Specific Cancers Flashcards
Benign histiocytic diseases
- Histiocytoma - solitary
Langerhaan cell origin - Cutaneous Langerhaans Histiocytosis: multiple cutaneous lesions, some have internal organ involvement. Tends to affect younger dogs with waxing/waning lesions
- Systemic histiocytosis: visceral organ involvement may be immune dysregulation. Seen in BMD
- Feline progressive histiocytosis. dendritic cell origin, multiple dermal masses that wax and wane and eventual spread internally
Histiocytic sarcoma and haemophagocytic HS differences.
CADET - diagnostic test use
HS - dendritic cell origin. May be localised (periarticular) or disseminated
HHS - macrophage origin
HHS more likely to have low albumin and cholesterol
CADET - histiocytic malignancy assay that determines mutation copy number to aid in diagnosis of HS in poorly differentiated samples
Current literature on Histiocytic sarcoma Tx
JAVMA - ORR to doxo sole therapy was 26%. Improved survival in localised disease
JVIM - patients with localised splenic disease treated with Sx and CCNU had MST >1y. Similar results in localised lung disease in VCO 2018.
AVJ - HHS treated with CCNU had no/minimal response and poor survival
STS Grading criteria
Differentiation of cells
Mitotic index (<9 =1; <19 = 2; >20 = 3)
Degree of necrosis: none, <50%; >50%
Reported metastatic disease in STS by grade
1 - 0-13% (6% JAVMA 2021 at diagnosis)
2. 7-27% (6%)
3. 22-44% (38%)
STS Tx in high grade disease recent information
Sx has <5% recurrence if complete.
Incomplete excision have 11-75% recurrence reported
JAVMA 2020 - Adjunctive radiation improved MST from 1031d to 2270d for incompletely excised high grade
- Adjunctive chemo combined with Sx/RT treatment did not have survival benefit
FISS - Prevention controversy
No definitve proof that vaccination induces FISS but a lot of circumstantial evidence
- increased incidence after adjuvanted vaccine introduction
- location associated with site of vacc
- study demonstrating ~50% had been vaccinated within 3y of tumour development
- one study reported reduced incidence with switch in vaccines but another did not find a difference in incidence.
- WSAVA and JFMS vaccine guidelines are to avoid adjuvanted killed vaccines and use liver/modified live instead
JFMS FISS Grading scheme survival times
Low - 900d
Med 514d
High - 283d
FISS Tx outcomes
Sx alone has 30-50% recurrence if complete, 70% if incomplete
Adjunctive brachytherapy following surgery reduced recurrence (54%) in incompletely excised and increased MST to 1242d
JFMS 2019 - definitive RT improved PFI if used in first line treatment with sx (no improvement if used in follow up surgery)
CAnine MCT Prognostic Factors
Histological grade - higher is worse
- Stage of disease - lower better
- Cellular proliferation indices - Ki67, MI, pCNA overexpression has been associated with poor prognosis
- Tumour growth rate - faster growth rate poorer prognosis
- Systemic signs - poor
- Ckit mutation - previously thought to be negative but this has since been contradicted
MCT risk of tumour related death and recurrence by grade (Vet Path 2021)
Low (I) - 2% TRD
Low (II) - 6% TRD
High (II) - 15%
High (III) - 75%
Risk of metastasis at Dx - up to 46% LN in high grade, 20% distant.
Canine MCT WHO Staging
0 - incompletely excised
1 - single tumour
2 - single tumour + LN
3 - Mutliple tumours or infiltrating dermis
4. Distant Mets
Staging only indicated in high grade tumours or those with multiple other negative prognostic factors.
Canine MCT Tx and evidence
Low grade - no evidence of need for adjunctive chemo as low risk of recurrence or metastasis and no evidnece these treatments reduce risk
2 recent papers have reported improved survival time in high grade MCT if the draining LN was removed /irradiated regardless of if metastatic disease present
Tigilanol Tiglate indications; MOA
Tx of low grade MCT of distal limb without evidence of metastasis
- intratumoral injection of compound ellicits rapid local inflammatory response (through mitochondrial dysfunction) and reduction in local blood supply that causes tumour cell death and results in necrosis and sloughing.
Recommend adjunctive treatment with H2 blockers and prednisolone to avoid histamine associated adverse effects
Tigilanol Tiglate Evidence
3 publications of same study population in JVIM. 123 dogs one of which was a randomised controlled clinical study, another a 12 month follow up and another evaluating wound healing. All from manufacturer of drug.
The prospective study reported 75% complete response to treatment, and no recurrence in 93% 84d after treatment (increased to 88% if second treatment given) though complete staging was not undertaken in this population. Wounds healed in all with minimal intervention
Only 64/116 dogs in later published 12 month follow up were evaluated. Of which 89% still tumour free based on clinical evaluation only.
No subsequent staging and grade of disease only confirmed on cytopathology (not histopathology) .
Wound healing was 4-6 weeks on average. 5 dogs needing bandaging.
Cytologically high grade tumours may be less responsive compared to low grade.
Types of Feline MCT and their Px/Tx
JFMS study reported beneficial response to toceranib in a majority of all MCT types in cats.
Cutaneous - most are low grade, but can have high mitotic index/grade and this is associated with prognosis. Sx removal is generally curative but up to 24% recur. Recent study reported 59% have nodal mets.
Visceral - prognosis with splenectomy is fair to good with MST of 12-18mo in some studies and adjunctive Tx with toceranib may be beneficial
Intestinal - 2018 VCO study found no difference in survival b/w treatment methods including Sx vs pred alone, May have been biased with more severe cases receiving more treatment. MST 16mo.
Proposed pathophysiology of hormonal influence on mammary gland neoplasia
Progesterone increases mammary gland cell expression of GH to induce local IGF-1 production. This is a proliferation and survival stimulus.
The combined effect of concurrent oestrogen exposure increases this.
This is why females with prior progestagin exposure have higher risk of MGT development in both cats and dogs.
Biology of Mammary Tumours
Begin as benign proliferations and as they continue to grow there is a drift towards loss of hormone reliance through reduced expression of hormone receptors which are all but gone in the highly malignant tumours. The disease is a continuum not separate disease entities.
