Robert M. Najarian, MD
Gastrointestinal, Liver, and Pancreatic Pathologist
Beth Israel Deaconess Medical Center
Boston, Massachusetts

Ductal adenocarcinoma of the pancreas (PDAC), the most common malignant tumor of the pancreas,1 is a leading cause of cancer death in the United States and now has a dismal 5-year survival rate of less than 10%.2 Much of its poor prognosis can be attributed to the non-specific clinical symptoms associated with early-stage disease.3 Additionally, challenges may arise with obtaining a confirmatory diagnosis for PDAC to aid in guiding surgical management. In the setting of metastatic disease, many clinical trials require sampling of either primary or metastatic tumor deposits to determine patient eligibility.

Until recently, standard of practice for the diagnosis of PDAC included cytopathologic examination of fine needle aspiration specimens and ductal brushings obtained under endoscopic ultrasound (EUS) guidance.4 Such cytologic samples can suffer from a lack of diagnostic sensitivity, especially in the setting of well-differentiated tumors that are comprised of neoplastic ducts that demonstrate homogeneous nuclear cytomorphology akin to normal or reactive ductal epithelium. Alternatively, ultrasound-guided surgical laparoscopic biopsy often yields more tissue,4 allowing for interpretation of the relationship between neoplastic ducts and surrounding microanatomic landmarks. However, this procedure involves an additional surgical procedure that may carry some morbidity risks to an already debilitated patient population.

Improved technology in EUS-guided core needle biopsy5 has advanced the primary diagnosis of PDAC and affords surgical pathologists the ability to assess for the presence of neoplastic ducts and evaluate their relationship to peripancreatic adipose tissue, nerves, and large vascular structures. Additionally, subtle cytopathologic changes such as mild nuclear enlargement and irregularity and cytoplasmic quality can be evaluated effectively alongside native non-neoplastic ductal structures.

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Case Presentation

An 80-year-old woman with multiple chronic medical problems including cryptogenic cirrhosis presented with abdominal pain, jaundice, and abnormal liver function tests, most notably, a markedly elevated total bilirubin of 18.7 and alkaline phosphatase of 873. Abdominal ultrasound demonstrated a liver with coarsened echotexture compatible with the known history of cirrhosis, as well as dilation of both the intrapancreatic common bile duct and main pancreatic duct. Magnetic resonance cholangiopancreatography was performed for further evaluation that revealed a 2.5 cm duct-obstructing mass within the pancreatic head. Endoscopy was performed to both stent the obstructed common bile duct and to obtain multiple SharkCore™ needle biopsies of the mass for diagnostic purposes.

On low magnification, hematoxylin and eosin–stained sections demonstrated a core of tissue containing ductal structures lined by epithelial cells with abundant eosinophilic cytoplasm and mild nuclear atypia relative to a group of reactive ductal structures (A). A single focus in which neoplastic ducts were identified within an endothelial-lined lymphatic space was consistent with lymphovascular invasion by the tumor (B). The combination of these findings confirmed the diagnosis of well-differentiated ductal adenocarcinoma of the pancreas.

Discussion

Unlike cytologic preparations which rely on changes in the size and shape of neoplastic nuclei, core needle biopsies obtain tissue cores4 which can allow the pathologist to assess the relationship of neoplastic ducts to normal pancreatic acinar tissue, large vascular structures and nerves, and any abnormal stromal tissue that PDAC commonly produces (C).

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Images courtesy of Robert M. Najarian, MD.

References

    1. Cid-Arregui A, Juarez V. Perspectives in the treatment of pancreatic adenocarcinoma. World J Gastroenterol. 2015;21(31):9297-9316.
    2. National Cancer Institute. Scientific framework for pancreatic ductal adenocarcinoma (PDAC). http://deainfo.nci.nih.gov/​advisory/​ctac/​workgroup/​pc/​pdacframework.pdf. Accessed October 14, 2015.
    3. Schober M, Javed MA, Beyer G, et al. New advances in the treatment of metastatic pancreatic cancer. Digestion. 2015;92(3):175-184.
    4. Clarke DL, Clarke BA, Thomson SR, et al. The role of preoperative biopsy in pancreatic cancer. HPB (Oxford). 2004;6(3):144-153.
    5. Wani S, Muthusamy VR, Komanduri S. EUS-guided tissue acquisition: an evidence-based approach (with videos). Gastrointest Endosc. 2014;80(6): 939-959.e7.