Unilateral amelanotic conjunctival malignant melanoma: a case report.

INTRODUCTION: Cutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately. CASE PRESENTATION: We present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis. CONCLUSIONS: Conjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis.

A Rare Case of Primary Vulval Amelanotic Melanoma Involving the Urethra.

A 60-year-old woman came to the Emergency Department complaining of a vaginal formation. The urologist suspected a urethral caruncle: the patient was discharged with vaginal oestrogen cream to relieve symptoms and a follow-up was suggested. After two months the patient returned to the Emergency Department since the mass was increasing in volume and complaining of dysuria and haematuria. Ultrasound, contrast-enhanced computed tomography, and contrast-enhanced magnetic resonance revealed a mass arising from the mucosa and involving the vulva and the urethra, suspicious of malignancy. We present a challenging diagnosis of an infiltrative and rapidly progressive primary vulval amelanotic melanoma with a complete imaging evaluation and a confirmed histological diagnosis.

Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

Spatial transcriptomic analysis of amelanotic acral melanoma versus pigmented acral melanoma reveals distinct molecular determinants.

BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma that has a poor prognosis. OBJECTIVES: To investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: Differences in the spatially resolved transcriptomic profiles of 9 patients with AAM with 29 regions of interest (ROIs) and 11 patients with PAM with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b+ tumour cell areas, we detected 11 upregulated differentially expressed genes (DEGs; including chaperone/ubiquitin--associated DEGs) and 82 downregulated DEGs (including human leucocyte antigen) in AAMs vs. PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signalling and melanin biosynthesis pathways in S100b+ ROIs of AAMs compared with PAMs. In tumour-associated immune cell areas, the numbers of CD8 T cells (P = 0.04) and M1 macrophages (P = 0.01) were significantly decreased, whereas those of monocytes (P = 0.04) and endothelial cells (P = 0.04) were increased in AAMs compared with PAMs. CONCLUSIONS: These findings could widen our understanding of the biological differences between AAMs and PAMs, which might result in a different clinical course.

Melanoma is one of the most serious types of skin cancer. As melanoma starts in cells that produce melanin (the substance that produces hair, eye and skin colouration), melanoma tumours are usually brown or black. 'Amelanotic melanoma' is a subtype of melanoma that has little or no melanin pigmentation. Less than 2% of melanomas are amelanotic melanomas. 'Acral melanoma' is a type of melanoma that occurs on the hands and feet. In acral melanoma, the lack of pigmentation has been associated with worse outcomes for patients. Why amelanotic acral melanoma (or 'AAM') has a worse prognosis than pigmented acral melanoma (or 'PAM') is unclear. Using a type of technology called 'spatial transcriptomic analysis', we analysed a type of nucleic acid called RNA in 9 people with AAM and 11 with PAM. Seventy-five 'regions of interest' were selected. These regions of interest are known to be associated with tumour cells or immune cells around tumours. We found that pathways involved in making proteins (translation) and in a process that removes faulty proteins called 'messenger RNA' were more active in AAM. However, pathways involved in processing and presenting antigens (substances that can trigger an immune response), the signalling of other proteins called 'interferons' and melanin production were less active in AAM. The number of specific types of white blood cells that recognize and attack tumours were decreased, whereas other cell types such as cells that line blood vessels were increased in AAM. Our findings could increase our understanding of the differences between AAMs and PAMs. This may lead to an improvement in prognosis.

Clinicopathological, dermoscopic features and circumstances of diagnosis of amelanotic or hypomelanotic melanoma: A prospective multicentric study in the French private medical sector.

BACKGROUND: Amelanotic or hypomelanotic melanomas (AHM) are difficult to diagnose, and are often diagnosed late, with a high Breslow index and a poor prognosis. PATIENTS AND METHODS: A total of 226 volunteer dermatologists consulting in private practice in France completed an online form for each new histologically proven case of melanoma diagnosed at their clinic in 2020. This anonymised survey collected data on the clinical, dermoscopic, and histological features of melanoma, as well as the circumstances of diagnosis and initial management. A group of 145 AHM was single out and compared to the 1503 pigmented melanomas (PM) from the same cohort. RESULTS: 1503 pigmented melanomas (PM) and 145 AHM (8.8% of these melanomas) were identified and included. In the AHM group, the mean age at diagnosis was 65 ±â€¯16 years, with no significant difference from the PM control group. AHM were not predominantly on the face and neck area, and there were no differences based on gender. Warning signs (local progression and bleeding) were significantly more frequent in the AHM group than in the PM group. AHM were more frequently ulcerated and nodular, with a higher median Breslow thickness than in the PM group (1.56 vs. 0.5 mm), and mitoses were more frequent. Dermoscopy was widely used and proved useful for distinguishing benign lesions, and for highlighting the vascular polymorphous pattern of malignant lesions. Patients noticed the suspicious lesion themselves in most cases of AHM (73.2%), as opposed to their general practitioner (17.2%) or entourage (9.5%). A total body skin examination enabled detection of 19.3% of AHM and 21.3% of PM where the patient consulted for another lesion, or for an unrelated reason. CONCLUSION: AHM are difficult to diagnose for the clinician because of the paucity or absence of pigmentary criteria. Knowledge of dermoscopic vascular patterns is critical and could help reduce the median Breslow index of AHM at the time of detection. Self-examination of the skin should be encouraged, and simple algorithms for earlier detection of skin cancers should be promoted among health professionals and the general population.

The combination of dermoscopy and reflectance confocal microscopy increases the diagnostic confidence of amelanotic/hypomelanotic lentigo maligna.

The dermoscopic diagnosis of amelanotic/hypomelanotic lentigo maligna/lentigo maligna melanoma (AHLM/LMM) may be very difficult in its early stages because of lack of pigment. Reflectance confocal microscopy (RCM) is an imaging technique that is especially helpful for the diagnosis of lentigo maligna. To determine the diagnostic performances of dermoscopy and RCM in the diagnosis of AHLM/LMMs we evaluated dermoscopic and RCM images of consecutive cases of histopathologically confirmed AHLM/LMMs, amelanotic/hypomelanotic basal cell carcinoma and squamous cell carcinoma (AHBCCs/AHSCCs), amelanotic/hypomelanotic benign lesions (AHBLs), and actinic keratoses (AKs) from five participating centers. Sensitivity, specificity, accuracy, predictive values, and level of diagnosis confidence were calculated for both diagnostic procedures. Both dermoscopy and RCM showed diagnostic performance >97% in the diagnosis of AHLM/LMMs versus AHBCC/AHSCCs and their combination slightly improved diagnostic performance, with accuracy increasing from 98.0% to 99.1%. Similarly, RCM in combination with dermoscopy showed a tiny increase in the diagnostic performance in the diagnosis of AHLM/LMMs versus AHBLs (accuracy increased from 87.2% to 88.8%) and versus AKs (accuracy increased from 91.4% to 93.4%). Although the increase in diagnostic performance due to RCM was modest, the combination of dermoscopy and RCM greatly increased the level of confidence; high confidence in the diagnosis of AHLM/LMMs versus AHBLs increased from 36.2% with dermoscopy alone to 76.6% with dermoscopy plus RMC. Based on our results, dermoscopy and RCM should be complementary to improve not only diagnostic accuracy but also the level of diagnostic certainty in the diagnosis of AHLM/LMMs.

Primary anorectal amelanotic melanoma with liver, lungs and lymph nodal metastases.

Anorectal melanoma (ARM) is an exceedingly rare and very aggressive malignancy. It originates from the melanocytic cells in the anorectal mucosa, which produces melanin. Other mucosal melanomas commonly found in the mucosa of the oral cavity, vulvovaginal, pharynx and urinary tract. Patients usually present with bleeding per rectum, perianal pain and difficulty in defaecation. Distinction of primary anorectal melanoma from other tumours of this region is difficult because of the lack of common imaging features. MRI is the modality of choice for its better tissue characterisation and resolution. There is no standard treatment protocol available mainly due to scarcity of data. Surgery is the mainstay therapy. Herein we present a case of a male patient in his 30s who presented with rectal bleeding and perianal pain. Haematological analysis revealed normocytic normochromic anaemia. MRI detected a mass lesion in the anorectal region. Contrast enhanced CT revealed multiple metastases in the liver, lungs, periportal, mesorectal and inguinal lymph nodes. The diagnosis of the ulcerated anorectal melanoma was established on histopathological examination. The patient underwent abdominoperineal resection (APR) followed by chemotherapy. Afterward the patient presented to the emergency room with respiratory distress for which he was on ventilator support. Sadly, the patient died after four days.

Amelanotic melanomas are often diagnosed at an advanced stage.

In this case report, a 62-year-old woman was diagnosed with lymph node metastasis from melanoma in the groin. Initially the primary tumour was unknown. The entire skin was examined without any suspicious moles. A PET-CT scan showed an area on the left heel with increased activity. The element surprisingly showed an amelanotic melanoma. Amelanotic melanomas have a significantly worse prognosis compared to pigmented melanomas, presumably because they are detected later and may be very difficult to detect clinically. This case shows the importance of paying attention to unpigmented elements when searching for a primary tumour.

Primary vulvar melanoma in an adolescent patient.

Herein we describe the case of a Black adolescent who was found to have widely metastatic melanoma originating from a primary vulvar lesion. The lesion presented as a pink, vegetative nodule of the clitoral hood which grew in size over several years and was confirmed to be melanoma on shave biopsy. This patient's amelanotic presentation in conjunction with the rare incidence of vulvar melanoma contributed to the delay in diagnosis. This case exemplifies the challenge of early recognition of potentially malignant vulvar lesions for primary care providers in adolescents.

Multifocal primary amelanotic meningeal melanomas mimicking lymphoma: a case report and literature review.

Primary meningeal melanoma is a rare type of melanocytic cancer originating from the melanocytes of the leptomeninges. It commonly presents as a solitary mass, and multifocal amelanotic lesions were scarcely reported. Diagnosis of multifocal melanoma is particularly challenging, clinically and diagnostically, especially in the absence of cutaneous nevi and melanin pigment. Surgical biopsy result is the gold standard. In this case study, we present an uncommon case of multifocal primary amelanotic meningeal melanomas mimicking lymphomas in the skull base and near the Sylvian fissure, which serves to provide reference value to the clinical diagnosis. Physicians should be aware of the existence of this special type in the clinical work.

Characterizing melanoma in the setting of oculocutaneous albinism: an analysis of the literature.

Although it is established that individuals with albinism have increased risks for nonmelanoma skin cancers, melanomas occurring in the setting of albinism are rare. PubMed and Google Scholar were searched for individual case reports describing melanoma in individuals with oculocutaneous albinism (OCA). All published cases characterizing individuals with albinism and melanoma in the medical literature were gathered to evaluate any epidemiologic or histologic differences from melanomas arising in the general population. Frequencies of melanoma characteristics between the OCA literature cohort and general population were compared using Clopper-Pearson confidence intervals. From 1952 to 2018, at least 64 cases of melanoma in 56 individuals with albinism were reported in the global medical literature. The median age of diagnosis for melanoma in individuals with albinism was 41 years, and the median Breslow depth at diagnosis was 2.0 mm. The subtypes of melanoma were nodular in 33% and superficial spreading in 46% of these cases, respectively. Amelanotic melanomas comprised 65% of the cases in our OCA cohort; however, histologic subtypes were only available for fourteen of the amelanotic cases. Finally, 17% of melanomas in patients with albinism arose from preexisting lesions. Despite their rarity, melanomas arising in oculocutaneous albinism have distinct characteristics from melanomas arising in the general population. Clinicians should consider a differential diagnosis of melanoma for any potential skin malignancies in individuals with albinism.