1. A 67-year-old male with behavioral and language problems
Leonidas Arvanitis, M.D.
Neuropathology Fellow, PGY-6

2. 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."

3. 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

4. Autopsy An autopsy was performed and showed the following (describe):

5. Autopsy An autopsy was performed and showed the following (describe):
Lobar atrophy involving the frontal (mostly) and temporal lobes. “Knife-like” gyri.

6. This is a section from the frontal lobe. What do you see?
Frontal lobe. (Click here for H&E)

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

8. This is a section from the frontal lobe. What do you see?
Eosinophilic cytoplasmic inclusions
Neuronal loss

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

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

11. This is a section from the frontal lobe. What do you see?
Vacuolization of the superficial cortical layer

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

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

14. Question:
In the work up of a neurodegenerative disease what immunohistochemical stains are helpful in highlighting intracellular inclusions?

15. Answer Tau A-synuclein TDP-43 Alzheimer’s disease Pick’s disease
Progressive Supranuclear Palsy
Corticobasal degeneration
A-synuclein
Parkinson’s disease
TDP-43
FTLD-TDP

16. 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

17. Tau stain

18. How are these spherical, intraneuronal inclusions known as?

19. Pick bodies

20. Answer Pick bodies are spherical intraneuronal cytoplasmic inclusions
They are most frequently found in the frontal and temporal lobes and limbic cortex

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

22. Answer
FTLD-Tau: Pick’s disease

23. Question
What are the clinical features of Frontotemporal Lobar Degeneration (FTLD)?

24. Answer The 3 main clinical syndromes are Behavioral variant
Cognitive decline and changes in social and personal conduct
Progressive nonfluent aphasia (PNFA)
Problems in word retrieval but with preservation of comprehension
Semantic dementia
Patients have impairment of the realm of memory that relates to the meaning of verbal and visual inputs

25. Question
What are the pathologic subtypes of FTLD?

26. Anwser
FTLD-Tau
FTLD-TDP
FTLD-FUS
FTLD-UPS
FTLD-ni (no inclusions)