Pathology of Brain Tumors: Types, Grading, and Diagnosis

A brain tumor is a peculiar growth of cells within the brain or central spinal cord. These tumors can be both primary (originating in the brain) or secondary (metastatic, originating somewhere else and spreading to the brain). Brain tumors can vary broadly in terms of their kind, location, and behavior, ranging from benign (non-cancerous) to malignant (cancerous).

Primary Brain Tumors: Grading

A - Atypia 

M - Mitosis 

E - Endothelial cell proliferation 

N - Necrosis 

• Grade 1: Atypia, mitosis, endothelial cell proliferation, and necrosis are absent. 
• Grade 2: Atypia is present. 
• Grade 3: Atypia and mitosis are present. 
• Grade 4: 3/4 features are present. 

Classification of Brain Tumors

Classification of Brain Tumors

Gliomas: glial cells

Astrocytoma

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Juvenile Pilocytic Astrocytoma: CCC factor

Age	Children
Site	Cerebellum
Gross	Cystic lesion with a mural nodule
Mutation	BRAF-KIAA fusion BRAF V E mutation
Microscopy	- Rosenthal fibers (thread-like structure, non-specific)  - Mulberry body  - Composition: alpha-beta crystallin, ubiquitin, heat shock proteins, and GFAP.
Prognosis	Good

Glioblastoma

Age	Most common malignant brain tumor in adults
Gross	Resembles a butterfly - crosses the midline
Microscopy	Serpentine necrosis - surrounded by pseudo-palisading of the tumor cells Glomeruloid Body - Endothelial cell proliferation
Mutation	IDH - wild type (90%)  - p53  - PTEN  - EGFR  - TERT IDH - mutant type ( problem)  - p53  - ATRX  - TERT
Prognosis	Very bad

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Oligodendroglioma 

• Site - Frontal Lobe 
• Gross - Calcification +
  • C - Craniopharyngioma 
  • O - Oligodendroglioma 
  • M - Meningioma 
• Microscopy -
  • Fried egg appearance: nucleus and & Perinuclear hal

• Chicken wire appearance of blood vessel

• Perineuronal satellitosis 
• Mutation - 
  • IDH mutation: most common 
  • Co-deletion 1p/19q-good response to chemotherapy

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Ependymoma

Grade II tumor

Site	Children, 4th Ventricle  Adults: Spinal Cord
Genetics	MIS M E  - Multiple Inherited - Schwannoma  - Meningiomas  - Ependymoma  - Neurofibromatosis-2
Microscopy	Perivascular Pseudorosettes

Updates

Myxopapillary Ependymoma 

• Myxoid + Papillae 
• Located in Filum Terminale 
• Grade 1 tumor

Rela Fusion Ependymoma

• R - Rela gene 
• EL - chr 11 
• A - above tentorium in the brain/supratentorial tumor 
• Occurs in children 
• Poor prognosis 

Neuronal Tumors

• Ganglioglioma: most common 
• Gangliocytoma 
• Neurocytoma 
• DNET (Dysembryoplastic Neuroepithelial Tumor)
  • Floating neurons in pools of mucopolysaccharide

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Undifferentiated Tumors 

Medulloblastoma - Grade IV tumor 

• Pseudorosettes: presence of material/blood vessels in the center.
  • Homer Wright pseudorosette (M/E/N): pink material in the center 
  • Perivascular pseudorosette—blood vessel in the center (seen in ependymoma) 
• True rosette: absence of material/blood vessel in the center (appears clear/empty).
  • Flexner-Wintersteiner rosette seen in retinoblastoma. 

Medulloblastoma: Genetics

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Gorlin syndrome 

• PTCH gene mutation 
• SHH pathway is affected 
• Desmoplastic Medulloblastoma 
• Basal cell carcinoma 
• Bilateral ovarian fibroma

Note : TURCOT syndrome 

• Colon tumor (COT) 
• Brain tumor : medulloblastoma (TUR - turban)

Atypical Teratoid/Atypical Rhabdoid- AT/AR 

• SNF/INI Mutation 
• Atypical rhabdoid : shows SNF mutation

Meningioma

• Risk factors
  • Females 
  • Pregnancy 
  • Radiation 
  • Nf2 
• Progesterone receptor +ve 
• It is a dura-based tumor—whorling of the tumor cells 
• Psammoma bodies 
• Grade depends on the progression of tumor

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Miscellaneous

Lymphoma of brain

• EBV infection in HIV-positive individuals 
• Most common is DLBCL 
• Angiocentric pattern 
• Hooping pattern 

Schwannoma

• Nf2 
• It can occur at any site. 
• Spinal cord: dumbbell-shaped appearance 
• Microscopically:

• Antony A: hypercellular area 
• Antony B: hypocellular area 
• Verocay bodies (two rows of palisading nuclei with cytoplasm in the center) 
• MPNST is different from schwannoma so mention it as different heading 

Malignant peripheral nerve sheath tumor (MPNST) 

• Malignant version of schwannomma 
• Triton tumor: MPNST+ rhabdomyoblasts

Craniopharyngioma 

• Origin: Rathke's pouch 
• Site: Suprasellar location + calcification
• Age: Children 
• Clinical feature: vision disturbance & headaches 
• Two types : Adamantinomatous and Papillary

• Palisading nuclei 
• Stellate reticulum 
• Wet keratin on gross examination : machine-oil appearance

Update: Diffuse Midline Glioma 

• Occurs in the midline of the brain 
• Seen in children 
• Glial tumor 
• It spreads out 
• Bad prognosis 
• H K M-mutation (H3 is histone)

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Important questions

Q. Which is the most common malignancy in the brain/lungs/heart/liver/bones? 

Ans. Metastasis 

Q. Most common cancer to cause brain metastasis? 

Ans. Small cell lung cancer 

Q. Cancer that never metastasizes to the brain? 

Ans. Prostate cancer 

Q. Which is the cancer that metastasizes to the meningeal part? 

Ans. Leptomeningeal carcinomatosis commonly from breast cancer

MCQs

Q. A 10-year-old male child shows a well-circumscribed cystic lesion in the cerebellum. A mural nodule is identified within the cystic lesion. Biopsy and microscopic evaluation show the following features: What is your diagnosis?

1. Oligodendroglioma 
2. Glioblastoma 
3. Meningioma 
4. JPA

Q. A 55-year-old man presents with seizures and muscle weakness but no other neurological signs. A CT scan reveals a mass in the left cerebral hemisphere. A left frontotemporal craniotomy is performed. A histological examination of the brain biopsy is shown.

1. Oligodendroglioma 
2. Glioblastoma 
3. Meningioma 
4. JPA 

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Q. A 35-year-old female patient presents with epileptic attacks. Radiological investigations reveal the presence of a frontal lobe mass with foci of calcification. Biopsy shows the presence of sheets of cells with a perinuclear halo. The patient is diagnosed with a Grade 2 brain tumor and advised genetic analysis. Treatment of the patient shows a good response to chemotherapy. Which of the following tumors best describes this? 

1. Oligodendroglioma 
2. Glioblastoma 
3. Meningioma 
4. JPA 

Q. A 33-year-old female with acoustic schwannoma. She also shows the presence of pigmented lesions over the trunk and lower back. On radiological investigations, she has a non-infiltrating brain tumor showing areas of calcification. On biopsy, the tumor shows positivity for PR. Diagnosis. 

1. Oligodendroglioma 
2. Glioblastoma 
3. Meningioma 
4. JPA 

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