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©The Author(s) 2022.
World J Gastroenterol. Oct 28, 2022; 28(40): 5827-5844
Published online Oct 28, 2022. doi: 10.3748/wjg.v28.i40.5827
Published online Oct 28, 2022. doi: 10.3748/wjg.v28.i40.5827
Table 1 Immunohistochemical profile from the differential diagnosis
Table 2 Summary of pertinent differential diagnostic features
Differential diagnoses | Age/sex | Imaging/gross findings | Histology | Prognosis |
ACC | Predominant in males; mean age of 62 yr | Solid, well-circumscribed, bulky tumors; hemorrhage and necrosis are also frequent | Predominant acinar or solid architecture; uniform cells; basally located nuclei; eosinophilic granular cytoplasm; prominent single nucleoli. minimal stroma | Overall aggressive, with high rates of recurrence and metastasis |
PDAC | Slightly higher in males; 6th-8th decade of life | Solid, poorly defined mass | Large, medium, or small malignant ducts with a tubular pattern; desmoplastic stroma. Processes of mitosis and necrosis | Poor survival rates |
PanNET | Even distribution between the genders; more prevalent in adults; mean age of 40 | Solid, well-circumscribed. 5% are cystic | Variable architectural patterns; uniform cells; oval or spherical nuclei; granular cytoplasm; undetected nucleoli; minimal stroma | Relatively languid, but with variable results |
SPN | Almost exclusively female; average age of 28 | Well-defined and encased with cystic degeneration | Pseudopapillae; cells with hyaline/myxoid stroma surrounding vessels; large cytoplasmic hyaline globules; nuclear groove | Overall low malignant potential: The majority are successfully treated surgically |
PBL | First decade of life, mean age of 4; adults can be affected | Partially encapsulated, frequently lobulated, and substantial | Solid and acinar structure; cellular stroma; keratinization of squamoid nests; heterologous mesenchymal elements | Aggressive; better outcomes for children |
Table 3 American Joint Committee on Cancer 8th Edition cancer staging for exocrine pancreatic tumor such as pancreatic acinar cell carcinoma
Stage | TNM | Description |
0 | Tis | Carcinoma in situ1 |
N0 | No regional lymph node metastases | |
M0 | No distant metastasis | |
IA | T1 | T1 = Tumor is ≤ 2 cm in any direction |
T1a = Tumor is ≤ 0.5 cm in any direction | ||
T1b = Tumor is > 0.5 cm and < 1 cm in any direction | ||
T1c = Tumor is 1–2 cm in any direction | ||
N0 | No regional lymph node metastases | |
M0 | No distant metastasis | |
IB | T2 | Tumor is > 2 cm and ≤ 4 cm in any direction |
N0 | No regional lymph node metastases | |
M0 | No distant metastasis | |
IIA | T3 | Tumor is > 4 cm in any direction |
N0 | No regional lymph node metastases | |
M0 | No distant metastasis | |
IIB | T1 | T1 = Tumor is ≤ 2 cm in any direction |
T1a = Tumor is ≤ 0.5 cm in any direction | ||
T1b = Tumor is > 0.5 cm and < 1 cm in any direction | ||
T1c = Tumor is 1–2 cm in any direction | ||
N1 | Metastasis in one to three regional lymph nodes | |
M0 | No distant metastasis | |
T2 | Tumor is > 2 cm and ≤ 4 cm in any direction | |
N1 | Metastasis in one to three regional lymph nodes | |
M0 | No distant metastasis | |
T3 | Tumor is > 4 cm in any direction | |
N1 | Metastasis in one to three regional lymph nodes | |
M0 | No distant metastasis | |
III | T1 | T1 = Tumor is ≤ 2 cm in any direction |
T1a = Tumor is ≤ 0.5 cm in any direction | ||
T1b = Tumor is > 0.5 cm and < 1 cm in any direction | ||
T1c = Tumor is 1–2 cm in any direction | ||
N2 | Metastasis in four or more regional lymph nodes | |
M0 | No distant metastasis | |
T2 | Tumor is > 2 cm and ≤ 4 cm in any direction | |
N2 | Metastasis in four or more regional lymph nodes | |
M0 | No distant metastasis | |
T3 | Tumor is > 4 cm in any direction | |
N2 | Metastasis in four or more regional lymph nodes | |
M0 | No distant metastasis | |
T4 | Regardless of tumor size, the cancer has grown outside the pancreas, into the nearby large blood vessels2 | |
Any N | NX = Regional lymph nodes cannot be assessed | |
N0 = No regional lymph node metastases | ||
N1 = Metastasis in one to three regional lymph nodes | ||
N2 = Metastasis in four or more regional lymph nodes | ||
M0 | No distant metastasis | |
IV | Any T | TX = Primary tumor cannot be assessed |
T0 = No evidence of primary tumor | ||
Tis = Carcinoma in situ1 | ||
T1 = Tumor is ≤ 2 cm in any direction | ||
T1a = Tumor is ≤ 0.5 cm in any direction | ||
T1b = Tumor is > 0.5 cm and < 1 cm in any direction | ||
T1c = Tumor is 1–2 cm in any direction | ||
T2 = Tumor is > 2 cm and ≤ 4 cm in any direction | ||
T3 = Tumor is > 4 cm in any direction | ||
T4 = Regardless of tumor size, the cancer has grown outside the pancreas, into the nearby large blood vessels2 | ||
Any N | NX = Regional lymph nodes cannot be assessed | |
N0 = No regional lymph node metastases | ||
N1 = Metastasis in one to three regional lymph nodes | ||
N2 = Metastasis in four or more regional lymph nodes | ||
M1 | Distant metastasis |
Table 4 Acinar cell carcinoma treatment options
Table 5 Characteristics of studies on various acinar cell carcinoma treatment regimes
Ref. | Year of publication | ACC sample size | Type of treatment | No. of patients | Conclusion |
Holen et al[8] | 2002 | 39 | Resection | 9 | A high recurrence rate following complete surgical resection suggests that micrometastases are present even in localized disease, and that adjuvant therapies may be indicated. Chemotherapy and radiation are ineffective, however, and novel treatments are required |
RT alone | 22 | ||||
Fluoropyrimidine-based chemotherapy and RT | 1 | ||||
Fluoropyrimidine-based chemotherapy | 7 | ||||
Kitagami et al[65] | 2007 | 115 | Resection | 88 | To improve prognosis, surgical resection should be pursued if possible. If ACC cannot be resected or recurs, chemotherapy is likely to be beneficial. A multidisciplinary treatment centered on the role of surgery must be developed |
Palliative operation | 12 | ||||
Exploratory laparotomy | 4 | ||||
Other treatment1 | 11 | ||||
Seth et al[11] | 2008 | 14 | Resection | 10 | When feasible, surgical resection is the optimal first-line treatment for resectable ACC due to its superior survival, which can be further improved by the addition of a planned neoadjuvant and/or adjuvant chemoradiation regimen |
Resection, mixed chemotherapy2 and RT | 4 | ||||
Wisnoski et al[64] | 2008 | 672 | Resection | 266 | ACC surgical resection appears to improve survival, and the findings support an aggressive strategy for resectable disease. In order to define the role of chemoradiation in the palliative, adjuvant, and neoadjuvant settings, additional research is required |
Other treatment1 | 406 | ||||
Schmidt et al[5] | 2008 | 865 | Resection | 190 | In these favorable pancreatic cancers, aggressive surgical resection with negative margins is associated with long-term survival. Second, cancer registries lack certain information, such as the specific type of chemotherapy administered and radiation therapy details. Consequently, institutional and multi-institutional reports of ACC continue to be essential for performing a more comprehensive analysis of the presentation, pathology, natural history, and treatment-related outcomes of ACC |
Resection and chemotherapy | 33 | ||||
Resection and RT | 10 | ||||
Resection and chemoradiation | 100 | ||||
Other treatment1 | 532 | ||||
Matos et al[75] | 2009 | 17 | Resection | 12 | ACC requires aggressive surgical resection. Importantly, some patients with locally advanced ACC have responded to a neoadjuvant approach allowing resection of a downstaged tumor; therefore, a combined modality approach should be considered for these patients |
Mixed chemotherapy2 | 3 | ||||
Mixed chemotherapy2 and RT | 2 | ||||
Seki et al[76] | 2009 | 4 | Gemcitabine-based chemotherapy | 1 | A partial response suggested that fluoropyrimidine-based chemotherapy may have some activity against this tumor. To confirm the efficacy of fluoropyrimidine in treating pancreatic ACC, prospective clinical trials are required |
Fluoropyrimidine-/gemcitabine-based chemotherapy | 3 | ||||
Lee et al[78] | 2010 | 29 | Resection | 12 | In Korea, the clinical characteristics of ACC include a young age, a large size, a location in the tail, and nonspecific tumour markers. ACC should always be actively treated with surgery, regardless of its size |
Resection, mixed chemotherapy2 and RT | 10 | ||||
Mixed chemotherapy2 and RT | 1 | ||||
Other treatment1 | 6 | ||||
Butturini et al[73] | 2011 | 9 | Resection | 2 | Using multiple chemotherapy regimens and regional treatments sequentially for recurrent disease allowed for 45-, 85-, and 52-mo post-primary survival. Long-term survival and clinical benefit may be possible with repeated surgery, neoadjuvant and adjuvant chemoradiation therapies, and locoregional therapy |
Resection and gemcitabine-based chemotherapy | 7 | ||||
Hartwig et al[79] | 2011 | 17 | Resection | 13 | ACC of the pancreas is a relatively uncommon tumor entity for which resection may lead to long-term survival, even in the presence of limited metastatic disease. Optimized adjuvant treatment protocols are required to improve the long-term survival of ACC patients |
Resection and gemcitabine-based chemotherapy | 4 | ||||
Lowery et al[77] | 2011 | 20 | Gemcitabine-based chemotherapy | 20 | Observed efficacy of combination chemotherapy in metastatic patients. ACC supports the use of combination therapies based on gemcitabine or 5-fluorouracil and incorporating irinotecan, a platinum analog, or docetaxel in patients with advanced disease. A potential association between germline mutations in DNA mismatch repair genes and ACC warrants further evaluation |
Zheng et al[80] | 2015 | 15 | Resection | 12 | Clinicians generally regard pancreatic acinar cell carcinoma as a low-grade malignancy due to its unique clinical features. Positive sentiments towards ACC should be held |
Resection and gemcitabine-based chemotherapy | 3 | ||||
Kruger et al[81] | 2016 | 15 | Resection | 3 | In contrast to PDAC, gemcitabine alone does not appear to have significant activity in ACC. Based on the findings, advanced ACC should be treated with chemotherapy regimens containing 5-FU and/or a platinum compound (such as oxaliplatin). Undetermined is whether this observation also applies to adjuvant chemotherapy administered after surgical resection of ACC |
Resection and gemcitabine-based chemotherapy | 8 | ||||
Chemoradiation | 1 | ||||
Mixed chemotherapy2 | 3 | ||||
Seo et al[82] | 2017 | 20 | Resection | 9 | Compared to PDAC, patients with resectable pancreatic ACC had a favorable prognosis after curative resection. Although adjuvant chemotherapy was not associated with improved survival in this study, it is unknown whether this was due to a selection bias or the ineffectiveness of 5-FU monotherapy in pancreatic ACC. On the basis of molecular analysis utilizing innovative genetic analytic tools, additional research on effective adjuvant chemotherapy is required |
Resection and 5-fluorouracil-based chemotherapy | 9 | ||||
Resection and gemcitabine-based chemotherapy | 1 | ||||
Resection and etoposide plus cisplatin-based chemotherapy | 1 | ||||
Pishvaian et al[83] | 2020 | 12 | Mixed chemotherapy2 | 12 | Molecularly guided treatments targeting oncogenic drivers and the DNA damage response and repair pathway require further prospective evaluation, based on these real-world findings |
Zong et al[84] | 2020 | 11 | Resection | 4 | For pancreatic acinar cell carcinoma, surgery is a potentially curative treatment contributing to long-term survival. It has been confirmed that adjuvant systemic therapy, including chemotherapy and chemoradiotherapy, significantly improves survival compared to surgery alone for resectable ACC. To investigate the role and protocol of perioperative and palliative treatments, additional research with a large sample size is required |
Resection and gemcitabine-based chemotherapy | 4 | ||||
Resection and capecitabine | 1 | ||||
Resection and mixed chemotherapy2 | 2 | ||||
Xu et al[85] | 2022 | 22 | Resection | 6 | Although the value of adjuvant chemotherapy remains obscure, fluoropyrimidine-based chemotherapy merits consideration. Fluorouracil-based chemotherapy, such as FOLFIRINOX, may be the preferred treatment for patients with metastasis, but additional research is required due to the small sample size in this study |
Resection and S1- based chemotherapy | 3 | ||||
Resection and SOX- based chemotherapy | 2 | ||||
Resection and fluoropyrimidine-based chemotherapy | 3 | ||||
Resection and AG- based chemotherapy | 1 | ||||
Resection and gemcitabine-based chemotherapy | 7 | ||||
Chen et al[86] | 2022 | 26 | Resection | 11 | After radical resection, patients with ACC had a longer overall survival than those with PDAC. ACC is also an aggressive tumor with a similar recurrence-free survival trend to PDAC, necessitating multidisciplinary treatment for resectable ACC disease |
Resection and adjuvant chemotherapy | 15 |
- Citation: Calimano-Ramirez LF, Daoud T, Gopireddy DR, Morani AC, Waters R, Gumus K, Klekers AR, Bhosale PR, Virarkar MK. Pancreatic acinar cell carcinoma: A comprehensive review. World J Gastroenterol 2022; 28(40): 5827-5844
- URL: https://www.wjgnet.com/1007-9327/full/v28/i40/5827.htm
- DOI: https://dx.doi.org/10.3748/wjg.v28.i40.5827