Neoplasms of the Canine, Feline and Lemur Liver:
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1 Neoplasms of the Canine, Feline and Lemur Liver: Classification and Prognosis Annual Seminar of the French Society of Veterinary Pathology John M. Cullen VMD PhD DACVP North Carolina State University
2 Primary Hepatic Neoplasia Hepatocellular Biliary Others Hepatocellular adenoma Hepatocellular carcinoma Cholangiocellular adenoma (Biliary adenoma) Cholangiocellular carcinoma (Biliary CA) Hemangiosarcoma Carcinoids Hepatoblastoma Myelolipoma Mixed hepatocellular and cholangiocellular carcinoma
3 Non-neoplastic Proliferative Lesions Nodular hyperplasia Age-related (start at 6 years) Solitary yellow to dark red masses Liver otherwise normal Lobular architecture retained No clinical significance
4 Nodular Hyperplasia
5 Nodular Hyperplasia
6 Multiple Nodules Regenerative Nodules Non-neoplastic: Regenerative Nodules Nodular Hyperplasia Metastasis Biliary CA Hepatocellular CA Carcinoids
7 Hepatocutaeous Disease
8 Regenerative nodule Sirius red
9 Hepatic Neoplasia: Hepatocellular adenoma Usually solitary Common Loss of lobular architecture Trabeculae uniform Some necrosis possible
10 Hepatic Adenoma
11 Hepatic Adenoma
12 Hepatocellular carcinoma Uncommon in domestic species Friable gray-yellow to red Single nodule or multinodular Necrosis Metastasis uncommon generally
13 Hepatocellular Carcinoma Histologic Variants Trabecular Glandular Solid Clear Cell Often mixed forms No relationship between histologic appearance and behavior (one exception)
14 Hepatocellular Carcinoma Key Features for Diagnosis of Malignancy Pleomorphism Mitoses Invasion Local Intravascular IHC (K19)
15 Trabecular Hepatocellular Carcinoma Irregular thickness
16 Solid-Pleomorphic
17 Clear Cell HCC
18 Invasion of HCC Normal liver Area of invasion
19 Dogs Can we predict the risk of metastasis in primary hepatocellular carcinoma? Take your pick! Reported Frequency 61% (Patnaik AK et al. 1981, Veterinary Pathology 18:427) 25% (Trigo FJ,et al. 1982, J Comp Pathol 92:21) 4.8% (Liptak JM et al. 2004, JAVMA, 225:1225) Quite uncommon-wsava working group
20 IHC markers can predict the risk of metastasis in dogs. Markers HepPar1 Cytokeratin 7 Cytokeratin 19 Glypican-3 Muc-1 CD-10 The Veterinary Journal, 2013, 197:596
21 Origin and Classification of Primary Hepatic Tumors in Humans van Sprundel et al. Vet J. 197:2013
22 Canine Nodular Hyperplasia H&E HepPar1 CD 10 Cytokeratin 19 Van Sprundel Vet. J 2013
23 Canine hepatocellular tumor with low risk of metastasis H&E HepPar-1 CD-10 Cytokeratin 19 Cytokeratin 19 MUC-1 Van Sprundel, 2013
24 Canine HCC with high potential for metastasis H&E H&E Cytokeratin 19 HepPar-1 CD-10 Van Sprundel Vet. J 2013
25 Van Sprundel Vet. J 2013
26 Van Sprundel Vet. J 2013
27 Canine Hepatocellular Carcinoma Risk A small subset of tumors stain with: Cytokeratin 19 (>5% of surface area) Glypican-3 Do not stain with HepPar1 These tumors are the most likely to metastasize Note: some tumors with HepPar1 do metastasize
28 Some HepPar1+ HCC do metastasize H&E HepPar1 Lamoureaux, J. et al. JAVMA, Vol 241, No. 12, December 15, 2012
29 Benign or Malignant?
30 Mixed Hepatocellularcholangiocellular carcinoma Uncommon
31 Mixed Hepatocellularcholangiocellular CA
32 Mixed Hepatocellular-cholangiocellular carcinoma
33
34 Scirrhous Hepatocellular Tumor
35 Canine Scirrhous Hepatocellular Carcinoma
36 Canine Scirrhous HCC variant: Metastasis risk not well characterized Cytokeratin 19 staining of ductules
37 HCC in Cats Metastasis Uncommon 3/18 with mets. IHC All tumors express HepPar1 None with >5% CK19
38 Feline HCC
39 HepPar-1+ metastasis in cats Lung Hepatic Lymph node HepPar1
40 Hepatocellular Carcinoma in Lemurs Metastasis Relatively common Metastasis = 6/15 Iron? Virus? Carcinogen?
41 HCC in Lemurs Pulmonary metastasis
42 Lemur HCC metastasis markers: HepPar1 and Cytokeratin 7 HepPar1 in lung metastasis CK7 in lung metastasis
43 Hepatoblastoma Rare! Foal Dr. D. Malarkey Mouse AFP stain
44 Old View? Cholangiocellular adenoma Most common in cats Ducts and cysts lined by well differentiated biliary epithelium Cystic variants-biliary cystadenomas
45 New View Cholangiocellular adenoma Rare Solitary, well circumscribed Slightly dilated structures Cuboidal to flattened epithelium
46 Cat: Biliary Adenoma vs. Anomaly
47 Kidney
48 Biliary Adenoma or Polycystic Disease
49 Hepatic Neoplasia: Cholangiocellular (biliary) carcinoma Single or multinodular masses Firm, umbilicated, whitish Histo: ducts or acini lined by poorly differentiated cuboidal biliary epithelium Mucin Mitoses Metastasis very common
50 Cholangiocellular Carcinoma Dog Metastasis common 10/10 cases Cat Metastasis common 25/25 Van Sprundel et al. Vet. J. 197:2013 and 202:2014
51 Cholangiocarcinoma
52 Cholaniocarcinoma/Biliary Carcinoma
53 IHC Cholangiocarcinoma All Cytokeratin positive Muc-1 positive NSE +/-
54 Cholangiocarcinoma Cytokeratin 19 Muc-1 Muc-1 HepPar1
55 Gall bladder Neoplasia Epithelial Gall bladder adenoma Gall bladder carcinoma Others Carcinoid Mesenchymal tumors
56 Carcinoids Canine and feline Neuroendocrine cells in biliary tree High rate of metastasis IHC: chromogranin A and neuron-specific enolase Cats +/- cytokeratin 19 (small cell carcinoma)
57 Hepatic carcinoid
58 Van Sprundel Vet. J 2013 synaptophysin Canine hepatic carcinoid
59 Hepatic Neoplasia Miscellaneous Stellate cells Rats Hemangiosarcoma fibrosarcomas, osteosarcomas, leiomyosarcomas Myelolipoma
60 Rat Stellate (Ito) Cell Proliferation
61 Hepatic Neoplasia: Hemangiosarcoma Dark red mass with hemorrhage and omental adhesions MUST CHECK WHOLE BODY
62 Corgi Telangiectasis
63 Leiomyosarcoma of the liver
64 Myelolipoma Cats > Dogs
65 Hepatic Splenosis
66 Metastasis Hepatic metastasis of an intestinal carcinoma Liver most common site of metastasis in most species
67 Hematopoietic Neoplasia Malignant lymphoma most common metastasis in most species Diffuse infiltration at the gross level Portal infiltration at the histological level
68 Hepatic Neoplasia: Conclusions Primary neoplasia of the liver is uncommon in dogs and cats. Metastasis from HCC is generally uncommon in dogs and cats, but occurs in about one half of lemur liver tumors. Metastasis from Cholangiocellular carcinoma is very common New markers associated with prognosis are being developed
69 Thank You
70 MixeHepatocellularcholangiocellular CA Cytokeratin 7 Cytokeratin 19
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