Histological assessment of chronic pancreatitis at necropsy.

AIMS: To evaluate the histological criteria used to diagnose chronic pancreatitis; and to assess interobserver variation among general pathologists. METHODS: Forty five cases of chronic pancreatitis diagnosed in necropsy were reviewed to determine whether the diagnosis was acceptable retrospectively. These cases were diagnosed initially as chronic pancreatitis in the final necropsy report complied by general pathologists. In reviewing these cases, special attention was paid to irregular fibrosis and destruction of the lobular architecture. RESULTS: The 45 cases were re-assigned to seven different diagnostic categories: chronic pancreatitis, 21 (47%) cases; interstitial fibrosis with or without chronic inflammation, 11 (24%) cases; repair stage of acute pancreatitis, four (9%) cases; severe fatty infiltration, three (7%) cases; chronic inflammation without interstitial fibrosis, two (4%) cases; haemochromatosis, one (2%) case; and undetermined, three (7%) cases. CONCLUSIONS: The histological spectrum of chronic pancreatitis was very wide and it was often misdiagnosed. Acinar atrophy, acinar dilation and intralobular fibrosis were diagnostic of chronic pancreatitis. Differential diagnoses include the repair stage of acute pancreatitis, severe fatty infiltration and haemochromatosis. Recognition of these findings may help to reduce overdiagnosis of chronic pancreatitis.     

Quantitative immunohistochemistry of immunoglobulin- and J-chain-producing cells in human parotid and submandibular salivary glands.

Ig-producing cells were quantified by paired immunohistochemical staining in saline-extracted and paraffin-embedded normal tissue specimens from human parotid (ten) and submandibular (seven) salivary glands. The density of such cells (number/mm2 of 6 micron thick tissue section) was significantly higher in the submandibular than in the parotid gland (P less than 0.005), but the Ig-class distribution was fairly similar. The mean percentage class ratios for IgG, IgA, IgM and IgD cells in the parotid were 4.5:86.5:5.9:3.1, and in the submandibular gland 3.7:86.9:7.9:1.6. In the parotid gland of a patient with selective IgA deficiency the same class ratios were 27:0:20:53. Thus, the IgA cells were especially replaced by IgD cells. In normal glands most of the IgA (80-93%), IgM (99-100%) and IgD cells (81-95%) were J-chain-positive; this was likewise true for a substantial proportion of the IgG cells (32-46%). Of additional interest was the finding that in the IgA-deficient parotid gland, 99% of the numerous IgD cells and 86% of the increased number of IgG cells contained cytoplasmic J chain. IgE-producing cells were virtually absent from the IgA-deficient as well as from the normal salivary glands.     

A granular cell in the proximal intercalated duct of human parotid and submandibular glands

In human parotid and submandibular gland unusual granulated cells are observed at the acinar-intercalated duct junction. These cells, which show a well developed Golgi apparatus, greatly differ from the typical elements of the intercalated ducts mainly due to the presence of abundant secretory granules of unknown nature. A complex substructure distinguishes these granules from those of conventional ductal cells and from those of acinar cells as well. In addition, some differences exist in the morphology of the granules observed in parotid with respect to those of submandibular gland.     

Morphological changes in collagen fiber during development of human fetal parotid and submandibular glands

Parotid and submandibular glands from human fetuses (16, 20, 24, 28, 32 weeks of gestation) were examined under a scanning electron microscope. Changes were found in the arrangement of collagen fibers in the connective tissue surrounding the salivary gland. In particular, several layers around the salivary gland were formed by a collagen network structure. These structures, although in varied arrangements, were recognizable in each stage of fetal growth. They are thought to play the role of a "cushion" against pressure created by accumulation of granules because of the reflex activity of myoepithelial cells during secretion. These structural changes are related to the mechanical performance of granule formation in the salivary gland and secretion during the development of the fetus.     

Intraglomerular metastasis: a necropsy study.

Intraglomerular metastasis is a rare phenomenon. Four cases are reported here. The primary malignancies in these four cases were squamous cell carcinoma of the lung, adenocarcinoma of pancreas, haematological malignancy with a malignant intrapulmonary teratoma, and undifferentiated pleural mesothelioma. There was no significant renal functional impairment in any case except for mild proteinuria in one. Histopathology showed tumour cells in the mesangium, in the glomerular tufts replacing the endothelial cells, as well as in an extracapillary location replacing the parietal cells. In one case, tumour cells formed crescent-like structures. Such tumour deposits were better appreciated with special stains. The presence of intraglomerular metastasis indicates dissemination of the malignancy and hence a poor prognosis even though there is no significant impairment of renal function.     

Further evidence for AQP8 expression in the myoepithelium of rat submandibular and parotid glands

Previously (Wellner et al., Pflugers Arch 441:49–56, 2000) we suggested that the localization of the aquaporins (AQPs) AQP5 and AQP8 in the apical and basolateral membranes of rat submandibular gland (SMG) acinar cells, respectively, provides for transcellular water flow during saliva formation. While the localization of AQP5 in this gland has been verified in several laboratories, there have been differing reports regarding AQP8 localization. Other investigators subsequently reported that AQP8 is not expressed in the acinar or ductal cells of the major salivary glands of the rat, but in the myoepithelium of each gland. Thus, we have carried out additional studies: (1) to reassess the localization of AQP8 in the rat SMG and (2) to assess the localization of AQP8 in the rat parotid gland (PG). Initially, we compared the localizations of AQP8 with recognized basolateral markers in acinar cells [the Na⁺,K⁺-ATPase and the Na⁺–K⁺–2Cl^– cotransporter (NKCC1)]. Our results indicated that Na⁺,K⁺-ATPase localized in both the basal and lateral membranes of rat SMG acinar cells, whereas AQP8 was detected only in the basal regions of the acini. In the rat PG, AQP8 was invested near intercalated ducts and adjacent acini, whereas NKCC1 localized in the basolateral membranes of acinar cells. As these results were suggestive of myoepithelial localization in both glands, we compared AQP8 localization with the localization of smooth muscle actin, a myoepithelial marker. We found that AQP8 and smooth muscle actin colocalized in both the rat SMG and PG, providing additional strong support for a myoepithelial localization of AQP8. Thus, in agreement with an earlier report by other investigators (Elkjaer et al., Am J Physiol Renal Physiol 281:F1047–F1057, 2001), we report that AQP8 is expressed in the myoepithelial cells, but not in the acinar cells, of both the rat SMG and PG.     

Immunolocalization of fibronectin and collagen types I and III in human fetal parotid and submandibular glands

We examined the distribution of fibronectin and collagen types I and III in human fetuses under a confocal laser scanning microscope using immunohistochemical staining (at 16, 20, 24, 28, 32 weeks' gestation). The collagen types I and III form the collagenous matrix components in the connective tissue of the parotid and submandibular glands. These extracellular matrix components were detected at various stages around the terminal portion and in the capsule-like connective tissue of the parotid and submandibular glands. However, the extracellular matrix components in the connective tissue around the terminal portion had a stronger reaction than those in the capsule-like connective tissue found on the fringe of the terminal portion. The collagen type I of the parotid gland at 16 weeks' gestation had a weaker reaction than that of the submandibular gland. When results of the reaction at other stages and other extracellular matrix components of the two salivary glands were compared, collagen type I appeared as early as at 16 weeks' gestation in either gland. Since collagen type I serves as the core connective tissue, these observations suggest that the formation of connective tissue around the parotid gland occurs before or after 16 weeks' gestation lagging behind that of the submandibular gland.     

Neurokinin A in the parotid and submandibular glands of the rat: immunohistochemical localization and effect on protein and peroxidase secretion.

An indirect immunofluorescence technique was used to study the distribution of neurokinin A immunoreactive (NKA-IR) nerve fibres in submandibular and parotid glands of the rat. The functional role of neurokinin A on protein and peroxidase secretion in these glands was evaluated by using in vitro methods. In the parotid gland neurokinin A immunoreactive fibres were mainly distributed around the secretory acini, but some were also in evidence around the stromal blood vessels and ducts. The number of the neurokinin A immunoreactive nerve fibres was lower in the submandibular gland than in the parotid gland. They were mainly distributed around the secretory acini and stromal blood vessels and ducts. In vitro, neurokinin A significantly stimulated the release of total amount of released proteins and peroxidase from parotid gland fragments, while in the submandibular gland only the release of peroxidase was increased. By using SDS polyacrylamide gel electrophoresis (SDS-PAGE) specific changes were found in the release of proteins after neurokinin A stimulation. The results of the present study demonstrate that neurokinin A immunoreactive nerve fibres are present in the rat parotid and submandibular glands. Their localization around the secretory elements of the glands and the effect of neurokinin A in vitro experiments indicates that neurokinin A might have a significant role in the regulation of salivary secretion.     

Planimetric correlation between the submandibular glands and the pancreas: a postmortem ductographic study

The salivary glands and pancreas have comparable anatomic and antigenic properties and can share common pathogenetic mechanisms involving toxic or autoimmune processes. The aim of this study is to assess the correlation in size between the normal submandibular glands and the pancreas. The study was based on human autopsy specimens of the pancreas, neck and oral base from 22 adults, both sexes (mean age, 57.9 years). The pancreatic and submandibular ducts were injected with a contrast medium, and the area of the salivary and pancreatic glandular ductograms was measured with the aid of software for quantification of visual information. Samples of tissue from the salivary glands and the pancreas were studied by means of light microscopy. A high correlation was found between the planimetric size of the pancreas and the submandibular glands (correlation coefficient 0.497 and 0.699 for the right and the left gland, respectively). This ratio was close to 5:1. There were no significant differences in size for the left vs. right submandibular gland (p = 0.39). The ductograms were significantly larger in size in males than in females (p < 0.001). This study has proven a positive correlation in planimetric size between the normal submandibular glands and pancreas, a result that is expected to have possible clinical implications in the long-term follow-up of patients with chronic pancreatitis.     

Quantitative analysis of aortic atherosclerosis in Korean female: a necropsy study

To assess the regional difference and influence of the biological variables on atherosclerosis in female, we analyzed 7 segments of aorta (2 ascending, 3 thoracic, and 2 abdominal) from 90 superficially healthy Korean women (39+/-14 yr of age) who died from external causes. Tissue specimens were macroscopically examined and histopathologically divided into 7 grades for scoring (ATHERO, from 0=intact, to 6=thrombi formation). Lumen diameter (LD), wall thickness (WT), intima thickness (INT), and media thickness (MED) were obtained by computed morphometry. Atherosclerosis was common in the distal infrarenal (C2), proximal thoracic (B1), and proximal ascending (A1) segments. Total 95.6% of all subjects had atherosclerosis of variable degree in one or more segments, but an aneurysmal change was not found. The number of atherosclerotic segments and atherosclerosis score in the 7 segments increased with aging. However, the body size did not affect the aortic size and ATHERO. With aging, LD and INT of the A1, B1 and C2 increased (p<.00001); WT of the B1 and C2 increased (p<.01); and MED of C2 decreased (p<.01). LD and WT of the B1 and C2 (p<.05), INT of the A1, B1 and C2 (p<.00001) increased, and MED of C2 decreased (p<.01) with ATHERO. These data suggest that age is simple but a reliable parameter for estimating the progression of atherosclerosis.     

Ultrastructural observations on luminal structures of pleomorphic adenoma of parotid and submandibular salivary glands of man

Summary Luminal structures found in salivary pleomorphic adenomas consisted of lumina surrounded by epithelial cells that varied from being packed together to being widely separated except at the luminal margin. Communication between lumina and the surrounding stroma was occasionally seen. Secretory material and cellular debris were seen in lumina, invaginations of the luminal surfaces of periluminal cells, associated vesicles, and vacuoles. Secretory granules, lysosomes and lipofuscin were seen in periluminal cells. Secretory material and debris from necrotic periluminal cells appear to accumulate in lumina, and to be endocytosed and degraded lysosomally by periluminal cells. The finding of communications between lumina and the surrounding stroma suggests that the stromalization of the epithelium includes the luminal structures. The present investigation supports the hypothesis that many of the cellular features of the pleomorphic adenoma relate to the microenvironment.     

Splenic macrophages in preterm infants: a necropsy study.

AIMS: To study the frequency and nature of histiocytes in the splenic red pulp of infants who died following complicated immaturity/prematurity. METHODS: Twenty four preterm/immature infants were investigated. Frozen sections of formalin fixed splenic tissue were stained with Oil Red O. Paraffin wax sections from the same tissue were conventionally stained with haematoxylin and eosin. Immunohistochemistry was carried out for a number of macrophage markers. The administration of Intralipid was compared with the presence and extent of tissue macrophages. RESULTS: The spleens of 10 infants showed varying degrees of Oil Red O positivity ranging from mild to strong. In all these cases varying numbers of macrophages were confirmed in the splenic parenchyma in ordinary sections. The immunomarkers indicated that the histiocytes belonged to the macrophage phagocytic system. Of the 10 cases with splenic macrophages all had received Intralipid. Of those not receiving Intralipid none showed splenic macrophages. Seven had received Intralipid but did not have splenic macrophages; they had either only received small amounts of Intralipid or Intralipid was discontinued before death. CONCLUSIONS: Splenic macrophages are common at necropsy in immature/preterm infants. The macrophages are most lucidly demonstrated using Oil Red O staining in frozen sections. There is a strong association between the presence of splenic macrophages and Intralipid administration.     

Fluid and protein secretion from ferret submandibular and parotid glands in response to sympathetic nerve stimulation or administration of sympathomimetics.

Electrical stimulation of the sympathetic innervation evoked secretion of submandibular and parotid saliva. By changing the mode of stimulation from a continuous to an intermittent one the fluid response increased and glandular blood flow improved. The volumes from the submandibular glands were larger than those from the parotid glands and further, the protein concentration of submandibular saliva was higher than that of parotid saliva. Adrenaline, isoprenaline and phenylephrine evoked larger fluid responses from submandibular than from parotid glands. However, the fluid response was small compared to the parasympathetic one. Substance P-evoked saliva was used as carrier for protein released by sympathetic nerve stimulation or administration of adrenaline and isoprenaline. In vitro tissues of submandibular and parotid glands responded to adrenaline with a dose-dependent release of protein. Taken together, the analytical pharmacology performed in vivo and in vitro, and including the antagonists phentolamine, dihydroergotamine, propranolol and metoprolol, showed that in submandibular glands, α(α₁)adrenoceptors were predominantly involved in fluid secretion and β(β₁)-adrenoceptors predominantly involved in protein secretion. In parotid glands, fluid secretion seemed solely to depend on α(α₁)-adrenoceptors, while β(β₁)-adrenoceptors seemed almost solely involved in protein secretion.     

Morphometric study of the microvasculature of the main excretory duct subepithelia of the rat parotid, submandibular and sublingual salivary glands

This study investigated the relationship between the fine structure of the main excretory duct (MED) epithelia and the subepithelial capillaries of the major salivary glands (parotid, submandibular, and sublingual) in the rat. The MED subepithelial capillaries vary in type (fenestrated and continuous), number of fenestrae present in the available fenestrated endothelium (the attenuated area of endothelium), and number of capillaries per unit length of epithelium. In the parotid gland, continuous capillaries predominate, and the capillary density per 200 microns of epithelium (1.73 in region I and 1.03 in region II) is lower than in the other two glands, as is the number of fenestrae per 10 microns of available endothelium (1.97 in region I and 1.25 in region II). The submandibular gland has mainly fenestrated capillaries. The capillary density per 200 microns of epithelium (4.46 in region I and 5.51 in region II) is higher than in the other two glands, as is the number of fenestrae per 10 microns of available endothelium (4.82 in region I and 7.90 in region II). Similarly, in the sublingual gland, fenestrated capillaries are dominant. The density of capillaries per 200 microns of epithelium (4.15 in region I and 4.31 in region II) is intermediate between the parotid and submandibular glands, as is the number of fenestrae per 10 microns of available endothelium (2.98 in region I and 3.83 in region II).     

Neurokinin A in the parotid and submandibular glands of the rat: immunohistochemical localization and effect on protein and peroxidase secretion

An indirect immunofluorescence technique was used to study the distribution of neurokinin A immunoreactive (NKA-IR) nerve fibres in submandibular and parotid glands of the rat. The functional role of neurokinin A on protein and peroxidase secretion in these glands was evaluated by using in vitro methods. In the parotid gland neurokinin A immunoreactive fibres were mainly distributed around the secretory acini, but some were also in evidence around the stromal blood vessels and ducts. The number of the neurokinin A immunoreactive nerve fibres was lower in the submandibular gland than in the parotid gland. They were mainly distributed around the secretory acini and stromal blood vessels and ducts. In vitro, neurokinin A significantly stimulated the release of total amount of released proteins and peroxidase from parotid gland fragments, while in the submandibular gland only the release of peroxidase was increased. By using SDS polyacrylamide gel electrophoresis (SDS-PAGE) specific changes were found in the release of proteins after neurokinin A stimulation. The results of the present study demonstrate that neurokinin A immunoreactive nerve fibres are present in the rat parotid and submandibular glands. Their localization around the secretory elements of the glands and the effect of neurokinin A in vitro experiments indicates that neurokinin A might have a significant role in the regulation of salivary secretion.     

Ultrastructure of the main excretory duct epithelia of the rat parotid and submandibular glands with a review of the literature

The fine structure of the main excretory duct (MED) epithelia of the rat parotid and submandibular glands was investigated by scanning and transmission electron microscopy. The structure of these two MED epithelia was compared. Five principal cell types were observed in the MED epithelium of the parotid gland--cuboidal, basal, light (types I and II), dark, and tuft cells. The cuboidal cells, which were stratified in two or three layers, were the most numerous. Basal cells were situated adjacent to the basal lamina of the epithelium. The type I light cells had well-developed basal plasma membrane infoldings. The type II light cells had poorly developed basal plasma membrane infoldings. The dark and tuft cells resembled those of the MED epithelium of the rat submandibular gland. Four principal cell types were observed in the MED epithelium of the submandibular gland--light cells (types I and II), dark, tuft, and basal cells. The two types of light cells were the most numerous. Dark cells with regular and dense microvilli were relatively narrow in shape and had complicated basal plasma membrane infoldings. There were numerous vesicles or channel-like vesicles in their apical cytoplasm. Tuft cells were characterized by prominent microvilli, many vesicles of various sizes in the apical cytoplasm, and no basal infoldings. Peroxisomes were present in the MED epithelia of the rat parotid and submandibular glands, especially in light and cuboidal cells.