The Prognostic Significance of Tumoral Melanosis

Abstract

Background: Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent.

Methods: We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non-TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence-free survival (RFS), distant disease-free survival (DDFS), melanoma-specific survival (MSS), and overall survival (OS).

Results: TM was reported in 79 patients. Their median age was 65 years (range 22-88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty-five TM patients were matched with 70 non-TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS.

Conclusions: TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.

Keywords: immunotherapy; melanoma; melanophages; melanosis; pathology; pigmentation; prognosis; regression; treatment; tumoral.

FIGURE 1

Clinical appearance of tumoral melanosis at the scar of a previous melanoma resection (a). Nodule of tumoral melanosis in the dermis (b). Tumoral melanosis in a lymph node following immunotherapy for metastatic melanoma, showing sheets of melanophages with no melanoma cells in this region (c and d). Dermal melanophages with viable melanoma cells (arrowhead), seen on H&E (e and f) and SOX‐10 immunohistochemistry (g), suggestive of partial regression.

FIGURE 2

The histological differential diagnosis of tumoral melanosis (TM) includes heavily pigmented melanocytic neoplasms such as blue nevus (a) and pigmented epithelioid melanocytoma (b and c). Venous stasis dermatitis can mimic TM (d, with adjacent basal cell carcinoma), but the iron from the hemosiderin pigment is readily distinguished by the use of Perl stain (e). Tattoo pigment is comprised of black carbon particles (f) seen here in a lymph node (right) as opposed to the dark brown melanin pigment present in TM (left).

FIGURE 3

Frequency of primary melanoma types occurring in melanoma patients with TM (n = 35) treated with surgery alone.

FIGURE 4

Kaplan–Meier survival estimates for melanoma patients with TM (n = 35) treated with surgery alone compared to matched control melanoma patients without TM (n = 70). (a) Recurrence‐free survival, (b) distant disease‐free survival, (c) melanoma‐specific survival, and (d) overall survival. Differences in survival were tested using the log‐rank test.