Begrijpen van Blauwe Naevus Huidziekten - Oorzaken, Symptomen en Behandelingen

Primary orbital melanoma arising in an atypical diffuse (plaque-like) blue naevus/melanocytosis: a case report and review of literature

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All data generated or analysed during this study are included in this published article.

Patient Management

If the microscopic features of the biopsy are concerning, with tumoral necrosis, cellular atypia and pleomorphism, the presence of mitoses (>2/mm 2 ), cell crowding, infiltrative growth pattern, expansile growth, or the presence of junctional activity (ie, pagetoid epidermal invasion), then an additional surgical procedure may be indicated. The role of sentinel lymph node biopsy in such a situation has not been clearly defined in patients with these confusing melanocytic lesions.

Gonzalez-Campora, R, Galera-Davidson, H, Vázquez-Ramírez, FJ, Díaz-Cano, S. “Blue nevus: classical types and new related entities. A differential diagnostic review”. Pathol Res Pract. vol. 190. 1994. pp. 627-35. (An overview of the microscopic characteristics of blue nevi.)

Murali, R, McCarthy, SW, Scolyer, RA. “Blue nevi and related lesions: A review highlighting atypical and newly described variants, distinguishing features and diagnostic pitfalls”. Adv Anat Pathol. vol. 16. 2009. pp. 365-82. (This article is a thorough review of blue nevi and associated lesions, focusing strongly on the histologic features and immunohistochemical profiles that distinguish these lesions from each other.)

Lee, HY, Na, SY, Son, YM, Kang, HK, Baek, JO, Lee, JR. “A malignant melanoma associated with a blue nevus of the lip”. Ann Dermatol. vol. 22. 2010. pp. 119-24. (A case report of a probable blue-nevus-like melanoma that highlights that these lesions can present in unusual mucocutaneous locations as well as extracutaneous locations. The authors also review the controversy regarding the term "malignant blue nevus" and melanoma in association with a blue nevus.)

Zembowicz, A, Phadke, PA. “Blue nevi and variants: An update”. Arch Pathol Lab Med. vol. 135. 2011. pp. 327-36. (A review of the histologic and immunohistochemical profiles of blue nevi and similar lesions, with a summary of recent investigations into the mutations and molecular markers present in blue nevi as compared with melanocytic nevi and melanoma.)

DISCUSSION

BN usually appears in childhood or adolescence and is rarely congenital. 1,2 The most common form, DBN, is presented as a solitary, symmetrical and intensely pigmented papule or nodule measuring less than 1cm and occurs mainly on the back of the hands or feet, or locations as face and scalp. 1,2 It can affect mucous membranes and extracutaneous sites. CBN variant is a nodule or plaque, usually 1 to 3 cm in diameter, with smooth or irregular surface, most commonly found in the glutei, sacrococcygeal area or scalp. 1,2 Growth is unusual and should raise suspicion of malignant degeneration. 1,2,4,5

CBN differentiates from DBN by pigmented melanocytes in the dermis, grouped spindle cells containing little or none melanin, that frequently penetrate the subcutaneous layer as well-defined islands. 1,2,3,4,5,6 Although, there is no uniform criteria for the distinction, high mitotic activity (>2/mm2), marked cytological atypia, necrosis, deep infiltration and atypical mitotic figures favor melanoma. 1,2,3,4,5,6 At least one of the following findings characterizes CBN as atypical: asymmetry, focal infiltration or hypercellularity, pleomorphism with hyperchromasia, proeminent nucleoli, and occasional mitoses (< 2/mm 2 ) . 1,2,3,4,5,6

Because of the overlapping intermediate features between atypical CBN and malignant BN/melanoma, its distinction remains a challenge. 5,7 ACBNs tend to show a higher proliferative index by proliferating cell nuclear antigen (PCNA) and Mib-1 as well as a significantly higher mitotic rate compared with typical CBN.

Argyrophilic nucleolar organizer regions (AgNORs) expression has been considered in skin melanocytic lesion prognosis. AgNOR mean number per nucleus (AgNOR count), their distribution (configuration) and the ratio AgNOR area/nuclear area can be useful to discriminate benign from malignant melanocytic lesions, although with considerable overlap. Usually, there is a linear relation between AgNOR counts and PCNA immunostaining scores, which can be additional parameters for the diagnosis of malignant CBN. 7

Nevus spilus (spilus: “speckled”)

Nevus spilus is an MN characterized by a brown macule. The café‐au‐lait component (of very varying size) is usually present at birth while speckles develop during the first years of life and can represent various different types of MN.

These include Clark or combined MN, Spitz nevi, and rarely also blue nevi. Nevus spilus is therefore a combined MN. Its risk of malignant transformation is not clearly defined but is reported to be between 0.13 % and 0.2 %. There is one case report in the literature of a patient with multifocal melanomas within a nevus spilus occuring in late adult life [43].

The underlying mutation in phacomatosis pigmentokeratotica (Table 1 ) is located in the HRAS gene. Sometimes this condition is associated with additional neurological symptoms such as epilepsy and deafness [47].

Deterrence and Patient Education

Counseling regarding the potential risks for the offspring with or at risk for Carney complex should be offered to adults and children before they reach childbearing age. The availability of prenatal and preimplantation genetic diagnosis should also be discussed. Genetic testing for mutations in the protein kinase A type I-alpha regulatory subunit (PRKAR1A) is indicated for other potentially affected family members of patients with Carney complex. However, clinical surveillance is advisable for at-risk family members even when a PKAR1A pathogenic variant is not identified.

Patients should be educated about the nature of their disease and concerning symptoms such as signs of cardiac embolism and tumor formation. Ongoing monitoring is crucial in decreasing the complications of Carney complex.