Editor's note: Primary central nervous system (CNS) melanoma is very rare, with an annual incidence of approximately 0.01 per 100,000 [1,2], accounting for 1% of all melanomas [3-5]. Clinical symptoms and imaging findings lack specificity, and diagnosis is currently based on tissue or cytopathological biopsy, immunohistochemistry, and molecular pathology. There is no standard treatment plan for primary CNS melanoma, and surgery, radiation therapy and chemotherapy are mostly used in clinical practice, but the efficacy is not ideal.
In this issue, Professor Wu Di from the First Hospital of Jilin University is the executive editor-in-chief, and Pengna Guo, Master of Medical Oncology from the First Hospital of Jilin University, shared the epidemiology, clinicopathological features and existing diagnosis and treatment methods of primary CNS melanoma, and proposed potential treatment strategies.
Expert presentation
Wu Di
Doctoral supervisor and chief physician of the Cancer Center of the First Hospital of Jilin University
Director and professor of the Comprehensive Cancer Treatment Area of the First Hospital of Jilin University
Director of the Chinese Society of Clinical Oncology (CSCO).
Vice Chairman of the Melanoma Expert Committee of the Chinese Society of Clinical Oncology
Member of the Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology
He is a member of the Expert Committee on Bone and Soft Tissue Sarcoma of the Chinese Society of Clinical Oncology
He is a member of the Tumor Metastasis Committee of the Chinese Anti-Cancer Association
He is a standing member of the Expert Committee of Oncology and Cardiology of the Chinese Society of Clinical Oncology
Guo Pengna
Master of Medical Oncology, First Hospital of Jilin University
Main research directions: targeted, immunological, chemotherapy and other comprehensive treatments for melanoma.
Title: Clinicopathological features, diagnosis and treatment status and progress of primary central nervous system melanoma
◾ Author: Guo Pengna
◾ Executive Editor-in-Chief: Wu Di
First, the characteristics of the disease
In a retrospective study, there were two peaks in the age of onset of primary CNS melanoma, the first decade and the fourth decade [1,6-9], accounting for 16.7 percent and 21.8 percent [6]. In a gender analysis of 59 patients, the male-to-female ratio was 1.46:1 [6]. There are also small samples or anecdotal reports that do not match the results [10-15]. The main site of onset is the meninges, followed by the brain parenchyma and spine. The temporal and frontal lobes are also commonly reported sites [16].
The majority of primary CNS melanomas are directly malignant transformation from melanocytes, and a few are associated with meningeal melanocytic tumors [7-10,17-23]. The clinical presentation depends primarily on the anatomical location of the tumor and the structure of the compressed nerve [22]. When tumors are located in the brain, they typically present with intracranial hypertension, hydrocephalus, focal neurologic deficits, subarachnoid hemorrhage, and seizures [1,6,24,25]. Lesions located in the spine are often associated with back pain, limb weakness, and sensory and motor impairments [6,26].
2. Imaging manifestations
MRI is the imaging modality of choice for diagnosing primary CNS melanoma [4], but imaging findings are affected by the amount of melanin and the presence or absence of hemorrhage [2,14,27]. When tumors with a melanin content of > 10 percent are more likely to exhibit hyperintensity on T1-weighted images and hypointensity on T2-weighted images, this is referred to as the "melanocyte" pattern and vice versa [2,14,19,23,27-31]. The paramagnetic products methemoglobin and hemosiderin of intratumoral hemorrhage in primary CNS melanoma can reduce the relaxation time of T1 and T2 and affect the diagnosis of primary CNS melanoma [10,22,32-35].
3. Diagnosis and differential diagnosis
According to the criteria proposed by Hayward in 1976, the diagnosis of primary CNS melanoma requires the absence of melanoma outside the CNS or elsewhere in the CNS and histopathologic confirmation of melanoma [1,10,36-38]. The clinical symptoms and imaging manifestations of primary CNS melanoma are very similar to those of melanoma brain metastases and CNS pigmented lesions, and it is difficult to distinguish them by histocytopathology and immunohistochemical detection alone. When there is a coexistence of melanoma in the CNS and outside the CNS or multiple melanoma in the CNS, it is extremely difficult to make a definitive diagnosis of whether the CNS tumor is primary and where it is primary.
4. Treatment
1. Traditional treatments
Surgical resection is preferred for early-stage primary CNS melanoma, and the location and size of the tumor determine the surgical approach to the tumor [39]. The addition of radical radiation therapy to incompletely unresectable tumors is beneficial for local tumor control and improved prognosis [40,41]. In the largest retrospective study to date, Carolina et al. included 54 cases of primary CNS melanoma. Seven patients underwent biopsy (B) and four patients underwent subtotal resection (STR), and the mean survival of patients after biopsy and partial resection were similar, which were 10 and 9.5 months, respectively. The average survival of the 22 patients who underwent gross total resection (GTR) was significantly improved to 31 months. The mean survival with a combination of GTR, chemotherapy (CT), and radiation therapy (RT) was 17.5 months, GTR+CT was 15 months, and GTR+RT was 34.5 months [42]. The results showed that patients with primary CNS melanoma who underwent GTR had obvious clinical benefits, while patients who could not complete GTR could significantly improve the prognosis of patients with STR + RT. However, due to the rarity of primary CNS melanoma and the lack of high-level evidence-based medical evidence, standard treatment options cannot be determined.
Treatment of advanced CNS melanoma is based on systemic chemotherapy. To date, no well-documented chemotherapy regimens have been found in the literature, and most of them are treated with temozolomide, dacarbazine, platinum, and intrathecal methotrexate, with a follow-up of between 2 and 48 months, a median progression-free survival (PFS) of 5 months, and a median overall survival (OS) of 12.5 months [1,2,23,43-49].
2. Targeted therapy and immunotherapy
Only a very small number of cases of primary CNS melanoma are treated with targeted therapy and immunotherapy. In the six primary CNS melanoma patients who received targeted therapy, all patients had varying degrees of improvement in symptoms and signs, and the median OS was 7.2 months (4.8-9.6 months). One patient with an NRAS mutation had a PFS of five months [50-52]. Five patients with primary CNS melanoma who received immunotherapy [5,53-56] had a median OS of 58 months (5-63 months).
summary
Primary CNS melanoma is rare [1,2], with atypical clinical and imaging findings, and diagnosis is mostly based on pathological biopsy. At present, there is no standard treatment option for primary CNS melanoma, surgical resection is the first treatment option, and postoperative adjuvant radiotherapy appears to confer some survival benefits. Targeted therapy and immunotherapy are expected to be potential treatment options for primary CNS melanoma, and multidisciplinary treatment may be more effective. However, there is still a lack of large-scale clinical studies in patients with primary CNS melanoma. In-depth study of the pathogenesis, molecular pathology, and tumor immune microenvironment characteristics of primary CNS melanoma can provide a theoretical basis for the development of future treatment strategies.
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