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.

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.

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.

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.

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.

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.

Primary amelanotic melanoma of anorectum - a rare case report with diagnostic challenge.

Anorectal melanoma is an exceptionally rare and aggressive form of cancer. One per cent of anorectal malignant tumours are anorectal malignant melanomas, which are exceedingly uncommon. We report a case of a 47-year-old woman who experienced painless rectal bleeding. On examination, an irregular lump was seen in the posterior rectal wall, measuring 4 × 3.7 cm. Biopsies were obtained under endoscopic guidance for histomorphology and immunohistochemistry. The biopsy examination showed nests of tumour mass in the lamina and muscularis mucosae. The tumour mass was composed of round to oval cells having enlarged nuclei, conspicuous nucleoli, and a scant amount of cytoplasm. No melanin pigmentation was noted in the tumour cells. HMB-45, S-100, and vimentin were all detected by immunohistochemistry. A definitive diagnosis of amelanotic malignant melanoma was rendered. The patient underwent abdominoperineal resection with a hysterectomy and bilateral salpingo-oophorectomy. Anorectal melanoma presents with bleeding per rectum and is often misdiagnosed as internal haemorrhoids or adenocarcinoma clinically. Amelanotic melanoma, which lacks melanin pigment, is difficult to diagnose. Patients who appear with rectal bleeding should have a malignant melanoma evaluation as a possible differential diagnosis, and suitable diagnostic procedures, such as a colonoscopy and a biopsy with immunohistochemistry, should be carried out to arrive at a conclusive diagnosis.

Urethral Caruncle Masquerading a Primary Amelanotic Melanoma, the Risk of a Poor Prognosis due to Misdiagnosis.

Objective: Primary malignant urethral melanoma is a rare condition, concerning less than 1% of melanomas and 4% of all urethral cancers. The early treatment of urethral melanoma is extremely important due to the tendency to early metastasis. Case report : 88-year-old Caucasian lady presented vaginal bleeding. At first Gynaecological examination an urethral caruncle with otherwise normal trans-vaginal ultrasound was diagnosed. The patient not reassured asked for a second consultation opting to remove the reddish fleshy polypoid lesion protruding from the urethra. Histology revealed a urethral amelanotic melanoma. The patient underwent an excission of the urethral lesion. Urologist, oncologist and gynaecologist at tumor board meeting, considering patient's age and negative PET, decided for conservative management with close clinical and imaging follow-up.7 months after, vaginal bleeding recurred and a nodule on the anterior vaginal wall was detected and biopsied and resulted a pigmented melanoma. The patient underwent a wide margin excision. At 10 months follow-up there were no evidence of recurrence nor distant metastasis. She started a prophylactic immunotherapy with Nivolumab; at her third administration she presented only asthenia as side effect. Conclusion: It is importanto to keep in mind the urethral amelanotic melanoma to allow an early removal or biopsy, preventing diagnostic delay/misdiagnosis and aiding either in better patient management or outcome.

Lesión nodular que sangra con facilidad en zona foto expuesta / Nodular lesion that bleeds easily in a photoexposed area

Las lesiones cutáneas son uno de los principales motivos de consulta en Atención Primaria por su frecuencia y por la preocupación de las personas afectadas ante la posibilidad de que degeneren en lesiones malignas, con las implicaciones que ello tiene para la vida del paciente. La fotoexposición y los agentes externos a los que exponemos nuestra piel están relacionados con la aparición y los cambios de diferentes lesiones cutáneas. La dermatoscopia es de gran ayuda para el diagnóstico diferencial, aunque a veces nos presenta dudas por las que debemos ampliar el estudio.Presentamos el caso de una mujer de 75 años que consulta por una lesión nodular excrecente con bordes eritematosos de casi 1 cm de diámetro sobre el dorso de la mano derecha de unas 3 semanas de evolución, con bordes erosionados y sangrado recurrente, que nos plantea como diagnóstico diferencial un granuloma piógeno frente a un melanoma amelanótico.(AU)

Skin lesions are one of the main reasons for primary care consultation, both because of their frequency and the possibility of degenerating into malignant lesions with the implications on the patient's life. Photoexposure and the external agents that our skin are exposed to are related to the appearance and changes of different skin lesions. Dermoscopy is a great help for differential diagnosis, although sometimes it may create doubts and induces further examinations, whereby we must expand the study.We report the case of a 75-year-old woman who consulted about an overgrowth nodular lesion with erythematous edges. Its diameter was approximately 1 cm on the back of the right hand of about three weeks clinical course. The lesion had eroded edges and presented recurrent bleeding, which suggests a pyogenic granuloma versus an amelanotic melanoma as a differential diagnosis.(AU)

Responses of melanoma cells to photobiomodulation depend on cell pigmentation and light parameters.

Melanoma is a highly aggressive skin cancer that requires new approaches for its management. Low-level laser therapy, currently named photobiomodulation therapy (PBM), has been used to improve different conditions but its effects and safe use on melanoma remain unexplored. Herein, we investigated the PBM impact on melanoma cells differing by pigmentation using near-infrared (NIR) and red lasers in vitro. In vivo, we evaluated the effects of the red laser on melanoma-bearing mice. Amelanotic (SK-MEL-37) and melanotic (B16F10) cells were exposed in vitro to a NIR (780 nm, 40 mW) or a red laser (660 nm, 40 mW) in 3 different light doses: 30, 90, and 150 J/cm2 and responses were assessed regarding mitochondrial activity, invasiveness, migration, and VEGF production. In vivo, melanoma-bearing mice received the red laser delivering 150 J/cm2 directly to the tumor on 3 consecutive days. Mice were monitored for 15 days regarding tumor progression and mouse survival. We noticed that amelanotic cells were unresponsive to NIR light. In contrast, NIR irradiation at 30 J/cm2 promoted an increase in the invasiveness of pigmented cells, even though all light doses have inhibited cell migration. Regarding the red laser on pigmented cells, the highest light dose (150 J/cm2) decreased the VEGF production and migration. In vivo, melanoma-bearing mice treated with red laser showed smaller tumor volume and longer survival than controls. We conclude that PBM appears to be safe for amelanotic non-pigmented melanoma but triggers different responses in melanotic pigmented cells depending on light parameters. Additionally, a high dose of red laser impairs the invasive behavior of melanoma cells, probably due to the decrease in VEGF synthesis, which may have contributed to tumor arrest and increased mouse survival. These findings suggest that red laser therapy could be a new ally in the supportive care of melanoma patients.

Acral Amelanotic Melanoma Mimicking a Foot Ulcer.

Acral amelanotic melanoma can be difficult to diagnose and is often clinically aggressive. The present report describes a case of an acral amelanotic melanoma presenting as a non-healing wound after mimicking a plantar wart for two years. The decision to biopsy a borderline-suspicious lesion on the lower extremity in an elderly individual must be weighed carefully, as lower extremity biopsy carries a risk of poor wound healing and other complications. We discuss clinical and epidemiologic features that can assist in deciding when to perform a biopsy in this setting and can improve the early detection of acral amelanotic melanoma.

Primary amelanotic malignant melanoma of parotid and submandibular salivary gland: A rare case report.

Primary amelanotic malignant melanomas (AMMs) of the parotid and submandibular salivary glands are extremely rare with only a few reported cases due to its low incidence and misdiagnosis. Malignant melanoma (MM) has a high predilection for the head-and-neck region and majority of the cases in the parotid gland reported as association with metastasis in and around the gland from a cutaneous primary tumor. Immunohistochemistry is solely needed for confirmation of diagnosis and MMs give positive reactivity for melan-A, HMB-45, and S-100. Prognosis for AMM in the mucosal or salivary gland regions is much poorer than cutaneous regions because of anatomic considerations and its delayed diagnosis. The treatment of choice is radical surgery and parotidectomy along with radiotherapy and chemotherapy.