We describe a case of carcinoma in the duodenal-pancreatic interface, firstly misdiagnosed as a duodenal pyloric gland adenoma. Final diagnosis of clear cell carcinoma belonging to the pancreas was made with an unusual difficulty to obtain a preoperative diagnosis.
In this case, CT and MRI, the well accepted tools to study the pancreatic lesions, failed. This is not a rare situation because atypical imaging features may be present and, in addition, many other diseases may mimic pancreatic adenocarcinoma [6, 7] even if usually a strong suspect arises when used sequentially.
In this patient, CT scan showed an inhomogeneous head of the pancreas, an alteration of the duodenal-pancreatic interface, a thickening of the duodenal wall, a modest proximal ectasia of the Wirsung duct and no signs of atrophy of the rest of the gland. Cholangio-MRI confirmed the over distension of the gallbladder but mentioned the presence of an hypointense in T2 mass in the papilla compatible with a gallstone and, again, no evidence of malignant lesions. So, direct, and indirect signs of cancer of the head of the pancreas were lacking. ERCP and echoendoscopy also failed to solve the problem because the instrument did not pass through the superior duodenal flexure for a partial stenosis. At the end of the diagnostic process, we solved the icterus with a percutaneous procedure, but we had no definitive diagnosis. The biopsy of the duodenal vegetation made during the cholangiopancreatography suggested a probable duodenal pyloric gland adenoma (PGA), originally defined in 1976 by Kurt Elster [8, 9]. This kind of lesion is typically found in the stomach, but it can also originate from duodenum (9% of the reported series) (9), gallbladder, bile duct, pancreas, rectum and in Barrett’s esophagus. It is most common in females in their 8th decade of life  likely due to their association with autoimmune gastritis. The identification of these lesions is important because they have a malignant potential, although this evolution is rarely reported (….).
At that point, we proposed an explorative laparotomy; the duodenal lesion compromised the duodenal lumen and determined an obstructing icterus. Furthermore, we considered the direct visualization and the intraoperative biopsy as the final steps to obtain a diagnosis. Literature permits an extensive resection till the duodenopancreatectomy without a histologic proof, but this strategy accounts for a rate of 7-8% of false positive diagnosis and resection is finally performed for a benign lesion of the pancreas (10). In this case, no evidence was clear towards a diagnosis of a pancreatic lesion; really, the most probable diagnosis was a benign process of the peri-ampullary area and not a pancreatic cancer.
The complicated and inconclusive diagnostic process was certainly the first unusual characteristic of this case, but the real unexpected feature was the histopathological result.
Histopathological examination of the surgical specimen revealed Clear-cell ductal adenocarcinoma of the pancreas with an unusual behavior regarding the invasion of the duodenum. This feature consisted of a changing in the phenotype of the neoplasia, starting from a clear cell component to a well-differentiated adenocarcinoma where the neoplasia infiltrated the duodenum up to the mucosa. Notably, where the neoplasia reached the duodenal mucosa, a various degree of dysplasia was observed and cells resembling the features detected in the previous biopsy specimen, which was mis-interpreted as a duodenal pyloric gland adenoma, were also found.
We were confident about the final diagnosis. Carcinomas with solid clear cell features are rare in the pancreas but common in other organs; the differential diagnosis must first consider the possibility of a metastasis of an extra pancreatic primary tumor, notably a renal Clear-cell carcinoma . The specific criteria to confirm this tumor have not yet been established. Kim L et al, Luttges J et al. and Ray S et al. classified Clear-cell carcinoma as those tumors with more than 75%, 90%,95% respectively of the tumor cells being clear cells [13, 14]. To define this disease entity and prognosis further investigation with other methods is needed. The finding, however, that our case of Clear-cell carcinoma had an intraductal papillary component excluded the possibility of a metastasis from a renal Cell-carcinoma or other similar extra pancreatic cancers, such as the carcinoma of the adrenal cortex or lung. Furthermore Clear-cell carcinomas of the kidney often stain not only for keratin but also for vimentin  and for the other non-pancreatic cancer, an intraductal papillary component is unusual. Moreover, the negativity for chromogranin A and synaptophysin excluded an endocrine neoplasm and the negativity for neuron-specific enolase (NSE), alpha-1-antitrypsin and vimentin a solid pseudo-papillary tumor [12, 13]. All these data give strength to our final diagnostic suggestion.
There are not clear treatment guidelines for Clear-cell carcinoma. In our case, the patient started adjuvant chemotherapy with FOLFIRINOX 3 months after surgery, which was replaced, after the first cure, with FOLFOX because he suffered profuse diarrhea, hyperpyrexia, and abdominal pain.
To date, 4 months later, there are no signs of disease recurrence.