Black and Brown Oro-facial Mucocutaneous Neoplasms

Abstract

Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority of pigmented lesions in the head and neck region are the result of benign, reactive factors such as post-inflammatory melanosis. However, it is not uncommon to discover a range of muco-cutaneous black and brown neoplasms in the oro-facial area. The majority of black/brown pigmented neoplasms are melanocytic in origin; these are neoplasms of neural crest derivation. Melanocytic nevi are a diverse group of benign neoplasms that are the result of specific oncogenic mutations. They are common on cutaneous surfaces but can manifest in mucosal sites. Currently, nevi are classified based on clinical and histological criteria. The most common cutaneous and oral mucosal nevus is the acquired melanocytic nevus; nevi do not pose an increased risk for the development of malignant melanoma. Emerging information on specific genetic differences supports the notion of biologically distinct nevi. This article will review the classic clinical and microscopic features of nevi commonly found in the head and neck region, and discuss emerging concepts in nevus pathogenesis and taxonomy. Melanoma is a malignant melanocytic neoplasm and is a result of cumulative genetic deregulation. The etiology of malignant melanoma (MM) is multifactorial and includes underlying genetic susceptibility, UV radiation, skin-type, and race. The majority of MM occurs on cutaneous surfaces and less commonly on mucosal and extra-cutaneous visceral organs. Regardless of location, MM exhibits clinical-pathological features that relate to horizontal or vertical tumor spread. Cutaneous and mucosal MM typically present as asymmetrical, irregularly bordered, large (> 0.5 cm), heterogeneous brown-black lesions with foci of erythema, atrophy or ulceration. As with melanocytic nevi, advances in melanomagenesis research have revealed primary oncogenic BRAF and NRAS mutations associated with cutaneous MM. Unlike their cutaneous counterparts, mucosal melanomas exhibit primary oncogenic alterations in c-KIT and other genes. This article will discuss the role of specific primary oncogenic and secondary/tertiary genetic defects in differential clinical presentation, anatomic distribution, future classification changes, and targeted therapy of melanoma. The clinical and microscopic features of mucosal melanomas and a summary of management guidelines will be discussed. Additionally, this article will cover the salient features of melanocytic neuroectodermal tumor of infancy, a neoplastic entity that can involve the oro-facial region, and the clinical-pathological features of selected, commonly occurring pigmented ectodermally-derived neoplasms that are often part of the clinical differential diagnosis of black-brown pigmented lesions.

Keywords: Melanocytic nevi; Melanoma; Oral melanocytic nevus; Oral melanoma; Pigmented neoplasm.

Fig. 1

Clinical features of cutaneous melanotic nevi—head and neck region. a Congenital nevus—typically presents at birth. Note the size, surface texture and presence of appendageal structures. b–d Acquired melanocytic nevi—present as discrete, symmetrical < 0.5 cm uniformly colored pigmented or non-pigmented lesions. b Junctional nevus—discrete macule. c Compound nevus—macule with a papular elevation on the right lower aspect corresponding to area of junctional nevocyte. d Intradermal nevus—nodule with focus of pigmentation. e Common blue nevus—discrete black-blue pigmented elevated lesion. f Cellular blue nevus—elevated blue-black pigmented lesion on the scalp

Fig. 2

Clinical features of acquired melanocytic nevi—oral mucosal and vermilion. a–c Acquired melanocytic nevi (junctional/compound/intramucosal) oral mucosal lesions present as discrete, symmetrical < 0.5–1 cm uniformly pigmented or non-pigmented mucosal lesions typically on the hard palate or gingival surfaces. d Intradermal nevus—discrete, mamillated nevus on the lower vermilion of the lip

Fig. 3

Microscopic features of acquired melanocytic nevus maturation—cutaneous. a Intradermal nevus (low magnification)—nevi exhibit cardinal signs of maturation and nesting. Nevocytes migrate from the epidermis to dermis in a regulated manner over their lifetime (black arrow). Nevus cells surround normal appendageal structures; ruptured pilosebaceous units may undergo dystrophic calcification (tip of black arrow). b Intradermal nevus—no evidence of junctional activity at epidermo-dermal junction. Note that nevocytes exhibit round theques/nests close to the epidermis and transform into spindle-shaped (neurotized) cells deeper in the dermis. c Nevus cells close to the epidermal surface arranged in round theques/nests. Cell exhibit banal cytology and intracytoplasmic melanin pigment. d Nevocytes in the deep dermis exhibit spindle-shaped nuclear features and surround normal dermal structures. Note nevus cells around nerve fiber and adipose tissue

Fig. 4

Microscopic features of oral mucosal nevi. a, b Compound nevus. Note nevocyte nests at the junction of the epithelium and lamina propria with intracytoplasmic melanin pigmentation. Nevocytes arranged in theques exhibit banal nuclear features. c, d Intramucosal nevus. This is a discrete nodule with no evidence of junctional nevocyte activity. Nevocytes exhibit maturation from the surface taking on a neurotized morphology deeper in the submucosa. Nevocytes exhibit S-100 expression (inset). e, f Common blue nevus. Nevocytes within the connective tissue (arrow); note the absence of junctional activity and theque formation. Nevus cells are spindle shaped, exhibit banal cytology, contain melanin pigment, and often arranged parallel to the surface epithelium; this distribution and the Tyndall effect corresponds to the blue-black appearance of these lesions

Fig. 5

Malignant melanoma—cutaneous and mucosal. a, b Melanoma of the right lower face and scalp. Note the asymmetry, irregular borders, variegation in color and size > 1.0 cm. c Primary oral mucosal melanoma. Irregularly shaped, asymmetrical and variegated black–brown lesion on the left maxillary gingiva. Note the multiple pigmented areas. This patient complained of mobile teeth in the upper left quadrant and tumor invasion into the surrounding periodontium and alveolar bone. There was ill-defined lytic change around the canine and lateral incisor. d Mucosal melanoma (high magnification) Tumor cells are large, polygonal and exhibit marked cytoplasmic and nuclear pleomorphism with prominent nucleoli, melanin pigmentation and high mitotic index. e, f Primary mucosal melanoma (low magnification; immunohistochemistry) Melanoma arising from oral mucosa infiltrating the lamina propria and submucosa. Immunohistochemistry (HMB-45) highlights tumor cells originating from overlying epithelium. Similar expression was noted with S-100 and Melan A

Fig. 6

Melanoma, Melanotic neuroectodermal tumor and other cutaneous pigmented neoplasms. a, b Metastatic melanoma—examples of melanoma metastatic to the jaw bone. Tumor cells resemble original tumor, infiltrate alveolar bone and exhibit melanoma immunohistochemical markers (HMB-45, Melan-A, S-100; insets), c Melanotic neuroectodermal tumor of infancy (MNTI) Rapidly growing, pigmented, ulcerated mass of the anterior mandible in an infant, d MNTI microscopic features. Biphasic tumor population—clusters of large polygonal epithelioid melanosome containing cells (yellow arrow), loosely arranged clusters of small, round cells with blue-black nuclei (black arrow), e Seborrheic keratosis—pigmented. Solitary, discrete, pigmented exophytic waxy cutaneous nodule on the left upper face, f Basal cell carcinoma—pigmented. Ulcerated, umbilicated nodule on the right tip of the nose with black–brown pigmentation