Hepatic neuroendocrine tumor

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Histological appearance of a canine hepatic neuroendocrine tumor showing neoplastic cells arranged in rows[1]

Hepatic neuroendocrine tumors are a rare, malignant neoplasm of the canine liver which result in neuroendocrine disease and constitute 14% of primary hepatic neoplasms[2].

Neuroendocrine cells, which produce peptides and amines, are distributed in many organs and tissues[3]. The most common sites are the respiratory and digestive tracts. In the past, these cells were called 'APUD' (amine precursor uptake and decarboxylation) cells. They were thought to be neuroectodermal in origin, arising from the neural crest[4]. At present, these neuroendocrine cells, especially the epithelial-associated cells, are considered to be endodermal in origin and are designated as diffuse endocrine system[5].

Hepatic neuroendocrine tumors arise from the diffuse neuroendocrine system[6] and range in clinical appearance from benign carcinoids to the aggressive neuroendocrine carcinoma (Merkel cell carcinoma)[1].

In dogs, primaru neuroendocrine tumors can arise in sites such as the intestines, esophagus, nasal cavity, skin, bile duct, gallbladder, liver, and nasopharynx[7]. Peritoneal carcinomatosis and metastasis to regional lymph nodes occurs frequently[2].

Clinically affected dogs present with rapid-onset (usually within one to two weeks) of weight loss, anorexia, icterus (uncommon), ascites and vomiting.

Hematological analysis often shows leucocytosis, elevated ALT, ALP, hyperalbuminemia and increased albumin/globulin ratio[8]. Prothrombin and activated prothrombin times should also be evaluated to asses clotting function.

In rare cases, ectopic adrenocorticotrophin hormone secretion by these tumors may produce hypercortisolism and hypokalaemia[9].

Abdominal cystocentesis may reveal hemoperitoneum[10] and urinalysis usually shows hematuria.

A definitive diagnosis requires histopathological examination of biopsied tissue[11]. These tumors stain positively with Grimelius silver as well as the immunohistochemical markers synaptophysin, neuron-specific enolase and chromagranin-A[12].

A differential diagnosis would include hepatic adenoma, cholecystitis, hepatitis, hepatic carcinoma, bile duct carcinoma, liver flukes (especially Clonorchis sinensis)[13], hepatic adenoma and secondary metastatic lymphoma.


  1. 1.0 1.1 Patnaik AK et al (2005) Canine hepatic neuroendocrine carcinoma: an immunohistochemical and electron microscopic study. Vet Pathol 42(2):140-146
  2. 2.0 2.1 Patnaik AK et al (1981) Canine hepatic carcinoids. Vet Pathol 18:445–453
  3. Arnold R (2001) Diagnosis and management of neuroendocrine tumors. United Eur Gastroenterol eek — Neuroendocrine Tumors 8:1–12
  4. Pearse AG & Takor-Takor T (1979) Embryology of diffuse neuroendocrine system and its relationship to the common peptides. Fed Proc 38:2288–2294
  5. Rawdon BB & Andrew A (1993) Origin and differentiation of gut endocrine cells. Histol Histopathol 8:567–580
  6. Kulve MH & Mayer RJ (1999) Carcinoid tumors. N Engl J Med 340:858–868
  7. Patnaik AK et al (2002) Neuroendocrine carcinoma of the nasopharynx in a dog. Vet Pathol 39:496–500
  8. Cooper ES et al (2009) Hyperalbuminemia associated with hepatocellular carcinoma in a dog. Vet Clin Pathol 38(4):516-520
  9. Churcher RK (1999) Hepatic carcinoid, hypercortisolism and hypokalaemia in a dog. Aust Vet J 77(10):641-645
  10. Aronsohn MG et al (2009) Prognosis for acute nontraumatic hemoperitoneum in the dog: a retrospective analysis of 60 cases (2003-2006). J Am Anim Hosp Assoc 45(2):72-77
  11. Stockhaus C et al (2004) A multistep approach in the cytologic evaluation of liver biopsy samples of dogs with hepatic diseases. Vet Pathol 41(5):461-470
  12. Patnaik AK et al (2001) Clinicopathologic and electron microscopic study of a cutaneous neuroendocrine (Merkel cell) carcinoma in a cat with comparison to human and canine tumors. Vet Pathol 38:553–556
  13. Rim HJ (2005) Clonorchiasis: an update. J Helminthol 79(3):269-281