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153 Melanoma 1351

Human Melanoma Immunotherapy tumor. On divergent ends of the spectrum would be a
VetBooks.ir A similar approach has been used in human patients 0.5 cm haired‐skin melanocytoma, which is highly likely
to be cured with simple surgical extirpation, in compari-
with metastatic melanoma in the minimal residual dis-
ease setting. Although no clinical response data are son to a 5 cm high‐grade malignant oral melanoma with
a poor to grave prognosis.
available since these patients did not have measurable Similar to the development of a rational staging, prog-
disease, several Phase I trials of xenogeneic DNA vac- nostic and therapeutic plan for any tumor, two primary
cines have been completed. Across studies of tyrosinase questions must be answered: what is the local invasive-
and gp100 DNA immunization, approximately 40% of ness of the tumor and what is the metastatic propensity?
patients develop quantifiable CD8+ T cell responses to The answers to these questions will ultimately determine
the target antigen. the prognosis and appropriate therapies.
Two exciting new approaches which appear to confer a
survival benefit in human metastatic melanoma are the
use of the anti‐CTLA‐4 antibody ipilimumab (Yervoy TM , Anatomic Site
Bristol‐Myers Squibb) and the selective BRAF inhibitors The anatomic site of melanoma is highly, though not
vemurafenib (Zelboraf TM , Genetech) and dabrafenib completely, predictive of local invasiveness and meta-
(GSK2118436, GlaxoSmithKline), in patients who are static propensity. Melanomas involving the haired skin
BRAF V600 mutation positive. As a small subset of dogs which are not in proximity to mucosal margins often
with malignant melanoma have exon 11 KIT gene muta- behave in a benign manner. Surgical extirpation through
tions, the more routine use of KIT testing by polymerase a lumpectomy is often curative, but histopathologic
chain reaction (PCR) of CMM and subsequent use of c‐ examination is imperative for delineation of margins as
kit small molecule inhibitors (particularly in dogs with well as a description of cytologic features. The use of
advanced stage disease and/or lack of response to Ki67 IHC has been reported to more reliably predict
Oncept) should be considered. potential malignant behavior compared to classic histol-
Canine malignant melanoma strongly appears to be a ogy for cutaneous melanoma.
more clinically faithful therapeutic model for human Oral and/or mucosal melanoma has been considered
melanoma when compared to more traditional mouse an extremely malignant tumor with a high degree of local
systems, as both human and canine diseases are invasiveness and high metastatic propensity. This bio-
chemoresistant, radioresistant, share similar peculiar logic behavior is similar to the typically grave prognosis
metastatic phenotypes/site selectivity, and occur sponta- associated with human oral and/or mucosal melanoma.
neously in an outbred, immunocompetent scenario. It is Two recent studies have called the veterinary portion of
hoped that in the future, this same vaccine may also play this dogma into question and suggest benign oral
a role in the treatment of melanoma in other species melanomas can occur more frequently than previously
(e.g., horses, cats, humans, etc.) due to its xenogeneic published. Caution is necessary when assessing histo-
origins, and in melanoma prevention once the genetic pathologic descriptions suggesting a benign course for
determinants of melanoma risk in dogs are further oral melanoma as this author has seen approximately 25
defined. dogs over the last 10 years presenting with florid sys-
temic metastases with an original histopathologic report
suggesting an expectation for a benign clinical course
Prognosis based on a high degree of differentiation. Similar to cuta-
neous melanoma, Ki67 appears to have prognostic
Melanomas in dogs have extremely diverse biologic import in canine oral melanoma.
behaviors, depending on a large variety of factors. A Anatomic sites of intermediate prognostic significance
thorough understanding of these factors helps the clini- between generally benign‐acting haired‐skin melanomas
cian to delineate in advance the appropriate staging, compared to often malignant and metastatic oral/
prognosis, and treatment options. The primary factors mucosal melanomas in dogs include melanomas of the
which determine the biologic behavior of an oral mela- digit and footpad. Dogs with melanoma of the digits
noma in a dog are site, size, stage, and histologic without lymph node or further metastasis treated with
parameters. Unfortunately, even with a comprehensive digit amputation are reported to have median survival
understanding of all these factors, there are melanomas times of ~12 months, with 42–57% alive at one year and
which have an unreliable biologic behavior; hence the 11‐13% alive at two years. Unfortunately, metastasis
need for additional research into this relatively common, from digit melanoma at presentation is reported to
heterogeneous, but frequently extremely malignant be ~30–40%, and the aforementioned outcomes with