Open Access

Secondary tumours of the ampulla of Vater: Case report and review of the literature

  • Authors:
    • Francesca Sarocchi
    • Magdalena M. Gilg
    • Florian Schreiber
    • Cord Langner
  • View Affiliations

  • Published online on: December 12, 2017     https://doi.org/10.3892/mco.2017.1535
  • Pages:274-280
  • Copyright: © Sarocchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Secondary tumours of the ampulla of Vater are rare. Underlying primary tumours, clinical presentation, macroscopic appearance, treatment strategies and outcome of secondary ampullary lesions have not been systematically analysed. The present case study reported a 57-year old patient with an ampullary metastasis from renal cancer and a literature review was performed in which a further 32 patients were included. The most common responsible primary tumours were malignant melanoma and renal clear cell carcinoma, followed by breast cancer. The time interval between the diagnosis of the primary tumour and the ampullary metastasis was highly variable, and may be as long as 10 years, particularly for renal cancer. Patients may present with unspecific abdominal discomfort, jaundice or upper gastrointestinal bleeding. The gross appearance was largely indistinguishable from that of a primary tumour. Lesions may present as polypoid or irregular, soft and friable tumour mass, in certain cases with superficial ulceration. In ~50% of cases, the ampullary metastasis was the only metastatic lesion, while in the remaining cases, the cancer had spread to one or more organs. The prognosis was generally poor. The management requires a multi-modal approach, including endoscopic, surgical and oncological procedure.

Introduction

The ampulla of Vater was first described in a detailed manner by Abraham Vater in 1720 and it consists of three different anatomical structures: the duodenum, the terminal tract of the pancreatic duct and the final portion of the common bile duct (1). These elements have distinct functions and histological features, comprising intestinal, pancreatobiliary and gastric mucosal types (2).

Primary ampullary cancer comprises two main histological subtypes, the pancreatobiliary type and the intestinal type, but also rarer variants such as signet ring cell, adenosquamous, mucinous, clear cell, papillary, and neuroendocrine carcinoma (3,4). Adsay et al (2) classified ampullary cancers into four subtypes based upon their location which reflects different prognosis: intra-ampullary, peri-ampullary/duodenal, ampullary-ductal and ampullary lesions not otherwise specified. Occasionally, tumours of the pancreatic head or distal bile duct may extend into the ampullary region, thereby mimicking a primary ampullary neoplasm.

Several malignancies have been reported to involve the upper gastrointestinal tract in a secondary manner and among these lung cancer, breast cancer and malignant melanoma seem to be the most common primary sites (5). Within the upper gastrointestinal tract, the stomach is more often affected by secondary tumours than the duodenum. However, metastasis to the ampulla of Vater is exceedingly rare, with only 31 cases reported so far (633).

Herein we report the case of a 57-year-old patient who developed ampullary metastasis from renal cell carcinoma 3.5 years following initial diagnosis. Additionally, we conducted a systematic and comprehensive literature review summarizing all cases of secondary ampullary tumours documented in MEDLINE/PubMed until December 2016.

Case report

A 57-year-old male patient presented with subacute upper gastrointestinal bleeding 3.5 years at the Department of Gastroenterology, Medical University of Graz (Graz, Austria) following nephrectomy for renal clear cell carcinoma (pT3b, G2, N0, M0, R0). The requirement for written informed consent was waived for the present case report. The patient did not undergo any further adjuvant treatment but had regular follow-up until the occurrence of upper gastrointestinal bleeding. Upon gastroscopy, the ampulla of Vater was irregularly enlarged, vulnerable (Fig. 1A), and multiple biopsies were taken. All other parts of the upper gastrointestinal tract were entirely normal.

Histology showed well differentiated cancer cells with clear cytoplasm and small to moderately enlarged, hyperchromatic nuclei. The tumour cells were arranged in alveolar pattern (Fig. 1B-C) and were detected mainly in the submucosa with secondary ulceration of the mucosal surface. Findings ultimately prompted diagnosis of secondary ampullary carcinoma, that is, metastatic disease from renal cell cancer.

Staging including CT of chest, abdomen and pelvis as well as whole body bone scan did not reveal further metastatic lesions. The patient underwent pylorus-preserving pancreaticoduodenectomy (Whipple procedure). Macroscopic workup of the surgical specimen showed a yellowish tumour mass within the ampulla, measuring 3 cm in largest diameter. All surgical resection margins and all dissected lymph nodes were free of cancer. The postoperative course was uneventful, and the patient discharged on postoperative day 15. Since then, the patient undergoes regular controls, including CT scans of the abdomen in regular intervals and there is now, four years after resection, no evidence of local recurrence or distant metastasis.

Discussion

We presented a rare case of secondary tumour of the ampulla of Vater. The corresponding primary tumour was renal clear cell carcinoma that had been operated 3.5 years earlier. Following pancreaticoduodenectomy, the patient is free of cancer for four years now.

A total of 32 secondary tumours, including our own case, have been reported to occur within the ampulla so far (Table I). Mean age at diagnosis of the secondary tumour is 56 years (median 55; range 27–81) (633). Renal carcinoma (n=11; 34%), malignant melanoma (n=10; 31%) and breast cancer (n=4, 13%) are the most common corresponding primary tumours. These three entities account for approximately three fourths of cases.

Table I.

Secondary tumours of the ampulla of Vater-literature overview and case report.

Table I.

Secondary tumours of the ampulla of Vater-literature overview and case report.

Authors, yearNo.SexAge at diagnosis of metastasisMacroscopy of ampullary lesionLocation of primary tumourDiagnosis of primary tumourTime interval between diagnosis of primary tumour and metastasisSymptomsaAdditional metastases (at time of diagnosis of ampullary tumour)TherapybOutcome(Refs.)
England and Sarr, 19901M70NSSkin: posterior thoraxMalignant melanoma3 years1, 3, 4Bone, liver3, 4, 5NS(6)
Sans et al, 19962M511Skin (NS)Malignant melanoma3 months1, 3Brain2Succumbed after 3 months(7)
Meyers et al, 19983M561, 3Skin: left upper backMalignant melanoma3 years2, 3Brain, skin3Succumbed after 4,5 months(8)
Caballero-Mendoza et al, 19994M48NSSkin: backMalignant melanomaSynchronous1, 3, 4Lungs, stomach, mediastinum, liver, spleen2, 4Succumbed after 4 months(9)
Le Borgne et al, 20005F623Skin (NS)Malignant melanoma8 years3No3, 4No evidence of disease 12 months after resection(10)
Le Borgne et al, 20006F333Skin (NS)Malignant melanomaNS3NS3Survived 2 months after resection(10)
van Bokhoven et al, 20067F661Skin: left side of the trunkMalignant melanoma (2 primary lesions)3 years1, 3No2NS(11)
Marks et al, 20108F661, 3Skin: right forearmMalignant melanoma4 years1, 3Right superior eyelid, chest, gallbladder, abdomen, pelvis, superficial soft tissue2, 4Succumbed after 15 months(12)
Uiterwaal et al, 20119F41NSSkin: left shoulderMalignant melanoma10 months1Brain4, 5Succumbed 8 months(13)
Nakayama et al, 201110F811VaginaMalignant melanomaSynchronous2, 4Liver, the primary lesion extended to the cervix of uterus and to the pelvis, behind the bladder1Succumbed after 1 month(14)
McKenna and Kozarek, 198911M521Kidney (right)Clear cell carcinoma10 years3, 4Left kidney, right lower pulmonary lobe2, 3NS(15)
Robertson and Gertler, 199012M701, 2, 3Kidney (left)Clear cell carcinoma12 years2, 4No3NS(16)
Venu et al, 199113M641, 2Kidney (left)Clear cell carcinoma11 years2, 4Bone3, 4Succumbed postoperatively due to massive pulmonary embolism(17)
Bolkier et al, 199114F551Kidney (left)Clear cell carcinomaNS3Left breast, brain2Succumbed after 2 months(18)
Leslie et al, 199615F781, 3Kidney (left)Clear cell carcinoma10 years3, 4No3No evidence of disease 2.5 years after resection(19)
Leslie et al, 199616M531, 3Kidney (right)Clear cell carcinoma8 years2, 4Mesenteric nodulation, retroperitoneal mass3, 4Alive with residual disease 6.5 years after resection(19)
Janzen et al, 199817M751, 3Kidney (left)Clear cell carcinoma17.5 years2, 3Spleen3NS(20)
Mendoza et al, 200118M491, 2, 3Kidney (right)Clear cell carcinoma2.5 years1, 2No3Succumbed after 3 months(21)
Hata et al, 201319F501, 2, 3Kidney (left)Clear cell carcinoma13 years2Bone, spleen3Alive with residual disease 1 year after resection(22)
20M571, 2, 3Kidney (left)Clear cell carcinoma3.5 years2No3No evidence of disease 4 years after resectionPresent case
Haidong et al, 201421M50NSKidney (right)Clear cell carcinomaSynchronous3No3,4No evidence of disease 5 years after resection(32)
Titus et al, 199722F501, 3Breast (left)Invasive carcinoma of no special type4 years3No3, 4alive after 4 months(23)
Rego et al, 200923F66NSBreast (left)Invasive carcinoma of no special type2 years4No4NS(24)
Rego et al, 200924F391Breast (NS)Invasive lobular carcinomaNS1NS3NS(24)
Bastos et al, 201425F631BreastInvasive lobular carcinoma1.5 years1,3Lumbar spine2NS(33)
Lee et al, 200526F501, 2Uterine cervixSquamous cell carcinoma2 years1No4NS(25)
Sreenarasimhaiah and Hoang, 200527M621OesophagusSquamous cell carcinomaSynchronousNSNo4, 5NS(26)
Buyukcelik et al, 200328M711, 2, 3LarynxSquamous cell carcinoma5 years1, 3Right adrenal gland, multiple pulmonary nodules2, 4Succumbed after 1 year(27)
Kamusella et al, 200729M411, 2Lung (right superior lobe)AdenocarcinomaSynchronousNSNo2NS(28)
Silva et al, 199630F53NSOvary and uterusEndometrioid adenocarcinoma (both ovaries and endometrium)5 years1, 2, 3NS2, 4No evidence of disease 9 months after resection(29)
Green et al, 200831M541BladderUrothelial carcinoma3 years1, 3No2, 4NS(30)
Kadakia et al, 199232M271, 2Right femurOsteosarcoma4 years1, 2, 4NSNSNS(31)

a 1, upper GI complaint (including nausea, vomiting and pain); 2, bleeding (including melena and anaemia); 3, jaundice and related symptoms (including pruritus, alterations in stool and urine); 4, general discomfort, weakness, weight loss and/or shortness of breath.

b 1, best supportive care; 2, drainage and/or stent; 3, surgery; 4, chemotherapy; 5, radiotherapy. F, female; M, male; DOD, dead of disease; NS, not specified. 1, polyp/mass; 2, ulcer; 3, pancreatic involvement

The mean time interval (known for 29 patients) between the diagnosis of the primary tumour and the ampullary metastasis is 4.8 years (median 3.5; range 0–17.5). However, lesions may also be detected synchronously with the primary tumour (n=5). Of note, time intervals for metastatic renal cancer lesions are particularly long (mean 8.8 years, median 10 years; range 0–17.5). In only one third of patients (n=12, 38%), as in the presented case, the ampullary metastasis was the only metastatic lesion, while in the remaining patients cancer spread to one or more organs was observed, most commonly to brain, liver, lungs, and bone. Notably, the majority of malignant melanomas showed involvement of several distant organs (Table I).

Clinical symptoms of secondary ampullary tumours are unspecific and similar to the presentation of primary tumours. Affected individuals may present with abdominal discomfort (n=13, 41%), jaundice and related symptoms (n=18, 56%), such as pruritus or alterations in stool and urine or with upper gastrointestinal bleeding (n=11, 34%).

Likewise, endoscopic presentation is indistinguishable from that of primary tumours apart from metastatic melanomas which occasionally appear as pigmented lesions (34,35). According to the data retrieved from literature, the majority (n=24/26, 92%) of lesions are polypoid and irregular, soft and friable masses which can also be ulcerated. In addition to endoscopy, several imaging methods, such as transpapillary intraductal ultrasonography and computed tomography, may be applied to detect small lesions of the papilla and to provide a proper staging (36). However, criteria to differentiate primary from secondary ampullary tumours have not been developed for these techniques. Definitive diagnosis requires clinical data and standard biopsies: cyto-architectural appearance and immunohistochemical profile are analysed to exclude primary neoplasms or less common lesions, e.g., sarcomas, GISTs and malignant lymphomas (37). In the evaluation of primary ampullary tumours, the diagnostic accuracy of forceps biopsies is known to range from 47 to 95% (37). False negative results may result from submucosal localisation of the tumour, and it is expected that the diagnostic accuracy for secondary tumours is lower, as these usually do not originate for the mucosa, but affect the luminal surface in a secondary manner (37).

As the prognosis of patients with secondary ampullary tumours is poor and a surgical approach bears a considerable risk of postoperative morbidity and mortality surgical intervention should be planned carefully (38). Outcome data was available for 19 patients. Three patients (16%), including our own patient, remained free of cancer after surgery for more than 2.5 years (2.5, 4, 5 years, respectively) and one patient is alive with residual disease 6.5 years following resection (Table I). Notably, all four of them were patients with metastatic renal cell carcinoma.

Data regarding therapeutic strategies were available in 31 (97%) patients and one half of patients underwent a surgical procedure (n=16), including Whipple resection (n=10). A total of 15 (48%) patients received chemotherapy, either in addition to surgery or alone. Drainage and/or stenting were applied in 10 (31%) patients, in five patients combined with chemotherapy. For small lesions, endoscopic (or surgical) ampullectomy appears to be an alternative with reduced length of inpatient stay, lower morbidity and mortality (38). However, endoscopic ampullectomy is considered a ‘high-risk’ procedure due to potential complications (39). These can be classified as early (pancreatitis, bleeding, perforation, and ampullectomy reported from large, tertiary care referral centres varies between 8 and 35% (39). So far, this technique has not been applied for secondary ampullary lesions, but it could be the best approach in cases presenting with mechanical cholestasis or even cholangitis and poor prognosis due to progress of the systemic malignant disease.

As seen in our case, ampullary metastases from renal cell cancer seem to behave differently both in terms of time intervals until the development of secondary tumours and overall prognosis. Similarly, in renal cell carcinoma metastatic to the stomach the mean time interval until the detection of a secondary tumour to the ampulla was around ten years (40). When complete resection of all metastatic lesions can be achieved patient show improved survival (41). Thus, Whipple resection with or without pylorus preservation which is the standard treatment for primary ampullary cancer may be also performed in these cases when all metastatic sites are amenable to wide resection (42,43).

In conclusion, secondary tumours of the ampulla of Vater are uncommon and malignant melanoma, renal and breast cancer are the most frequent primaries. Patients may present with jaundice or upper gastrointestinal bleeding. The time interval between the diagnosis of the primary tumour and the ampullary metastasis is highly variable and may be >10 years, particularly in patients with renal cancer. The management of metastatic ampullary lesions requires a multi-modal approach, including endoscopic, surgical, and oncological procedures.

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APA
Sarocchi, F., Gilg, M.M., Schreiber, F., & Langner, C. (2018). Secondary tumours of the ampulla of Vater: Case report and review of the literature. Molecular and Clinical Oncology, 8, 274-280. https://doi.org/10.3892/mco.2017.1535
MLA
Sarocchi, F., Gilg, M. M., Schreiber, F., Langner, C."Secondary tumours of the ampulla of Vater: Case report and review of the literature". Molecular and Clinical Oncology 8.2 (2018): 274-280.
Chicago
Sarocchi, F., Gilg, M. M., Schreiber, F., Langner, C."Secondary tumours of the ampulla of Vater: Case report and review of the literature". Molecular and Clinical Oncology 8, no. 2 (2018): 274-280. https://doi.org/10.3892/mco.2017.1535
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