Gall bladder carcinoma with ampullary carcinoma: a rare case of double malignancy.

Simultaneous double cancers in the biliary system are rare. Most are associated with pancreaticobiliary maljunction (PBM). However, it can occur in patients without PBM. Differentiation between these events is important since these two mechanistic origins imply different stages of disease, as well as different subsequent treatments and prognoses. Herein, we report a case of ampullary carcinoma associated with gall bladder carcinoma diagnosed nonoperatively and palliated with biliary metal stenting.

INTRODUCTION

Simultaneous double cancers in the biliary system are rare. Most are thought to be associated with pancreaticobiliary maljunction (PBM) owing to the action of the same carcinogen on the mucosa of the entire extrahepatic biliary system.[12] However, it can occur in patients without PBM. The possible explanations for such an occurrence could range from the rare synchronous malignancies to local spread, to metastasis. Differentiation between these events is important since these two mechanistic origins imply different stages of disease, as well as different subsequent treatments and prognoses.

CASE REPORT

The patient, a 57-year-old lady, presented with progressive jaundice with severe pruritus for 2 months. She had pain in right upper quadrant for last 2 months. She also had anorexia with a weight loss of about 10 kg in last 2 months. There was no history of gastrointestinal (GI) bleed or vomiting. Examination showed deep icterus and a 2-cm firm supraclavicular lymph node. On abdominal examination, there was soft hepatomegaly 3 cm below the costal margin with no free fluid. Rest of the systemic examination was normal. The laboratory findings were: Conjugated hyperbilirubinemia (total 23.0 mg/dl, conjugated 18.0 mg/dl) with raised alkaline phosphatase (362 IU/ml). On contrast-enhanced computed tomography (CECT) abdomen, there was a mass lesion in gall bladder (GB) fundus and lower end of the common bile duct (CBD), with CBD compression at two sites (just below the hilum and the lower end of CBD), and bilobar intrahepatic biliary radical dilatation [Figure 1] with no evidence of local or distant spread. Magnetic resonance chalangiopancreaticography (MRCP) was done for delineation of the biliary anatomy and revealed a patent confluence and narrowing at multiple sites [Figure 2]. Fine needle aspiration cytology (FNAC) from the left supraclavicular lymph node was positive for malignant cells [Figure 3]. The patient was taken up for endoscopic retrograde cholangiopancreatography (ERCP) for palliative biliary drainage. On side viewing endoscopy (SVE), there was a large periampullary growth [Figure 4]; biopsy was taken [Figure 5], choangiogram was done [Figure 6], and a metal stent was placed in the CBD [Figure 7]. Post ERC, the patient was asymptomatic and USG revealed no intrahepatic biliary radical dilatation and pneumobilia and a normal caliber CBD. Post procedure, the liver function tests (total bilirubin 9.7mg/dl, alkaline phosphatase (ALP) 768 IU/ml) showed an improvement. Ampullary biopsy revealed atypical cells, high nuclear-cytoplasmic ratio, round nuclei, fine chromatin, inconspicuous nucleoli, granular cytoplasm, and significant mitotic figures. She was discharged and has normal liver function tests at 1 month of follow-up.

Figure 1

CECT showing eccentric thickening of gall bladder wall

Figure 2

MRCP showing dilated bile duct with multiple sites of narrowing

Figure 3

Smear shows cluster of malignant cells displaying round to oval hyperchromatic nuclei, condensed chromatin, prominent nucleoli, and moderate amount of cytoplasm (MGG, ×40 magnification)

Figure 4

Side viewing endoscopy showing ampullary growth

Figure 5

Biopsy section lamina infiltration by tumor arranged in glands, tumor cells displaying round to oval hyperchromatic nuclei, condensed chromatin, prominent nucleoli in ‘some’ and moderate amount of cytoplasm (H and E, ×40 magnification)

Figure 6

ERCP showing dilated bile duct with multiple sites of narrowing

Figure 7

Metal stent in the bile duct

DISCUSSION

There have been many case reports of double cancers of the GI tract. However, the reported cases of multiple cancers involving ampulla Vater carcinoma are relatively rare. Warren and Gates reported multiple malignant tumors in 1.84% of 1259 cancer cases on the basis of the world literature, and the frequency was 3.9% in their own series of 1078 cancer autopsies.[3] Schlippert et al. reported nine cases of coincident cancers among 57 cases of carcinoma of the ampulla of Vater.[4] The other types of malignancies were as follows: prostatic carcinoma in two, mainstem bronchus adenocarcinoma in two, rectal cancer in two, endometrial carcinoma in one, and epidermoid carcinoma in two patients. There were 20 reported cases of multiple cancers involving the ampulla of Vater and other organs in the world literature, in which 16 cases were synchronous and 4 were metachronous. Of these 20 patients, 8 had early gastric cancer and 6 had colon cancer. Therefore, it is recommended that preoperative GI examinations including the colon should be done when an ampulla Vater carcinoma is diagnosed. The stomach is an important organ to reconstruct when pylorus preserving pancreaticoduodenectomy (PPPD) is considered; therefore, the GI study is necessary before operation. According to Offenhaus et al., patients of familial adenomatous polyposis (FAP) have a high incidence of occurrence of the ampulla Vater carcinoma.[5678] In our patient, polyposis was not associated.

It is unclear whether the double cancers each have the same mechanism of carcinogenesis, or whether the other organ malignancies associated with Ampulla of Vater develop independently according to the age and gender distribution of the patients. The p53 gene mutation and loss of heterozygosity of various chromosomes which are linked to carcinoma GB need to be studied in patients with synchronous malignancies as the molecular mechanisms.

For treatment, a radical operation with lymph node dissection should be done when curative surgical management for the malignancies is expected in the patient. If the lesion is unresectable due to advanced state or the presence of metastatic lesions, a palliative operation such as papillectomy or bypass operation for ampulla Vater carcinoma, and palliative resection for the other organ malignancy should be done. However, in our patient, the disease was disseminated and performance status was poor, so only palliative biliary stenting was done.