Around 75% of pancreatic cancers occur in the head or neck of the pancreas, with about 15–20% in the body and 5–10% in the tail. Because the majority of tumors arise in the head and neck area, the most characteristic sign of pancreatic cancer is painless jaundice. Usually, patients will first notice changes in stool color, darkening of urine, and some pruritus before their jaundice reaches the point where it is clinically recognizable, which does not occur until total bilirubin reaches 2.5–3 mg% [1]. This patient presented with fairly classical symptoms; however, the difficulty of diagnosing pancreatic cancer purely based on presentation lies in the overlap it has with many more common conditions—such as gallbladder pathology or liver disease.

The clinical presentation of pancreatic cancer may be extremely nonspecific and subtle with early diagnosis particularly difficult. Some other common signs of clinical presentation include anorexia with or without weight loss, malaise, nausea, and midepigastric or back pain. Weight loss can be related to the cancer-associated anorexia but can also be malabsorption from pancreatic exocrine insufficiency [2]. The latter may also present with diarrhea and greasy, malodorous stools.

New-onset diabetes mellitus can sometimes be associated with pancreatic adenocarcinoma, which has prompted discussion on whether this may be a manifestation of the disease and possible clue to early presentation. However, only about 1% of those with new-onset diabetes develop pancreatic cancer, making preventative screening inefficient and ineffective [3]. It is recommended to consider pancreatic cancer in patients with diabetes associated with unusual weight loss and abdominal problems, but there are currently no specific recommendations for imaging or lab tests. Given that the majority of presentations occur as such an advanced stage, early detection will have to be done in asymptomatic individuals. Further study needs to be performed on the role of hyperglycemia and new-onset diabetes in relation to the detection of early stage pancreatic cancer [4, 5].

Currently, the primary form of assessment in a patient suspected of pancreatic cancer is cross-sectional imaging. The most common forms used are CT, endoscopic ultrasound (EUS), MRI, endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiopancreatography (MRCP). The decision on which to proceed with depends on the need for ongoing characterization of the pancreatic mass and surrounding organs, obtaining tissue samples for cytologic evaluation, and the possibility for therapeutic intervention if there is obstruction present [6]. CT angiography with pancreas-specific protocol is recommended for patients who do not show signs of distant metastases on initial CT. This type of imaging is used to evaluate the vascular system in relation to the pancreatic mass as this is an important factor when determining the feasibility of surgical resection [7]. EUS, if done by an expert, has been shown to be the most sensitive and specific imaging technique for the detection of pancreatic cancer. In addition, it provides the option of a fine-needle aspiration as a relatively noninvasive way to sample tissue for a more definitive diagnosis [8]. Though imaging remains one of the primary tools in initial diagnosis, it may be difficult to differentiate a pancreatic cancer in a patient with chronic pancreatitis where both imaging and tumor markers may have similar abnormalities [9].

Given the results of the CT scan on this patient, it was determined that histologic categorization of the mass would be an appropriate next step; therefore, EUS with FNA was scheduled. While cytologic results of benign or malignant are fairly straightforward, there is some debate as to the interpretation of the “indeterminate” results—atypical and suspicious. Often, they can lead to repeat procedures and an ill-defined course of therapy, which can delay potentially life-saving treatments in the case of pancreatic cancer, which has the lowest 5-year survival rate among recalcitrant cancers at 6% [8]. Lethality of the disease is credited to the inability to detect it in the early stages as most pancreatic cancer becomes clinically visible as a late-stage disease. Rapid growth and spread throughout the body are also a barrier to cure. Surgery is currently the only treatment proven to improve that survival rate, though only about 20% of patients qualify for surgical resection given that the disease usually presents at advanced stages [10].