Clinical Reasoning: A case of multiple intracerebral hemorrhages
Linda C. Wendell, MD,
Stefanie H. Freeman, MD,
Scott R. Plotkin, MD, PhD and
John R. Sims, MD
From the Department of Neurology, Rhode Island Hospital/Brown University, Providence, RI (L.C.W.); and Department of Pathology (S.H.F.), Department of Neurology (S.R.P.), and Stroke and Neurocritical Care, Departments of Neurology and Radiology (J.R.S.), Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Dr. John R. Sims, CNY149 Rm. 6403, Charlestown, MA 02129 jsims{at}partners.org
Case presentation:
A 47-year-old right-handed man presented with acute onset ofright face, arm, and leg weakness; word-finding difficulties;and bifrontal headache. His medical history was remarkable forhyperlipidemia and spontaneous dissection of a distal coronaryartery a year and a half previously. On examination, he hadright lower face weakness, a plegic right arm, and distal greaterthan proximal right leg weakness. His speech was mildly dysarthricwith word-finding difficulty. Comprehension was intact. Cardiacauscultation was normal.
Results of laboratory investigations, including complete bloodcount, electrolytes, renal function, liver function, prothrombintime, partial thromboplastin time, cardiac enzymes, antinuclearantibody test, erythrocyte sedimentation rate, and urine toxicologyscreen, were all normal or negative.
Initial noncontrast CT brain revealed a 3 x 3.5 x 3.5-cm leftfrontal subcortical intracerebral hemorrhage with surroundingedema, but no appreciable underlying mass (figure 1).
Brain MRI with gadolinium revealed two additional small enhancinglesions in the right frontal cerebral cortex at the gray–whitejunction (figure 2A) and within the white matter at the forcepsminor (not seen in the selected slice of figure 2A). The largeranterior right frontal lesion was 1.5 cm and had a 1.0 x 1.2-cmfocus of hemorrhage that was not present on the initial CT scantaken 4 days earlier (figure 2B). An evaluation for metastaticdisease was initiated.
Figure 2 Brain MRI: gadolinium (A) and susceptibility (B); cardiac imaging: MRI (C) and PET (D)
(A) MRI performed 4 days after initial head CT, T1 sequence with gadolinium, shows left lobar lesion and right frontal lesion at the gray–white junction with enhancement (arrow) and a suggestion of occipital leptomeningeal enhancement (arrow). (B) MRI susceptibility sequence shows right frontal lesion has decreased intensity (arrow) consistent with hemorrhage. (C) Cardiac MRI shows a nonmobile mass (arrow) attached to the left atrial wall. (D) Whole body PET scan demonstrates focal fluorodeoxyglucose uptake (arrow) superior to the left ventricle, which localizes to the intra-atrial mass seen on cardiac MRI.
Whole body CT was negative for masses. A transthoracic echocardiogramvisualized a 2.5 x 2.2-cm left atrial mass fixed to the lateralwall. Cardiac MRI confirmed the left atrial mass with a broadbase of attachment along the posterolateral wall suggestiveof a malignant lesion with possible left ventricular wall metastasis(figure 2C). Whole-body PET showed fluorodeoxyglucose uptakewithin the left atrium; no other metastases were seen on thePET (figure 2D).
Questions for consideration:
What is your differential diagnosis at this point?
What additionaldiagnostic tests would you consider at thispoint?
A brain biopsy of the left frontal lesion was performed. Theinitial sections from the block were nondiagnostic, demonstratingextensive reactive brain parenchyma with areas of inflammationand necrosis. Further sections from the pathology block wererequested along with special stains. Before processing the pathologicspecimen, an attempt to biopsy the cardiac mass via esophagogastroduodenoscopy(EGD)/endoscopic ultrasound was performed. However, the EGDrevealed an ulcerated mass in the stomach cardia, which wasbiopsied instead. Further analysis of the brain specimen andstomach cardia specimen revealed similar atypical spindle cellproliferation (figure 3). Immunohistochemical evaluation ofthe brain biopsy was positive for vimentin but negative forepithelial, melanoma, smooth muscle, vascular, or glial cellmarkers. The tumor had five mitoses per high-power field, andelectron microscopy demonstrated no specific line of differentiation.These findings confirmed an undifferentiated malignant epithelioidand spindle cell sarcoma.
Figure 3 Immunohistochemical evaluation of the brain biopsy
Brain biopsy revealed a densely cellular tumor composed of pleomorphic cells with both epithelioid and spindle cell components, within a background of reactive brain with areas of inflammation and necrosis (hematoxylin and eosin, 20x).
Questions for consideration:
How would you manage a patient with multiple intracerebral hemorrhagesdue to metastatic spindle cell cardiac sarcoma?
Approximately 1 month after presentation, the patient underwentbifrontal craniotomy for resection of right and left frontallobe metastases. Interstitial radioactive iodine-125 pelletswere placed intraoperatively to prevent local recurrence. Hewas also treated with six cycles of 2-mercaptoethanesulfonate(MESNA), doxorubicin, ifosfamide, and dacarbazine chemotherapy.His course was complicated by partial complex seizures withsecondary generalization.
One month after completion of chemotherapy, a repeat brain MRIrevealed two regions of enhancement in the bilateral occipitallobes with leptomeningeal enhancement along the occipital lobesbilaterally (not shown, but suggested by subtle enhancementof occipital leptomeninges noted by the arrow on his originalMRI; figure 2). Lumbar puncture did not reveal malignant cytology.Two months after completion of chemotherapy, he was to undergoresection of the primary atrial sarcoma; however, his coursewas further complicated by bilateral occipital intracerebralhemorrhage into metastatic lesions (figure 4, A and B). He underwenta course of palliative whole-brain radiation to treat new frontalleptomeningeal enhancement. However, 2 days after completionof radiation treatment, the patient had new left frontal intracerebralhemorrhages. He died approximately 10 months after the initialintracranial hemorrhage.
(A) MRI, performed 7 months after initial presentation and 1 month after completing chemotherapy, shows two large bilateral occipital lobe lesions which caused acute blindness. (B) MRI, zero-b sequence shows both occipital lesions are low intensity, consistent with bilateral hemorrhages.
We present an unusual case of undifferentiated cardiac spindlecell sarcoma presenting with multiple recurrent intracerebralhemorrhages. Primary cardiac tumors are rare, with an incidenceof 0.02%.1 The majority of these tumors are benign, with myxomacomprising 50% of primary cardiac tumors. Malignant tumors accountfor 25% of primary cardiac tumors. Sarcoma is the main typeof malignant cardiac tumor, accounting for 20% of primary cardiactumors. They are often poorly differentiated, making an exacthistologic diagnosis difficult.2 The two most common types ofsarcomas are angiosarcomas and undifferentiated sarcomas. Othergroups include leiomyosarcomas, malignant fibrous histiocytomas,osteosarcomas, and fibrosarcomas. The most common presentingsymptom is dyspnea.3 Other common symptoms are chest pain, congestiveheart failure, and pericardial effusion.2
Approximately 80% of patients with cardiac sarcomas have metastasesat the time of diagnosis.2 Malignant cardiac tumors primarilymetastasize to the lungs or mediastinal lymph nodes by the timeof diagnosis.2 Our review of the literature suggests that only21 (including our case) of 225 (9%) patients with a cardiacsarcoma have metastases to the brain. Our patient is unusualin that he had no cardiac signs or symptoms at presentation,nor a previously diagnosed primary cardiac sarcoma at the timeof intracerebral hemorrhage.
Presentation of cardiac sarcomas with neurologic symptoms israre, and documentation is limited to case reports. We founda total of 3 cases in the English literature in which a neurologicevent was the presenting symptom of a metastatic cardiac sarcoma.One of these patients presented with neurologic symptoms froma mass lesion.4 Another presented with intracranial hemorrhagesfrom an angiosarcoma.5 A third patient presented with an embolicstroke.6 We found only 5 cases in which the intracerebral metastaseswere reported with hemorrhage.5,7–10 Most cases did notspecifically note whether hemorrhage was present. Given thelow number of intracerebral metastases (21 total cases, with6 documented hemorrhages), it seems that intracerebral hemorrhageis a common complication of metastasis.
Complete resection of the cardiac tumor and treatment with chemotherapyand radiation has been shown to prolong survival.3 However,in our case, as well as two other cases with initial neurologicpresentation,4,6 rapid clinical deterioration prevented surgicalresection of cardiac tumor.
Disclosure: The authors report no conflicts of interest.
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