Multiple brain metastases from malignant peripheral nerve sheath tumour (MPNST)

Malignant peripheral nerve sheath tumours (MPNSTs) are rare soft tissue neoplasms arising from elements of the nerve sheath that often occur in the context of neurofibromatosis (NF) type 1. Their poor prognosis results from high local recurrence rate and distant dissemination. Nevertheless, the brain metastases are exceptional. We are presenting an unusual case of intrathoracic MPNST in a 33-year-old man with a five-year clinical course characterised by multiple times local recurrences of primary tumour and multiple remote metastases into the brain structures, thyroid and suprarenal gland. Moreover, the cerebellar metastasis regrew in spite of its total excision. Histologically, brain metastatic tumours were composed of spindle cells closely arranged in interlacing and woven fascicles. This highly cellular nerve tissue exhibited an advanced nuclear hyperchromasia and a high mitotic activity. The tumour exhibited rich delicate reticulin network. The schwannian nature of brain metastases has been confirmed by immunohistochemical findings showing S-100 protein and GFAP expression and ultrastructural evidences of the pericellular basal lamina.     

Cerebral metastases from malignant melanoma

Six hundred and fifty-two patients with histologically proven primary malignant melanoma have been followed by the London Regional Cancer Centre from 1960 to 1985. Neurological signs and symptoms secondary to metastases to the brain developed in fifty-five patients (8.4%). The median age was 49 years; 71% were male and 29% female. Multiple lesions were found in 61% and a single metastasis in 39%. The most common site for the primary lesion was the trunk in males (44%) and the lower limb in females (37%). Six month survival for patients with a single metastasis was 58% if surgical excision was possible and 25% of these patients survived greater than two years. In patients with multiple metastases that received radiotherapy, survival times of greater than six months were found in 12% of the patients. Patients with a single metastasis appear to benefit by being managed by surgical removal of the lesion.     

Eaton-Lambert syndrome and malignant thymoma

Eaton-Lambert syndrome is most frequently associated with small-cell carcinoma of the lung. We describe the first case of this disorder in a patient with malignant thymoma. Guanidine treatment had no clinical or electrophysiologic effects.     

Multiple brain metastases: a surgical series and neurosurgical perspective

Despite review papers claim for radical treatment of oligometastatic patients, only few surgical series have been published. In this study, we analyze results and actual role of surgical resection for the management of patients with multiple brain metastases. This retrospective study compares surgical results of two groups of patients consecutively treated in our Institute from January 2004 to June 2015. The first group comprises all 32 patients with multiple brain metastases with only 2–3 lesions who underwent surgical resection of all lesions; the second group comprises 30 patients with a single surgically treated brain mestastasis compatible with the first group (match-paired control series). Median survival was 14.6 months for patients with multiple brain metastases (range 1–28 months) and 17.4 months for patients with a single brain metastasis (range 4–38 months); the difference was not statistically significant (P?=?0.2). Neurological condition improved in 59.4% of patients with multiple metastases, it remained unchanged in 37.5% and worsened in 3.1%. In our series, selected patients with only 2–3 lesions with well-controlled systemic disease, life expectancy of more than 3 months, Karnofsky’s performance status >?60, and surgically accessible lesions, benefited from surgical treatment in terms of survival and quality of life, with reduction or disappearance of significant neurological deficits. The prognosis for these patients is similar to that of patients with a single metastasis. It seems that patients with breast cancer included in our series had the worst prognosis if compared to other histotypes.     

Symptomatic pituitary metastasis of malignant thymoma

Pituitary metastases from malignant thymoma are extremely rare. We report an 86 year-old-man with pituitary metastasis of malignant thymoma who complained of visual impairment and right ptosis. A pituitary lesion, which was partially removed by trans-sphenoidal surgery, was pathologically similar to the primary lesion and was diagnosed as pituitary metastasis of malignant thymoma. One autopsied case of pituitary metastasis of malignant thymoma has been found in the literature, and one case of this condition has been previously described in life. The present paper is the second report of symptomatic pituitary metastasis of malignant thymoma. Surgical removal of the pituitary lesion is a reasonable choice for the relief of progressive visual symptoms and for good quality of life in these patients.     

Management of brain metastases.

Brain metastases are common and often occur in patients whose systemic cancer is quiescent. When brain metastases occur, they considerably decrease the quality of life in patients who otherwise might be functional. An early diagnosis and vigorous treatment of the brain metastasis, while only rarely curative, may lead to a useful remission of the brain symptoms and may both enhance the quality of the patient's life and prolong survival. Patients with known cancer and neurological symptoms should all undergo appropriate diagnostic tests which include either CT scan or magnetic resonance imaging and, if a lesion is found and a definitive diagnosis can not be established, biopsy. Single or solitary brain metastases in patients with good systemic performance status should be strongly considered for surgical extirpation which will both make the diagnosis and deliver definitive treatment to the lesion. Patients with poor systemic performance status and/or multiple brain metastases are candidates for whole brain radiation therapy. Whole brain radiation therapy is also indicated in patients after successful surgical extirpation of a single metastasis. The role of focal radiation therapy and chemotherapy in the treatment of brain metastases is still being evaluated. Preliminary evidence suggests that focal radiation therapy is probably useful for the treatment of relapsed metastases and that chemotherapy may be useful in the primary treatment of small or asymptomatic brain metastases. Appropriate use of therapeutic modalities directed at brain tumors will ameliorate symptoms in most patients and usually increase survival and enhance the quality of the patient's life.     

Multiple brain abscesses from isolated cerebral mucormycosis.

A report is presented of a patient with cerebral mucormycosis without rhinosinusal or systemic evidence of the disease. The predisposing condition was drug-induced immunosuppression. Computed tomography (CT) showed focal areas of abnormal enhancement which correlated with necropsy findings of localised parenchymal brain damage; this represented encapsulated brain abscesses, a rare form of presentation of cerebral mucormycosis.     

Multiple paraneoplastic diseases associated with thymoma

Here we report a patient with a lymphoepithelial thymoma who developed in chronological sequence limbic encephalitis, neuromyotonia and myasthenia gravis.

The patient presented with limbic encephalitis associated with an invasive thymoma and improved after surgery and cytotoxic therapy. Two months after thymectomy, neuromyotonia associated with hyperhidrosis and mild motor neuropathy occurred and the patient was given plasma-exchange and prednisone therapy. Five months later he developed mild generalised myasthenia gravis. Anti-acetylcholine receptor antibodies, previously repeatedly negative, were found positive at the onset of clinical signs of myasthenia gravis.     

Brain metastases from post-radiation malignant peripheral nerve sheath tumour

A 45-year-old female patient developed a malignant peripheral nerve sheath tumour (MPNST) arising from the left brachial plexus, ten years after regional radiation treatment for Hodgkin's disease. The clinical course was characterized by local recurrence, pulmonary and cerebral metastases with endocranic hypertension syndrome, and the death of the patient 18 months after the onset of symptoms. The tumour presented a histopathological picture of schwannoma with a high grade of malignancy. A particular feature of this case was the exceptional occurrence of the early and massive invasion of the brain.This work was partly supported by CTN CNR 92.02771.CT04.     

Multiple cerebral and leptomeningeal metastases from ovarian carcinoma: unusual early presentation.

Although virtually any systemic malignancy is capable of metastasizing to the brain, ovarian carcinoma, one of the more common female genital malignancies, is one of the rarer forms of brain metastases. In general, the outcome for ovarian carcinoma with brain metastases is extremely poor as most of these patients have widespread lesions elsewhere. This report describes the first known case of multiple cerebral and leptomeningeal metastases as the initial manifestation of ovarian carcinoma in a 41-year old woman who presented with a one-week history of headache, vomiting and confusion. CT scan of the brain was unremarkable, but lumbar puncture revealed atypical cells in the CSF. MRI scan of the brain showed multiple small enhancing lesions. Craniotomy for excision of one of these lesions demonstrated metastatic adenocarcinoma. A large ovarian tumour identified on pelvic CT scan was resected and the patient subsequently received chemotherapy and radiotherapy. Unfortunately she continued to decline and died within six months. Unlike primary tumours such as malignant melanoma, ovarian carcinoma does not have a predilection for the central nervous system (CNS), but the rare instances with CNS involvement occur at an advanced stage of the disease. Once the CNS is involved, the outcome is abysmal, even with multimodality therapy. It is extremely unusual for ovarian carcinoma to present with multiple CNS involvement.     

Multiple intracranial metastases from a gastric gastrointestinal stromal tumor

Intracranial metastases are rare from gastrointestinal stromal tumor (GIST). We report a 60-year-old male with a history of stomach GIST who presented with ataxia 2.5 years after a partial gastrectomy. MRI revealed enhancing masses in the cerebellum and frontal lobe. A suboccipital craniotomy revealed metastatic GIST. With subsequent radiosurgical boost to the resection cavity and frontal lobe lesion, the patient is doing well 15 months postoperatively. To our knowledge, this is one of only a few reports on cerebral GIST metastases from the stomach.     

Respiratory insufficiency from myasthenia gravis and polymyositis due to malignant thymoma triggering Takotsubo syndrome

Abstract

Background: Takotsubo syndrome (TTS) is a non-ischaemic cardiomyopathy with sudden but transient systolic dysfunction. TTS mimics myocardial infarction clinically, chemically, and electrocardiographically but echocardiography typically shows apical ballooning and coronary angiography is normal. TTS has not been reported in a patient with myasthenia gravis (MG) and polymyositis due to a malignant thymoma.

Case report: Two weeks prior to admission, a 76-year-old female developed dysarthria, chronic coughing and disabling myalgias of the entire musculature. Since there was hyper-CKemia and elevated troponin, myocardial infarction was suspected. During swallowing of the antithrombotic medication on admission, she experienced apnoea, requiring cardio-pulmonary resuscitation with intubation and mechanical ventilation. Further diagnostic work-up precluded coronary heart disease but revealed TTS. Upon neurologic work-up, MG and polymyositis were diagnosed but the response to cholinergic drugs and plasmapheresis was poor. TTS was attributed to stress and anxiety from MG-associated respiratory insufficiency. The further course was complicated by recurrent supraventricular bradyarrhythmias and respiratory insufficiency. Upon thoracic CT a thymoma was suspected. Two months after admission, the mediastinal tumour was resected and malignant thymoma WHO BII infiltrating the mediastinum (modified Masaoka-Koga II/2) was diagnosed.

Conclusions: This case shows that TTS may be triggered by stress from respiratory insufficiency during a myasthenic crisis, MG may be associated with polymyositis, cholinergic medication may trigger bradyarrhythmias, and cholinergic drugs and plasmapheresis may exhibit a poor effect if malignant thymoma and polymyositis are present.     

Paraneoplastic encephalitis associated with myasthenia gravis and malignant thymoma

We present a patient with type B2 thymoma (World Health Organization Thymoma Classification) with the complications of anti-muscle acetylcholine receptor antibody-positive myasthenia gravis and anti-voltage-gated potassium channel antibodies associated with paraneoplastic encephalitis. A timing difference between the onset of these neurological disorders and a dissociation of clinical symptoms was observed during the disease. This report alerts clinicians that long-term follow-up is needed where patients have a residual thymoma and attention should be paid to other concomitant autoimmune disorders.     

The diagnosis and management of brain metastases.

The median survival after whole-brain irradiation of patients with brain metastases is 4 months. Because half the patients with brain metastases die of systemic cancer, for most the benefit of intensive local treatment (surgery or stereotactic radiosurgery) of brain metastases will be minimal. In particular, patients with controlled systemic disease and one to three brain metastases are candidates for intensive local treatments. Combined local treatment with whole-brain irradiation therapy improves the local control of brain metastases in comparison with whole-brain irradiation only. After the local treatment of brain metastases by either surgery or radiosurgery, overall survival is not adversely affected if whole-brain irradiation is only administered as salvage treatment at the time of relapse. New randomized trials are needed, however, to investigate this further. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumour and non-cerebral metastases.     

Management of brain metastases from non-small cell lung carcinoma

IntroductionIn France, approximately 30 000 new patients per year develop brain metastases (BM), most of them resulting from a lung cancer.State of the artSurgery and radiosurgery of all the BM must be considered when possible. In other cases, whole brain radiotherapy remains the standard of care.PerspectivesThe role of chemotherapy, poorly investigated so far, should be revisited.ConclusionThis review focused on BM secondary to a non-small cell lung carcinoma.     

Management of brain metastases

Brain metastases represent a common and devastating complication of cancer. With advances in surgery, radiology, and medical and radiation oncology, the number of treatment options have greatly increased. In addition, the prognosis for patients can vary widely depending on factors such as the number of lesions, extent of extracranial disease, age, and functional status. Recently, the possible impairment of whole brain radiation therapy on neurocognitive function has been a subject of concern and debate. Thus, the use of whole brain radiation therapy in conjunction with other treatment modalities should be optimized to ensure the best outcomes with regard to tumor control and functional status. As a result, patient management has become controversial, with strong opinions often dictating “optimal” therapy. This review of the management of brain metastases focuses on whole brain radiation therapy, surgery, stereotactic radiosurgery, radiation sensitizers, and clinical trials.     

Management of brain metastases

Brain metastases occur in 20–40 % of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15 % of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3–3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligeable; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated. Received: 20 May 2002, Accepted: 23 May 2002 Correspondence to Riccardo Soffietti, MD