Dermoscopy for the Identification of Amelanotic Acral Melanoma.

Acral lentiginous melanoma is commonly misdiagnosed, and when detected late it portends a poor prognosis. Acral lentiginous melanoma can be mistaken for verruca, pyogenic granuloma, poroma, an ulcer, or other benign skin conditions. Patients with acral skin growths often present initially to a podiatric physician or their primary care physician. It is at this point when the growth is triaged as benign or potentially malignant. Dermoscopy aids in this decision making. Historically, dermoscopy training has been geared toward dermatologists, but there is increasing recognition of the need for dermoscopy training in primary care and podiatric medicine. Dermoscopy is particularly helpful in pink (amelanotic) growths, which can lack the traditional clinical findings of melanoma. A literature review of acral melanoma and dermoscopy was performed in PubMed. We also describe a case of amelanotic acral melanoma in a 58-year-old with a rapidly enlarging painful mass on her heel. The lesion was initially thought to be a pyogenic granuloma and was treated with debridement (curettage). She was ultimately seen in the dermatology clinic, and the findings under dermoscopy were worrisome for amelanotic melanoma. Biopsy confirmed the diagnosis. The cancer metastasized, and the patient died less than 2 years later.

Oral Amelanotic Melanomas: Clinicopathologic Features of 8 Cases and Review of the Literature.

Mucosal melanomas are aggressive tumors, rarely observed in the oral cavity. The diagnosis is based on the clinical and microscopical features. Often these tumors had variable amounts of melanin pigmentation. However, when melanin is absent, the tumors are denominated amelanotic, presenting a tendency to misdiagnosis and delayed treatment. The aim of this study was to describe the clinicopathologic features of a series of oral amelanotic melanomas (OAM). Records of all cases of OAM were retrospectively retrieved from oral pathology services from January 2002 to January 2019. Data regarding the clinical features, morphological aspects, immunohistochemical reactions, treatment, and follow-up status were collected. Eight cases of OAM were included, 6 in men and 2 in women (ratio of 3:1) ranging in age from 33 to 77 years (mean 53.6 years). Clinically, the tumors presented as masses or ulcerated swellings. The most common intraoral locations of the tumors were gingiva and palate. Cervical lymph node metastasis was detected in 3 patients at the first examination. All but one patient died from complications of the tumors after a mean follow-up period of 8.5 months. In conclusion, OAM is a very aggressive malignant tumor, and when melanin is absent, an immunohistochemical panel comprising S100, melan A, HMB45, and SOX10 should be performed.

Matched analysis of the prognosis of amelanotic and pigmented melanoma in head and neck.

Background: The prognosis of mucosal melanoma is poor, and the difference in clinical prognosis between patients with and without pigment needs further study.Aim: To analyze data with head and neck mucosal melanoma, and compare the prognosis of patients with and without pigment.Material and methods: The patients of amelanotic melanoma were matched with pigmented type according to age, sex, stage, location of disease, treatment history, tobacco and alcohol history. The Kaplan-Meier and Cox proportional risk regression model was used for analyzation.Results: 46 patients of amelanotic melanoma and 46 of pigmented type were included in this study. The overall survival rate and progression-free survival rate of patients with pigmented melanoma were higher than in patients with amelanotic melanoma (HR = 0.533, p = .035, 95% CI = 0.296-0.957; HR = 0.530, p = .034, 95% CI = 0.294-0.953, respectively), and the risk of distant metastases in patients with amelanotic melanoma was significantly higher than that in patients with pigmented melanoma (HR = 0.474, p = .046, 95% CI = 0.228-0.987).Conclusions and significance: The prognosis and disease-free survival of amelanotic melanoma is worse than for the pigmented type group. More identifying the differences in clinical characteristics will help to further individualized treatment decisions.

A pink enlarging plaque on the plantar foot: amelanotic acral lentiginous melanoma.

Acral lentiginous melanomas account for less than 5% of all melanomas, whereas amelanotic melanomas account for around 2-8% of all melanomas. Amelanotic acral lentiginous melanomas are even less common and can often be mistaken for other clinical entities, including pyogenic granulomas, non-melanoma skin cancers, and warts. We describe a man in his 50s with a twenty-year history of a skin-colored plaque on the right plantar foot; after enlargement and failure of wart treatment, a shave biopsy revealed an amelanotic melanoma. A subsequent wide local excision and sentinel lymph node biopsy revealed melanoma in 4 lymph nodes and the patient underwent an abbreviated course of interferon-alpha therapy. The patient remained stable until 2 ? years after diagnosis, at which time he presented with in-transit metastases on the foot and right thigh; he has since been stable on nivolumab. This case represents the challenge of diagnosing amelanotic melanomas on acral surfaces and highlights the importance of considering a skin biopsy for diagnosis of any changing, atypical amelanotic lesions on the feet or hands.

Amelanotic melanoma.

Cutaneous amelanotic melanoma (AM) is a rare amelanotic or a hypomelanotic subtype of melanoma, comprising only 0.4-27.5% of all melanoma cases. The mean age of the patients is over 50 years, and the male/female ratio varies from 0.5 to 4. Patients with red hair, type I skin, freckles, lack of nevi on the back, a sun-sensitive phenotype, or previous AM history are more likely to develop AMs. As AMs lack pigmentation, their appearances vary and can mimic many benign and malignant conditions, thus presenting a diagnostic challenge. AMs are composed of greater proportions of nodular melanoma, acral lentiginous melanoma, and desmoplastic melanoma than pigmented melanomas. They also present with thicker Breslow thickness, higher mitotic rate, more frequent ulceration, higher tumor stage, and lower survival than pigmented melanomas.

Reflectance confocal microscopy margin mapping and monitoring of an amelanotic melanoma in situ of the ear.

In situ amelanotic melanoma represents a diagnostic and therapeutic challenge for clinicians. Poor demarcation of these lesions often results in repeated therapeutic intervention until appropriate clearance has been achieved. Reflectance confocal microscopy (RCM) is a noninvasive bedside imaging modality which allows real-time visualisation, to a near-histological level, of the epidermis and reticular dermis. We present a case of an amelanotic melanoma in situ in which reflectance confocal microscopy margin mapping allowed for demarcation of the melanocytic proliferation and targeted therapeutic intervention with topical imiquimod. Reflectance confocal microscopy was further utilised for noninvasive assessment of therapeutic response.

Clinically amelanotic or hypomelanotic melanoma: Anatomic distribution, risk factors, and survival.

BACKGROUND: The recognition and diagnosis of clinically amelanotic or hypomelanotic melanoma is a challenge. OBJECTIVE: This study aimed to examine the anatomic distribution and risk factors associated with clinically amelanotic or hypomelanotic melanoma and compare the survival of patients with clinically amelanotic or hypomelanotic melanoma with that of patients with pigmented melanoma. METHODS: A prospective cohort study of all cases of primary invasive melanoma managed at a tertiary referral center was performed. RESULTS: There were a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow thickness; and mitoses were independently associated with amelanotic or hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the face, ears, lateral aspect of the neck, upper portion of the arm, posterior aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the lower portion of the leg were associated with increased odds of amelanotic or hypomelanotic melanoma when compared with the upper portion of the back (P < .05). Mortality risk from melanoma appeared greater for amelanotic or hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken into account. LIMITATIONS: Single tertiary referral center. CONCLUSION: Although clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it is more common on chronically sun-exposed areas. Clinicians should have an increased index of suspicion in patients with a sun-sensitive skin phenotype, red hair, and associated actinic keratoses.

Malignant melanoma presenting as amelanotic caruncular lesion in a child.

Conjunctival melanoma is a rare malignant neoplasm that can present in childhood in any part of the conjunctiva. The infrequency with which conjunctival melanoma is encountered in childhood caruncular lesions makes it a formidable but important aspect of the differential diagnosis. We report the case of a 10-year-old boy who presented with a left caruncular lesion. On histopathologic analysis, the lesion was determined to be BRAF-negative invasive melanoma arising in association with melanocytic nevus. The melanoma was excised using no-touch technique and double freeze thaw cryotherapy. A full systemic work-up revealed no metastasis or abnormality.

Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports.

INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients. Hence, many studies have promoted the synergy of RT and anti-programmed cell death protein 1 (PD-1) treatment for antitumor immunity. However, outcome may be improved when more therapies are combined, but risk of side effects can be increased. CASE PRESENTATION: We herein present 3 advanced cancer patients with pulmonary metastasis and who received RT. Later, they underwent anti-PD-1 treatment and unfortunately suffered from anti-PD-1-related pneumonitis over the nonirradiated areas after 4 cycles of treatment. The upregulation of cellular PD-1 expression in these areas was considered and the immune overreaction by anti-PD-1 treatment may cause these severe pulmonary adverse effects. CONCLUSION: Our review of 3 cases warrants careful workup to reduce the risk of side effects by combinative therapy with RT and anti-PD-1 treatment.

BRACHYTHERAPY ALONE OR WITH NEOADJUVANT PHOTODYNAMIC THERAPY FOR AMELANOTIC CHOROIDAL MELANOMA: Functional Outcomes and Local Tumor Control.

PURPOSE: To compare visual outcomes and local tumor control between two groups of patients with amelanotic choroidal melanoma treated with brachytherapy alone, or neoadjuvant photodynamic therapy before brachytherapy. METHODS: Patients diagnosed with amelanotic choroidal melanoma were recruited for the study and divided into two groups: brachytherapy alone (Group A) and photodynamic therapy preceding brachytherapy (Group B). Patients of both groups were selected to be comparable. RESULTS: Twenty-six patients with amelanotic choroidal melanoma were enrolled in the study. Within Group B, 1 month after photodynamic therapy, ultrasonography showed reduction of tumor height in 11 patients (73.4%). The mean doses of irradiation to macula and optic nerve, at baseline were 74.37 and 52.07 Gy, whereas after photodynamic therapy there was a decrease of 17.26% (P = 0.008) and 21.22% (P = 0.025), respectively. In terms of visual acuity, a mean decrease of 14 ETDRS letters and 5 ETDRS letters was observed at 24 months follow-up, in Groups A and B, respectively (P = 0.001). CONCLUSION: Photodynamic therapy as neoadjuvant therapy before brachytherapy reduces tumor thickness in 73.4% of cases. As a result, a decrease of radiation toxic effects on visual function could be obtained, without compromising disease control.

Desmoplastic melanoma of the eyelid and conjunctival melanoma in neurofibromatosis type 1: a clinical pathological correlation.

A 56-year-old woman with neurofibromatosis type 1 (NF1) presented with a left upper eyelid amelanotic nodule with adjacent eyelid margin hyperpigmentation. Physical examination additionally revealed primary acquired melanosis (PAM) on the palpebral conjunctiva of the same eyelid. Full thickness eyelid excision and conjunctival map biopsy identified desmoplastic melanoma of the eyelid in addition to invasive conjunctival melanoma and conjunctival melanoma in situ. Sentinel lymph node biopsy was negative for metastasis. She was treated with surgical excision for the eyelid melanoma and topical mitomycin C for the conjunctival melanoma. We discuss the rare entity of desmoplastic melanoma of the eyelid and its possible association with NF1.

Molecular imaging with bioluminescence and PET reveals viral oncolysis kinetics and tumor viability.

Viral oncolysis, the destruction of cancer cells by replicating virus, is an experimental cancer therapy that continues to be explored. The treatment paradigm for this therapy involves successive waves of lytic replication in cancer cells. At present, monitoring viral titer at sites of replication requires biopsy. However, repeat serial biopsies are not practically feasible for temporal monitoring of viral replication and tumor response in patients. Molecular imaging provides a noninvasive method to identify intracellular viral gene expression in real time. We imaged viral oncolysis and tumor response to oncolysis sequentially with bioluminescence and positron emission tomography (PET), revealing the kinetics of both processes in tumor xenografts. We demonstrate that virus replication cycles can be identified as successive waves of reporter expression that occur ∼2 days after the initial viral tumor infection peak. These waves correspond to virions that are released following a replication cycle. The viral and cellular kinetics were imaged with Fluc and Rluc bioluminescence reporters plus two 18F-labeled PET reporters FHBG [9-(4-18F-fluoro-3-[hydroxymethyl] butyl) guanine] and FLT (18F-3'-deoxy-3-'fluorothymidine), respectively. Correlative immunohistochemistry on tumor xenograft sections confirmed in vivo results. Our findings show how PET can be used to identify virus replication cycles and for real-time measurements of intratumoral replicating virus levels. This noninvasive imaging approach has potential utility for monitoring viral oncolysis therapy in patients.

Primary amelanotic melanoma of the nasal cavity: a case report.

Primary mucosal malignant melanomas of the nose are rare, accounting for only 0.3 to 2% of all cases of malignant melanoma and about 4% of all head and neck melanomas. The amelanotic variant of mucosal malignant melanoma is even more rare, and the prognosis is poor. This variant usually arises in locations in which it is not noticeable, and therefore it is usually diagnosed at an advanced clinical stage when symptoms eventually manifest. We report a case of locally advanced amelanotic melanoma of the nasal cavity in a 55-year-old woman who presented with complaints of nasal obstruction and intermittent bleeding on the right side of the nose for 3 months and a gradually progressive diffuse swelling over the right periorbital and maxillary areas for 2 months with associated pain for 15 days. She was diagnosed with amelanotic melanoma on the basis of clinical, radiologic, and pathologic findings. In view of her advanced disease, she declined surgery and was treated with chemoradiotherapy, and she experienced a significant alleviation of her symptoms.

Primary amelanotic melanoma of the breast: combating a rare cancer.

BACKGROUND: Malignant melanoma is the foremost cause of metastasis to the breast from extramammary solid neoplasm. However primary melanoma of the breast is a distinct rarity. Primary melanoma involves the skin and less commonly the glandular parenchyma of the breast. METHOD: We herein describe a case of primary amelanotic melanoma of the breast parenchyma in a 32-year-old female managed with a combination of surgery, adjuvant radiotherapy and immunotherapy. CONCLUSION: This case report aims to increase awareness of unusual neoplasms of the breast which might require a different surgical and adjuvant therapeutic approach.