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Uncommon Variants of Melanoma and Collision Scenarios

The purpose of this chapter is to present unusual morphologic variants of primary cutaneous melanomas, which are not the subject of specific chapters elsewhere in the book. The main value of mentioning and describing these variants is for the practicing pathologist to be aware of the morphologic spectrum of melanomas. Since there is no known clinical significance or associated molecular signature to the variants described herein,…

Melanoma Arising in Association With and/or Simulating a Blue Nevus

Melanoma may develop in association with a blue nevus (BN), in particular a cellular blue nevus (CBN), or closely simulate the appearance of a BN (BN-like melanoma). Such tumors have historically been referred to as malignant blue nevus . Malignant blue tumor would be a preferable term to avoid the oxymoron of “malignant nevus.” Melanomas arising in association with a blue nevus may also be termed…

Spitzoid Melanoma

There is currently no consensus definition on what constitutes a “spitzoid” melanoma. The term is most often used in a practical sense referring to a diagnostic pitfall: a melanocytic neoplasm that at first glance simulates the appearance of a Spitz nevus but is classified as melanoma, either based on clinical follow-up (distant metastasis or death), compelling scientific evidence (e.g., detection of genomic aberrations associated with melanoma),…

Nevoid Melanoma

The term nevoid melanoma refers to melanomas, which closely resemble a melanocytic nevus under the microscope. It primarily refers to a diagnostic pitfall. In principle any type of nevus could be mistaken for melanoma, and the term “nevoid” melanomas could therefore include melanomas simulating a Spitz nevus (spitzoid melanoma), blue nevus (blue nevus–like melanoma), deep penetrating nevus (deep penetrating nevus–like melanoma), or other nevi. One may…

Desmoplastic Melanoma

Desmoplastic melanoma (DM) is a rare variant of melanoma that is histopathologically characterized by the dispersion of invasive tumor cells in a collagen-rich stroma. The tumor cells are usually amelanotic and predominantly fusiform in appearance. DM can be confused with a scar or fibroma, with potentially tragic consequences. Errors related to DM are disproportionally common among medical malpractice claims of melanoma misdiagnosis. Clinical Findings DM accounts…

Nodular Melanoma

Any melanoma, including the common variants superficial spreading, lentigo maligna, and acral lentiginous melanoma, may form an invasive tumor nodule. However, the presence of a prominent nodule does not equate a nodular melanoma (NM) subtype ( Fig. 15.1 ). According to the World Health Organization (WHO) classification of skin tumors, the NM subtype is defined conceptually as “malignant melanoma exclusively in vertical growth phase.” Or in…

Acral and Subungual Melanoma

General Comments Melanocytic lesions of acral skin are at particular risk of being misdiagnosed for a variety of reasons. On the one hand, acral melanoma (AM) may have very subtle histologic features, particularly in the early in situ stage and at its periphery. Such lesions may not be diagnosed as melanoma by the unwary pathologist. Indeed, misdiagnosis and delayed treatment of AM represents a common cause…

Superficial Spreading Melanoma

The term superficial spreading melanoma (SSM) is commonly used to refer to melanomas characterized by a combination of clinical and histopathologic findings. They usually occur at intermittently sun-exposed sites, manifest as peripherally spreading surface lesions, and display an intraepidermal growth of melanocytes characterized by the presence of nests and/or pagetoid melanocytes. SSM is the most common melanoma variant among adolescents and young to middle-aged adults. In…

Lentigo Maligna Melanoma

Nomenclature Lentigo maligna melanoma (LMM) refers to a variant of melanoma that tends to occur on chronically sun-exposed skin of elderly Caucasians and is usually histopathologically characterized by a distribution of predominantly solitary units of melanocytes at the dermoepidermal junction. Both clinically (brown macules or patches) and with regard to the associated epidermal changes (hyperpigmentation, slight elongation of rete ridges), the lesions often display lentigo-like features.…

Histopathologic Diagnosis of Melanoma

Microscopic examination and clinic-pathologic correlation represent the “gold standard” for the diagnosis of melanoma. Among experienced pathologists, the assessment of melanocytic lesions by histopathologic criteria is fairly accurate and reliable in most cases, but it cannot be expected to provide a definitive answer about the nature of a melanocytic tumor in every case. Diagnostic uncertainty and controversy tend to be associated with tumors displaying features overlapping…

Pigmented Epithelioid Melanocytoma

Pigmented epithelioid melanocytoma (PEM) is a rare melanocytic neoplasm composed of pigmented epithelioid and dendritic melanocytes with large vesicular nuclei. It was first described in patients with Carney complex under the rubric of epithelioid blue nevus. Carney complex is a rare familial cancer and lentiginous syndrome associated with mostly benign or indolent neoplasms, including myxomas, psammomatous melanotic schwannomas, and endocrine neoplasms. In spite of significant cytological…

Combined Melanocytic Nevi

Combined melanocytic nevi are benign melanocytic proliferations with two (or more) histopathologic nevus phenotypes in the same clinical lesion. Their clinical importance lies in the diagnostic pitfall they pose—their possible confusion with melanoma. Knowledge of the clinical and histopathologic spectrum of features that occur in combined nevi is useful to enable the pathologist to avoid an erroneous diagnosis of melanoma associated with a preexisting nevus. Combined…

Persistent/Recurrent Melanocytic Nevi, Traumatized Nevi, and Nevi Changing Under Therapy

Features of traumatized or persistent nevi appearing at the site of prior surgery may mimic melanoma, a phenomenon recognized for several decades. The histologic distinction between a persistent nevus and a regressing melanoma may in some cases, especially in partial biopsy specimens, be very challenging; therefore correlation with the clinical context and the histology of the prior specimen is essential. This chapter discusses the clinical and…

Melanocytic Nevi of Special Sites

Special site nevi or nevi with site-related atypia are terms used to describe melanocytic nevi located in some anatomic regions that, although benign, show unusual or atypical microscopic findings that may lead to diagnostic confusion with melanoma. A number of special sites have been proposed, including the ear, acral skin, genital region, the breast, and scalp ( Table 7.1 ). One may also include nevi of…

Deep Penetrating Nevi

The so-called deep penetrating nevus (DPN) is a variant of a benign melanocytic nevus. It is composed of distinctive pigmented spindled, ovoid, or occasionally epithelioid melanocytes with a characteristically inverted triangle-like downward architecture. Its clinical significance lies in the potential confusion with melanoma. Clinical Findings The clinical appearance of a DPN often resembles that of a blue nevus. The lesions usually present as circumscribed, dark brown,…

Blue Nevi and Dermal Melanocytosis

Blue nevi (BN) and dermal melanocytoses share clinical, histologic, and molecular features. Clinically most lesions are characterized by bluish discoloration. Under the microscope there is an aggregate of melanocytes typically confined to the dermis unassociated with epithelium (i.e., there are usually no junctional nests). Cytologically there are slender fusiform and dendritic melanocytes with melanin pigment. Molecularly mutations involving GNA11 or GNAQ are common in this group…

Spitz Nevi

The diagnosis of Spitz nevi and their distinction from melanoma is one of the most difficult tasks in neoplastic dermatopathology. Before a group of melanocytic proliferations was accepted as benign and named Spitz's nevus, similar lesions in children had been reported as melanoma. Sophie Spitz, after whom this nevus variant was named, published a landmark case series on childhood melanoma in 1948. All but one of…

Congenital Melanocytic Nevi

The term congenital melanocytic nevus (CMN) refers to a melanocytic nevus that either was present at birth or became apparent by the end of the first year of life. The term tardive CMN is used for a melanocytic nevus not visible at birth that becomes clinically apparent in early childhood. Congenital melanocytic nevi can have a variety of presentations and may not involve only the face,…

Acquired Melanocytic Nevi

Acquired melanocytic nevi are thought to result from activation of oncogenes either through an activating mutation or translocation, allowing for clonal proliferation of the affected melanocytes. In the majority of common acquired, including the so-called dysplastic, nevi, the initiating oncogenic event is either an activating mutation in BRAF (80%) or NRAS (5%). Mutations in GNAQ or GNA11 are associated with blue nevi, whereas most Spitz nevi…

Melanotic Macules

The term melanotic macule is used to refer to benign flat pigmented lesions, which are histopathologically characterized by melanin pigment deposited in basilar keratinocytes without or at times with a slight increase in the density of solitary units of junctional melanocytes. Cutaneous and mucosal melanotic macules are often labeled lentigo . The conjunctival equivalent has historically been termed acquired melanosis . In contrast to melanocytic nevi,…