Uterine cervix squamous cell carcinoma metastatic to the Ampulla of Vater: a case report with review of the literature

© 2013 Dalma Udovièiæ-Gagula et al.; licensee University of Sarajevo Faculty of Health Studies. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES ABSTRACT

Uterine cervix squamous cell carcinoma metastatic to the Ampulla of Vater: a case report with review of the literature

INTRODUCTION
Primary tumors of the ampulla of Vater are rare and are usually adenocarcinomas (1,2).Metastases to the gastrointestinal tract (GI) tract are uncommon, while metastases to the ampulla of Vater are extremely rare and therefore may pose a signifi cant diagnostic pitfall.Not many cases of metastasis to the ampulla of Vater are described, most of them being metastasis of primary melanoma of the skin (3)(4)(5)(6)(7), renal cell carcinomas (8-10) and a few cases of squamous cell carcinoma (SCC) from diff erent primary sites (11)(12)(13).SCC of the uterine cervix is likely to early metastasize into the adjacent lymph nodes, but hematogenous dissemination is the least common metastatic pathway of this carcinoma (14).Only one case of uterine cervix SCC metastasis to the ampulla of Vater has been described up to now (13).
Here, we report a second case of metastasis of squamous cell carcinoma (SCC) of the uterine cervix to the ampulla of Vater.

Clinical history
A 45-year-old woman presented with one month history of abdominal pain, jaundice and dark-colored urine.Physical examination revealed skin and conjunctival jaundice.Two years earlier she had been diagnosed with the primary squamous cell carcinoma of the uterine cervix (grade 3, FIGO stage IIIB).Due to the advanced stage, it was treated with a concomitant radiochemotherapy.Laboratory tests on admission revealed elevated levels of total bilirubin 114.8 μmol/L, aspartate amino transferase (AST) 158 IU/L and alanin amino transferase (ALT) 210 IU/L.Other laboratory fi ndings were within or close to normal: white blood cell (WBC) count 7x10 9 /L, red blood cell (RBC) count 4.16x10 12 /L, platelet (Plt) count 459x10 9 /L, hemoglobin (Hb) 121 g/L, glucose 6.4 mmol/L, urea 4.4 mmol/L and creatinine 74 μmol/L.Abdominal ultrasound revealed a folded gall bladder and dilatation of intra-and extrahepatic bile ducts, while common bile duct and pancreatic duct were not clearly exposed due to the presence of air within the intestinal lumen.Abdominal and pelvic CT scan revealed enlarged retroperitoneal lymph nodes with possible external compression of excretory bile ducts causing obstruction and jaundice.Endoscopic retrograde cholangiopancreatography was performed and during the endoscopy a polypoid tumor with ulcerated surface was found at the ampulla of Vater site (Figure 1).In the same procedure, papillectomy was performed and stent was placed.Th e specimen was submitted for histopathologic evaluation.

Histopathology and immunohistochemistry
Grossly, the specimen measured 20x15x4 mm, oval shaped, grayish tissue with smooth surface and visible superfi cial ulceration.Histological examination revealed a highly cellular tumor, composed of heterogeneous population of the neoplastic cells with oval to round nuclei and cells with spindle appearance, diff usely infi ltrating mucosa and submucosa of the ampullar region.Tumor cells were arranged as solid islands with focal fascicular pattern.Th ere was a sporadic mitotic activity and focal necrosis (Figure 1).Tumor surface was ulcerated and replaced by granulation tissue.Th e morphology indicated poorly diff erentiated malignant neoplasm including primary tumors (e.g.neuroendocrine carcinoma, gastrointestinal stromal tumor (GIST) with spindled pattern and poorly diff erentiated carcinoma).Because of her history of primary cervical cancer the metastasis was also considered in diff erential diagnosis.Immunochistochemical (IHC) analysis revealed that the tumor cells were negative for Chromogranin-A, CD56, c-Kit (CD117), CD34, ruling out the neuroendocrine carcinoma and GIST (Figure 2).Cytokeratins (CK)7 and 20 were also negative which excluded primary, poorly diff erentiated ampullary carcinoma (Figure 2).Th e tumor cells were strongly positive for CK5/6 and p16 (Figure 2), which favored metastatic poorly diff erentiated squamous cell carcinoma originating from uterine cervix.Th e patient was administered new cycles of cisplatinbased chemotherapy.

DISCUSSION
Primary carcinomas of the ampulla of Vater comprise about 0.5% of all GI tumors and most of them are adenocarcinomas (90%) (15).Metastases to the ampulla of Vater are unusual and small number of cases are reported in the available literature.We report here a second case of metastatic squamous cell carcinoma from the uterine cervix that presented as an isolated metastasis to the ampulla of Vater, two years after the initial diagnosis.Our extended literature search (PubMed, Google Scholar, Scopus, Web of Science) revealed only three metastatic squamous cell carcinomas to the ampulla of Vater, including single cases originating from larynx, esophagus and uterine cervix (11)(12)(13).
Majority of these patients present with obstructive symptoms of the biliary tract.Our patient also presented with jaundice and abdominal pain; her laboratory fi ndings showed elevated bilirubin and liver enzymes in the serum and dark-colored urine, which was consistent with cholestasis and presence of obstructive pathology.Although there was a known history of uterine cervix carcinoma, the most common cause of obstructive jaundice, i.e. trapped gallstones, had to be excluded.Recent studies suggest that one third of patients with ampullary carcinoma could have synchronous malignancy (16).Endoscopic fi ndings and morphologic appearance of the tumor were inconclusive and therefore we performed an extended IHC panel to render the correct diagnosis.Negativity for CK7, CK20, Chromogranin-A, CD56, CD34, and c-Kit along with diff use and strong positivity for CK5/6 and p16 (INK4a) strongly favored metastatic squamous cell carcinoma originating from uterine cervix.We conclude that metastatic tumors to the GI sites such as the ampulla of Vater are exceptionally rare and may pose a substantial diagnostic challenge.In such cases, a thorough histopathologic examination and an extended immunohistochemical panel, along with clinical history, are of utmost importance for the appropriate diagnosis and optimal clinical management of the patients.

FIGURE 1 .
FIGURE 1. Polypoid tumor with ulcerated surface at the Ampulla of Vater (A).Histopathologic examination revealed a highly cellular tumor nests and islands composed of heterogenous population of malignant cells diffusely infi ltrating mucosa and submucosa of the ampullar region (B, C).