The Presence of Pigment Incontinence in Sinonasal Mucosal Melanoma

Background: It has long been recognized that the host immune system plays a role in the progression and survival of patients with melanoma. Regression is an immunological phenomenon that has been described in cutaneous melanoma whereby the tumor is replaced with tumor-infiltrating lymphocytes (early regression), immature fibroblasts and granulation tissue (intermediate regression), and mature fibroblasts (late regression) often accompanied by pigment incontinence (accumulation of melanin in the upper dermis) and pigment-laden macrophages. Melanin deposited in macrophages results in grossly pigmented lesions that may be mistaken for viable tumor and has not been described in sinonasal mucosal melanoma (SNMM). Pigmented lesions that can be composed of pigmented macrophages or tumor cells can pose a dilemma on if the lesion should be resected. There is a paucity of literature on the presence of regression and the role of frozen biopsy for pigmented macrophages in SNMM. The aim of this study was to investigate the presence and stage of regression and pigment-incontinence and its relationship with treatment in patients with SNMM.

Methods: A retrospective chart review was conducted on patients from 2007 to 2023 diagnosed with SNMM at Thomas Jefferson University Hospital. Demographic information, chemoradiation therapy, recurrence, and disease status were reviewed. Pathology slides from surgical resection were examined by a pathologist blinded to patient treatment information for the presence and extent of pigment-laden macrophages and regression.

Results: Seventeen patients (11 female, 6 male) with sinonasal mucosal melanoma were included in this study who underwent surgical resection. The average age at the time of biopsy was 73.46 ± 11.41. Three patients received neoadjuvant therapy followed by surgical resection. Pigment incontinence was present in 11/17 patients (65%) including all 3 (27%) patients that received neoadjuvant therapy (1 radiation, 2 immunotherapy). One patient received neoadjuvant immunotherapy and demonstrated a complete pathological response and displayed late regression with mature fibrosis extensive pigment incontinence. Regression was present in 15/17 patients and was associated with pigment incontinence in 10/15 patients. Early regression without other phases of regression was present in 4 patients and 2 of these patients had pigment incontinence. Intermediate regression was present without other phases of regression in 4 patients and 3 of these patients had pigment incontinence. Late regression without early or intermediate regression was noted in 2 patients and 1 patient had pigment incontinence. Five patients had mixed presence of early, intermediate and late regression.

Discussion: This study highlights that SNMM displays characteristics of immunological regression on histopathologic analysis. Additionally, this study is one of the first to comment on the presence of pigment incontinence in patients with SNMM. The findings of this study indicate that pigment incontinence can be a part of the natural tumor life cycle and grossly pigmented lesions could easily be confused for melanoma especially after neoadjuvant therapy. The presence of pigment incontinence is also noted in treatment naïve specimens. Developing an understanding of spontaneous regression and pigment incontinence within SNMM on histologic analysis is important for diagnosis and clinical management along with understanding the tumor microenvironment.

Publication History

Article published online:
05 February 2024