Animal-Type Melanoma – a Mini-Review Concern­ing One of the Rarest Variants of Human Melanoma

Summary

The authors declare they have no potential conflicts of interest concerning drugs, pro­ducts, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE recommendation for biomedical papers.

Submitted: 17. 6. 2017

Accepted: 1. 11. 2018

Described for centuries in the equines, especially gray horses, as “equine me­lanotic dis­ease”, it was later recog­nized in non-equine animal models and in humans, particularly on non UV-exposed skin. Animal-type melanoma, also known as pigmented epithelioid melanocytoma (PEM), is characterized by nodules and fascicles of epithelioid transformed melanocytes with pleomorphic nuclei and strik­ing pigmentation, dendritic cells, numerous melanophages and, sometimes, lymphocytic infiltrate [1,2]. Up-to-date, only small series have been reported in humans and, therefore, its bio­logical behavior remains unclear [3]. In 2010, Ludgate et al. examined the clinical behavior of 8 cases of equivocal and 14 cases of unequivocal PEM, conclud­ing that it shows a propensity for regional nodal metastases [4]. By systematic review and meta-analysis of the English literature, in 2015, Vyas et al. have identified 190 cases of PEM. The median Breslow depth was 3.8 mm, loco-regional recurrence was found in 15 cases, recurrence with distant metastases in 6 cases and death occurred in 5 patients [5]. Recently, Bax et al. have suggested that the tumor follows an indolent clinical course, with very low risk of spread beyond regional lymph nodes [6]. Given the complexity of the matter, Elder and Murphy proposed a histological categorization of PEM and PEM-like lesions, with distinctive clinicopathological and bio­logic attitudes [7]. In this review, we briefly highlight the current information about this rare dis­ease.

Epithelioid blue nevus resembl­ing PEM

It is a hyperpigmented, poorly circum­scribed, dermal lesion, which shows heavily pigmented globular mela­no­cytes, intermingled with hypo­pig­­ment­ed spindle melanocytes. Commonly misinterpreted as classical blue ne­vus, in which markedly pig­mented, bipolar, spindled cells are associated with a host-derived fibroblastic react­ion, or as cellular blue nevus, a der­mal-hypo­dermic benign neoplasm characterized by an alveolar or fasci­cular pattern of growth sometimes with neuronevoid aspects, or as PEM (see later); its exact identification is important because it is strongly as­sociated with the Carney complex [8]. Conservative excision is generally recommended; moreover, affected patients (and their relatives) should be considered at risk for other diseases of the Carney complex, espe­cially cardiac myxoma [8].

PEM

Not associated with the Carney com­plex, it is quite similar to epithelioid blue nevus at scann­ing magnification, but cytological atypia and sparse low mitogenicity are encountered by a careful histological inspection, exactly as observable in melanocytic tumors of uncertain malignant potential (MELTUMP) [9– 11]. When epidermal pa­getoid diffusion and overtly anaplastic nuclei are present, a dia­gnosis of malignant melanoma with prominent pigment synthesis can be also proposed [2]. Although the tumor can be lethal given the depth of invasion accord­ing to Magro et al., it seems to be less aggressive than other usual or unusual vertical growth phase melanomas [1,2]. Local lymph nodes are often involved by metastases –⁠ lymph node sentinel bio­psy is recommended and a wide re-excision (1– 2 cm margins) must be performed. Follow-up, as in any case of invasive malignant melanoma, should be conducted [2].

Tumoral melanosis mimick­ing PEM

It is a nodular cluster of melanophages, and it may represent a complete re­gression of a vertical growth phase melanoma or of a pigmented basal cell carcinoma [7]. In the radial and vertical growth phases, regression has negative impact on prognosis [12– 16]; therefore, the follow-up should be very accurate since the lesion could be the result of a preceding, completely regressed melanoma [17– 21].

A proper dia­gnostic fram­ing is crucial in these controversial cases and a good histology in the hands of an expert dermatopathologist remains the most reliable dia­gnostic start­ing point. Moreover, a loss of expression of cAMP-dependent protein kinase type I-alpha regulatory subunit, an enzyme encoded by the tumor-suppressor gene PRKAR1A, has been found in PEM, but not in common melanoma or other melanocytic lesions [22]. Therefore, it appears to have a great dia­gnostic value in help­ing to distinguish PEM from PEM-like lesions, which mimic the former histologically.

The authors declare they have no potential conflicts of interest concerning drugs, pro­ducts, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE recommendation for biomedical papers.

Submitted: 17. 6. 2017

Accepted: 1. 11. 2018

Dr. Luca Roncati, MD, PhD

Department of Medical and Surgical Sciences

Institute of Pathology

University Hospital of Modena

Policlinico

via del Pozzo, 71

I-41124 Modena, Italy

e-mail: emailmedical@gmail.com