Pigmented epithelioid melanocytoma


    Pigmented epithelioid melanocytoma (PEM) is a recently recognized citation melanocytic neoplasm which can occur in the setting of Carney complex or in a sporading. It encompases lesions previously diagnosed as epithelioid blue nevus of Carney complex and the majority of cases previously considered as so-called "animal-type" malignant melanoma.

    Histological features of PEM were first described by Dr. Aiden Carney who coined the term epithelioid blue nevus for a histologically distinct, rare melanocytic proliferation occuring in patients with Carney Complex. citation

    The term animal-type melanoma was referred to a group of darkly pigmented melanocytic proliferations, reminiscent of melanomas occuring in animals and especially gray horses. This tumors were considered malignant as they had known potential for lymph node metastases.

    In 2004, Zembowicz et al., recognized that most cases considered to be animal-type melanoma are histologically indistinguishable from epthelioid blue nevus of Carney complex. Importantly, they results suggested that these lesions frequently metastasize to lymph nodes. Yet, they clinical behaviour appeared to be better then in conventional melanoma. Therefore, they coined the term PEM to emphasize unique nature of this tumor and need to distinguish it from benign nevi and malignant melanoma. They proposed that PEM is a neoplasm which can arise in the context of a Carney complex, or outside of the complex in a sporadic setting.

    Clinical Presentation:

    PEM usually presents as a slowly-growing darkly pigmented dermal nodule.

    The key clinical featuers include:

    • wide age distribution (from infancy to older) with the mean age in late 20's and early 30's (early 20's in PEM arising in Carney complex)
    • equal occurence in both sexes
    • frequent occurence in ethnic groups resistant to conventional melanoma (Hispanics, Asians, etc)
    • generalized site distribution
    • involvement of mucosa and sun protected areas (penis, vulva)

    Clinical differential diagnosis:

    • blue nevus
    • cellular blue nevus
    • congenital blue nevus
    • malignant melanoma

    Histological features:

    At a scanning magnification, PEMs are heavily pigmented dermal melanocytic tumors with infiltrative borders. They often extend into subcutaneous tissue along periadnexal connective tissue of hair follicles, pilar muscle, eccrine coils, or neurovascular bundles. At the periphery, tumor cells permeate between preexisting collagen fibers with no or minimal desmoplastic stromal response.

    Many but not all lesions abutt  the epidermis and induce epidermal hyperplasia. However some are separated from the epidermis
    by a Grenz zone of uninvolved dermis. Ulceration can be present in sporadic tumors and was the only feature distinguishing sporadic from Carney complex associated PEMS, where it is rare.  

    Junctional component is either absent of consists of isolated dendritic cells with epithelioid cell features along dermo-epidermal junction. Nest formation is very rare but can occur. In some cases, PEM is a component of a combine nevus.  

    All tumors were composed of a mixture of 3 distinct cell types: dendritic, darkly pigmented polygonal and large epithelioid. Dendritic cells resemble dendritic cells of blue nevus but their nuclei are epithelioid with vesicular nuclei and visible nucleoli. In many cases, the most abundant are medium-sized round to polygonal cells with heavily pigmented cytoplasm obscuring nuclear detail. The most characteristic cells are large epithelioid cells. They are easiest to find at the periphery of the lesion. The large epitheloid cells are usually less pigmented or have a had dot-like melanin granules distributed at the periphery of the cell forming a concentric rim around a halo of
    nonpigmented cytoplasm. The nuclei are large, vesicular with round or rarely irregular contours and prominent eosinophilic or amphophilic nucleoli. Occasional cells contain multiple nuclei. The number of atypical epithelioid cells varies from few to numerous.
    Mitotic activity in PEM is infrequent and rangeds from 0 to 3 mitoses/mm2. Non-brisk lymphocytic infiltrate can be present focally in
    some cases, expecially focally  in the areas con-taining melanophages.

    Histological differential diagnosis: 

  • blue nevus with epithelioid cells
  • cellular blue nevus
  • Spitz nevus
  • congenital blue nevus
  • malignant blue nevus
  • Histological pearls:

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    Management and treatment:

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    80% of PEM show loss of expression of protein kinase A regulatory subunit 1 alfa (R1alfa). citation The R1alfa gene is mutated in 44% of families with Carney complex. R1alfa in a key regulatory cofactor in cAMP signalling pathway, which is involved in the regulation of melanogenesis and proliferation of melanocytes.