_Rare exocrine pancreatic malignancy with biology and treatment responsiveness distinct from PDAC._ --- ### Essential Takeaway **Acinar cell carcinoma (ACC)** accounts for ~1–2% of pancreatic malignancies. It often presents as a **large, relatively circumscribed mass**, but potentially has a better prognosis than PDAC following resection. The major practical distinction from PDAC is its molecular profile: **HRR/BRCA alterations and kinase fusions are relatively common**, making **germline testing and comprehensive tumor sequencing important**. --- ### Presentation - Usually presents with **abdominal/back pain, weight loss, or an incidental pancreatic mass** - Obstructive jaundice is **less common than in PDAC** - Tumors are often **large at diagnosis** - **Lipase hypersecretion syndrome** occurs in a minority: - Pancreatic panniculitis / subcutaneous fat necrosis - Polyarthritis - ± eosinophilia - Usually reflects advanced disease CA 19-9 is often normal or only modestly elevated. --- ### Diagnosis **Pathology is essential**, as ACC can resemble a pancreatic NET. Typical IHC: - **Trypsin +** - **Chymotrypsin +** - **BCL10 +** - Neuroendocrine markers may be focally positive → do not mistake for PanNET based on synaptophysin alone. Stage using the standard **AJCC pancreatic exocrine carcinoma staging system**. --- ### Treatment #### Localized Disease **Surgical resection is the treatment of choice** when technically and oncologically resectable. - Standard oncologic pancreatectomy based on location - Recurrence remains common despite R0 resection - Nodal disease, particularly heavy nodal burden, is associated with worse prognosis. **Adjuvant therapy:** There is **no established prospective standard**. Retrospective studies have not consistently demonstrated a survival benefit, although systemic therapy is commonly considered for fit patients with high-risk disease. --- #### Locally Advanced / Metastatic Disease ACC appears particularly responsive to **fluoropyrimidine-, platinum-, and irinotecan-containing chemotherapy**. Common approaches: - **FOLFIRINOX / mFOLFIRINOX** - FOLFOX - FOLFIRI Available retrospective data generally favor these approaches over gemcitabine-based therapy. Significant responses may occasionally permit **conversion to resection**. --- ### Molecular Testing — Don't Miss This Obtain **comprehensive tumor NGS and germline testing**, particularly in advanced disease. Important alterations include: - **BRCA1/2, PALB2 and other HRR alterations** - Consider platinum sensitivity - PARP inhibition may have a role in selected patients - **BRAF / RAF1 fusions** — enriched in ACC and potentially targetable - Less commonly: **NTRK, RET, ALK and other kinase fusions** - **MSI-H / dMMR** → immune checkpoint inhibition - Unlike PDAC, **KRAS mutations are uncommon**. > **Pearl:** A pancreatic carcinoma that is KRAS-wild type with unusual morphology should prompt consideration of ACC and assessment for actionable fusions/HRR abnormalities. --- ### Prognosis Generally **better than PDAC**, particularly after complete resection, but recurrence is frequent. Modern surgical series report approximately **55–60% 5-year OS after resection**, with nodal status an important prognostic factor. --- ### References >[!quote]- References >1. Ikezawa K, et al. _Jpn J Clin Oncol._ 2024. Comprehensive review of pancreatic acinar cell carcinoma. >2. Woo KP, et al. _J Surg Oncol._ 2024. The role of chemotherapy in pancreatic acinar cell carcinoma. >3. Survival Outcomes and Genetic Characteristics of Resected Pancreatic Acinar Cell Carcinoma. 2024.