Amelanotic Melanoma Invading the Heart.

We present a case of a middle-aged woman who initially presented with shortness of breath but was ultimately found to have a large mass-like lesion in the right atrium of the heart with multi-modality imaging including cardiac computed tomography, cardiac magnetic resonance imaging, and echocardiogram. Biopsy results were positive for amelanotic melanoma. The patient underwent extensive debridement surgery, and she was started on chemotherapy with a close follow-up with an oncologist. In the setting of an aggressive course of disease, unfortunately, the patient passed away secondary to sudden cardiac arrest.  Cardiac melanoma, also known as melanoma of the heart, is an extremely rare type of melanoma that originates in the heart. This case attributes to the professional growth and competency of healthcare providers involved in the care of patients with cardiac melanoma, ultimately aiming to optimize patient outcomes and quality of life. Due to its rarity and the challenges associated with its diagnosis and treatment, prognosis for cardiac melanoma is generally poor. However, advancement in cancer research and treatment may offer hope for improved outcomes in some cases.

Challenges in the Diagnosis and Treatment of Oral Amelanotic Malignant Melanoma: A Case Report.

Oral malignant melanoma (OMM) is extremely rare and usually has a poor prognosis. Early diagnosis is very important and can improve survival but it is usually difficult due to a lack of symptomatology. We present the first case of a 39-year-old East European woman with oral amelanotic melanoma, who underwent surgery and adjuvant immunotherapy; however, after six months, she developed local recurrence. The patient continued immunotherapy with external radiotherapy targeting the oral tumor recurrence. During therapy, imagistic reevaluation brought evidence of bones, lungs, liver, endotracheal, and brain metastases. Histological differential diagnosis between amelanotic OMM and leiomyosarcoma was necessary to establish the right course of treatment. A series of complications further delayed chemotherapy administration, making the treatment in this case very challenging. The patient had a significant, although late response to immunotherapy, and maintained a good performance status during disease progression with a survival of 15 months until present.

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma-A Systematic Review.

BACKGROUND: Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies. METHODS: A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed. RESULTS: Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas. CONCLUSIONS: The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.

Unusual location of subungual amelanotic melanoma in 39-year-old patient: a rare case report.

Introduction and importance: Melanoma represents only 1% of all skin cancers. Acral lentigious melanoma (ALM) which usually arises from feet, is the rarest main subtype of melanoma. Subungual melanoma (SUM) is a rare variant of ALM. Amelanotic melanoma (AM) is found only in 4-27.5% of melanomas, and the mean age for patients affected by AM exceeds 50 years. Late diagnosing leads to unfavourable prognosis. Case presentation: The authors present a case of subungual amelanotic melanoma that affected the nail unit of the right thumb which is a rare case, especially when the patient is only 39 years old. The lesion enlarged over a year and was misdiagnosed many times and treated with no response. Sentinel node biopsy was positive and the patient was moved to a specialized hospital for treatment. Clinical discussion: Diagnosing subungual amelanotic melanoma is challenging, not only because it is the rarest, but also it mimics many benign and malignant neoplasms due to the lack of pigmentation, in addition to the absence of clinical diagnostic features. AM exhibits a high growth rate helping in limiting the window for early detection. Conclusions: Lately diagnosed subungual amelanotic melanoma usually associates with an increased risk of metastases, So it should be considered as a cause of any non-healing lesion. Early diagnosing gives patients the best chance for survival.

Challenges in diagnosing canine spindle cell tumours using immunohistochemistry, illustrated by three nonpigmented malignant cases from the nictitating membrane.

BACKGROUND: Nonpigmented malignant spindle cell tumours of the membrana nictitans are rare in dogs. In twenty-three years only three cases have been diagnosed in Scandinavia. This study describes the three cases of malignant tumours of the membrana nictitans recorded by the Eye Pathology Section, University of Copenhagen, Denmark, with reference to the clinical appearance and work-up, the treatment and prognosis, and the histopathological description including immunohistochemistry. The three cases are compared to previous publications on canine tumours of the nictitating membrane. We emphasize the importance of using protocols that are adapted to the specific species such as dogs. Opposite the human tissue responses, we even need more than one marker when diagnosing melanomas in dogs. RESULTS: The dogs presented were an 8-year-old Dachshund, a 12-year-old Akita and a 14-year-old Shetland Sheepdog. All three dogs were entire females. All three nictitating membrane tumours developed on the right nictitating membrane as firm or multilobulated hyperaemic masses. Two of the tumours were macroscopically nonpigmented, the third being partly pigmented on the surface and ulcerated. According to the histopathology and for two of the cases immunohistochemistry with dog-adapted protocols the diagnoses included one hemangiosarcoma and two amelanotic melanomas. Tumour regrowth developed in all three cases and repeated resections were completed 1, 2 and 3 times, respectively, with recurrence experienced within 1.5 months - 3 years. CONCLUSIONS: Nonpigmented malignant spindle cell tumours of the canine membrana nictitans are rare. Treatment of choice should be complete excision with a minimal histologic tumour-free distance and in case of a recurrence a full resection of the nictitating membrane. We strongly recommend a dog-adapted protocol for immunohistochemistry.

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.

The Cytodiagnosis of Amelanotic Primary Signet Ring Cell Melanoma at the Unusual Site of the Axilla: A Case Report of a Rare Entity.

Amelanotic primary signet ring cell melanoma is a rare variant of cutaneous malignant melanoma. The diagnosis of amelanotic primary signet ring cell melanoma is rarely made based on cytological examinations. Most of the cases reported in the routine practice involve metastatic lesions of known cutaneous amelanotic primary signet ring cell melanoma. The diagnosis of amelanotic primary signet ring cell melanoma on fine needle aspiration cytology (FNAC) is scarce. We present one such extremely rare diagnosis of amelanotic primary signet ring cell melanoma at the unusual site of the axilla, which was established on FNAC. We also discuss its histological differential diagnosis and confirmative immunohistochemistry (IHC).

Amelanotic Malignant Melanoma: A Case Report.

Amelanotic malignant melanoma (AMM) is a skin cancer that arises from mutated melanocytes that lack pigmentation. AMM represents 2-8% of all malignant melanomas. This rare subtype is difficult to diagnose clinically as it mimics other benign skin lesions. AMM can occur in any part of the body with various presentations and has a predilection for male gender and fair skin tones. We present a case report of a 62-year-old Caucasian male with AMM of the right lower extremity. The patient presented with a painless nodule on his right lower extremity that rapidly increased in size for seven months with no signs of malignancy, such as fever, night sweats, fatigue, bruising, weight loss, or headache. Simultaneously, the patient presented with right inguinal lymphadenopathy and pitting edema of the right lower extremity. The patient had a previous medical history of basal and squamous cell carcinoma and psoriasis with no personal or family history of melanoma. The mass was excised and sent to a pathologist along with a right inguinal sentinel lymph node biopsy. The final pathology report revealed an ulcerated AMM on the right lower extremity and a positive node for melanoma with a metastatic deposit. The patient underwent adjuvant immunotherapy resulting in the clearance of the cancer cells. This report highlights the importance of early diagnosis, appropriate surgical management, and adjuvant therapy to improve the prognosis of this rare melanoma subtype.

Histopathologic abundance of pigmentation correlates with disease-specific survival in malignant melanoma but is not independent of current AJCC pT stage.

The increasing number of melanoma patients makes it necessary to develop best possible strategies for prognosis assessment in order to recommend appropriate therapy and follow-up. The prognostic significance of tumor cell pigmentation has not been fully elucidated. Hematoxylin and eosin (H&E)-stained sections of 775 melanomas diagnosed between 2012 and 2015 were independently assessed for melanin pigment abundance by two investigators, and the impact on melanoma-specific survival was calculated. Unpigmented melanomas (n = 99) had a melanoma-specific survival of 67.7%, melanomas with moderate pigmentation (n = 384) had a melanoma-specific survival of 85.9%, and strongly pigmented melanomas (n = 292) had a melanoma-specific survival of 91.4% (p < .001). In an analysis of melanoma-specific survival adjusted for pT stage and pigmentation, we found a nonsignificant impact of pigmentation abundance with a hazard ratio of 1.277 (p = .74). The study presented here provides evidence in a German cohort that patients with pigmented melanomas have a more favorable prognosis than those diagnosed with nonpigmented melanomas. Moreover, the abundance of pigmentation already seems to provide a first prognostic estimate. However, it does not appear to provide significant additional value for prognostic assessment according to the AJCC 2017 pT classification.

Amelanotic Melanoma: A Great Masquerader.

Malignant melanoma is an aggressive, notorious tumor showing great variability in morphological and immunohistochemical expression, thus commonly leading to an erroneous diagnosis. Within the melanoma group, amelanotic melanoma, with its wide clinical presentations, lack of pigmentation, and varied histological appearances, has taken on a new persona as a master masquerader. Use of immunohistochemistry in the diagnosis of malignant tumors, including melanoma, is primordial and indispensable. However, the problem gets compounded in scenario of aberrant antigenic expression. The present case posed multiple diagnostic challenges in form of atypical clinical presentation, variant morphology, as well as aberrant antigenic expression. Here, we present the case of a 72-year-old male who, upon his initial presentation, was thought to be sarcomatoid anaplastic plasmacytoma, but 5 months later another biopsy from a different site revealed the actual diagnosis of amelanotic melanoma.

The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells.

BACKGROUND: Non-steroidal anti-inflammatory drugs have been shown to inhibit the development of induced neoplasms. Our previous research demonstrated that the cytotoxicity of sulindac against melanoma cells is comparable to dacarbazine, the drug used in chemotherapy. The aim of this study was to investigate the mechanism of sulindac cytotoxicity on COLO 829 and C32 cell lines. METHODS: The influence of sundilac on the activity of selected enzymes of the antioxidant system (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of hydrogen peroxide as well as the level of proteins initiating (p53, Bax) and inhibiting (Bcl-2) apoptosis were measured in melanoma cells. RESULTS: In melanotic melanoma cells, sulindac increased the activity of SOD and the content of H2O2 but decreased the activity of CAT and GPx. The level of p53 and Bax proteins rose but the content of Bcl-2 protein was lowered. Similar results were observed for dacarbazine. In amelanotic melanoma cells, sulindac did not cause an increase in the activity of measured enzymes or any significant changes in the level of apoptotic proteins. CONCLUSION: The cytotoxic effect of sulindac in the COLO 829 cell line is connected to disturbed redox homeostasis by changing the activity of SOD, CAT, GPx, and level of H2O2. Sulindac also induces apoptosis by changing the ratio of the pro-apoptotic/anti-apoptotic protein. The presented studies indicate the possibility of developing target therapy against melanotic melanoma using sulindac.

A Unique Case of Intracranial Amelanotic Melanoma with BRAF V600E Mutation Successfully Treated via Molecular-targeted Therapy.

Melanoma carries a high risk of brain metastasis. A small subset of metastatic melanomas, known as amelanotic melanomas, does not present black coloration, reflecting a lack of melanin pigmentation. Here, we report a case of B-Raf proto-oncogene (BRAF) V600E mutation associated with a metastatic brain tumor caused by the amelanotic melanoma. A 60-year-old man was transferred to our department following acute onsets of left upper limb paralysis and convulsion. In the brain imaging, multiple lesions in the right frontal lobe and left basal ganglia were detected, and the presence of an enlarged left axillary lymph node was revealed. Consequently, we removed the right frontal lesion and performed a biopsy of the left axillary lymph node. Histological analysis of both specimens indicated an amelanotic melanoma, and genetic testing revealed a BRAF V600E mutation. The residual intracranial lesions were treated with stereotactic radiotherapy and molecular-targeted therapy, with dabrafenib and trametinib as the systemic treatment. Based on the Response Evaluation Criteria in Solid Tumors, we determined that the patient achieved complete remission (CR) under uninterrupted molecular-targeted therapy over a period of 10 months. After the temporary withdrawal of dabrafenib and trametinib to avoid hepatic dysfunction, a new intracranial lesion appeared. CR of this lesion was achieved following reinstatement of the two drugs. These results suggest that, under limited conditions, molecular-targeted therapy can produce a sustained response against the intracranial metastasis of melanoma, and the therapy with reduced dose is still effective against a recurrent case after cessation of the therapy due to the toxicity.

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment.

Background: Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described. Purpose: To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure. Methods: We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq). Results: The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability. Conclusion: Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.

Melanoma primario maligno variedad rabdoide. A Propósitode un caso / Malignant primary melanoma rhabdoid variety. about a case

Resumen El melanoma primariovariedad rabdoide es unapresentación pocofrecuente.Reconocido como un subtipo histopatológico distinto de melanoma maligno generalmente observado en tumores metastásicos o recurrentes.El diagnóstico definitivo requiere el estudio de inmunomarcación y la identificación de células neoplásicas con marcadores melanocíticos. Clínicamente se han reportado mayormente de tipo nodular y amelanótico.

Summary Rhabdoid melanoma has been recognized as a histopathological subtype of malignant melanoma. It generally presents as a recurrent tumor, so its presentation as a primary lesion is infrecuent.Definitive diagnosis requires the study of immunostaining and the identification of neoplastic cells with melanocytic markers. Clinically, mostly nodular and amelanotic types have been reported.