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): Lobar atrophy involving the frontal (mostly) and temporal lobes. “Knife-like” gyri. http://library.med.utah.edu/WebPath/TUTORIAL/CNS/CNSDG008.html

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 A-synuclein TDP-43 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 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

Question What are the pathologic subtypes of FTLD?

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