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Diagnostic Dilemmas in Oncology

Case 1. Lung Cancer With Miliary Brain Metastases Undetected by Imaging Studies

First Department of Internal Medicine and Laboratory Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

A 44-year-old man with lung adenocarcinoma was referred to our hospital for treatment. He had stage IV disease (T2N1M1, multiple bone metastases) with an Eastern Cooperative Oncology Group performance status of 1. After two courses of chemotherapy with cisplatin and docetaxel, he had a partial response and returned to work for 3 months. However, subsequently, local police found the patient wandering and disoriented. He exhibited stupor and could not explain his actions. With a diagnosis of psychiatric emergency, he was admitted to our hospital and further examination was performed. An EEG showed a slow wave pattern. Brain metastases were suspected, but results of brain computed tomography with contrast were normal, and magnetic resonance imaging (MRI) on T1- and T2-weighted images with gadolinium enhancement revealed no remarkable findings (Fig 1A, T1 image). Herpes simplex encephalitis¹ or a paraneoplastic syndrome² was considered to be the cause of his mental symptoms. However, anti–herpes simplex virus antibody in samples of CSF was normal, and MRI images showed no distinctive findings of herpes simplex encephalitis. Immunologic markers recognized as indicators of paraneoplastic syndrome, including anti–Hu-1 antibody,³ showed no rise in serum levels. In addition, cytologic analysis showed that his CSF was class I and CSF glucose was normal, while CSF protein was elevated at 227 mg/dL.

View larger version (59K): [in this window] [in a new window]   Fig 1.

The autopsy results were highly unexpected. Pathologic findings revealed diffuse miliary brain metastases located in all parts of brain tissue examined, including the cerebral cortex of the frontal, parietal, temporal, and occipital lobes, the pons, the medulla oblongata, and the cerebellum (Fig 1B, microscopic finding of the parietal lobe indicated by square on Fig. 1A; gland structure by adenocarcinoma cell is revealed diffusely). These results suggested an explanation for the refractory psychotic symptoms (wandering, disorientation, aphasia, and so on) demonstrated by this patient.

Nemzek et al⁴ reported on contrast-enhanced MRI images in the case of diffuse miliary brain metastases. Furthermore, Shirai et al⁵ suggested the usefulness of contrast enhancement by gadolinium in MRI studies for the examination of miliary brain metastases. However, in our case, the radiologic findings published thus far were absent in our patient. Nemzek et al have proposed that the absence of findings of miliary brain metastases by MRI is due to both the effects of chemotherapeutic agents and the failure of gadolinium to cross through the intact blood-brain barrier.

We conclude that in cases of unexplained psychoses observed in patients with any type of cancer, it is necessary to consider the presence of miliary brain metastases, which may be undetectable by conventional diagnostic and imaging methods. In such cases, positron emission tomography may be a more promising method of detecting this type of lesion.⁶ However, because of the financial expenditure involved, positron emission tomography scanning may not be generally available. Therefore, presently it is reasonable to repeat multiple MRI studies until metastases are detected, if this disease is suspected.

REFERENCES

1. Coren ME, Buchdahl RM, Cowan FM: Imaging and laboratory investigation in herpes simplex encephalitis. J Neurol Neurosurg Psychiatry 67: 243-245, 1999[Abstract/Free Full Text]

2. Duyff RF: Paraneoplastic limbic encephalitis. Lancet 350: 1250-1251, 1997 (letter)[Medline]

3. Tanaka K, Tanaka M, Inuzuka T: Cytotoxic T lymphocyte-mediated cell death in paraneoplastic sensory neuropathy with anti Hu antibody. J Neurol Sci 163: 159-162, 1999[Medline]

4. Nemzek W, Poirer V, Salamat MS: Carcinomatous encephalitis (miliary metastases): Lack of contrast enhancement. AJNR Am J Neuroradiol 14: 540-542, 1993[Abstract]

5. Shirai H, Imai S, Kajihara Y: MRI in carcinomatous encephalitis. Neuroradiology 39: 437-440, 1997[Medline]

6. Au WY, Shek TW, Ma SK, et al: Case 2: Meningeal granulocytic sarcoma (chloroma) in essential thrombocythemia. J Clin Oncol 18: 3996-3997, 2000[Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nakamura, H. Articles by Saito, A. Search for Related Content PubMed PubMed Citation Articles by Nakamura, H. Articles by Saito, A. Social Bookmarking                            What's this?