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Year : 2018  |  Volume : 61  |  Issue : 2  |  Page : 300-302
Primary squamous cell carcinoma of the ampulla

Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

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Date of Web Publication20-Apr-2018

How to cite this article:
Sekhri R, Kamboj M, Gupta G, Pasricha S. Primary squamous cell carcinoma of the ampulla. Indian J Pathol Microbiol 2018;61:300-2

How to cite this URL:
Sekhri R, Kamboj M, Gupta G, Pasricha S. Primary squamous cell carcinoma of the ampulla. Indian J Pathol Microbiol [serial online] 2018 [cited 2021 Mar 1];61:300-2. Available from: https://www.ijpmonline.org/text.asp?2018/61/2/300/230547


A 55-year-old male presented with complaints of yellow discoloration of the sclera, dark-colored urine, and generalized pruritus for the past 1 month. On physical examination, he had icterus with unremarkable local and systemic examination. Biochemical investigations showed a markedly deranged liver function test with elevated total and direct serum bilirubin level.

Radiological investigations using ultrasonography, magnetic resonance cholangiopancreatography (MRCP), and computed tomography (CT) scan [Figure 1] revealed a dilated common bile duct (CBD) with an intraluminal mass in the terminal part of CBD measuring 3 cm × 2 cm, along with bilateral intrahepatic biliary radical dilatation. Upper gastrointestinal endoscopy showed a bulky ampullary papilla with irregular friable mucosa, and the biopsy was reported as a poorly differentiated carcinoma. The patient underwent Whipple's pancreaticoduodenectomy with cholecystectomy and regional lymph node dissection for periampullary carcinoma.
Figure 1: Computed tomography scan showing an intraluminal mass in the terminal part of common bile duct, abutting the uncinate process of the pancreas and 2nd part of the duodenum

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The specimen received composed of duodenum with the head of the pancreas and gallbladder (GB). The periampullary region showed a solid gray-white infiltrative tumor extending horizontally into the CBD and grossly seen infiltrating into the adjacent pancreas, measuring 4 cm × 2 cm × 2 cm. No stones were identified in the biliary tract including GB.

Histopathological examination of the tumor revealed a poorly differentiated carcinoma, arranged in solid nests and trabeculae embedded in a dense desmoplastic stroma [Figure 2]. The tumor cells were large-to-polygonal with abundant cytoplasm, pleomorphic hyperchromatic nuclei, and conspicuous nucleoli. No evidence of differentiation toward squamous (intercellular bridges or keratinization) or glandular origin was identified. On immunohistochemical stain, the tumor cells expressed p40 and high-molecular-weight cytokeratin strongly and diffusely [Figure 3]a and [Figure 3]b and were negative for carcinoembryonic antigen, CK7 and all the neuroendocrine markers (synaptophysin and chromogranin), thus excluding a neuroendocrine differentiation. Exhaustive sampling of the tumor failed to detect any focus of adenomatous component.
Figure 2: Section from ampulla showing a poorly differentiated carcinoma with large polygonal cells, arranged in solid nests and trabeculae, inciting a dense desmoplastic stroma (H and E, ×200)

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Figure 3: (a) Tumor cells express p40 strongly and diffusely (nuclear stain) on immunohistochemistry (DAB, ×200). (b) Tumor cells express high-molecular-weight cytokeratin, diffuse membranous positivity on immunohistochemistry (DAB, ×200)

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The tumor was infiltrating into the duodenal wall, distal CBD, and pancreatic parenchyma, and the attached GB was unremarkable. All the regional lymph nodes and margins of resection were free of tumor. No evidence of perineural or lymphovascular invasion identified.

Thus, after thorough processing, a final diagnosis of pure squamous cell carcinoma (SCC) of the ampulla, nonkeratinizing type with poor differentiation, was rendered. Radiology did not reveal any other site with tumor, ruling out metastatic deposit of tumor from primary of any other site, and there was no history of any previous SCC.

The postoperative course was uneventful, and the patient is being treated with gemcitabine and carboplatin-based adjuvant chemotherapy. CT scan of the abdomen after 6 cycles showed no evidence of residual or recurrent abdominal disease.

Ampullary carcinomas are centered on the ampulla and originate from head of the pancreas in 40%–60% of cases, followed by ampulla of Vater in 10%–20%, distal CBD in 10%, and duodenum in 5%–10% cases.[1] They represent 0.5% of all gastrointestinal malignancies and are less common than other biliary tract carcinomas due to relatively small area of the mucosa.[2] Most of these tumors have adenocarcinoma as the usual histopathology. They present between 60 and 80 years of age and are more common in males.[2] Other rare histopathological diagnoses are adenosquamous carcinoma, SCC, neuroendocrine carcinoma, and signet ring cell carcinoma.[1] To the best of our knowledge, there are only five reported cases of primary SCC [1] and six cases of adenosquamous carcinoma [3] at this site. The presented case is possibly the sixth case of primary SCC of ampulla in literature.

Primary SCC in the biliary tract mostly involves the GB and intrahepatic biliary radicals, with ampulla of Vater being a rare site.[4] There have been reported cases of neuroendocrine carcinoma of ampulla with squamous components, and two metastatic cases of SCC to ampulla from larynx and esophagus have also been reported.[1] Before labeling a tumor as pure SCC, other primary SCC malignancies should be ruled out. In our case, no other tumor was detected on radiology, ruling out primary SCC at any other site. We also had a nonpublished case of moderately differentiated SCC in the periampullary region in a known case of SCC of head-and-neck region.

As the extrahepatic biliary tract including the ampulla of Vater is devoid of squamous mucosa, the pathogenesis of ampullary SCC remains difficult to ascertain. It has been postulated that conversion of ectopic squamous epithelium into carcinoma, or chronic inflammation leading to squamous metaplasia and intraepithelial neoplasia, or differentiation of pluripotent stem cells of duodenum could be the possible mechanisms.[3],[5] The well-established predisposing factors for SCC of biliary tract include hepatolithiasis, recurrent pyogenic cholangitis, clonorchiasis, ascariasis, ulcerative colitis, Caroli's disease, choledochal cyst, and primary sclerosing cholangitis, which are known to cause squamous metaplasia of the biliary epithelium.[4] The case in discussion here had none of these risk factors, and the adjacent mucosa did not show any metaplasia or dysplasia.

The clinical presentation of SCC of ampulla is similar to other ampullary tumors, with painless obstructive jaundice as the most common symptom along with biochemical alterations.[5] Radioimaging studies, such as abdominal CT scan, magnetic resonance imaging, MRCP, transhepatic cholangiograms, and endoscopic retrograde cholangiopancreatography are essential for exact localization of the tumor in EHBD.[2],[5]

Grossly, the EHBD carcinomas can be polypoid, nodular, scirrhous constricting, or diffusely infiltrating types. The diffusely infiltrating types tend to spread linearly along the ducts as was evident in our case. Endoscopic biopsy is required to ascertain the histopathological diagnosis. SCCs are graded as well, moderately, or poorly differentiated, and a thorough examination is needed to rule out adenosquamous carcinoma. Stage of tumor is the best predictor of prognosis for the disease.[2]

Pure SCCs of the biliary tract have been observed to show decreased survival rates as compared to adenocarcinomas and adenosquamous carcinomas.[3] Due to symptoms of obstructive jaundice in carcinomas of the EHBDs, patients present early and progress rapidly [2] as compared to intra-hepatic SCCs which present in advanced stage and have a poorer prognosis.[4] A patient with 5-month overall survival developed liver metastasis 4 months postsurgery without adjuvant CT.[5]

Surgical resection remains the cornerstone in the management of ampullary tumors.[5] It has been conferred that the squamous component signifies aggressive nature with worse prognosis.[5] The optimal treatment, prognosis, and survival rates for SCC, being a rare tumor, are not well established, and further course cannot be predicted due to the limited experience.

However, it has been suggested that SCCs being more aggressive should be administered with postoperative adjuvant chemotherapy and/or radiotherapy as have been used in adenosquamous GB and EHBD carcinomas. Gemcitabine has shown longer median survival as compared to 5-fluorouracil and gemcitabine.[1]

Pathologists should be aware of this common tumor at uncommon site, with vague pathogenesis and poor prognosis, and immunohistochemistry must be performed to accurately characterize the tumor as it will prevent the future confusions in case of distant metastasis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Balci B, Calik B, Karadeniz T, Sahin H, Ugurlu L, Aydin C, et al. Primary squamous cell carcinoma of the ampulla of Vater: A case report. Surg Case Rep 2016;2:2.  Back to cited text no. 1
Albores-Saavedra J, Hruban RH, Klimstra DS. Tumours of the ampullary region. In: Bosman FT, Carneiro F, Hruban RH, editors. World Health Organization Classification of Tumours of the Digestive System.4th ed. Lyon (France): International Agency for Research on Cancer (IARC); 2010. p. 81-94.  Back to cited text no. 2
Kshirsagar AY, Nangare NR, Vekariya MA, Gupta V, Pednekar AS, Wader JV, et al. Primary adenosquamous carcinoma of ampulla of Vater – A rare case report. Int J Surg Case Rep 2014;5:393-5.  Back to cited text no. 3
Sewkani A, Kapoor S, Sharma S, Naik S, Juneja M, Jain A, et al. Squamous cell carcinoma of the distal common bile duct. JOP 2005;6:162-5.  Back to cited text no. 4
Bolanaki H, Giatromanolaki A, Sivridis E, Karayiannakis AJ. Primary squamous cell carcinoma of the ampulla of Vater. JOP 2014;15:42-5.  Back to cited text no. 5

Correspondence Address:
Meenakshi Kamboj
Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi - 110 085
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_340_17

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