Spectrum of Causes of Pancreatic Calcifications
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1 Pictorial Essay Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved Spectrum of Causes of Pancreatic Calcifications T he discovery of pancreatic calcifications has long been used in the diagnosis of pancreatic disease, and for many years imaging of the pancreas was largely limited to the radiographic identification of these calcifications. Today, our ability to image the pancreas has greatly advanced with modalities including CT, sonography, endoscopic retrograde cholangiopancreatography, and MR imaging. This improved visualization of the pancreas allows better identification of pancreatic calcifications and their underlying cause. Traditionally, pancreatic calcifications have been largely associated with chronic calcific pancreatitis from alcohol abuse. lthough alcohol abuse remains the predominant cause of pancreatic calcifications, many other causes also deserve attention. Knowing what entities cause calcifications and their typical appearance can help in an accurate diagnosis. However, imaging alone cannot be trusted for a definitive diagnosis because many of these entities overlap in their appearance [1]. We report a spectrum of causes and imaging appearances related to calcification of the pancreas. Inflammatory Chronic alcoholic pancreatitis is the most common cause of pancreatic calcifications in the United States. lthough the exact mechanism of chronic alcoholic pancreatitis has not been clearly elucidated, the characteristic pathologic changes are well known. The ducts become obstructed by proteinaceous plugs that can eventually accumulate calcium carbonate. This obstruction results in ductal ectasia and periductal fibrosis. The calculi occur in ducts of all sizes and vary from microscopic to greater than 1 cm in diameter. The radiographic appearance is generally that of numerous irregular small calcifications throughout the pancreas (Fig. 1). The head of the pancreas is usually involved more prominently than the tail. The degree of calcification appears to parallel the course of the disease [2]. lthough these intraductal, calcified concretions generally progress, the stone load occasionally will decrease. Calcifications related to chronic alcoholic pancreatitis may rarely be appreciated when mural calcification develops in a chronic pseudocyst. Chronic pancreatitis caused by hyperparathyroidism, tropical pancreatitis, and idiopathic pancreatitis can also result in intraductal calculi. Notably, other causes of pancreatitis, including gallstones, drugs, trauma, and viruses, do not characteristically cause pancreatic calcifications. Developmental lthough hereditary pancreatitis is rare, it is a well-known cause of pancreatic calcifications in the pediatric population. Hereditary pancreatitis has an autosomal dominant pattern of inheritance with an estimated 80% penetrance [3]. It generally manifests itself during childhood with a peak incidence at 5 years old. However, a second peak at 17 years old may be attributable to the introduction of alcohol in the diet. Intraductal calcifications occur in approximately 50% of patients. These stones have a characteristic large, rounded appearance (Fig. 2). long with hereditary pancreatitis, cystic fibrosis accounts for most of the pancreatic calcifications in children. Cystic fibrosis is an autosomal recessive disease affecting one in 3000 children in the United States. The most common finding on CT is fatty replacement of the pancreas. Intraductal calcifications occur in a minority of patients and are generally limited to patients with advanced pancreatic fibrosis. These fine granular calcifications occur in the smaller pancreatic duct radicals [4] (Fig. 3). Robert J. Lesniak 1, Mark D. Hohenwalter 1, ndrew J. Taylor 2 Neoplasms The most common primary pancreatic tumor, ductal adenocarcinoma, characteristically does not calcify. However, pancreatic carcinoma may develop in a pancreas with underlying chronic calcific pancreatitis (Fig. 4). Or, calcifications may develop in the setting of chronic pancreatitis from an obstructing ductal adenocarcinoma (Fig. 5). number of less common tumors have associated calcifications. Islet cell tumors are known for the presence of tumoral calcifications. Islet cell tumors are classified as functional or nonhyperfunctional. Functional tumors are typically detected early because of their symptoms and thus are frequently less than 2 cm in diameter. Nonhyperfunctioning tumors tend to be larger at the time of diagnosis, measuring over 8 cm in diameter [5]. direct correlation exists between islet cell tumor size and the increasing likelihood of cystic necrosis with subsequent dystrophic calcification in the mass. greater percentage of the nonhyperfunctioning variety develop tumoral calcifications. These calcifications tend to be focal, coarse, irregular, and located relatively centrally in a large pancreatic mass (Fig 6). However, insulinoma, which is the most common functioning islet cell tumor, may contain calcifications in up to 20% of cases (Fig. 7). Intraductal papillary mucinous neoplasms consist of abnormal ductal epithelium, which ranges from hyperplasia to carcinoma, and usually produce a large amount of mucin. The abnormal epithelial cells may be located in the main pancreatic duct or a side branch. The mucin distends the local duct system and frequently extends downstream to widen the papillary orifice. Intraductal papillary neoplasms may produce a multilocular mass in the pancreatic head or occasionally distend the main pancreatic duct, resulting in a unilocular cystic mass. lthough Received December 21, 2000; accepted after revision ugust 2, Department of Radiology, Medical College of Wisconsin, 9200 W. Wisconsin ve., Milwaukee, WI Department of Radiology, University of Wisconsin Medical School, 600 Highland ve., Madison, WI ddress correspondence to. J. Taylor. JR 2002;178: X/02/ merican Roentgen Ray Society JR:178, January
2 Lesniak et al. Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved C Fig. 1. Calcifications associated with chronic alcoholic pancreatitis., Radiograph of abdomen of 57-year-old man with chronic abdominal pain shows numerous dense calcifications over pancreatic area. Subsequently, history of chronic alcohol abuse was obtained. and C, Contrast-enhanced CT of abdomen in 58-year-old man with history of alcohol abuse who presented with jaundice. In this case, calcifications in enlarged pancreatic head and biliary tree dilatation are due to pancreatitis. Rarely, pancreatic adenocarcinoma can be associated with ductal calcifications. However, pancreatitis is more common. D, Transverse sonogram of pancreas in 52-year-old man with chronic alcoholic pancreatitis displays some large concretions that shadow (curved arrow). However, many smaller stones are represented as bright reflectors but without accompanying sonic shadow (arrowhead). This is a common finding. lso present are segments of abnormally dilated pancreatic duct (arrow). D 80 JR:178, January 2002
3 Causes of Pancreatic Calcifications Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 2. Hereditary pancreatitis in 18-year-old man with abdominal pain and distended abdomen. His brother was previously diagnosed with hereditary pancreatitis., On endoscopic retrograde pancreatogram, large intraductal concretions (arrows) are present., On subsequent contrast-enhanced CT, calcified concretions in pancreatic body and tail are seen. Massive ascites is pancreatic in origin. Fig. 3. Cystic fibrosis in 23-year-old woman. and, Contrast-enhanced CT scan shows small pancreatic calcifications (arrows) throughout gland. Fig. 4. denocarcinoma superimposed on chronic calcific pancreatitis in 71-year-old woman with history of alcohol abuse who presented with jaundice., On CT scan, pancreatic head contains calcifications displaced by poorly defined mass (arrows)., Radiograph of pancreatic head obtained before injection on endoscopic retrograde pancreatogram shows these calcifications to be in form of ducts (arrow). Subsequent biopsy reveals carcinoma in head of pancreas. JR:178, January
4 Lesniak et al. Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved not commonly seen, dystrophic calcifications may develop in the mucus [6] (Fig. 8). Mucinous cystic neoplasms have been previously referred to as mucinous or macrocystic Fig. 5. Calcifications develop upstream from malignant obstruction in 81-year-old woman who presented with epigastric pain. Patient had no history of alcohol abuse., On CT scan, small calcification is present in dilated main pancreatic duct (arrow). lso note dilated intrahepatic biliary ducts., On endoscopic retrograde pancreatogram, ductal concretion (arrow) is present behind malignant stricture. Pancreatic carcinoma was found at surgery. cystadenomas or cystadenocarcinomas [7]. They are most commonly found in women in their sixth decade. The tumors may be unilocular or multilocular cystic lesions with individual loculi Fig. 6. Nonhyperfunctioning islet cell tumor in 41-year-old woman who presented with vague epigastric pain. Complex mass is found on contrast-enhanced CT scan. Note central calcifications and low-attenuation areas of necrosis in mass. bsence of biliary ductal dilatation is unusual for pancreatic adenocarcinoma in this location. Subsequent biopsy confirmed diagnosis of nonhyperfunctioning islet cell tumor. of at least 2 cm. The mucinous cystic neoplasm consists of a thick outer capsule with its inner portion characteristically composed of ovarian stroma. Mucus fills the cyst, but septations and polypoid excrescences may also be present. Calcifications occur in the cyst wall or septa and tend to be curvilinear (Fig. 9). Serous cystadenomas, also called microcystic adenomas, are considered a benign pancreatic neoplasm. These tend to occur in patients more than 60 years old [8]. They are slow growing and frequently have grown to 10 cm in diameter. Serous cystadenomas are made up of numerous, small, thin-walled cysts. These characteristics give the tumor an overall nodular border with a honeycomb internal architecture. The tumors commonly calcify (Fig. 10). The pattern of calcification is characteristic of a Fig. 7. Insulinoma in 24-year-old woman who presented with hypoglycemia., ecause of clinical likelihood of insulinoma, noncontrast CT scan was initially obtained. Subtle cm area of high attenuation in pancreas (arrow) is found to represent calcified insulinoma at surgical pathology., Tumoral hypervascularity is seen as blush with contrast enhancement. 82 JR:178, January 2002
5 Causes of Pancreatic Calcifications Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 8. Intraductal papillary neoplasm in 52-year-old woman with pancreatic stent recently placed for pancreatitis outside our institution., Radiograph obtained before endoscopic retrograde pancreatogram shows pancreatic stent adjacent to moderate-sized focus of calcification with smaller calcifications (arrows) also visualized., Contrast-enhanced CT scan depicts dominant calcification in pancreatic head (arrow) and smaller flecks of calcium (arrowheads). On endoscopic retrograde pancreatogram (not shown), other, noncalcified, mucinous filling defects were seen. Fig. 9. Mucinous cystic neoplasm in 79-year-old woman with pancreatic mass found during imaging workup for lower back pain., Noncontrast CT scan was obtained because of renal compromise. Mucinous cystic neoplasm has small linear focus of calcification in its wall (arrow)., Fast spin-echo T2-weighted MR image better displays internal network of septations. However, as is common with MR imaging, mural calcification is not seen. Fig. 10. Serous cystadenoma in 65-year-old woman with mass in pancreatic head. Delayed contrast-enhanced CT scan shows nodular pancreatic mass with honeycombed appearance (arrow). Central scar is only faintly calcified. JR:178, January
6 Lesniak et al. Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 11. Solid and pseudopapillary epithelial neoplasm in 34-year-old woman with back pain., Left upper quadrant curvilinear calcifications are shown on lateral radiograph of lumbar spine. and C, Subsequent contrast-enhanced CT scans define calcification as part of pancreatic mass. Portion of this mass is soft tissue (arrow), whereas second component appears as peripherally calcified cyst (arrowhead). Fig. 12. Pancreatic metastases in 63-year-old man with mucinous colon carcinoma. Contrast-enhanced CT scan shows pancreatic mass with calcification (straight arrow) present with similar calcifications in liver (curved arrows). iopsies showed both liver and pancreatic lesions were metastatic. C Fig. 13. Senescent pancreatic calcifications in 77-year-old man without significant medical history who presented with steatorrhea., CT section through body and tail of pancreas shows tiny peripheral calcifications (arrowheads). lso apparent is glandular atrophy and main duct dilatation., CT scan on slightly more caudad section shows that large intraductal calculus (arrow) is cause of ductal obstruction. 84 JR:178, January 2002
7 Causes of Pancreatic Calcifications Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved central calcified scar with calcified septations radiating outward, resulting in a sunburst pattern. Solid and pseudopapillary epithelial neoplasms are rare tumors found almost exclusively in young women. They are considered to be a low-grade malignant tumor and are usually large at the time of diagnosis, measuring an average of 9 cm [9]. Most commonly, solid and pseudopapillary neoplasms are found in the pancreatic tail and are composed of solid and cystic areas that are separated by pseudopapillary epithelium. Calcification of these tumors (Fig. 11) is common [9]. The calcification is characteristically peripheral and frequently punctate. Metastases to the pancreas are uncommon. The most common sources are breast, lung, kidney, melanoma, and colon cancer. Calcifications have been reported in cases of metastatic renal cell carcinoma and metastatic colon carcinoma [10] (Fig. 12). nother uncommon pancreatic tumor, the pancreatoblastoma, can develop calcifications in 20% of cases [11]. Senescent Occasionally, intraductal calculi occur in the older population with no identifiable cause (Fig. 13). These idiopathic calculi are rarely seen in patients less than 70 years old, with their incidence increasing with age [12]. The calculi occur in the peripheral ducts and are generally 1 3 mm. They can cause atrophy and fibrosis of the pancreas as a result of duct obstruction. Mimics Several potential mimics of pancreatic calcification exist. Calcification of the splenic artery is generally identifiable by its characteristic linear, tram-track appearance. However, in some cases it can be difficult to distinguish from pancreatic calcification (Fig. 14). On CT, dense arterial contrast enhancement in the pancreas can simulate calcifications (Fig. 15). Calcified gall- Fig. 14. Splenic artery mimic in 51-year-old woman with no symptoms relating to her pancreas., Portal venous phase contrast-enhanced CT scan shows ring-like area of high attenuation in pancreas (arrow). Question of small islet cell tumor with peripheral calcification was raised. t least one area is definitely calcified (arrowhead)., Patient was brought back for double-helical CT scan using thinner slice section. Sections during arterial phase of this examination better show tortuous splenic artery that indents into normal pancreas. Fig. 15. Contrast-enhanced intrapancreatic artery mimicking calcification in 5-year-old girl who presented with pancreatitis., On contrast-enhanced CT scan, small focus of increased attenuation was thought to be pancreatic calcification (arrow). Possibility of hereditary pancreatitis was raised. Normal endoscopic retrograde cholangiopancreatogram followed (not shown)., Subsequent unenhanced CT scan was obtained that showed normal-appearing pancreas and failed to visualize any pancreatic calcification verifying that area of increased attenuation on initial examination was intrapancreatic vessel. JR:178, January
8 Lesniak et al. Downloaded from by on 12/21/17 from IP address Copyright RRS. For personal use only; all rights reserved stones in the distal common bile duct are a potential mimic (Fig. 16). Retained contrast in duodenal diverticula can also be mistaken for calcification in the pancreas. References 1. Curry C, Eng J, Horton KM, et al. CT of primary cystic pancreatic neoplasms: can CT be Fig year-old man with abdominal pain. Contrast-enhanced CT scan shows distal common bile duct stone (arrow) masquerading as pancreatic calcification. used for patient triage and treatment? JR 2000; 175: Minagi H, Margolin F. Pancreatic calcifications. m J Gastroenterol 1972;57: Dodge J. Paediatric and hereditary aspects of chronic pancreatitis. Digestion 1998;59[suppl 4]:49S 59S 4. Ring EJ, Eaton S, Ferrucci JT, Short WF. Differential diagnosis of pancreatic calcification. JR 1973; 117: uetow PC, Parrino TV, uck JL, et al. Islet cell tumors of the pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status. JR 1995;165: Procacci C, Graziani R, icego E. Intraductal mucin producing tumors of the pancreas: imaging findings. Radiology 1996;198: Compagno J, Oertel J. Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). m J Clin Pathol 1978;69: Rattner D, Fernandez-del Castillio C, Warshaw. Cystic pancreatic neoplasms. nn Oncol 1999;10[suppl 4]:104S 106S 9. uetow P, uck J, Pantongrag-rown L, et al. Solid and papillary epithelial neoplasm of the pancreas: imaging-pathologic correlation in 56 cases. Radiology 1996;199: Klein K, Stephens D, Welch T. CT characteristics of metastatic disease of the pancreas. Radio- Graphics 1998;18: Montemarano H, Lonergan GJ, ulas DI, Selby DM. Pancreatoblastoma: imaging findings in 10 patients and review of the literature. Radiology 2000;214: Nagai H, Ohtsubo K. Pancreatic lithiasis in the aged: its clinicopathology and pathogenesis. Gastroenterol 1984;86: JR:178, January 2002
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