Long-term follow-up of vanishing tumors in the brain: How should a lesion mimicking primary CNS lymphoma be managed?

doi:10.1016/j.clineuro.2012.02.053

Clinical Neurology and Neurosurgery

Volume 114, Issue 9, November 2012, Pages 1217-1221

https://doi.org/10.1016/j.clineuro.2012.02.053 Get rights and content

Abstract

Objectives

The spontaneous disappearance of a tumor is referred to as a vanishing tumor. Most vanishing tumors in the brain are eventually diagnosed as malignant tumors or multiple sclerosis. However, their long-term clinical course remains unclear. This study aims to elucidate the management of vanishing tumors in the brain.

Patients and methods

We defined a vanishing tumor as a case in which the tumor spontaneously disappeared or decreased to less than 70% of the initial tumor volume before definitive diagnosis and treatment (other than steroid treatment). Ten cases of vanishing tumors are reviewed.

Results

Nine patients underwent biopsy at least once. Five patients, all of whom had malignant tumors (primary central nervous system lymphoma: 4, germinoma: 1) that recurred in 4–45 months (median: 7 months), underwent a second biopsy after the reappearance of the tumors. Five patients (tumefactive demyelinating lesion: 1, undiagnosed: 4) who had no relapse are alive, and their median follow-up time is 44 months. No cases have yet been reported of malignant brain tumors that recurred more than 5 years after spontaneous regression.

Conclusions

Patients with vanishing tumors should be followed up carefully by magnetic resonance imaging for at least 5 years, even after the disappearance of an enhancing lesion.

Introduction

Spontaneous regression of a malignant tumor is highly unusual, but this phenomenon is encountered on some occasions. These spontaneously disappearing, enhancing lesions are observed by magnetic resonance imaging (MRI) or computed tomography (CT). This clinical condition is referred to as a vanishing tumor, tumor regression, ghost tumor, or burned-out tumor [1], [2], [3]. It is estimated that this phenomenon may occur in 1:60,000–1:100,000 patients with cancer; this phenomenon has been observed in renal cell carcinomas, neuroblastomas, malignant melanomas, and germ cell tumors of the testes [1], [4]. Most vanishing tumors in the central nervous system are eventually diagnosed as primary central nervous system lymphoma (PCNSL) [1], [2], [3], [5] or as a demyelinating disease such as multiple sclerosis (MS) [1], [6]. This unusual clinical phenomenon presents diagnostic difficulties and thus leads to confusion in determining treatment options. Occasionally, it may be difficult to distinguish between malignant tumors, such as PCNSL, and many other central nervous system diseases by using clinical, radiological, and laboratory findings, and a biopsy is therefore necessary for definitive diagnosis. However, when a first biopsy is performed and the pathological findings show only nonspecific lymphocyte inflammatory changes with or without demyelination, it is very difficult to identify the cause of these inflammatory changes. Repeated biopsies at the time of tumor recurrence are sometimes necessary for the diagnosis of PCNSL [6].

This study addresses the management of a lesion that mimics primary CNS lymphoma with spontaneous radiological improvement and inconclusive biopsies of the brain. This phenomenon represents a recurrent problem in daily practice and has not yet been addressed in depth in the literature. Here, we report 10 cases of vanishing tumors and clarify the treatment and follow-up of the vanishing tumors after lesion disappearance. We also estimated histological confirmation of demyelination in undiagnosed cases.

Section snippets

Materials and methods

A vanishing tumor is defined as a case in which there is a strong suspicion of brain tumor from the clinical history and in which there are gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhancing lesions on initial MRI that spontaneously disappear or decrease to less than 70% of the initial tumor volume before a definitive diagnosis and treatment, other than steroid treatment, for more than 3 months. From January 2000 to December 2010, clinical charts and radiological examination

Patient characteristics

Ten patients who exhibited a spontaneously disappearing or decreased mass lesion from 2000 to 2010 and who met our criteria for a vanishing tumor were selected. Clinical and radiological features of these 10 patients are summarized in Table 1, Table 2. The follow-up time ranged from 19 to 96 months (median: 50 months). The age of the patients ranged from 25 to 70 years (median: 54 years).

Definitive diagnoses were made in 6 of the 10 patients. Of these 6 patients, 4 had PCNSL (40.0%), 1 had

Discussion

In this study, we report the cases of 10 patients with vanishing tumors exhibiting the radiological feature of spontaneous disappearance or reduction to less than 70% of the initial tumor volume on MRI with Gd-DTPA enhancement before definitive diagnosis and treatment with drugs other than steroid. Vanishing tumors are not symptomatic of a specific disease; instead, they appear on radiological findings and include malignant tumors (such as PCNSL), demyelinating disease, localized cerebral

Conflict of interest

There is no conflict of interest.

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Cited by (27)

Spontaneously changing MRI findings of primary central nervous system vasculitis: A case report
2021, Journal of Clinical Neuroscience
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To the best of our knowledge, this is the first report to describe PCNSV presenting as spontaneously changing brain lesions on MRI. Spontaneously disappearing lesions on MRI has been described in primary central nervous system lymphoma [1]. In PCNSV, characteristic findings such as microinfarction and microhemorrhage can be detected occasionally.
Spontaneously disappearing lesions on magnetic resonance imaging (MRI) has been described in primary central nervous system lymphoma. In this case, we report our experience of spontaneously changing MRI findings of primary central nervous system vasculitis (PCNSV) confirmed histopathologically. A 69-year-old man presented with sudden unsteady gait. Fluid-attenuated inversion recovery (FLAIR) images showed high-intensity areas in the right deep white matter. Contrast-enhanced T1-weighted MRI demonstrated a nodular lesion in the white matter of the left occipitoparietal lobe. On repeat MRI 7 days later, FLAIR hyperintense lesions had spontaneously disappeared and contrast-enhanced lesions had progressed, with new contrast lesions in the right corpus callosum. Repeat MRI 14 days after admission demonstrated contrast-enhancing lesions either increased or decreased in intensity in both occipitoparietal lobes. Contrast-enhancing lesions were therefore biopsied. Histopathological examination revealed vasculitis with fibrinoid necrosis. PCNSV was diagnosed without any signs of inflammation in blood vessels other than cerebral blood vessels. Spontaneously changing MRI findings may play an important role in diagnosing PCNSV.
Vanishing midbrain mass lesion - A germinoma?
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2018, Practical Surgical Neuropathology: A Diagnostic Approach A Volume in the Pattern Recognition Series
This chapter focuses on the surgical neuropathology of demyelinating diseases of the central nervous system, that is, diseases in which myelin itself or the oligodendrocytes (or astrocytes in neuromyelitis optica) represent the targeted element with relative (although, in most cases, not absolute) preservation of axonal integrity. The chapter also includes diseases in which white matter is preferentially targeted by processes that are often more destructive than they are demyelinating (e.g., fat embolism, human immunodeficiency virus [HIV]–induced leukoencephalitis/vacuolar myelopathy). Diseases of the white matter are often neglected in surgical neuropathology, given the greater focus on neoplastic disease that forms the majority of diagnostic biopsies. Nonetheless, an important part of surgical neuropathology is the recognition of neoplasia in the presence of reactive myelinopathy and the need to avoid traps in the false recognition of reactive tumorous myelinopathic processes as neoplasm (“tumefactive multiple sclerosis”). Neuroradiologic techniques are more capable of localizing processes to permit stereotactic biopsies and increase the variety of diseases discussed in this chapter, diseases which would not have been previously considered for biopsy and were only confirmed at autopsy. Molecular genetic analysis now contributes substantively to the workup of white matter disease, particularly leukodystrophies. Thus, in this chapter there are discussions of common demyelinating disorders (multiple sclerosis, acute disseminated encephalomyelitis), destructive leukoencephalopathy, and leukoencephalitis, as well as rare forms of hereditary leukodystrophies, which are, admittedly, infrequently encountered in surgical biopsies.
Neuroinflammation Preceding and Accompanying Primary Central Nervous System Lymphoma: Case Study and Literature Review
2016, World Neurosurgery
Citation Excerpt :
Our present case exhibits predominantly destructive inflammatory features despite the presence of focal demyelination. It is unlikely that those destructive inflammatory foci would be steroid-induced and/or vanishing tumors,4,10,11 as the patient in our case was not treated with steroids until the late stage of her disease (4 months after the resection) and her newly developed lesions were steroid resistant. The pathogenic relationship between the “sentinel” and accompanying inflammatory process and subsequent development of PCNSL warrants further investigation.
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma confined to the CNS. Although the pathogenesis of PCNSL in immunocompetent individuals remains unclear, there have been several case studies demonstrating the “sentinel” inflammatory lesions months before the manifestation of PCNSL. However, the pathologic relationship between the inflammatory lesions and subsequent PCNSL is still unknown.
We present the case of a 44-year-old immunocompetent woman who developed several cerebral and cerebellar lesions on magnetic resonance imaging (MRI). A partial resection of the cerebellar contrast-enhancing lesion showed active inflammation with large destructive process but no evidence of B-cell lymphoma. Her disease was in a relapsing-remitting course for 28 months and progressed with new MRI findings of more contrast-enhancing lesions. She died at 33 months after the initial presentation. Postmortem examination revealed B-cell PCNSL with extensive involvement but sparing a few brain regions, including the previous resection site, with only an inflammatory destructive process.
PCNSL may be preceded and accompanied by an inflammatory process that is pathologically distinct from PCNSL. Our case study, in combination with a review of previously published similar cases, supports the hypothesis that the “sentinel” inflammatory lesions may be the first immune response against PCNSL.
Neuro-oncology dilemma: Tumour or tumefactive demyelinating lesion
2015, Multiple Sclerosis and Related Disorders
Citation Excerpt :
This early dramatic response is however, only temporary and lesions will rebound in a few weeks or months. PCNSL can pose a major diagnostic challenge if based solely on the response to corticosteroids, as they demonstrate more sustained clinical and radiological improvement which might lasting 6–12 months, and rarely up to 5 years (Bromberg and Siemers, 2002; Alderson et al., 1996; Okita et al., 2012; Ng et al., 2007; Kürtüncü et al., 2009). Reported “sentinel demyelinating lesions” several months prior to the onset of PCNSL also pose another diagnostic challenge (Alderson et al., 1996).
Tumefactive demyelinating lesions (TDLs) are not an uncommon manifestation of demyelinating disease but can pose diagnostic challenges in patients without a pre-existing diagnosis of multiple sclerosis (MS) as well as in known MS patients. Brain tumours can also arise in MS patients and can be seen in chronic MS patients as co-morbidities. Delayed diagnosis or unnecessary intervention or treatment will affect the ultimate prognosis of these patients. In this article, we will review some typical cases illustrating the dilemma and review the information that helps to differentiate the two conditions.
The intention is not to present an extensive differential diagnosis of both entities, but to examine some typical examples when the decision arises to decide between the two. We take a somewhat different approach, by presenting the cases in “real time”, allowing the readers to consider in their own minds which diagnosis they favour, discussing in detail some of the pertinent literature, then revealing later the actual diagnosis. We would urge readers to consider re-visiting their first thoughts about each case after reading the discussion, before reading the follow-up of each case.
The overall objective is to highlight the real possibility of being forced to decide between these two entities in clinical practise, present a reasonable approach to help differentiate them and especially to focus on the possibility of TDLs in order to avoid unnecessary biopsy.
Ghost Tumors of the Central Nervous System: Definition, Clinical Implications, and Proposal of Classification Portions of this work were presented as an oral presentation at the Fifteenth World Federation of Neurosurgical Societies World Congress of Neurological Surgery in Seoul, Korea, September 2013.
2015, World Neurosurgery
Citation Excerpt :
More rarely, spontaneous regression of malignant tumors other than lymphoma has been reported (29). Vanishing lesions also may appear in nonneoplastic conditions, such as demyelinating disease, localized cerebral infarction, and focal encephalitis of unknown cause, and a biopsy is sometimes necessary for definitive diagnosis (28). Neurofibromatosis warrants particular attention because either unidentified bright objects or enhancing tumor may disappear spontaneously (13, 25).
A ghost tumor (GhT) is a space-occupying lesion with radiologic features consistent with the diagnosis of tumor that on further investigation is revealed not to be a tumor, although definitions in the literature are inconsistent, and the incidence of GhT remains undefined.
A review of the pertinent literature was performed to identify pediatric patients in whom a misleading initial diagnosis of space-occupying lesion was described. Analysis of the differentiating features of the final diagnosis and related clinical and radiologic issues was performed.
GhT may be categorized as follows: GhT I, lesions spontaneously disappearing during follow-up, also known as “vanishing tumors”; GhT II, nonneoplastic space-occupying lesions showing a tumor appearance, also known as “tumor-like lesions”; GhT III, anatomic variants of normal structures mimicking a tumor, also defined as “false tumors.” The most deceptive conditions and critical points in the differential diagnosis of these cases were discussed.
GhT is an entity with significant implications in regard to treatment and outcome. In this context, the integration of clinical and radiologic clues is crucial for a careful differential diagnosis and a consistent diagnostic approach, which is necessary for adequate decision making regarding management. A thorough radiologic work-up is mandatory. Atypical radiologic images should raise a high level of suspicion, including incidental lesions, which are encountered with increasing frequency in daily practice as a result of greater access to radiologic examinations, increasing sensitivity of imaging, and the impact of defensive medicine. A wait-and-see policy should be considered whenever indicated.

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View full text

Long-term follow-up of vanishing tumors in the brain: How should a lesion mimicking primary CNS lymphoma be managed?

Abstract

Objectives

Patients and methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Patient characteristics

Discussion

Conflict of interest

Is a vanishing tumor always a lymphoma

Neurology

A spontaneously vanishing primary cerebral lymphoma ghost tumour

J Neurol Neurosurg Psychiatry

Spontaneous regression of intracerebral lymphoma

Radiology

Burned-out testicular tumor: a case report

Hinyokika Kiyo

Spontaneous remission of primary central nervous system lymphoma: report of 3 cases and discussion of pathophysiology

J Neurooncol

Distinguishing primary central nervous system lymphoma from other central nervous system diseases: a neurosurgical perspective on diagnostic dilemmas and approaches

Neurosurg Focus

Case series: tumefactive demyelinating lesions: a diagnostic challenge

Can J Surg

Giant lesions in multiple sclerosis—a diagnostic challenge

Harefuah

Monophasic, solitary tumefactive demyelinating lesion: neuroimaging features and neuropathological diagnosis

Br J Radiol

Primary cerebral lymphoma with a 5-year remission to single-agent corticosteroids

Leuk Lymphoma