Dedifferentiated Melanoma: A Diagnostic Histological Pitfall-Review of the Literature with Case Presentation

Abstract

Dedifferentiated melanoma is a particular form of malignant melanoma with a progressive worsening of the patient's clinical outcome. It is well known that melanoma can assume different histo-morphological patterns, to which specific genetic signatures correspond, sometimes but not always. In this review we address the diagnostic difficulties in correctly recognizing this entity, discuss the major differential diagnoses of interest to the dermatopathologist, and conduct a review of the literature with particular attention and emphasis on the latest molecular discoveries regarding the dedifferentiation/undifferentiation mechanism and more advanced therapeutic approaches.

Keywords: dedifferentiated melanoma; diagnosis; immunohistochemistry; malignant melanoma (MM); pitfall.

Figure 1

(A) Lesion consisted of a nodular part of about 3 cm in diameter and a flat, blackish, elongated part of about 1.5 cm. (B) Dermoscopically, the lesion was characterized by marked chromatic asymmetry, with radial striae and peripheral pigment escape, with irregular globules.

Figure 2

(A) The “shoulder” of the lesion was made up of atypical melanocytes, which ascended to the level of the dermoepidermal junction, morphologically suggestive of malignant melanoma. Note that the neoplastic cells had a tendency to invade the superficial/middle dermis (Hematoxylin-Eosin, Original Magnification: 10×). (B) Histological micrograph that highlights the two morphologically different components of dedifferentiated melanoma (Hematoxylin–Eosin, original magnification: 20×). (C,D) Nodule consisting of pleomorphic, atypical elements, with very numerous typical and atypical mitotic figures, eosinophilic intracytoplasmic paranuclear inclusions, nuclei with thinned chromatin and numerous central and peripheral nucleoli (Hematoxylin–Eosin, original magnification: 20× and 40×). (E) Immunostaining for HMB-45, which is strongly represented in the melanocyte proliferation constituting the “shoulder” of the lesion morphologically represented in (A). Note the total negativity of HMB-45 of atypical nodular proliferation (Immunohistochemistry, original magnification: 10×) (F) Immunostaining for CD10 strongly positive in the exophytic polypoid nodular component and negative in the shoulder of the lesion (Immunohistochemistry, original magnification: 10×).

Figure 2

(A) The “shoulder” of the lesion was made up of atypical melanocytes, which ascended to the level of the dermoepidermal junction, morphologically suggestive of malignant melanoma. Note that the neoplastic cells had a tendency to invade the superficial/middle dermis (Hematoxylin-Eosin, Original Magnification: 10×). (B) Histological micrograph that highlights the two morphologically different components of dedifferentiated melanoma (Hematoxylin–Eosin, original magnification: 20×). (C,D) Nodule consisting of pleomorphic, atypical elements, with very numerous typical and atypical mitotic figures, eosinophilic intracytoplasmic paranuclear inclusions, nuclei with thinned chromatin and numerous central and peripheral nucleoli (Hematoxylin–Eosin, original magnification: 20× and 40×). (E) Immunostaining for HMB-45, which is strongly represented in the melanocyte proliferation constituting the “shoulder” of the lesion morphologically represented in (A). Note the total negativity of HMB-45 of atypical nodular proliferation (Immunohistochemistry, original magnification: 10×) (F) Immunostaining for CD10 strongly positive in the exophytic polypoid nodular component and negative in the shoulder of the lesion (Immunohistochemistry, original magnification: 10×).

Figure 3

Literature search and article selection according to PRISMA guidelines.