Three cases of metastatic meningeal carcinomatosis from lung cancer]

We report three cases of meningeal carcinomatosis that metastasized from lung cancer. The patients were men of 73, 65 and 77 years old. The histological type was adenocarcinoma in all cases. At the time of emergence of neurological symptoms such as nausea, headache and cataplexy, enhanced CT of the brain did not disclose brain metastasis. Although brain MRI failed to detect abnormal meningeal findings in cases 1 and 2, meningeal carcinomatosis was diagnosed by cerebrospinal fluid cytology in all three cases. As for treatment, in case 1, methotrexate and prednisolone were administered intrathecally, while the optimum supportive care was given in cases 2 and 3. Because it is difficult to detect meningeal carcinomatosis by brain CT and MRI alone, careful neurological observation and cerebrospinal fluid cytology are necessary for its diagnosis.     

Insidious hearing loss and facial palsy as the presenting symptoms of meningeal carcinomatosis resulting from adenocarcinoma of the lung]

An 80-year-old man was admitted to our hospital with a complaint of insidious hearing loss and facial palsy. Chest X-ray film showed an abnormal shadow in the right lower lobe. Adenocarcinoma of the lung was diagnosed by transbronchial brushing cytology. During admission, headache and dysphagia appeared, although no abnormality was detected in the brain CT and MRI. Lumbar puncture yielded adenocarcinoma cells in the cerebrospinal fluid. A diagnosis of leptomeningeal metastasis from the adenocarcinoma of the lung was considered and intrathecal administration of methotrexate was performed. The patient's condition deteriorated gradually and he died of respiratory failure. Autopsy revealed massive invasion of tumor cells in the leptomeninges of the brain and spinal cord. This case illustrates that facial nerve palsy with insidious hearing impairment may appear as the initial symptoms in meningeal carcinomatosis resulting from lung cancer metastasis.     

A case of meningeal carcinomatosis from lung cancer successfully treated with aggressive multimodal therapy]

A 44-year-old man was admitted to our hospital because of brain metastasis and intrapulmonary exacerbation of lung adenocarcinoma. Systemic chemotherapy (PAC + CBDCA) was administered, but neurological symptoms (muscle weakness of limbs and disorientation) appeared. Lumbar puncture and enhanced MRI of lumber vertebrae revealed meningeal carcinomatosis. MTX 20 mg/week (+ Ara-C 40 mg/week) was injected into the meningeal space. There was a clear improvement in the neurological symptoms, but it did not last long. Meningeal injection was performed 7 times. Whole-brain and whole-marrow radiation along with systemic chemotherapy gave a marked improvement in the symptoms and in the metastatic shadow on the chest CT scan.     

Two cases of meningeal carcinomatosis during gefitinib therapy for non-small cell lung cancer]

"Case 1" A 56-year-old woman who suffered from postoperative recurrent non-small cell lung cancer received gefitinib therapy. Approximately 7 months after the therapy was begun, although the intrathoracic disease responded to the treatment, she developed meningeal carcinomatosis and died of rapidly progressive central nervous system disease. "Case 2" A 46-year-old man with stage IV non-small cell lung cancer started gefitinib therapy after chemotherapy. The pulmonary lesions markedly improved responding to gefitinib therapy, however, approximately 6 months after the therapy was begun, multiple brain metastasis and meningeal carcinomatosis were detected. Approximately 4 months after the diagnosis of meningeal carcinomatosis, he died of disease progression and disturbance of consciousness. It has been reported that the central nervous system is a frequent metastatic site of non-small cell lung cancer in patients treated with gefitinib. We report two cases of meningeal carcinomatosis that occurred during the period in which their intrathoracic disease was responding to gefitinib therapy. We should consider the possibility of metastatic central nervous system disease, even in patients in whom gefitinib therapy is apparently successful.     

Rare case of pancreatic cancer with leptomeningeal carcinomatosis

Leptomeningeal carcinomatosis occurs very rarely in patients with pancreatic cancer.Leptomeningealcarcinomatosis is characterized by multifocal seeding of the leptomeninges by malignant cells that originate from a solid tumor.To the best of our knowledge,brain metastasis from pancreatic cancer is extremely rare.Leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of cases of solid tumors.The clinical manifestation usually involves neurological symptoms,including dizziness,headache,vomiting,nausea,and hemiparesis,symptoms similar to those of meningitis or brain tumors.Diagnostic methods for leptomeningeal carcinomatosis include brain magnetic resonance imaging and cerebrospinal fluid examination.Here,we describe a case of leptomeningeal carcinomatosis in which the primary tumor was later determined to be pancreatic cancer.Brain magnetic resonance imaging findings showed mild enhancement of the leptomeninges,and cerebrospinal fluid cytology was negative at first.However,after repeated spinal taps,atypical cells were observed on cerebrospinal fluid analysis and levels of tumor markers such as carbohydrate antigen 19-9 in cerebrospinal fluid were elevated.Abdominal computed tomography,performed to determine the presence of extracerebral tumors,revealed pancreatic cancer.Pancreatic cancer was confirmed histopathologically on examination of an endoscopic ultrasound-guided fine needle aspiration specimen.     

Meningeal carcinomatosis in gastric cancer]

Meningeal carcinomatosis is an uncommon complication in patients with advanced gastric cancer. We report four cases of meningeal carcinomatosis occurring 18 months (mean) after the diagnosis. The presenting manifestations were headache, visual troubles and seizure. Cytological cerebrospinal fluid (CSF) examination was the most useful diagnostic tool for leptomeningeal carcinomatosis, considering the normality of brain CT scan and MRI in our patients. Intrathecal methotrexate administration achieved a rapid improvement in neurological symptoms in all cases, but for a short 2-3 months duration. We conclude that survival improvement in advanced gastric cancer, due to chemotherapy, may allow emergence of unusual complications such as carcinomatous meningitis. This diagnosis should be evoked in the presence of unexplained neurologic symptoms and confirmed by CSF examination in order to propose a treatment and to delay serious neurologic disability and prolong survival.     

Long-term outcome after multidisciplinary approach for leptomeningeal carcinomatosis in a non-small cell lung cancer patient with poor performance status

The present study describes a case of a 60-year-old Japanese man who was histologically diagnosed with lung adenocarcinoma harboring L858R mutation of epidermal growth factor receptor. He was successfully treated with gefitinib, but eventually developed leptomeningeal carcinomatosis. He underwent ventriculoperitoneal shunting for hydrocephalus and received erlotinib in place of gefitinib with concurrent whole brain radiotherapy; this resulted in dramatic improvement in his symptoms and performance status from four to one and he survived for as long as 13.6 months after the initiation of erlotinib therapy. This multidisciplinary approach may be particularly useful in terms of increasing survival and improving quality of life.     

Meningeal carcinomatosis as first manifestation of carcinoma of the bladder: report of 2 cases

Meningeal carcinomatosis may occur in 0.8-8% of patients with solid tumors. The most common tumors associated with that condition are breast and small cell lung cancer. Meningeal carcinomatosis from urothelial cancer is rare, and it appears described in advanced stages of disease, generally, after chemotherapy. Two cases of meningeal carcinomatosis as the first manifestation of bladder cancer were reported. In the first case, a 46-year-old man presented signs and symptoms indicative of involvement of the spinal roots, subsequently neurologic dysfunction of the brain and cranial nerves appeared. In the second case, a 68-year-old man was admitted to our hospital with a history compatible with panhypopituitarism and pulmonary lymphangitic carcinomatosis from cancer of unknown primary site. Follow-up revealed a transitional cell carcinoma of the bladder and hydrocephalus due to cerebrospinal fluid outflow obstruction. We emphasize in the polymorphic presentation of meningeal carcinomatosis and the necessity to consider the bladder as primary tumor localization.     

Paraneoplastic neurological syndromes associated with gastric cancer: a case report and review of the literature

Paraneoplastic neurological syndromes (PNS) are associated with small-cell lung cancer, breast and gynecological cancers. We describe a gastric neoplasm presented with neurological symptoms. A 74-year-old male presented with tonic?Cclonic seizures. Initial investigations were normal; however, brain magnetic resonance imaging showed abnormal signal intensity in the hippocampi. A diagnosis of PNS was suspected. The patient was then diagnosed with a gastric neuroendocrine carcinoma with N-type voltage-gated calcium channel antibodies. The neurological impairments improved after the primary was resected and the patient remains free of cancer and paraneoplastic syndrome. We reviewed 10 cases of PNS associated with gastric cancer and found several characteristics: (1) older men, (2) neuroendocrine component or predominance, (3) oncological outcome for patients with PNS is better than for patients without PNS, and (4) neurological impairment is diagnosed 6?months prior to the diagnosis of gastric malignancy. In conclusion, elderly men with symptoms suggestive of PNS should be investigated for a gastric neuroendocrine malignancy.     

Bilateral adrenal hyperplasia complicated with severe ischemic stroke in a young patient

A young patient suffered from acute right hemiparesis, facial weakness and Broca's aphasia with multiple brain lesions due to severe hypertension. His evaluation for secondary causes of hypertension revealed hyperaldosteronism due to bilateral adrenal hyperplasia. Treatment is based primarily on spironolactone and ACE inhibitors. Two years later he was in an outstanding clinical condition with few remained neurological symptoms and his blood pressure well controlled.     

A case of pulmonary adenocarcinoma accompanied by minimal change nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia]

A 49-year-old man was urgently admitted due to edema in both leg and left toe pain. A chest radiograph revealed a solitary nodule in the right lung field. Detailed investigations including bronchoscopy and renal biopsy led to a simultaneous diagnosis of clinical stage IIIB pulmonary adenocarcinoma, minimal change nephrotic syndrome, antiphospholipid syndrome, and warm-type autoimmune hemolytic anemia. Prednisolone was administered for nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia, and 6 courses of chemotherapy with 70Gy radio-therapy were performed. The pulmonary nodule significantly decreased in size and the other three autoimmune diseases appeared to be well-controlled. Thirteen months after admission, multiple brain metastases developed along with worsening antiphospholipid syndrome symptoms including lupus anticoagulant. Following whole-brain irradiation, the brain metastases decreased in size and antiphospholipid syndrome symptoms improved. Thirty-nine months after the initial visit, the primary lung cancer, its brain metastasis and the 3 other autoimmune diseases appeared to be well-controlled. The temporal correlation of the lung cancer and the three autoimmune diseases suggests the latter may be paraneoplastic syndrome.     

Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: a case report

A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient's neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.     

Small cell lung cancer associated with anti-Hu antibody-positive paraneoplastic neurologic syndrome]

We report a case of small cell lung cancer with anti-Hu antibody-positive paraneoplastic neurologic syndrome preceded by variable neurological symptoms. A 57-year-old man first noticed a numbness on the inner side of his right leg in April 1998. He was later admitted to a hospital following the development of polyneuropathy, cerebellar dysfunction, and psychological symptoms. Chest plain X-ray films and computed tomographic scans disclosed a mass shadow in the right upper lobe, in addition to enlarged mediastinal lymph nodes. Small cell lung cancer was suspected on the basis of pathologic findings on an enlarged right supraclavicular lymph node and radiologic findings. The patient was referred to our hospital in October 1998. Anti-Hu antibody was detected both in serum and cerebrospinal fluid. Small cell lung cancer (clinical T1N3M0, stage IIIB) with paraneoplastic neurologic syndrome was diagnosed. Three courses of combination chemotherapy (carboplatin and etoposide) were administered with a partial response. However, the patient's neurological symptoms were not alleviated. We discussed the mechanism, clinical symptoms, and treatment of this disease.     

Paraneoplastic neurological syndrome accompanied by severe central hypoventilation and expression of anti-Hu antibody in a patient with small cell lung cancer]

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.     

A case of non-small-cell lung cancer with intramedullary spinal cord metastasis diagnosed pre-mortem]

The patient was a 54-year-old man who in May 1999 received a diagnosis of squamous cell carcinoma, T4 N2 M1, stage IV. Systemic chemotherapy and stereotactic radiosurgery were performed only to result in further progression of the disease. In August 1999, he experienced gait disturbance due to lumbar pain. Rehabilitation improved the gait disturbance and he was discharged. In October, since the pain reappeared and there was numbness in the right leg, he was readmitted. Brain MRI revealed multiple brain metastasis and whole brain irradiation was performed. But his symptoms deteriorated, and palsy of the right leg ensued. Later, bladder dysfunction also developed. Since spinal cord MRI revealed intramedullary metastasis at Th 12 and L1 levels, we performed radiotherapy for the lumbar medullary lesion, together with systemic chemotherapy. After chemoradiotherapy the tumor size decreased and the pain improved. Cases of lung cancer with intramedullary metastasis are rare, especially those diagnosed before death.     

Asynchronous leptomeningeal carcinomatosis from pancreatic cancer: a case report and review of the literature

Central nervous system (CNS) metastases from pancreatic cancer are an exceedingly rare occurrence and have been predominantly described as focal lesions within the brain parenchyma. Even fewer reports exist of tumor spread to the leptomeninges, and most cases are discovered at autopsy. No report of leptomeningeal carcinomatosis without brain parenchymal involvement has been described to date. We describe a 72-year-old female diagnosed with inoperable, stage IV pancreatic cancer. She was treated with combination chemotherapy comprising Reolysin (reovirus serotype-3 Dearing strain), carboplatin, and paclitaxel. After 4 months of treatment, her tumor had decreased in size by 55 %, and CA19-9 levels had dropped 25-fold. However, 7 months after her initial cancer diagnosis, she presented with clinical symptoms and radiographic findings consistent with leptomeningeal carcinomatosis. Lumbar puncture did not reveal malignant cells in the cerebrospinal fluid (CSF), and biopsy was requested for tissue diagnosis. This confirmed pancreatic leptomeningeal carcinomatosis. Our case report demonstrates that leptomeningeal spread from pancreatic tumors may develop independent of focal brain parenchymal involvement and in the setting of controlled systemic disease. Furthermore, the present study describes the first case of CNS progression in the setting of systemic response to Reolysin therapy, suggesting this newly developing treatment may not prevent neurological spread of disease. If repeat cytology of CSF fails to detect malignant cells, biopsy should be pursued for definitive diagnosis. Surgery may also concurrently provide an opportunity to place an intraventricular catheter for delivery of intrathecal chemotherapies.     

A case of paraneoplastic cerebellar degeneration associated with small cell lung cancer showing marked response to intravenous immunoglobulin

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD), one of the paraneoplastic neurological syndromes (PNS), develops a subacute cerebellar dysfunction and its neurological prognosis is poor in most cases. Because it is considered to be immune-mediated, immunosuppressive therapy may be effective, but its past outcomes are not constant. CASE: A 59-year-old woman presented with deteriorating cerebellar manifestations such as ataxic gait, nausea, and dysarthria. Chest CT revealed a nodule in the upper lobe of the right lung, and small cell lung cancer was diagnosed by transbronchoscopic lung biopsy and sputum cytology. Although known antineuronal antibodies were not detected, no other causative diseases were recognized, so PCD associated with SCLC was diagnosed. The cerebellar manifestations improved remarkably with immediate intravenous immunoglobulin (IVIG) therapy. SCLC showed complete response (CR) after chemoradiotherapy, and the neurological symptoms have not worsened at present. CONCLUSION: Treatment with IVIG at the early stage may lead to the improvement of PCD and is worth attempting.     

A case of meningeal carcinomatosis due to gastric cancer treated with intrathecal chemotherapy

A 71-year-old man was admitted to our hospital in September 2009 because of severe headache due to meningeal carcinomatosis. In July 2007, subtotal gastrectomy was carried out for gastric cancer. Because intraabdominal cytodiagnosis was positive, he received systemic chemotherapy for 2 years. Recurrent signs were not found on chest or abdominal CT just before hospitalization. He was given NSAIDs and corticosteroid, but his symptom did not improve. Subsequent intrathecal chemotherapy with MTX and Ara-C improved clinical symptoms dramatically. He received care at home for 3 months before he passed away due to pleural and peritoneal recurrence. Recently, since the frequency of meningeal carcinomatosis is increasing, combination treatment of intrathecal chemotherapy and systemic chemotherapy should be considered not only for improvement of clinical manifestations, but also for prognostic improvement.     

Three cases of pulmonary atypical mycobacteriosis associated with lung cancer and adult T-cell leukemia

Three cases of pulmonary atypical mycobacteriosis (AM) were reported. Two cases were associated with lung cancer in which the diagnosis of malignancy was difficult and delayed by the coexistence of AM. The third was a case of adult T-cell leukemia (ATL) which manifested during the course of AM. In case 1 (73 years, male) and case 2 (86 years, male), chest roentgenogram abnormalities as well as clinical symptoms were considered to be caused by mycobacteriosis because of positive smear of acid-fast bacilli in sputa on admission. Therefore it took four months and three months respectively for final diagnosis of lung cancer. The autopsy of case 1 revealed a poorly differentiated adenocarcinoma with coexisting foci of squamous cell carcinoma in right lower lung, and granulomatous inflammations with caseating necroses in right mid and lower lungs. M. avium complex was cultured from sputum on admission, and also a high titer of HTLV-I antibody was demonstrated. In case 2 malignant cells were detected in sputa (class V), however his general condition did not allow an aggressive anticancer chemotherapy and he died of malignancy with complication of thromboangiitis obliterans on right lower leg. Case 3 was a 76-year-old male who had been diagnosed as lung AM for more than two years. His chest radiography showed bilateral infiltrative shadows with frequent positive cultures of M. avium complex (more than 100 colonies) from sputum. A generalized lymphadenopathy including right hilar lymph node on chest X-ray film was followed by the presence of atypical lymphocytes in peripheral blood and the elevation of HTLV-I antibody in serum. Four months later he died with hypercalcemia and renal failure in spite of chemotherapy (CPM + VCR + ADR + PLS). The above cases suggest that AM as well as tuberculosis should be considered when pulmonary infiltrates were observed in malignant patients, especially in patients with retrovirus infections.     

Palliative care for brain metastases of solid tumour types

Prognostic factors for survival were analyzed retrospectively in 214 patients with brain metastases of the solid tumour type. The most frequent neurological signs and symptoms at diagnosis of cerebral involvement were headache-nausea-vomiting and focal weakness. Similar numbers of patients were found to have solitary metastasis and multiple lesions. Non-small cell lung cancer, small cell lung cancer, breast cancer, melanoma, and renal cell cancer comprised the majority of the primaries. Most patients received high-dose corticosteroids, while in a third, anticonvulsant agents were administered. Of 157 patients treated with radiation alone, or surgery with or without radiation, 110 experienced alleviation of symptoms or stabilisation of the disease. In 38 patients with a solitary lesion, craniotomy was carried out, either with or without postoperative radiation; the latter group showed the longest survival with a median of 37 wk. The remaining group of 73 patients with one brain metastasis had a median survival of only 15 wk. The 69 patients with multiple lesions who had been irradiated had a median survival of 15 wk, while that for 34 untreated patients was 7 wk. A short median survival of 11 and 13 wk, respectively, was observed in patients with concurrent progressive extracerebral disease and in those with progressive neurological symptoms regardless of treatment. It is concluded that in patients with a solitary brain metastasis without progressive extracerebral disease surgery should be considered the treatment of first choice aiming at a long-term survival with a good quality of life.