Unknown age and
gender, guinea pig, (Cavia porcellus).The animal
developed a skin tumor of 1 cm in diameter at the right flank. The mass was
completely resected. Unfortunately, further clinical data were not available.
A 2 x 1
cm skin sample was submitted for histopathologic examination. Centrally there
was a well-demarcated, 1 x 1 cm partially exophytic firm nodule. The cut
surface was light brown.
skin: Elevating an ulcerated epidermis and infiltrating into the underlying
dermis (in some slides, tumor overlies an intact epidermis) is densely
cellular, well-demarcated, exophytic, partly infiltrative and ulcerated,
unencapsulated neoplasm composed of sheets of pleomorphic round cells within a
scant fibrovascular stroma. Neoplastic cells are round to polygonal, up to 40
um in diameter with variable distinct cell borders and moderate amounts of eosinophilic
cytoplasm. Nuclei are round to oval, centrally located with finely stippled
chromatin and up to four prominent magenta nucleoli. Mitoses average 2-3 per
high power field (some bizarre) and cells show moderate anisocytosis and
anisokaryosis. Occasionally, vascular invasion of tumor cells can be observed
(not in all slides). There are multifocal hemorrhages within and around the
tumor and hemorrhagic and serocellular crusts at the ulcerated surface. The
adjacent skin is hyperplastic with a moderate perivascular infiltration with
lymphocytes, plasma cells, and few heterophils.
Haired skin: Amelanotic malignant melanoma, guinea
pig, Cavia porcellus
the neoplastic cells were positive for Melan-A and PNL2.
described in a variety of animal species including domestic animals and
wildlife species. However, they are most common in dogs, horses and some breed
of swine10, only few reports of melanoma in birds, laboratory
animals and more recently in reptiles exist.6,16 The histologic
diagnosis of melanoma is complicated due to variable degree of pigmentation and
the high variability of cell shapes. With the help of immunohistochemistry,
most amelanotic melanoma can be routinely diagnosed.3,4,10
With our case, we present a well-known neoplasm in an unusual species. Case reports of spontaneous melanoma in the guinea pig are extremely rare, but the guinea pig is a well-defined model of experimental melanoma using the potent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon.7 This substance is proven to transform cells in different oncogenic pathways.2
Mutations that affect cell cycle control (p16/INK4a, CDK4), pro-growth pathways (growth factor receptors, RAS, BRAF), and telomerase were identified in the patho-genesis of malignant melanoma. Furthermore, melanomas can be inherited, and UV light-induced DNA damage plays a role as do other factors.8 The most common naturally occurring skin tumors in guinea pigs are trichofolliculomas. They are a subtype of trichoepithelioma and occur as expansible, often centrally cystic neoplasia in the skin often of the lumbosacral region.13,15,18 Other tumors, like fibrosarcoma, lipoma, sebaceous gland adenoma, and hemangioma were also reported in this species.
In this melanoma, there is abundant vascularity. As observed in other species5,12 the amount of blood vessels may be a prognostic factor for this neoplasia in guinea pigs, and particularly mast cells may play a significant role in angiogenesis as the major source of VEGF.1Unfortunately, further information regarding the clinical course of the presented case was not available.
Amelanotic melanoma, guinea pig, Cavia porcellus.
Melanocytic neoplasms arise from melanocytes or melanoblasts which are derived
from the neural crest ectoderm. As mentioned by the contributor, melanomas have
been identified in most veterinary species and humans. The histologic diagnosis
of melanomas is sometimes complicated due to the variability of pigmentation
and arrangement of neoplastic cells into clear cells (balloon cell), spindle
cell, epithelioid cell, and signet ring cell histomorphology.10
Additionally, there are often multiple different tumor cell morphologies within
a single neoplasm. For this reason, melanomas are sometimes referred to as one
of the great imitators due to their common embryologic connection with both
neural and epithelial origin.10
This case nicely demonstrates this point, due to variation in round to polygonal cellular appearance across various regions of the neoplasm. Despite the rarity of melanocytic neoplasms in guinea pigs and the lack of melanin granularity in this case, most conference participants included amelanotic melanoma high within their differential diagnosis. Prior to the conference, the Joint Pathology Center ran the histochemical stain Fontana-Masson and immuno-histochemical stains melan-A and S100. The Fontana-Masson stain highlighted multifocal positive argentaffin granules and melanin within the cytoplasm of neoplastic cells. Additionally, neoplastic cells are immunopositive for S100 and melan-A red, confirming the diagnosis of an amelanotic melanoma, in this case.
As mentioned by the contributor, trichofolliculomas are the most common tumor in the skin of guinea pigs; although, spontaneous neoplasms in this species are rare in animals under three years old.13 These benign dome-shaped subcutaneous nodules, typically less than 2cm in diameter, most commonly occur along the dorsal lumbar region and may represent a hamartomatous rather than a neoplastic process.10,13 Trichofolliculoma development is thought to occur secondary to inhibition of bone morphogenic protein (BMP), an important tumor suppressor gene.13,14,18 Studies indicate that BMP plays a critical role in maintaining homeostasis of hair follicles and regulation of skin develop-ment.14 In addition, BMP is an important growth factor for a variety of tissues throughout the body and its con-centration is tightly regulated in health. Interestingly, recent research in humans have shown that absence of BMP signaling leads to the progression of colorectal carcinoma; conversely, overexpression of BMP signaling induces epithelial-mesenchymal transition, tumor invasion, and metastasis in a variety of malignant neoplasms.9,11,14
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