Internal Medicine, Endocrinology and Oncology 10%

Question 1

Nodular dermatofibrosis is associated with the a)_____ mutation, on the b)_______ gene of chromosome c)_______.

Answer 1

a) H255R mutation
b) folliculin gene
c) chromosome 5

Question 2

What breeds has nodular dermatofibrosis been reported in?

Answer 2

German Shepherds, a Golden Retriever, Boxer, Australian Shepherd and mixed breed dogs.

Question 3

Nodular dermatofibrosis is associated with an elevated cutaneous levels of which cytokine?

Answer 3

Transforming growth factor beta 1 (TGF-beta1)

Question 4

What risk factors are associated with developing doxorubicin induced alopecia?

Answer 4

Cumulative dose of doxorubicin and coat type (curly or wire coated animals predisposed)

Question 5

What breeds are overrepresented with canine ischemic dermatopathy (i.e. not hereditary dermatomyositis)?

Answer 5

Toy and miniature poodles, Chihuahuas, Jack Russell and Yorkshire terriers.

Question 6

What does PARR stand for?

Answer 6

PCR for Antigen Receptor Rearrangment (PARR)

Question 7

Describe the principles of clonality testing.

Answer 7

• PCR amplification of the lymphocyte antigen receptor
• Size separation of amplicons by gel electrophoresis
• Lymphocyte antigen receptor genes are amplified using primers upstream and downstream of the junctional region
• Polyclonal results are suggestive of a reactive/inflammatory process
• Clonal results are indicative of lymphoma

Question 8

What are three causes of false negative test results when performing clonality testing?

Answer 8

1) Use of primer sets that do not recognize all rearranged gene segments
2) Reactive lymphocytes that quench a clonal signal
3) Mutation of primer sites due to hypermutation

Question 9

What are the three forms of cutaneous epitheliotropic lymphoma recognized in animals?

Answer 9

1) Mycosis fungoides (most common, spanning epidermal/dermal junction)
2) Pagetoid reticulosis (neoplastic cells confined to epidermis and adnexa)
3) Sezary syndrome (neoplastic cells found in blood and skin)

Question 10

How does the immunophenotype of cutaneous T-cell lymphoma differ between humans an dogs

Answer 10

Human CTCL’s consist of CD4+ alpha/beta T-cell populations where as in dogs, the majority of cutaneous lymphomas are CD8+ or CD3+ gamma/delta T-cell malignancies.

Question 11

What is c-Kit?

Answer 11

• A mutation of the tyrosinase rinse growth factor receptor, specifically for “stem cell factor”, seen in a large minority (i.e. 15-35%) of canine mast cell tumors
• Mutations can render KIT active even in the absence of bound stem cell factor
• Receptor important for maturation of mast cells and other hematopoietic cells

Question 12

What is the most useful histologic information regarding excised mast cell tumors?

Answer 12

1) Histologic grade
2) Margins
3) Mitotic index

Question 13

Erythema multiforme, graft-vs-host disease and feline thymoma associated exfoliative dermatitis all share striking histologic similarities. What is the source of the antiepithelial T cells in each of these diseases?

Answer 13

Graft-vs-host disease : exogenous
Erythema multiforme : pre-existing
Thymoma-associated exfoliative dermatitis : newly generated

Question 14

What are the clinical features of thymoma-associated exfoliative dermatitis?

Answer 14

• Can either be in association with a thymoma or not
• Regions of erythema and exfoliation develop with gradually increasing severity; alopecia develops secondarily to the exfoliative erythroderma
• Head neck and ears commonly first affected before the syndrome generalizes
• Large sheets of exfoliated stratum corneum develop, often greater than 1 cm, and may become entrapped in the remaining haircoat
• Clinical differentials include mycosis fungoides, pemphigus foliaceus, SLE, EM, dermatophytosis, demodicosis, or underlying hypercortisolemia or diabetes mellitus with secondary dermatophytosis.

Question 15

What are the histologic features of thymoma-associated exfoliative dermatitis?

Answer 15

• Mild transepidermal and follicular apoptosis and hyperkeratosis; may be subtle in some cases
• Vacuolation along the dermal-epidermal junction occurs
• Interface dermatitis is variably present and extends to superficial hair follicles to the level of the isthmus
• Follicular interface inflammation with scattered basal cell apoptosis is striking
• Sebaceous glands often absent
• Tends to have milder transepidermal apoptosis relative to erythem multiforme

Question 16

What are the histologic features of SLO?

Answer 16

• Interface inflammation obscuring the junction between clawbed epithelium and adjacent dermis is the hallmarkk feature
• In severe cases, inflammation may be more lichenoid or band-like
• Pigmentary incontinence; inflammation consisting of lymphocytes, macrophages intermingled with neutrophils
• Apoptosis and vacuolation of basal cells are common; suprabasilar apoptosis may occur.
• Frequently subepithelial vesiculation
• Secondary ulceration of claw-bed epithelium is common
• Osteomyelitis of the distal phalangel bone may occur

Question 17

What diseases have been associated with superficial necrolytic dermatitis in dogs?

Answer 17

• Idiopathic vacuolar hepatopathy
• Glucagon-producing endocrine tumours
• Phenobarbital and phenytoin administration
• Mycotoxin ingestion

Question 18

What diseases have been associated with superficial necrolytic dermatitis in cats?

Answer 18

• Pancreatic carcinoma (probably endocrine origin)
• Thymic amyloidosis
• Hepatopathy
• Intestinal lymphoma

Question 19

What are the clinical manifestations of “Generic dog food dermatosis”?

Answer 19

• Fever, depression, dependent edema, lymphadenopathy, pain
• Eroded/ulcerated fissured, well-demarcated annular plaques with thick, adherent crusts and erythematous borders
• Located on muzzle, mucocutaneous junctions, pressure points, flexure surfaces, distal extremities
• Usually seen in puppies during their rapid growth phase

Question 20

What are the defining histologic features of generic dog food dermatosis?

Wha

Answer 20

• Diffuse epidermal parakeratosis and prominent laminar edema, swelling and degeneration (similar to SND)

Question 21

Aside from thermal and chemical burns, what physgiologic stresses can result in a histologic lesion that appears very similar to a burn?

Answer 21

Combinations of

• pressure
• sheering forces
• ischemia
• diminished perfusion due to underlying disease
• heat
• Dorsal thermal necrosis from sunlight in short, dark colored hair breeds