Pathology – malignant

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The most common and severe form of malignant change of the pancreas is duct cell adenocarcinoma. There are other forms of benign, borderline and malignant tumors (listed below – type IIIa is typical “pancreatic cancer”).   This figure illustrates a pancreatic adenocarcinoma in the head of the pancreas.  A=tumor mass, B=its spread to lymph nodes, C=a dilated main pancreatic duct upstream of the tumor.

Pancreatic cancer is one of the most dreaded of all cancers, being responsible for greater than 35,000 deaths in the United States each year and having the highest case-fatality rate of any major cancer.  The reason that it is so deadly is because it difficult to detect, early to metastasize, resistant to treatment, and causes death with relatively little tumor burden (meaning that a small tumor can still be fatal).  The best hope for curing pancreatic cancer is early detection and surgery, although specialists focus on early detection because discovering pancreatic cancer at a stage when surgery can be performed only happens in a minority of all cases.  Chemotherapy has been shown to be of some help in treating pancreatic cancer, while radiation therapy is more controversial.

Recognized risk factors for pancreatic cancer include cigarette smoking, chronic/hereditary pancreatitis, obesity, type II diabetes, blood types A/B/AB (O is protective) and genetic factors.   Genetic factors are not fully understood at this time.  Major inherited genetic mutations called germline mutations cause cancers to run in families, while potentially deadly combinations of important minor inherited genetic mutations  are likely to be even more important risk factors.  Combinations of factors coming together from both sides of a pancreatic cancer patient’s family means that the cancer may appear to be “sporadic,” in that the problem does not run in the family. These risk factors eventually lead to the development of new mutations in pancreatic cells (called somatic mutations), with the cells becoming more and more malignant as the mutations accumulate.  Eventually, dozens and dozens of mutations occur, which changes the character of the pancreatic cell into a rapidly growing and spreading ‘mutant’ cell that is resistant to all of the body’s defenses.

Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) have lead to major advances in understanding the evolution and pathology of pancreatic cancer.  These techniques are capable of detecting small and early tumors and cysts which are sometimes benign, sometimes of borderline character (partly benign and partly malignant), and sometimes malignant.  The World Health Organization (WHO) list of tumors is commonly used to classify these different pancreas tumor characteristics.

WHO Classificantion of pancreatic tumors:

I.  Benign

a.  Serous cystadenoma
b.  Mucinous cystadenoma
c.  Intraductal papillary mucinous adenoma
d.  Mature cystic teratoma

II.  Borderline

a.  Mucinous cystic tumor with moderate dysplasia
b.  Intraductal papillary mucinous neoplasm (IPMN)
c.  Solid-pseudopapillary tumor

III.  Malignant

a.  Ductal adenocarcinoma
b.  Osteoclast-like giant cell tumor
c.  Serous cystadenocarcinoma
d.  Mucinous cystadenocarcinoma
e.  Intraductal papillary mucinous carcinoma
f.  Acinar cell carcinoma
g.  Pancreatoblastoma
h.  Solid-pseudopapillary carcinoma
i.  Miscellaneous carcinoma