Page 419 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 21 Mast Cell Tumors 397

dissemination. Buffy coat smear may also be performed although, References
unlike in splenic MCT, peripheral mastocytosis is rarely associated 1. Bostock DE: Neoplasms of the skin and subcutaneous tissues in
with intestinal MCT and only two reports of peripheral eosino-
VetBooks.ir philia exist in the literature. 277 2. Carpenter JL, Andrews LK, Holzworth J: Tumors and tumor-like
dogs and cats, Br Vet J 142:1–19, 1986.
Intestinal MCT in cats often carries a poor prognosis because
metastasis is common at the time of diagnosis and many cats lesions. In Holzworth J, editor: Diseases of the cat: medicine and
either die or are euthanized soon after diagnosis. 2,277–279 How- surgery, Philadelphia, 1987, WB Saunders, pp 406–596.
ever, two recent reports totaling 48 cats suggest a more favor- 3. Finnie JW, Bostock DE: Skin neoplasia in dogs, Aust Vet J 55:602–
604, 1979.
able outcome for cats with intestinal MCT. 279,280 MSTs after 4. Miller MA, Nelson SL, Turk JR, et al.: Cutaneous neoplasia in 340
surgical and/or medical (TKIs/corticosteroids) management cats, Vet Pathol 28:389–395, 1991.
were approximately 1.5 years. Histologic differentiation and 5. Rothwell TL, Howlett CR, Middleton DJ, et al.: Skin neoplasms of
MI were found to be prognostic, whereas c-kit mutation was dogs in Sydney, Aust Vet J 64:161–164, 1987.
not prognostic. 279 Surgery is the treatment of choice and wide 6. Kumar V, Sharma A: Mast cells: emerging sentinel innate immune
surgical margins are necessary (5–10 cm), as the tumor typi- cells with diverse role in immunity, Mol Immunol 48:14–25, 2010.
cally extends histologically well beyond the gross disease. 2,277 7. Noviana D, Mamba K, Makimura S, et al.: Distribution, histo-
Undifferentiated tumors and those with a MI >2 may have chemical and enzyme histochemical characterization of mast cells
worse postsurgical outcomes. 279 Recently, a variant of feline in dogs, J Mol Histol 35:123–132, 2004.
intestinal MCT, termed sclerosing MCT, was described in 50 8. Metz M, Piliponsky AM, Chen CC, et al.: Mast cells can enhance
resistance to snake and honeybee venoms, Science 313:526–530, 2006.
cats. 278 Metastatic disease to the LN and/or liver was present 9. Lin TY, London CA: A functional comparison of canine and
in 23 of 36 cats evaluated. Of the 25 cases with clinical follow- murine bone marrow derived cultured mast cells, Vet Immunol
up information, 23 died or were euthanized within 2 months Immunopathol 114:320–334, 2006.
of diagnosis. 278 Limited information exists regarding the use of 10. Lin TY, Rush LJ, London CA: Generation and characterization
chemotherapy and/or TKIs for the treatment of feline intesti- of bone marrow-derived cultured canine mast cells, Vet Immunol
nal MCT, although responses to lomustine and TOC have been Immunopathol 113:37–52, 2006.
reported. 263,268 11. Lin TY, London CA: Characterization and modulation of canine
mast cell derived eicosanoids, Vet Immunol Immunopathol 135:118–
127, 2010.
Comparative Aspects of Mast Cell Tumors 12. Brodey RS: Canine and feline neoplasia, Adv Vet Sci Comp Med
14:309–354, 1970.
Neoplastic diseases of MCs are rare in people and present as 13. Patnaik AK, Ehler WJ, MacEwen EG: Canine cutaneous mast
three main clinical entities. 281–285 Cutaneous mastocytosis, also cell tumor: morphologic grading and survival time in 83 dogs, Vet
known as urticaria pigmentosa, is a benign disease in which Pathol 21:469–474, 1984.
MC infiltration is confined to the skin. It occurs primarily in 14. Peters JA: Canine mastocytoma: excess risk as related to ancestry,
young children and usually regresses spontaneously before pro- J Natl Cancer Inst 42:435–443, 1969.
gression into adulthood. Systemic mastocytosis (SM) occurs 15. White CR, Hohenhaus AE, Kelsey J, et al.: Cutaneous MCTs: asso-
primarily in adults and includes four major subtypes: (1) indo- ciations with spay/neuter status, breed, body size, and phylogenetic
lent SM, the most common form involving mainly skin and cluster, J Am Anim Hosp Assoc 47:210–216, 2011.
bone marrow that does not progress to aggressive disease; (2) 16. Arendt ML, Melin M, Tonomura N, et al.: Genome-wide asso-
a unique subcategory termed SM with an associated non-MC ciation study of golden retrievers identifies germ-line risk factors
predisposing to mast cell tumours, PLoS Genet 11:e1005647, 2015.
clonal hematologic disease; (3) aggressive SM usually present- 17. McNiel EA, Prink AL, O’Brien TD: Evaluation of risk and clinical
ing without skin lesions; and (4) MC leukemia, probably rep- outcome of mast cell tumours in pug dogs, Vet Comp Oncol 4:2–8,
resenting the rarest variant of human leukemias. Lastly, rare 2004.
localized extracutaneous MCT (either benign or malignant) 18. Davis BJ, Page R, Sannes PL, et al.: Cutaneous mastocytosis in a
have been reported. Dysregulation of KIT is also found com- dog, Vet Pathol 29:363–365, 1992.
monly in human neoplastic MC diseases and is primarily driven 19. Dunn TB, Patter H: A transplantable mast cell neoplasm in the
by a point mutation in exon 17 of c-kit that induces ligand- mouse, J Natl Cancer Inst 18:587–601, 1957.
independent activation. 282,286 More recently, mutations have 20. Hottendorf GH, Nielsen SW: Pathologic survey of 300 extirpated
also been identified in exons 8 to 11, most of which are also canine mastocytomas, Zentralbl Veterinarmed A 14:272–281, 1967.
activating. 282,286 21. Peterson SL: Scar-associated canine mast cell tumor, Canine Pract
12:23–29, 1985.
Treatment of the benign human MC disorders is focused pri- 22. Bowles CA, Kerber WT, Rangan SRS, et al.: Characterization of
marily on supportive therapy, including H and H antagonists, a transplantable, canine, immature mast cell tumor, Cancer Res
2
1
and topical or systemic therapy with corticosteroids. Unfortu- 32:1434–1441, 1972.
nately, an effective treatment protocol for people with aggressive 23. Lombard LS, Moloney JB: Experimental transmission of mast cell
mastocytosis or MC leukemia has not been identified. Treatment sarcoma in dogs, Fed Proc 18:490–495, 1959.
with interferon-alpha and/or cladribine is often used, although 24. Nielson SW, Cole CR: Homologous transplantation of canine neo-
response rates are typically low. 281,286 Most of the currently avail- plasms, Am J Vet Res 27:663–672, 1961.
able small molecule KIT inhibitors, including imatinib, nilotinib, 25. Stone JM, Jacky PB, Prieur DJ: Chromosomal fragile site expres-
and dasatinib, have been ineffective in treating human mas- sion in boxer dogs with mast cell tumors, Am J Med Genetics
tocytosis. 286 This may in part be due to the fact that inhibiting 40:223–229, 1991.
phosphorylation of KIT expressing activating exon 17 mutations 26. Ginn PE, Fox LE, Brower JC, et al.: Immunohistochemical detec-
tion of p53 tumor-suppressor protein is a poor indicator of prog-
is extremely challenging. More recently, the protein kinase C nosis for canine cutaneous mast cell tumors, Vet Pathol 37:33–39,
inhibitor midostaurin has demonstrated activity in human MC 2000.
disease. 286