A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance.

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.

Characteristics of dermal vascularity in melasma and solar lentigo.

BACKGROUND /PURPOSE: Melasma and solar lentigo (SL) are major benign hyperpigmented lesions, and both have been shown to involve the dermal vasculature. This review discusses current knowledge regarding the clinical characteristics of dermal vascularity in melasma and SL, as well as the results of relevant molecular biological investigations. METHODS: PubMed and Google Scholar were searched in December 2023 to identify articles related to melasma, SL, and the dermal vasculature in these lesions. RESULTS: Vascular morphologies in melasma and SL have been detected by histological and non-invasive methods, including modalities such as optical coherence tomography. Biological studies have indicated that factors secreted from vascular endothelial cells, such as stem cell factor and endothelin-1, can promote melanogenesis. With respect to phototherapy, blood vessel-targeting laser treatments are expected to provide long-term suppression of pigmentation, but this regimen is only effective when dilated capillaries are visible. CONCLUSION: In both melasma and SL, clinical and experimental investigations are revealing the contributions of dermal vascularity to hyperpigmentation. More effective treatment may require identification of hyperpigmentation subtypes. In the future, knowledge of treatment (including phototherapy) is expected to accumulate through reliable and validated non-invasive measurements.

Idiopathic eruptive macular pigmentation in a pediatric patient and a review of the literature.

Idiopathic eruptive macular pigmentation (IEMP) is a rare, benign, self-resolving melanosis consisting of hyperpigmented macules typically on the face, trunk, and extremities that can occur in children and adolescents and often presents a diagnostic conundrum. We report a case involving an 8-year-old female whose previous clinical presentation was concerning for an atypical presentation of cutaneous mastocytosis or neurofibromatosis. The clinical and histopathologic evaluation was consistent with the diagnosis of IEMP, and no active intervention was pursued. Our accompanying literature review serves to better characterize this condition, highlight key diagnostic features, and emphasize the tendency for spontaneous resolution to avoid unnecessary treatments with limited clinical efficacy.

Melanoma Arising Beneath the Lateral Rectus Muscle in a Teenager With Ocular Melanocytosis: Possible Origin From Intrascleral Melanocytes.

Ocular melanocytosis is a well-established risk factor for choroidal melanomas but, despite its reported associations in the literature, it is infrequently discussed in relation to orbital melanomas. The authors describe a teenage patient with ocular melanocytosis who presented with an asymptomatic ipsilateral right orbital mass associated with the lateral rectus muscle. An exploratory orbitotomy revealed a lesion lightly adherent to the underlying sclera. Histopathology demonstrated a markedly atypical epithelioid melanocytic proliferation, bound by a thin rim of superficial sclera, implying an origin from intrascleral melanocytes, likely within an emissary canal. Next-generation sequencing identified GNAQ and NF1 mutations. The histopathology and molecular genetics designated the lesion as having a uveal melanoma-like profile, suggesting that it may behave as a choroidal melanoma. This case underscores the importance of the association between ocular melanocytosis and orbital melanoma and provides additional evidence for primary orbital melanoma etiopathogenesis.

Clinicopathologic profiles of canine ocular melanosis: A comparative study between cairn terriers and non-cairn terriers.

OBJECTIVES: To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non-Cairn Terriers (NCTs). DESIGN: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis. PROCEDURES: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at-risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow-up surveys. One hundred fifty-seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs. RESULTS: At-risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p = .0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p = .0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p = .008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically. CONCLUSIONS: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs.

Congenital melanocytic naevus syndrome and Dandy-Walker malformation - a mistaken association: case report and literature review.

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy-Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst.

A novel treatment for Riehl's melanosis targeting both dermal melanin and vessels.

BACKGROUND/PURPOSE: Riehl's melanosis is a difficult-to-treat condition characterized by persisting dermal hyperpigmentation. This study aimed to evaluate the efficacy of a histology-specific targeted therapy for Riehl's melanosis. METHODS: Skin biopsy samples of Riehl's melanosis were assessed to identify histology-specific targets for treatment. Subsequently, the efficacy of a combination involving a fractional picosecond laser and a pulsed dye laser (PDL) targeting the dermal melanin and vessels, respectively, was evaluated. Clinical improvement was assessed using the dermal pigmentation area and severity index (DPASI). The treatment outcomes were compared to those of a control, in this case a single laser treatment solely targeting pigmentation. RESULTS: Histological and immunohistochemical analyses identified dermal melanin pigment and dilated vessels as treatment targets for Riehl's melanosis. The combined treatment of the fractional picosecond laser and PDL showed a significant reduction of the DPASI scores, which was significantly better than the control group. Patients who underwent the combined laser treatment indicated high levels of satisfaction with no adverse events except of transient erythema and oedema. CONCLUSION: The combined treatment of a fractional picosecond laser and a PDL was more effective for Riehl's melanosis compared to single laser treatment. The treatment targets both dermal pigmentation and dilated vessels, offering promising results for those working to manage Riehl's melanosis.

Skin Barrier Function and Its Relationship With IL-17, IL-33, and Filaggrin in Malar Melasma.

BACKGROUND: The pathogenesis of melasma remains unclear. Interleukin (IL)-17, a proinflammatory mediator, disturbs barrier function. Filaggrin (FLG) is a protein involved in epidermal barrier homeostasis and may be affected by IL-17 and IL-33. OBJECTIVE: To evaluate epidermal barrier function in malar melasma and its association with the expression of FLG, IL-17, and IL-33. METHODS: Twenty patients with malar melasma were included in this study. Colorimetric and transepidermal water loss (TEWL) was measured in lesional and adjacent unaffected skin at baseline and 30 minutes after barrier disruption using the tape-stripping test. Biopsies from melasma and perilesional skin were performed to evaluate the presence of FLG by immunohistochemistry, and profilaggrin, IL-17, and IL-33 expression were analyzed by reverse transcription-qualitative polymerase chain reaction. RESULTS: After the stripping test, the erythema and TEWL values were higher in the melasma than in the unaffected skin ( P = 0.01). Thirty minutes later, TEWL diminished, but it remained higher than in the perilesional skin. Profilaggrin increased as TEWL gradually decreased (R = -0.68, P = 0.04). FLG and IL-17 were higher in the melasma than in the perilesional skin ( P = 0.003). IL-17 and profilaggrin expression were positively associated (R = 0.60, P = 0.04). IL-33 expression was higher in the adjacent normal skin than in the melasma ( P = 0.01). CONCLUSION: This study found subclinical inflammation in the skin adjacent to the melasma, dysfunction of the epidermal barrier in lesions associated with chronic inflammation, and an abnormal differentiation process promoting an increase in FLG. These findings highlight the need to preserve the integrity of the facial stratum corneum in these patients.

[Analysis of 14 cases of melanosis caused by 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene].

14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.

Acinar Melanosis of the Bartholin Gland: A Report of 3 Cases.

Melanocytic pigmentation occurs in multiple sites in the lower female genital tract, but is rare within benign cysts of the vulva. We report 3 patients with multiloculated cystic lesions of the vulvar vestibule exhibiting prominent melanocytic pigmentation. The current cases differ from a previous report of melanosis in a Bartholin gland cyst in that the population of melanocytes occupies the acinar structures of the gland, rather than a squamous-lined surface. A similar cell population is demonstrated by immunoperoxidase methods in a fourth patient's nonpigmented gland, suggesting that melanin production may arise in a native, rather than metaplastic, cell population.

Central nervous system magnetic resonance imaging abnormalities and neurologic outcomes in pediatric patients with congenital nevi: A 10-year multi-institutional retrospective study.

BACKGROUND: High-risk congenital melanocytic nevi (CMN) are associated with abnormalities of the central nervous system (CNS), prompting magnetic resonance imaging (MRI) screening guidelines. OBJECTIVE: Describe MRI brain and spine abnormalities in children with CMN and report trends between nevus features, MRI findings, and neurologic outcomes. METHODS: Retrospective review of individuals aged ≤18 years with an MRI of the brain and/or spine and at least 1 dermatologist-diagnosed CMN. RESULTS: Three hundred fifty-two patients were identified. Forty-six children had CMN that prompted an MRI of the brain and/or spine (50% male, average age at first image, 354.8 days). In these children, 8 (17%) had melanin detected in the CNS, of whom all had >4 CMN. One developed brain melanoma (fatal). In patients without CNS melanin, 4 had concerning imaging. Concerning MRI patients had more neurodevelopmental problems, seizures, neurosurgery, and death than individuals with unremarkable imaging. Three hundred six patients received MRIs for other reasons; none detected melanin. No children with only multiple small CMN (n = 15) had concerning imaging. LIMITATIONS: Lack of a control group, cohort size, and retrospective methods. CONCLUSION: MRI of the brain and spine is useful for detecting intervenable abnormalities in high-risk children. Healthy infants with few small CMN may not require screening MRI.

Melanosis Coli Is Not Associated with Colonic Dysmotility Nor Severity of Pediatric Functional Constipation.

BACKGROUND: Sennosides are commonly used for the treatment of constipation and associated with melanosis coli. In the present study, we evaluated the utility of melanosis coli as a marker of severity and its association with colonic motility in children with functional constipation. METHODS: Prospective study includes pediatric patients undergoing colonic manometry and colonic biopsies. Demographic data, medication history, surgical history, colonic manometry results (gastrocolonic response to a meal, high-amplitude propagating contractions, and nonpropagating contractions), colonic manometry catheter position, and pathologic results were collected and analyzed. We compared those variables with outcome (need for surgery) between both patient groups (presence or absence of melanosis coli). RESULTS: A total of 150 patients were included, median age was 9.9 years (range 2.1-18) and 77 (51.3%) were female, 17 had melanosis. Patients who took sennosides had higher rates of melanosis coli compared to those who did not (adjusted OR 13.88; 95% CI 4.05-47.57; P < 0.001), and we did not find an association between melanosis coli and use of other medications (osmotic laxatives, bisacodyl, lubiprostone), age, gender, weight, and height. We found no significant difference in the results colonic manometry between patients with and without melanosis coli. The rates of surgery for constipation between patients with and without melanosis coli were not statistically different. (OR 3.00; 95% CI 0.45-20.07; P = 0.257). CONCLUSIONS: Melanosis coli is associated with sennosides use, but it does not influence colonic motility nor is associated with increased subsequent need for surgery in pediatric functional constipation.

PRAME Expression in Junctional Melanocytic Proliferations of the Conjunctiva: A Potential Biomarker for Primary Acquired Melanosis/Conjunctival Melanocytic Intraepithelial Lesions.

ABSTRACT: Conjunctival melanocytic proliferations are diagnostically challenging, often complicated by small specimen size, and are separated into 3 broad categories. The first group includes benign nevi and primary acquired melanosis (PAM) without atypia. The second group includes junctional melanocytic proliferations with a risk of progression to invasive melanoma (PAM with atypia). The last category is conjunctival melanoma, of which 65% of tumors arise in the setting of PAM with atypia. Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has been widely adopted to differentiate cutaneous nevi and melanoma. However, there are limited studies on its utility in the evaluation of conjunctival melanocytic proliferations with little data regarding its potential utility in stratifying PAM. Twenty-eight clinically annotated cases (14 PAM without atypia and 14 PAM with atypia) were retrospectively evaluated with PRAME/MART-1 duplex immunohistochemistry and were assigned the commonly used PRAME immunoreactivity score: 0 for no staining, 1+ for 1%-25% of cells positive, 2+ for 26%-50%, 3+ for 51%-75%, and 4+ for >75%. PAM without atypia showed low (0-3+) PRAME expression in 14 of 14 cases (100%). PAM with atypia showed strong and diffuse (4+) PRAME expression in 12 of 14 cases (86.7%). Seven of eight (87.5%) PAM with severe atypia, 4 of 4 PAM (100%) with moderate atypia, and 1 of 2 PAM (50%) with mild atypia showed 4+ PRAME expression. In addition, all 5 cases that recurred or progressed (all classified as PAM with atypia) showed 4+ PRAME expression. Although additional larger studies are needed, PRAME seems to be a useful adjunct in evaluating junctional melanocytic proliferations of the conjunctiva.

Treatment of linear and whorled nevoid hypermelanosis using QS 694-nm ruby laser.

Laser is being widely used in treating pigmented lesions nowadays. Linear and whorled nevoid hypermelanosis (LWNH) is a rare pigmentary anomaly, and there are only a handful of cases of successful treatment, all with QS 532- and 755-nm laser. The objective of this study was to examine the clinical outcome of QS 694-nm ruby laser in the treatment of LWNH. We report on a 4-year-old boy presented with asymptomatic macular hyperpigmentation over the entire cheek who underwent 3 treatment sessions with QS 694-nm ruby laser. One month after the last treatment, the patient demonstrated significant improvement to the treatment area. Aside from post-procedural purpura lasting approximately 1 week, the patient experienced no serious adverse effects. No recurrence was observed during the 3-month follow-up. Given the excellent results seen in our patients, we recommended the use of QS 694-nm ruby laser as a safe and effective treatment in patients with LWNH.

Neurosurgical management of patients with neurocutaneous melanosis: a systematic review.

OBJECTIVE: Neurocutaneous melanocytosis (NCM), also referred to as neurocutaneous melanosis, is a rare neurocutaneous disorder characterized by excess melanocytic proliferation in the skin, leptomeninges, and cranial parenchyma. NCM most often presents in pediatric patients within the first 2 years of life and is associated with high mortality due to proliferation of melanocytes in the brain. Prognosis is poor, as patients typically die within 3 years of symptom onset. Due to the rarity of NCM, there are no specific guidelines for management. The aims of this systematic review were to investigate approaches toward diagnosis and examine modern neurosurgical management of NCM. METHODS: A systematic review was performed using the PubMed database between April and December 2021 to identify relevant articles using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search criteria were created and checked independently among the authors. Inclusion criteria specified unique studies and case reports of NCM patients in which relevant neurosurgical management was considered and/or applied. Exclusion criteria included studies that did not report associated neurological diagnoses and neuroimaging findings, clinical reports without novel observations, and those unavailable in the English language. All articles that met the study inclusion criteria were included and analyzed. RESULTS: A total of 26 extracted articles met inclusion criteria and were used for quantitative analysis, yielding a cumulative of 74 patients with NCM. These included 21 case reports, 1 case series, 2 retrospective cohort studies, 1 prospective cohort study, and 1 review. The mean patient age was 16.66 years (range 0.25-67 years), and most were male (76%). Seizures were the most frequently reported symptom (55%, 41/74 cases). Neurological diagnoses associated with NCM included epilepsy (45%, 33/74 cases), hydrocephalus (24%, 18/74 cases), Dandy-Walker malformation (24%, 18/74 cases), and primary CNS melanocytic tumors (23%, 17/74 cases). The most common surgical technique was CSF shunting (43%, 24/56 operations), with tethered cord release (4%, 2/56 operations) being the least frequently performed. CONCLUSIONS: Current management of NCM includes CSF shunting to reduce intracranial pressure, surgery, chemotherapy, radiotherapy, immunotherapy, and palliative care. Neurosurgical intervention can aid in the diagnosis of NCM through tissue biopsy and resection of lesions with surgical decompression. Further evidence is required to establish the clinical outcomes of this rare entity and to describe the diverse spectrum of intracranial and intraspinal abnormalities present.

[A Case of Esophageal Malignant Melanoma during Follow-Up of Esophageal Melanosis Metastasis].

Man 62-years-old as for the case. In 2019, he was diagnosed with right hypopharyngeal cancer, and esophageal melanosis was noted on upper gastrointestinal endoscopy before treatment. We did a follow-up upper gastrointestinal endoscopy every year. At a follow-up upper gastrointestinal endoscopy performed in February 2021, he was histologically diagnosed with an esophageal primary malignant melanoma. Computed tomography showed no metastatic lesions. He underwent esophagectomy. He is currently being followed on an outpatient basis and has had no recurrence. Careful follow-up for esophageal melanocytosis is important for early diagnosis of esophageal primary malignant melanoma.

Paracrine roles of hormone receptors in Riehl's melanosis: A quantitative analysis of oestrogen and progesterone receptor expression patterns.

The incidence of Riehl's melanosis (RM) is most common in the fifth or sixth decade of life with a female preponderance. As the skin is regarded a non-reproductive organ on which sex steroid hormones act, a possible relationship between the pathogenesis of RM and sex steroid hormone receptors can be inferred. This study intended to evaluate the expression profile of oestrogen receptor (ER)ß and progesterone receptor (PR) in RM. Twelve lesional and perilesional normal-appearing skin samples of RM patients and the skin of 12 healthy controls were retrieved for the analysis. Real-time PCR analysis and immunohistochemical studies were conducted for ERß and PR, respectively. The lesional and perilesional normal-appearing skin of 12 patients with RM and the skin of 12 healthy controls were retrieved for the analysis. Interestingly, the dermal ERß immunostaining intensity was increased more in lesional skin than in perilesional skin. When compared to healthy controls, increased expression of ERß and PR mRNAs was observed in the lesional skin of patients with RM. Of note, epidermal and dermal ERß and dermal PR expressions showed increased staining intensities in the lesional skin of RM patients compared with healthy controls. The altered expression of ERß and PR in RM supports the possible role of these hormone receptors in the pathogenesis of RM.

Observed progression from melanosis with melanocyte hyperplasia to sinonasal melanoma with distant metastasis and a unique genetic rearrangement.

Melanosis, clinically presenting as a benign macular hyperpigmentation, consists of increased pigmentation (melanotic or melanocytic) either in the mucosal epithelial cells or as subepithelial pigment-laden macrophages. On the other hand, primary sinonasal mucosal melanoma (SNMM) is a rare disease with poor prognosis and high rates of local recurrence and metastasis. We report follow-up on a previously presented case of a 53-year-old man with recurrent clinical melanosis that progressed from histopathological melanocytic hyperplasia to melanoma in situ over a period of 4.8 years (Yao et al. Allergy Rhinol (Providence), 2016;7(3):164-167). The patient experienced multiple recurrences and local spread despite multiple extensive surgeries. We now report that this patient ultimately developed bilateral invasive SNMM and died with metastatic melanoma. Molecular analysis of the invasive melanoma revealed ALK rearrangement, specifically an EML4-ALK fusion, which represents the first report of this particular genetic variant in mucosal melanoma.

Neurocutaneous Melanocytosis and Leptomeningeal Melanoma.

Neurocutaneous melanocytosis (NCM) is a disorder characterized by multiple or large congenital nevi and excessive proliferation of melanocytes in the leptomeninges and brain parenchyma. The majority of NCM is a result of somatic mosaicism due to a single postzygotic mutation in codon 61 of NRAS. Patients with NCM are at high risk of developing leptomeningeal melanoma. The prognosis for leptomeningeal melanoma is poor with no known effective treatment options. We describe the clinical features, treatment, and outcome of 4 children with NCM and leptomeningeal melanoma and discuss the latest molecular findings and treatment options for this rare condition.

Tumoral Melanosis in the Setting of Targeted Immunotherapy for Metastatic Melanoma-A Single Institutional Experience and Literature Review.

BACKGROUND: Tumoral melanosis clinically resembles metastatic melanoma, occurs in the context of regressed disease, and requires evaluation to rule out underlying melanoma and metastatic disease. Histopathology demonstrates a nodular infiltrate of melanophages in the dermis, subcutaneous tissue, deep soft tissue, or lymph nodes in the absence of viable melanocytes. Recent limited reports of tumoral melanosis in the context of immunotherapy with ipilimumab (monoclonal antibody targeting CTLA-4) as well as nivolumab and pembrolizumab (humanized monoclonal antibodies against programmed death 1 receptor) highlight a unique presentation representative of treatment-related tumor regression and an association with a favorable clinical response. OBJECTIVE: To describe our experience with tumoral melanosis in the setting of immunotherapy for metastatic melanoma and elucidate the clinical and histopathological features. METHODS: Retrospective case series from a single tertiary care institution. RESULTS: We describe 10 cases of patients with metastatic melanoma who received treatment with immunotherapy before the development of tumoral melanosis. Length of time between the initiation of therapy and the onset of tumoral melanosis ranged from 2 to 20 months with a mean time of 10 months. At the end of the follow-up period, 8 patients were classified as having a complete or partial response to treatment with immunotherapy. One patient had progression of visceral and cutaneous disease on ipilimumab despite developing tumoral melanosis, and 1 patient had yet to undergo repeat imaging. Furthermore, at the end of follow-up, 3 patients were alive with no evidence of active disease, 5 patients were alive with disease, and 1 patient was deceased, although this patient died of a cardiovascular event unrelated to his underlying melanoma. Of the patients who were classified as alive with disease, 2 patients had minimal remaining disease, and 2 patients had an almost complete response on immunotherapy with recurrence of visceral metastases after immunotherapy was discontinued. One patient developed new peritoneal and cutaneous metastases on pembrolizumab despite development of tumoral melanosis. CONCLUSIONS: The underlying biologic mechanisms and prognostic implications of tumoral melanosis in the setting of immunotherapy remain to be elucidated. Further prospective studies with a larger cohort and prolonged follow-up are necessary to better understand the incidence, prevalence, and oncologic outcomes in patients with tumoral melanosis who receive immunotherapy.