Leslie S. Cutler

Melanotic neuroectodermal tumor of infancy: An ultrastructural study, literature review, and reevaluation

Two cases of melanotic neuroectodermal tumor of infancy were examined by electron microscopy and an extensive review of the literature was performed. Ultrastructural examination revealed several features not previously described for this lesion. Three different types of melanin granule formation were observed, many cells had a single cilium, and cell junctions of the “close” or “modified‐tight” type were seen, but no desmosomes were found. The morphologic data were consistent with the concept that the tumor arises from neural crest cells. The review of the literature indicated that there have been 158 reported cases of this lesion, including the two reported here. There were five cases of malignant tumor reported for a rate of 3.2%. This rate of malignancy is very high in view of the fact that the tumor has been described as universally benign. The significance of this finding is discussed with regard to melanin‐producing lesions of the oral cavity.

Histogenesis of adenoid cystic carcinoma of the salivary glands: light and electronmicroscopic study

This ultrastructural study, based on 12 cases of adenoid cystic carcinoma of the major and minor salivary glands, was conducted to determine the role and extent of participation of myoepithelial cells in their histogenesis. The tumors were composed of four major cell types: intercalated duct, myoepithelial, secretory, and pluripotential reserve/stem cells. The cellular composition of adenoid cystic carcinoma is similar to that in the “terminal tubule” complex stage of a developing salivary gland except that in the tumor the pluripotential reserve/stem cells differentiate predominantly along the intercalated duct cell line rather than secretory cells as in the acinic cell carcinoma. Furthermore, adenoid cystic carcinoma appears to contain a far greater number of myoepithelial cells than acinic cell carcinomas. Cancer 58:72–82, 1986.

Myoepithelial cell adenoma of the parotid gland: A light and ultrastructural study

Light, histochemical, and ultrastructural features of a myoepithelial cell adenoma of the parotid gland are described. Ultrastructurally, the neoplasm was almost entirely composed of myoepithelium. The spindle‐shaped myoepithelial cells and their processes were filled with longitudinally oriented myofilaments with characteristic densities along their course and marginal attachment plaques. The tumor cells were interconnected by desmosomes. The role of myoepithelium in the genesis of some salivary gland tumors is discussed.

Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus

Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.

An electrophysiological study of the postnatal development of the autonomic innervation of the rat submandibular salivary gland

The development of the functional relationship between the autonomic nerves that regulate secretion and the acini of the gland (SMG) was studied. Electrophysiologic studies indicated that stimulation of the parasympathetic nerves at birth caused the secretion of fluid from the duct system but did not cause protein secretion from the developing acini or terminal tubules. Stimulation of the sympathetic innervation (superior cervical ganglion) did not cause protein secretion from developing acini or terminal tubules until 5 days after birth. The amount of protein released progressively increased in response to electrical stimulation of the cervical ganglion as the animals aged. This increased secretory response was correlated with the appearance of increasing numbers of catecholamine-containing neurones in the gland parenchyma.

Glycogen‐rich tumor of the oral minor salivary glands a histochemical and ultrastructural study

A detailed electronmicroscopic study on glycogen‐rich tumor is presented. The neoplasm originated from the minor salivary glands on the ventral surface of the tongue. The role of myoepithelial cells in the histogenesis of this lesion is not supported. It is proposed that the tumor arises from “undifferentiated” stem cells analogous to cells in the “end bud” stage of salivary gland morphogenesis. The presence of a large amount of glycogen is secondary to defective carbohydrate metabolism within the tumor cells. Cancer 52:105‐111, 1983.

Chapter 32 Development of Stimulus—Secretion Coupling in Salivary Glands

Publisher Summary This chapter provides evidence that the secretory cells of the developing rat submandibular gland (SMG) acquire the ability to synthesize and package secretory proteins prior to attaining the ability to release the packaged product in response to hormonal stimuli. The chapter correlates the development of the secretory response with studies on hormonal activation of cell surface–associated adenylate cyclase and with direct measurements of β -adrenergic and α -adrenergic binding sites. The chapter thus provides a picture of the development of the stimulus–secretion coupling system in this model exocrine system. Electrophysiological and morphological evidence indicates that in this system, development of the stimulus–secretion-coupling mechanism precedes the establishment of the neural connections that regulate secretion in vivo . The data presented in the chapter give a comprehensive picture of the maturation of those factors that regulate protein secretion in this model exocrine system. It appears that differentiating SMG secretory cells first develop the structural and synthetic machinery required to produce and package their secretory product.

Monomorphic adenomas of the parotid glands their ultrastructure and histogenesis

Three cases of monomorphic basal cell adenoma of the parotid glands were studied with light microscopy. In one patient, fresh tissue was available for electron microscopic observations. On the basis of ultrastructural findings it was concluded that myoepithelial cells play little, if any, role in the histogenesis of this lesion. The tumor originates from the undifferentiated stem cells analogous to the cells seen at the “end bud” stage of salivary gland morphogenesis prior to their further cytodifferentiation and functional maturation into secretory and myoepithelial cells. In fully developed salivary glands such undifferentiated stem cells reside as “reserve” cells in the intercalated ductal system. Cancer 52:112‐120, 1983.

The influence of the sympathetic nervous system on the development of β-adrenergic receptors in the rat submandibular salivary gland

During the development of the rat submandibular gland (SMG) there is a clearly-defined sequence in the maturation of the beta-adrenergic receptor/adenylate cyclase-linked stimulus-secretion coupling system. The sympathetic nervous system does not become functionally linked to the exocrine process in the SMG until approximately six days after birth. The temporal correlation of the ingrowth of catecholamine-containing nerve processes, the appearance of beta-adrenergic receptors and the functional coupling of the stimulus-secretion system suggested the possibility of a cause and effect relationship between the appearance of the catecholamine-containing nerves in the gland and the maturational increase in the number of beta-adrenergic receptors. Chemical sympathectomy in neonates did not effect the time of appearance or the number of beta-adrenergic receptors seen in the developing gland. However, chronic isoproterenol treatment resulted in accelerated maturation of the gland with a concomitant premature appearance of the beta-receptors. These data suggest that the increase in the number of beta-adrenergic receptors which normally occurs in the developing gland at 5-6 days after birth is a specifically-programmed step closely associated with the degree of maturation attained by the cells and is independent from the ingrowth of catecholamine-containing nerves.

Glycosaminoglycan synthesis by adult rat submandibular salivary-gland secretory units.

The synthesis of glycosaminoglycans (GAG) by a preparation of purified, functional submandibular-gland secretory units (acini and intercalated ducts) was examined. Such units were isolated from Sprague-Dawley rats by digestion of minced gland with hyaluronidase and collagenase followed by gentle sieving of the digest through a graded series of Teflon screens. They incorporated amino acids into exocrine proteins which could be released by stimulation with isoproterenol as in vivo, indicating their functional integrity. Secretory units, incubated for 2 h in medium containing [35S]-sodium sulphate alone or in combination with [3H]-glucosamine, were then washed, homogenized and digested in pronase. The resulting material was then sequentially digested by specific enzymic and chemical procedures and analysed by chromatography on Sephadex G-50 columns to identify the various GAG synthesized. Secretory units synthesized a GAG mixture which was 20-25 per cent hyaluronic acid, 70-75 per cent heparan sulphate, and only 3-5 per cent chondroitin or dermatan sulphates, similar to that synthesized in vivo. No GAG was present in the secretory material, suggesting that all the GAG synthesized was destined for the basement membrane or cell surface.