เนื้องอกชนิดมาสท์เซลล์ในผิวหนังสุนัข: การวินิจฉัยและการพยากรณ์โรค
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ก.ค. 11, 2018
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เนื้องอกชนิดมาสท์เซลล์ ฮีสโตเคมี อิมมูโนฮีสโตเคมี การวินิจฉัยโรค ตัวบ่งชี้การพยากรณ์โรค สุนัข
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บทคัดย่อ
Mast cell tumor เป็นเนื้องอกที่พบได้บ่อยในผิวหนังของสุนัข ลักษณะที่ปรากฏและพฤติกรรมของเนื้องอกมีความแปรผันจึงทำให้ยากต่อการรักษา การวินิจฉัย mast cell tumor ด้วยการตรวจเซลล์และลักษณะทางจุลพยาธิวิทยานั้นทำได้โดยการตรวจดูลักษณะรูปร่างและการติดสีของเซลล์เป็นหลัก นอกจากนี้การย้อมเนื้อเยื่อด้วยเทคนิคฮีสโตเคมีชนิดต่างๆ ยังสามารถให้ข้อมูลในการตรวจวินิจฉัยเพิ่มขึ้นด้วย โดยย้อมเนื้อเยื่อด้วยสีพิเศษและการทดสอบปฏิกิริยาทางเคมีของเอ็นไซม์ที่มีความจำเพาะเจาะจง อย่างไรก็ตามเนื้องอกที่มีพัฒนาการของเซลล์น้อยมากนั้นยังยากต่อการจำแนกชนิดของเซลล์ และมักทำให้เกิดความสับสนกับเนื้องอกในกลุ่ม round cell tumor ชนิดอื่นที่มีรูปร่างคล้ายกัน การวินิจฉัยจึงอาจผิดพลาดได้ เทคนิคทางอิมมูโนฮีสโตเคมีซึ่งใช้แอนติบอดีที่มีความจำเพาะเจาะจงต่อเซลล์หรือตัวบ่งชี้ต่างๆ ที่ต้องการตรวจสอบจึงถูกนำมาใช้เพื่อประกอบการวินิจฉัยและการพยากรณ์โรคเนื้องอก บทความนี้ทบทวนลักษณะ mast cell tumor ในผิวหนังสุนัข รวมทั้งการย้อมเนื้อเยื่อด้วยเทคนิคฮีสโตเคมีและอิมมูโนฮีสโตเคมีชนิดต่างๆ ซึ่งสามารถนำมาใช้ในการตรวจวินิจฉัยและการพยากรณ์โรค ซึ่งเมื่อนำมาประกอบกับข้อมูลทางคลินิกและตัวบ่งชี้อื่นๆ จะช่วยให้การวินิจฉัยและพยากรณ์โรคมีความแม่นยำมากขึ้น ส่งผลต่อการวางแผนการรักษาและการเฝ้าระวังโรคที่มีประสิทธิภาพ
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Suebkhampet, A. (2018) “เนื้องอกชนิดมาสท์เซลล์ในผิวหนังสุนัข: การวินิจฉัยและการพยากรณ์โรค”, สัตวแพทย์มหานครสาร, 11(2), น. 159–176. available at: https://li01.tci-thaijo.org/index.php/jmvm/article/view/133922 (สืบค้น: 18 ธันวาคม 2025).
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Bancroft, J. and Gamble, M. 2008. Theory and Practice of Histological Techniques. 6th ed. Churchill Livingstone/Elsevier, Philadelphia. 725 p.
Beaven, M.A. and Metzger, H. 1993. Signal transduction by Fc receptors: the Fc epsilon RI case. Immunol. Today 14(5): 222-226.
De Souza Junior, D.A., Santana, A.C., da Silva, E.Z., Oliver, C. and Jamur, M.C. 2015. The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis Biomed. Res. Int. 1-13.
Derenzini, M. 2003. The AgNORs. Micron 31: 117–120.
Dopson, J.M. and Scase, T.J. 2007. Advances in the diagnosis and management of cutaneous mast cell tumours in dogs. J. Small Anim. Pract. 48: 424-431.
Dorn, C.R., Taylor, D.O., Schneider, R., Hibbard, H.H. and Klauber, M.R. 1968. Survey of animal neoplasms in Alameda and Contra Costa counties, California II. Cancer morbidity in dogs and cats from Alameda Country. J. of the National Cancer Institute 40: 307-318.
Dos Santos Costa Poggiani, S., Terra, E.M., Neto, R.T., Costa, M.T. and Amorim, R.F. 2012. Canine Cutaneous Mast Cell Tumor: Biologic Behavior and Its Correlation with Prognostic Indicators. Open J. Vet. Med. 2: 255-261.
Downing, S. Chien, M.B., Kass, P.H., Moore, P.E. and London, C.A. 2002. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am. J. Vet. Res. 63: 1718–1723.
Duncan, J.R. and Prasse, K.W. 1979. Cytology of canine cutaneous round cell tumors. Vet. Pathol. 16: 673-679.
Epstein, J.B., Scully, C. and Spinelli, J. 1992. Toluidine blue and Lugol's iodine application in the assessment of oral malignant disease and lesions at risk of malignancy. J Oral Pathol Med. 21:160–163.
Fernandez, N.J., West, K.H., Jackson, M.L. and Kidney, B.A. 2005. Immunohistochemical and histochemical stains for differentiating canine cutaneous round cell tumors. Vet. Pathol. 42: 437–445.
Furitsu, T., Tsujimura, T. and Tono, T. 1993. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J. Clin. Invest. 92: 1736–1744.
Galli, S.J., Zsebo, K.M. and Geissler, E.N. 1994. The kit-ligand, stem-cell factor. Adv. in Immunol. 55:1-96.
Gleixner, K.V., Rebuzzi, L., Mayerhofer, M., Gruze, A., Hadzijusufivic, E., Sonneck, K., Vales, A., Kneidinger, M., Samorapoomichit, P., Thaiwong, T., Pickl, W.F., Yuzbasiyan-Gurkan, V., Sillaber, C., Willmann, M. and Valent, P. 2007. Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells. Exp. Hematol. 35: 1510–1521.
Goldschmidt, M.H. and Shofer, F.S. 1992. Skin tumours of the cat and dog. Pergamon press. Oxford, NY, USA. 316p.
Howard, E.B., Sawa, T.R., Nielsen, S.W. and Kenyon, A.J. 1969. Mastocytoma and gastroduodenal ulceration. Pathol. Vet. 6:146-158.
Huntley, JF. 1992. Mast cells and basophils: a review of their heterogeneity and function. J.Comp. Pathol. 107(4): 349-372.
Jackson, D. 1994. The cytology of the contagious (venereal) tumor of dog. Onderstepoort J. Vet. Res. 20:433-442.
Jones, C.L., Grahn, R.A., Chien, M.B., Lyons, L.A. and London, C.A. 2004. Detection of c-kit mutations in canine mast cell tumors using fluorescent poly acrylamide gel electrophoresis. J. Vet. Diagn. Invest. 16: 95–100.
Kitamura, Y. and Fujita, J. 1989. Regulation of mast cell differentiation. Bioessays 10: 193–196.
Kiupel, M., Webster, J.D., Bailey, K.L., Best, S., DeLay, J., Detrisac, C.J., Fitzgerald, S.D., Gamble, D., Ginn, P.E., Goldschmidt,, M.H., Hendrick, M.J., Howerth, E.W., Janovitz, E.B., Langohr, I., Lenz, S.D., Lipscomb, T.P., Miller, M.A., Misdorp, W., Moroff, S., Mullaney, T.P., Neyens, I., O’Toole, D., Ramos-Vara, J., Scase, T.J., Schulman, F.Y., Sledge, D., Smedley, R.C., Smith, K., Snyder, P.W., Southorn, E., Stedman, N.L., Steficek, B.A., Stromberg, P.C., Valli, V.E., Weisbrode, S.E., Yager, J., Heller, J. and Miller, R. 2011. Proposal of a Two-Tier Histologic Grading Sys- tem for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior. Vet. Pathol. 48(1) 147-155.
Kiupel, M., Webster, J.D., Kaneene, J.B., Miller, R. and Yuzbasiyan-Gurkan, V. 2004. The use of KITand tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors. Vet. Pathol. 41: 371–377.
Kiupel, M., Webster, J.D., Miller, R.A. and Kaneene, J.B. 2005. Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours. J. Vet. Med. A. 52: 280-286.
Kube, P., Audige, L., Kuther, K. and Welle, M. 1998. Distribution, Density and Heterogeneity of Canine Mast Cells and Influence of Fixation Techniques Histochem. Cell Biol. 110 (2): 129-135.
Kurz, H. and Wittekind, D. 2001. A new panoptic stain for developmental biology - The mouse placenta paradigm. Annual of Anat. 183: 437-441.
Leclere, M., Desnoyers, M., Beauchamp, G. and Lavoie, J.P. 2006. Comparison of Four Staining Methods for Detection of Mast Cells in Equine Bronchoalveolar Lavage Fluid. J. Vet. Intern. Med. 20:377–381.
Leder, L.D. 1979. The chloroacetate esterase reaction. A usefulmeans of histological diagnosis of hematological disorders from paraffin sections of the skin. Anim. J. Dermatopathol. 1:39-42.
Linnekin, D., DeBerry, C.S and Mou, S. 1997. Lyn associates with the Juxtamembrane region of c-Kit and is activated by stem cell factor in haemopoietic cell and normal progenitor cells. J. Biol. Chem. 272: 27450-27455.
London, C.A., Kisseberth, W.C., Galli, S.J., Geissler, E.N. and Helfand, S.C. 1996 Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine MCTs. J. Comp. Pathol. 115: 399-414.
London, C.A. and Segun, B. 2003. Mast cell tumors in the dog. Vet Clin. North Am. Small An. Pract. 33: 473-489.
Metcalfe, D.D., Baram, D. and Mekori, Y.A. 1997. Mast cells. Physiol. Rev. 77: 1033-1079.
Misdrop, W. 2004. Mast cells and canine mast cell tumuors. A review Vet. Q. 26:156-169.
Morini, M., Bettini, G., Preziosi, R. and Mandrioli, L. 2004. C-kit gene product (CD117) immunoreactivity in canine and feline paraffin sections. J. Histochem. Cytochem. 52: 705–708.
Nocka, K., Buck, J., Levi, E. and Besmer, P. 1990. Candidate ligand for the c-kit transmembrane kinaseb receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors Embo. J. 9: 3287-3294.
Northrup, N.C., Howerth, E.W., Harmon, B.G., Brown, C.A., Carmicheal, K.P., Garcia, A.P., Latimer, K.S., Munday, J.S., Rakich, P.M., Richey, L.J., Stedman, N.L. and Gieger, T.L. 2005. Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J. Vet. Diagn. Invest. 17: 561-564.
Ogura, S., Abe, S., Sukoh, N, Kunikane, H., Nakajima, I., Inoue, K. and Kawakami, Y. 1992. Correlation between nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma. Cancer 70: 63–68.
O’Keefe, D.A. 1990. Canine mast cell tumors. Vet. Clin. N. Am.-Small 20:1105-1115.
Pakhrin, B., Kang, M.S., Bae, I.H., Park, M.S., You, M.H., Kim, J.H., Yoon, B.I., Choi, Y.K. and Kim, D.Y. 2007. Retrospective study of canine cutaneous tumors in Korea. J. Vet. Sci. 8(3): 229-236.
Patnaik, A.K., Ehler, W.J. and Macwem, E.G. 1984. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet. Pathol. 21: 469-474.
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Webster, J.D., Yuzbasiyan-Gurkan, V., Miller, R.A., Kaneene, J.B. and Kiupel, M. 2007. Cellular proliferation in canine cutaneous mast cell tumors: associations with c-KIT and its role in prognostication. Vet. Pathol. 44: 298–308.
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Bancroft, J. and Gamble, M. 2008. Theory and Practice of Histological Techniques. 6th ed. Churchill Livingstone/Elsevier, Philadelphia. 725 p.
Beaven, M.A. and Metzger, H. 1993. Signal transduction by Fc receptors: the Fc epsilon RI case. Immunol. Today 14(5): 222-226.
De Souza Junior, D.A., Santana, A.C., da Silva, E.Z., Oliver, C. and Jamur, M.C. 2015. The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis Biomed. Res. Int. 1-13.
Derenzini, M. 2003. The AgNORs. Micron 31: 117–120.
Dopson, J.M. and Scase, T.J. 2007. Advances in the diagnosis and management of cutaneous mast cell tumours in dogs. J. Small Anim. Pract. 48: 424-431.
Dorn, C.R., Taylor, D.O., Schneider, R., Hibbard, H.H. and Klauber, M.R. 1968. Survey of animal neoplasms in Alameda and Contra Costa counties, California II. Cancer morbidity in dogs and cats from Alameda Country. J. of the National Cancer Institute 40: 307-318.
Dos Santos Costa Poggiani, S., Terra, E.M., Neto, R.T., Costa, M.T. and Amorim, R.F. 2012. Canine Cutaneous Mast Cell Tumor: Biologic Behavior and Its Correlation with Prognostic Indicators. Open J. Vet. Med. 2: 255-261.
Downing, S. Chien, M.B., Kass, P.H., Moore, P.E. and London, C.A. 2002. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am. J. Vet. Res. 63: 1718–1723.
Duncan, J.R. and Prasse, K.W. 1979. Cytology of canine cutaneous round cell tumors. Vet. Pathol. 16: 673-679.
Epstein, J.B., Scully, C. and Spinelli, J. 1992. Toluidine blue and Lugol's iodine application in the assessment of oral malignant disease and lesions at risk of malignancy. J Oral Pathol Med. 21:160–163.
Fernandez, N.J., West, K.H., Jackson, M.L. and Kidney, B.A. 2005. Immunohistochemical and histochemical stains for differentiating canine cutaneous round cell tumors. Vet. Pathol. 42: 437–445.
Furitsu, T., Tsujimura, T. and Tono, T. 1993. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J. Clin. Invest. 92: 1736–1744.
Galli, S.J., Zsebo, K.M. and Geissler, E.N. 1994. The kit-ligand, stem-cell factor. Adv. in Immunol. 55:1-96.
Gleixner, K.V., Rebuzzi, L., Mayerhofer, M., Gruze, A., Hadzijusufivic, E., Sonneck, K., Vales, A., Kneidinger, M., Samorapoomichit, P., Thaiwong, T., Pickl, W.F., Yuzbasiyan-Gurkan, V., Sillaber, C., Willmann, M. and Valent, P. 2007. Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells. Exp. Hematol. 35: 1510–1521.
Goldschmidt, M.H. and Shofer, F.S. 1992. Skin tumours of the cat and dog. Pergamon press. Oxford, NY, USA. 316p.
Howard, E.B., Sawa, T.R., Nielsen, S.W. and Kenyon, A.J. 1969. Mastocytoma and gastroduodenal ulceration. Pathol. Vet. 6:146-158.
Huntley, JF. 1992. Mast cells and basophils: a review of their heterogeneity and function. J.Comp. Pathol. 107(4): 349-372.
Jackson, D. 1994. The cytology of the contagious (venereal) tumor of dog. Onderstepoort J. Vet. Res. 20:433-442.
Jones, C.L., Grahn, R.A., Chien, M.B., Lyons, L.A. and London, C.A. 2004. Detection of c-kit mutations in canine mast cell tumors using fluorescent poly acrylamide gel electrophoresis. J. Vet. Diagn. Invest. 16: 95–100.
Kitamura, Y. and Fujita, J. 1989. Regulation of mast cell differentiation. Bioessays 10: 193–196.
Kiupel, M., Webster, J.D., Bailey, K.L., Best, S., DeLay, J., Detrisac, C.J., Fitzgerald, S.D., Gamble, D., Ginn, P.E., Goldschmidt,, M.H., Hendrick, M.J., Howerth, E.W., Janovitz, E.B., Langohr, I., Lenz, S.D., Lipscomb, T.P., Miller, M.A., Misdorp, W., Moroff, S., Mullaney, T.P., Neyens, I., O’Toole, D., Ramos-Vara, J., Scase, T.J., Schulman, F.Y., Sledge, D., Smedley, R.C., Smith, K., Snyder, P.W., Southorn, E., Stedman, N.L., Steficek, B.A., Stromberg, P.C., Valli, V.E., Weisbrode, S.E., Yager, J., Heller, J. and Miller, R. 2011. Proposal of a Two-Tier Histologic Grading Sys- tem for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior. Vet. Pathol. 48(1) 147-155.
Kiupel, M., Webster, J.D., Kaneene, J.B., Miller, R. and Yuzbasiyan-Gurkan, V. 2004. The use of KITand tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors. Vet. Pathol. 41: 371–377.
Kiupel, M., Webster, J.D., Miller, R.A. and Kaneene, J.B. 2005. Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours. J. Vet. Med. A. 52: 280-286.
Kube, P., Audige, L., Kuther, K. and Welle, M. 1998. Distribution, Density and Heterogeneity of Canine Mast Cells and Influence of Fixation Techniques Histochem. Cell Biol. 110 (2): 129-135.
Kurz, H. and Wittekind, D. 2001. A new panoptic stain for developmental biology - The mouse placenta paradigm. Annual of Anat. 183: 437-441.
Leclere, M., Desnoyers, M., Beauchamp, G. and Lavoie, J.P. 2006. Comparison of Four Staining Methods for Detection of Mast Cells in Equine Bronchoalveolar Lavage Fluid. J. Vet. Intern. Med. 20:377–381.
Leder, L.D. 1979. The chloroacetate esterase reaction. A usefulmeans of histological diagnosis of hematological disorders from paraffin sections of the skin. Anim. J. Dermatopathol. 1:39-42.
Linnekin, D., DeBerry, C.S and Mou, S. 1997. Lyn associates with the Juxtamembrane region of c-Kit and is activated by stem cell factor in haemopoietic cell and normal progenitor cells. J. Biol. Chem. 272: 27450-27455.
London, C.A., Kisseberth, W.C., Galli, S.J., Geissler, E.N. and Helfand, S.C. 1996 Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine MCTs. J. Comp. Pathol. 115: 399-414.
London, C.A. and Segun, B. 2003. Mast cell tumors in the dog. Vet Clin. North Am. Small An. Pract. 33: 473-489.
Metcalfe, D.D., Baram, D. and Mekori, Y.A. 1997. Mast cells. Physiol. Rev. 77: 1033-1079.
Misdrop, W. 2004. Mast cells and canine mast cell tumuors. A review Vet. Q. 26:156-169.
Morini, M., Bettini, G., Preziosi, R. and Mandrioli, L. 2004. C-kit gene product (CD117) immunoreactivity in canine and feline paraffin sections. J. Histochem. Cytochem. 52: 705–708.
Nocka, K., Buck, J., Levi, E. and Besmer, P. 1990. Candidate ligand for the c-kit transmembrane kinaseb receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors Embo. J. 9: 3287-3294.
Northrup, N.C., Howerth, E.W., Harmon, B.G., Brown, C.A., Carmicheal, K.P., Garcia, A.P., Latimer, K.S., Munday, J.S., Rakich, P.M., Richey, L.J., Stedman, N.L. and Gieger, T.L. 2005. Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J. Vet. Diagn. Invest. 17: 561-564.
Ogura, S., Abe, S., Sukoh, N, Kunikane, H., Nakajima, I., Inoue, K. and Kawakami, Y. 1992. Correlation between nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma. Cancer 70: 63–68.
O’Keefe, D.A. 1990. Canine mast cell tumors. Vet. Clin. N. Am.-Small 20:1105-1115.
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