Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis,and paraduodenal pancreatitis can present as mass lesions and may mimicpancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thoroughhistologic examination with attention to certain morphologic features can assist indeciphering neoplastic from reactive, however small biopsies often remain achallenge. Variable histologic patterns in conventional PDAC may also confoundthe diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such asadenosquamous and squamous cell carcinoma, colloid carcinoma, medullarycarcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitateexcluding metastasis from other sites prior to rendering the diagnosis ofpancreatic carcinoma. The use of immunohistochemical staining and molecularmarkers can aid in separating benign from malignant and PDAC from metastasis.PDAC expresses a few non-specific epithelial and mucin immunomarkers such asCK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemicalmarker that is specific for PDAC in the right clinical context is SMAD4.Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDACin a limited sample. Unfortunately, this finding is seen only in 50% of PDACcases. The identification of certain mutations can help support a diagnosis ofPDAC when benign conditions are in the differential. At the molecular level,KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequentneoplastic progression is driven by additional mutations of tumor suppressorgenes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also providean insight to the prognosis. For instance, the loss of SMAD4 is associated with apoor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associatedwith improved survival.
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