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Brain tumor

Brain Tumor

Epidemiology:

Brain tumors comprise a wide range of neoplasms, with approximately 24,000 new cases diagnosed annually in the United States1. Among these tumors, spontaneous remission (SR) is an exceedingly rare phenomenon, likely occurring in less than 1% of brain tumor cases2,,3. Documented instances of spontaneous regression primarily involve less malignant variants, such as low-grade gliomas, specific meningiomas, and astrocytomas4,5. Clinical observations indicate that SR may be associated with non-specific immune responses or trauma, complicating the accurate measurement of its incidence, as many cases may remain unreported, thereby obscuring the true prevalence of this rare event6.

Clinical Characteristics:

To date, 51 well-documented cases of spontaneous remission involving primary brain tumors have been reported between 1977 and 2025. The ages of affected individuals ranged from 3 months to 84 years, with a peak incidence in the middle-aged to older adult group. A modest female predominance (approximately 1.2:1) was observed, consistent with previous reports suggesting a slightly higher frequency of spontaneous regression among women. Pituitary and cerebral tumor associated remissions were more common in females. Overall, spontaneous remission tended to occur in adults with benign or low-grade lesions, often in those with hormonally or immunologically influenced tumor types. See Table 1 for further details.

Histological Characteristics:

Patients who experienced spontaneous remission of brain tumors typically presented with headaches, visual disturbances, seizures, or focal neurological deficits. Diagnosis was usually established by MRI or CT, followed by histopathological confirmation. Most cases involved benign or low-grade lesions, commonly affecting the pituitary gland, cerebral hemispheres, pineal region, or optic pathways. Remission was confirmed through imaging or surgical assessment, revealing tumor necrosis, calcification, or fibrotic replacement. Nearly all cases showed long-term stability or sustained remission, in some lasting more than a decade, far exceeding the expected clinical course.

Proposed Contributing Mechanisms:

Various potential mechanisms of spontaneous remission in brain tumors have been proposed. The most frequently reported involve immune-mediated antitumor responses, sometimes initiated by infection, biopsy, or local inflammatory reactions. Other suggested contributors include vascular occlusion leading to ischemia or necrosis, hormonal fluctuations, and tumor apoplexy with subsequent resorption of necrotic tissue. Recent reports also highlight immune reactivation following biopsy or surgical manipulation, supporting the hypothesis that antigen exposure may stimulate a host-mediated antitumor response. Additional contributing factors include infection resolution, radiation-induced abscopal effects, and alterations in vascular or growth factor signaling pathways.

Site and Extent of Remission:

The brain and pituitary regions remain the most common primary sites affected by spontaneous remission. However, remission has also been observed in the pineal gland, optic pathway, cerebellum, and skull base. Among reported cases, remission involved the primary tumor site in most patients, with multifocal or distant regression noted in a few, including corpus callosum and meningeal lesions. Several recent cases (2020–2025) described remission following radiotherapy or biopsy-related immune activation at the original site. The median follow-up across reported cases was around five years, with most patients maintaining long-term clinical stability or surviving well beyond this interval. Unlike several other malignancies where spontaneous remission may precede recurrence, most brain tumor cases exhibited durable remission and long-term disease control.

Table 1: Brain Tumor SR Cases and Clinical Characteristics

Author–year

Age/sex

Primary site

Remission site

Proposed mechanisms

Follow-up

Vogt, 19777

Not reported/F

Pituitary

Sella turcica

Not reported

Not reported

Vaughn et al., 19808

Not reported/F

Pituitary

Sella turcica

Not reported

Not reported

Zeller et al., 19829

18/F

Pituitary

Pituitary

Hormonal factors

Not reported

Lindholm et al., 198310

Not reported

Pituitary

Pituitary

Tumor necrosis

Not reported

Ikeda et al., 198711

29/F

Pituitary

Pituitary

Hormonal factors

4 months

Brzowski et al., 199212

6 weeks/F

Optic nerve

Optic nerve

Not reported

32 months

Liu et al., 199213

9/F

Optic nerve

Optic nerve

Immune mechanism

32 months

Liu et al., 199213

16/M

Optic nerve

Optic nerve

Immune mechanism

9 years

Liu et al., 199213

22/F

Optic nerve

Optic nerve

Immune mechanism

5 years

Lindvall et al., 200814

61/M

Brain

Frontal and trigone regions

VEGF regulation

1 year

Huang et al., 201315

68/F

Brain

Corpus callosum

Infection resolution

1 year

Hirota et al., 201416

66/Not reported

Falx cerebri

Falx cerebri

Tumor calcification

7 years

Durnford et al., 201417

60/F

Hypoglossal canal

Hypoglossal canal

Not reported

3 years

Pruzan et al., 201518

15 months/M

Optic chiasm

Optic tracts and midbrain

Not reported

Several months

Peddi et al., 201619

55/M

Frontal lobes

Frontal lobes

Drug-induced effect

2 years

Mattogno et al., 201620

15/F

Pineal gland

Pineal gland

Tumor apoplexy

1 year

Mattogno et al., 201620

12/F

Pineal gland

Pineal gland

Tumor apoplexy

5 years

Mattogno et al., 201620

3 months/M

Pineal gland

Pineal gland

Tumor apoplexy

10 years

Spallone et al., 201621

44/M

Septum pellucidum

Septum pellucidum

Vascular coagulation

2 years

Schipmann et al., 201722

5/Not reported

Pineal gland

Pineal gland

Tumor apoplexy

30 months

Santander et al., 201723

54/F

Hypoglossal canal

Hypoglossal canal

Not reported

1 year

Ishihara et al., 201724

15/F

Brain stem

Brain stem

Biopsy-induced apoptosis

1 year

Sebök et al., 201825

61/Not reported

Vestibular nerves

Bilateral vestibular nerves

Vascular thrombosis

11 years

Eichberg et al., 201826

46/F

Pituitary gland

Pituitary gland

Tumor apoplexy

Not reported

Zhang et al., 201927

12/M

Suprasellar region

Corpus callosum

Immune reaction

3 months

Golub et al., 201928

84/M

Parietal region

Frontal region

Immune response

2.5 years

Yamaguchi et al., 201929

55/F

Medulla oblongata

Fourth ventricle

Immune response

1 month

Ghalaenovi et al., 201930

28/M

Pituitary gland

Pituitary gland

Not reported

1 year

Kumaria et al., 202031

51/F

Middle cranial fossa

Middle cranial fossa

Hormonal withdrawal

7 years

Gao et al., 202132

40/F

Temporal lobe

Temporal lobe

Viral antigenicity

Not reported

Noureldine et al., 202133

40 days/M

Brain

Brain and skin

Not reported

3 years

Aldakhil et al., 202234

70/F

Skull base and falx

Intracranial meningiomas

Abscopal effect

6 months

Elavarasi et al., 202235

46/M

Cerebellum

Cerebellar hemispheres

Steroid-induced regression

18 months

Pinkawa et al., 202536

66/F

Falx cerebri

Multiple meningiomas

Abscopal effect

7.5 years

Kameno et al., 201637

13/F

Suprasellar mass

Possible microhemorrhage or physiological enlargement

Up to 2 years

Cefalo et al., 201438

6 months/M

Left congenital cystic eye

Cerebellar lesion

Immune response from partial resection

Confirmed at 24 months

Yilmaz et al., 201639

17/M

C2-C3 meningioma

C2-C3 meningioma

Apoptosis, immune mediated

Complete regression at 6 months

Patra et al., 201740

36/M

Hypothalamo-pituitary

Pituitary apoplexy leading to acromegaly cure

Chentli et al., 201241

9.5/M

Pituitary

Pituitary

2 months

Zieliński et al., 201342

59/F

Pituitary

None

3 months

Amico et al., 199043

26/F

Sellar mass

Possible cyst rupture/hemorrhage

Asymptomatic at 1.5 years

Cinar et al., 201344

38/M

Pituitary macroadenoma

Sella

3 months

Armstrong et al., 199145

66/M

Pituitary

Pituitary

Tumor infarction

MRI 11 months later confirmed involution

Di et al., 200146

16/F

Pineal Gland

Pineal Gland

Normalization of intraventricular pressure

3 years

Inaba et al., 200947

58/F

CNS/pituitary gland

Sarcoidosis elucidated uveitis

16 weeks

Nishio et al., 200148

14/M

Pituitary gland

Pituitary gland

Cyst resorption or rupture

12 months

Nishio et al., 200148

31/F

Pituitary gland

Pituitary gland

Cyst resorption or rupture

3 years

Sayama et al., 200649

36/M

Cavum Septi Pellucidi, Pituitary gland

Rupture of the cyst, possible fenestration

15 months

Popa, 202150

51/F

Pituitary gland

None reported

Hasebe, 202351

31/F

Pituitary gland

Pituitary stalk

1 year

Dawoud, 202152

32/F

Left eye

Left eye

2 weeks

Van & Oven et al., 202053

31/F

Pituitary gland

Pituitary gland

Pituitary apoplexy

Alam, 202154

40/M

Pituitary gland

Pituitary apoplexy

Komić, 202155

54/M

Pituitary gland

Pituitary

Infarction, hemorrhage, necrosis

3 months

Machado, 201356

36/F

Pituitary gland

None reported

Tumor shrinkage observed

Kim, 202257

73/F

Brain

Decreased blood supply due to calcification

Yang, 202358

1/M

Skin

Skin

1 year

Yamaguchy, 201959

55/F

Brain

Brain

Immune response

1 month

Jacobsson et al., 198960

59/M

Intracranial

8 years

Smithers, 196261

Balance in tissue growth

Kowada et al., 197462

42/M

Aneurysm

2 weeks

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  59. Yamaguchi, J., Motomura, K., Ohka, F., Aoki, K., Tanahashi, K., Hirano, M., Nishikawa, T., Shimizu, H., Wakabayashi, T., & Natsume, A. (2019). Spontaneous Tumor Regression of Intracranial Solitary Fibrous Tumor Originating From the Medulla Oblongata: A Case Report and Literature Review. World neurosurgery, 130, 400–404. https://doi.org/10.1016/j.wneu.2019.07.052
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