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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 with both nevus and melanoma, or reflect limited information related to a small biopsy sample capturing only a part of the lesion, thereby excluding the use of important parameters, such as symmetry and circumscription.

In many cases, assessment of the silhouette and gestalt of a lesion (comparing it with stored mental images of previously observed nevi and melanomas) is diagnostic for an experienced pathologist. However, for didactic (and for beginners also practical) purposes a stepwise approach is presented here. Scanning magnification allows assessment of the architectural features of a lesion: the more complex its architecture, the more likely is the diagnosis of melanoma. Assessment of melanocytic lesions by the ABCD parameters provides a useful first impression.

ABCD Parameters and Cytology

Clinically, A symmetry, irregular B orders, variation in C olor, and D iameter greater than 6 mm are features typical of cutaneous melanoma ( Fig. 11.1 ). Three of these parameters (asymmetry, ill-defined borders, and size/horizontal diameter) are readily assessable histopathologically at scanning magnification of an excisional biopsy of a suspected melanoma, and the findings related to these parameters represent key evidence in support of the diagnosis ( Fig. 11.2 ; Box 11.1 ). The ABCD parameters have been extended to ABCDE to include the clinical aspect of E volution. Whether a lesion has clinically changed is relevant for the diagnosis and attests to the importance of clinic-pathologic correlation. A clinical change may be focal (e.g., new darker area at the edge of a nevus conveying an asymmetric appearance), and it is important for the pathologist to know about this to ensure representative histologic sampling of the tissue to correlate the microscopic features with the clinical change.

Fig. 11.1, Melanoma—Clinical Appearance.

Fig. 11.2, Melanoma—Histopathology (of Lesions Shown in Fig. 11.1 ).

Box 11.1
Histopathologic Features Associated With Melanoma

Silhouette: Asymmetry

  • Borders: usually ill-defined

  • Size: often >6 mm in diameter, but bona fide small (2 mm) diameter melanomas exist

Intraepidermal Melanoma

  • Irregular pagetoid spread and/or broad lentiginous junctional proliferation

  • Predominance of solitary units of melanocytes

  • Irregular distribution and shape of junctional nests with skip areas

  • Confluency of melanocytes along the dermoepidermal junction

  • Cytologic atypia of melanocytes (variable)

Dermal and/or Subcutaneous Melanoma Component

  • Complex asymmetric growth pattern

  • Lack of maturation or only minimal maturation

  • Expansile nodules

  • Infiltrative growth

  • Oddly shaped nests

  • Mitotic figures

  • Nuclear atypia

Stromal Changes

  • Lichenoid inflammatory reaction common

  • Fibrosis and dermal regression may be present

Associated Surface Changes

  • Ulceration and/or “consumption of the epidermis” (obliteration/effacement of rete ridges) are more often seen with melanomas than with nevi

Asymmetry

Asymmetry applies primarily but not only to the silhouette of a tumor at low magnification. However, the symmetry of the distribution of melanocytes (even or uneven density or organization as nests vs. solitary units, “skip areas”), melanin pigment (even or uneven melanization in the horizontal plane, reduction of melanin pigment within melanocytes from top to bottom), epidermal changes (uneven vs. even hyperplasia or atrophy, focal loss of epidermal rete ridges), and cytology (uniform bland appearance vs. pleomorphism) are also relevant for the diagnosis. A conventional melanocytic nevus is usually symmetric ( Fig. 11.3 ), whereas asymmetry is a hallmark of melanoma ( Fig. 11.4 ).

Fig. 11.3, Symmetric Melanocytic Nevus.

Fig. 11.4, Melanoma—Pathology.

Irregular Borders

Most conventional melanomas display ill-defined peripheral margins, at least on one side. There is an uneven distribution in cell density, often associated with a predominance of solitary units and their gradual tapering off. However, some melanomas may have sharp lateral borders ( Fig. 11.5 ). Peripheral circumscription is commonly seen in nodular, spitzoid, and nevoid melanomas or generally in melanomas with a predominant nested growth pattern.

Fig. 11.5, Melanoma—Pathology.

Variation in Color

Variation in color may reflect irregular distribution of melanin pigment within the tumor cells (see Fig. 11.4 ) and/or the sum of additional stromal changes, such as inflammation, dermal fibrosis, vascular ectasia, or melanophages. Marked variation in color is typical of melanoma. Most nevi display a uniform color. However, there are exceptions, when nevi are inflamed or biphenotypic (e.g., combined ordinary and deep-penetrating nevus). They may then clinically simulate the appearance of a melanoma.

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