A 67-year-old male with behavioral and language problems

Leonidas Arvanitis, M.D.

Neuropathology Fellow, PGY-6

History• The patient was a 67-year-old male with a long

standing history of progressive difficulty with language and thinking.

• His wife stated that his overall problems began approximately 17 years ago during which time he was drinking approximately 2 cases of beer per week.

• Approximately at that time he first started having "trouble placing words in sentences."

History• Further cognitive evaluation revealed marked

problems with language function and suggested that he had primary progressive aphasia.

• An MRI showed extensive temporal and frontal lobe atrophy.

• His MMSE was 20/30. • The patient further declined and eventually died

Autopsy• An autopsy was performed and showed

the following (describe):

http://library.med.utah.edu/WebPath/TUTORIAL/CNS/CNSDG008.html

Autopsy• An autopsy was performed and showed

the following (describe):

http://library.med.utah.edu/WebPath/TUTORIAL/CNS/CNSDG008.html

Lobar atrophy involving the frontal (mostly) and temporal lobes. “Knife-like” gyri.

This is a section from the frontal lobe. What do you see?

Frontal lobe. (Click here for H&E)

This is a section from the frontal lobe. What do you see?

This is a section from the frontal lobe. What do you see?

Eosinophilic cytoplasmic inclusions

Neuronal loss

This is a section from the frontal lobe. What do you see?

Severe gliosis

This is a section from the frontal lobe. What do you see?

This is a section from the frontal lobe. What do you see?

Vacuolization of the superficial cortical layer

This is a section from the frontal lobe. What do you see?

This is a section from the frontal lobe. What do you see?

Balloon cell

Question:

• In the work up of a neurodegenerative disease what immunohistochemical stains are helpful in highlighting intracellular inclusions?

Answer• Tau

– Alzheimer’s disease– Pick’s disease– Progressive Supranuclear Palsy– Corticobasal degeneration

• A-synuclein– Parkinson’s disease

• TDP-43– FTLD-TDP

Question:

• The intracellular inclusions on this case were negative for a-synuclein and TDP-43, but Tau showed the following staining pattern:

– Click here to view Tau stain

Tau stain

How are these spherical, intraneuronal inclusions known as?

Pick bodies

Answer

• Pick bodies are spherical intraneuronal cytoplasmic inclusions

• They are most frequently found in the frontal and temporal lobes and limbic cortex

Question

• What is the most likely diagnosis of a patient with behavioral and language difficulties that showed these associated pathologic features?

Answer

• FTLD-Tau: Pick’s disease

Question

• What are the clinical features of Frontotemporal Lobar Degeneration (FTLD)?

Answer• The 3 main clinical syndromes are

1.Behavioral variant– Cognitive decline and changes in social and

personal conduct

2.Progressive nonfluent aphasia (PNFA)– Problems in word retrieval but with preservation of

comprehension

3.Semantic dementia– Patients have impairment of the realm of memory

that relates to the meaning of verbal and visual inputs

Question

• What are the pathologic subtypes of FTLD?

Anwser

• FTLD-Tau

• FTLD-TDP

• FTLD-FUS

• FTLD-UPS

• FTLD-ni (no inclusions)