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Regenerative process of hyaline membrane disease. Electron microscopic, immunohistochemical, and biochemical study.

Regression of hyaline membrane disease was studied with light and electron microscopy, immunohistochemistry using the factor VIII-related antigen, lysozyme, alpha 1-antichymotrypsin and surfactant apoprotein antisera, and biochemical quantitation of surfactant disaturated phosphatidylcholine. The repair of hyaline membrane disease occurred by two processes; expansion of atelectatic alveoli and absorption of the hyaline membrane. Regenerative type II pneumocytes containing numerous organelles and lamellar inclusion bodies could be seen three days following birth. Disaturated phosphatidylcholine content also increased three days after birth. Absorption of the hyaline membrane occurred on part of several types of cells such as intra-alveolar macrophages and spindle-shaped cells appearing below or above the hyaline membrane. Intra-alveolar macrophages showed positive immunoreactivity with lysozyme and alpha 1-antichymotrypsin antisera. The spindle-shaped cells indicated negative immunoreactivity with these antisera, though some of them showed positive immunoreactivity with surfactant apoprotein or factor VIII-related antigen antisera. It thus appears that cells of different origin may possibly participate in the absorption of hyaline membrane.

Antigens↗

Respiratory epithelial cell necrosis is the earliest lesion of hyaline membrane disease of the newborn.

The pathogenesis of hyaline membrane disease of the newborn remains controversial. In an attempt to identify early morphologic lesions of hyaline membrane disease, the authors reviewed the histologic sections of lung of all infants that survived for 12 hours or less and all stillborns on which autopsies had been performed at the Johns Hopkins Hospital between 1975 and 1983. Subjects showing more than trivial autolysis or with major congenital malformations were excluded from the study. Among the 70 live births included in this study, 10 (14%) surviving for 7-12 hours had typical hyaline membranes, which are composed of predominantly necrotic epithelial cells. Nine (13%) subjects surviving for 1-10 hours had hyaline membranes plus intraairway necrotic epithelial cell clumps, and 15 (21%) subjects surviving for 10 seconds to 4 hours had only intraairway necrotic epithelial cell clumps. Among the 44 stillborns, 3 (7%) had intraairway necrotic epithelial cell clumps, and 1 of them given resuscitation had hyaline membranes in addition. The results suggest that the initial lesion of hyaline membrane disease of the newborn is necrosis of respiratory epithelial cells, and that this process may begin before birth.

Autopsy↗

Morphologic variants of alcoholic hyalin.

Liver biopsies obtained from 24 patients with alcoholic liver disease were studied by light and electron microscopy. Comparisons of the same cells in adjacent sections revealed that alcoholic hyalin is a fibrillar deposit without limiting membranes and is readily distinguished from giant mitochondria. This characteristic fibrillar structure was encountered in hepatocytes, ductular cells and in benign and malignant hepatomas. Three distinct morphologic forms of alcoholic hyalin were observed: a) bundles of filaments in parallel arrays, b) clusters of randomly oriented fibrils and c) a granular or amorphous substance containing only scattered remains of fibrils. Closely associated with alcoholic hyalin and often found along its entire circumference, were bundles of fine filaments in parallel arrangement of much smaller size. These occasionally displayed variations in orientation and merged with the filaments in the alcoholic hyalin body. Similar fine filaments were observed, in considerable excess, in cells which did not contain alcoholic hyalin. According to our findings, the fine filaments and the significantly larger filaments in alcoholic hyalin could be parts of a contractile system elaborated by host cells during the course of hepatic injury.

Alcoholism↗

A ten-year retrospective study of pink and yellow neonatal hyaline membrane disease.

Since it was first described several years ago, yellow bilirubin staining of the pulmonary membranes in neonatal hyaline membrane disease has apparently become more common. In a retrospective study of neonatal autopsy experience, it was found that as more of the premature infants survived longer, yellow hyaline membrane disease was a more frequent finding, increasing from 7% of all newborns having hyaline membrane disease at autopsy in 1970 to 50% in 1980. In comparing 499 cases with eosinophilic hyaline membranes with 168 cases of yellow membranes, newborns with bilirubin staining of the pulmonary membranes were found to be more premature (P less than .02), had smaller autopsy weight (P less than .002), and survived longer (P less than .00001). When multiple clinical parameters were compared between a group of infants with yellow membranes and a group of infants with pink membranes who were matched for gestational age, year of birth, and length of survival, no differences were found between the two groups. No correlation was found between kernicterus and yellow staining of the pulmonary hyaline membranes in the first years of the study, but there was a strong correlation in the last 5 years, coincident with the increase in the rate of yellow hyaline membrane disease found at autopsy. The gross bilirubin staining of the brain was the secondary type of kernicterus, not toxic bilirubin encephalopathy. The observation of bilirubin staining in the lung and in the brain correlates with prolonged survival in some very small premature infants. This does not appear to be a manifestation of bilirubin toxicity, but rather a marker of prior tissue damage.

Body Weight↗

A 9.6 S protein is the third calcium-insoluble component of the sea urchin hyaline layer.

A third major, calcium-insoluble component of the sea urchin (Strongylocentrotus purpuratus) hyaline layer has been purified and physically characterized. In the absence of divalent cations, the native, soluble protein has a sedimentation coefficient of 9.6 S and a molecular weight of 4.5 +/- 0.1 x 10(5). These data indicate that this large protein assumes an elongated, nonspherical conformation in solution. Its sedimentation behavior and its mobility on nondenaturing electrophoretic gels distinguish the 9.6 S protein from the 11.6 S and 6.4 S hyalin proteins we have previously characterized. That the 6.4 S, 9.6 S, and 11.6 S proteins are the major calcium-insoluble structural components of the hyaline layer is supported by the fact that we have found them in a variety of hyalin protein fractions prepared by a number of standard approaches. All three proteins are precipitated by calcium ions, thus fitting the operational definition of hyalin. Evidence is presented that the 11.6 S protein may overlie the 9.6 S protein in the hyaline layer.

Animals↗

Hyalinizing trabecular carcinoma of the thyroid gland.

We report four unusual cases of hyalinizing trabecular thyroid tumors, three of which displayed capsular and/or blood vessel invasion and were classified as minimally invasive carcinomas. These three patients were all euthyroid women aged 18, 39, and 62 years. The youngest patient also had familial polyposis, while the oldest patient was being followed for Hashimoto's thyroiditis. All three lesions were solitary nodules, were "cold" by radioactive iodine thyroid scan, and ranged from 2.5 to 4.0 cm in diameter. The tumors were encapsulated and had growth patterns and cytologic features similar to those described for hyalinizing trabecular adenomas. In fact, the only difference between these minimally invasive hyalinizing trabecular carcinomas and the corresponding adenomas was the presence of capsular invasion in all three of the cases and vascular invasion in two. All three patients are free of recurrent or metastatic disease at 1 to 2 years' follow-up. The fourth patient, a 48-year-old woman, had a micropapillary carcinoma within a hyalinizing trabecular adenoma. She is also free of disease 5 years following excision of the involved lobe. These findings suggest that hyalinizing trabecular thyroid tumors have a malignant counterpart, similar to conventional follicular adenomas, and that papillary thyroid carcinomas may arise within hyalinizing trabecular thyroid tumors.

Adenocarcinoma↗

Characterization of spontaneous and decalin-induced hyaline droplets in kidneys of adult male rats.

Studies were conducted to gain additional information about the spontaneous and decalin-exacerbated formation of hyaline droplets within the cytoplasm of proximal convoluted tubule (PCT) epithelial cells of the adult male rat. Renal cortical tissue protein patterns determined through two-dimensional gel electrophoresis revealed four species of a low-molecular-weight protein (18,000-20,000 daltons). Treatment groups differed only with respect to this protein, the relative concentrations of which paralleled the numbers of hyaline droplets in mature treated and untreated male rats. The increase in the numbers of hyaline droplets and protein accumulation were dose related. Neither this protein or hyaline droplets were detected in the renal cortical tissues of untreated or decalin-exposed adult female or immature male control rats. However this protein, and hyaline droplet formation, could be induced in the kidneys of adult, ovariectomized female rats by repeated testosterone injections. This protein was then demonstrated to be immunologically identical to alpha 2u-globulin, a protein synthesized by hepatic parenchymal cells. Alpha 2u-globulin protein has also been shown to be the major urinary component responsible for the proteinuria routinely observed in normal control adult male rats. PCT epithelial cell reabsorption and lysosomal accumulation of alpha 2u-globulin, reflected morphologically as hyaline droplets, occurs spontaneously only in the mature male rat. Decalin, a model compound, exacerbates this accumulation as a specific integral step in the pathogenesis of the nephropathy induced in male rats by volatile hydrocarbons. Hence, since men and women lack this specific PCT cell peculiarity, they would not be expected to respond to decalin exposure in a manner similar to the male rat.

Aging↗

Hyalinizing trabecular adenoma and papillary carcinoma of the thyroid gland express different cytokeratin patterns.

It has recently been suggested that hyalinizing trabecular adenoma of the thyroid is an encapsulated variant of papillary carcinoma because of certain similarities of their histology, the occasional occurrence of both tumors in the same gland, and their similar pattern of expression of cytokeratins, including staining for cytokeratin 19. To investigate this notion further, we examined immunocytochemically the expression of a series of cytokeratins in 12 hyalinizing trabecular adenomas and six papillary carcinomas. Hyalinizing trabecular adenoma showed no or minimal reactivity for cytokeratin 19, whereas papillary carcinoma was almost always strongly reactive. Also, hyalinizing trabecular adenoma showed no staining for high-molecular-weight (HMW) cytokeratin, whereas papillary carcinoma was strongly positive. Thus, there are different patterns of cytokeratin 19 and HMW cytokeratin expression in hyalinizing trabecular adenoma and papillary carcinoma. The findings do not support the suggestion that hyalinizing trabecular adenoma is an encapsulated variant of papillary carcinoma.

Adenoma↗

Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics.

Hyalinizing trabecular tumors of the thyroid are interesting but uncommon neoplasms. They have been classified as benign hyalinizing trabecular adenomas or malignant hyalinizing trabecular carcinomas. They share both epidemiologic and morphologic features with papillary carcinoma, and there has been much speculation about the relationship between these two entities. Because RET/PTC gene rearrangements are specific to papillary thyroid carcinoma, the authors examined the presence of RET/PTC-1, -2, and -3 in eight hyalinizing trabecular tumors using reverse transcription-polymerase chain reaction with Southern hybridization and immunohistochemistry. They detected the presence of a RET/PTC gene rearrangement in six of the eight hyalinizing trabecular tumors. This confirms the long-standing suspicion that hyalinizing trabecular tumors do indeed represent a morphologic variant of papillary carcinoma.

Adenoma↗

Chondroid syringoma with hyaline cell change.

Four cases of chondroid syringoma containing large numbers of hyaline or plasmacytoid cells are described. Three cases occurred in the hand and one in the foot. Hyaline cells are commonly seen in mixed tumours and myoepitheliomas of salivary glands and rarely in chondroid syringomas. The hyaline-cell change in three of the cases initially caused diagnostic difficulties and the possibility of sarcoma was raised in two cases. In addition to the characteristic hyaline cells, the presence of tubulo-glandulo-ductal structures, benign squamous epithelium and myxochondroid stroma aided diagnosis. Immunohistochemically, the hyaline cells exhibited positivity for vimentin, cytokeratin, S-100 protein, carcino-embryonic antigen, focal glial fibrillary acidic protein (3 cases), neuron-specific enolase (3 cases) and focal alpha-smooth muscle actin (2 cases). Occasional cells were Ber EP4 positive (2 cases). In some cells, a striking peripheral ring-like positivity for cytokeratin and S-100 protein was noted. Ultrastructurally, desmosomes, varying numbers of tonofibrils and non-bundling intermediate filaments were seen. Scanty fine filaments with vague focal densities were detected in some cells. Our studies suggest that the hyaline cells represent modified epithelial as well as myoepithelial cells. One of our cases also exhibited collagenous spherulosis.

Actins↗

Follicular dendritic cell sarcoma complicated by hyaline-vascular type Castleman's disease in a schizophrenic patient.

Follicular dendritic cell (FDC) sarcoma is an exceedingly rare neoplasm of unknown pathogenesis. A case of FDC sarcoma complicated by the hyaline-vascular type Castleman's disease occurring in a schizophrenic male is presented. Swelling of the left cervical lymph node appeared in a 44-year-old male schizophrenic who had been medicated with major tranquilizers for 20 years. He had had a history of cervical lymphadenopathy 14 years before, for which a diagnosis of hyaline-vascular type Castleman's disease had been made. The present specimen, obtained from the same site, was an enlarged lymph node heavily infiltrated with oval to spindle-shaped atypical cells but was uninvolved at the periphery. The infiltrating cells showed nodular or sheet-like growth, occasionally taking fascicular or storiform patterns. Follicular involvement was also common. Peculiarly, various amounts of small lymphocytes were intermingled with the neoplastic cells. The atypical cells expressed two FDC-specific antigens, DRC-1 and Ki-M4 antigen, together with a few other markers that are shared by FDC, including CD21 and HLA-DR. These findings clearly show the tumor to be FDC sarcoma. In addition, a peculiar fibro-hyalinous change in the lymph follicle, which is compatible with hyaline-vascular type Castleman's disease, was noted at the periphery of the lymph node where neoplastic cells had not infiltrated. Surprisingly, similar hyaline-vascular changes were observed in the previous biopsy taken 14 years ago. Meanwhile, Kaposi's sarcoma-associated herpesvirus, which is often identified from generalized Castleman's disease, was not identified in the present case by polymerase chain reaction study. Thus, this case is unique in two aspects: (i) the overlap of FDC sarcoma with hyaline-vascular type follicular changes; and (ii) its occurrence in a schizophrenic patient.

Adult↗

Demonstration of fibrils in the hyaline globules of yolk sac tumor with parietal differentiation in fine-needle aspiration smears.

Hyaline globules of the yolk sac tumor (YST) have been described as homogeneous pink intracellular globules and intercellular basement membrane material [Akhtar et al.: Diagn Cytopathol 1990:6:184-192]. In Diff-Quik-stained air-dried smears of a lung fine-needle aspiration (FNA) of YST metastatic from anterior mediastinum, short curvilinear nonbranching fibrils are demonstrated in the metachromatic hyaline substance. The fibril-containing hyaline substance, which presents as intracellular globules as well as extracellular matrix deposits, is a diagnostic clue for YST with parietal differentiation [Ulbright et al.: Am J Surg Pathol 1986; 10:151-164]. The fibrils are not observed in the translucent homogeneous golden yellow hyaline substance in the Papanicolaou preparation. The fibrils are speculated to be the core protein of proteoglycans. To the best of the author's knowledge, this is the first demonstration of fibrils in the hyaline substance of YST with parietal differentiation.

Adult↗

Changes in anti-oxidant enzymes and lipid peroxidation in hyaline membrane disease.

This study was conducted to elucidate the changes in key antioxidant enzymes e.g. Superoxide dismutase (SOD), Catalase and Glutathione peroxidase (GPx) along with lipid peroxidation (LPO) in preterm newborns having hyaline membrane disease (HMD) and thus to find out role of free radicals mediated injury in this disease. Twenty one preterm appropriate for gestational age newborns were included in the study. Eleven of them had hyaline membrane disease and ten were controls without any disease. Status of superoxide dismutase, glutathione peroxidase and catalase, the three main antioxidant enzymes and lipid peroxidation was monitored at 12-24 hours of age. SOD and catalase were found significantly elevated in cases having hyaline membrane disease along with significantly more lipid peroxidation. It is evident that free radicals result in the induction of the antioxidant enzymes; however, the elevated enzymes are unable to counteract the high concentration of the free radicals which are being produced in the diseased cases and leads to increase in lipid peroxidation in hyaline membrane disease. It is concluded that free radicals play a significant role in hyaline membrane disease and the preterm newborns have ability to induce antioxidant enzymes in response to oxidative stress.

Catalase↗

Surfactant replacement therapy in utero for prevention of hyaline membrane disease in the preterm baboon.

OBJECTIVE: A previous study of intraamniotic administration of surfactant in preterm rabbit fetuses demonstrated that exogenous surfactant can be taken up into the lungs from amniotic fluid in quantities sufficient to alter pulmonary mechanical properties. On the basis of these findings we chose to test the hypothesis that intraamniotic administration of surfactant to the preterm baboon 24 hours before delivery will prevent the development of clinical and pathological aspects of hyaline membrane disease. STUDY DESIGN: Characteristics of hyaline membrane disease in the preterm baboon model include atelectasis, the formation of hyaline membranes in the airways and distal air saccules, overexpansion of distal airways, and disruption of airways by barotrauma associated with neonatal intensive care practices. Nine preterm baboons were treated with either saline solution (n = 4) or surfactant (n = 5) by intraamniotic injection on 136 to 137 days' gestation. One day later fetuses were delivered by cesarean section and maintained for 24 hours with standard neonatal intensive care techniques. RESULTS: All neonates completed the protocol, and surfactant-treated animals had better clinical courses as documented by Pao2/PAO2 (p < 0.05), FIO2 (p < 0.005), and Paco2 (p < 0.05). Significant radiographic differences (p < 0.02) were noted to be the result of surfactant treatment. No differences in ventilator pressures or neonatal cardiovascular parameters were found. Significant differences in pulmonary pathologic conditions (p < 0.01) were also found, but all animals had some degree of pathologic pulmonary changes associated with hyaline membrane disease. CONCLUSION: Therefore a single treatment with surfactant in utero significantly improved the clinical course but did not completely prevent hyaline membrane disease in an established animal model.

Amniocentesis↗

"Hyaline cells" in pleomorphic adenoma of salivary gland origin.

Fifty-two cases of pleomorphic adenoma of minor salivary gland origin and seventy-two cases of pleomorphic adenoma of major salivary gland origin were examined for the presence of hyaline cells (plasmacytoid cells). Hyaline cells were found in 38 percent of the minor salivary gland cases and 21 percent of the major salivary gland cases. When stained with hematoxylin and eosin, the hyaline cells exhibited an eccentric nucleus and a striking homogenous, ground-glass, eosinophilic cytoplasm. At the ultrastructural level, the cytoplasm of the hyaline cells was closely packed with intermediate-sized filaments having no apparent orientation. It is suggested that the hyaline cells are modified myoepithelial cells.

Adenoma, Pleomorphic↗

Actin, myosin and alpha-actinin containing filament bundles in hyaline cells of the caiman cochlea.

Hyaline cells of the auditory organ of the spectacled caiman contain smooth muscle-like filament bundles within their basal cell pole. These bundles were heavily labeled with antibodies to actin, myosin and alpha-actinin (muscular Z-line protein). Since hyaline cells are firmly attached to the basilar membrane these cells may actively modify the stiffness of the basilar membrane. A contractile mechanism in hyaline cells might affect frequency tuning of primary auditory afferents. This frequency tuning has been shown to be a temperature-dependent process in caimans and other submammalian species. The presence of synaptic contacts between efferent nerve fibres and hyaline cells suggests neural control of hyaline cell activity.

Actinin↗

Further observations on cytoplasmic hyaline in the lung.

Cytoplasmic hyaline material resembling Mallory's alcoholic hyaline has previously been described in pulmonary alveolar cells of patients with asbestosis. We present 14 new cases of cytoplasmic hyaline found in patients with a variety of processes causing damage to the alveolar lining; these include cases of radiation pneumonia, diffuse interstitial fibrosis, organizing bacterial pneumonia, as well as asbestosis. Hyaline was found only in the setting of an unusual type II cell change, which ultrastructurally appeared to represent squamous metaplasia. We conclude that pulmonary cytoplasmic hyaline is not specific for asbestosis but rather is a nonspecific reaction to injury;

Adult↗

Hyaline globules in renal cell carcinomas and oncocytomas.

Hyaline globules (extracellular collections of amorphous material) are identified in 10 of 59 renal cell carcinomas (RCC) and in 2 of 9 oncocytomas. Immunohistochemical characterization of these PAS-positive structures revealed the presence of basement membrane material in most cases. Collagen type IV and laminin were the predominant constituents, whereas fibronectin was detected only occasionally. Electron microscopic examination of the globules showed concentric multilayered accumulations of basement membrane material. No such structures were recognized in 8 renal pelvic transitional cell carcinomas nor in 2 metanephric adenomas. RCC associated hyaline globules were always negative for alpha1-antitrypsin (AAT), alpha-fetoprotein (AFP), amyloid A, cytokeratin, vimentin, or lysozyme. These features differ from those of the hyaline globules previously described in other malignant neoplasms, notably AAT-positive hyaline globules in ovarian tumors, and AFP-positive globules in yolk sac tumors. Identification and immunohistochemical characterization of hyaline globules in metastases may be helpful in determining the origin of occult primary tumors.

Adenoma↗