Chapter 18 - Tumors of the Skin and SQ Tissues Flashcards
What is the overall incidence of skin tumors in dogs and cats and what percentage is considered to be malignant?
- Overall incidence 25.5 to 43% - difficult based on literature - 20 to 40% malignant Ref: 1-6 and 2, 3
In dogs, what is the incidence of skin and connective tissue tumors in a survey of California counties from 1963 to 1966? Excluding melanomas?
- 150.4/100,000 (0.15%) - 90.4/100,000 (0.09%)
In cats, what is the incidence of skin and connective tissue tumors in a survey of California counties from 1963 to 1966?
- 51.7/100,000 (0.05%)
In a study of 3,564 cats that were examined by biopsy or necropsy during a 41-month period from January 1, 1986 through May 31, 1989, what percentage of cats were diagnosed with cutaneous neoplasia? In this study, skin tumors accounted for what percentage of all tumors that were diagnosed?
- 9.6% - 29.6% Ref: 5
Similar to previous studies, other studies report that what percentage of tumors arise from the skin in cats?
19.3% to 21% Ref: 6, 7
With the exception of basal cell tumors, what percentage of skin tumors are considered to be malignant in cats?
69.7 to 82% Ref: 6, 5
What is the incidence of cutaneous MCT in dogs?
16.8%
What is the incidence of cutaneous lipomas in dogs?
8.5%
What is the incidence of cutaneous histiocytoma in dogs?
8.4%
What is the incidence of cutaneous perianal gland adenoma in dogs?
7.8%
What is the incidence of cutaneous sebaceous gland hyperplasia/adenoma in dogs?
6.5%
What is the incidence of cutaneous SCC in dogs?
6%
What is the incidence of cutaneous melanoma in dogs?
5.6%
What is the incidence of cutaneous fibrosarcoma in dogs?
5.4%
What is the incidence of cutaneous basal cell tumor in dogs?
5%
What is the incidence of cutaneous peripheral nerve sheath tumor in dogs?
4.3%
What is the incidence of cutaneous papilloma in dogs?
2.8%
What is the incidence of cutaneous sweat gland adenocarcinoma in dogs?
1.1%
What is the incidence of cutaneous sebaceous adenocarcinoma in dogs?
0.5%
What are the 4 most common tumors in dogs?
MCT, lipoma, histiocytoma, perianal gland adenoma (in order)
What is the incidence of cutaneous basal cell tumor in cats?
23%
What is the incidence of cutaneous fibrosarcoma in cats?
17.8%
What is the incidence of cutaneous mast cell tumor in cats?
16.5%
What is the incidence of cutaneous SCC in cats?
10.4%
What is the incidence of cutaneous apocrine adenoma in cats?
3.4%
What is the incidence of cutaneous lipoma in cats?
3.3%
What is the incidence of cutaneous hemangiosarcoma in cats?
2.9%
What is the incidence of cutaneous sebaceous adenoma in cats?
2.8%
What is the incidence of cutaneous fibroma in cats?
2.7%
What is the incidence of cutaneous hemangioma and melanoma in cats?
1.7%
What is the incidence of cutaneous malignant fibrous histiocytoma in cats?
0.7%
What are the 4 most common cutaneous tumors in cats?
Basal cell tumor, FSA, MCT, SCC (in order); they make up approximately 70% of skin tumors in cats
What factors have been associated with increased risk of skin cancer?
Ionizing radiation, thermal injury, UV radiation, papillomavirus infection, immunosuppression
White cats in California have an ___ increased risk of developing cutaneous SCC due to solar exposure. What are the most common locations? In another study of 61 cats with cutaneous SCC, what percentage of cats were white and what percentage spent time outside?
13.4x Head, neck 95% 96% Ref: 18, 23
What viral infection can lead to cutaneous tumors in dogs? What cells are affected?
Papillomavirus; keratinocytes (papillomaviruses are only able to replicate in terminally differentiated cells an can stimulate increases proliferation and terminal differentiation)
How does neoplastic transformation arise in cells infected with papillomavirus?
Neoplastic transformation arises from the viral effects on cell proliferation, integration into the genoma, and interaction of the viral proteins with cellular proteins, particularly the destabilization of p53 by viral protein E6 and the inhibition of pRB by viral protein E7. Disruption of p53 results in increased levels of p16 protein, which can be detected with IHC.
The presence of what tumor can be seen in dogs and cats infected with papillomavirus?
SCC, usually invasive and metastatic
What virus has been detected in dogs and cats with oral and cutaneous SCC?
Papillomavirus; these SCC cases are usually invasive and metastatic
What are two presentations in cats infected with papillomavirus?
Viral plaques -> can turn into SCC Fibropapillomas or feline sarcoids
Although papillomavirus can be detected with IHC in the majority of feline viral plaques, what happens as the plaques progress to SCC? What can be used instead?
Ability to detect it using IHC for Ag decreases PCR
In cats, ___% of UV protected SCC test positive for papillomavirus using PCR vs ___% of UV exposed SCC.
76% 42%
In a study of cats with Bowen’s in situ carcinoma, what % of lesions tested were positive for papillomavirus using PCR?
25%
What strains of human papillomavirus have been found in cats?
5, 21, 38
What protein has been found to be elevated in cats with viral plaques, Bowenoid tumors, and non-solar induced invasive SCC, consistent with the presence of papillomavirus? This is compared to cats with trichomonas (control) and solar induced SCC.
p16
Humans that have received organ transplants have a ____ increased risk for developing SCC
100x Also, humans that are immunosuppressed are at increased risk for developing SCC
In humans, basal cell carcinomas can arise from mutations in which signaling pathway?
Hedgehog
Which reciprocal translocation has been reported in a dog with a basal cell tumor? What gene is involved?
t(10;35) Chromosome 10 contains the gene GLI1, which is the effector transcription factor of the HH signaling pathway Translocations result in chimeric fusion of proteins that have an overall oncogenic effect
What two aberrant karyotypes have been found in cats with basal cell tumors?
Trisomy E3 Monosomy E3
Out of 24 cats with BCT, how many were positive using IHC for expression of the apoptotic regulatory proteins Bcl-2 and Bax? Which one of these is specific for human BCC?
Bcl-2 expressed in 23/24 cats Bax expressed in 7/24 cats Bcl-2
Mutation in what gene is commonly found in humans with cutaneous SCC?
p53
A series of 3 IHC studies of p53 in canine cutaneous SCC revealed that ___% were positive for overexpression of this gene.
29.5%
A series of 3 IHC studies of p53 in feline cutaneous SCC revealed that ___% were positive for overexpression of this gene. What other form of solar induced change can result in overexpression of p53 in cats?
47.5% Actinic keratosis
What prevents positive IHC staining when p53 is present in its wild-type form?
Its short half life
In dogs, which protein is expressed at much lower levels in SCC vs benign cutaneous neoplasms?
p27 -> responsible for maintaining cells in G0
What protein has been shown to be present in the nucleus of 100% of dogs with trichoepitheliomas and pilomatricomas (hair follicle tumors)?
B-catenin; this represents pathway activation
Cyclin ___ is present in ___% of feline SCC and ___% of canine SCC?
Cyclin A - important for cell cycle regulation 90% of feline SCC 44% of canine SCC
Which cyclin is rarely expressed in skin tumors of any type?
Cyclin D1
A mutation in what gene is associated with development of renal cystadenocarcinoma and nodular dermatofibrosis? What does the gene code for? Most common dog breed seen? What’s another dog breed?
Birt-Hogg-Dube gene; codes for folliculin protein, which is a tumor suppressor protein German Shepherd dog #1 Alsatians
The use of which TKI has been associated with development of actinic keratosis and invasive SCC in humans? Which receptors are blocked with this TKI?
Sorafenib - blocks Raf, VEGFR, PDGFR
Which two factors are potentially synergistic towards the development of cutaneous SCC in dogs and cats?
UV light exposure and papillomavirus infection
What diagnostic technique is recommended to obtain a diagnosis for lesions that appear malignant or are non-diagnostic on cytology?
Biopsy- because of all the information you can obtain (histopath, grade, IHC, PCR etc). Tru-Cut or needle biopsies are not recommended as tissues obtained are small and limit the info you may get. Multiple punch biopsies or incisional biopsies are preferred.
In dogs with skin tumors, advanced imaging such as US and CT increases the stage of the primary tumor in what % of patients?
69%
What is the mainstay treatment for local control of cutaneous tumors?
Surgery
What tumors are considered to be basal cell tumors?
Basal cell carcinomas (malignant version) and basal cell epitheliomas (benign version)
Which two tumor types are no longer considered basal cell tumors?
Trichoblastomas Solid-cystic ductular sweat gland tumors (adenomas and carcinomas)
Where do basal cell tumors arise from?
Stem cells in the outer follicular root sheath that present variable differentiation; origin is not absolutely determined
What are basosquamous cell carcinomas? What is the incidence of these tumors in dogs and cats?
Tumors with characteristics of both BCC and SCC; immunohistochemically, they are more closely related to BCC. Incidence is unknown
What types of cells are seen on cytology samples from BCC?
Inflammatory cells, squamous cells, sebaceous epithelial cells, melanin, melanophages Well differentiated fibroblasts, reactice fibroblasts, and mast cells can also be present
When evaluating a BCC with cytology alone, how are they collectively called?
Cutaneous basilar epithelial neoplasms; because the subtypes cannot be identified using cytology alone
What IHC marker is specific for BCC in humans?
BerEP4 - very specific membrane glycoprotein marker Used to differentiate a BCC from a SCC or a solid-cystic ductular sweat gland epithelial tumor in humans
What IHC marker can be used to differentiate a sweat gland epithelial tumor in humans?
Cytokeratin 8 - expressed in sweat gland epithelial tumors
What % of skin tumor are BCT in dogs and cats?
Dogs: 5.5 to 8.4%; unclear if trichoblastomas included Cats: 10 to 26%
What 2 dog breeds and 1 cat breed have been reported to be at increased risk for developing BCC?
Cocker spaniels Poodles Siamese One study found no breed association
How do BCC clinically appear?
Plaques or nodules, often darkly pigmented (may resemble melanoma) Overlying skin may be alopecic, intact, or ulcerated
What is the median age of dogs and mean age of cats at the time of BCC diagnosis?
Dogs - 9 years Cats - 9.6 to 10.8 years
What are the the BCC histologic subtypes?
Solid, keratinizing, clear cell
Are BCC considered a low-grade malignancy or high-grade?
Low-grade
BCC recurrence rate and metastatic behavior in dogs? What can be useful in differentiating BCC that can potentially recur from those that cannot?
Can recur after sx excision but no reports of metastasis Morphometric analysis of cell nuclei
Although now thought of as rare, what is the reported second most common solid tumor in cats after mammary carcinoma?
BCC - this is likely not true as these are now considered to be rare after they were changed to being either apocrine ductular carcinomas or trichoblastomas
In cats, what % of previously called BCC are now called apocrine ductular carcinoma and trichoblastoma?
Solid cystic apocrine ductular carcinoma 60% Trichoblastoma 40% Literature still calls them BCT
What are common locations for BCC in cats?
Head and neck; can occur anywhere in the body though
Although the majority of BCT in cats appear to have a benign behavior, what % is considered malignant? Based on what 6 criteria?
10% (10/97 cats in one paper) Stromal invasion, lymphovascular invasion (5 cats), necrosis, high mitotic index, LN mets (1 cat), pulmonary mets (1 cat) Despite this, met rate appears to be low Ref: 79, 82
_________ was able to predict recurrence of BCC in one study of 23 cats.
Nucleomorphometric analysis Ref: 83
What is the treatment of choice for cats with BCC? What other treatments have been reported?
Surgery is TOC; RT and doxorubicin -> unknown survival impact
What are papillomas?
Benign epidermal proliferative lesions often associated with papillomavirus infection.
Cutaneous papillomas are typically found in younger dogs, with an average age of ___ years.
3.2 years
What 3 treatment options are available for dogs with papilloma?
Sx resection Benign neglect - can go away on their own Azithromycin Ref: 86
What type of papilloma is seen in cats?
Fibropapilloma - demonstrate proliferation of mesenchymal cells covered by hyperplastic epithelium. Evaluation for PV demonstrated an apparent non-productive infection of the mesenchymal cells (Ref: 87)
Feline papillomas are more similar to _______ than papillomas.
Equine sarcoids
What is the definition and difference between SCC in situ, actinic keratosis, and Bowen’s carcinoma?
SCC in situ - carcinoma that has not penetrated the basement membrane of the epithelium. Can occur anywhere in the body, haired and non-haired skin. AK - SCC in situ that arises as a consequence of UV exposure; usually lightly haired skin. Bowen’s carcinoma, Bowenoid carcinoma in situ, multicentric papillomavirus-induced SCC - multiple carcinoma in situ. Can occur anywhere in the body, haired and non-haired skin. This is usually seen in cats, with only a few reports of it in dogs. Solitary lesions are uncommon. All of these are IN SITU
Where do AK lesions usually occur and what histopathologic changes can be seen in these lesions?
Lightly haired skin with UV exposure Solar elastosis and fibrosis of the skin > consistent with chronic UV exposure
What can happen with untreated carcinoma in situ?
They can become invasive and put the patient at risk for metastasis
How does BISC usually behave?
Typically patients will continue to develop new lesions over time, but metastasis appears to be uncommon
What is the median DFI and MST in cats with carcinoma in situ treated with surgery (TOC)?
DFI - 594d MST - 675d Ref: 23; study of 39 cats
What topical treatment can be used in cats with Bowen’s carcinoma? What is the treatment regimen?
Imiquimod cream 5% 5/12 cats had at least 1 lesion disappear (CR) Treatment regimen: SID (mostly) or 3x/week
Besides surgery and Imiquimod cream, what other treatment options (4) are available for cats with SCC in situ?
Palliative RT - can control dz for 8 months Photodynamic therapy - up to 100% RR Strontium 90 plesiotherapy Etretinate - showed promise but d/c
What was the response rate, recurrence rate, and overall MST seen in a study of 14 cats with nasal planum SCC in situ that were treated with strontium 90?
Response rate 100% No recurrence MST >3,000 days
What is the metastatic behavior (high or low? met rate?) in cats with SCC in situ or AK?
Low; in a study of 61 cats with tumors in the nasal planum and pinnae -> 1.6% (1 cat) to regional LN mets at the time of recurrence
What topical treatment has been used in cats for SCC in situ and BISC, but did not demonstrate clinical efficacy?
13-cis-retinoic acid
What has been associated with prognosis in cats with carcinoma in situ?
Tumor stage
What is the definition of squamous cell carcinoma?
Malignant tumors of the epidermis in which the cells demonstrate differentiation to squamous cells (keratinocytes)
What is the median age in dogs and cats diagnosed with SCC?
Dogs - 10 to 11 years Cats - >10 years
What is the predilection site in cats with SCC?
Head, particularly lightly haired areas in white cats. Reflects the role of UV light exposure