Diagnosis Of Metastatic Melanoma Research Articles

Diagnosis of metastatic melanoma by fine-needle aspiration biopsy (FNAB) and primary melanoma using the skin and mucousa imprints

BACKGROUND: Determination of the cytogenetic origin and morphological type of metastatic or primary tumor determines the prescription of therapy and affects to the patient’s efficiency treatment. Currently, a number of publications evaluate the potential of cytological diagnostics of melanoma.AIM: To evaluate the significance of diagnostics of metastatic melanoma by fine-needle aspiration biopsy (FNAB) and primary melanoma using the skin and mucosa imprints. MATERIALS AND METHODS In a retrospective study, a comparative analysis of cytological “melanoma” samples, in comparison with clinical and anamnestic information and the results of histological, immunohistochemical, and molecular genetic studies were carried out.Information about 109 patients from the cancer registry of the Altai Regional Oncology Dispenser (Barnaul) for 2022 was used in the work. Traditional and liquid based methods for patterns preparing were used. The samples were stained using Pappenheim and Papanicolaou methods. In some observations, cytological material was used for molecular genetic studies. Using the cancer registry data of the dispensary, the results of histological and of molecular genetic studies, and a final conclusion was given about each patient. RESULTS: Fine needle biopsy (FNA) was carried out in 80 patients. Tumor smears were obtained from 29 patients. The cytological diagnose “melanoma” was consistent with the data of histological and immunohistochemical studies (p 0.001) for all 109 patients. Melanoma was diagnosed for the first time in 64 (58.7%) patients. In other cases, the process of progression was noted from one year to 20 years. Epidermal melanoma was noted in 101 (92.7%) cases, including 9 patients with acral melanoma, and 2 cases on the vulva. Melanomas of mucosa were found in 5 cases (4.5%): in the rectum and anal canal, vagina, and in 2 cases on the hard palate. Non-epidermal (uveal) melanomas metastases were diagnosed in liver by FNAB in 3 patients (2.8%). Based on the cellular composition, epithelioid cell melanoma was determined in 91 (83.5%) patients, mixed cell in 10 (9.2%) cases, spindle cell in 6 (5.5%), pigmentless in two (1.8%) cases and nevoid melanoma(0.9%) in 1 case. The mutation status was determined in 96 patients (88.1%). Of these, in 8 patients the study was determined using cytological material. In epidermal melanomas, mutations in codon 600 of exon 15 of the BRAF gene were found in 43 (44.8%) patients, including 2 cases of acral melanoma. Mutations V600K, V600E/Ec were found in one observation (1.1; 1.1%). In mucousal melanomas: vaginal melanoma, the Q61R mutation was found in exon 3 of the NRAS gene; In anal canal melanoma, the G12C mutation was identified in exon 2 of the NRAS gene. In uveal melanomas, the assessed mutations were absent (the determining GNAQ11 and BAP1 mutations is necessary). CONCLUSIONS: Cytological diagnosis of melanoma by fine-needle aspiration biopsies and imprints from the tumor mass is a highly informative method that allows diagnosing melanoma verifying the tumor subtype.The obtained results indicate tumor heterogeneity and differences in mutational status depending on the location of melanomas. The molecular classification of melanoma is important when choosing individualized therapy.

Hearing loss, why bronchial tree may be involved?

A 62-years-old man former occasional smoker was hospitalized for progressive hearing loss and Magnetic Resonance Imaging (MRI) detected multiple round hyperdense lesions in each cerebral hemisphere. Total body Computed Tomography (CT) scan showed a lobulated consolidative lesion on the right lung lower lobe associated to conglomerate lymph nodes (11R) suspected for primary lung cancer. Endoscopy showed an endobronchial invasion and integrated endobronchial ultrasound did not demonstrate any accessible lymph node for sampling. Forceps biopsy report on the endobronchial specimen led to histopathological diagnosis of metastatic melanoma. Skin and ophthalmologic examinations were negative for suspicious pigmented lesions findings and patient had no history of familiarity for melanoma. Malignant melanoma is rarely observed to metastasize to endobronchial tissue and it is represented only in the 4.5% of cases. The vast majority of endobronchial metastases are metachronous, even after several years. Nevertheless, the anachronous manifestations are possible.

Combining Biomarkers for the Diagnosis of Metastatic Melanoma.

The early detection of melanoma relapse can improve patient survival; thus, there is a great need for easily accessible biomarkers that facilitate the diagnosis of metastatic disease. We investigated the diagnostic effect of blood biomarkers such as lactate dehydrogenase (LDH), S100B, and osteopontin in the detection of metastases. Clinical data and peripheral blood samples of 206 melanoma patients were collected (no metastasis, N = 120; metastasis, N = 86). The discriminative power of blood biomarkers, patient demographics, and clinicopathological parameters of primary melanomas were evaluated using univariate and multivariate logistic regression models and receiver operating characteristic (ROC) analysis to determine the area under the curve (AUC). Plasma osteopontin levels showed a significant and independent effect on the probability of metastasis, similar to serum S100B levels. In addition, the location of the primary tumor on the lower extremities and the American Joint Committee on Cancer (AJCC) categories pT2b-3a, pT3b-4a, and pT4b were associated with the diagnosis of metastasis. Importantly, the combination of the three blood biomarkers and primary tumor localization and AJCC pT category yielded excellent discrimination (AUC: training set: 0.803; validation set: 0.822). In conclusion, plasma osteopontin can be classified as a melanoma biomarker; moreover, by combining clinicopathological prognostic variables, the diagnostic effect of blood biomarkers in the detection of metastatic melanoma can be improved.

Characteristics of long-survivor metastatic melanoma after polychemotherapy and interferon: a retrospective study.

The development of immunotherapy and tyrosine kinase inhibitors dramatically improved the prognosis of metastatic melanoma. Consequently, chemotherapy is now rarely used. Here, we describe the characteristics of long-surviving patients with metastatic melanoma treated with immunochemotherapy. We retrieved retrospective clinical and pathological data for patients diagnosed with metastatic melanoma between January 1993 and December 2015 who received the CVD-INF (cisplatin, vinblastine, dacarbazine, and interferon α-2b) regimen at the Hôpitaux Universitaires de Genève. We estimated their progression-free survival and overall survival. This ad hoc study's primary aim was to describe the clinical and biological characteristics of long-term survivors, defined as patients surviving more than two years after immunochemotherapy initiation. The spatial distribution pattern of CD8+T cells (inflamed, excluded, or desert) was immunohistochemically determined. Ninety patients received CVD-INF. Their median age at metastatic melanoma diagnosis was 55 years (20-75). Their median progression-free survival was 2.8 months, and median overall survival was 7.2 months. Eleven (12%) patients were long-term survivors. In multivariate analysis, central nervous system metastases (hazard ratio [HR]: 2.66; 95% confidence interval [CI]: 1.43-4.95; p = 0.001), multiple metastases (HR: 1.82; 95% CI: 1.01-3.29; p = 0.047), and elevated lactate dehydrogenase (LDH) (HR: 1.92; 95% CI: 1.12-3.30; p = 0.016) were independently associated with shorter survival. Most long-survivors (6/8; 75%) had a tumour-inflamed pattern compared to 25% of non-long survivors (5/20; Fisher's test p = 0.030). A subset of patients with metastatic melanoma and a tumour-inflamed phenotype treated with CVD-INF survived over two years. Factors associated with prolonged survival are consistent with those previously reported in metastatic melanoma.

Disparity in initiation of checkpoint inhibitors among commercially insured and Medicare Advantage patients with metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma, but racial disparities in melanoma outcomes continue. These inequities are not fully explained by individual factors. OBJECTIVE: To investigate the associations of neighborhood factors with the use of ICIs in metastatic melanoma. METHODS: We conducted a retrospective cohort study of commercially insured US adults with metastatic melanoma diagnosed between January 2011 and December 2020. We examined the associations between the county-level percentage of population from racial and ethnic minority groups and the time from metastatic melanoma diagnosis to initiating ICIs using Cox proportional hazards models adjusting for patient characteristics. RESULTS: We identified 4,052 patients with metastatic melanoma, of which 49% used ICIs. We found that the adoption of ICIs in a county declined with increasing minority quintile (quintile 1: 52.4%, quintile 2: 50.4%, quintile 3: 50.1%, quintile 4: 45.8%, and quintile 5: 44.7%). The delay in ICI initiation also went up as the percentage of minorities in a county increased (log-rank test P = 0.03). Compared with the lowest quintile, the adjusted hazard ratio of ICI initiation of the second, third, fourth, and highest minority quintile was 0.94 (95% CI = 0.81-1.08), 0.88 (95% CI = 0.76-1.02), 0.81 (95% CI = 0.68-0.97), and 0.77 (95% CI = 0.66-0.91), respectively. Secondary analysis revealed that the slower initiation was driven by the counties with the highest percentage of Hispanic population (hazard ratio = 0.74; 95% CI = 0.61-0.89) in both Cox models and sensitivity analyses. High-minority counties correlated with metro areas, higher poverty levels, and a greater number of medical oncologists. CONCLUSIONS: We found that patients with metastatic melanoma living in counties with higher proportion of minorities, particularly of Hispanic origin, are more likely to experience delays in ICI treatment. This study provides important population-level data on neighborhood-level disparity in medication use. More research is needed on the underlying provider- and system-level factors that directly contributed to the lower use of cancer medicines in high-minority areas, which can help inform the development of evidence-based medication use strategies that can improve health outcomes and equity.

42670 Diagnostic accuracy of image-guided biopsies for the diagnosis of metastatic melanoma in a real-life setting

42670 Diagnostic accuracy of image-guided biopsies for the diagnosis of metastatic melanoma in a real-life setting

820 Atypical Presentation of Muscular Metastasis of Melanoma in the Contralateral Limb

Abstract Case Presentation A gentleman in his 50s presented to his GP with an asymptomatic, soft, enlarging mass on his left upper arm. He had previously been diagnosed with a 4.5mm cutaneous malignant melanoma (MM) on his right arm, which was treated with an excision biopsy and a further 2cm wide local excision. He further had a sentinel lymph node biopsy (SLNB), which confirmed no residual melanoma. He was subsequently followed up routinely by the skin cancer multidisciplinary team (MDT) for five years with no concern. The patient subsequently underwent an ultrasound scan, a Magnetic Resonance Imaging (MRI) scan, and a final staging Computed Tomography (CT). Imaging was suspicious for an intramuscular soft tissue malignancy. Core biopsy of this mass suggested a diagnosis of metastatic MM. Excision was performed within three weeks of his core biopsy. The lesion was completely excised, and formal pathology confirmed the diagnosis of metastatic MM. He has been referred to the oncology services for the commencement of Nivolumab (anti PD-1 antibody) immunotherapy according to the genetic analysis. Summary This case highlights a rare example of muscular metastasis of MM, presenting in a distant site, despite a negative SLNB, over five years from the original diagnosis. Such cases highlight the unpredictable nature of MM, reminding clinicians of the need for a low threshold for investigation of soft tissue masses in patients with a history of cutaneous malignancy.

August 2023 Medical Image of the Month: Cannonball Metastases from Metastatic Melanoma

No abstract available. Article truncated after 150 words. A 48-year-old man with a significant smoking history presented with progressive dyspnea, a mildly productive cough with brown-tinged sputum, headache, weight loss, and progressive back pain over a period of 8 weeks. The patient had no known history of lung conditions. As part of their initial evaluation, the patient received a frontal CXR and was found to have innumerable rounded pulmonary nodules throughout the lungs, which were consistent with a “cannonball” pattern of pulmonary metastatic disease (Figure 1A). A subsequent CT confirmed innumerable pulmonary metastases (Figure 1B). An MRI of the brain and spine revealed hemorrhagic brain metastases (Figure 2), spinal metastases, and bone metastases. A biopsy of a lesion in the left iliac bone confirmed the diagnosis of metastatic melanoma. This case highlights the so-called “cannonball” pattern of pulmonary metastatic disease with innumerable round nodules throughout the lungs with a slight lower lung predilection, consistent with a hematogenous spread …

DP08 Next-generation sequencing: the future for malignant melanoma diagnostic precision? A case of a BAP1 mutation

Abstract A 48-year-old man presented to the hand surgeons with a 5-year history of a subcutaneous swelling on his right wrist, associated with paraesthesia and pain, initially thought to be a benign ganglion. Excision biopsy of the lesion on histology revealed an encapsulated pleomorphic tumour attached to a nerve, thought to represent a sarcoma. Immunohistochemistry showed a positive reaction to S100, SOX10, calretinin and synaptophysin. Ki67 showed a 20% proliferation index. Multiple pathology opinions were sought, and further testing was performed at a specialist genomic laboratory. Detailed questioning regarding family history of malignancy revealed that the patient’s mother had died from metastatic uveal melanoma, a maternal aunt had died of a brain tumour and his maternal grandmother had lung cancer. Pan-cancer gene panel DNA next-generation sequencing showed a BAP1 mutation with a very high variant allele fraction, suggestive of germline inheritance. Given the clinical history, morphology, immunoprofile and DNA result, a favoured diagnosis of metastatic malignant melanoma with a BAP1 mutation was made. The patient was referred to the specialist skin cancer multidisciplinary team meeting and reviewed by the dermatology team. Full skin check examination revealed two long-standing atypical naevi (> 10 years), one on the left forearm and another on his back, and these were excised urgently. Histology of the back lesion showed a polypoid melanocytic tumour comprising large epithelioid melanocytes with mild-to-moderate nuclear pleomorphism, multinucleated cells and intranuclear inclusions. This was in keeping with a pT4a nodular malignant melanoma with 7-mm Breslow thickness, associated with BAP1-inactivated syndrome. Histology of the left forearm lesion was consistent with a combined BAP1-inactivated melanocytoma, otherwise known as a ‘BAPoma’. An ophthalmology review did not identify a primary uveal melanoma. Staging scans of his chest, abdomen and pelvis and magnetic resonance imaging of his head showed no evidence of metastatic disease. The patient was referred for genetics counselling, wide local excision of the melanoma on his back, for consideration of adjuvant therapy with oncology and long-term follow-up with dermatology. BAP1 tumour predisposition syndrome is a newly recognized cancer syndrome that predisposes the patient to uveal melanoma, malignant mesothelioma, renal cell carcinoma, cutaneous melanomas and a range of other cancers (Masoomian B, Shields JA, Shields CL. Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. J Curr Ophthalmol 2018; 30:102–9). BAP1-related cancers tend to occur earlier in life and are more aggressive. Our case highlights the need for early identification of germline mutations through sequencing to improve outcomes and treatment-related morbidity by early diagnosis in these rare cancer syndromes.

Safety and preliminary efficacy of intrathecal (IT) and intravenous (IV) nivolumab (N) for patients (pts) with leptomeningeal disease (LMD).

9554 Background: Pts with LMD have a dismal prognosis, with median overall survival (OS) < 3 months, no approved therapies and extremely limited clinical trial options. We previously reported initial safety findings from the dose escalation of an open label, single arm, single center phase I/IB trial (NCT03025256) for pts with metastatic melanoma (MM), in which IT/IV N were well tolerated, without any CNS-specific or unexpected toxicity. Here we report an update on safety, maximum tolerated dose (MTD), and dose expansion cohort (including 2 pts with NSCLC) and preliminary efficacy. Methods: Pts aged ≥18 with evidence of LMD by MRI and/or CSF cytology, ECOG PS ≤2 were treated with IT/IV N. Dexamethasone (dexa) ≤4mg/daily and concurrent BRAF/MEK inhibitor(i) therapy (tx) were allowed. For cycle 1, IT N was administered via ommaya reservoir on day (D)1. For subsequent cycles (every 14 days) pts received IT N on D1, followed by IV N 240 mg on D2. IT N doses evaluated were 5, 10, 20, and 50 mg. Blood and CSF were collected at multiple time points for translational research. The primary objectives were to determine safety and/or recommended dose/MTD of IT N given with IV N in pts with LMD and the safety of the MTD in an expansion cohort. OS was a secondary objective. Bayesian mTPI methodology was used to define the MTD. Results: 50 pts were treated: 17 in the dose escalation (2 at 5; 3 at 10; 6 at 20; 6 at 50 mg IT N), 8 in the initial expansion of 20mg, and 25 at the MTD 50 mg IT N. 48 pts had a diagnosis of MM, 2 NSCLC. Median age at LMD was 49 (19-74); 27 pts are male. All pts had radiographic evidence of LMD; 26 pts had positive baseline CSF cytology. 46 pts received prior systemic tx including checkpoint inhibitors (n = 42) and targeted tx (n = 34). 39 pts had prior CNS radiation (RT), including whole brain RT (n = 14). 18 pts used concurrent steroid, with a median dose of 2mg (0.9-4) dexa equivalent and 27 pts used concurrent targeted tx with BRAF/MEKi. The median number of IT N doses was 6 (1- 92). The combination regimen was well tolerated by all evaluable pts (n = 50), with 9 pts (18%) experiencing grade (gr) 3 AEs and no reported gr 4 or 5 toxicities. Rash (58%), nausea (44%), vomiting (34%), and dizziness (22%) were the most common AEs. Thirty pts (60%) experienced AEs after IT N administration, all gr 1/2 and 1 gr 3 (vasogenic edema). At a median follow-up of 4.6 months (mths) (0, 54.8 mths), median OS was 7.0 mths. OS was 66.6% at 3 mths, 53.1% at 6 mths and 34.8% at 12 mths. Conclusions: IT + IV nivo was safe and well-tolerated in MM pts with LMD, with no unexpected toxicities of the 50 mg MTD of IT N. OS rates at 6 and 12 mths are encouraging and support further evaluation of IT immunotherapy for LMD, including in other tumor types. Overall results also demonstrate the feasibility of prospective clinical trials in pts with LMD. Final presentation will also include immunological analysis of longitudinally collected CSF samples collected in the trial. Clinical trial information: NCT03025256 .

Recurrent malignant melanoma of the left foot with metastasis: A case report

The initial diagnosis of metastatic melanoma is relatively uncommon, and the 5-year survival rate is less than 15%. We present a case of late melanoma recurrence that manifested as an in-transit metastasis in the iliac bone, occurring two years after the excision of the tumour. In the present case report; A 59 year female was reported to the outpatient department of the medical college & associated hospital. The patients past medical history stated that she is known case of foot melanoma diagnosis and was operated in 2019. In July 2020, the patient developed recurrence in July 2020. A wide local surgical excision to achieve a 2-centimeter margin with skin graft was undertaken with an associated sentinel lymph node biopsy. Upon follow-up, it was discovered that the patient had been disease-free for a full year. However, the lesion started to reoccur in the period of July 2022. A PET-CT of her whole blood was performed. The patient received IV fluids, antibiotics, analgesics, and other supportive care before being released once the hemodynamics were determined to be stable. A 10-year period of disease-free living cannot usually be regarded as a definitive cure for melanoma. Always let your doctor know if you've previously been diagnosed with melanoma.

Atrial Flutter Leads to Diagnosis of Metastatic Melanoma Involving the Heart

Atrial Flutter Leads to Diagnosis of Metastatic Melanoma Involving the Heart

Diagnostic Accuracy of Image-guided Biopsies for Diagnosis of Metastatic Melanoma in a Real-life Setting

Early detection of melanoma metastasis is essential in order to initiate treatment and improve patient prognosis. The aim of this study was to determine the diagnostic accuracy of different image-guided biopsy techniques in patients with melanoma. A cohort study of patients diagnosed with melanoma who had undergone image-guided biopsies (ultrasound-guided fine-needle aspiration cytology, ultrasound-guided core-needle biopsy, computerized tomography--guided fine-needle aspiration cytology and computerized tomography-guided core-needle biopsy) to detect melanoma metastasis between 2004 and 2021 was conducted. The reference standard was histological confirmation and/or clinical-radiological follow-up. Sensitivity, specificity, positive and negative predictive values were calculated. A total of 600 image--guided biopsies performed on 460 patients were included for analysis. Locoregional lesions represented 459 (76.5%) biopsies, and 141 (23.5%) were distant lesions. Of the included biopsies, 49 (8.2%) were insufficient for diagnosis. Overall, sensitivity and specificity were 92% (95% confidence interval 89-94) and 96% (95% confidence interval 91-99), respectively. Sensitivity sub-analyses revealed lower diagnostic accuracy values in the lung, inguinal lymph nodes, and computerized tomography-guided lesions under 1 cm. Limitations include spontaneous metastasis regression and arbitrary minimum follow-up period. Image-guided biopsies in patients with melanoma have high sensitivity and specificity for detection of regional or distant metastasis. Tissue type, location and tumour burden may influence the diagnostic accuracy of the test.

Metastatic Common Bile Duct Melanoma Presenting as Obstructive Jaundice: A Case Report and Review

Abstract Introduction/Objective Malignant melanomas (MM) account for 4-7% of all new cancer cases. The most common primary site is the skin, however, in 1.3% of cases, these tumors originate from the mucous membranes of the respiratory, genitourinary, and gastrointestinal tracts. The metastatic spread to the biliary system is extremely infrequent, with rare reports in the literature. Herein, we report a case of history of cutaneous MM with metastasis to the biliary tract. Methods/Case Report A 35-year-old Caucasian female presented with pruritis, dark urine, and jaundice. Laboratory results favored the cholestatic process (total bilirubin – 10 mg/dL, alkaline phosphatase – 500 U/L, AST- 400 U/L, ALT – 1000 U/L). She had a remote diagnosis of MM of the left chest with metastases to bilateral axillary and periclavicular lymph nodes 8 years ago. She underwent wide local excision of the skin lesion and lymph node dissection then. ERCP with direct cholangioscopy revealed a 3 x 2 cm obstructive mass in the common bile duct which was biopsied to reveal cohesive, pleomorphic, epithelioid cells containing black-brown pigment with enlarged, irregular, and hyperchromatic nuclei. These atypical cells stained strongly with SOX10 and Mart-1 immunohistochemical stains, confirming the diagnosis of metastatic malignant melanoma. Results (if a Case Study enter NA) NA. Conclusion MM is cancer that originates from melanocytes, derived from the neural crest during embryogenesis. The pathogenesis of metastatic spread to the biliary system is still unknown due to the paucity of literature describing this. Diagnosis is often difficult, with many patients completely asymptomatic or occasionally presenting with biliary symptoms. There should be a detailed history, and extensive clinical workup along with extensive histological and immunoprofile, esp. in cases with a history of cutaneous melanoma for early detection of a potential metastasis leading to adequate management.

Undifferentiated Melanoma: A Rare Phenomenon and a Challenging Diagnosis

Abstract Introduction/Objective Undifferentiated melanoma is defined as a primary or metastatic melanoma lacking histologic and immunophenotypic features of melanoma. Dedifferentiated melanoma shows transition between undifferentiated and conventional melanoma components. Dedifferentiation and transdifferentiation (implying dedifferentiation with heterologous elements) in melanoma are exceedingly rare and occur mostly in metastatic deposits. The purpose of this report is to describe a case of undifferentiated melanoma that proved to be a diagnostic challenge and to highlight the importance of the multimodality approach and utilization of advanced diagnostic tools in reaching an accurate diagnosis. Methods/Case Report Methods: A 43-year-old white male who was diagnosed with metastatic melanoma on the right axillary biopsy at a local hospital presented to our institution with a rapidly enlarging 30 cm peritoneal mass. He underwent debulking surgery to lower his tumor burden. On pathologic evaluation, the tumor showed a heterogeneous appearance ranging from highly cellular fascicles of spindle cells to sheets of primitive round cells and epithelioid cells with abundant eosinophilic cytoplasm. One metastatic focus showed heterologous cartilaginous differentiation. This morphologic appearance elicited the differential diagnosis of metastatic melanoma, primitive neuroectodermal tumor, synovial sarcoma, and metastatic germ cell tumor with somatic transformation. Immunochemical staining showed the tumor cells to be positive for SALL4, CD99 (patchy), and TLE1 (patchy) and negative for pan-cytokeratin, S100, SOX- 10, HMB-45, desmin, myogenin, DOG1, CD 117, CDX2, TTF-1, PAX-8, CK7, CK20, chromogranin, CD30, and OCT4. Fluorescence in situ hybridization for EWSR1, SS18(SYT), and isochromosome 12p were negative. BRAF gene mutation analysis detected p.V600E / p.V600D. Subsequently, a diagnosis of undifferentiated melanoma was rendered after expert consultation. Unfortunately, the patient passed away 1 month after surgery. Results (if a Case Study enter NA) NA. Conclusion Diagnosis of undifferentiated melanoma by the conventional H&E and immunohistochemical profile is extremely challenging. Multimodality approach and utilization of advanced diagnostic tools such as molecular studies are helpful in this regard.

Severe irAEs in patients with immune checkpoint inhibitor therapy: Experience in a Mexican cancer center.

e14559 Background: A relationship has been found between a better response to treatment and the presence of irAEs. Different potential factors for developing them have been described, including the type of immunotherapy and their combination. Rare (< 1%) and potentially life-threatening irAEs have been reported, which due to severity lead to treatment discontinuation, and a prolonged effective response is seen in these patients if they survive the irAE. Methods: Observational study in patients with solid tumors who received treatment with immune checkpoint inhibitor and their characteristic, that presented irAEs grade 3 and 4 using the CTCAE version 4, from January to December 2021 in a Mexican cancer center. Results: irAEs grade 3 or 4 were observed in 7 (5.6%) of 125 patients, with an age range of 60 to 69 years, most of the patients had a diagnosis of metastatic melanoma (43%) and secondly urothelial carcinoma with 29%. The predominant treatment was pembrolizumab monotherapy (56%), with an average of 5 applications after those who presented irAEs. The rare irAEs presented were myocarditis (2.4%), myositis (1.6%), myasthenia gravis and interstitial nephritis, both with 1%. 70% of these patients were managed with three boluses of methylprednisolone and subsequently prednisone 1 mg/kg as maintenance. The median appearance of these irAEs was 72 days. Myocarditis and myositis had an earlier onset with an average of 32 days. One of the seven patients presented myasthenia gravis, myositis and myocarditis concomitantly, with complete response of the neoplasia, however, due to the prolonged use of immunosuppressants to control irAEs, the disease recurred at 7 months. Two of the three patients with myocarditis had a complete response and remain disease free. 57% survived more than 90 days, of which 75% are still alive. Conclusions: Among the 125 patients who received an immune checkpoint inhibitor in our cancer center in 2021, the most prevalent serious irAE was myocarditis, with a higher incidence than that reported by other centers, and a prolonged therapeutic response was found in the patients who presented it.

Comparison of PET-based criteria of evaluation of response to immunotherapy in patients with advanced melanoma.

e21536 Background: Immune checkpoint inhibitors (ICI), such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1), have evolved as a dominant strategy in the treatment of metastatic melanoma (MM) in the last decade. At least three PET-based criteria are available for the early assessment of response to immunotherapy: PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy (PECRIT), PET Response Evaluation Criteria for Immunotherapy (PERCIMT) and European Organization for Research and Treatment of Cancer (EORTC) criteria. The aim of this study was evaluation of the concordance of different PET-based criteria for the assessment of response to immunotherapy and to assess their capability of properly stratifying patients in terms of overall survival (OS) and progression free survival (PFS). Methods: We retrospectively enrolled patients with the following inclusion criteria: diagnosis of MM, treatment with ICI for MM and tumor assessment performed by at least two [18F]F-fluorodeoxyglucose (FDG) PET/CT scans (a baseline and ad interim scan). [18F]F-FDG PET/CT scans were analyzed according to PECRIT, PERCIMT and EORTC criteria. Agreement was assessed using Fleiss' kappa and Cohen’s kappa. Prognostic curves of PET/CT response according to different criteria were evaluated in terms of PFS and OS by Kaplan-Meier estimates and were compared by log-rank test. Results: From December 2021 to January 2022, 30 patients were enrolled. 18/30 patients received nivolumab, 8/30 pembrolizumab, 3/30 ipilimumab and 1/30 the combination of nivolumab and ipilimumab. According to PECRIT criteria, 6 patients achieved complete metabolic response (CMR), 7 partial metabolic response (PMR), 5 stable metabolic disease (SMD) and 12 (40%) progressive metabolic disease (PMD). By PERCIMT criteria, 6 patients had response classified as CMR, 9 PMR, 8 SMD and 7 (23.4%) PMD. Finally, by EORTC criteria there were 6 CMR, 10 PMR, 2 SMD and 12 (40%) PMD. In 9 cases out of 30, one criteria assessment differed from the other two and in one patient each criteria evaluation differed from the others (PMD by PECRIT, SMD by PERCIMT, PMR by EORTC). The percentage of patients concordantly evaluated by the three criteria was 68% (Fleiss’ kappa = 0.68). PECRIT and EORTC criteria showed the highest agreement (Cohen’s kappa 0.719), followed by PERCIMT and PERCRIT (Cohen’s kappa 0.69). PERCIMT and EORTC showed 64.4% of concordance. Furthermore, all three criteria were successful in stratifying patients in terms of OS and PFS (p-value < 0.05). Conclusions: We observed substantial agreement among different PET evaluation criteria, with PECRIT and EORTC criteria showing the highest concordance. Analysis of a larger population is needed to prove the utility of PET response evaluation in early prognostic stratification.

Delayed metastatic melanoma to the pharyngeal tonsil in a Chinese male

Background: Melanoma is a relatively uncommon malignant neoplasm, either primary or secondary. We present a case of delayed metastatic melanoma to the pharyngeal tonsil. Case report: A 70-year-old Chinese male presented for half a year due to vague speech and snoring and then found tonsil enlargement. Three years prior to presentation, he had undergone primary resection and systemic therapy for cutaneous melanoma on the sole of his foot. Tonsil biopsy confirmed the diagnosis of metastatic melanoma. Currently the patient is undergoing chemotherapy. Conclusion: Metastatic melanoma is a rare disease, and metastatic lesions may occur at any location. For the long-term survival of patients, careful examination should be done during the follow-up period, including head and neck. Keywords: metastatic melanoma; tonsillar neoplasms.

Value of screening and follow-up brain MRI scans in patients with metastatic melanoma.

BackgroundNovel treatments make long‐term survival possible for subsets of patients with melanoma brain metastases. Brain magnetic resonance imaging (MRI) may aid in early detection of brain metastases and inform treatment decisions. This study aimed to determine the impact of screening MRI scans in patients with metastatic melanoma and follow‐up MRI scans in patients with melanoma brain metastases.MethodsThis retrospective cohort study included patients diagnosed with metastatic melanoma or melanoma brain metastases between June 2015 and January 2018. The impact of screening MRI scans was evaluated in the first 2 years after metastatic melanoma diagnosis. The impact of follow‐up MRI scans was examined in the first year after brain metastases diagnosis. The number of MRI scans, scan indications, scan outcomes, and changes in treatment strategy were analyzed.ResultsIn total, 116 patients had no brain metastases at the time of the metastatic melanoma diagnosis. Twenty‐eight of these patients (24%) were subsequently diagnosed with brain metastases. Screening MRI scans detected the brain metastases in 11/28 patients (39%), of which 8 were asymptomatic at diagnosis. In the 96 patients with melanoma brain metastases, treatment strategy changed after 75/168 follow‐up MRI scans (45%). In patients treated with immune checkpoint inhibitors, the number of treatment changes after follow‐up MRI scans was lower when patients had been treated longer.Conclusion(s)Screening MRI scans aid in early detection of melanoma brain metastases, and follow‐up MRI scans inform treatment strategy. In patients with brain metastases responding to immune checkpoint inhibitors, treatment changes were less frequently observed after follow‐up MRI scans. These results can inform the development of brain imaging protocols for patients with immune checkpoint inhibitor sensitive tumors.

S2666 Recurrence of Uveal Melanoma Presenting as Hepatic Metastases

Introduction: Uveal melanoma is considered a rare cancer with a stable incidence of 5.1 per million for many years. This is contrast to cutaneous melanoma that has had steadily increasing incidence since the 1970s. Due to the lack of lymphatics in the uveal tract, ocular melanomas spread hematogenously with the liver being a commonly affected organ. Case Description/Methods: A 69-year-old man presented to the hospital with progressive right upper quadrant pain over the past 3 weeks. He had a history of uveal melanoma status post enucleation in 2016 without evidence of recurrence on several years of follow up. On arrival to the hospital, the patient was hemodynamically stable with laboratory values significant for a bilirubin of 7.2 mg/dL (direct of 5.7 mg/dL), alkaline phosphatase of 212 IU/L, AST 90 U/L, and ALT 42 U/L. Computerized Tomography (CT) showed multiple hypoattenuating lesions in the liver without biliary obstruction. MRI demonstrated several different types of hepatic lesions. This included an increased T2 signal with heterogeneous enhancement measuring 16.2 x 9.7cm, several foci of arterial phase hyperenhancement with the largest measuring 4.4 x 5.3 cm, and several rim enhancing lesions. The patient received a liver biopsy with tumor cells positive for SOX 10 and Melan A (Figure) consistent with metastatic melanoma. He underwent complete staging, including a brain MRI, with only other findings of a sclerotic L1 lesion. The patient decided to pursue comfort care and was discharged to home. Discussion: We report here a case of recurrent melanoma of uveal origin presenting as hepatic metastases. Uveal melanoma has low incidence but carries a very poor prognosis as median overall survival is 4-15 months. Even if treated, there is a high risk of recurrence with metastatic disease, largely to the liver, with majority appearing within 10 years of initial treatment. Survival is directly related to the presence and progression of liver metastases. There are currently no guidelines for surveillance or standard of care treatment modalities for metastatic uveal melanoma. Our patient was closely monitored by his oncologist, and follow-up was discontinued after several disease-free years. This case demonstrates that patients with a history of uveal melanoma may benefit from continued surveillance with liver enzyme tests and liver imaging, akin to hepatocellular carcinoma screening. Heightened physician vigilance and patient awareness may aid in early diagnosis of recurrence.Figure 1:: A) Hematoxylin and eosin stain, B) SOX-10 immunostaining. The tumor cells are positive for SOX10, Melan A, negative for arginase and HSA. The results support the diagnosis of metastatic melanoma.