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Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

Simpson RM, Bastian BC, Michael HT, Webster JD, Prasad ML, Conway CM, Prieto VM, Gary JM, Goldschmidt MH, Esplin DG, Smedley RC, Piris A, Meuten DJ, Kiupel M, Lee CC, Ward JM, Dwyer JE, Davis BJ, Anver MR, Molinolo AA, Hoover SB, Rodriguez-Canales J, Hewitt SM - Pigment Cell Melanoma Res (2013)

Bottom Line: The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis.Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation.We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

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Lentiginous-like in situ involvement in mucosal melanomas by malignant melanocytes in the mucosal epithelium. Clusters of malignant melanocytes occur in the epithelial stratum basale and ascend into superficial strata. Photomicrographs of hematoxylin–eosin-stained (A) human mucosal melanoma and (B) canine mucosal melanoma. (C) Radial extension of malignant melanocytes is evident in the intact mucosal epithelium lateral to the vertical tumor component in some canine melanomas; (same canine patient as in B). Antimelan-A immunohistochemistry, red chromogen label, hematoxylin counter stain. Bar = 50 μm.
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fig02: Lentiginous-like in situ involvement in mucosal melanomas by malignant melanocytes in the mucosal epithelium. Clusters of malignant melanocytes occur in the epithelial stratum basale and ascend into superficial strata. Photomicrographs of hematoxylin–eosin-stained (A) human mucosal melanoma and (B) canine mucosal melanoma. (C) Radial extension of malignant melanocytes is evident in the intact mucosal epithelium lateral to the vertical tumor component in some canine melanomas; (same canine patient as in B). Antimelan-A immunohistochemistry, red chromogen label, hematoxylin counter stain. Bar = 50 μm.

Mentions: No well-recognized classification scheme exists for mucosal melanomas from either species; therefore, evaluation included review of melanoma features previously documented (Goldschmidt and Hendrick, 2002; Patel et al., 2002; Pfister et al., 2012; Prasad et al., 2004; Smedley et al., 2011b). The salient histopathological features of mucosal melanoma were tabulated for both species (Table S2). Near universal concordance of these features was observed between canine and human melanoma (Table S2). Analogous architectural features important for diagnosing and staging melanoma were noted in both species (Figure 1). As recognized for cutaneous melanomas, both human and canine mucosal melanomas included the range of epithelioid, spindloid, mixed epithelioid/spindloid, or small round blue cell melanocyte morphologies. Some dog specimens included a lentiginous-like growth pattern within stratified squamous mucosal epithelium and a significant radial growth phase involving mucosal epithelium flanking the vertical growth phase (Figure 2). By the time of clinical recognition, mucosal melanomas are typically advanced with considerable local invasion, ulceration, focal necrosis, and even metastasis, particularly in the dog. In both species, there was considerable pleomorphism with significant variation in cell and nuclear size, shape, and presence of nucleoli (Figure S1 and Table S2). Given the substantial difference in incidence between various anatomic sites, the board chose not to compare frequencies of all features.


Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

Simpson RM, Bastian BC, Michael HT, Webster JD, Prasad ML, Conway CM, Prieto VM, Gary JM, Goldschmidt MH, Esplin DG, Smedley RC, Piris A, Meuten DJ, Kiupel M, Lee CC, Ward JM, Dwyer JE, Davis BJ, Anver MR, Molinolo AA, Hoover SB, Rodriguez-Canales J, Hewitt SM - Pigment Cell Melanoma Res (2013)

Lentiginous-like in situ involvement in mucosal melanomas by malignant melanocytes in the mucosal epithelium. Clusters of malignant melanocytes occur in the epithelial stratum basale and ascend into superficial strata. Photomicrographs of hematoxylin–eosin-stained (A) human mucosal melanoma and (B) canine mucosal melanoma. (C) Radial extension of malignant melanocytes is evident in the intact mucosal epithelium lateral to the vertical tumor component in some canine melanomas; (same canine patient as in B). Antimelan-A immunohistochemistry, red chromogen label, hematoxylin counter stain. Bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4066658&req=5

fig02: Lentiginous-like in situ involvement in mucosal melanomas by malignant melanocytes in the mucosal epithelium. Clusters of malignant melanocytes occur in the epithelial stratum basale and ascend into superficial strata. Photomicrographs of hematoxylin–eosin-stained (A) human mucosal melanoma and (B) canine mucosal melanoma. (C) Radial extension of malignant melanocytes is evident in the intact mucosal epithelium lateral to the vertical tumor component in some canine melanomas; (same canine patient as in B). Antimelan-A immunohistochemistry, red chromogen label, hematoxylin counter stain. Bar = 50 μm.
Mentions: No well-recognized classification scheme exists for mucosal melanomas from either species; therefore, evaluation included review of melanoma features previously documented (Goldschmidt and Hendrick, 2002; Patel et al., 2002; Pfister et al., 2012; Prasad et al., 2004; Smedley et al., 2011b). The salient histopathological features of mucosal melanoma were tabulated for both species (Table S2). Near universal concordance of these features was observed between canine and human melanoma (Table S2). Analogous architectural features important for diagnosing and staging melanoma were noted in both species (Figure 1). As recognized for cutaneous melanomas, both human and canine mucosal melanomas included the range of epithelioid, spindloid, mixed epithelioid/spindloid, or small round blue cell melanocyte morphologies. Some dog specimens included a lentiginous-like growth pattern within stratified squamous mucosal epithelium and a significant radial growth phase involving mucosal epithelium flanking the vertical growth phase (Figure 2). By the time of clinical recognition, mucosal melanomas are typically advanced with considerable local invasion, ulceration, focal necrosis, and even metastasis, particularly in the dog. In both species, there was considerable pleomorphism with significant variation in cell and nuclear size, shape, and presence of nucleoli (Figure S1 and Table S2). Given the substantial difference in incidence between various anatomic sites, the board chose not to compare frequencies of all features.

Bottom Line: The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis.Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation.We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Show MeSH
Related in: MedlinePlus