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WHO Classification of Tumours
Secondary tumours of the pancreas


Definition
Neoplasms that have spread to the pancreas from an extra-pancreatic primary.

Origin
Both epithelial and nonepithelial neoplasms can metastasize to the pancreas. The pancreas may be involved by direct extension, or by lymphatic or haematogenous spread from distant sites. Cancers of the ampulla of Vater, duodenum and distal common bile duct often involve the pancreas by direct extension. The most common more distant malignancies that metastasize to the pancreas are renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas and sarcomas

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Reddy S, Edil BH, Cameron JL, Pawlik TM, Herman JM, Gilson MM, Campbell KA, Schulick RD, Ahuja N, Wolfgang CL (2008)
Pancreatic resection of isolated metastases from nonpancreatic primary cancers.
Ann Surg Oncol 15: 3199-206



. Occasionally, neoplasms may metastasize to the pancreas many years after diagnosis of the primary neoplasm
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Akatsu T, Shimazu M, Aiura K, Ito Y, Shinoda M, Kawachi S, Tanabe M, Ueda M, Kitajima M, Kitagawa Y (2007)
Clinicopathological features and surgical outcome of isolated metastasis of renal cell carcinoma.
Hepatogastroenterology 54: 1836-40




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Haque S, Gopaldas RR, Plymyer MR, Glantz AI (2005)
Pancreatic mass of unusual etiology: case report of metastatic disease after a prolonged lag phase.
Am Surg 71: 1082-5



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Epidemiology
Secondary neoplasms of the pancreas account for 415% of all malignancies in the pancreas found at autopsy

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Adsay NV, Andea A, Basturk O, Kilinc N, Nassar H, Cheng JD (2004)
Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature.
Virchows Arch 444: 527-35




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Crippa S, Angelini C, Mussi C, Bonardi C, Romano F, Sartori P, Uggeri F, Bovo G (2006)
Surgical treatment of metastatic tumors to the pancreas: a single center experience and review of the literature.
World J Surg 30: 1536-42




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Nakamura E, Shimizu M, Itoh T, Manabe T (2001)
Secondary tumors of the pancreas: clinicopathological study of 103 autopsy cases of Japanese patients.
Pathol Int 51: 686-90



. Secondary neoplasms affect males and females equally. As is true for metastases in general, the highest incidence is in the sixth and seventh decades of life.

Localization
Any anatomical region of the pancreas may be involved and there is no site predilection

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Klein KA, Stephens DH, Welch TJ (1998)
CT characteristics of metastatic disease of the pancreas.
Radiographics 18: 369-78



. Although usually multiple, metastases to the pancreas can also be solitary, or they may diffusely involve the gland
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Klein KA, Stephens DH, Welch TJ (1998)
CT characteristics of metastatic disease of the pancreas.
Radiographics 18: 369-78



.

Clinical features
Similar to primary pancreatic neoplasms, the early signs and symptoms of isolated pancreatic metastases are often nonspecific and subtle. The most common symptoms are abdominal pain, jaundice and gastrointestinal bleeding

Click to access Pubmed
Reddy S, Edil BH, Cameron JL, Pawlik TM, Herman JM, Gilson MM, Campbell KA, Schulick RD, Ahuja N, Wolfgang CL (2008)
Pancreatic resection of isolated metastases from nonpancreatic primary cancers.
Ann Surg Oncol 15: 3199-206



. Many lesions are asymptomatic and detected on imaging studies performed to follow-up the patient's original primary neoplasm.

Macroscopy
Metastases to the pancreas are most often seen as circumscribed masses that may have extensive haemorrhage and/or a cystic component

Click to access Pubmed
Adsay NV, Andea A, Basturk O, Kilinc N, Nassar H, Cheng JD (2004)
Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature.
Virchows Arch 444: 527-35



. Pigmented melanomas can form discrete black or brown masses surrounded by normal pancreatic parenchyma; renal cell carcinomas often have a yellow-orange cut surface.

Histopathology
The diagnosis of a secondary neoplasm of the pancreas is often straightforward as most patients will have a known history of an extra-pancreatic primary malignancy. Metastases to the pancreas are histologically similar to their primary tumour of origin. Multiple tumour foci with an abrupt transition from normal pancreas to the neoplastic tissue without signs of chronic pancreatitis in the surrounding parenchyma support metastatic origin

Click to access Pubmed
Adsay NV, Andea A, Basturk O, Kilinc N, Nassar H, Cheng JD (2004)
Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature.
Virchows Arch 444: 527-35



. As expected, renal cell carcinomas metastatic to the pancreas often have clear cytoplasm, while the cells of metastatic melanoma may produce melanin and have prominent nucleoli.

Immunohistochemistry
A panel of immunohistochemical markers can be employed to narrow possible organs of origin in problematic cases or to validate a clinical impression.

Cytopathology
Endoscopic ultrasound (EUS)-guided fine-needle aspirations have a high sensitivity in diagnosing a pancreatic metastasis, even after a previously negative or inconclusive imaging study

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DeWitt J, Jowell P, Leblanc J, McHenry L, McGreevy K, Cramer H, Volmar K, Sherman S, Gress F (2005)
EUS-guided FNA of pancreatic metastases: a multicenter experience.
Gastrointest Endosc 61: 689-96




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Volmar KE, Jones CK, Xie HB (2004)
Metastases in the pancreas from nonhematologic neoplasms: report of 20 cases evaluated by fine-needle aspiration.
Diagn Cytopathol 31: 216-20



. Lesions with the impression of having well-defined borders by EUS are more likely to be a secondary tumour
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DeWitt J, Jowell P, Leblanc J, McHenry L, McGreevy K, Cramer H, Volmar K, Sherman S, Gress F (2005)
EUS-guided FNA of pancreatic metastases: a multicenter experience.
Gastrointest Endosc 61: 689-96



.

Differential diagnosis
The most problematic secondary neoplasms to differentiate from a primary pancreatic neoplasm are metastases from the gastrointestinal tract, renal cell carcinomas and melanomas. Renal cell carcinomas can be difficult to distinguish from well-differentiated pancreatic neuroendocrine neoplasms, especially in patients with von Hippel-Lindau syndrome

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Colonna J, Plaza JA, Frankel WL, Yearsley M, Bloomston M, Marsh WL (2008)
Serous cystadenoma of the pancreas: clinical and pathological features in 33 patients.
Pancreatology 8: 135-41




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Hoang MP, Hruban RH, Albores-Saavedra J (2001)
Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma: a distinctive neoplasm of von Hippel-Lindau disease.
Am J Surg Pathol 25: 602-9



. Melanomas may mimic solid pancreatic neoplasms with brisk mitotic activity and nuclei with single prominent nucleoli, such as acinar cell carcinomas or medullary carcinomas of the pancreas
Click to access Pubmed
Adsay NV, Andea A, Basturk O, Kilinc N, Nassar H, Cheng JD (2004)
Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature.
Virchows Arch 444: 527-35



. Breast cancer metastatic to the pancreas is important to recognize because of the specific therapies available to treat some metastatic breast cancers. The patient's history and immunolabelling studies can help establish the correct diagnosis.

Prognosis
Since in most cases pancreatic metastases indicate an advanced stage of disease, the prognosis is generally poor. Surgical resection may be beneficial in selected patients

Click to access Pubmed
Reddy S, Edil BH, Cameron JL, Pawlik TM, Herman JM, Gilson MM, Campbell KA, Schulick RD, Ahuja N, Wolfgang CL (2008)
Pancreatic resection of isolated metastases from nonpancreatic primary cancers.
Ann Surg Oncol 15: 3199-206



.







Christine Iacobuzio-Donahue
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Christine Iacobuzio-Donahue
Department of Pathology
The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Baltimore
USA




Noriyoshi Fukushima
Click to contact editor
Noriyoshi Fukushima
Department of Pathology
Jichi Medical University
Tochigi
Japan





Renal cell carcinoma metastatic to the pancreas.
Renal cell carcinoma metastatic to the pancreas.

Renal cell carcinoma (left) metastatic to the pancreas.
Renal cell carcinoma (left) metastatic to the pancreas.