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Acinar Cell Carcinoma of the Pancreas
Acinar cell carcinoma of the pancreas, also acinar cell carcinoma, is a rare malignant exocrine tumor of the pancreas. It represents 5% of all exocrine tumors of the pancreas, making it the second most common type of pancreatic cancer. It is abbreviated ACC. Acinar cell carcinoma of the pancreas is a rare neoplasm, comprising 1-2 % of exocrine pancreatic tumors (Solcia 7). The tumor most commonly occurs in middle-aged or elderly Caucasian men.
Patients may present with vague abdominal pain, or the mass may be found incidentally. Patients (up to 15%) can also present with widespread subcutaneous fat necrosis, polyarthritis, and eosinophilia (Schmidt’s triad) due to increased circulating lipase secreted by the tumor (Solcia, Ashley and Lauwers 22). Acinar cell carcinomas can involve the head or tail of the pancreas. They are usually well circumscribed, partly encapsulated, pink to tan, homogeneous fleshy mass, averaging 11 cm in greatest diameter, occasionally demonstrating extensive hemorrhage and necrosis (Klimstra DS 92). Microscopically, most tumors are highly cellular with minimal stroma and lack the stromal desmoplasia commonly seen with ductal adenocarcinomas. Four patterns of growth have been described (Klimstra DS.)
The disease is more common in men than women are and the average age at diagnosis is about 60. Symptoms are often non- specific and include weight loss. A classic presentation, found in around 15% of cases includes subcutaneous nodules (due to fat necrosis) and arthralgias, caused by release of lipase. The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying Acinar content.
The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of Acinar and non-Acinar tissue in 21 sections at various stages of pancreatic injury and recovery termed the “ground truth”. After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high- resolution images in order to validate the process. For baseline, non- injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline Acinar tissue area with only a difference of 1%±0.05% (p = 0.21
The Acinar pattern is present in most tumors, often admixed with trabecular and glandular patterns; the solid pattern is also often seen. The tumor cells resemble normal pancreatic acinar cells. The nuclei are round to oval, with only mild pleomorphism and single prominent nucleoli. The cytoplasm tends to be abundant, eosinophilic, and granular due to zymogen granules, which are PAS-positive and diastase-resistant, but in the solid tumors, PAS positivity may be scant. Mitotic activity is variable, form rare mitoses to >50 per 10 HPF. In the present case, the differential diagnosis, based on morphology, included an acinar cell carcinoma and a pancreatic endocrine tumor because the pattern of growth was mostly solid with rare areas of acinar type structures. However, the lack of classic “salt and pepper” chromatin distribution and the presence of prominent single nucleoli are unusual for endocrine neoplasms.
Since normal pancreatic acinar cells secrete pancreatic enzymes, the most useful histochemical and/or immunohistochemical stains for acinar cell carcinoma are for the pancreatic enzymes, such as trypsin, chymotrypsin, amylase, elastase, and lipase. When the neoplastic cells exhibit nuclear polarity, these stains usually demonstrate positivity in the apical portions of the cells, while the stains are more focal and usually restricted to single cells in tumors with solid patterns. Tumor cells that are positive for synaptophysin and chromogranin A can be found in 30-50% of cases (Notohara 20).
Usually they occur in tumors with a solid pattern, where they are scattered throughout the tissue. Although only a small number of cases with synaptophysin immunohistochemistry have been reported, the diffuse positive staining for synaptophysin in our case appears to be uncommon for Acinar cell carcinoma and is a potential pitfall, thus emphasizing the need to perform the stains to demonstrate positivity for at least one pancreatic enzyme.
Ultra structural studies of Acinar cell carcinomas have demonstrated a resemblance to normal pancreatic Acinar cells with well-developed endoplasmic reticulum and zymogen granules (mean diameter 400-500nm), which are commonly oriented toward the luminal space. An interesting finding in Acinar cell carcinomas is the presence of membrane- bound filamentous inclusions, which are thought to be within the spectrum of zymogen granules (Tucker JA et al., 1994, Chong JM et al., 1996, and Ordonez NG et al., 2000). Similar inclusions have only rarely been identified in endocrine tumors (Ordonez NG et al., 2001), therefore, these inclusions may serve as an ultra-structural marker in the diagnosis of Acinar cell carcinomas.
Acinar cell carcinomas are aggressive tumors and most patients die from their cancer within a mean of 18 months after diagnosis and a 5 year survival of 5.9%; however, the overall survival is better than pancreatic ductal adenocarcinoma (Klimstra 12). Younger patients (less than 60 years old) and patients with tumors less than 10 cm tend to have longer survival than patients over 60 years do or with larger tumors. Patients who present with symptoms of elevated lipase do much worse.
Resection is the treatment of choice, with or without chemo radiation therapy, and metastases may be present at the time of diagnosis. In summary, we presented a case of pancreatic acinar cell carcinoma with an almost exclusively solid growth pattern. While the tumor showed, some immunophenotypic evidence of endocrine cell differentiation, clinical, histologic, and electron microscopic features, along with the positive immunostaining for trypsin, was all consistent with acinar cell carcinoma.
In conclusion, although the most common cells in the pancreas are the acinar cells, malignant transformation of these cells is very rare. Pancreatic adenocarcinomas, derived from epithelial cells lining the pancreatic ducts are the most common pancreatic malignancy followed by neuroendocrine tumors; with Acinar cell carcinomas (ACC) of the pancreas representing less than 1% of all pancreatic tumors. Patients with ACC are more likely to present at a younger age and with earlier stage tumors as compared to patients with the more common and deadlier pancreatic adenocarcinomas. ACC affects males more commonly than females.
There are also significant differences in the clinical presentation of ACC as compared to pancreatic adenocarcinoma. Contrary to pancreatic adenocarcinoma cases, patients with early stage ACC frequently present with abdominal pain and bloating as the dominant symptoms. Occasionally, ACC tumors produce excessive lipase causing systemic fat necrosis 9 -16. Clinical manifestations of this syndrome of fat necrosis can include panniculitis, discrete skin lesions and subcutaneous nodules. Pathologic fractures related to intraosseus necrosis have been described as well. Laboratory abnormalities include elevated serum lipase levels, eosinophilia, and occasionally elevated serum alpha-fetoprotein levels.
Because of the rarity of this malignancy, studies have primarily consisted of retrospective chart reviews and case reports. Very limited data are available about effective systemic treatments for patients with recurrent, unresectable or metastatic disease. The rarity of the disease has thus far precluded systematic approach to treatment through clinical trials, and only a handful of retrospective reviews and case reports describing empiric treatments have been published.
Works cited
Ashley SW, Lauwers GY. Case Records of The Massachusetts General Hospital. Weekly Clinic Pathological Exercises. Case 37-2002. A 69-Year-Old Man with Painful Cutaneous Nodules, Elevated Lipase Levels, And Abnormal Results On Abdominal Scanning. N Engl J Med. 2002 Nov 28; 347(22): 1783-91.
Chong JM, Fukayama M, Shiozawa Y, Hayashi Y, Funata N, Takizawa T, Koike M. Fibrillary Inclusions In Neoplastic And Fetal Acinar Cells Of The Pancreas. Virchows Arch. 1996 Jul; 428(4-5): 261-6.
Hoorens A, Lemoine NR, Mclellan E, Morohoshi T, Kamisawa T, Heitz PU, Stamm B, Ruschoff J, Wiedenmann B, Kloppel G. Pancreatic Acinar Cell Carcinoma. An Analysis Of Cell Lineage Markers, P53 Expression, And Ki-Ras Mutation. Am J Pathol. 1993 Sep; 143(3): 685-98.
Eisses JF, Davis AW, Tosun AB, Dionise ZR, Chen C, Et Al.(2014) A Computer-Based Automated Algorithm For Assessing Acinar Cell Loss After Experimental Pancreatitis. Plos ONE 9(10)
