Lymphoma summary
• Abstract-common type neoplasia in dog-mostly wide variation in clinical presentation-most present with generalised lymphadenopathy-hypercalcemia w/ T cell type-chemo w. doxorubicin-based multidrug protocol is the choice-remisision last for median period 7-10 months-MST 10-14 months -prognostic factors: stage, immunophenotype, tumour grade and response to chemo-chemo has drug resistance issue
• Epidemiology -most common hematopoietic neoplasia-increasing cases due to closed gene ppol + willingness to treat-middle-sized to larger dog breed (Rottweiler and Scottish terrier)-middle aged to older dog-intact female has lower risk
• Etiology-genetic/molecular factors-waste, pollute, perbicide-autoimmue disease or drug related (history of cyclosporine use)
• Molecular biology -proto-oncogene c-kit (tyrosine protein kinase) ∝ ↓proliferation, survival & differentiation of hematopoietic stem cell
• Clinical presentation
1. Multicentric lymphoma-75% of all cL-five stage w/ suffix a & b (a=absence of systemic signs and b = presence of systemic sign such as fever, weight loss or hypercalcemia)
2. Mediastinal lymphoma-thymic or cranial mediastinal cL common in young dogs-exclusively T cell origin-CSx: dyspnea, polyuria, polydipsia-characterised by pitting edema of the head and neck resulting from a large mediastinal mass that restricts venous return to the heart-cytological or histological biopsy = definitive diagnosis-cytology sufficient
3. Gastrointestinal lymphoma-no age, sex, breed predisposition-boxer and sher-pei-u/s to discriminate Gi tract from intestinal neoplasia (25% false negative)-u/s looking for loss of normal wall layering, lesser extent increased wall thickness, mesenterial lymphadenopathy-definitive dx: mucosal biopsy-local T cell lymphoma or systemic eosinophilia
4. Hepatic lymphoma-rare and poor-MST 63 days-two forms primary hepatic T-cell lympoma (MST 24 days)
5. Cutaneous lymphoma-T cell lymphoma -3 forms: mycosis fungoides, Sezary syndrome, pagetoid reticulosis-atopic dermatitis increase risk of mycosis fungoides-mycosis fungoides is CD8+ T cell mainly affect mean age 11 year
6. Ocular lymphoma -mostly B cell origin-present both as an intraocular mass or conjunctival disease 7. Nervous system lymphoma-rare
8. Pulmonary lymphoma
9. Atypical form of canine lymphoma-oral, nasal, choanal, vertebral, skeletal muscle
10. Paraneoplastic syndromes-hypercalcemia resulted from the production of PTH-related peptide by CD4+ T cell lymphoblasts-hypercalcemia reduces the collecting ducts response to ADH-cause polyuria-increase risk for hypoxia of the renal tubule and acute renal failure -PTH level are low in hypercalcemia of malignancy
• Epidemiology -most common hematopoietic neoplasia-increasing cases due to closed gene ppol + willingness to treat-middle-sized to larger dog breed (Rottweiler and Scottish terrier)-middle aged to older dog-intact female has lower risk
• Etiology-genetic/molecular factors-waste, pollute, perbicide-autoimmue disease or drug related (history of cyclosporine use)
• Molecular biology -proto-oncogene c-kit (tyrosine protein kinase) ∝ ↓proliferation, survival & differentiation of hematopoietic stem cell
• Clinical presentation
1. Multicentric lymphoma-75% of all cL-five stage w/ suffix a & b (a=absence of systemic signs and b = presence of systemic sign such as fever, weight loss or hypercalcemia)
2. Mediastinal lymphoma-thymic or cranial mediastinal cL common in young dogs-exclusively T cell origin-CSx: dyspnea, polyuria, polydipsia-characterised by pitting edema of the head and neck resulting from a large mediastinal mass that restricts venous return to the heart-cytological or histological biopsy = definitive diagnosis-cytology sufficient
3. Gastrointestinal lymphoma-no age, sex, breed predisposition-boxer and sher-pei-u/s to discriminate Gi tract from intestinal neoplasia (25% false negative)-u/s looking for loss of normal wall layering, lesser extent increased wall thickness, mesenterial lymphadenopathy-definitive dx: mucosal biopsy-local T cell lymphoma or systemic eosinophilia
4. Hepatic lymphoma-rare and poor-MST 63 days-two forms primary hepatic T-cell lympoma (MST 24 days)
5. Cutaneous lymphoma-T cell lymphoma -3 forms: mycosis fungoides, Sezary syndrome, pagetoid reticulosis-atopic dermatitis increase risk of mycosis fungoides-mycosis fungoides is CD8+ T cell mainly affect mean age 11 year
6. Ocular lymphoma -mostly B cell origin-present both as an intraocular mass or conjunctival disease 7. Nervous system lymphoma-rare
8. Pulmonary lymphoma
9. Atypical form of canine lymphoma-oral, nasal, choanal, vertebral, skeletal muscle
10. Paraneoplastic syndromes-hypercalcemia resulted from the production of PTH-related peptide by CD4+ T cell lymphoblasts-hypercalcemia reduces the collecting ducts response to ADH-cause polyuria-increase risk for hypoxia of the renal tubule and acute renal failure -PTH level are low in hypercalcemia of malignancy
- • Diagnosis
- 1. Clinical pathology
- -mild to moderate non-regenerative anemia from blood loss or immune-mediated hemolytic anemia
- -morphological erythrocyte abnormalities
- -both luekocytosis, leukopenia
- -inflammatory response w/ leukemia accounting 20% leukocytosis cases
- -mild asymptomatic thrombocytopenia common
- -hypercalcemia almost exclusive w/ T cell lymphoma
- 2. Diagnostic imagining
- -thoracic radiographs reveal 70% of cL cases (thoracic lymphadenopathy, pulmonary infiltrate, cranial mediastinal mass)
- -u/s of abdomen and lymph node helpful to assess lymph node size and architecture
- -u/s to check hepatic splenic involvement
- -abominal u/s not suitable to exclude GI lymphoma
- -CT = excellent choice, not able to discriminate between a thymoma & mediastinal lymphoma
- -scintigraphy using radiolabeled peptide nucleic acid peptide conjugate targeting Bcl-2 mRNA for B-cell lymphoma in dogs
- 3. Cytology, histology, immunophenotyping
- -FNA = diagnostic method of choice
- -low grade cL, FNA might not be sufficient
- -histo for diagnosis of low grade cL and subclassification cL
- -histo criteria: growth patter, nuclear size, nuclear morphology, mitotic index, immunophenotypes
- -5 subtypes: diffuse large B-cell lymhoma, marginal zone B cell lymphoma, peripheral T cell lymphoma, nodal T zone lymphoma, T lymphoblastic lymphoma
- -majority of cL B-cell origin (70%)
- -immunophenotype dependent on breed
- -T cell>80% in Irish wolfhound, Shih Tzu, Airedale terrier, York shire terrier, cocker spaniel and Siberian huscky, bocer
- -B-cell >80% in Doberman pinscher, Scottish terrier, border collie, cavalier king Charles spaniel, basset hound
- 4. PCR-based techniques
- -PCR assay for antigen receptor rearrangement (PARR)
- 5. Biomarkers
- -serum protein electrophoresis
- -TK1 correlate with stage and prognosis
- • Staging
- -physical examination, peripheral blood, bone marrow evaluation
- -strong negative effect of hypercalcemia and T-cell immunophenotype on prognosis incl these two tests
- -thoracic radiograph & abdominal u/s more correct staging
- -cytological examination of FNA of extra nodal site = most common
- -use of PARR
- -flow cytometry
- • Therapy
- - CHEMO
- 1. Glucocorticoid
- -induce lymphocyte and lymphoblast apoptosis
- -should be considered as a palliative tx
- -use of glucocorticoid should be withheld until decision of not pursue tx with cytostatic drug as glucocorticoid results in lower response rates and shorter remission period
- 2. Single agent therapy
- -L-asparaginase
- -mitoxantrone
- -doxorubicin either as a continours (5x q3 weeks) or intermittent followed by additional doses (most effective)
- 3. Multi agent thearpy
- -combine cyclophosphamide, doxorubicin, vincristine,
- prednisolone (CHOP)
- -L-asparaginase (L-CHOP)
- -adding prednisolone to a doxorubicin-based multidrug
- protocol = reserved for later use in a rescue protocol
- 4. Drug resistance in canine lymphoma
- -intrinsic DR more common in T cell than B-cell lymphoma
- • Clinical data
- -sex, weight, WHO stage, substage = prognostic for remission and survival
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Oral ameloblastoma summary
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