Clinical Aspects of Cancer

What dog breed is a risk of lymphoma?

Golden Retrievers

What dog breed is at risk of Hemangiosarcoma

German Shepards

What dog breed is at risk of Histiocyticsarcoma?

Saint Bernard

What dog breed is at risk of mast cell tumors?

Boxers

What are some internal risk factors for cancer?

• Age

• Hormones

• Immunity

What are some external risk factor associated with UV?

• White cat predisposed

• UV radiation → DNA break and ROS production

• On ears, above eyes, nasal planums

• Squamous cell carcinoma

What are some external risk facters associated with toxins/chemicals?

• Aflatoxin b1: fungal toxin in the feed → metabolized in the liver → block DNA polymerase → hepatitis/liver cancers

• Pesticides/herbicides

• Bracken fern

STUDY THE EXTERNAL RISK FACTORS CHART IN LECTURE

YOU GOT THIS

Papillomavirus risk factors:

• viral oncogenes E6 and E7 suppress apoptosis in virus infected cells → immortal growth → wart/papilloma → carcinoma

• Horse sarcoid: BPV-1,2 infection, NOT equine PV

Inflammation/trauma risk factors for cats:

injection-site sarcoma, ocular post-traumatic sarcoma

Inflammation/trauma risk factors for dogs:

skin irritation → cancer

Paraneoplastic Syndromes

• Systemic clinical signs by the release of tumor cell products

• NOT the direct effects of the tumor itself

• Via hormones, cytokines, immune reactions

  • May be first clue of hidden neoplasia

Cachexia

• Weight loss and metabolic alterations

• Cytokines TNF-a, IL-1, IL-6 → contribute to anorexia → accelerate cachexia

• Irreversible (Paraneoplastic syndrome)

Humoral Hypercalcemia of malignancy

• PTHrP: parathyroid hormone-related protein (paraneoplastic syndrome

• Associated with PU/PD, anorexia, vomiting

• renal damage

Humoral hypercalcemia of malignancy in dogs:

T cell lymphoma, AGASACA and many others

Humoral hypercalcemia of malignancy in cats:

Lymphoma, SCC, multiple myeloma

Hypoglycemia

• Insulinoma

• Other non-endocrine tumors: Hepatocellular carcinoma, leiomyosarcoma, hemangiosarcoma

Hyperestrogenism

• Testicular tumors of male dog

• Feminization

• Bilateral symmetrical alopecia/hyperpigmentation

• bone marrow suppression → aplastic anemia/pancytopenia

Feline acromegaly

• “Big face” cats

• Functional adenoma in the pars distalis of the anterior pituritary gland

• Excessive GH secretion

• GHGH antagonize insulin → cats present with DM hepatomegaly, renomegaly, adrenomegaly, hypertrophic cardiomyopathy, clubbing of the paws and distal extremities

How do you determine Feline acromegaly?

IGF-1 measurements can confirm acromegaly

Equine hirsutism

• Pituitary Pars Intermedia Adenoma (PPID)

• Low ACTH secretion

• α-MSH, β-endorphins, corticotrophin-like intermediate peptide (CLIP)

• Laminitis, hypertrichosis, hyperglycemia, hyperhidrosis, PU/PD

How to test for anemia related paraneoplastic syndrome?

Blood work

What is paraneoplastic syndrome caused by?

HSA: due to excessive blood loss (regenerative anemia)

What are the signs of anemia caused paraneoplastic syndrome?

Lymphoma/leukemia/multiple myelona: associated with IMHA or decreased erythropoiesis due to effacement by cancer

What are some hematologic paraneoplastic syndromes?

• Anemia

• Hyperviscosity syndrome

• Thrombocytopenia

• DIC

Hyperglobulinemia and Bence Jones Proteinuria

• Multiple myeloma (Mature plasma cell origin)

• High globulin on chemistry (“hyperglobulinemia)

• Abundant M component of Ig in blood

• Excreted in urine: Bence-Jones proteinuria (casts/nephritis) 

What is this cutaneous manifestation?

Feline thymoma-associated exfoliative dermatitis

What is this cutaneous manifestation?

Feline paraneoplastic alopecia (pancreatic carcinoma or biliary carcinoma

What is this cutaneous manifestation?

Canine nodular dermatofibrosis in GSD-renal cystadenoma/carcinomas

What is this cutaneous manifestation?

Superficial necrolytic dermatitis-glucagonoma

Myasthenia Gravis

• associated commonly with thymoma

• Osteosarcoma, cholangiocellular carcinoma are reported

• Auto-antibodies targeting the Ach receptor within the neuromuscular junctions

• Muscle weakness

• Esophagus, pharynx, larynx, face

Hypertrophic Osteopathy

• Pulmonary carcinoma

• space-occupying thoracic mass or urinary bladder rhabdomyosarcoma

• Cats, dogs, and horses

• Symmetric lameness

• Thickening of the periosteum (outmost lay of the bone)

Tumor Grading

• given by pathologists

• features differentiation, mitoses, and necrosis

• grade of I, II, III

  • Canine mast cell tumor and canine soft tissue sarcoma

Tumor staging

• Extent of tumor growth and metastatic spread in a patient

• WHO TNM (tumor size, lymph node involvement, extent of metastasis) stage

• CBC/Chem/UA/3CXR/AUS ± lymph node and bone marrow aspirates

• Guides prognosis and treatment

PCR for antigen receptor rearrangements:

• For lymphoma clonality

• Helpful when cytology and histopathology are ambiguous

• Most commonly used in GI biopsy

Flow cytometry

• Immunophenotyping (B/t cells), cell size, granularity

  • Preferred method for distinguishing B vs T cell lymphoma along with immunohistochemistry

Genomic tests

• helpful in confirming cancer diagnosis

• BRAF mutation in Urothelial carcinoma

• c-KIT tandem duplication in mast cell tumor