Clinical, Dermoscopic, Pathologic, and Molecular Correlations

Pathologists will inevitably encounter melanocytic neoplasms, which are difficult to classify as melanocytic nevus or melanoma by histopathologic examination alone. While diagnostic confidence and uncertainty depend on one's level of experience and expertise, even the most experienced melanocytic lesion expert will face cases for which a definitive diagnosis by microscopic assessment alone cannot be provided due to the presence of ambiguous morphologic features. Some of these cases can be solved by clinical or molecular correlation. Depending on the differential diagnosis, either clinical information such as the history of the lesion and dermoscopic findings or molecular assessment may provide critical evidence that permits a more definitive diagnosis. In this section several diagnostically challenging cases are presented, and we illustrate how clinical or molecular assessment can assist in the diagnostic workup.

Clinical History and Dermoscopy

The distinction of dysplastic nevi, particularly severely atypical dysplastic nevi, from melanoma can be challenging. In fact, the findings that some dermatopathologists use to categorize a lesion as “severely atypical” are often the same findings that support a melanoma diagnosis, including pagetoid spread, confluent lentiginous growth, expansile nesting, or high grade nuclear atypia. Whereas the focal presence of such findings may be used to support the diagnosis of a severely atypical nevus, a melanoma diagnosis is commonly supported when these findings are more widespread. In “borderline” cases (where the quantity and quality of abnormal microscopic findings overlap with severely atypical nevus and early melanoma), dermoscopic assessment and/or a history of significant change during short-term dermoscopic monitoring can be highly valuable information for diagnosis ( Figs. 31.1 and 31.2 ).

Fig. 31.1, (A) Melanocytic proliferation with the differential diagnosis between atypical nevus and melanoma. (B) There is confluence of solitary units of melanocytes along the dermoepidermal junction (DEJ) with clefting between the epidermis and dermis. (C) Gross examination showed an oval-shaped uniformly tan-colored patch on the back of the 40-year-old woman. (D): Dermoscopy assessment shows an inverse pigmented pattern that extends from the center of lesion to the far left of the lesion. Vascular blush and chrysalis are also noted. These dermoscopic features favor a diagnosis of melanoma.

Fig. 31.2, (A) Melanocytic neoplasm with epithelioid spitzoid cytomorphology. The differential diagnosis is between a pagetoid variant of junctional Spitz nevus and evolving melanoma in situ. (B) Large epithelioid melanocytes scattered above the basal layer. (C) Gross examination shows a two-toned area with light brown in one side and dark brown in the other side. (D) The light brown area demonstrates a fingerprint pattern, and in the dark brown site there are pigment streaks extending away from the body of the lesion, consistent with radial streaming. This dermoscopic finding favors a diagnosis of melanoma in situ.

The differential diagnosis of severely atypical nevus versus melanoma is particularly common in pigmented lesion clinics where high-risk patients with numerous atypical nevi are being monitored. Early changes of melanoma may be quite evident by the dermoscopic assessment, displaying 1 of the 10 melanoma-associated dermoscopic changes, such atypical network, irregular blotches, asymmetric radial streaming, atypical dots or globules, blue-white areas over raised or flat areas, inverse pigment pattern, chrysalis structures, peripheral brown structureless areas, or polymorphous vascular structures. In some cases the development of these changes may be observed via serial dermoscopic monitoring of lesions. If in fact the dermoscopic criteria or dermoscopic evolution of a lesion is highly convincing for an evolving melanoma in an otherwise morphologically borderline lesion, it seems reasonable to directly state this in the report and to explain that while light microscopic findings are equivocal, the clinical and dermoscopic findings favor melanoma. Alternatively, if the clinical history is that of a stable lesion without significant dermoscopic alteration over time, one may use that information to favor a diagnosis of a melanocytic nevus, albeit one with microscopically atypical features.

The diagnosis of spitzoid melanocytic neoplasms with potential for aggressive behavior has been and continues to be the subject of many studies in dermatopathology. In cases of conventional melanoma with spitzoid features the clinical and dermoscopic findings may be a valuable piece of evidence that should be considered in the comprehensive assessment of a lesion. For example, if a lesion is markedly asymmetric and/or located on sun-damaged skin of a middle-aged or elderly individual, that information is relevant for assessing the odds of an atypical Spitz tumor versus melanoma with spitzoid features ( Fig. 31.3 ). However, spitzoid melanomas that display spitzoid cytomorphology throughout and are fusion driven may have clinical and dermoscopic features that do not allow for differentiation from benign Spitz nevi. For example, from a dermoscopic perspective, Spitz nevi/tumors and spitzoid melanoma may both have inverse pigment pattern and chrysalis and show starburst patterns with a tiered globular or radial streaming, or pseudopods all around the lesion ( Fig. 31.4 ). Furthermore by history, clinically benign Spitz nevi and tumors often go through a rapid growth phase, can become eroded, form a serohemorrhagic crust, and spontaneously bleed. Hence the clinical information may not solve the diagnostic dilemma in these cases.