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.

Gross Description:  

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.

Histopathologic Description:

Haired 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.

Morphologic Diagnosis:  

Haired skin: Amelanotic malignant melanoma, guinea pig, Cavia porcellus

Lab Results:  

Immuno-histochemically the neoplastic cells were positive for Melan-A and PNL2.


Amelanotic melanoma

Contributor Comment:  

Melanomas are 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.

JPC Diagnosis:  

Haired skin: Amelanotic melanoma, guinea pig, Cavia porcellus.

Conference Comment:  

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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Click the slide to view.

2-1. Haired skin, rabbit.

2-2. Haired skin, rabbit.

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