Tumors of the skin and SQ tissue

Question 1

Percent of malignant skin tumors is higher in cats than in dogs?

Reported percentage?

Answer 1

True - 69.7-82%

Question 2

Dog skin tumors represent what percentage?

What percent are malignant?

Answer 2

25-43%, 20-40%

Question 3

Cat skin tumors represent what percent?

Answer 3

10%

Question 4

Top 5 skin tumor in dogs and percent?

Answer 4

MCT - 16.8%
Lipoma - 9%
Histiocytoma - 9%
Perianal gland adenoma - 7%
Sebaceous gland hyperplasia/adenoma-6%

Question 5

Top 5 skin tumors in cats and percent?

Answer 5

Basal cell tumor - 23%
MCT - 16%
SCC - 10%
Fibrosarcoma-17%
Apocrine adenoma -3%

Question 6

Role of UV radiation/sun exposure in cancer?

Answer 6

Cutaneous HSA (dogs)
SCC (Light colored cats) - 13.4x risk on nasal planum and pinnae

Question 7

How do viral factors play a role in neoplastic transformation?

Answer 7

Affects proliferation, integration into genome, viral proteins interact with cellular proteins

E7 - inhibits pRB
E6 - destabilizes p53 –> increasing p16

Question 8

Genetic abnormalities associated with basal cell carcinoma?

Feline BCC?

Answer 8

Reciprocal translocation (10:35) - Chromosome 10 contains GLI1 gene - TF in hedgehog pathway - altered in human BCC

Feline BCC - aberrant karyotype, negative expression of p53, down regulation of Bax protein (apoptotic protein)

Question 9

1. Genetic abnormalities associated with squamous cell carcinoma?
2. Renal cystadenocarcinoma and nodular dermatofibrosis in GSD?

Answer 9

1. p53 over expression in 30% of canine and 47.5% feline SCC
   Decreased expression of p27 (CDKI)
   Altered expression of B-catenin (skin homeostasis)
   Overexpression of cyclin A
2. Loss of function mutation in Bird-Hogg-Dube that encodes TSG folliculin

Question 10

TNM staging system for skin tumors

Answer 10

Question 11

Incidence of BCC in dogs?

Appreance on skin?

Behaivour in dogs and cats?

Median age in dogs and cats?

Breeds predisposed?

Location?

Treatment?

Answer 11

Rare in dogs (5.5-8.4%) of all skin tumors

Plaques or nodules, darkly pigmented, alopecic or ulcerated

Dogs - low grade malignancy (small chance of local recurrence)

Cats - benign behaivour, but malignant behaivour has been decribed malignant based on histopthological observations of high mitotic indexes, stromal/vascular/lymphatic invasion

Median age in dogs is 9 years and in cats is 9.6 to 10.8 years

Cocker spaniels and poodles and Siamese cats (although other studies reported no breed predispositions in dogs or cats)

Most common location in cats is the head and neck but can appear anywhere

Surgical excision

Question 12

Basosquamous cell carcinoma

Answer 12

Characteristics of both SCCs and BCCs.

Clinically, these tumors are indistinguishable from both BCCs and SCCs.

The true incidence and clinical behavior of these tumors in dogs and cats are unknown.

Question 13

What are papillomas?

Growth pattern?

Mean age?

Treatment?

Answer 13

Benign epidermal proliferative lesions associated with papillomavirus infection

Exophytic growth pattern

Young age with mean age 3.2 years

Surgical excision, spontaneously regress, azithromycin for multiple lesions

Question 14

What is SCC in situ?

Appearnce on skin and location?

Answer 14

Carcinoma that has not penetrated the basement membrane of the epithelium. When it appears in multiple sites, it is known as Bowen’s carcinoma and Bowenoid carcinoma in situ (BISC), vs actinic keratosis which is the name used for SCC in situ that arises as a consequence of UV exposure

Present as erosions of the epidermis, proliferations, or crusted plaques that can occur anywhere on the body and are usually multiple for BISC, and can be single lesions and appear on lightly haired skin with UV exposure for actinic keratosis

Left untreated - invasive carcinoma

Question 15

Treatment for SCC in situ

Answer 15

1) Surgical excision is the treatment of choice (Lana et al JAAHA 1997; n=39 cats, DFI=594 and OS=675 days),
2) 5% Imiquimod cream (Gill et al, VCO 2008; n=12 cats with BISC, CR in at least one lesion=5 cats),
3) Photodynamic therapy (Peatson et al, JAVMA 1993; very effective in the treatment of Bowen’s disease with ORR~100%),
4) Strontium-90 plesiotherapy (Hammond et al, JAVMA 2007; n=14 cats, CR=14 cats OS>3000 days),
5) 13-cis-retinoic acid (Evans et al, AJVR 1992).

Question 16

What is SCC?

Mean age for cats and dogs?

Location in cats?

Breeds at risk and breeds with decreased risk?

Answer 16

Tumors of epidermis and cells differentiate to squamous cells (keratinocytes)

Mean age of diagnosis is 10 years for cats and 10 to 11 years in dogs

Head, particularly in lightly haired areas of white cats, which reflect the role of UV light in the induction of many of these tumors

A decreased risk has been reported in Siamese, Himalayan, and Persian breeds; while an increased risk have been reported in Labradors and golden retrievers (nasal planum), Bloodhounds, Bassett hounds, and standard poodles (cutaneous)

Question 17

Treatment for cutaneous SCC

Nasal planum

Answer 17

1. Wide surgical resection

Nasal planum SCC, complete surgical excision of nasal planum resulted in long-term control in dogs (4/6 dogs; Lascelles et al, JAAHA 2004) and RT did not appeared to be effective in one study (Thrall et al, Vet Radiol, 1982, old study, gross disease, n=4 dogs, 1/4=durable remission, n=+7 dogs Sx + RT, recurrence at 9 weeks=7/7 dogs)

Strontium-90 plesiotherapy (Hammond et al, JAVMA 2007; n=49 cats, ORR=98%, CR=88%, DFI=1710 days, OS=3076 days)

Proton therapy (Fidel et al, JVRU 2001; n=15 cats, CR=9 cats and PR=5 cats, 64% DFI at 1 year, MST=946 days).

Question 18

Infundibular Keratinizing Acanthomas (aka intracutaneous epithelioma, keratoacanthoma and squamous papilloma)

Mean age?

Breeds at increased risk?

Location?

Treatment?

Answer 18

Common and benign tumors in dogs (not reported in cats).

Mean age is 4 to 9 years;

Belgian sheepdogs, Lhasa Apsos, GSDs, Nordic breeds and terriers.

Can be single or multiple and can appear at any location. Rupture can allow keratinized tissue into the adjacent dermis and incite a marked inflammatory response.

Treatment is surgery; but when it can’t be done, another option is using isotretinoin (ORR=3/7 dogs with 1CR/2PR; White et al, JAVMA 1993)

Question 19

Tricholomemma

Common location?

Treatment?

Answer 19

Rare and benign dermal and/or SQ tumors in dogs

Most common location is the head

Usually well-encapsulated masses with +/- alopecia.

There may be hair loss in the overlying skin.

Treatment is surgery.

Question 20

Trichoblastoma (aka basal cell tumors in dogs and spindle cell variant BCTs in cats)

Mean age in dogs and cats?

Breeds at increased risk?

Common location?

Treatment?

Answer 20

Common tumors in dogs and cats (represented 26% of canine and also feline follicular lesions, in a large study with >300 lesions in dogs 50 in cats; Abramo, JSAP, 1999).

Mean ages is 7 years for dogs and 10 for cats;

Breeds at increased risk are poodles and setters.

Most common location are the head/neck, and also the limbs and trunk in cats.

Treatment is surgery

Question 21

Trichoepitheliomas

Breeds at risk? Cats?

Common location?

Treatment?

Answer 21

Uncommon (4% of follicular tumors) and benign dermal tumors of dogs and cats that can extend to the SQ. Their surface can be ulcerated or alopecic.

Breed at increased risk are coonhounds, Bassett hounds and English springer spaniels (these two breeds may present with multiple tumors), and setters, and Persians cats.

Most common location in dogs are the limbs, neck, and back.

Unless multicentric presentation, the treatment is surgery.

Question 22

Malignant Trichoepithelioma (aka matrical carcinoma)

This malignant version is differentiated from their benign counterparts by the presence of?

Treatment?

Answer 22

Uncommon.

Higher mitotic index, invasion into the surrounding tissues, lymphatic involvement and high metastatic rate to the lungs.

Treatment is wide surgical resection, beyond that no information is available.

Question 23

Pilomatricomas

Appearance?

Mean age?

Breeds at risk?

Common location?

Treatment?

Answer 23

Uncommon (13% of follicular tumors in dogs and 1/898 skin biopsies in cats, in two studies) and benign follicular tumors that demonstrate only matrical differentiation.

These tumors present as very firm (due to ossification) well-circumscribed masses.

Mean age is 6.5 years

Kerry blue terrier, soft-coated Wheaton terrier, Bouvier des Flandres, standard poodle, Old English sheepdog, Bichon Frise, and Airedale terrier.

Most common locations are the neck, back, and trunk.

Treatment is surgery.

Question 24

Malignant Pilomatricomas

Answer 24

Rare in dogs and unreported in cats. If their malignant nature is not obvious on initial histologic evaluation, the presence of invasion into underlying tissues (particularly bone) may be a reasonable indicator of malignancy.

A high metastatic rate to lungs, bone, lymph node, mammary gland, or skin 11/12 dogs had been reported in one study (Carroll et al, Vet Path 2010). There is one report of surgery followed by RT for a recurrent mass with a DFI of 14 months, time at which diffuse pulmonary metastasis was documented (Johnson, Can Vet J 1983). No information on response to chemo is available.

Question 25

Sebaceous Hyperplasia, Sebaceous Adenoma, Sebaceous Ductal Adenoma and Sebaceous Epithelioma

Behaivour?

Mean age?

Breeds at risk?

Common location?

Treatment?

Answer 25

Very common in dogs and rare in cats.

Benign, lymphatic metastasis has been reported; therefore, thought as low-grade malignancies rather than absolutely benign.

Mean age is 7 to 13 years, a predilection for females have been reported, breeds at increased risk for hyperplasia are miniature schnauzers, beagles, poodles and cocker spaniels; and for tumors are Coonhounds, Nordic breeds and some terriers.

Most common locations are limbs, trunk, and eyelids. Treatment is surgery (unless metastasis), but recurrence have been reported.

Question 26

Sebaceous Gland Carcinomas

How common are these tumors?

Predilection?

Breeds at risk?

Common locations in dogs and cats?

Treatment?

Answer 26

Uncommon tumors in dogs and cats, that can behave as low-grade malignancies characterized most commonly by local infiltration and metastasis beyond the lymph node found only in one report (to bones, skin and lungs; Case et al, JAVMA 1963).

A predilection for intact male dogs has been reported,

Breeds at increased risk are Cavalier King Charles spaniel, cocker spaniel, and terrier breeds.

Most common locations are the head and neck in dogs and the head, thorax, and perineum in cats.

Treatment is surgery.

Question 27

Apocrine Gland Adenomas and Solid-Cystic Apocrine Ductal Adenomas (previously grouped into BCTs)

How common ar these tumors?

Common location in cats?

Treatment?

Answer 27

Common tumors in dogs, uncommon in cats. May be fluid filled or firm on palpation.

Most common location in cats is the head.

Treatment is surgery.

Question 28

Apocrine (sweat) Gland Carcinomas

Answer 28

relatively uncommon in dogs and a bit more common in cats (1.1 and 3% of all skin tumors, respectively). Two main studies looking at these tumors are available (Simko et al, Can Vet J 2003 and Kalaher, Vet Rec, 1990), one reported 40/44 apocrine gland tumors in dogs and 8/10 in cats to be malignant. Most commonly seen as solitary nodular lesions (indistinguishable from benign counterparts), but an “inflammatory” more diffuse and erosive form also exists. Local invasion is common (66% noted invasion of the capsule, and 11% and 22.5% noted vascular and lymphatic invasion), but the rate of distant metastasis is reported as low (2% to the lungs, contrasts high metastatic rate of anal sac apocrine gland carcinomas. Mean age in dogs is 9 years and in cats is from 6-17 years, breeds at increased risk are Golden retrievers and Treeing Walker coonhounds (no breed predilections in cats have been reported). Most common locations for dogs are the front legs, and for cats are the head, limbs, and abdomen. Treatment is wide surgical resection (if no metastasis, 4% recurrence rate), beyond this no information is available.

Question 29

What are Eccrine Adenomas and Carcinomas?

Treatment?

Answer 29

Tumors of the sweat glands of the foot pads.

Rare in dogs and cats, and no reports on clinical behavior or outcome are available.

Treatment is wide surgical excision.

Question 30

Neuroendocrine Carcinomas (aka Merkel cell carcinomas)

What are merkel cells?

Behaivour in humans vs. pets

Answer 30

Merkel cells are thought to be part of the mechanoreceptor system in the skin.

These are highly malignant tumor in humans (associated with Merkel cell polyomavirus infection), but generally have a more benign clinical behavior in pets, although all of our information is based on isolated case reports.

Although some of these reports do document instances of multiple recurrence and widespread metastasis to the lungs, abdomen and skin. Molecular evaluation of 2 dogs noted expression of β-catenin, E-cadherin (usually lost on more malignant human variants in people), and c-KIT (da Costa, Vet Dermatol, 2010). Treatment is wide surgical excision, beyond this no information (including response to c-KIT-TKi) is available (one report of a dog with multiple lesions and metastatic disease treated with various chemotherapeutics, and had an OS of 8 months; Joiner et al, Vet Pathol 2010).

Question 31

Renal Cystadenocarcinoma and Nodular Dermatofibrosis Syndrome

Breeds at increased risk?

Treatment?

Cause of death?

Answer 31

Present as multiple firm, haired masses. On histopathology these nodules are dense, irregular collagen. They typically do not result in clinical problems.

Breeds at increased risk are GSD and Alsatians; one case report of a non-lethal version of this syndrome was overserved in an Australian cattle dog (Gardiner, et al, Vet Pathol, 2008).

Treatment is wide surgical excision in patients that are doing otherwise well.

However, Most of these dogs will die from renal failure or progressive renal cystadenocarcinoma, in ~3 years.

Question 32

What are ceruminous glands?

Most tumors of the ear canal are diagnosed due to the mass effect, which may result in clinical signs such as ?

Negative prognostic factors include?

Answer 32

Modified apocrine glands found in the external ear canal

Chronic otitis or partial deafness

Mitotic index of >3 (Bacon et al, JSAP 2003), extension beyond the ear canal (“stage” see box), presence of neurologic signs, and histology of SCC (over CGA).

Question 33

Ceruminous Gland Adenomas and Cysts

Appearance?

Mean age?

Breeds at risk?

Ceruminous cysts are seen in cats as darkly pigmented small single or multiple masses

Treatment?

Answer 33

Benign tumors, typically exo­phytic, pedunculated and sometimes ulcerated.

Dogs is 9 years old, in cats adenomas present in younger patients than the malignant variants

Breeds at increased risk are cocker spaniels and poodles.

Treatment is surgery

Question 34

Ceruminous Gland Adenocarcinomas

Behaivour?

Breeds at increased risk?

Treatment?

Answer 34

Most common malig­nant tumors of the ear canal in both dogs and cats

These cancers can be very invasive locally and have important metastatic potential, thus a CT to assess local extension and full staging are recommended before planning definitive therapy.

Cocker spaniels and GSDs

The treatment of choice is complete surgical resection- TECA or a lateral bulla osteotomy, which are associated with significantly lower rate of recurrence than less aggressive techniques such as lateral ear canal resections (a study in dogs by Marino et al, JAAHA 1993 reported a DFI >36 months vs 4 months respectively; while a study in cats by Marino et al, JAAHA 1994 reported a DFI of 42 months vs 10 months respectively).

Radiation therapy also appears to be an effective treatment modality, with a reported PFS of 39.5 months after therapy (orthovoltage, 48 Gy in 12 4-Gy; Theon et al, JAVMA 1994). Evidence from various studies seem to suggest that long-term survival is possible with appropriate local therapy.

Question 35

Tumors of the digit in dogs?

How common and how frequent?

Answer 35

SCC are the most common malignancy of the digits in dogs (47%, with 3% being multi-digital, mostly in black-big-dogs, e.g., Rotties, black labs, giant schnauzers), followed by melanomas (24%, mostly in Scotties) and STS (13%)

These tumors can invade bone (SCC=80%, melanomas=21%) and metastasize (SCC=9% noted at diagnosis and 23% later, melanomas=28% at diagnosis and 39% later), thus appropriate staging is indicated.

For SCC of the digit, 1 and 2-year survival rates after surgery range from 50% to 83% and 18% to 62% respectively (subungual > other sites). Digital melanoma reported similar survival numbers, with 42% to 57% alive at 1-year post surgery and 13% to 36% at 2-years; the addition of adjuvant immunotherapy with the HuTyr vaccine reported an OS=476 days and a 63% and 32% 1 and 2-year survival rate after surgery (n=57, surgery and vaccination Manley et al, JVIM 2011).

Question 36

Tumors of the digit in cats?

Metastatic risk?

Answer 36

One study on digital tumors in cats (n=60, mostly on the front paws, some affecting multiple digits; Wobeser et al, Vet Pathol 2007) reported almost equal numbers for SCC (25%), fibrosarcoma (23%) and adenocarcinomas (22%).

Staging is also indicated in cats, especially in SCC as up to 87.5% of digital tumors were suspected to represent metastasis from primary lung carcinomas in one study (n=64 cats, “lung-digit syndrome”, MST=only 4.9 weeks, Van der Linde et al, Vet Q 2000), and also on melanomas (one study, n=5 cats only; mets=4, Luna et al, J Feline Med Surg, 2000). Median survival times for cats with SCC ranged from 10 to 29 weeks, and for the five cats with melanoma ranged from 0 to 577+ days.