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
What feline breeds (3) have a decreased risk for developing SCC?
Siamese Himalayan Persian
What canine breeds (2) may be predisposed to develop nasal planum SCC?
Labradors Golden Retrievers
What canine breeds may be predisposed to develop cutaneous SCC?
Bloodhounds Basset hounds Standard poodles Labs and goldens -> nasal planum SCC
What is the clinical presentation of cutaneous SCC?
Very variable Plaquelike to papillary Crateriform to fungiform May be erythemic, ulcerated, or covered with a crust
What paraneoplastic syndrome has been reported in cats with cutaneous SCC?
Hypercalcemia
What is the metastatic rate at the time of death in cats with invasive nasal planum SCC? What are the sites?
40% (6/15 cats) Regional lymph nodes, lungs LN are more common*
What is the metastatic rate in dogs with invasive nasal planum SCC? What are the sites?
23.5% (4/17 dogs) Regional LN (mandibular) - mets to distant sites not reported
What is the metastatic behavior in dogs with cutaneous SCC/how many cases are reported in literature? Sites?
Very uncommon 4 cases reported in literature lung, liver, bone
Treatment of choice for cutaneous SCC?
Surgery; results in excellent long-term control in both spp
In a series of 61 cats with SCC that were treated with surgery, RT, and cryotherapy, which of these treatment options resulted in the longest median DFI? What was the DFI?
Surgery; DFI 594 days *many of the cats did not have invasive dz
What treatment modality is effective for the treatment of nasal planum SCC in cats, but not in dogs?
RT
Besides surgery, what other treatment modalities are effective for the treatment of nasal planum SCC?
RT Strontium
90 plesiotherapy
Proton therapy
Intralesional carboplatin/sterile sesame oil
Chemotherapy: Intralesional carbo, bleomycin, mitoxantrone, actinomycin D, cisplatin
What was the 1-year survival rate in a study of 90 cats with nasal planum SCC that were treated with orthovoltage definitive RT (10 x 4Gy)? What was found to be predictive for PFS in this study?
60% 1 year survival rate Histologic tumor stage Ref: 101
What was the 1-year PFS rate in a study of 90 cats with nasal planum SCC that had stage T1 and T3 tumors when treated with definitive RT (10 x 4Gy)?
T1 - 85% 1 yr PFS rate T3 - 45.5% 1 yr PFS rate Ref: 101
In a study of 15 cats with nasal planum carcinoma, proton RT with a dose equivalent to 40Gy yielded a CR of ___% and a PR of ___%. The 1-year PFS in this study was ___% and the MST was ___ days.
60% CR 33% PR 6.6% SD (no response, 1 cat) 1-year PFS 64% MST 946 days (2.6 years)
A study evaluating the use of strontrium-90 plesiotherapy in 49 cats with with invasive SCC of the nasal planum yielded an overall RR of ___% and a CR of ___%. The median dose delivered was ___Gy and ___% developed recurrence with a median time to recurrence of ___ days. The median PFS was ___ days and the overall MST was ___ days.
Overal RR 98% CR 88% 128 Gy RR 28.5% Median time to recurrence 308 days Median PFS 1710 days MST 3076 days Ref: 94
Another study evaluating hypofractionated strontium in 15 cats with nasal planum SCC showed the CR was ___% and the PR was ___%. The recurrence rate in the cats that had a CR was ___%. The total dose delivered was ___Gy.
CR 86% PR 13.3% RR 0% at median follow up time of 652 days 50Gy Ref: 104
In a group of 4 dogs with nasal planum SCC treated with RT alone, only ___ dog achieved a durable remission. In this same study, ___ dogs were treated with a combination of surgery and RT, ___% of dogs had local recurrence at a median time of ___ weeks.
1 dog achieved a durable remission 7 dogs tx with sx + RT, 100% had local recurrence at a median time of 9 weeks.
Ref: 98
What was the local recurrence rate in a study of 8 dogs with nasal planum SCC treated with either orthovoltage RT or radon 222 implants?
100%
Ref: 106
What chemotherapy drugs have been used for the treatment of nasal planum SCC in dogs and cats?
Intralesional carbo, bleomycin, mitoxantrone, actinomycin D, cisplatin
Cats: intralesional carboplatin/sterile sesame oil, bleomycin, mitoxantrone
Dogs: cisplatin, bleomycin, actinomycin-D, mitoxantrone
In one study, intralesional carboplatin/sterile sesame oil in cats with SCC has a CR of ___% and 1-year PFD of ___%.
CR 73%
1-yr PFS 55%
Ref: 107
In a study, 2 dogs with metastatic SCC were treated with cisplatin chemotherapy. One of the dog had metastasis to the axillary LN and lungs; what type of response did this patient had and what was the PFI?
The other dog (metastatic sites not mentioned in Withrow) had whay type of response and what was the PFI?
First dog: PR consisting of a marked reduction in the number and size of the lung nodules as well as reduction in size of the axillary LB; PFI was 4.5 months.
Second dog: CR; PFI >22 months (died of tumor unrelated causes).
Ref: 108
The use of actinomycin-D in two dogs with SCC has been reported. One dog had ___ after 1 dose and the other dog had a ___ and receiveced a total of 6 doses.
(PD, SD, PR, CR)
SD, PR
Ref: 110
What is the overall response rate of mitoxantrone in dogs and cats with SCC?
Dogs: 44.4% (4/9 dogs)
Cats: 12.5% (4/32 cats)
Ref: 111, 112
When bleomycin chemotherapy is used in dogs and cats wtih SCC, how is the response? (short lived or long lived)
Short-lived
Red: 109
What tumors of the skin and SQ tissues are categorized as tumors with adnexal differentiation (7)? Which of these has only been reported in dogs and which ones have a malignant counterpart (2)?
Infundibular keratinizing acanthomas*
Tricholemmoma*
Trichoblastoma
Trichoepitheliomas
Malignant trichoepithelioma*
Pilomatricomas
Malignant pilomatricomas*
*Only in dogs
Malignant counterparts: malignant trichoepithelioma and malignant pilomatricoma
Where do tumors with adnexal differentiation arise from? Are these typically benign or malignant? Main treatment?
Majority arises from the hair follicle
Usually benign
Surgery
What other names are used for IKA?
Intracutaneous keratinizing epithelioma, keratoacanthoma, squamous papilloma
What dog breeds may be at increased risk for the development of infundibular keratinizing acanthomas (IKA)?
Nordic breeds; particularly Norweigan elkhounds
Belgian sheepdogs
Lhasa Apso
German shepherd dogs
Terriers
IKAs are benign common tumors in dogs. Although the peak incidence of IKAs is from ___ to ___ years of age, they can also occur in dogs younger than ___ years.
Peak: 4 to 9 years
<4 years
What are common locations for IKAs (6) and what is a special physical characteristic they may have?
Back, neck, sides of thorax, tail, shoulders, limbs
Central pore communicating with the surface
A dog can have multiple tumors
What happens when an IKA ruptures?
Rupture allows for keratinized tissue into the adjacent dermis and this creates a marked inflammatory response
Besides surgery, what other therapy could potentially be beneficial in dogs with IKAs?
Isotretinoin at a dose of 1.7-3.7 mg/kg/day
When isotretinoin therapy is used in dogs with IKA, what is the ORR, CR and PR?
ORR: 42.8% (3/7 dogs)
CR: 14.2% (1/7 dogs)
PR: 28.5% (2/7 dogs)
Ref: 115
What are tricholemommas? Describe their gross appearance.
What is the most common location?
Rare benign tumor of dogs
Gross appearance: well-encapsulated mass in dermis or SQ tissues
There may be hair loss in the overlying skin
Most common location: head
Trichoblastoma, which are common benign tumors in dogs and cats, is the new designation for which previous tumors in dogs and cats?
Dogs - basal cell tumor
Cats: Spindle cell variant basal cell tumor
What histologic characteristic is seen with trichoblastomas?
Differentiation to the hair germ of the developing follicle
What is the mean age of dogs and at trichoblastoma diagnosis?
Dogs 7 years
Cats 10 years
What dog breeds are at increased risk for the development of trichoblastomas (2)?
Poodles
Setters
In one large review of follicular tumors and tumor-like lesions presenting to a VTH, trichoblastomas comprised ___% of the samples in the 308 canine follicular lesions and ___% of the samples in the 50 follicular lesions from cats. They represented ___% and ___% of all canine and feline biopsies, respectively
25.6% of the canine follicular lesions submited; 2% of all skin biopsies
26% of the feline follicular lesions submited; 1.5% of all skin biopsies
What are the most common locations for trichoblastomas in dogs and cats?
Dogs: head,neck
Cats: Head, neck, limbs, trunk
What are the six subtypes of trichoblastomas and how do they behave?
Ribbon, medusoid, trabecular, spindle, granular cell, and clear cell
Benign behavior
What are trichoepitheliomas; are they common or uncommon? What are their main gross and histopathologic characteristics?
Benign uncommon dermal tumors that can originate in the dermis but can extend into the subcutis. Histopathologically, they demonstrate differentiation into all segments of the hair follicle.
Surface can be ulcerated or alopecic.
Present in dogs and cats.
In the previously mentioned large review of follicular tumors and tumor-like lesions presenting to a VTH, trichoepitheliomas comprised approximately ___% of all tumors.
4%
What dog (4) and cat (1) breeds are predisposed to the development of trichoepitheliomas? Which dog breeds (2) may present with multiple tumors?
Dogs: Basset hounds, coonhounds, English springer spaniels, setters
Cats: Persioan
Multiple tumors: Basset hounds and English springer spaniels
What are 3 ways malignant trichoepitheliomas can be differentiated from their benign counterpart? What is another name for malignant trichoepithelioma and from what tumor can it be difficult to differentiate it from?
(1) invasion into the surrounding tissues and lymphatic involvement, (2) much higher mitotic index, (3) high metastatic rate to LN and lungs
Matrical carcinoma
Difficult to differentiate from malignant pilomatricoma
Malignant trichoepithelioma or matrical carcinomas can be difficult to differentiate from which tumor?
Malignant pilomatrixoma (pilomatricoma)
What are pilomatricomas? Are they common or uncommon? What are alternative names for this type of tumor?
Benign uncommon follicular tumors of mainly dogs that demonstrate only matrical differentiation
Alternative names: necrotizing and calcifying epitheliomas of Malherbe, pilomatrixomas
Extremely rare in cats (only 1 case reported)
Pilomatricomas are uncommon tumors that represented ___% of the follicular lesions and ___% of all skin biopsies in the previously mentioned large study of follicular tumors and tumor-like lesions.
13% of the follicular lesions
1% of all skin biopsies
Extremely rare in cats (only 1 case reported)
Ref: 112
What is an alternative name for malignant pilomatrixoma?
Pilomatrix carcinoma
What dog breeds (7) are predisposed for the development of pilomatricomas?
Kerry blue terrier, soft-coated Wheaton terrier, Bouvier de Flandres, Standard poodle, Old English sheepdog, Bichon Frise, Airedale terrier
How are malignant pilomatricomas differentiated from their benign counterpart (3)?
(1) Invasion into underdlying tissues, particularly bone, (2)histologic characteristics, and (3) presence of metastasis.
What histologic characteristics are present in malignant pilomatricomas?
Trabeculae of basaloid cells, abrupt keratinization, “ghost” or “shadow” cells, etc.
Malignancy is generally distinguished histologically from benign processes by: lack of differentiation, atypical histologic structure, anaplasia, erratic or rapid growth, increased mitotic index, infiltrative growth, and—the definitive criterion—metastasis. The diagnosis of malignant pilomatricoma is best made when lymphatic invasion can be identified, usually at the periphery of the tumor.
What is the average age for diagnosis, gross appearance, and most common locations for pilomatricomas?
Average age 6.5 years
Gross appearance: well-circumscribed and very firm due to ossification
Neck, back, trunk
Although malignant pilomatricomas are thought to be rare, in a study of pilomatricomas diagnosed over a 2 year period, ___% were considered malignant based on histopathology. Out of cases reviewed, ___ had evidence of metastasis, with ___% having metastasis to the bones.
30.7% (4/13 dogs)
Evidence of metastasis: 91.6% (11/12)
Metastasis to bones: ~50%
Ref: 123
What are metastatic locations for malignant pilomatricomas?
Lungs, bone, lymph node, mammary gland, skin
A case report of the use of surgery, followed by radiation therapy to control a recurrent malignant pilomatricoma, prevented local recurrence until ___ months later, when diffuse pulmonary metastasis was noted.
14 months
Ref: 124
Mention the skin tumors of glandular origin (9)
Sebaceous adenoma
Sebaceous ductal adenoma
Sebaceous epithelioma
Sebaceous gland carcinoma
Apocrine gland adenoma and carcinoma
Solid cystic apocrine ductal adenoma
Eccecrine adenoma and carcinoma
Neuroendocrine carcinoma
Renal cystadenocarcinoma and nodular dermatofibrosis
Sebaceous hyperplasia, sebaceous adenoma, sebaceous ductal adenoma, and sebaceous epithelioma are very common in what spp and rare in what spp?
Common in dogs, rare in cats
The division between these tumors is arbitrary
A review of 172 tumors of sebaceous gland origin revealed a propensity of the ___ sex for ___. What 4 breeds were overrepresented?
Female, sebaceous hyperplasia
Miniature schnauzers, beagles, poodles, cocker spaniels
What dog breeds (3) may be predisposed to develop of benign sebaceous tumors?
Coonhounds, Nordic breeds, some terriers
Although benign sebaceous tumors can occur in young dogs, peak occurrence ranges from ___ to ___ years of age.
7 to 13 years
What are the 3 most common locations for benign sebaceous tumors?
Limbs, trunk, eyelids
Which of the following “benign” sebaceous tumors of glandular origin has been reported to recur locally, invade ajacent lymphatic vessels, spread to distant sites, and is therefore sometimes considered a low-grade malignancy?
a. Sebaceous hyperplasia
b. Sebaceous adenoma
c. Sebaceous ductal adenoma
d. Sebaceous epithelioma
Sebaceous epithelioma
May recurr locally and lymphatic metastasis has been reported anecdotally. Because lymphatic invasion may occasionally be noted at the margins of this tumor, they are sometimes considered a low-grade malignancy
Sebaceous epitheliomas have been reported to metastasize in 1 dog to which 2 places?
Lungs, CNS
Ref: 129
Although sebaceous gland carcinomas are uncommon in both dogs and cats, they are most frequently reported in spp with what signalment?
Intact male dogs
What is the most common location for sebaceous gland carcinomas?
What are common locations in dogs and cats?
Head
Dogs: head, neck
Cats: head, thorax, perineum
What breeds are at increased risk for developing sebaceous gland carcinomas?
Cavalier King Charles, Cocker spaniel, terrier breeds
Describe the biologic and metastatic behavior of cutaneous sebaceous gland carcinomas
Low grade malignancy, with reported metasasis beyond the lymph node reported in only one report
Widespread metastasis beyond the regional LN has been reported in one dog with cutaneous sebaceous gland carcinoma. What were the places of metastasis (3)?
Bone, skin, and lungs
What is the most common finding of malignancy in dogs/cats with sebaceous gland carcinoma?
Local infiltration
Apocrine gland adenomas are considered fairly common in ___, although uncommon in ___. Grossly, these tumors may be ___. Feline apocrine gland adenomas have a high predilection for the ___.
Common in dogs, uncommon in cats
May be fluid filed
Head
Apocrine ductal adenomas are ___ on palpation.
Firm
Solid-cystic apocrine ductal adenomas are benign tumors that were previously designated as ___.
BCT
Apocrine sweat gland tumors are relatively uncommon in ___ and represent ___% of all skin tumors. They are more common in ___ and represent ___% of all skin tumors.
Uncommon in dogs; 1.1% of all skin tumors
More common in cats; 3% of all skin tumors
Apocrine sweat gland carcinomas occur at a median age of ___ years in dogs and at ___ to ___ years in cats.
Median age in dogs 9 years
6 to 17 years in cats
What is the most common location for apocrine gland carcinoma in dogs and cats?
Dogs: front legs
Cats: head, limbs, abdomen
How do apocrine gland carcinomas typically look grossly? What is a less common presentation and a term commonly used for it?
Usually solitary and nodular
May present as erosive and inflammatory skin disease, also known as inflammatory carcinoma
What 2 dog breeds may be predisposed to develop apocrine gland carcinomas?
Golden retrievers, Treeing Walker coonhounds
In series of apocrine gland tumors of 44 dogs and 10 cats, ___ and ___ were considered malignant on histopathologic evaluation, respectively.
91% malignant in dogs
80% malignant in cats
Local invasion of apocrine gland carcinomas is common, with ___% invading the capsule and/or stroma, ___% invading the vasculature, and ___% invading lymphatics.
Capsular/stromal invasion - 66%
Vasculature invasion - 11%
Lymphatic invasion - 22.5%
Ref: 133, 134
What % of dogs with cutaneous apocrine gland carcinoma develop tumor recurrence and metastatic disease? What metastatic location has been reported?
local recurrence/continued growth - 4%
metastasis - 2%
lungs
What are eccrine adenomas and carcinomas?
Tumors of the sweat glands of the foot pads
Rare in dogs and cats
No reports on their clinical behavior
Neuroendocrine carcinomas are also known as _____.
Merkel cell carcinomas
What are Merkel cells?
Thought to be part of the mechanoreceptors in the skin
In humans, what virus has been associated with development of cutaneous neuroendocrine carcinoma or Merkel cell carcinoma?
Polyomavirus
As opposed to humans, cutaneous neuroendocrine carcinomas are associated with what type of clinical disease course in dogs and cats?
Highly malignant in humans, but a more benign clinical course seen in vet med
What are reported metastatic sites in dogs and cats with cutaneous neuroendocrine carcinoma?
Case report of cat with mets to lungs and case report of dog with multiple skin masses and widespread metastasis within adbomen
Ref: 138, 139
The use of which 3 chemotherapies haven been reported in a dog with multiple cutaneous neuroendocrine carcinomas? Broadly, what response was seen?
Carboplatin, doxorubicin, metronomic chemotherapy
Progressive disease
Histopathologic evaluation of canine cutaneous neuroendocrine carcinomas demonstrates expression of which 7 immunohistochemical markers?
B-catenin, E-cadherin, chromogranin A, neurone-specific enolase, S100, c-Kit
*two cases only
Ref: 141
In humans with neuroendocrine carcinoma, loss of expression of which 2 markers is associated with a more malignant disease behavior?
E-cadherin, B-catenin
What is the only established effective treatment in patients with neuroendocrine carcinoma?
Surgery
The syndrome of renal cystadenocarcinoma and nodular dermatofibrosis has been described in what 2 dog breeds?
German shepherds, Alsatians
Grossly, how are lesions from dogs with renal cystadenocarcinoma and nodular dermatofibrosis described?
Multiple firm, haired masses distributed over the body
Histopathologically, how are nodules from dogs with renal cystadenocarcinoma and nodular dermatofibrosis described?
Nodules of dense and irregular collagen
When is surgery indicated in dogs with renal cystadenocarcinoma and nodular dermatofibrosis?
Whenever the lesions cause a problem or disrupt normal function
From what do dogs with renal cystadenocarcinoma and nodular dermatofibrosis die of? On average, when do they die?
Renal failure or progressive renal cystadenocarcinoma
On average, 3 years after initial detection of the dermatofibrosis
Condition is lethal
A case of nodular dermatofibrosis without any evidence of renal cysts or adenocarcinoma was reported in what dog breed?
Australian cattle dog
May represent a nonlethal version of the syndrome
What are ceruminous glands?
Modified apocrine glands found in the external ear canal
What is the most common malignant tumor of the ear canal in both dogs and cats?
Ceruminous gland adenocarcinoma
In the largest publication of dogs and cats with tumors of the ear canal, out of 81 dogs, ___% and ___% of tumors were malignant and benign, respectively.
- 3% malignant
- 7% benign
Ref: 147
In the largest publication of dogs and cats with tumors of the ear canal, out of 64 cats, ___% and ___% of tumors were malignant and benign, respectively.
- 5% malignant
- 5% benign
Ref: 147
In the previously mentioned publication, what were the different types of benign tumors found in dogs in order from most common to least common.
Polyp - 8
Papilloma - 6
Sebaceous gland adenoma - 5
BCT - 5
Ceruminous gland adenoma - 4
Histiocytoma - 2
Plasmacytoma, melanoma, fibroma - 1 each
In the previously mentioned publication, what were the different types of benign tumors found in cats in order from most common to least common.
Polyps - 4
Ceruminous gland adenoma - 3
Papilloma - 1
In the previously mentioned publication, what were the different types of malignant tumors found in dogs in order from most common to least common.
Ceruminous gland adenocarcinoma - 23
Undifferentiated carcinoma - 9
Squamous cell carcinoma - 8
Round cell tumors - 3
Sarcoma - 2
Melanoma - 2
HSA - 2
In the previously mentioned publication, what were the different types of malignant tumors found in cats in order from most common to least common.
Ceruminous gland adenocarcinoma - 22
Squamous cell carcinoma - 20
Carcinoma of undetermined origin - 13
Sebaceous gland adenocarcinoma - 1
How are most tumors of the ear canal diagnosed?
Due to the mass effect, which may result in clinical signs such as chronic otitis or partial deafness
What are common gross characteristics of ceruminous gland adenomas ans cysts? What 2 dog breeds are predisposed for the development of these? At what age are these usually diagnosed?
Exophytic and pedunculated growth; can be ulcerated
Cocker spaniels and poodles
9 years
How do ceruminous gland cysts look in cats?
Darkly pigmented, sessile masses, that are usually smaller than 5mm in diameter and can be multiple
What 2 dog breeds are reported to be at increased risk for development of ceruminous gland adenocarcinoma of the ear canal?
Cocker spaniels, German Shepherds
When skull radiographs are performed in dogs and cats with malignant tumors of the ear canal, what % of dogs and cats have bulla bone lysis and sclerosis?
Dogs: 48% bulla lysis, 30% bulla sclerosis
Cats: 19% both bulla lysis and sclerosis
Ref: 147
What neurologic clinical signs can be seen in dogs and cats with malignant tumors of the ear canal?
Facial paralysis, head tilting, circling
In the largest study of ear canal tumors in dogs and cats, what characteristic was noted on malignant tumors, but was not present in benign?
Cartilage invasion
Ref: 147
What is the overall metastatic rate in dogs with malignant tumors of the ear canal at the time of diangosis?
10% (3 lungs, 1 scapular, 1 LN)
What % of dogs with malignant tumors of the ear canal have regional LN metastasis at the time of diagnosis?
3% (1/30 dogs)
Ref: 147
What overall % of dogs with malignant tumors of the ear canal have evidence of distant metastasis at the time of diagnosis? What are the reported distant metastatic sites?
11%
Lungs (3/35 dogs), bone/scapula (1/35 dogs)
Ref: 147
What is the overall metastatic rate in cats with malignant tumors of the ear canal at the time of diagnosis? Most common location?
9% (4 mandibular, 1 PS)
Ref: 147
What is the preferred surgical technique in px with tumors of the ear canal? Why?
TECA and lateral bulla osteotomy
Recurrance is less with this technique vs lateral ear canal ablation
What is the local recurrence rate in dogs with ear canal tumors that undergo TECA and BO vs lateral ear canal ablation?
TECA/BO: 0% at 36 months (7 dogs)
Lateral ear canal ablation: 75% at 4 months (4 dogs)
Ref: 151, 153
What is local the recurence rate and median DFI in cats with tumors of the ear canal that are treated with TECA/BO?
RR 25-27%, DFI 42 months (16 cats, 18 cats)
Ref: 151, 152, 153
What is local the recurence rate and median DFI in cats with tumors of the ear canal that are treated with lateral ear canal resection?
RR 67%, DFI 10 months
Ref: 151, 152
What is the reported MST in cats with malignant tumors of the ear canal undergoing a TECA/B?
50.3 months
Ref: 153
Treatment of 6 cats and 5 dogs with orthovoltage, 48Gy in 12 4Gy fractions, resulted in an estimated mean PFS of ___ months and a 1-year PFS of ___ months. In this study, how many px had previous surgery and what was the local recurrence rare, and what was the metastatic rate?
Mean PFS 39.5 months
1-year PFS 56%
6 had previous sx
36%
Ref: 150
In cats with tumors of the ear canal, a MI of ___ or less predicts improved survival.
MI of 2 or <
What negative prognostic factors have been identified in cats with malignant tumors of the ear canal (4)?
MI of 3 or >
Presence of neurologic clinical signs
SCC or cancer of unknown origin
Extension beyond the ear canal
What negative prognostic factors have been identified in dogs with malignant tumors of the ear canal (1)?
Extension beyond the ear canal
What is the MST in cats with malignant tumors of the ear canals with a MI of 2 or < versus 3 or >?
2 or < MST 180 months
3 or > MST 12 months
What is the MST in cats with malignant tumors of the ear canals that have presence of neurologic clinical signs vs those that dont?
w/clinical signs 1.5 months
w/o 15.5
What is the MST in cats with ear canal ceruminous gland adenocarcinoma vs SCC vs of unknown origin?
Adenocarcinoma 49 months
SCC 3.8 months
Of unknown origin 5.7 months
What is the MST of cats with ear tumors that extend beyond the ear canal vs those that dont?
Extension MST 4 months
No extension MST 21.7 months
What is the MST of dogs with malignant tumors of the ear canal that extend beyond the canal vs of those that dont?
Extension 5.9 months
No extension 30 months
Describe the staging system for primary tumors of the ear canal
T1 - tumor confinded to the external or horizontal ear canal
T2 - tumor extendinf beyond the tympanic membrane
T3 - tumor extending beyond the middle ear or presence of bone destruction
What are the most common clinical signs in dogs with digital tumors (2)?
Presence of a mass
Lameness
What is the median age of dogs diagnosed with cutaneous digital tumors?
10 years
What are the 3 most common cutaneous digital tumors in dogs?
1 Squamous cell carcinoma
In a large retrospective study of 362 dogs with digital tumors, ___% were SCC, ___% were melanoma, ___% were STS, and ___ were OSA.
Approximately ___% of dogs with digital SCC demonstrated involvement of multiple digits.
- 2% SCC; 3% demonstrate multiple digit involvement
- 8% melanoma
- 3% soft tissue sarcoma
- 3% osteosarcoma
Other tumors present: round cell sarcoma, adenocarcinoma, malignant adnexal tumors, HSA, plasmacytoma
Ref: 156-158
What is the most common signalment in dogs with digital cutaneous SCC in which multiple digits are affected?
Large breed dogs with black skin
What canine breeds are predisposed to developing digital cutaneous SCC (7)?
Standard poodles, black Labradors, giant Schnauzers, Gordon setters, Rottweilers, Dachshunds, flat coated retriever
But especially, LARGE BLACK DOGS
In a series of 60 cats with digital tumors, what were the 3 most commonly diagnosed and what % did they represent? What % did OSA and HSA represent?
1 SCC - 25%
Ref: 160
Cats with what 3 types of digital tumors can have multiple digits affected? Which type of tumor causes this most commonly?
adenocarcinoma (30%), fibrosarcoma (14%)
reports of SCC
In cats with digital tumors, there may be predilection for tumor development where?
Front feet
Diagnosis of digital masses seems to be difficult based on a report that demonstrated an approximate ___% disagreement rate, with ___% of the changes in diagnosis being clinically significant.
20% disagreement rate in the diagnosis
75% clinically important
Ref: 163
In dogs with digital SCC, the overall reported 1-year survival rate ranges from ___% to ___% and the 2-year survival ranges from ___% to ___%.
1-year survival rate 50 to 83%
2-year survival rate 18-62%
Ref: 156-158
In dogs with digital SCC, what location has been associated with a more favorable prognosis?
When comparing the survival rates in dogs with digital SCC based on location, what are the 1- and 2-year survival rates for dogs with SCC in this location vs other digital sites?
Subungual epithelium
1-year SR 95%, 2-year SR 74%
Other locations: 1-year SR 60%, 2-year SR 40%
Ref: 156
In dogs with digital SCC, ___% have evidence of metastasis at diagnosis and an additional ___% develop metastasis.
What % of dogs with digital SCC have evidence of bone lysis on radiographs?
Mets at presentation 8.8%
Development of mets later on 23%
Bone lysis 80%
Ref: 155-158
In dogs with digital melanoma, ___% have evidence of metastasis at diagnosis and an additional ___% develop metastasis.
Evidence of bone invasion is present on ___% of radiographs and ___% of histopathologic samples.
Mets at diagnosis 28%
Development of mets later on 39%
Bone lysis 21% on radiographs and 100% on histopathology
Ref: 155-158
In dogs with digital melanoma, the overall reported 1-year survival rate ranges from ___% to ___% and the 2-year survival ranges from ___% to ___%.
1-year survival rate 42 to 57%
2-year survival rate 13-36%
Ref: 156-158, 164
In a series of 64 cats with digital carcinoma, what % of the lesions represented metastasis from primary lung tumors?
What is the MST for cats with lung-digit syndrome vs the MST for those with primary digital carcinomas (days to weeks)?
88% represented metastasis; only 13% were primary digital tumors
digit-lung syndrome MST: 5 weeks
primary digital SCC MST: 73 days to30 weeks
Ref: 160, 161
In cats with digital SCC, ___% had metastasis to the draining lymph node and ___% had evidence of bone lysis on radiographs.
12.5% had mets (1/8 cats; only 3/8 had chest rads and no mets found)
75% bone lysis
Ref: 161
Small study of 8 cats; not all fully staged
What is the reported MST for cats with digital SCC (days to weeks)?
MST 73 days to 30 weeks
Ref: 160, 161
Of the 5 reported cases of cats with digital melanoma, ___% had metastatic disease. What were the 4 locations for metastasis?
The MST ranged from ___ to ___+ days.
80% had mets
Regional LN, lungs, bone, vertebrae
MST: ranged from 0 to 557+ days
Ref: 162
What is the only treatment that has been shown to be effective for digital tumors?
Surgery; either toe amputation and if large, leg amputation
The use of a xenogenic (murine) tyrosinase vaccine was evaluated in 58 dogs with digital melanoma. Prior to the vaccine 57 dogs had surgical excision of the tumor, 3 received adjuvant chemotherapy, and 2 received RT. Approximately 28% of had regional or distant metastasis on presentation. What was the overall MST from the time of amputation and what were the 1-and 2-year survival rates?
Overal MST 476 days
1-yr SR 63% and 2-yr SR 32%
Dogs with distant mets had a significantly worse prognosis when compared to regional LN
Ref: 165
What negative prognostic factor has been identified in dogs with digital melanoma?
Presence of distant metastasis
Ref: 165
Just this study found a negative prognostic indicator; others have not
Overall, what factor has been associated with a more favorable outcome in dogs with digital tumors?
Surgical excision
Ref: 157
