Chapter 20 - tumours Flashcards
Name three of the seven dog breeds with the highest reported incidence of cutaneous neoplasia (in USA)?
Boxers Scotties Bullmastiffs Bassets Weimeraners Kerry Blues Norweigan Elkhounds
What type of virus is a papillomavirus?
a) DNA or RNA
b) enveloped or non-enveloped
Non-enveloped DNA virus
What type of inclusion bodies do you see with papillomaviruses?
Basophilic intranuclear inclusion bodies (and grey intracytoplasmic inclusion bodies in cats)
Live autologous papillomavirus vaccines have been associated with which adverse effect?
Injection site squamous cell carcinoma
Which breeds are predisposed to keratinisng acanthoma?
Norweigan Elkhound Keeshond GSDs Old English Sheepdogs Collies Lhasa Apso Yorkies
What are the two clinical variants of squamous cell carcinoma?
Proliferative (papillary) and ulcerative
Which canine signalment is most associated with subungal squamous cell carcinoma?
Large breeds with black coats
Which immunohistochemistry stain can be used to help identify poorly differentiated squamous cell carcinomas?
Cytokeratin (AE1, AE3, CK5, CK6)
p63 protein
In dogs, which body site is associated with a higher rate of metastasis of squamous cell carcinomas?
The digit
Multicentric squamous cell carcinoma in situ lesions develop in which type of skin?
Haired, darkly pigmented skin
Which topical therapy has been reported to successfully treat mutlicentric squamous cell carcinoma in situ?
Imiquimod
Which virus might be associated with multicentric squamous cell carcinoma in situ?
Papillomavirus
What are the three major histopathological variants of multicentric squamous cell carcinoma in situ?
Solid - most common in cats
Keratinising (basosquamous) - most common in dogs
Clear cell
Trichoepitheliomas arise from keratinocytes that differentiate toward which segments of the hair follicle?
Germinal cells that differentiate to all three layers of the hair follicle
Tricholemmomas arise from which part of the hair follicle?
Outer root sheath
What are the four basic histopathological subtypes of trichoblastomas?
Ribbon - most common in dogs
Trabecular - most common in cats
Granular
Clear cell
Rank the below in order of commonality: Nodular sebaceous hyperplasia Sebaceous epithelioma Sebaceous adenoma Sebaceous adenocarcinoma
Nodular sebaceous hyperplasia - 53%
Sebaceous epithelioma - 37%
Sebaceous adenoma - 8%
Sebaceous adenocarcinoma - 2%
Which drug therapy has been reported to treat sebaceous hyperplasia in dogs?
Oral retinoids
Which type of sweat gland tumour can be found on the footpads?
Atrichial (eccrine)
Metastasis occur in what percentage of circumanal gland carcinomas? 5% 30% 45% 65%
30%
Which paraneoplastic syndrome can be seen with anal gland carcinomas?
Hypercalcaemia
What percentage of salivary gland tumours are malignant? 12% 37% 61% 85%
85%
Which condition is associated with fibropruritic nodules?
Canine flea bite hypersensitivity
Which histopathological finding correlates positively with prognosis for fibrosarcomas?
Mitotic index correlates positively with prognosis
Which anatomical site is more commonly involved in nodular fasciitis?
Eye, periocular and face
Schwannomas stain positively with which immunohistochemical stain?
S-100 protein
Vimentin
Which type of haemangiosarcomas can be multiple in number? subcutaneous or solar-induced?
Solar-induced
Which histopathology stain can help differentiate muscle, collagen and neural origin tumours?
Masson trichrome
Name three risk factors for vaccine induced sarcoma
Repeated site of vaccination
Rabies or FeLV vaccines
Adjuvated vaccines
What is a darier sign?
Palpation of a tumour causing release of vasoactive substances leading to local oedema and inflammation
Which breed of cat is predisposed to mast cell tumours?
Siamese
In UK also Ragdoll, Russian Blue and Burmese
Canine mast cell tumours stain positive for which enzyme?
Serine protease tryptase
Which common histopathological finding in canine mast cell tumours is rarely seen in cats?
Tissue eosinophilia and collagen degeneration
What is Sezary syndrome?
Epitheliotropic lymphoma with leukaemia
What are the adverse effects of lomustine?
Neutropaenia, thrombocytopaenia (myelosuppression)
Hepatotoxicity
Which histiocytic cell is involved in cutaneous histiocytoma?
Langerhans cell
Which breed of dog is predisposed to multiple cutaneous histiocytomas with regional lymph node involvement?
Shar-Peis
On histopathology, is the mitotic index of histiocytomas low or high?
High
Which of the below do histiocytomas express?
E-cadherin
Thy-1
CD4
E-cadherin
Which breeds, other than Bernese Mountain Dogs, are reportedly predisposed to systemic histiocytosis?
Rottweilers Irish Wolfhounds Golden Retrievers Labradors Flat coat Miniature schnauzers Corgi
Which systemic treatments are reported to provide long-term control of systemic histiocytosis?
Azathioprine
Ciclosporin
Leflunomide
Approximately what percentage of localised histiocytic sarcomas metastasize?
91%
Which two cell types do melonocytic neoplasms arise from?
Melanocytes and melanblasts
What percentage of melonocytic neoplasms are metastatic?
~10%
Which single agent chemotherapy treatment can be successful in 90-95% of dogs with transmissible venereal tumour?
Vincristine
Which cell shows dual epithelial and neural differentiation?
Merkel cell
What is the most commonly reported secondary skin tumour?
Bronchogenic or squamous cell carcinomas of the lungs in cats
Multiple epitrichial cysts occur in Persian and Himalayan cats at which body site?
Eyelids
What is another name for a nevus?
Harmatoma
Nodular dermatofibrosis in GSDs is associated with which diseases?
Polycystic kidneys
Renal cystadenoma/carcinoma
Bilateral renal disease
Leiomyomas
Cutaneous horn can be associated with which viral infection?
FeLV
Metastatic calcinosis cutis is associated with which disease?
Chronic renal disease (can be seen on the footpads)
How long does calcinosis cutis take to regress once hypercortisolism is corrected?
2-12 months
At which body site is calcinosis circumscripta most commonly seen?
Pressure points, bony prominences, tongue and over the 4-6th cervical vertabrae
Which histopathology stains can be used to identify mucin?
Alcian Blue
Colloidal Iron
In the 2021 paper by Azuma et al., what were considered to be prognostic factors for cutaneous lymphoma in dogs?
Overall survival time in dogs diagnosed with epitheliotropic CTCL was significantly shorter than that in dogs diagnosed with nonepitheliotropic CTCL.
Several clinical variables (presence of neoplastic lymphocytes in peripheral blood, thrombocytopenia and initial chemotherapeutic response) and CD20 expression in conjunction with CD3 expression were associated with poor prognosis of canine CTCL.
Is cutaneous lymphocytosis in dogs and cats pruritic?
It is typically pruritic in cats but not in dogs
How does canine cutaneous lymphocytosis differ from ETCL histopathologically in dogs?
In cutaneous lymphocytosis the infiltrate is within the superficial dermis and is separated from the epidermis by a grenz zone (although mild epitheliotropism has been reported)
In canine ETCL, T cells most often carry which receptor, alpha-beta or gamma-delta?
Gamma-delta
80-90% of canine ETCL patients express which CD marker?
CD8 +
True or false:
neoplastic cells in canine CTCL possess both types of retinoid receptors (RAR, RXR), indicating that these may be potential targets for improved therapies
True
What is rabacfosadine/VCD-1101?
An acyclic nucleoside phosphonate
Rabacfosadine is a propro-drug of [9-(2-phosphonylmethoxyethyl)guanine] (PMEG).
It is phosphorylated twice to its active metabolite PMEGpp.
What is the cytotoxic action of PMEGpp (the active metabolite of rabacfosadine)?
This active metabolite has cytotoxic activity by acting on and inhibiting DNA polymerases and by incorporating PMEG into DNA
Has Sezary syndrome been reported in cats?
Yes
Is ETCL in cats associated with FeLV?
No - cats diagnosed with cutaneous epitheliotropic lymphoma are rarely positive for feline leukaemia virus infection
Mast cell granules contain which interleukin that induces eosinophil migration?
IL-5
Which other cells can be commonly seen on aspirates of MCTs?
Eosinophils
Fibroblasts
Which cytological feature is reported to be most predictive of biological behaviour of MCT?
Granularity - poorly granular MCTs have a greater tendency to metastasize
FNA is diagnostic in what % of MCTs?
~95% but not reliable for differentiating high/low grade (up to 1/3rd falsely identified as high grade on cytology)
Using the two tier histological (Kiupel) grading system, what are the median survival times for low and high grade canine cutaneous MCTs?
Low grade > 2 years
High grade < 4 months
What are the features of high grade MCTs using the Kiupel histopathological grading?
One of:
At least 7 mitotic figures in 10 HPFs
At least 3 bizarre nuclei in 10 HPFs
Karyomegaly (at least 10% of neoplastic cells)
At least 3 multinucleate giant cells with 3 or more nuclei in 10 HPFs
What are argyrophilic nucleolus organizer regions (AgNORs) and what are their prognostic value?
A commonly used marker of proliferation rate
Visualised using silver stains
Large numbers and small size of AgNORs correlate with an increased speed of cell cycle progression
>4 AgNORs per nucleus is associated with poor survival
What is Ki67 and what is its prognostic value?
A nuclear protein that labels all cycling cells but cannot be detected in resting cells
A marker of growth fraction
A high Ki67 index has been associated with shorter survival times and a high risk of metastatic disease
What is KIT and what is its prognostic value?
- KIT (tyrosine kinase receptor) - mutations cause activation of the KIT receptor in the absence of its ligand (SCF)
- Associated with decreased survival time and increased incidence of local recurrence
- Mutations at axon 11 predict aggressive behaviour
- Mutations at axon 8 are not associated with aggressive behaviour
What is considered the most reliable prognostic indicator for MCTs in dogs?
- Histological grading (usually combination of Kiupel (2 tier) and Patnaik (3 tier))
- Plus mitotic count
Up to 15% of low grade MCTs can be metastatic (often to local LNs) – don’t forget staging!
Which KIT expression patterns are associated with decreased survival and increased local recurrence of MCTs?
Type 2 pattern: focal perinuclear or stippled cytoplasmic labelling and loss of peri-membranous labelling in >10% of neoplastic cells
Type 3 pattern: diffuse cytoplasmic labelling in >10% of neoplastic cells
Type 1 pattern: perimembranous is not associated with decreased survival!
Which breeds of dog are predisposed to MCTs?
Boxer, golden retriever, Labrador, Staffordshire bull terrier, Weimaraner, Pug, Frenchie, Shar-pei, Dachshund
Which breed of dog is prone to MCTs with less aggressive behaviour?
Pug (and boxer)
Which breeds of dog tend to develop more aggressive MCTS?
Shar-pei, American SBT, BMD, cocker spaniel, dachshund, Maltese, poodle, Rottweiler, Shih-Tzu
In dogs, which body sites are MCTs most often found at?
50% on trunk, perineum and inguino-genital regions,
40% limbs
10% head and neck
What other clinical signs/paraneoplastic syndromes can be seen with MCTs?
Darier’s sign (effects of degranulation during physical examination)
Delayed wound healing
Coagulation abnormalities
Hypotension and circulatory collapse
GI ulceration (histamine stimulating H2 receptor)
Hypereosinophilia
Are subcutaneous MCTs associated with a better or worse prognosis than cutaneous MCTs?
Considered to have a better prognosis
Tigilanol tiglate (Stelfonta) is indicated for what?
Canine cutaneous MCTs in any location
Subcutaneous MCT on limbs below the elbow and hock
Without regional LN involvement
>1cm in size and no more than 10cm3 in volume
Without ulceration (so drug does not escape!)
How does tigilanol tiglate (Stelfonta) work?
Causes vascular rupture and acute local inflammatory response within 4 h, followed by necrosis within 1–4 days and tumor destruction for a period of 4–7 days, with subsequent resolution of the wound within a period varying from28 to 35 days
Do all incompletely excised canine cMCTs require adjunctive therapy e.g. radiotherapy?
No – recurrence in low grade tumours with incomplete margins is low (12-23%)
Which agents are the first-line chemotherapeutic therapy for canine cutaneous MCTs?
Vinblastine (+ prednisolone)
Lomustine (CCNU)
What type of drug are toceranib (Palladia) and masitinib (Masivet)?
Tyrosine kinase inhibitors
Can be used even if KIT mutations not demonstrated as presence of KIT mutation may not be predictive of treatment response
In cats, which body sites are commonly affected by cMCTs?
What % of skin tumours are MCTs?
Head and trunk
20%
What is the treatment of choice for cutaneous MCTs in dogs and cats?
Surgical excision
Incomplete excision of the tumor does not seem to be associated with tumour recurrence in cats, nor to decrease survival time. Thus, the surgical safety margins in cats are not as crucial as in dogs, because feline cMCTs tend to behave benignly.
In amelanotic melanocytic tumours, which IHC stains can be performed?
Melan-A, PNL2, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) were highly sensitive and 100% specific for the diagnosis of canine oral amelanotic melanocytic neoplasms.
S-100 and vimentin (not specific)
Melanocytic tumours at which sites are associated with a poorer prognosis?
Tumours located at the nail bed, lips, oral cavity, nasal mucosa and nasal planum are associated with a poorer prognosis - more often malignant than cutaneous tumours.
They should be considered high grade if they show intratumoral necrosis or have at least four mitoses per 10 high-power fields.
What is a reported predisposing factor for melanocytic tumours on the nasal planum of cats? Reck and Kessler (2021).
Pigmentation of the nasal planum
Which IHC stain is most specific for canine cutaneous histiocytic tumours?
The expression of Iba1 is specific for canine cutaneous histiocytic tumours, and more sensitive than CD18.
ionized calcium-binding adapter molecule 1 (Iba1)
The diagnosis of cutaneous lymphoma is based on the immunoexpression of either CD3, CD20 or CD79a. Which cells are CD3 , CD20 and which are CD79a +?
CD3 - T cells
CD20 and CD79a - B cells
CETL T cells can co-express CD3 and CD20!
Which IHC stain can be used to identify mast cells?
Mast cell tryptase
Why is it important to submit intact, junctional epithelium with melanocytic tumours?
Histologically, junctional activity may be the strongest diagnostic criterion for amelanotic melanocytic neoplasms, making it essential to submit intact epithelium overlying the neoplasm. Lentiginous spread may be observed in the adjacent intact epithelium.
What are the histopathological prognostic indicators for melanocytic tumours?
Nuclear atypia, mitotic count, degree of pigmentation (more = better), level of infiltration and vascular invasion.
Ki67 index provides the most accurate prognostic assessment.
Can melanocytes/melanophages be found in normal canine lymph nodes?
Even normal lymph nodes may contain melanocytes, melanophages, or pigment granules, especially mandibular nodes from dogs with highly pigmented oral epithelium. The best way to distinguish between melanocytes and macrophages is to perform IHC for a melanocyte marker such as Melan-A or PNL-2.
What is the suspected mechanism through which UV-light contributes to the development of SCC?
- Overexpression of p53 as a result of UV-induced mutations of the p53 tumor suppressor gene
- p53- the guardian of the genome, tumor suppressor, essential for apoptosis
- Mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions that endow cells with growth and survival advantages
Which aetiologies (other than UV light) have been associated with SCC development in the dog?
Papillomavirus
Burn scar
Chronic inflammation or infection (eg. OE, DLE)
Multiple follicular cysts
Name the histologic variants of SCC
Well-differentiated SCC Poorly-differentiated SCC Acantholytic SCC Spindle-cell SCC Verrucous SCC
In which veterinary species has the rare verrucous form of SCC been reported?
Dog
Which breeds of dog are predisposed to subungual/digital SCC?
Large, dark-haired breeds e.g. poodle, black Labrador retriever, giant(+ standard) Schnauzers, Rottweilers, Beauceron, Briards.
Which growth factors may contribute to the increased aggressiveness of subungual SCCs compared to other cutaneous SCCs?
TGF-β1 (Transforming growth factor-β1)
- Immunolabeling was elevated significantly compared to healthy controls in SCC originating from nailbeds, while expression of other growth factors did not change significantly
- Increased TGF-β levels are associated with poor prognosis in many types of cancers owing to increased tumor invasion due to paracrine effects of TGF-β1 on tumor stroma, inducing angiogenesis or causing immunosuppression
Metastases occur in what % of canine dermal SCC at the time of presentation and to what sites?
14.6%
Draining lymph node and lung
How are actinic changes on histopathology correlated to outcome in dermal SCC and how common are they?
Dogs with actinic changes on histopathology had a significantly longer survival time (median 1359 Vs 680 days)
38.9% of cases
What are the treatment options for SCC in dogs?
Surgical excision (choice)
Radiation
Cryosurgery
Electrochemotherapy
Has SCC in the base of cutaneous horn in guinea pigs been reported?
Yes
Have papillomaviruses been associated with SCC in snakes?
Yes
At which body sites have spindle-cell SCC been reported in cats and are they associated with papillomavirus?
Face (pinnae > periorbital > dorsal muzzle)
No
Spindle-cell SCC at which body site in cats are more likely to be aggressive?
Periorbital
Which types of feline papilloma viruses have been associated with BISC?
FcaPV-2, 3 and 5
Which types of feline papilloma viruses have been associated with cutaneous SCC?
FcaPV-2, 4 and 6
Have feline papilloma viruses have been associated with oral SCC?
No
Which protein can be identified in SCC caused by FcaPV?
Cytoplasmic immunostaining against p16CDKN2A protein (p16)
What are the oncogenes in feline papilloma virus?
E6 and E7
Which atypical presentations of SCC have been reported in cats?
SCC of the anal sac (Kopke et al.2020)
Follicular isthmus cysts (Layne and Graham 2016)
What are the treatment options for SCC in cats?
Surgical excision
Cryosurgery
Radiotherapy (orthovoltage radiotherapy, Strontium-90 plesiotherapy)
Chemotherapy (intratumoral carboplatin in sesame oil, iv mitoxantrone, toceranib very few cases)
Electrochemotherapy with bleomycin
Imiquimod cream
Photodynamic therapy
What are the four most common cutaneous neoplasms in the cat?
Basal cell tumours, fibrosacomas, SCC and MCTs
Are pedigree or non-pedigree cats more likely to develop skin tumours?
Non-pedigree cats, some pedigrees have a lower odds ratio e.g. Persian, Siamese, Burmese, Ragdoll, British Blue, Birman and Norwegian Forest
Which type of dermal fibroma in the dog contains hyalinized collagen fibres?
Keloid type of dermal fibroma
Feline injection-site sarcoma (FISS) is an aggressive tumor believed to arise from the proliferation of fibroblasts and ____________ in areas of chronic inflammation, particularly at sites of injection.
Myofibroblasts
Gelatinases (___ and ___) and their inhibitor (TIMP-2) are endopeptidases pivotal in extracellular matrix remodelling and therefore in tumor invasiveness in feline injection site sarcomas.
MMP-2 and MMP-9
What are the useful prognostic markers for feline injection site sarcomas?
Size of the tumor, measured after formalin fixation, with an optimal cutoff of 3.75 cm (accuracy¼86%;P< .05), and the mitotic count, with an optimal cutoff of 20 mitoses/10 HPF (accuracy¼80%;P< .05).
FISS/feline vaccine-associated sarcomas are charactersied by high mitotic rates, central ____________ and intense infiltration by lymphocytes, macrophages and multinucleated giant cells
Areas of necrosis
Foreign material engulfed within the cytoplasm of these macrophages and giant cells and in the necrotic centers has been identified as what?
Aluminium
Apart from sarcomas, what other histopathological variants of FISS have been reported?
Rhabdo-myosarcoma, myxosarcoma, chondrosarcoma, osteosarcoma,and histiocytic sarcoma
What is another name for feline sarcoid?
Cutaneous fibropapilloma
In the study by Wood et al. (2020), the majority of feline sarcoids occurred at which body site?
The face, in particular the rostral locations e.g. lips and nasal planum
In the study by Wood et al. (2020), what were the 1 and 2 year local recurrence rates following complete and incomplete excision of feline sarcoids?
Complete: 0% and 7%
Incomplete: 67% at both intervals
What are the most common cutaneous neoplasms in gerbils?
- Sebaceous gland adenoma of the ventral scent gland
- SCC of the ventral scent gland, feet and pinnae
- Basal cell carcinomas of the ventral scent gland
- Melanoma and melanocytoma of the paw and pinnae
What are the most common cutaneous neoplasms in guinea pigs and where to they occur?
Trichofolliculomas (benign, usually solitary nodular lesions with a central pore through which keratinous or haemorrhagic material discharges)
Dorsum
What are the most common types of cutaneous neoplasia in the ferret?
Sebaceous epitheliomas (58% of 57 tumours in Parker and Picut 1993) MCTs (16% in Parker and Picut 1993)
What are the most common cutaneous neoplasms in hamsters?
Melanomas (melanotic and amelanotic) and melanocytomas
What are the most common types of cutaneous neoplasia in caged birds?
Fibrosarcoma (head and wing tips), lymphosarcoma (head) and SCC
Are virally caused tumours in fish seasonal?
Yes, water temperature can affect viral replication and immune response
Cases and/or viral load can be highest spring
What type of neoplasia do retroviruses cause in fish?
Dermal sarcomas, epidermal hyperplasia, leukaemia, lymphosarcoma, papillomatosis, fibroma/fibrosarcoma, neurofibromatosis
Which breeds of dog are predisposed to CTCL?
English cockers
Boxers
Golden retrievers
Cutaneous lymphoma in accounts for what % of canine lymphoma cases?
5% (3-8%)
What are the three subtypes of canine CTCL?
Mycosis fungoides
Pagetoid reticulosis
Sezary syndrome
Canine non-epitheliotropic lymphoma has been subclassified into which three types?
Anaplastic large T-cell lymphoma (ALTCL)
Subcutaneous panniculitis-like T-cell lymphoma
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)
Canine CTCL is characterised by a proliferation of which T cells? How does this differ from people?
CD3 +
CD8 +
In people it is mostly CD4 +
CD4+ CETL lymphoma has rarely been reported in dogs
Which has a longer survival time in dogs, epitheliotropoic or non-epitheliotropic CTCL?
Non-epitheliotropic CTCL (374 days vs 141 for epitheliotropic)
____ expression in conjunction with CD3 expression in canine CTCL was associated with a poor prognosis
CD20
What are the treatment options for feline epitheliotropic lymphoma?
Lomustine Surgery Electron-beam irradiation Vincristine and cyclophosphamide Either intravenous or intralesional injections of fibronectin
What are the treatment options for canine epitheliotropic lymphoma?
- Lomustine (CCNU - overall response rate 78-83%),
- Masitinib
- Polyethylene glycol (PEG)ylatedL-asparaginase,
- PEGylated liposomal doxorubicin
- Prednisolone
- Oclacitinib (case report)
- Isotretinoin (1-3 mg/kg/d, response may take 60 days, ORR 58%, CR 33%)
- Radiotherapy of localised disease (overall response rate 67%)
- Surgery for solitary lesions
- lokivetmab for pruritus only
Lomustine and pegylated liposomal doxorubicin appear to yield the highest rate of complete remission in approximately one-third of dogs
Which treatment option for epitheliotropic lymphoma in dogs is associated with the longest survival time?
- With retinoids (isotretinoin and/or etretinate), the median survival time was 11 months
- With PEG L- asparaginase, the median survival time was 9 months
- With lomustine protocols, the median survival time was 6 months
- With prednisolone, the median survival time was 4 months
Sézary cells or ‘Lutzner cells’ are abnormal, small lymphocytes (8–20 μm) characterized by a hyperchromatic convoluted nucleus with a _________ appearance
cerebriform
Histiocytoma is the most common skin mass diagnosed in dogs under 12 months of age, what is the second most common?
Papilloma
In dogs chronically treated for cAD, which malignant neoplasia was most common?
MCT (3.4-3.8% dogs)
In dogs chronically treated for cAD, which benign neoplasias were most common?
Lipoma
Sebaceous hyperplasia or adenoma
Histiocytoma
Canine cutaneous lymphoma represents what % of canine skin tumours?
1%
What are the clinical signs of cutaneous lymphocytosis in dogs and cats?
Alopecia, erythema, and scales
+/- ulcers, crusts, macules and plaques
What is cutaneous plasmacytosis?
A form of multiple cutaneous plasmacytoma that appears as red-brown plaques or raised cutaneous lesions
Chan et al. (2018); which type of CETL lesions were associated with a worse prognosis?
A shorter median survival time was associated with the cutaneous form and the presence of multiple lesions
Chan et al. (2018); in dogs with multiple cutaneous lesions of CETL, which factors were associated with a longer survival time?
- Chemotherapy
- Retinoid treatment
- Achieving complete remission
What is PAX-5 a marker for?
B cells
What is the difference between pagetoid reticulosis and mycosis fungoides in CETL?
PR = limited to epidermis and adnexa MF = includes dermal infiltrates forming patches, plaques, and tumors
Which cytokines are increased in CETL?
mRNA transcription levels of type-1 cytokines such as IL-12p35, IL-12p40, IFN-gamma and LT-alpha in lesional skin were significantly higher than those in normal skin
- cytotoxic markers including perforin and granzyme B were also increased
Is a grenz zone typically present in plasma cell tumours?
Yes
Are multinucleated cells seen in plasma cell tumours?
Yes - binucleate and multinucleate neoplastic cells are observed commonly throughout the neoplasm
CD117 can be used to identify which round cell tumour?
MCT
What cytological findings other than poor granularity are signs of high grade MCTs?
At least 2 of the below:
- mitotic figures
- nuclear pleomorphism
- 2 more nuclei
- > 50% anisokaryosis
What type of mutations are associated with MCTs?
- Internal tandem duplication of exons 8 or 11
- Point mutations in exons 8, 9, 11, and 17
Sebaceous epitheliomas arise from which cells?
Sebaceous basal cells
Are there reports of metastases with sebaceous epithelioma?
Yes, rarely
Which epithelial tumour can have spindle like ‘tadpole’ cells on cytology?
Poorly differentiated SCC
This type of keratin on cytology comes from which part of the hair follicle?
Infundibulum
If you only see lamellar keratin on cytology, which type of follicular mass is most likely?
Infundibular cyst
If you see lamellar keratin AND clusters of nucleated basaloid and squamous epithelial cells, which follicular mass is most likely?
IKA
If you see amorphous keratin on cytology of a follicular mass, what is most likely?
Isthmic cyst
What do you see on cytology of trichoepithelioma?
Lamellar and amorphous keratin, keratin ghost cells (from inferior portion) and basal keratinocytes
If you see matrical (ghost cell) keratin and basal cell clusters on cytology, which follicular mass is most likely?
Pilomatrixoma
What % of skin tumours in dogs are MCTs?
11%
What type of mutations are associated with MCTs?
- Internal tandem duplication of exons 8 or 11
- point mutations in exons 8, 9, 11, and 17
What is BAX and is it a prognostic indicator for canine cMCTs?
- An apoptotic pathway effector
- High BAX expression is associated with poor prognosis
Is the prognosis for MCTs in dogs <12 months of age better or worse than in adult dogs?
Better, even without extensive treatment
What do Merkel cells do?
Neuro-transmitters or neuromodulators are secreted from Merkel cells through exocytosis in response to mechanical stimuli to the skin = mechanoreceptor
What are the markers for Merkel cells?
Cytokeratin 20, cytokeratin 18, p63, neuron-specific enolase, and synaptophysin
What are the arrows pointing at?
Merkel cells - often vacuolated and protrude into the dermis
Dermal dendritic cells are also known as what?
Interstitial DCs
Do Langerhans or dermal dendritic cells express E-cadherin and CD90?
Langerhans = E-cadherin
Dermal DCs = CD90
What is the presentation of feline progressive histiocytosis?
Feline progressive histiocytosis is essentially a low-grade histiocytic sarcoma with indolent behavior initially:
- begins as cutaneous nodules and plaques
- firm, nonpruritic, and nonpainful
- surface is often alopecic and may be ulcerated
- mostly located on the head, lower extremities, or trunk
In canine histiocytoma regression, which type of lymphocyte infiltrates, CD4+ or CD8+?
CD8+
What type of histiocytic disease is in the image (dog)?
Cutaneous Langerhans cell histiocytosis - may have literally hundreds of cutaneous lesions ranging from nodules to masses, which elevate the epidermis and may be accompanied by redness, alopecia, and ulceration
Which breed of dog is over-represented in cases of canine Langerhans cell histiocytosis?
Shar-pei
What are the clinical signs of histiocytic sarcoma?
- Clinical signs are vague and include anorexia, weight loss, and lethargy.
- Other signs depend on the organs involved and are a consequence of destructive mass formation
Should you submit overlying and/or lateral flanking epithelium to help diagnose melanomas?
Yes - can help to identify junctional activity.
Why is wide excision of lateral flanking epithelium essential in removal of mucosal melanomas?
As lentiginous spread is common for malignant mucosal melanomas
Name differentials for cutaneous melanomas based on cytological findings?
- Pigmented basal cell tumors
- Schwannomas
- Peripheral nerve sheath tumors
What is the function of p53?
- It can activate DNA repair proteins when DNA has sustained damage. Thus, it may be an important factor in aging
- It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition to fix the damage and continue the cell cycle
- It can initiate apoptosis (i.e., programmed cell death) if DNA damage proves to be irreparable.
- It is essential for the senescence response to short telomeres.
What is a proto-oncogene and how is it affected in neoplasia?
Before an oncogene becomes mutated, it is called a proto-oncogene, and it plays a role in regulating normal cell division; when it is mutated it changes into an oncogene and causes the cell to divide and multiply uncontrollably.
Some oncogenes work like an accelerator pedal in a car, pushing a cell to divide again and again. Others work like a faulty brake in a car parked on a hill, also causing the cell to divide unchecked.
A prognostic role for IDO and FoxP3 has been suggested in canine melanoma; what are they markers for?
FoxP3 = Treg
IDO = a cytosolic enzyme involved in the acquisition of peripheral tolerance
- possibly related to the establishment of an immunosuppressive microenvironment
Which marker may be useful in distinguishing canine well-differentiated haemangiosarcomas from haemangiomas?
Ki-67 index
Persistent activation of the signaling pathway phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) has shown to be a frequent event in human cutaneous SCC and in which veterinary species?
Dogs and cats
What are the treatment options for nasal SCC in cats?
- Photodynamic therapy
- Strontium-90 plesiotherapy
- Intralesional chemotherapy
- Curettage
- Diathermy
Larger or more invasive tumors: - Extensive surgical removal
- Curative-intent radiation therapy (+/- accelerated fractionation schedule)
How effective is acelerated fractionation schedule curative intent radiation therapy to treat nasal SCC in cats? Which factor was associated with tumour recurrence?
All cats showed complete response to therapy.
- Median disease-free interval (DFI) for all cases was 916 days.
- One- and two-year DFIs were 71% and 60%
Tumour size (larger associated with recurrence)
Where are Merkel cell carcinomas found on cats and what is their prognosis?
- Most commonly found in the head and neck
- Poor prognosis
Cats with Merkel cell carcinomas often have other proliferative diseases of the skin, such as what?
Epidermal dysplasia, carcinoma in situ, squamous cell carcinoma and basal cell carcinoma
- in up 80% of cases
20/21 cats in Ito et al. (2022) showed evidence of which virus in Merkel cell carcinomas?
FcaPV2
- also demonstrated subsequent inhibition of pRb and p53 induced by integrated viral oncogenes
Loft et al. (2022); which signalment was associated with feline cystadenomatosis?
- Cystadenomatosis was more prevalent in senior non-purebred cats, over-represented in male cats
- Did not appear to be associated with papillomavirus, feline infectious peritonitis, feline immunodeficiency virus/feline leukemia virus status or other identifiable illnesses
- Previously reported in middle-aged to older Abyssinian, Himalayan and Persian cats
Cystadenomatosis typically affects which body sites?
- Primarily the preauricular region, concave pinna, concha, tragus and antitragus, and the external ear canal of cats
- Less commonly the periocular, perioral and perianal
regions
Cystadenomatosis primarily involes which glands?
Ceruminous and apocrine
Why are cystadenomatosis lesions blue/black in colour?
- Partially a reflection of the distended skin
- Partially attributed to the pigmentary contributions from hemosiderin and ceroid of the thick acellular or cell-poor fluid filling the cystic lumen
Feline cMCTs are classified as high grade if they show which features?
> 5 mitotic figures in 10 fields (400x) and at least 2 of the following criteria:
- tumor diameter >1.5 cm
- irregular nuclear shape
- nucleolar prominence/chromatin clusters
What % of feline cMCTs can show aggressive behaviour?
Up to 22% - lymph node metastases, visceral organ involvement, and/or cutaneous dissemination
