Case 9: Acinic Cell Carcinoma

Key features: Typically a triphasic (or more) neoplasm, though one pattern and cell type often predominates

• Patterns: solid/lobular⬇️, microcystic, papillary, cystic⬇️, follicular
• Cell types: serous acinar, intercalated duct cells, vacuolated cells, clear cells
• Typical low to intermediate grade

Clinical considerations:

• Generally has a good prognosis w 5yr survival rate = 90%
• Complete surgical excision is treatment of choice
• Local recurrence in about 35% of cases

High grade transformation ⬇️ can occur and warrants more aggressive treatment

Immunohistochemistry for acinic cell carcinoma:

🐶 DOG1 shows delicate membranous staining

📌 NR4A3 highly specific, strong nuclear staining - though not (yet) widely-used

🍬 PAS+ granules sometimes seen (often patchy)

https://pubmed.ncbi.nlm.nih.gov/31094928/

https://www.nature.com/articles/s41467-018-08069-x

Now for some #MolecularPath

(wouldn’t be one of my cases otherwise 😝)

t(4;9) is present in 80% of cases, which translocates the enhancer of SCCP gene to upstream of NR4A3 gene

✨ Overexpression of NR4A3 is the most common oncogenic driver of acinic cell carcinoma ✨

NR4A3 is interesting 🤔 because its activity is tissue-specific (sometimes it’s a tumor suppressor, sometimes an oncogene)

One theory is that NR4A3 interacts with a variety of cofactors in target tissues to exert these varied effects

Recent studies ⬇️ have identified MYB gene as one of these co-factors (particularly in HG acinic cell)

Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma - PubMed

The combination of NR4A3 and MYB showed cooperativity in regulating a distinct set of genes, as shown in this heatmap from the Lee et al paper (🔴 indicates ⬆️regulation and 🔵 indicates ⬇️regulation)

The combination of NR4A3 plus MYB shows more transcription activation activity than either alone (oncogene cooperativity)

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