Case Series: Pancreatic Acinar Cell Carcinoma

Pancreatic acinar cell carcinoma (ACC), a very rare exocrine tumor of the pancreas, is thought to have a more favorable prognosis than pancreatic ductal adenocarcinoma (PDAC). However, the majority of knowledge comes from small institutional series.

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Vishwajith Sridharan, MD, MBA, a medical resident with the Department of Medicine at Massachusetts General Hospital, Yasmin G. Hernandez-Barco, MD, a medical pancreatologist in the Division of Gastroenterology at Mass General, and colleagues present in Pancreatology an in-depth analysis of one of the largest cohorts of patients with ACC compiled in the modern era. It confirms the aggressive nature of the disease but shows that treatment can improve survival in both localized and metastatic settings.

Study Cohort

The researchers identified 66 patients with biopsy-confirmed ACC treated at Mass General Brigham between January 1996 and August 2019. The median age at diagnosis was 64 (range, 38–91). The stage at the time of diagnosis was:

• I—4 patients (6%)
• II—29 (44%)
• III—5 (8%)
• IV—28 (42%); the most common metastatic site was the liver (47%)

Genetic Testing

Six patients had genetic sequencing as a part of their care. Two showed abnormalities in the DNA repair gene BRAC2. Other genetic anomalies seen more than once were alterations in TP53 and mismatch repair genes.

Survival

Over the median follow-up period of 24.7 months, median overall survival (OS) from the time of diagnosis was:

• Entire cohort—24.7 months
• Localized disease at diagnosis—38 months
• Metastatic disease at diagnosis—15 months (P=0.002 vs. localized)

Survival was not influenced by sex, age, primary tumor size or primary tumor site.

Survival by treatment modality was reported as follows:

Localized disease

• Tumor resection—median OS 41.6 months vs. 7.2 months without resection (P=0.006)
• Adjuvant chemotherapy—no survival benefit; the variability in regimens over time and the small number of patients may have affected the ability to detect a benefit

Metastatic disease

• Surgery for tumor debulking—no survival benefit
• Adjuvant chemotherapy—median OS 22 months vs. 1.5 months without (P<0.0001)

These results cannot be considered definitive given the observational nature of the study, the rarity of ACC and the small sample size.

16 of the 38 patients (42%) who presented with localized disease and underwent surgery ultimately developed metastases.

Pre- and Post-2010 Comparison

In 2011, FOLFIRINOX was shown to provide a survival advantage over gemcitabine in patients with metastatic PDAC, which changed the management of that disease. The researchers, therefore, compared patients with metastatic ACC in this series who were treated before 2010 (n=9) or after 2010 (n=18):

• Regimens—After 2010, more patients were treated with platinum-based agents (FOLFOX, FOLFIRINOX) and fewer with gemcitabine-based regimens as first-line therapy (P=0.002)
• OS was better with FOLFOX- or FOLFIRINOX-based regimens than with or gemcitabine- or capecitabine-based regimens (P=0.005)

Clinical Pearls

The results of this study have contributed the following information to the collective knowledge surrounding ACC. Some findings include:

• Genetic analysis of ACC samples may prove valuable in identifying mutations that can help guide screening and treatment decisions. Detection of these mutations in ACC patients should prompt screening of germline mutations in family members, as is now the norm in PDAC
• Tumor resection may cure a majority of patients with localized ACC, but a subset probably already has micrometastatic deposits
• For patients with metastatic ACC, there is a clear benefit to adjuvant chemotherapy; first-line FOLFOX- or FOLFIRINOX-based regimens were linked to improved OS compared with capecitabine- and gemcitabine-based regimens, but prospective, randomized studies are needed for confirmation
• Close to half of the patients in this series who had distant metastases harbored liver disease, so there may be a place for resection of liver metastases after curative resection of ACC, as is being discussed for PDAC

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