This document provides information on astrocytoma neuroimaging and classification. It describes various types of astrocytomas including their cell of origin, common locations, histology, progression, and radiology characteristics. Key points covered include: - Astrocytomas include low-grade diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma. - Radiology can show tumor infiltration and characteristics vary from non-enhancing to ring enhancement with necrosis. - Pathology examines features like cell type, mitoses, and staining for markers like GFAP.

1. Astrocytoma Neuroimaging Dr Deb

2. I. Tumors of neuroepithelial tissue Astrocytic tumors Oligodendroglial tumors Ependymal tumors Mixed gliomas Choroid plexus papilloma Neuroepithelial tumors of uncertain origin Neuronal and mixed neuronal-glial tumors Pineal tumors Embryonal tumors

6. A. Astrocytic tumors Astrocytoma Variants : fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma

7. Astrocytoma Cell of Origin: ASTROCYTE Synonyms: diffuse astrocytoma, "ordinary" astrocytoma Common Locations: cerebral hemispheres, in children in the pons ("brainstem glioma") Demographics: 4th and 5th decades (30's and 40's) Histology: ill-defined, diffusely infiltrating, overrun (trap) neurons, enlargement but not destruction of the invaded structures, mitoses, vascular proliferation, and necrosis are not present Special Stains: GFAP+ (Glial Fibrillary Acidic Protein) Progression : naturally progress to anaplastic astrocytoma, and then to glioblastoma

8. Radiology : Astrocytoma The lesion is usually recognized by causing expansion of the infiltrated portion of the cerebrum or brainstem. Mass effect may be minimal for the overall size of the signal/attenuation abnormality, and the lesion may be surprising large at the time of presentation with minimal symptoms. Regions of signal and attenuation change usually represent the neoplasm itself - since the intact blood-brain-barrier does not cause enhancement nor vasogenic edema. Hemorrhage is rare, however, calcification can occur. The tumor tends to follow white-matter tracts and may cross the corpus callosum, or follow the peduncles to/from the brainstem

9. Astrocytoma of the Brain • Axial T2 weighted spin-echo image of the head. • There is an intra-axial mass in the left frontal lobe with surrounding vasogenic edema. • There is mass effect on the surrounding structures with compression of the left frontal horn and displacement of the falx to the right.

11. A 45 year old woman with a two year history of infrequent headaches presented with a seizure 4 years ago and was found to have a nonenhancing left posterior temporal and parietal lesion that was stereotactic biopsied and shown to be a low grade anaplastic astrocytoma grade 3. She was subsequently treated with radiotherapy, and later with chemotherapy. Despite treatment, the tumor recurred and radiosurgery was performed six months later. Six months following radiosurgery she developed visual field loss and speech problems. SPECT was normal. Several weeks following surgery, a MRI showed a questionable area of enhancement in the resection bed adjacent to the occipital horn.

13. Parietal lobe perfusion defect (HMPAO) with faint focal parietal thallium uptake, consistent with radiation necrosis.

14. Astrocytoma the tumor completely replaces the basal ganglia and infiltrates profusely into surrounding tissue. Note also that this is an expanding intercranial mass. The nature of gliomas is such that they infiltrate subtly into surrounding tissue, making them very difficult to remove

15. Fibrillary Astrocytoma Coronal gross brain section. There is gross expansion of the left cerebral hemisphere. This is caused by infiltration of a diffuse low-grade (WHO Grade 2) fibrillary astrocytoma. This is "gliomatosis cerebri". In addition, the superior surface of the expanded hemisphere has a discoloration from a local area of transformation from Grade 2 into a Grade 4 astroctyoma (Glioblastoma Multiforme or GBM). This is a natural progression, from low-grade to high-grade. At least 50% of GBM's arise from a pre-existing lower grade lesion

16. Gemistocytic Astrocytoma

17. Anaplastic Astrocytoma

18. CC: Episodic confusion HX: This 65 y/o RHM reportedly suffered a stroke on 1/17/92. He presented locally at that time with complaint of episodic confusion and memory loss lasting several minutes per episode. The "stroke" was reportedly verified on MRI scan dated 1/17/92. He was subsequently placed on ASA and DPH. He admitted that there had been short periods(1-2 days duration) since then, during which he had forgotten to take his DPH. However, even when he had been taking his DPH regularly, he continued to experience the spells mentioned above. The episodes of confusion and memory loss last 1-2 minutes in duration, and have been occurring 2-3 times per week. PMH: Bilateral Hearing Loss of unknown etiology, S/P bilateral ear surgery many years ago. MEDS: DPH and ASA SHX/FHX: 2-4 Beers/day. 1-2 packs of cigarettes per day. EXAM: BP 111/68, P 68BPM, 36.8C. Alert and Oriented to person, place and time, 30/30 on mini-mental status test, Speech fluent and without dysarthria. CN: Left superior quandranopia only. Motor: 5/5 strength throughout. Sensory: unremarkable except for mild decreased vibration sense in feet. Coordination: unremarkable. Gait and station testing were unremarkable. He was able to tandem walk without difficulty. Reflexes: 2+ and symmetric throughout. Flexor plantar responses bilaterally.

19. Review of outside MRI Brain done 1/17/92 revealed decreased T1 and increased T2 signal in the Right temporal lobe involving the uncus and adjacent hippocampus. The area did not enhance with gadolinium contrast

20. MRI Brain with/without contrast: 8/31/92: Decreased T1 and increased T2 signal in the right temporal lobe. The lesion increased in size and enhances more greatly when compared to the 1/17/92 MRI exam. There is also edema surrounding the affected area and associated mass effect.

21. Neuropsychological testing: Low-average digit symbol substitution, mildly impaired verbal learning, and severely defective delayed recall. There was relative preservation of other cognitive functions. The findings were consistent with left mesiotemporal dysfunction. COURSE: Patient underwent right temporal lobectomy on 9/16/92 following initial treatment with Decadron. Pathologic analysis was consistent with a Grade 2 astrocytoma. GFAP staining positive. Following surgery he underwent 5040 cGy radiation therapy in 28 fractions to the tumor bed.

22. Shown here is the displaced sensorimotor cortex of a patient with a low grade astrocytoma, demonstrated by fMRI

23. A seventeen year-old boy with numbness in the left foot was examined. Sagittal T1, axial T2 (middle), axial FLAIR and axial post-gadolinium (right) MRI revealed a 5cm (anterior-posterior) x 4 cm (right to left) x 3.5 cm (superior-inferior) right parietal lobe mass. The imaging characteristics suggested either as astrocytoma or dysembryoblastic neuroepithelial tumor

26. Three-dimensional mod of this patient's MRI was reconstructed. The brain is shown in white, the tumor is shown in green, the vessels are shown in red and the ventricles are shown in light blue.

27. This model helped visualize the lesion in 3D space. The location of the tumor was confirmed as being in the motor and primary sensory cortex. After discussion with the parents of the patient, it was decided to perform resection of the lesion under local anesthesia to monitor the patient's motor and sensory functions.

32. Grade II Astrocytoma

33. A. Astrocytic tumors Astrocytoma Variants : fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma

34. Anaplastic Astrocytoma WHO Grade III Cell of Origin: ASTROCYTE Synonyms: Common Locations: cerebral hemispheres, brainstem Demographics: Histology: astrocytes with anaplastic features: increased cellularity, pleomorphism, mitotic activity, and nuclear atypia Special Stains: GFAP+ Progression : great probability of progression to glioblastoma Radiology: Variable appearance for features of enhancement and surrounding edema. Necrosis (ring enhancement) does not occur, and cyst formation is extremely rare. COMMENTS: This stage of astrocytoma is the least common, and may represent a short-term intermediate lesion during the transition from Grade II to Grade IV astrocytoma.

35. Male, 45 years, suffering from a first generalised seizure two weeks ago. On MR images, subcortical, slightly hyperintense (T2 WI), ill-delimited lesion in left temporal lobe. Heterogeneous and mild contrast enhancement. We firstly read this lesion as a probable aspecific vascular versus inflammatory (infectious?) lesion. A control MR, one month later, demonstrates an enlargement of the lesion. Final diagnosis after surgery: anaplastic astrocytoma.

36. A. Astrocytic tumors Astrocytoma Variants : fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma

37. GBM WHO Grade IV Cell of Origin: ASTROCYTE Synonyms: GBM, glioblastoma multiforme, spongioblastoma multiforme Common Locations: cerebral hemispheres, occasionally elsewhere (brainstem, cerebellum, cord) Demographics: peak from 45-60 years Histology: grossly heterogeneous, degeneration, necrosis and hemorrhage are common Special Stains: GFAP varies, often present in areas of better differentiation Progression : Can't get any worse.

38. Radiology: GBM Glioblastoma is usually seen as a grossly heterogeneous mass. Ring enhancement surrounding a necrotic center is the most common presentation, but there may be multiple rings. Surrounding vasogenic edema can be impressive, and adds significantly to the mass effect. Signs of recent (methemoglobin) and remote (hemosiderin) hemorrhage are common. Despite it’s apparent demarcation on enhanced scans, the lesion may diffusely infiltrate into the brain, crossing the corpus callosum in 50-75% of cases.

39. Glioblastoma

40. Glioblastoma is usually seen as a grossly heterogeneous mass. Ring enhancement surrounding a necrotic center is the most common presentation, but there may be multiple rings. Surrounding vasogenic edema can be impressive, and adds significantly to the mass effect. Signs of recent (methemoglobin) and remote (hemosiderin) hemorrhage are common. Despite it’s apparent demarcation on enhanced scans, the lesion may diffusely infiltrate into the brain, crossing the corpus callosum in 50-75% of cases.

41. Admission scans after first seizure

42. One month later

43. Two months later

44. GBM thalamus This T1W MR after Gadolinium infusion reveals a thalamic mass lesion. This is characterized by irregular ring-enhancement surrounding a central non-enhancing region of necrosis. Note the shaggy inner-margin of the ring, and the remakable variation in its thickness. The small foci of internal enhancement represent islands of living tumor within the regions of necrosis.

45. GBM 61-year-old RH white male with history of multiple CVAs with new onset of right sided hemiparesis of one week duration. Axial post Gadolinium T1 W1 of the brain reveals a large necrotic butterfly mass involving the corpus callosum with enhancing borders. There is no evidence of herniation

46. GBM

47. GBM Axial Gd Enhanced T1W MR Axial T2W MR

48. Fusion imaging - Grade IV astrocytoma . (a) Contrast-enhanced axial CT scan . (b) Tc-99m HMPAO SPECT image at the same anatomic level. (c) Fused imag

49. Recurrence and upgrading of a grade IV astrocytoma. (a) T1-weighted contrast-enhanced MR image. (b) F-18 DG SPECT image at the same anatomic level. (c) Fused image before stereotactic biopsy.

50. GBM - Gross a massive neoplasm in the left hemisphere replacing the ventricle and much of the temporal and parietal lobe. Note that it is variegated in color and appearance indicating necrosis and hemorrhage. The apparent sharp boundaries of the tumor are deceptive because actually it, like any other glioma, has infiltrated beyond its apparent margins.

51. GBM Gross A coronal section through the parietal-occipital junction. The large variegated mass represents a glioblastoma multiforme - multiform in shape, color, texture and histology.

52. GBM - Microscopy the typical type of necrosis seen in a glioblastoma surrounded by more dense layer of tumor cells referred to as "pseudopalisading". Note also in the lower corner a vessel that is thrombosed

53. GBM- Mesencephelalon There is an irregular red-brown-black lesion of the brainstem, with dramatic enlargement of the affected area. Histologically, this was a glioblastoma.

55. A. Astrocytic tumors Astrocytoma Variants : fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma

59. Pilocytic Astrocytoma

60. JPA – WHO Grade 1 Contrast enhanced CT of a juvenile pilocytic astrocytoma (JPA). Notice that there is a characteristic "cyst and mural nodule" morphology. The key feature here is that most of the cyst lining does NOT show contrast enhancement. Notice that this nodule has a central area without enhancement - due to a cyst within the nodule (NOT necrosis). Although the appearance can be variable, both JPA and hemangioblastoma can be suggested when a cerebellar lesion has a "cyst and nodule" appearance.

61. JPA – WHO - 1 This Gadolinium enhanced T1W MR shows a characteristic "cyst and mural nodule" morphology for a pilocytic astrocytoma (JPA). Notice that part of the cyst lining does NOT enhance. Although the appearance can be variable, both JPA and hemangioblastoma should be suggested when a cerebellar lesion has this "cyst and nodule" appearance .

62. This coronal T1W Gadolinium enhanced MR shows a cerebellar mass with a "cyst with nodule" morphology.

63. JPA – WHO –1 This CT scan shows a posterior fossa mass ("Cyst with Nodule") causing obstructive hydrocephalus with temporal horn dilatation.

64. JPA – WHO - 1 This is also a pathologically-proven JPA, presenting in a 14 y.o. boy. This one did not "read the book" and the mass, although partially cystic and partially solid, has a grossly heterogeneous morphology - rather than the classic "cyst with nodule" shape. A lesion with this complex configuration could be a malignant glioma with necrosis. However, the cerebellar location and the young age make JPA a more likely possibility.

65. Pilocytic Astrocytoma This sagittal T1W image demonstrates a large suprasellar pilocytic astrocytoma of the hypothalamus. The mass is heterogeneous, and extends downward into the region of the sphenoid sinus, as well as behind the clivus

66. JPA - Angiogram Lateral posterior fossa angiogram, subtracted image. Cerebellar pilocytic astrocytoma. Notice how there is vascular displacement - but not neovascularity. Pilocytic astrocytomas enhance because of increased capillary permeability, not because of arterial neovascularity.

67. JPA – WHO - 1 This gross picture demonstrates a cystic lesion in the left cerebellar hemisphere. There is a thin white line surrounding the cavity - representing compressed cerebellar tissue with gliosis. However, the "cyst lining" is NOT composed of neoplastic tissue, accounting for the absence of enhancement.

68. JPA - Gross Coronal gross photograph. This juvenile pilocytic astrocytoma shows a well-defined "mural nodule" inside of a "cystic" region.

69. JPA - Gross This section of cerebellum shows a cystic tumor occupying the central white matter of the cerebellar and part of the dentate nucleus. This is an example of a pilocytic astrocytoma. It is usually very slow growing, occurs most commonly in children and will cause symptoms referable to the cerebellum where it most commonly occurs

71. JPA- Histology This HE photomicrograph shows some of the classic features of a juvenile pilocytic astrocytoma: a biphasic pattern (alternating dense and loose areas), microcysts, and an absence of aggressive features (no necrosis, no mitoses, no hemorrhage).

72. Pilocytict Astroctytoma

74. This 16-year-old young man presented in 1993 with headache, nausea, and vomiting. Magnetic resonance imaging (MRI) study revealed a solitary brain tumor at the trigonum of the right lateral ventricle

75. No contrast enhancement was noted. The tumor was totally removed in 1994 as demonstrated by the preoperative scan (left) and a postoperative scan (right).

76. MRI in February 1995 showed recurrent tumor tissue lateral to the temporal horn of the right ventricle. In October 1995, tumor recurrence had enlarged in size. A concentric limitation of the visual field occurred seven months later in May 1996. In November 1996 the recurrent tumor tissue demonstrated for the first time contrast enhancement on MRI.

77. In February of 1998, extensive dissemination of the tumor along the supratentorial ventricular system and the spinal leptomeninges was noted during a routine control MRI scan No recurrent tumor tissue was present at the primary site of operation. The patient had no clinical symptoms. Multiple nodules, up to 5 mm I size and markedly contrast enhancing, were found in both lateral ventricles, the III ventricle

78. Spinal cord dissemination

79. With MRI criteria they all looked identical. One of them was removed using neuronavigation

80. An Ommaya reservoir was implanted. The patient recieved systemic chemotherapy with vincristin and carboplatinum, under which tumor nodules had not changed in size by the end of December 1998.

81. H&E sections of the tumor operated in 1994 showed a moderately cellular glial neoplasm. Some areas were composed of piloid astrocytes and displayed few Rosenthal fibers

82. Sometimes larger multinuclear cells were present

83. The regions near the ventricle were composed of loosely arranged piloid cells and large glial cells with one or more nuclei A broad glial fibrillary acidic protein (GFAP)-positive cytoplasm Areas immediately at the ventricle site ('V' in Fig. 3C and Fig. 3D ) showed five or six 'layers' of densely packed smaller astrocytic cells with shorter processes and only slight GFAP-immunoreaction. Mitoses, necroses and endothelial proliferations were absent.

84. The biopsy of one of the ventricular tumor disseminations in 1998 revealed histological and immunohistochemical features which were very similar with the initial resection specimen. The density of capillaries was however higher

85. The smaller neoplastic astrocytes which formed a 'layer' at the ventricle site were also demonstrable in the tumor spreadings (Fig. 8A). They could sometimes be found in the ventricular space without connection to the other tumor cells As in 1994, no histologic signs of anaplasia or malignancy could be found. Mitoses were absent. The Ki67-positivity was very low, especially in the densely packed cells in close vicinity to the ventricle (not shown). Cebrospinal fluid cytology revealed no anaplastic cells.

86. DIAGNOSIS Pilocytic astrocytoma (WHO grade I) with widespread dissemination in the CNS. The diagnosis was confirmed by the German reference center for brain tumors in Bonn.

87. A. Astrocytic tumors Astrocytoma Variants : fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma

88. Pleomorphic xanthoastrocytoma WHO Grade II - III Cell of Origin: ASTROCYTE (subpial?) Common Locations: cerebral hemispheres, usually superficial, often temporal Demographics: children and young adults Histology: A frightening mixture of unusually pleomorphic cells, ranging from fibrillary to bizarre giant multinucleated cells with intracellular lipid vacuoles ("xanthoma" cells). Special Stains: GFAP positive Progression : may progress in some cases to Grade III (anaplastic) or even Grade IV (GBM)

89. Radiology : PXAC Usually a large hemispheric mass, closely related to the cerebral surface. May have a disturbingly heterogeneous appearance with cyst formation, variable calcification, and prominent enhancement. The superficial location and presentation in childhood are the most helpful features. Dural involvement and a "dural tail" are possible

90. PLEOMORPHIC XANTHOASTROCYTOMA Axial T1W Gd Enhanced MR Axial CT

91. A. Astrocytic tumors Astrocytoma Variants : fibrillary, protoplasmic, gemistocytic, mixed Anaplastic (malignant) astrocytoma Glioblastoma Variants giant cell glioblastoma, gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma

92. Synonyms: Ventricular tumor of Tuberous Sclerosis Common Locations: Lateral ventricle, attached to caudate head. Demographics: children, young adults Histology: Large cells that variously resemble astrocytes, although may express neuronal markers Special Stains: GFAP variable (usually present), neuronal markers +/- Progression : No Radiology: Usually seen with other features of Tuberous Sclerosis. May obstruct f. of Monro and cause hydrocephalus. Enhancement and calcification are both common. Plane Contrast

93. SUBEPENDYMAL GIANT CELL ASTROCYTOMA T1 Gd T1

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