Case Report: Malignant Melanoma Associated With COVID-19: A Coincidence or a Clue?

Abstract

Following SARS-CoV-2 infection in humans, there is upregulation of proinflammatory molecules S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), osteopontin (OPN), tumor necrosis factor alpha (TNF-α), and other cytokines that promote hyperinflammation. The same immunoregulatory proteins that fuel the COVID-19 “cytokine storm” are also produced by melanoma cells and various other cancers to promote tumorigenesis. We report three cases of malignant melanoma (MM) associated with severe COVID-19, the first two with amelanotic melanoma and the third with hypopigmented melanoma. It is noteworthy that we did not search for these cases. Patient 1 is a personal acquaintance and cases 2 and 3 were hospitalized and worked at our rehabilitation center, respectively. We hypothesize that SARS-CoV-2 induced inflammatory tumorigenic proteins in the microenvironment that may have contributed to the de novo development (case 1), aggressive growth (case 2), or recurrence (case 3) of these malignant tumors. Moreover, high concentrations of the same proinflammatory proteins found in the “cytokine storm” associated with COVID-19, including TNF-α, interleukin (IL)-1α, IL-1β, IL-6, and ferritin, also induce skin depigmentation or hypopigmentation by interfering with tyrosinase synthesis, the enzyme that catalyzes the rate-limiting step of pigmentation. Hence, the marked elevation of the biological effectors that decrease skin pigmentation may also reduce pigmentation in MMs, resulting in amelanotic or hypopigmented lesions. Although it is certainly possible that the occurrence of melanoma following COVID-19 is coincidental, the ability of SARS-CoV-2 to increase expression of proinflammatory and tumorigenic molecules warrants further investigations to determine if there is an association between these disease processes or implications for patients with melanoma or other cancers who develop COVID-19.

A Disguising Fast-Growing Metachronous Melanoma and COVID-19

“…On the other hand, some authors have described an oncolytic effect of the virus in lymphoma patients [ 18 ]. Leis et al published three melanoma cases (amelanotic and hypopigmented) diagnosed after SARS-CoV-2 infection and hypothesized a potential tumorigenesis effect of the COVID-19 "cytokines storm" [ 19 ]. Similar to this patient, the tumors displayed either decreased or no pigmentation.…”

Covid-19, leukemia, and secondary malignancies of the skin – is there a connection: a case report and literature analysis

“…There are also some data indicating, that malignant melanoma itself could be associated with the SARS-CoV-2 virus ( 4 ). Following SARS-CoV-2 infection we often observe upregulation of proinflammatory molecules like S100 calcium-binding protein B (S100B), high-mobility group box-1 (HMGB1), osteopontin (OPN), tumor necrosis factor-alpha (TNF-α), and other cytokines that promote hyperinflammation.…”

“…Following SARS-CoV-2 infection we often observe upregulation of proinflammatory molecules like S100 calcium-binding protein B (S100B), high-mobility group box-1 (HMGB1), osteopontin (OPN), tumor necrosis factor-alpha (TNF-α), and other cytokines that promote hyperinflammation. The same immunoregulatory proteins that contribute to the Covid-19 “cytokine storm” are also produced by melanoma cells and various other cancers promoting tumorigenesis ( 4 ). The authors suggest, that previous SARS-CoV-2 infection may provoke malignant tumor de novo development, its aggressive growth, or recurrence.…”

“…All these molecular events can also cause flare-ups of chronic inflammatory skin diseases and appearance of adverse skin reactions (like for example urticaria, pernio-like reactions of the acral sites, herpes zoster, morbilliform rashes, diffuse hair loss) which can potentially lead to the development of different non-melanoma skin cancers ( 8 ). To sum up, the ability of SARS-CoV-2 to increase the expression of proinflammatory and oncogenic molecules may have a pro-carcinogenic effect and may contribute to the emergence or development of various types of cancers, especially in patients who suffered from severe form of Covid-19 ( 4 ).…”

“…At the same time, it’s very important to register all cases of melanoma and non-melanoma, especially because they may be associated (just like other types of cancer) with Covid-19 pandemic ( 3 , 4 ). Indeed, Costa et al.…”