Case 4 -

Melanoma with Underlying Regression Bruce R. Smoller University of Arkansas for Medical Sciences Little Rock, AK

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Clinical History 56 year old man with variegated, pigmented lesion on the back. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: in situ melanoma with underlying fibrosis, inflammation and nests of atypical melanocytes elastic tissues stains demonstrate pattern characteristic of regression with vertical fibers pushed down to base of melanocytic prolfieration, but still present (unlike in a scar) Differential Diagnoses: Melanoma with regression Melanoma with adjacent scar formation Dysplastic nevus with underlying fibrosis Final Diagnosis: Melanoma with underlying regression Case Discussion: Historically, it has been difficult to distinguish between regression and fibrosis secondary to other causes such as previous biopsy, rupture of nearby hair follicles or other non-specific inflammatory processes. This distinction is not one of an entirely academic nature but may well have significant prognostic implications. The exact significance of regression remains unknown. The literate is replete with multivariate analyses suggesting that regression is of no significance. As many articles can be found suggesting that regression may portend a worse prognosis, especially when extensive (extending over more than 80% of the breadth of the lesion). Some authors argue that in melanomas with underlying regression, it is important to measure and report the thickness of the melanoma to the base of the focus of regression. These investigators postulate that this measurement provides an indication of the deepest point of penetration of the primary tumor and represents the truest prognostic indicator. To date, there has been no study suggesting that regression plays a beneficial role in the biologic behavior of this malignancy. Based upon the uncertainty regarding the significance of regression associated with melanoma, it is important, whenever possible, to indicate the presence of regression, especially when extensive. It is often difficult to distinguish regression from reactive fibrosis underlying a dysplastic nevus and from scarring secondary to other processes. During this year, Dr. Kamino and her co-workers completed a study in which they demonstrated subtle, but reproducible changes in the distribution of elastic tissue fibers in these three conditions. In normal skin, the papillary dermis is characterized by delicate elastic tissue fibers that are oriented perpendicular to the surface epidermis. The reticular dermis has much more dense and broader elastic tissue fibers oriented parallel to the epidermis. The fibrotic dermis beneath a dysplastic nevus demonstrates a similar pattern. The nests of melanocytes within the papillary dermis are surrounded by thin elastic tissue fibers demonstrating a "normal" vertical orientation. Areas of regression associated with a melanoma demonstrate a similar pattern, but displaced downward. At the base of the area of fibrosis, vertically oriented elastic tissue fibers are present. These fibers are identical in size and shape to those in the "normal" papillary dermis, but are displaced to the base of the area of fibrosis, or regression. The broader, denser reticular dermal elastic tissue fibers are similarly downwardly displaced, but otherwise retain their "normal" configuration. In contrast, the fibrosis seen in a scar is lacking in all papillary dermal-type elastic tissue fibers and all that remain at the base of the fibrosis is the reticular dermal type fibers oriented parallel to the skin surface. Conclusion(s): Use of elastic tissue stains can be helpful in distinguishing between melanoma with underlying regression, benign nevus cells trapped within a fibrotic dermis, and a scar underlying a melanoma in situ. The changes in staining patterns are characteristic and reproducible. References: Blessing K, McLaren KM, McLean A, Davidson P. Thin malignant melanomas (less than 1.5 mm) with metastasis: a histological study and survival analysis. Histopathology 1990; 17: 389-395. Cooper PH, Wanebo HJ, Hagar RW. Regression in thin malignant melanoma. Microscopic diagnosis and prognostic importance. Arch Dermatol 1985; 121: 1127-1131. Kamino H, Tam S, Roses D, Toussaint S. Elastic fiber pattern in regressing melanoma: a histochemical and immunohistochemical study. J Cutan Pathol 2010; 37: 723-729. Kamino H, Tam S, Tapia B, Toussaint S. The use of elastin immunostains improves the evaluation of melanomas associated with nevi. J Cutan Pathol 2009; 36: 845-852. McGovern VJ, Shaw HM< Milton GW. Prognosis in patients with thin malignant melanoma: influence of regression. Histopathology 1983; 7: 673-680.