I. What is Molluscum Contagiosum Metastatic Carcinoma? Molluscum contagiosum is a serious complication of systemic cancer with high morbidity and mortality. Its primary foci are mostly lung cancer, breast cancer, hematological malignant tumor and primary tumor of central nervous system, and the tumor cells invade the meninges and grow with the cerebrospinal fluid circulation diffusely or multiply. The diagnosis mainly relies on medical history, clinical manifestations, imaging examination and cerebrospinal fluid analysis. The main treatment strategies include intrathecal or systemic chemotherapy, radiotherapy, surgery and other palliative treatments, and new therapies such as novel chemotherapeutic drugs and immunotherapy are expected to bring new hope for improving the prognosis of LM. What diseases are most likely to cause Meningeal Metastatic Carcinoma? Molluscum contagiosum usually occurs in the late stage of tumor disease, often accompanied by metastasis from other systems or brain parenchyma. Solid tumors, hematological malignant tumors and intracranial primary malignant tumors can all have molluscum contagiosum metastasis, especially the molluscum contagiosum metastasis of leukemia, lymphoma (such as aggressive non-Hodgkin’s lymphoma), multiple myeloma, breast cancer (especially those who overexpress the HER2 gene), lung cancer, and melanoma are common. Among primary intracranial malignancies, the risk of soft meningeal metastasis is higher for medulloblastoma, retinoblastoma, and supratentorial primitive neuroectodermal tumors, e.g., up to 30% of medulloblastoma soft meningeal metastasis. In addition, ovarian endodermal sinus tumors, embryonal tumors and choriocarcinomas and other non-germ cell germ cell tumors also have high risk of meningeal dissemination. C. What are the manifestations of Molluscum Contagiosum? Since soft meningeal metastases are mainly diffuse lesions, their clinical manifestations lack of specificity and often coexist with multiple neurological localization symptoms and signs. In general, headache, diplopia, and muscle weakness are the most common neurological symptoms, while delirium, motor nerve palsy, and bilateral physiologic reflex asymmetry are the most common neurological signs. Depending on the location of the molluscum contagiosum metastases, the clinical manifestations can be mainly: (1) Cerebral hemisphere-related symptoms. Seen in about half of the patients, with hydrocephalus and high cranial pressure as the main manifestations. Patients may present with headache, nausea and vomiting, and even symptoms such as unsteady gait, cognitive impairment, and confusion; those with combined brain parenchyma involvement may also present with seizures, mild hemiparesis, or other neurological localization signs. (2) Symptoms of cranial nerve involvement. It is seen in about half of the patients, with cranial nerves III, IV, and VI most commonly involved, followed by cranial nerves VII and VIII. Therefore, diplopia may be present as the main manifestation of cranial nerve involvement, and some of them may manifest as acute blindness due to optic nerve involvement. If patients with tumor develop progressive hearing loss and loss of balance, they should be alerted to the possibility of soft meningeal metastasis in the cerebellar angle of the pontine brain. (3) Symptoms of crural or crural nerve root involvement. In about 3/4 patients, radiating pain, weakness, numbness, bilateral tendon reflex asymmetry, and dysfunction of bowel movements are often seen in the corresponding areas; the cauda equina involvement can be seen as weakness of both lower limbs, loss of ankle reflexes, and diminished bowel sounds. (3) Meningeal irritation sign. It is seen in about 15% of the patients, which can be manifested as neck stiffness and positive Kernig’s sign. What examination can confirm the diagnosis of molluscum contagiosum? 1. Enhanced CT: about 25~50% of patients with molluscum contagiosum can find meningeal linear/nodular enhancement, cerebral pool obstruction and cerebral edema. 2. MRI: Diffuse enhancement of the meninges; nodular occupying lesions in the subarachnoid space, especially in the cerebral pools and cerebral fissures; and linear enhancement of the whole crural medulla or segmental crural medulla, linear or nodular enhancement of the cauda equina nerve roots in those with crural medulla involvement. Among them, the abnormal thickening and strengthening of cranial nerves, nodular foci of the cauda equina, and diffuse thickening with strengthening of the surface of the cerebral and crural medulla are of high specificity. 3. Cerebrospinal fluid examination. Cerebrospinal fluid cytology to find malignant tumor cells is the gold standard for the diagnosis of LM. Cerebrospinal fluid pressure, cell count, protein and sugar concentration, tumor marker levels (e.g., β2-microglobulin associated with lymphoid malignancies, CA 125 associated with ovarian cancer, CA15-3 associated with breast cancer, PSA associated with prostate cancer, β-hCG associated with choriocarcinoma or stem cell tumors, colorectal tumor and other solid tumor-associated β2-microglobulin) are all important factors in the diagnosis of LM. Carcinoembryonic antigen (CEA) associated with colorectal tumors and other solid tumors, etc.) are of reference value for diagnosis. 4. Radionuclide examination of cerebrospinal fluid circulation. It can find tiny lesions that cannot be shown by conventional imaging examination. V. How to treat soft meningeal metastatic cancer? Is there any hope? In view of the fact that it is not yet possible to completely eradicate the tumor cells in the subarachnoid space, the treatments of LM are palliative. The aim of treatment is to relieve symptoms, improve and stabilize neurological function, and prolong survival. The main methods are surgery, radiotherapy and chemotherapy, and individualized treatment plans should be made according to the patient’s condition. 1. Surgery. As LM is widely distributed along the subarachnoid space, radical resection is not possible, so the main surgical treatments are: subcutaneous placement of ventricular fluid storage capsule used for repeated intrathecal injections of chemotherapeutic drugs; ventriculo-peritoneal shunt used for patients with hydrocephalus and high cranial pressure who are obviously symptomatic and insensitive to glucocorticoid therapy, but there is a risk that the tumor may disseminate to the peritoneal cavity, therefore, it is often necessary to supplement with systemic chemotherapy. 2.Radiation therapy. (1) Local radiation therapy. The purpose is to alleviate the neurological localization symptoms caused by the isolated lesion and to improve the cerebrospinal fluid circulation for subsequent intrathecal chemotherapy. Patients should start local radiotherapy once neurological dysfunction occurs, lumbosacral radiotherapy for those with cauda equina symptoms, and cranial radiotherapy for those with cranial neuropathy at the base of the skull. (2) Whole brain radiotherapy. It is the most commonly used radiotherapy method, and its acute complications mainly include bone marrow suppression, mucositis and esophagitis; long-term complications include neuropsychological disorders and cerebral leukoencephalopathy. (3) Whole-brain whole-crest-medulla radiotherapy. It is the preferred option for the treatment of molluscum contagiosum metastases before the appearance of intrathecal chemotherapy, but its application is limited due to the obvious bone marrow suppression often caused and the poor tolerance and cooperation ability of patients. 3.Chemotherapy. (1) Intrathecal chemotherapy. It is the most important treatment modality for molluscum contagiosum metastases, and methotrexate, acitretin and cetirizine are the most commonly used intrathecal chemotherapeutic agents, and it is generally not necessary to adjust the dosage of drugs according to the body weight and surface area. Intrathecal chemotherapy is usually given twice weekly for 4-6 weeks to those with normal cerebrospinal fluid circulation. (2) Systemic chemotherapy. Combination with intrathecal chemotherapy significantly prolongs the average survival of patients, with preference given to lipid-soluble chemotherapeutic agents that are able to cross the normal blood-brain barrier (e.g., cetipapir) or to safer agents that are applied in high doses (e.g., methotrexate or cytarabine). (3) Complications of chemotherapy. ①Aseptic meningitis, mainly manifested as sudden headache, nausea, vomiting and fever a few hours after intrathecal drug injection, which can last for 12 to 72 hours, and can be prevented by short-term oral or intrathecal steroid injection. ② Delayed cerebral leukopathy is the most serious complication of chemotherapy, manifested by apathy, memory loss, altered mental status and ataxia, which can occur after whole brain radiation therapy alone or intrathecal chemotherapy alone. (iii) Acute systemic toxic reaction of chemotherapeutic agents. 4, immunotherapy. Such as cytokines (interleukin-2 and α-interferon, etc.) intrathecal injection, monoclonal antibodies and so on. 5, Symptomatic treatment ⑴ glucocorticoids to reduce neuroedema to relieve headache, radicular pain. (2) Antiepileptic drugs can be applied prophylactically if there are epileptic seizures. Prognosis LM is a serious complication of systemic cancer with poor clinical prognosis. Untreated patients often die within 1 month, and the primary focus of the tumor also has a large impact on survival.The long-term remission rate of LM is very low, and most patients die due to the progression of neurological metastases.