S-100 Protein-positive Cells Research Articles

Dendritic Cell Infiltration In A Patient With Seminomatous Germ Cell Tumor Of The Testis: Is There A Relationship With Infertility And Tumor Stage?

Inflammatory cells, such as dendritic cells, are considered to trigger the antitumoral immune response against tumors, such as testicular cancer. Male infertility associated with cancer may be due to endocrine or immunological factors. We investigated possible associations of antigen expression with dendritic cells, histiocytic cells and seminoma stage as well as with impaired spermatogenesis. From 1992 to 1999, 30 patients with seminoma underwent orchiectomy at our center, including 14 who underwent spermiography before orchiectomy. Streptavidin-biotin immunostaining was performed on paraffin -embedded tumor specimens using antibodies against protein S-100 for dendritic cells and CD68-KP1 antigen. Light infiltration by less than 20 dendritic cells and less than 103 CD68+ cells was associated with tumor size greater than 1.5 cm. in 75% and 80% of patients, respectively. Strong infiltration by greater than 20 dendritic cells and greater than 103 CD68+ cells was associated with negative lymph nodes in 86% of patients. Slight infiltration by dendritic cells was observed in 71% of patients with a sperm count of greater than 8.6 million per ml. and in 100% with more than 45% motile sperm (p not significant and 0.02, respectively). Necrospermia increased with dendritic and CD68+ cell infiltration. No association was noted among preoperative serum tumor marker levels, the sperm count and immunostaining. Sperm autoimmunity is a plausible mechanism of infertility in men with germ cell tumors. Dendritic cells may induce antitumor cell cytotoxic reactions, but may also be cytotoxic to sperm cells or lead to inhibited spermatogenesis. Further studies focusing on tumor rejection antigen and the cloning of specific cytotoxic T lymphocyte against gametes are required to confirm these finding.

Topical application of HIV DNA vaccine with cytokine-expression plasmids induces strong antigen-specific immune responses

The topical application of DNA vaccine to the skin is a useful method of immunization because of its simplicity, painlessness and economy. But the immune responses that it elicits are relatively low. In this study, we administered human immunodeficiency virus type-1 (HIV-1) DNA vaccine with cytokine-expressing plasmids to the skin of mice by a new topical application technique involving prior elimination of keratinocytes using fast-acting adhesive. Our results revealed that the topical application of HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. Co-administration of the DNA vaccine with cytokine expression plasmids of IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by this new method raised the levels of both the HIV-specific cytotoxic T lymphocyte (CTL) response and delayed-type hypersensitivity (DTH) and facilitated the induction of substantial immune responses by DNA vaccine. Skin biopsy sections, thus, immunized showed significant increases of S-100 protein-positive dendritic cells (DCs). These results suggest that the topical application method described here is an efficient route of DNA vaccine administration and that the immune response may be induced by DNA plasmids taken in by DCs, Langerhans cells (LCs), or others such as antigen-presenting cells. This new topical application is likely to be of benefit in clinical use.

NF1 Deletions in S-100 Protein-Positive and Negative Cells of Sporadic and Neurofibromatosis 1 (NF1)-Associated Plexiform Neurofibromas and Malignant Peripheral Nerve Sheath Tumors

Although plexiform neurofibroma (PN) is thought to represent a benign neoplasm with the potential for malignant transformation (malignant peripheral nerve sheath tumor; MPNST), its neoplastic nature has been difficult to prove due to cellular heterogeneity, which hampers standard molecular genetic analysis. Its mixed composition typically includes Schwann cells, fibroblasts, perineurial-like cells, and mast cells. Although NF1 loss of heterozygosity has been reported in subsets of PNs, it remains uncertain which cell type(s) harbor these alterations. Using a dual-color fluorescence in situ hybridization and immunohistochemistry technique, we studied NF1 gene status in S-100 protein-positive and -negative cell subpopulations in archival paraffin-embedded specimens from seven PNs, two atypical PNs, one cellular/atypical PN, and eight MPNSTs derived from 13 patients, seven of which had neurofibromatosis type 1 (NF1). NF1 loss was detected in four of seven PNs and one atypical PN, with deletions entirely restricted to S-100 protein-immunoreactive Schwann cells. In contrast, all eight MPNSTs harbored NF1 deletions, regardless of S-100 protein expression or NF1 clinical status. Our results suggest that the Schwann cell is the primary neoplastic component in PNs and that S-100 protein-negative cells in MPNST represent dedifferentiated Schwann cells, which harbor NF1 deletions in both NF1-associated and sporadic tumors.

Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma.

Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate-shaped S100 protein-positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese-superoxide dismutase. In addition to faint reactivity with anti-cytokeratin 8, 18 antibody, many cells were densely positive with anti-cytokeratin 1, 5, 10, 14 antibody. These results indicate that radiation- induced fibrosis is associated with an increased number of folliculo-stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.

Vaginal Leiomyoma with Heterologous Paragangliomatous Elements

A vaginal leiomyoma with heterologous paragangliomatous elements is reported. The patient was a 62-year-old woman who presented with uterovaginal prolapse and an asymptomatic vaginal mass that had been present for many years. Histology of the excised mass showed a leiomyoma in a submucosal location, with irregularly shaped islands of chief cells scattered throughout the lesion. These cells were arranged in nests and were surrounded by S100 protein-positive sustentacular cells. The chief cells showed immunoreactivity with chromogranin, synaptophysin, and neuron-specific enolase. Although various heterologous elements are commonly encountered within uterine leiomyomata, such elements have not been described within vaginal leiomyomata. Furthermore, the occurrence of paragangliomatous tissue within leiomyomata has not been reported to date. Int J Surg Pathol 8(4):359-365, 2000

Occult neurofibroma and increased S100 protein in the skin of patients with neurofibromatosis type 1: new insight to the etiopathomechanism of neurofibromas.

Neurofibromas represent proliferation of the connective tissue cells of peripheral nerves and deposition of collagenous extracellular matrix. There is evidence that the appearance and growth of neurofibromas may be associated with prior or ongoing mechanical trauma in patients with neurofibromatosis type 1 (NF1). To study the histologic characteristics of apparently healthy skin of patients with NF1. The histologic features of healthy-looking skin of patients with NF1 were analyzed. University hospital. Ten patients who fulfilled the criteria for NF1. Punch biopsy specimens of healthy-looking skin of the forearm from 9 volunteer patients and of the upper eyelid during cosmetic operation from 1 volunteer patient were obtained. The main outcomes were not predicted, and the hypothesis was formulated during data collection. Apparently unaffected skin of 5 patients with NF1 was studied by routine histologic testing with respect to expression of S100 protein. Unexpectedly, analysis of the samples revealed the presence of a small neurofibroma tumor in one of the samples. The tumor was located in deep dermis around a hair follicle. In addition, neurofibromatous tissue not large enough to be called a tumor was found on the same anatomical location in another patient. In further studies, 10 punch biopsy specimens of apparently healthy skin from patients with NF1 were similarly sectioned and analyzed. No tumors were found in these additional samples. In 4 patients, however, abundant S100 protein-positive cells were located within collagenous extracellular matrix surrounding hair follicles. The skin of patients with NF1 might be more widely affected than previously thought and occult neurofibromas are not rare.

The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine.

The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c+, CD8+ cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100+ cells or both CD8+ and CD11c+ cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.

An immunocytochemical study of mitochondrial manganese-superoxide dismutase in the rat hippocampus after kainate administration

We examined the immunocytochemical distribution of mitochondrial Mn-superoxide dismutase (SOD-2) in the rat hippocampus after systemic injection of kainic acid (KA), in order to understand SOD-2-responsible antioxidant defense mechanism during the neurodegenerative process. SOD-2 immunostaining was more intense in CA3 pyramidal neurons than in CA1 neurons in the normal hippocampus. The immunoreactivity in region CA1 was reduced without significant neuronal losses within 12 h of KA injection. The CA1 and CA3 neurons lost their immunoreactivity, whereas SOD-2-positive glia-like cells proliferated, mainly throughout the CA1 sector, and had intense immunoreactivity 3 and 7 days after KA injection. This immunocytochemical distribution of SOD-2-positive non-neuronal elements was similar to that of glial fibrillary acidic protein (GFAP) and S-100 protein-positive cells. Activated microglial cells selectively marked with lectin occurred in the areas affected by the KA-induced lesion. Double-labeling immunocytochemistry showed the co-localization of SOD-2-positive non-neuronal cells and GFAP or S-100 protein-like immunoreactivity in the same cells. This suggests that astroglial cells mobilized to synthesize of SOD-2 protein in a response to KA toxicity designed to reduce the oxidative damage.

Expression of c-erbB-2 and Distribution of S-100 Protein Positive Dendritic Cells in Squamous Cell Carcinoma of the Uterine Cervix

Expression of c-erbB-2 and Distribution of S-100 Protein Positive Dendritic Cells in Squamous Cell Carcinoma of the Uterine Cervix

Folliculo-stellate Cells in Pituitary Adenomas of Patients with Acromegaly

Pituitary adenoma tissue from patients with acromegaly (n = 286) was obtained by surgery and examined for folliculo-stellate cells by immunostaining for S100 protein. The number of immunostained cells varied from one adenoma to another. A hundred and ninety-eight pituitary adenomas (69%) contained S100 protein positive cells corresponding to folliculo-stellate cells (FSC): in 100 cases (35%), only few sparse FSC were found, in 43 cases (15%) FSC were scattered throughout the adenoma, and in 55 cases (19%) there was an abundance of FSC. There were no significant differences regarding sex or age of the patients. The relative amount of FSC vaired among different adenoma types. Plurihormonal adenomas showed the highest FSC density, whereas the majority of monohormonal adenomas contained only few or no FSC. Patients with pituitary adenomas containing scattered FSC had a significantly higher preoperative mean GH level than patients with pituitary adenomas not having FSC. There was a negative correlation between the FSC density in adenoma tissue and the preoperative mean PRL level. There was no correlation between the tumour size and the amount of FSC. Our data indicate no effect of the duration of symptoms on the FSC density and do not suggest a correlation between FSC density and the percentage of a certain hormone-secreting cell type.

Squamous Cell Carcinoma of the Tongue with a Sarcomatoid Micronodule: Report of a case.

We report a case of squamous cell carcinoma of the tongue with a sarcomatoid micronodule in a 76-year-old man. A white lesion with erosion was observed on the right inferior surface of the tongue, and carcinomatous change of leukoplakia was suspected. Microscopic examination of a biopsy specimen revealed a micronodular proliferation of spindle cells with continuity to invasive squamous cell carcinoma . Although spindle cells did not demonstrate epithelial characteristics immunohistochemically , S-100 protein-positive cells were observed among them. Based on these findings, sarcomatoid differentiation of squamous cell carcinoma to nerve sheath cells, myofibroblasts or Langerhans cells was suggested.

Searching for an intrinsic neuroendocrine cell in the kidney: An immunohistochemical study of the fetal, infantile and adult kidney

The pathogenesis of primary renal carcinoid tumor is unknown. One hypothesis has implied derivation from a yet unrecognized intrinsic neuroendocrine cell in the renal parenchyma/hilum either as a minute endocrineparacrine constituent or resulting from entrapped/misplaced progenitor cells of the so-called dispersed neuroendocrine system during organogenesis. Immunohistochemical staining for chromogranin and serotonin was systematically performed on a whole-mount and geographically mapped normal adult kidney, kidneys from 15 fetuses (age range: 15 to 38 weeks), and renal specimens from 18 infants/children (age range: 7 days to 123 months). Minute paraganglion nests (composed of chromogranin positive/serotonin negative chief cells and S-100 protein positive dendritic cells) were incidentally detected within the renal hilum primitive stroma (unilaterally) of two fetuses at 22 and 26 weeks. Sequestration and persistence of such paraganglion nests during renal growth and maturation would offer a basis for the rare occurrence of extra-adrenal paraganglioma involving the renal hilum/pedicle. Otherwise, no neuroendocrine cell was detected within the renal parenchyma or hilum, therefore not validating/sustaining the aforementioned hypothesis in the pathogenesis of renal carcinoid tumor.

S-100 protein-positive dendritic cells in follicular lesions of the thyroid.

Little is known about the role of S-100 protein-positive dendritic cells in follicular lesions of the thyroid. In 36 cases of adenomatous goitre, 18 cases of follicular adenoma, and 7 cases of follicular carcinoma, we investigated the incidence and distribution of S-100 protein-positive dendritic cells using immunohistochemical staining. Four cases (10.5%) of adenomatous goitre, five cases (31.3%) of follicular adenoma, and 6 cases (85.7%) of follicular carcinoma contained S-100 protein-positive dendritic cells in the subcapsular area and/or the hyalinized stroma. Dendritic cells in the subcapsular area were observed only in lesions with thick capsules and not those with thin capsules. In most cases of follicular carcinoma, + + to + + + of the dendritic cells was seen together with a few lymphocytes and fibroblasts in the subcapsular areas. In contrast, cases of adenomatous goitre and follicular adenoma showed only a few dendritic cells without any inflammatory cells. Dendritic cells in follicular thyroid lesions may play some role in capsular formation or may be a secondary phenomenon due to capsular formation.

Pulmonary paraganglioid carcinoids and bcl-2 oncoprotein expression

Bcl-2 protein immunoreactivity was examined in 10 pulmonary carcinoid tumors with abundant S-100 protein-positive sustentacular cells (SCs) diagnosed as paraganglioid carcinoids. Its positivity in the mentioned tumors was compared with that of neoplasms formed of neuroendocrine cells only (30 pulmonary carcinoids), and with another group of 30 lesions consisting of neuroendocrine and sustentacular elements, i.e., paragangliomas (11 paragangliomas of the glomus caroticum and 9 jugulotympanic paragangliomas [JPTGs]), pheochromocytomas (5 cases), and a rare form of pulmonary tumorlets (PTUs) with a high frequency of SCs (5 cases). Bcl-2 protein was found in all 70 examined cases, and its expression showed no difference between the examined groups. On the basis of these results, bcl-2 protein expression was not found to be an indicator for either survival or useful for the differential diagnosis of pulmonary carcinoid tumors.

Class III β‐Tubulin isotype (β III) in the adrenal medulla: III. Differential expression of neuronal and glial antigens identifies two distinct populations of neuronal and glial‐like (sustentacular) cells in the PC12 rat pheochromocytoma cell line maintained in a gelfoam matrix system

Background The rat PC12 pheochromocytoma cell line provides an established system for the study of neuronal differentiation. To our knowledge, glial differentiation has not been reported in this cell line. Methods We have studied, by immunohistochemistry and immunoblotting, the presence of neuronal cytoskeletal antigens [class III β-tubulin isotype (β III), microtubule associated proteins MAP2, MAP1B and tau, and different neurofilament (NF) protein components], and synaptophysin in comparison with the glial fibrillary acidic protein (GFAP) and S-100 protein in the PC12 cell line. In three different experiments, PC12 cells were maintained in a three-dimensional gelatin foam (Gelfoam) matrix system for up to 34 days with and without treatment with 1 mM dibutyryl cyclic (dc)AMP. Immunohistochemistry was performed on explants ranging from 2 to 32 days-in vitro, which were fixed in either Bouin's solution, 70% ethanol, or 10% neutral-buffered formalin and embedded in paraffin. Immunoblotting was performed on Gelfoam explants with a panel of antibodies against all aforementioned neuronal and glial markers. Additional immunoblot experiments using anti-GFAP and anti-β III monoclonal antibodies in cell suspensions and homogenates from PC12 monolayer cultures were carried out to compare growth conditions in relation to the expression of these proteins. Results β III and MAP2 were demonstrated by immunohistochemistry and immunoblotting of PC12 explants maintained for up to 32 days in Gelfoam matrices with and without treatment with dcAMP. Intense filamentous and granular β III staining of PC12 cells was observed in dcAMP-treated cultures concomitant with neuronal morphologic alterations (neuritogenesis and ganglionic phenotype). In untreated cultures, β III staining was present in less differentiated cells, as well in cells undergoing neuritic development. The neuronal phenotype of PC12 cells was confirmed by staining for MAP2, tau, and NF proteins, as well as for synaptophysin. The presence of β III, MAP2, MAP1B, tau, and NF proteins was confirmed by immunoblotting. Clusters of GFAP-positive and S-100 protein-positive spindle cells, phenotypically distinct from the chromaffin-like or neuronal cells, were demonstrated in Gelfoam explants at 5–30 days in vitro. In 30-day-old cultures treated with dcAMP, there was strong filamentous GFAP and diffuse S-100 protein staining in an increased number of sustentacular-like PC12 cells. GFAP staining was corroborated by immunoblotting of explants maintained under identical conditions in vitro. In contrast, immunoblots performed on homogenates from PC12 suspension and monolayer cultures were GFAP-negative. Conclusions Neuronal and glial-like, presumed sustentacular, phenotypes were demonstrated in PC12 cells grown in Gelfoam matrices with and without treatment with dcAMP for up to 34 days. To our knowledge, the occurrence of glial differentiation in the PC12 line is a hitherto unreported finding. Adult rat medullary sustentacular cells are known to express S-100 and GFA proteins (Suzuki and Kachi, Kaibogaku Zasshi—J Anat 70(2): 130–139, 1995), and the organ culture system employed in our study may well have favored this direction of differentiation. Anat. Rec. 250:351–365, 1998. © 1998 Wiley-Liss, Inc.

Class III β-Tubulin isotype (β III) in the adrenal medulla: III. Differential expression of neuronal and glial antigens identifies two distinct populations of neuronal and glial-like (sustentacular) cells in the PC12 rat pheochromocytoma cell line maintained in a gelfoam matrix system

The rat PC12 pheochromocytoma cell line provides an established system for the study of neuronal differentiation. To our knowledge, glial differentiation has not been reported in this cell line. We have studied, by immunohistochemistry and immunoblotting, the presence of neuronal cytoskeletal antigens [class III beta-tubulin isotype (beta III), microtubule associated proteins MAP2, MAP1B and tau, and different neurofilament (NF) protein components], and synaptophysin in comparison with the glial fibrillary acidic protein (GFAP) and S-100 protein in the PC12 cell line. In three different experiments, PC12 cells were maintained in a three-dimensional gelatin foam (Gelfoam) matrix system for up to 34 days with and without treatment with 1 mM dibutyryl cyclic (dc)AMP. Immunohistochemistry was performed on explants ranging from 2 to 32 days-in vitro, which were fixed in either Bouin's solution, 70% ethanol, or 10% neutral-buffered formalin and embedded in paraffin. Immunoblotting was performed on Gelfoam explants with a panel of antibodies against all aforementioned neuronal and glial markers. Additional immunoblot experiments using anti-GFAP and anti-beta III monoclonal antibodies in cell suspensions and homogenates from PC12 monolayer cultures were carried out to compare growth conditions in relation to the expression of these proteins. Beta III and MAP2 were demonstrated by immunohistochemistry and immunoblotting of PC12 explants maintained for up to 32 days in Gelfoam matrices with and without treatment with dcAMP. Intense filamentous and granular beta III staining of PC12 cells was observed in dcAMP-treated cultures concomitant with neuronal morphologic alterations (neuritogenesis and ganglionic phenotype). In untreated cultures, beta III staining was present in less differentiated cells, as well in cells undergoing neuritic development. The neuronal phenotype of PC12 cells was confirmed by staining for MAP2, tau, and NF proteins, as well as for synaptophysin. The presence of beta III, MAP2, MAP1B, tau, and NF proteins was confirmed by immunoblotting. Clusters of GFAP-positive and S-100 protein-positive spindle cells, phenotypically distinct from the chromaffin-like or neuronal cells, were demonstrated in Gelfoam explants at 5-30 days in vitro. In 30-day-old cultures treated with dcAMP, there was strong filamentous GFAP and diffuse S-100 protein staining in an increased number of sustentacular-like PC12 cells. GFAP staining was corroborated by immunoblotting of explants maintained under identical conditions in vitro. In contrast, immunoblots performed on homogenates from PC12 suspension and monolayer cultures were GFAP-negative. Neuronal and glial-like, presumed sustentacular, phenotypes were demonstrated in PC12 cells grown in Gelfoam matrices with and without treatment with dcAMP for up to 34 days. To our knowledge, the occurrence of glial differentiation in the PC12 line is a hitherto unreported finding. Adult rat medullary sustentacular cells are known to express S-100 and GFA proteins (Suzuki and Kachi, Kaibogaku Zasshi-Anat 70(2): 130-139, 1995), and the organ culture system employed in our study may well have favored this direction of differentiation.

Unusual expression of S-100 protein in histiocytic neoplasms.

Twenty-nine cases of histiocytic neoplasms, some resembling juvenile xanthogranuloma (JXG) and others resembling reticulohistiocytoma (RH), were evaluated. Immunohistochemical stains were performed. In this series, seven cases were identified that expressed S-100 protein positive cells. The S-100 positive cells were predominantly large mononuclear and multinucleated histiocytes with eosinophilic cytoplasm, but also in some cases xanthomatous cells and Touton giant cells. These cells also expressed a positive reaction for vimentin, KP-1, and Factor XIIIa. There was no reactivity observed for monoclonal antibody 010(CD1a). A positive reaction for S-100 protein is conventionally accepted as a useful differentiating feature between histiocytosis X and non-X histiocytosis such as JXG and RH. The conflicting results of the immunohistochemical stains in the lesions we studied could be potential pitfalls in diagnosing histiocytic neoplasms.

Solitary malignant schwannoma of the duodenum with metastasis to the liver: Report of a case

Solitary malignant schwannoma of the duodenum is extremely rare. In fact, only two previous reports on successful radical resection of a solitary malignant schwannoma of the duodenum have been documented in the Japanese literature, and there are none in the English literature. We report herein the unique case of a 64-year-old man with a malignant schwannoma of the duodenum in whom both the primary lesion and a metachronous metastatic lesion were successfully resected. The patient initially underwent a Whipple procedure for a hypervascular tumor in the head of the pancreas. The tumor was composed of palisading spindle cells and scattered S-100 protein-positive cells with prominent mitotic figures, and was diagnosed as a malignant schwannoma of the duodenum. A second admission, 3 years later, revealed the presence of a solitary hypervascular hepatic tumor in the anterior segment of the right lobe of the liver. The hepatic tumor was resected and confirmed, microscopically and immunohistochemically, as a metastasis from the malignant schwannoma of the duodenum. The patient is alive 3 years and 6 months after his initial operation. To our knowledge no other report on the successful radical resection of both primary and metastatic lesions has been documented. This case report therefore highlights the importance of performing follow-up examinations focusing on the liver, and encourages an aggressive surgical attitude for the treatment of this unusual disease.

Folliculo-stellate cells and intercellular communication within the rat anterior pituitary gland.

Folliculo-stellate (FS) cell are agranular and arranged around a follicle. They contain the S-100 protein and beta-adrenergic receptors. It has been suggested that they can act as stem cells, since they show mitotic figures, and could transform into granular or chromophilic cells according to the concept of a "cell renewal system." Cell-to-cell interactions among pituitary cells have been described, and recent progress with freeze-fracture electron microscopy has provided novel observations of the cell surface and gap junctions within the rat or teleost fish pituitary gland, or in cultured rat pituitary cells. In adult rats, the anterior pituitary was composed of lobules incompletely separated by a basement membrane. Follicles consisted exclusively of FS cells. Gap junctions were observed only between adjacent FS cells, in rare cases on the tips of their cytoplasmic processes. Thus, the FS cells, connected by gap junctions, made up a dense cellular network throughout the pituitary. Gap and tight junctions were absent on granular cells. Elongated follicles with columnar FS cells were observed in 10-day-old rats and were separated into smaller units. The number of gap junctions rapidly increased with age until 40-45 days of age. Few S-100 protein positive cells were observed on day 10, along the marginal cell layer and near the so-called postero-lateral wing. The frequency of positive cells increased with age and by day 40; numerous cells were observed throughout the anterior lobe. Gap junction number also varied with the stage of the estrous cycle, and frequency; during diestrus, they were half of that during proestrus or estrus. The number of gap junctions increased in late pregnancy and in lactating rats, probably due to changes in estrogen and progesterone. Hormone (LH-RH and testosterone) treated groups of rats showed accelerated development by almost 10 days, compared with controls. In castrated male rats, the ultrastructure of the pituitary remained immature even at 40 days of age, when the number of gap junctions was a quarter or less than the number in intact rats. Testosterone treatment restored the frequency of gap junctions to a normal level. We conclude that the appearance of gap junctions in the pituitary cells and maturation of the gland are dependent to a large degree upon gonadal steroids.

Verruciform xanthoma of the oral mucosa: An immunohistochemical and ultrastructural study of two cases

Verruciform xanthoma is an uncommon benign lesion of unknown aetiology and pathogenesis. Two cases of verruciform xanthoma are presented together with an immunohistochemical and ultrastructural study. One case co-occurred with an odontogenic keratocyst which, to our knowledge, has not been previously reported, and another case occurred on masticatory mucosa with an asymptomatic, granular, exophytic lesion causing a cleft-like gingival recession. In an immunohistochemical study using antibodies to macrophage (CD 68[KP1]), alpha-1-antitrypsin, vimentin, desmin, keratin, neuron-specific enolase (NSE) and S-100 protein, the characteristic foam cells of verruciform xanthoma showed strong positive staining for CD 68[KP1] and vimentin and weak positive staining for alpha-1-antitrypsin, while the other antibodies were negative. As in previous studies, S-100 protein positive dendritic cells were detected in lesional connective tissue. In addition, the ultrastructural findings revealed characteristics of macrophages containing varying sized lipid vacuoles and degenerating epithelial cells. These findings support the concepts that the foam cells in verruciform xanthoma are of monocyte-macrophage lineage and that the epithelial degeneration from uncertain causes may be related to the pathogenesis of the lesion.