Age Related Pathological Findings in the Pancreas

Metaplasia/Hyperplasia of Pancreatic Ductal Epithelium

There are two types of epithelial metaplasia of the pancreatic duct: mucous cell metaplasia, or goblet cell metaplasia, and squamous cell metaplasia, including basal cell metaplasia. The former is composed of a tall columnar/mucinous epithelium, non-papillary or flat in a layer, often arranged in papillary protrusion, compatible with mucous cell hyperplasia and found in all sizes and levels of the pancreatic ducts, but predominantly in the branches and smaller ducts (fig. 1). The latter is composed of small nests of squamous cells, seldom in keratinization and malignant change, and found also in all sizes and levels of the pancreatic ducts, especially in the branching-off portion (fig. 2) [4].

Recently, Hruban et al. [5] proposed the terminology of pancreatic intraepithelial neoplasia (PanIN), which was a new nomenclature and classification sys-

Fig. 2. Squamous cell metaplasia. A nest of mature stratified squamous or pseudos-tratified transitional epithelium was found just beneath the columnar epithelium. HE. X250.

tem for pancreatic duct lesions and putative precursor lesions of invasive ductal carcinoma (IDC) in the smaller-caliber pancreatic ducts. The revised definition of PanIN is defined as non-invasive epithelial neoplasms arising in any part of the pancreatic ducts, including the main duct, while PanIN was usually <5 mm in diameter [6]. Most of the mucous cell metaplasia/hyperplasia in our previous study corresponded with PanlN/L-lA and PanlN-lB (mucinous duct proliferation without atypia), and less often PanIN-2 (mucinous duct neoplasia with atypia), but never PanIN-3 (severe dysplasia/carcinoma in situ). PanIN-1 and -2 are thought to be common incidental findings in the general population [7, 8].

Mucous cell metaplasia/hyperplasia occurs at multiple sites and shows an age-related increase in frequency; it is first detected in the first decade of life and increases thereafter, finally becoming very close to 100% in elderly persons. The average frequency of mucous cell metaplasia/hyperplasia is 52.6% (206 of 392 cases). The frequency by site for the head, body, and tail is 155 cases, 120 cases, and 129 cases, respectively. The pancreatic ducts with meta-plasia/hyperplasia tend to dilate through both secreted mucinous fluid retention and cell proliferation/hypertrophy. Mucous cell metaplasia/hyperplasia is usually associated with naked islets of Langerhans due to parenchymal loss and the remnants of branch ducts, which appear as in elastosis, in upstreaming lobules (fig. 3) [4, 9, 10], because epithelial hyperplasia may cause obstruction/stenosis of the branch pancreatic ducts. Detlefsen et al. [11] cite that narrowing of the duct lumen can be caused by papillary proliferations of hypertrophic epithelium and may hamper secretion and cause fibrosis of the drained lobule. According

Fig. 3. Mucous cell hyperplasia in the branch duct and parenchymal loss in the upstreaming lobule. Branch duct with hyperplasia (large arrow) was dilated and associated with parenchymal loss, resulting in naked islets of Langerhans. A remnant of the pancreatic duct (small arrow) was found. Elastica van Gieson. X41.

Fig. 3. Mucous cell hyperplasia in the branch duct and parenchymal loss in the upstreaming lobule. Branch duct with hyperplasia (large arrow) was dilated and associated with parenchymal loss, resulting in naked islets of Langerhans. A remnant of the pancreatic duct (small arrow) was found. Elastica van Gieson. X41.

to our studies [9, 10], however, not only fibrosis but also fat replacement occur in the upstreaming lobule.

Cystic Dilatation ofBranch Ducts, or 'Bubbles'

According to a postmortem pancreatography series by Komatsu [12], cystic dilatation of the branch pancreatic ducts was found in 37 of 85 cases (43.5%), showing age-related increases in frequency, and was found in multiple sites in all but 5 cases (fig. 4a). The lesion was also called a 'bubble'. The frequency by site was 28 cases in the head, 27 cases in the body and 16 cases in the tail. The size of the cystic dilatation ranged between 15.4 X 8.2 and 6.8 X 0.8 mm on postmortem X-ray.

The epithelia of the cystic-dilated duct are composed of tall columnar/mucous cells, with or without papillary protrusion, similar to those of mucous cell metaplasia/hyperplasia described above, and also associated with naked islets of Langerhans in the surrounding tissue (fig. 4b).

Both cystic dilatation of the branch duct and naked islets of Langerhans begin to be detected in about the fourth decade, about 20 years later than mucous cell hyperplasia, and also show age-related increases in frequency, as shown in figure 5.

Fig. 4. Cystic dilatation of the branch pancreatic duct (44-year-old male). a Pancreatography at autopsy showing three cystic dilatations in the peripheral pancreatic ducts. b The cystically dilated duct in the center was lined/replaced by tall columnar/muci-nous cells and associated with parenchymal loss and naked islets of Langerhans in the surrounding tissue. HE. Low magnification. (From [9] with permission.)

Fig. 5. Age-related frequency of (a) mucinous cell metaplasia/hyperplasia, (b) cystic dilatation of branch pancreatic duct and (c) naked islets of Langerhans.

Relationships between Hyperplasia, Cystic Dilatation of Branch Duct, and Naked Islets of Langerhans

Hyperplasia of the pancreatic duct epithelium begins in the first decade, and both cystic dilatation of the branch pancreatic ducts and naked islets of

Fig. 6. Multiple cystic dilatations of branch ducts aggregating due to parenchymal loss. HE. X20.

Langerhans occur about 20 years later, as described above. These lesions all show age-related increases in frequency. Hence, epithelial metaplasia/hyperpla-sia of the pancreatic ducts occurs first, then these ducts tend to dilate due to retention of mucus production and epithelial hypertrophy/proliferation, which also causes ductal narrowing [11], finally leading to cystic dilatation and surrounding or upstreaming parenchymal atrophy.

Therefore, age-related pathological conditions of the pancreas consist of mucous cell metaplasia/hyperplasia, cystic dilatation, or 'bubble', of the branch ducts and naked islets of Langerhans, which occur in this order.

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    What types of psedous cyst on the pancreas?
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