Neuropathology-Q&A-Feb22 by IHC001

Neuropathology Questions FRCPath - Part 1

Dr Azzam Ismail Consultant Neuropathologist Leeds Teaching Hospital 2022

MCQ 1 You are asked to provide an intraoperative opinion on a frozen section from intr-axial posterior cranial fossa tumour stained with H&E. The patient is a 6 year old boy that presented with headache and vomitting. The lesion is biphasic composed of loose microcystic and more dense areas have low cellularity, composed of elongated cells with very thin and long cystoplasmic processes with occasiaol bright red round bodies. Vascular endothelial proliferation is noted. The preferred diagnosis is:

Ependymoma Neurofibroma Haemangioblastoma Schwannoma Pilocytic astrocytoma

Pilocytic astrocytoma

MCQ 2 At a multi-disciplinary team meeting (MDT), a diffusely infiltrating glial tumour in the left parietal lobe from a 55 y old man is discussed. A neurosurgeon asks to see the features associated with poor prognosis. Identify which of the following features you should demonstrate:

Mitotic figures Nuclear atypia High cellularity Necrosis Endothelial Vascular proliferation

Necrosis

MCQ 3 50y old woman was admitted to hospital with seizures following 2 weeks of progressive headache. MRI scan shows non-enhancing diffusely infiltrating frontal lobe tumour. Partial lobectomy was done and histology shows a diffusely infiltrating glioma and molecular genetic was done . Which of the following molecular genetic tests confirm the diagnosis of oligodendroglioma:

IDH1/2 mutation & MGMT methylation

IDH1/2 BRAF V600E mutation, P53 mutation mutation & ATRX loss

IDH1/2 mutation H3 K27M & 1p/19q Comutation & deletion EGFR amplification

IDH1/2 mutation & 1p/19q Codeletion

MCQ 4 During a Clinico-Pathological Conference a case of Parkinson disease was discussed. A range of Immunocytochemical stains were presented. Which of the following stains will establish the diagnosis conclusively?

Tau

Ubiquitin

BetaA4

Alpha synuclein

GFAP

Alpha synuclein

MCQ 5 31 year old male diagnosed with acquired immunodeficiency syndrome since age 25. Gradual deterioration with visual loss and hemiparesis. Dies suddenly. At post-mortem, there are numerous softened coalescing lesions throughout the brain of yellowish/white colour involving the optic nerves, cortical/subcortical region and periventricular white matter. The microscopical examination showed enlarged oligodendrocytes, abnormal astrocytes and myelin pallor. What is the likely aetiology of these lesions?

Cytomegalovirus HIV

Toxoplasmosis JC virus

HSV type II

JC virus

MCQ 6 60 year old man presented with a few months history of progressive left side headache and visual impairment progressed to perminant visual loss. What is the most likley diagnosis?

Giant cell arteritis

Thrombosis of Dissection of vertebrointernal basilar system carotid

Antiphospholipid Venous syndrome thrombosis

Giant cell arteritis

EMQ 1 Each one of these subjects had a brain biopsy. For each one select the most likely condition from the list of options. Each option must be used once only.

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Subependymal Giant Cell Astrocytoma

Central neurocytoma

Oligodendroglioma

Astrocytoma

Medulloblastoma

Pilocytic astrocytoma

Simple pineal cyst

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Ependymoma

Lymphoma

Meningioma

Colloid cyst

Acoustic Schwannoma

Metastatic melanoma

Haemangioblast oma

Option 0

Option P

Option Q

Option R

Option S

Option T

Gliosarcoma

Pleomorphic Xanthoastrocytoma

Subependymoma

Giant cell Glioblastoma

Ganglioglioma

Metastatic carcinoma

Question 1

Note 1

5 year old male child exhibiting an enhancing lesion in the cerebellum associated with a cyst. On biopsy there are elongated astrocytes associated with Eosinophilic granular bodies (EGB) and Rosenthal fibres. Mitotic figures are not a feature Question 2

Note 2

24 year old female with an intraventricular tumour near the foramen of Monro. The cut surface of the tumour is uniform, grayish with abundant microcalcifications. Microscoy showed round uniform cells with neuropil islands Question 3

Note 3

23 year old female with a mass in the left temporal lobe. The lesion is well-demarcated and showed reticulin fibres surrounding individual cells associated with Eosinophilic granular bodies. No mitotic figures are seen. Question 4

Note 4

48 year old male with an enhancing cerebellar tumour associated with a cyst. Histologically one can see numerous capillary-size blood vessels and xanthomatous change in stromal cells. Question 5 72 year old male with a tumour in the 4th ventricle, incidental finding at post-mortem due to ischaemic heart disease. The tumour is of low cellularity with a suggestion perivascular pseudorosettes and extensive calcification

Note 5

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Subependymal Giant Cell Astrocytoma

Central neurocytoma

Oligodendroglioma

Astrocytoma

Medulloblastoma

Pilocytic astrocytoma

Simple pineal cyst

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Epnedymoma

Neurofibroma

Meningioma

Colloid cyst

Acoustic Schwannoma

Metastatic melanoma

Haemangioblast oma

Option 0

Option P

Option Q

Option R

Option S

Option T

Gliosarcoma

Pleomorphic Xanthoastrocytoma

Subependymoma

Giant cell Glioblastoma

Ganglioglioma

Metastatic carcinoma

Question 1

Note 1

Intrinsic low grade lesion. No mitotic activity. Rosenthal fibres + EGB

Question 2

Note 2

Intraventricular tumour in a young patient with neuropil islands.

Question 3

Note 3

Well demarcated tumour with individual cells surrounded by reticulin fibres

Question 4

Note 4

48 year old male with an enhancing cerebellar tumour associated with a cyst. Histologically one can see numerous capillary-size blood vessels and xanthomatous change in stromal cells.

Cystic lesion with enhancing nodule in the posterior fossa.

Question 5

Note 5

72 year old male with a tumour in the 4th ventricle, incidental finding at post-mortem due to ischaemic heart disease. The tumour is of low cellularity with a suggestion perivascular pseudorosettes and extensive calcification

Perivascular pseudorosettes are also diagnostic of Subependymomas, which is the most common tumour in IVth ventricle in patients of any age that give rise to clinical symptoms only exceptionally.

Answer 1

Comment 1

The most common posterior fossa lesion in the paediatric group is Pilocytic astrocytoma

Answer 2

Comment 2

Most common intraventricular tumour with neuropil islands is Central Neurocytoma

Answer 3

Comment 3

PXA is a rare tumour but individual cells surrounded by reticulin fibres is a diagnostic feature

Answer 4

Comment 4

Haemangioblastoma is the most common type of tumour in patients over 40 in the posterior fossa

Answer 5

Comment 5

These tumours are usually incidental findings at post-mortem.

Reasoning and Comments (in bullet points please)

References (Essential Book, medical publication etc)

Features of high grade: mitotic activity, necrosis, microvascular proliferation. Well circumscribed tumours include Pilocytic astrocytoma, PXA and Subependymal Giant Cell Astrocytoma Rosenthal fibres and Granular Eosinophilic Bodies are seen in low grade tumours

( Notes ) Focus e.g. J – Clinical Investigation

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Subependymal Giant Cell Astrocytoma

Central neurocytoma

Oligodendroglioma

Astrocytoma

Medulloblastoma

Pilocytic astrocytoma

Simple pineal cyst

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Ependymoma

Neurofibroma

Meningioma

Colloid cyst

Acoustic Schwannoma

Metastatic melanoma

Haemangioblast oma

Option 0

Option P

Option Q

Option R

Option S

Option T

Gliosarcoma

Pleomorphic Xanthoastrocytoma

Subependymoma

Giant cell Glioblastoma

Ganglioglioma

Metastatic carcinoma

Question 1

Note 1

Question 2

Note 2

Question 3

Note 3

Question 4

Note 4

48 year old male with an enhancing cerebellar tumour associated with a cyst. Histologically one can see numerous capillary-size blood vessels and xanthomatous change in stromal cells.

Question 5

Note 5

EMQ 2 Each of these individuals had a lesion in the suprasellar region. For each one select the most likely condition from the list of options. Each option should be used once only.

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Pituitary adenoma

Adamantinomatous Craniopharyngioma

Lymphoma

Germinoma

Rathke’s cleft cyst

Meningioma

Pilocytic astrocytoma

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Granuloma

Granular cell tumour

Immature Teratoma

Teratoma

Chordoma

Chondroma

Papillary Ependymoma

Option 0

Option P

Option Q

Option R

Option S

Option T

Hypothalamic Hamartoma

Ganglioglioma

Papillary craniopharyngioma

Central Neurocytoma

Neuroblastoma

Colloid cyst

Question 1

Note 1

40 year old male with a history of headache and brainstem dysfunction. CT scan showed a clival lesion with irregular enhancement. Biopsy shows physallipherous and eosinohilic cells arranged in a lobular pattern in a pseudocartilagenous matrix. Tumour cells are positive with EMA. Question 2

Note 2

34 year old female with pituitary dysfunction, headache and decreased visual acuity. MRI shows a 2 mm supratentorial nodule located in the pituitary stalk. Histology shows a biphasic tumour composed of large Eosinophilic cells with vesicular nuclei and prominent nucleoli associated with numerous clusters of lymphocytes. Question 3

Note 3

3 year old male with a tectal plate variably enhancing lesion with lobular appearance on MRI. The histology of the small biopsy taken showed low cellularity cartilage with foetal-type glands and embryonic mesenchyme-like sroma Question 4

Note 4

40 year old female died suddenly due to acute hydrocephalus. At post-mortem, there is a cyst in the third ventricle containing proteinaceous material. Histological examination showed a benign epithelial lining on the wall of the cyst. Of cylindrical ciliated epithelium Question 5 45 year old male presenting with headaches. CT/MRI showed an intrasellar enhancing lesion. The working diagnosis was pituitary adenoma. Intraoperative smear shows a monolayer of monotonous cells.

Note 5

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Pituitary adenoma

Adamantinomatous Craniopharyngioma

Lymphoma

Germinoma

Rathke’s cleft cyst

Meningioma

Pilocytic astrocytoma

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Granuloma

Granular cell tumour

Immature Teratoma

Teratoma

Chordoma

Chondroma

Papillary Ependymoma

Option 0

Option P

Option Q

Option R

Option S

Option T

Hypothalamic Hamartoma

Ganglioglioma

Papillary craniopharyngioma

Central Neurocytoma

Neuroblastoma

Colloid cyst

Question 1

Note 1

Physalliperous cells are quite characteristic of chordomas

Question 2

Note 2

Immunocytochemistry is of assistance in framing the diagnosis.

Question 3

Note 3

DDx should include Teratoma versus Immature Teratoma

Question 4

Note 4

Differential diagnosis should include midline epithelial cysts

Question 5

Note 5

45 year old male presenting with headaches. CT/MRI showed an intrasellar enhancing lesion. The working diagnosis was pituitary adenoma. Intraoperative smear shows a monolayer of monotonous cells.

A single layer on smear preparations in the suprasellar region should include in the differential diagnosis: lymphoma, pituitary adenoma, germinoma.

Answer 1

Comment 1

Chordomas are most commonly found at the extremes of the spinal column i.e. clivus or sacrum, although they can also present in other parts of the vertebral column.

Answer 2

Comment 2

Location and clinicopathological correlation is important in framing the diagnosis

Answer 3

Comment 3

Immature teratoma contains primitive mesenchyme whereas Teratoma (Mature) showed mature elements.

Answer 4

Comment 4

Colloid cyst is classically located in the third ventricle. Other possible diagnoses include epidermoid/dermoid cysts, craniopharyngioma.

Answer 5

Comment 5

Primary CNS Lymphoma in this location should be confidently differentiated from pituitary adenoma (polygonal cells with spheroidal nuclei, binucleation) and germinomas (biphasic population of cells – large cells with vesicular nuclei and mature lymphocytes)

Reasoning and Comments (in bullet points please)

References (Essential Book, medical publication etc)

Is the lesion intrasellar, suprasellar orf both? Are the symptoms neurological or related to endocrine dysfunction? Is there a cystic component or is it a solid mass? If it is a cyst, what type of lining does it show?

( Notes ) Focus e.g. J – Clinical Investigation

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Pituitary adenoma

Adamantinomatous Craniopharyngioma

Lymphoma

Germinoma

Rathke’s cleft cyst

Meningioma

Pilocytic astrocytoma

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Granuloma

Granular cell tumour

Immature Teratoma

Teratoma

Chordoma

Chondroma

Papillary Ependymoma

Option 0

Option P

Option Q

Option R

Option S

Option T

Hypothalamic Hamartoma

Ganglioglioma

Papillary craniopharyngioma

Central Neurocytoma

Neuroblastoma

Colloid cyst

Question 1

Note 1

Question 2

Note 2

Question 3

Note 3

Question 4

Note 4

Question 5

Note 5

45 year old male presenting with headaches. CT/MRI showed an intrasellar enhancing lesion. The working diagnosis was pituitary adenoma. Intraoperative smear shows a monolayer of monotonous cells.

EMQ 3 You have undertaken a post-mortem examination on a patient that died with a previous history of ‘dementia’. The cause of death is bronchopneumonia. For each of the following case scenarios please choose the most appropriate diagnosis.

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Alzheimer’s Disease

Diffuse Lewy body Disease

Cerebrovascular disease

Pick’s Disease

Creutzfeldt-Jakob Disease

Motor Neurone Disease

Cortico-basal Degeneration

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Huntington’s Disease

Progressive Supranuclear Palsy

Dementia pugilistica

Wernicke’s encephalopathy

Multiple system atrophy

Parkinson’s Disease

Question 1

Note 1

64 year old male with previous history of parkinsonism and dementia. Post-mortem examination showed pallor of substantia nigra and atrophy of cerebrum. Histology showed Lewy bodies in substantia nigra, subiculum, cingulate gyrus and insular cortices. No neurofibrillary tangles bodies were found. Question 2

Note 2

46 year old female with history of gaze paralysis, nystagmus and ataxia associated with confusion. She had recently been diagnosis with breast cancer, was not eating properly and was somewhat lethargic. At postmortem, brain showed focal haemorrhage in the wall of the third ventricle. Histology showed asymmetrical necrosis of the mammillary bodies associated with numerous newly-formed capillary size blood vessels. Similar changes were identified in the periaqueductal grey matter. Question 3

Note 3

60 year old male with rapid onset of a dementing illness of less than 1 year progression. At post-mortem the brain showed atrophy of the caudate nuclei bilaterally. Histology shows neuronal loss and gliosis in the striatum. No plaques or tangles are seen. Question 4

Note 4

58 year old female with history of progressive asymmetrical parkinsonism who became confused, irritable and forgetful over the last 3 years before death. No diagnosis was ever established. At post-mortem the brain appeared somewhat small with severe atherosclerosis and état lacunare and état criblé. Histology of the brainstem showed no inclusions in the substantia nigra or cortex. Lacunes were quite prominent in the globus pallidus with abundant calcification. Question 5 50 year old male with spatial disortientation, personality changes and impairment of intellect. Brain showed weight of 990 gm, knife-like atrophy of temporal gyri, hydrocephalus ex-vacuo, atrohy of basal ganglia. Histology showed rounded nuclear inclusions in the dentate gyrus of the hippocampus reacting with tau antibodies. No Lewy bodies or senile plaques in neocortex.

Note 5

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Alzheimer’s Disease

Diffuse Lewy body Disease

Cerebrovascular disease

Pick’s Disease

Creutzfeldt-Jakob Disease

Motor Neurone Disease

Cortico-basal Degeneration

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Huntington’s Disease

Progressive Supranuclear Palsy

Dementia pugilistica

Wernicke’s encephalopathy

Multiple system atrophy

Parkinson’s Disease

Question 1

Note 1

The main differential diagnosis is Parkinson disease –vs- Lewy body disease

Question 2

Note 2

Necrosis of mammillary bodies with newly-formed blood vessels

Question 3

Note 3

Caudate nuclei arophy

Question 4

Note 4

No inclusions, severe microinfarcts

Question 5

Note 5

50 year old male with spatial disortientation, personality changes and impairment of intellect. Brain showed weight of 990 gm, knife-like atrophy of temporal gyri, hydrocephalus ex-vacuo, atrohy of basal ganglia. Histology showed rounded nuclear inclusions in the dentate gyrus of the hippocampus reacting with tau antibodies. No Lewy bodies or senile plaques in neocortex.

Taupathy?

Answer 1

Comment 1

Lewy bodies in the Substantia Nigra, insula, cingulate gyrus and subiculum are quite characteristic of Diffuse Lewy Body Disease, which may give rise to a subcortical dementia. This is part of the Synucleinopathies.

Answer 2

Comment 2

The involvement of the mammillary bodies is quite characteristic of Wernicke’s Encephalopathy.

Answer 3

Comment 3

The caudate nuclei is part of the stratum, which include the putamen. There is neuronal loss and gliosis in these locations in Huntington’s disease.

Answer 4

Comment 4

Neuronal loss due to ischaemia secondary to vascular disease may give rise to both dementia (cortical or subcortical neuronal loss) and parkinsonism due to loss of pigmented cells in the substantia nigra.

Answer 5

Comment 5

Pick’s disease is one of the taupathies, which classically shows fronto-temp;oral atrophy with hydrocephalus ex-vacuo and clinically may be indistinguishable from Alzheimer’s Disease.

Reasoning and Comments (in bullet points please)

References (Essential Book, medical publication etc)

Brain weight: <1000 gm is indicative of atrophy What are the histological hallmarks: senile plaques, neurofibrillary tangles, spongiform change, neuronal inclusions (Lewi bodies, ubiquitin inclusions, alpha synuclein) What is the distribution of the neuronal inclusions: basal structures, neocortex or both?

( Notes ) Focus e.g. J – Clinical Investigation

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Alzheimer’s Disease

Diffuse Lewy body Disease

Cerebrovascular disease

Pick’s Disease

Creutzfeldt-Jakob Disease

Motor Neurone Disease

Cortico-basal Degeneration

Option H

Option I

Option J

Option K

Option L

Option M

Option N

Huntington’s Disease

Progressive Supranuclear Palsy

Dementia pugilistica

Wernicke’s encephalopathy

Multiple system atrophy

Parkinson’s Disease

Question 1

Note 1

Question 2

Note 2

Question 3

Note 3

Question 4

Note 4

Question 5

Note 5

EMQ 4 The following are a series of case scenarios associated with the development of CNS infections. Please indicate what is the most likely aetiological agent.

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Herpes simplex encephalitis

Meningogoccal Meningitis

Tuberculous Meningitis

Viral Meningitis

Crytococcus Meningitis

Fungal abscess

Bacterial abscess

Option H

Option I

Option J

Option K

Option L

Option M

Option N

HIV encephalitis

Progressive Multifocal Leukoencephalopathy

Toxoplasmsis

Cerebral Amoebiasis

Cerebral malaria

Cytomegalovir us

Congenital rubella

Option 0

Option P

Option Q

Option R

Option S

Option T

Subacute Sclerosing Panencephilitis

Acute Disseminated Encephalomyelitis

Haemorrhagic Leukoencephalopathy

E. coli Meningitis

Pneumococcus Meningitis

VaricellaZoster

Question 1

Note 1

35 year old female IV drug user diagnosed with HIV infection. Developed sudden onset of headache, fever followed by seizure. MRI showed multiple cotton-wool enhancing lesions in the deep white matter of the centrum semiovale. Question 2

Note 2

8 year old boy recently vaccinated against influenza who developed fever, headaches and seizures. Biopsy showed multiple coalescing perivenular demyelinating lesions at the junction of the cortex and subcortical white matter. Question 3

Note 3

13 year old female with chronic otitis media, developed fever, headache, seizures and coma. MRI showed a ring enhancing temporal lobe lesion with a cystic component. Histology of the edge of the lesion showed numerous neutrophils and reactive gliosis with newly-formed blood vessels. Question 4

Note 4

30 year old male who presented with photophobia, headache and vomiting. CSF samples showed increased cellularity with numerous neutrophils, raised protein and low glucose. Question 5 5 year old boy died in a road traffic accident. At post-mortem, he showed microcephaly and intracranial calcifications. He had a previous medical history of severe mental retardation, seizures and deafness. Mother suffered viral infection during the first trimester of pregnancy.

Note 5

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Herpes simplex encephalitis

Meningogoccal Meningitis

Tuberculous Meningitis

Viral Meningitis

Crytococcus Meningitis

Fungal abscess

Bacterial abscess

Option H

Option I

Option J

Option K

Option L

Option M

Option N

HIV encephalitis

Progressive Multifocal Leukoencephalopathy

Toxoplasmsis

Cerebral Amoebiasis

Cerebral malaria

Cytomegalovir us

Congenital rubella

Option 0

Option P

Option Q

Option R

Option S

Option T

Subacute Sclerosing Panencephilitis

Acute Disseminated Encephalomyelitis

Haemorrhagic Leukoencephalopathy

E. coli Meningitis

Pneumococcus Meningitis

VaricellaZoster

Question 1

Note 1

Patient is immunosuppressed and therefore, at risk of infection.

Question 2

Note 2

Post-vaccination

Question 3

Note 3

Changes consistent with acute inflammatory process.

Question 4

Note 4

30 year old male who presented with photophobia, headache and vomiting. CSF samples showed increased cellularity with numerous neutrophils, raised protein and low glucose.

Increased cellularity with neutrophilia

Question 5

Note 5

5 year old boy died in a road traffic accident. At post-mortem, he showed microcephaly and intracranial calcifications. He had a previous medical history of severe mental retardation, seizures and deafness. Mother suffered viral infection during the first trimester of pregnancy.

Differential diagnosis of Microcephaly

Answer 1

Comment 1

Toxoplasmosis is the most common parasitic infection seen patients with acquired immunodeficiency syndrome.

Answer 2

Comment 2

ADEM usually follows an upper respiratory infection or vaccination and is an immune mediated demyelination sometimes accompanied by necrosis.

Answer 3

Comment 3

Chronic ear infections is one of the risk factors associated with the development of Cerebral Abscess.

Answer 4

Comment 4

CSF hypercellularity with neutrophilia and low glucose is diagnostic of bacterial meningitis.

Answer 5

Comment 5

The highest risk of fetal malformation occurs with materal rubella infection in the first trimester of pregnancy. The differential diagnosis should include CMV, Toxoplasmosis, herpes simplex.

Reasoning and Comments (in bullet points please)

References (Essential Book, medical publication etc)

Identify age and risk factors to make a list of potential agents. Assess the range and location of the lesions as specific agents exhibit characteristic locations. Look for histological hallmarks of infection

( Notes ) Focus e.g. J – Clinical Investigation

Option A

Option B

Option C

Option D

Option E

Option F

Option G

Herpes simplex encephalitis

Meningogoccal Meningitis

Tuberculous Meningitis

Viral Meningitis

Crytococcus Meningitis

Fungal abscess

Bacterial abscess

Option H

Option I

Option J

Option K

Option L

Option M

Option N

HIV encephalitis

Progressive Multifocal Leukoencephalopathy

Toxoplasmsis

Cerebral Amoebiasis

Cerebral malaria

Cytomegalovir us

Congenital rubella

Option 0

Option P

Option Q

Option R

Option S

Option T

Subacute Sclerosing Panencephilitis

Acute Disseminated Encephalomyelitis

Haemorrhagic Leukoencephalopathy

E. coli Meningitis

Pneumococcus Meningitis

VaricellaZoster

Question 1

Note 1

Question 2

Note 2

Question 3

Note 3

Question 4

Note 4

30 year old male who presented with photophobia, headache and vomiting. CSF samples showed increased cellularity with numerous neutrophils, raised protein and low glucose.

Question 5

Note 5

ANY QUESTIONS?