John J. Sauk

Malignant melanotic neuroectodermal tumor of infancy. A clinical, pathologic, ultrastructural and tissue culture study

The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4‐month‐old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin‐containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast‐like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast‐like cells were initially difficult to identify by electron microscopy, a melanin‐producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast‐like cells. In the final biopsy and autopsy material, only the neuroblast‐like cells remained and the tumor resembled a conventional neuroblastoma.

Globodontia in the otodental syndrome

A family of Polish extraction was studied in which massive, globe-shaped posterior teeth were found in a father and two of his sons, similar to those described in a previous family in which persons with this type of teeth also had a high-frequency sensorineural deafness. The audiograms in this family showed high-frequency air-conduction thresholds in the father and one son with globodontia and in other relatives without the tooth defect. The other son with abnormal teeth had a normal-appearing audiogram. Absence of premolar teeth and yellow-white spots of local hypomaturation of enamel on canine teeth were also findings in this kindred, as reported or observed in other kindreds. The disorder illustrates the problem of variable expressivity of a trait which makes it difficult to predict the risk of having an affected child when only one feature of a syndrome is present in a relative of a fully affected patient.

Electromyography of oral-facial musculature in craniocarpaltarsal dysplasia (Freeman-Sheldon syndrome)

Electromyography and biopsy of the oral‐facial musculature of a patient with craniocarpaltarsal dysplasia (Freeman‐Sheldon syndrome) supports the thesis that facial muscle hypoplasia is a significant component of this evolving syndrome complex.

Clinical, histologic, cytologic, and ultrastructural characteristics of the oral lesions from hereditary mucoepithelial dysplasia: A disease of gap junction and desmosome formation☆

Hereditary mucoepithelial dysplasia is an autosomal, dominantly inherited disorder affecting all of the orificial mucosa with cataracts, follicular keratosis of skin, nonscarring alopecia, bouts of pneumonia, spontaneous pneumothorax, and terminal cor pulmonale. The oral lesion is a fiery red, flat or micropapillary-appearing mucosa most frequently involving the gingiva and hard palate. All oral and pharyngeal mucosa may be involved, however. Red scrotal mucosa of the tongue is common. Histologically, the oral mucosa shows a lack of cornified and keratinized cells, a decrease in the thickness of the epithelial cell layer, dyshesion, and dyskeratosis. Papanicolaou smears show lack of epithelial cell maturation, poikilocytosis, anisocytosis, large paranuclear cytoplasmic vacuoles, and cytoplasmic strand-shaped inclusions. Ultrastructural features include a paucity of desmosomes, intercellular accumulations of amorphous material, cytoplasmic vacuoles, and paranuclear lesions with strands of material resembling gap junctions and desmosomes. The condition most likely represents a basic defect in gap junction and desmosome formation.

Histopathology and electron and immunofluorescence microscopy of gingivitis granulomatosa associated with glossitis and cheilitis in a case of Anderson-Fabry disease

A 17-year-old white boy with signs, symptoms, and family history of angiokeratoma corporis diffusum universale, Anderson-Fabry disease (AFD), developed recurrent and then persistent swelling of both lips, erythematous hyperplastic gingivae, and a pebbled tongue. Positive blood findings were raised serum IgE, decreased T-cell level, and increased B-cell level. Histopathology of the gingiva showed noncaseating granulomas with multinucleate giant cells containing Schaumann bodies and large plasma-cell infiltrates in which immunofluorescence demonstrated immune globulins of several classes. Electron microscopy and histochemistry demonstrated ceramide in the vasculature. No glycolipid was found in the macrophages or giant cells of the granulomas which, in contrast, resembled sarcoid reactions. Plasma cells with Russell bodies and immune reaction-induced degranulation of mast cells were also identified. The pathogenesis of the oral findings possibly relates to altered immune reactivity associated with damage to the microvasculature analogous to that in Melkersson-Rosenthal syndrome.

The interaction of bovine dentine phosphophoryn and collagen during fibrillogenesis of collaten in vitro

Bovine dentinal phosphophoryn retards the rate of collagen self-assembly when monomeric collagen is the kinetic unit in fibrillogenesis in vitro. This inhibition is dependent on phosphorylation of the protein and affects the lag period rather than the growth phase for the formation of collagen fibrils. Treatment of the phosphophoryn with calcium markedly increases the inhibitory effect. The use of several fluorescent hydrophobic probes indicates that the calcium-binding to phosphophoryn does not expose any additional interacting hydrophobic domains, thus suggesting that calcium potentiates this interaction, probably by providing a different spatial arrangement of charged groups on this polyelectrolyte, phosphophoryn.

Glycosaminoglycans of predentin, peritubular dentin, and dentin: A biochemical and electron microscopic study

Abstract The glycosaminoglycan (GAG) content of human predentin, peritubular dentin, and dentin was investigated. Predentin and peritubular dentin contain more GAG than dentin proper. The role of GAG in dentin formation and pathosis is discussed.

Abnormal binding of negatively charged serum proteins to diabetic basement membranes is largely a systemic phenomenon

Direct immunofluorescence employing goat anti-human IgG, IgA, IgM, C3 component of complement, fibrinogen, albumin, and polyvalent immunoglobulins was performed on postmortem samples of gingiva, parotid gland, thyroid, kidney, and pancreas tissue of 15 diabetic and 15 control patients. Basement membrane thickness quantification of kidney tubules, gingival capillaries, and parotid gland ducts and acini was also done utilizing a calibrated magnifier on uniformly enlarged photomicrographs which had been specially stained to highlight basement membranes. Results revealed binding of IgG, albumin, and polyvalent immunoglobulin to kidney glomerular and tubular basement membranes and parotid ductal and acinar basement membranes in all diabetic subjects. Thyroid follicular basement membranes were positive in 8 of 15 diabetic patients for the same antisera. All gingival and pancreatic tissue from diabetic and control patients was negative for binding of all serum proteins tested. Basement membrane thickening in kidney tubules and gingival capillaries was observed in diabetic subjects; however, there was no apparent difference between diabetic and control patients in thickness of ductal or acinar basement membranes of the parotid gland.

Collagen synthesis and turnover following particle phagocytosis in dermal fibroblasts.

Dermal fibroblast collagens were isolated after cold pepsin/acetic acid extraction and characterized by differentiated salt precipitation, agarose molecular sieve chromatography, CM-cellulose chromatography, and identification of cyanogen bromide cleavage peptides. Subsequent to particle phagocytosis, collagens recovered as secretory products from latex-treated cells were quantitatively less in total collagen and deficient in type III collagen. Although the total levels of hydroxyproline synthesized were similar to control cell populations, hydroxyproline recovered as non-dialyzable material was only 32% of the total hydroxyproline synthesize. Recovery of exogenous labeled collagen following dialysis, molecular sieve chromatography (Bio-Gel A-5m), and [14C]proline pulse-chase labeling of endogenous collagen, indicates that the alteration in types and quantities of recoverable collagen chains are primarily the result of rapid intracellular turnover.

Expression of melanoma neutral proteinase and collagenase potential by endocytosis.

Abstract Neutral proteinases and collagenase production were determined for four cell lines of B-16 melanoma grown in culture. Endocytosis of 1 μ latex beads by cells in vitro revealed the proteinase production potential of three cell lines. These results were correlative to the proteinases from isolated metastatic lung foci. The association of proteinase secretion to intracellular latex accumulation was best associated with a cell line with low in vitro basal proteinase activities. The role of endocytosis of material by tumor cells to metastases is discussed.