowel or colonic obstruction [5]. The gastrointestinal manifestations of Gardner syndrome include colonic adenomatous polyps (tubular, villous, tubulovillous), gastric and small intestinal adenomatous poly ps (2% of patients) and periampullary carcinomas (2% of patients) [3]. There is nearly 00% rate of malignant transformation of the gastrointestinal adenomatous polyps into adenocarcinoma. Progression to malignancy is usually in patients aged 30 to 50 years, with the average age at 39.2 years [6]. Prophylactic total colectomy and removal of all colonic mucosa are advocated but do not ensure cure because these patients are at the high risk of developing other tumors [7]. Other manifestations of Gardner syndrome include osteomas, dental anomalies, cutaneous sebaceous cysts, retinal pigmentation anomalies, epidermoid cysts, desmoid tumors, and papillary thyroid cancer. Therefore, lifelong follow-up including gastrointestinal surveillance, ophthalmologic evaluation, thyroid screening and other imaging techniques is necessary [7]. Osteoma is one of triad for the diagnosis of Gardner syndrome. Approximately 50% of patient with Gardner syndrome develop osteomas [, 3, 7]. Osteoma is a benign neoplasm consisting of well-differentiated cancellous or compact bone that increases in size by continuous osseous growth [6]. Although the mandible and skull are the most common locations, osteomas may be seen in other bones as well. Treatment for osteomas of Gardner syndrome, similar to treatment of cutaneous manifestations, depends on the symptomatic or cosmetic nature. Desmoid tumors occur infrequently in the general population with an incidence of 2.4 to 4.3 cases per million inhabitants per year [8]. However, patients with Gardner syndrome or familial adenomatous polyposis are at near 000-fold increased risk of developing desmoid tumors as compared with the general population [9, 0]. Surgical trauma also seems to precipitate a majority of desmoid tumors. These tumors occur predominantly in relatively young female patients. A high rate of postoperative recurrence in patients with Gardner syndrome with mesenteric desmoid tumors has been reported []. Epidermoid cysts of Gardner syndrome occur at an earlier age in less common locations (eg, face, scalp, extremities) and tend to be multiple, but often asymptomatic [2]. Other skin findings include the following: fibromas, lipomas, leiomyomas, neurofibromas, and pigmented skin lesions [6]. In about 90% of population, retinal pigmented lesions occur, and may be the first marker of disease detected at an early age. Papillary thyroid cancer is noted with increasing frequency in patients with Gardner syndrome and is often multicentric [3, 7]. Gardner syndrome has been reported to cause acute pancreatitis as a consequence of an adenoma of the ampulla of Vater and acute relapsing pancreatitis related to an adenoma of the common bile duct [3]. A rare case of sudden death from hyponatremia and hypokalemia associated with florid gastric polyps in a woman with Gardner syndrome has also been reported [4]. The metabolic state of these patients should be noticed. Considering the autosomal dominant nature of the disease, all first-degree relatives of patients with Gardner syndrome or familial adenomatous polyposis should be screened [6]. Ophthalmological examination can detect the pigmented lesions of the fundus. Double-contrast barium enema studies, upper gastrointestinal series, small bowel series, or colonoscopy and UGI endoscopy are essential studies for the evaluation of gastrointestinal manifestations. CT colonoscopy is a noninvasive, rapidly evolving technique that is a potential alternative to conventional colonoscopy for screening [5]. Panoramic radiography, skull or long bone radiographs may demonstrate the osteomas. Physical examination and sonography can be performed for screening of thyroid tumors [7]. In summary, we report a woman with Gardner syndrome. Physicians should be aware of this disease if one of the manifestations of Gardner syndrome is found, especially polyposis. Further surveillance and follow-up should be performed due to the high incidence of malignant transformation of intestinal polyps. REFERENCE. Harned RK, Buck JL, Olmsted WW, et al. Extracolonic manifestations of the familial adenomatous polyposis syndromes. AJR Am J Roentgenol 99; 56: 48-485

Gardner syndrome 55 2. Gardner EJ, Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet 953; 5: 39-47 3. Fotiadis C, Tsekouras DK, Antonakis P, et al. Gardner s syndrome: A case report and review of the literature. World J Gastroenterol 2005; : 5408-54 4. Watne AL. Colon polyps. J Surg Oncol 997; 66: 207-24 5. Nelson RL, Orsay CP, Pearl RK, Abcarian H. The protean manifestations of familial polyposis coli. Dis Colon Rectum 988; 3: 699-703 6. Bilkay U, Erdem O, Ozek C, et al. Benign osteoma with Gardner syndrome: review of the literature and report of a case. J Craniofac Surg 2004; 5: 506-509 7. Newman CA, Reuther WL 3rd, Wakabayashi MN, et al. Gastrointestinal case of the day. Gardner syndrome. Radiographics 999; 9: 546-548 8. Reitamo JJ, Scheinin TM, Haeyry P. The desmoid syndrome: new aspects in the cause, pathogenesis, and treatment of the desmoid tumor. Am J Surg 986; 5: 230-237 9. Gurburz AK, Giardiello FM, Petersen GM, et al. Desmoid tumours in familial adenomatous polyposis. Gut 994; 35: 377-38 0. Misiakos, Evangelos P.; Pinna, et al. Recurrence of desmoid tumor in a multivisceral transplant patient with gardner s syndrome. Transplantation 999; 67: 97-99. Hizawa K, Iida M, Mibu R, et al. Desmoid tumors in familial adenomatous polyposis/gardner s syndrome. J Clin Gastroenterol 997; 25: 334-337 2. Marshall KA, Kuhlmann TP, Horowitz JH, et al. Excision of multiple epidermal facial cysts in Gardner s syndrome. Am J Surg 985; 50: 65-66 3. Herman LL, Kurtz RC, Brennan MF, Shike M. Acute pancreatitis from intussusception of a gastric polyp in a patient with Gardner s syndrome. Dig Dis Sci 992; 37: 955-960 4. Burke MP, Opeskin K. Sudden death from hyponatremia and hypokalemia in a woman with Gardner syndrome. Am J Forensic Med Pathol 200; 22: 84-87 5. Silva AC. Vens EA. Hara AK. et al. Evaluation of benign and malignant rectal lesions with CT colonography and endoscopic correlation. Radiographics 2006; 26:085-099

56 Gardner syndrome 年輕女性病患有 Gardner 氏症 : 病例報告 崔祐堃 吳仁宏 曾慶誠 2 吳德昌 陳泰源 吳泰清 曾文盛 財團法人奇美醫院放射線部 病理部 2 Gardner 氏症為家族性腺瘤性瘜肉症的一種變化 我們在此報告一個 Gardner 氏症的病例合併有大腸與胃瘜肉症 大腸癌 腹部硬纖維瘤與頭部骨瘤 一位 37 歲女性遭受間歇性腹部上腹悶痛與絞痛的情形約一個星期 ; 同時也發現有食慾不振 嘔吐與無排便的情形 腹部電腦斷層掃瞄顯示一浸潤性腫瘤位在大腸肝彎處以及兩個腹壁腫瘤 大腸鏡顯示大腸瘜肉症, 切片顯示為管狀腺瘤 病患接受手術後診斷為大腸肝彎大腸癌, 腺瘤性瘜肉症與腹壁硬纖維瘤 三個月後, 病患發生上消化道出血與意識改變的情形, 上消化道內視鏡發現有胃部瘜肉症以及頭部電腦斷層檢查發現有頭部骨瘤 依據這些臨床表現診斷為 Gardner 氏症 如果臨床上發現有其中一項 Gardner 氏症的表徵, 我們要留意此診斷的可能性與進行進一步的評估