The prenatal human submandibular gland: a histological, histochemical and ultrastructural study

The submandibular glands of 6 human fetuses, 13.5-16 weeks old, were studied using light and electron microscopic techniques. The developing gland at this stage consisted of a bush-like network of terminal buds (primitive acini) and primary ducts surrounded by a loose mesenchyme. Both components had a lumen which was surrounded by 1 or 2 layers of epithelial cells. Those cells adjacent to the lumen were attached by desmosomes but lacked well developed terminal bars. The cells were separated by an intercellular space, into which projected numerous microvilli. The cytoplasm of the epithelial cells contained the usual organelles with some cells containing large accumulations of glycogen granules. Serous granules and the luminal contents were both strongly PAS and AB positive. The function of this secretory material, at this stage of human development, is unknown. No mucus-like granules were observed. The terminal buds and primary ducts were surrounded by a well developed basal lamina and contained a few elongated cells which appeared morphologically as developing myoepithelial cells. Morphologically the development of the human submandibular gland, at 13.5-16 weeks of age, is roughly equivalent ot the developmental stage of the gland seen in the newborn rat or mouse. By birth, the human submandibular gland would likely reach a mature state, because there would be ample time remaining, in a normal gestation, for the maturation process to be completed.     

Development of the rat sublingual gland: A light and electron microscopic immunocytochemical study

Cell differentiation in the rat sublingual gland occurs rapidly and is largely complete by birth. To study differentiation of the serous and mucous cells of the sublingual gland, we used antibodies to the secretory proteins CSP‐1, SMGB, PSP, and SMGD, and sublingual mucin as specific cell markers. Glands from rats at ages 18, 19, and 20 days in utero, and postnatal days 0, 1, 5, 9, 14, 18, 25, 40, and 60 were fixed and prepared for morphological analysis and immunocytochemical labeling. At age 18 days in utero, a few cells in the developing terminal bulbs contained mucous‐like apical granules that labeled with anti‐mucin. Other cells had mixed granules with a peripheral lucent region and a dense core of variable size that occasionally labeled with anti‐SMGD. Additionally, presumptive serous cells with small dense granules that contained CSP‐1 and SMGB were present. At age 19 days in utero, the dense granules of these cells also labeled with anti‐SMGD. By age 20 days in utero, mucous cells were filled with large, pale granules that labeled with anti‐mucin, and serous cells had numerous dense granules containing CSP‐1, SMGB, PSP, and SMGD. Fewer cells with mixed granules were seen, but dense regions present in some mucous granules (MGs) labeled with anti‐SMGD. After birth, fewer MGs had dense regions, and serous cells were organized into well‐formed demilunes. Except for PSP, which was undetectable after the fifth postnatal day, the pattern of immunoreactivity observed in glands of neonatal and adult animals was similar to that seen by age 20 days in utero. These results suggest that mucous and serous cells have separate developmental origins, mucous cells differentiate earlier than serous cells, and cells with mixed granules may become mucous cells. Anat Rec 266:30–42, 2002. © 2002 Wiley‐Liss, Inc.     

Differentiation of myoepithelial cells in the developing rat sublingual gland

Sublingual glands of rats were prepared for light and electron microscopy and for the histochemical demonstration of myofibrils and alkaline phosphatase (AkPase) activity. Through 17 days in utero, the epithelial cells of the glandular rudiment are relatively undifferentiated. At 18 days, the inner cells of the terminal buds begin to assemble around a lumen and accumulate secretory granules, while the outer cells flatten and form long processes. At 19 days, many of the outer cells have dilated cisternae of rough endoplasmic reticulum engorged with finely granular material. At 20 days, some of the outer cells have thin bands of microfilaments in their processes, suggesting that they are differentiating into myoepithelial cells (MEC). Though the secretory cells are almost mature at birth, only a few of the MEC have myofibrils detected with an actomyosin reaction, and AkPase activity is very weak. Progressive increases in AkPase activity and in myofibril size and number continue until the acini and intercalated ducts are fully invested with mature MEC at about 14 days after birth. Thus, the MEC and secretory cells begin to differentiate at the same time, but the MEC subsequently differentiate asynchronously with the secretory cells and with each other. Although the sublingual MEC are only partly differentiated in the newborn rat, their overall development occurs somewhat more rapidly than in the adjacent submandibular gland.     

Megalomastia: histological,histochemical and immunohistochemical study

Summary Megalomastia is a rare entity characterized by an uncommon enlargement of both breasts. Unilateral megalomastia is extremely rare. The purpose of this study was to collect information concerning the history of patients with this condition and to investigate its histology in order to outline the profile of this peculiar entity. Fifty cases of megalomastia were studied. In 41 data concerning the history of the patients was complete; there were 32 juvenile, 7 gravid and 2 adult type cases. All three unilateral megalomastias were in the juvenile group. A family history of megalomastia was frequently present; gravid megalomastia was more closely connected with a maternal familial history. A case of simultaneous megalomastia in monozygotic twins is included. The final size achieved by the breasts was independent of the type of megalomastia, the rapidity of breast development and the body weight of the patients. It was greater in breasts containing abundant adipose tissue and less in fibrous breasts. In all cases of megalomastia associated with pregnancy the breasts had lost the ability to produce milk. The main histological feature in all cases was severe damage and destruction of the lobular units associated with extensive fibrosis. In some breasts of all three types of megalomastia ramified new ducts named juvenile units had developed and had proceeded to atrophy. Immunohistochemistry revealed that the epithelium of these units was negative for oestrogen and positive to progesterone receptors. A biphasic pathological appearance, consisting of atrophic lobular units and juvenile units, is diagnostic of megalomastia.     

Formation of secretory granules in the Golgi apparatus of prolactin cells in the rat pituitary gland: A stereoscopic study

The mode of secretory granule formation in prolactin cells was analyzed in thin or thick sections of pituitary glands from non-lactating or lactating female as well as from male rats. In all these animals, the Golgi apparatus of prolacting cells consists of a continuous twisted ribbon-like structure that branches and anastomoses to form a hollow sphere located in the juxtanuclear area. The early signs of secretory granule formation are observed along the trans-aspect of the Golgi ribbon where progranules appear as focal distensions simultaneously occurring anywhere in the last trans thiamine pyrophosphatase (TPPase)-containing Golgi element. In the transmost Golgi saccule, such dilatations usually contain several nodular masses of electron opaque material which are separated from each other and from the saccular membrane by a less intensely stained material. While this transmost saccule becomes more fenestrated, its focal polynodular distensions seemingly yield polynodular tubular progranules which are initially closely apposed and usually parallel to the trans face of the Golgi ribbon. Subsequently, these progranules, which frequently show small membranous tubules or tubular networks attached to them, are seen some distance from the Golgi stacks and progresively transform into the more compact polymorphous granules characteristic of prolactin cells. These observations suggest that the polynodular tubular progranules arise by fragmentation of portions of the trans-Golgi elements rather than by fusion of small uninodular granules budding from the edges of a trans-Golgi saccule. Once the progranules have been liberated, the rest of the transmost Golgi element appears to break down into small residual networks, tubules, and vesicles. Thus, in prolactin cells as in other glandular cells, the whole transmost Golgi element would fragment during formation of prosecretory granules.     

Development of the rat sublingual gland: a light and electron microscopic immunocytochemical study.

Cell differentiation in the rat sublingual gland occurs rapidly and is largely complete by birth. To study differentiation of the serous and mucous cells of the sublingual gland, we used antibodies to the secretory proteins CSP-1, SMGB, PSP, and SMGD, and sublingual mucin as specific cell markers. Glands from rats at ages 18, 19, and 20 days in utero, and postnatal days 0, 1, 5, 9, 14, 18, 25, 40, and 60 were fixed and prepared for morphological analysis and immunocytochemical labeling. At age 18 days in utero, a few cells in the developing terminal bulbs contained mucous-like apical granules that labeled with anti-mucin. Other cells had mixed granules with a peripheral lucent region and a dense core of variable size that occasionally labeled with anti-SMGD. Additionally, presumptive serous cells with small dense granules that contained CSP-1 and SMGB were present. At age 19 days in utero, the dense granules of these cells also labeled with anti-SMGD. By age 20 days in utero, mucous cells were filled with large, pale granules that labeled with anti-mucin, and serous cells had numerous dense granules containing CSP-1, SMGB, PSP, and SMGD. Fewer cells with mixed granules were seen, but dense regions present in some mucous granules (MGs) labeled with anti-SMGD. After birth, fewer MGs had dense regions, and serous cells were organized into well-formed demilunes. Except for PSP, which was undetectable after the fifth postnatal day, the pattern of immunoreactivity observed in glands of neonatal and adult animals was similar to that seen by age 20 days in utero. These results suggest that mucous and serous cells have separate developmental origins, mucous cells differentiate earlier than serous cells, and cells with mixed granules may become mucous cells.     

Morphological and histochemical changes in the secretory granules of mucous cells in the early postnatal mouse parotid gland

It has previously been known that the developing parotid glands in humans and rats contain mucous cells in their terminal clusters and acini, but these cells disappear within a short period of time. Using rat parotid glands, IKEDA and AIYAMA (1997, 1999) suggested that the mucous cells might change into serous cells in the early postnatal period, but it is uncertain whether mucous cells appear only in the developing parotid gland of a few species such as humans and rats, or whether the cell transformation actually occurs. To clarify these points, the present study investigated the developing mouse parotid glands. Light microscopy showed cells with secretory granules that stained extensively with PAS and alcian blue in the terminal clusters of a 1-day-old mouse parotid gland. Mucous cell numbers in the terminal clusters and the acini reached a peak on day 5 and decreased on day 7. By day 10, the mucous cells had disappeared altogether. Thus, the presence of mucous cells in the developing mouse parotid gland was confirmed. Electron microscopy showed granules of low-electron-density and bipartite granules in the mucous cells. Bipartite granules and highly electron-dense granules sometimes co-existed in a single cell. Immuno-electron microscopy revealed a positive reaction for amylase to the low-electron-density granules and the low-electron-density portions of the bipartite granules, in addition to the highly electron-dense granules and the electrondense cores of the bipartite granules. No mucous cells with nuclei displaying characteristics of apoptosis were recognizable. Lectin histochemistry both at the light and electron microscopic levels showed that the secretory granules in the mouse parotid gland mucous cells had sugar residues similar to those of the mature serous granules. These findings demonstrate that mucous cells appear in the early postnatal mouse parotid gland, and that almost all of these cells may be converted into serous cells.     

Microcalcifications in breast carcinomas. A histological and histochemical study

Microcalcification in breast carcinomas were studied histologically and histochemically in 332 prospectively collected mastectomy consecutive specimens, without previous roentgenographic examination. Microcalcifications were found in 41% of breast carcinomas. The incidence was higher in comedo-carcinomas, duct carcinomas nonotherwise specified (N. O. S.) and papillary carcinomas. In situ and infiltrative lobular carcinomas did not show any microcalcification. Histochemically, calcium was shown to be deposited in compound lipids. The morphology and localization of microcalcifications was similar to those described in fibrocystic disease. This should be ascribed to similar structural and cellular conditions in both diseases.     

Changes in the secretory acinar cells of the rat parotid gland during aging

The secretory acinar cells of parotid glands from rats of varying ages have been examined by electron microscopy to determine what age-related changes occur in these cells. The most prominent change noted in these cells is the progressive increase in the amount of lipofuscin granules with age. Lipofuscin granules are membrane-bound structures consisting of lipids, other subcomponents, and a matrix. In addition, these cells contain lipid droplets that are not associated with any other components and tend to accumulate at the base of the cells in older rats. Also, many acinar cells in the glands of old rats contain altered secretory granules which appear to be in the process of degeneration. The accumulation of lipid and degenerating secretory granules appears to be related to the reduced level of cellular secretory activity in the glands of older rats. It is possible that these two types of inclusions contribute to the formation of lipofuscin granules. Lipofuscin and degenerating secretory granules are associated with acid phosphatase, which is demonstrated cytochemically, indicating that these granules are lysosomal structures.     

Formation of secretory granules in the Golgi apparatus of prolactin cells in the rat pituitary gland: a stereoscopic study.

The mode of secretory granule formation in prolactin cells was analyzed in thin or thick sections of pituitary glands from non-lactating or lactating female as well as from male rats. In all these animals, the Golgi apparatus of prolacting cells consists of a continuous twisted ribbon-like structure that branches and anastomoses to form a hollow sphere located in the juxtanuclear area. The early signs of secretory granule formation are observed along the trans-aspect of the Golgi ribbon where progranules appear as focal distensions simultaneously occurring anywhere in the last trans thiamine pyrophosphatase (TPPase)-containing Golgi element. In the transmost Golgi saccule, such dilatations usually contain several nodular masses of electron opaque material which are separated from each other and from the saccular membrane by a less intensely stained material. While this transmost saccule becomes more fenestrated, its focal polynodular distensions seemingly yield polynodular tubular progranules which are initially closely apposed and usually parallel to the trans face of the Golgi ribbon. Subsequently, these progranules, which frequently show small membranous tubules or tubular networks attached to them, are seen some distance from the Golgi stacks and progressively transform into the more compact polymorphous granules characteristic of prolactin cells. These observations suggest that the polynodular tubular progranules arise by fragmentation of portions of the trans-Golgi elements rather than by fusion of small uninodular granules budding from the edges of a trans-Golgi saccule. Once the progranules have been liberated, the rest of the transmost Golgi element appears to break down into small residual networks, tubules, and vesicles. Thus, in prolactin cells as in other glandular cells, the whole transmost Golgi element would fragment during formation of prosecretory granules.     

Microcalcifications in benign breast diseases. A histological and histochemical study

A hundred cases of fibroadenomas and 300 cases of benign breast diseases were studied without previous roentgenographic examination of the specimens. Microcalcifications were found in 19% of the fibroadenomas, in 26% of the cases of "fibrous disease" and in 57% of the cases of fibrocystic disease. Benign microcalcifications were not found in normal mammary tissue. They were steadily associated with metaplastic epithelial cells and with their abnormal secretions. Two basic types of microcalcifications were encountered: The granular microcalcifications with a predominately intracellular location and the homogeneous (with or without concentric rings) mainly associated with secreted materials. Microcalcifications were associated with metaplastic epithelial cells of the small eosinophilic variety and with their secretions, with the foam cells and with materials secreted by the apocrine cells. A common histochemical feature in cells or matrixes containing microcalcifications was the presence of compound lipids. The possible relationship of benign breast microcalcifications to the calcifications of other tissues, in connection with their association with lipids is discussed.     

Mucinous cystic tumour of the pancreas. A histological and histochemical study

A histological and histochemical analysis of two new cases of mucinous cystic tumors of the pancreas is reported. Histochemical study revealed a predominantly sulphated acidic mucin secretion with some neutral mucins. Argyrophilic elements were also observed. The authors propose an origin from intestinal type epithelium through a metaplastic process.