Papiloma invertido: aspectos radiográficos / Inverted papiloma: radiologic findings

O papiloma invertido é um tumor epitelial incomum que compromete a regiäo nasal e os seios paranasais. Este tumnor, embora originariamente benigno, tem alto grau de recorrência, podendo sofrer transformaçäo maligna. Ele pode destruir estruturas ósseas e se estender para as fossas cranianas anteriores e média, e tornar-se, desse modo, indistinguível radiologicamente de lesäo malígna. 8 pacientes com papiloma invertido histologicamente confirmados säo descritos e os seus achados radiológicos apresentados e comparados com os da literatura

Secreted phosphoprotein mRNA is induced during multi-stage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts.

Secreted phosphoprotein I (SPP), also known as 2ar, osteopontin, 44-kDa bone phosphoprotein, bone sialoprotein I, and transformation-related phosphoprotein, is a 41.5-kDa glycosylated phosphoprotein secreted by many mammalian cell lines and expressed in a limited set of tissues. Using a cDNA probe, we found that SPP mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderate-to-high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous-cell carcinomas induced by an initiation-promotion regimen. This contrasts with the transient induction we had previously observed after a single application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In a set of 5 independently isolated T24-H-ras-transfected mouse C3H 10T1/2 cell lines, the levels of SPP mRNA correlated well with ras mRNA levels and with both experimental and spontaneous metastatic ability. SPP mRNA expression was also elevated in a derivative of mouse LTA cells transfected with genomic DNA from B16F1 melanoma cells and selected for increased experimental metastatic ability in the chick embryo. This apparent association of SPP expression with invasion, progression and metastasis, along with the presence of a functional ArgGlyAsp (RGD) cell adhesion site in SPP (osteopontin), leads us to propose that SPP may act as an autocrine adhesion factor for tumor cells.

A marker for primary choroid plexus neoplasms.

Primary choroid plexus (CP) tumors are rare neoplasms that present in childhood or, less frequently, in adult life. The majority are benign and amenable to complete surgical excision, but occasionally more invasive variants are encountered. Although generally pathologically distinct, occasionally primary CP neoplasms may be difficult to distinguish from metastatic papillary carcinomas or papillary ependymomas. Conventional cytologic markers are not sufficiently specific to permit accurate diagnosis of primary CP tumors. The authors have reported that the CP is the unique site of synthesis within the brain of transthyretin (TTR, prealbumin), a transport protein for thyroxine and retinol. They therefore investigated the utility of TTR as a biochemical marker for CP tumors. They detected intense immunoreactivity for TTR at high dilutions of primary antiserum in the neoplastic epithelium of all of nine primary CP tumors (six papillomas and three carcinomas), but not in eight cellular or three papillary intracerebral ependymomas, meningiomas, oligodendrogliomas, astrocytomas, primary extracerebral papillary carcinomas (three thyroid, two breast) or five of six cerebral metastases from systemic papillary carcinomas. In one case of cerebral metastasis from papillary thyroid carcinoma, rare isolated immunoreactive cells were observed. Faint staining of the stromal-ependymal junction was seen in myxopapillary ependymomas of the filum terminale, which were otherwise nonreactive. By in situ hybridization, TTR mRNA was abundant in neoplastic CP epithelium, confirming local TTR synthesis. The authors conclude that TTR is synthesized by neoplastic CP epithelium and is an excellent marker for primary CP neoplasms.

Keratin expression in equine normal epidermis and cutaneous papillomas using monoclonal antibodies.

Keratin expressions in normal equine epidermis and experimentally induced equine papillomas were studied by immunohistochemical methods with three different human cytokeratin monoclonal antibodies, 34 beta B4 (directed against component 1), 34 beta E12 (directed against components 1, 5, 10, 11) and 35 beta H11 (directed against component 8). Staining patterns with 34 beta B4 and 34 beta E12 in the normal equine epidermis did not differ from those in the normal human epidermis. In the early developing papilloma, keratinocytes showed an abnormal suprabasal staining pattern and expressed an additional 56 kD keratin protein detected by 34 beta E12. In the advanced papilloma, cytolytic cells in the outer spinous and the granular layers did not stain positively with any of the three antibodies used. In both early and advanced papillomas, the expression of high molecular weight keratin proteins, as detected by 34 beta B4 and 34 beta E12, did not correlate with the degree of keratinization. By electron microscopy, keratinocytes in the advanced papilloma showed a marked decrease of tonofibrils and desmosome-tonofilament complex. These alterations may result from an abnormality in both proliferation and functional terminal differentiation of keratinocytes in the papilloma. There were obvious differences in staining patterns with 35 beta H11 between the normal human and equine epidermis; 54 kD keratin protein was expressed in suprabasal layers of the equine normal and papillomatous epidermis. Thus, this keratin protein may be regarded as a "permanent" marker for the equine epidermis.

Florid papillomatosis of the nipple: immunohistochemical and flow cytometric analysis of two cases.

The immunohistochemical and DNA profiles of two cases of florid papillomatosis of the nipple (FPN) were compared with the immunohistochemical and DNA profiles of mammary intraductal carcinomas (IC) to assess the relationship between these two proliferative neoplasms. Both examples of FPN were circumscribed papillary tumors in the subareolar breast that showed cytologic atypia, intraductal necrosis, and a distinct myoepithelial cell layer. An antibody to muscle-specific actin (MSA) decorated a continuous myoepithelial layer in one case that was confirmed by electron microscopy. MSA showed patchy, discontinuous staining of apparent myoepithelium in the ICs. Flow cytometric analysis showed that both FPN lesions were diploid, rapidly proliferating lesions with S-phase fractions of 10.9% and 34.4%. One IC was aneuploid, and the five diploid neoplasms showed S-phase fractions ranging from 6.4 to 15.8%. In FPN many epithelial cells stained intensely for S-100 protein, but each IC also showed at least focal expression of S-100 protein. One case of FPN was focally positive for gross cystic disease fluid protein 15 (GCDFP-15), but neither stained for tumor-associated glycoprotein-72 (TAG-72) nor for the product of the c-erbB-2 oncogene. In comparison, three ICs expressed focal GCDFP-15, four stained for TAG-72, and one was positive for the c-erbB-2 oncogene product. These preliminary observations suggest that the tandem proliferation of epithelial and myoepithelial cells and the preservation of a normal structural relationship between the two appears to separate FPN from intraductal carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenz[a]anthracene.

The incidence of tumor and the time of expression, cellular localization and the molecular weight of tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) with or without 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were studied. The time of the development of skin tumors in 0.1% DMBA-TPA treated rats was significantly shorter than that in rats which were treated with DMBA alone. In the complete carcinogenesis case, papillomas developed more slowly and were less common and also squamous cell carcinomas appeared much later. From the analysis of the proteins of each experimental group by SDS-PAGE and two dimensional gel electrophoresis, at least three tumor associated proteins were identified (54kd, pl = 5.66; 27kd, pl = 5.85; 11kd, pl = 4.90). Also these proteins were found in rat dorsal skin from 14 days gestation to 21 days postpartum, and disappeared after 28 days. In conclusions, two stage skin carcinogenesis could be successfully demonstrated in Sprague-Dawley rats and abnormal proteins were produced in DMBA or DMBA-TPA induced skin tumor. The tumor associated proteins of skin tumor induced by DMBA or DMBA-TPA were appeared at the late initiation stage or early promotion stage, and they were localized in plasma membrane and were glycoproteins that are thought to be related to the epidermal differentiation process.

Papillary adenoma of the stomach. Pathologic and immunohistochemical study.

A total of 13 gastric papillary adenomas composed of 8 papillary and 5 papillotubular adenomas were examined pathologically and immunohistochemically. They showed a dome-like or pedunculated appearance and were located at the antrum, except for one adenoma. Histologically, the adenoma cells showed atypia in varying degree and focal adenocarcinoma was noted in seven lesions. The number of goblet cells was apparently smaller in the papillary than in the tubular portion. Lysozyme was present at the supranuclear region in most papillary adenoma cells, whereas it was concentrated in Paneth's granules in tubular adenoma cells. No difference was found in the distribution and frequency of carcinoembryonic antigen, secretory component, and carbohydrate antigen CA 19-9 between papillary and tubular adenomas. Paucity of endocrine cells also characterized gastric papillary adenoma. Different phenotypic expressions might reflect the difference in histogenesis between papillary adenoma and tubular adenoma.

Lysozyme and mucins in gastric adenomas.

A method for the simultaneous demonstration of lysozyme and mucins in 39 cases of gastric adenomas differentiated two intermediate cell types. The first was similar to a columnar cell comprising a single cell population which covered extensive areas of the adenomas. This cell type often showed supranuclear lysozyme reactivity and apical neutral mucins, sialomucins, and sulphomucins in variable amounts. The second cell type was found in 11 adenomas, located mainly in the fundal area. It seemed to be a transitional form between the goblet cell and the Paneth cell. This cell type was scattered among columnar cells, occasional Paneth-like cells, and small goblet cells. These two types of intermediate cells may be regarded as abnormally differentiated integral elements of gastric adenomas. They may be associated with the neck stem cells in the cytogenesis of gastric adenomas.

Sensitive detection of nucleic acids and protein of human papillomavirus type 6 in respiratory and genital tract papillomata.

We have developed a sensitive method to detect and localize HPV-6 viral DNA, mRNA and protein in biopsy specimens of genital and respiratory tract lesions by using in situ hybridization and immunoperoxidase assays on sections of plastic-embedded tissue. This modified in situ hybridization technique, using ultrathin sections and strand-specific 3H-labelled riboprobes, offers the advantages of superior morphological preservation and detection of viral genomes at low copy number with good resolution. This modified immunocytochemistry provides better sensitivity when compared to previous methods using paraffin-embedded materials. In respiratory tract lesions, immunoperoxidase assay detected only a few capsid antigen positive cells, while in the genital tract lesions, there were more capsid antigen positive cells. Southern transfer analyses and in situ hybridizations demonstrated the presence of more viral nucleic acids in genital tract papillomata than respiratory tract papillomata. Epithelial cells throughout the papillomata were infected by HPV-6 as evidenced by positive hybridization, with more viral DNA present in superficial cells. Our results suggest that genital tract epithelium is more permissive for HPV-6 replication than respiratory tract epithelium. Using stand-specific probes synthesized from subgenomic fragments of the HPV-6 genome in conjunction with nuclease digestions, we were able to demonstrate that HPV-6 transcripts specific to open reading frames (ORFs) E6, E7, E1, L1, and L2 occur in maturing superficial cells. In contrast, transcripts specific to ORFs E1, E2, E4, E5a, and E5b could be detected throughout the whole of the epithelium with more signals noted at the basal cell areas. In addition, the distribution of HPV-6 nucleic acids and protein in a carcinoma in situ of the larynx was analyzed. In comparison to benign respiratory tract papillomata, more viral DNA was found in the malignant lesion, but the pattern and distribution of transcription and capsid antigen was similar.

Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes.

We have localized transforming growth factor-beta (TGF-beta) in many cells and tissues with immunohistochemical methods, using two polyclonal antisera raised to different synthetic preparations of a peptide corresponding to the amino-terminal 30 amino acids of TGF-beta 1. These two antibodies give distinct staining patterns; the staining by anti-CC(1-30) is intracellular. This differential staining pattern is consistently observed in several systems, including cultured tumor cells; mouse embryonic, neonatal, and adult tissues; bovine fibropapillomas; and human colon carcinomas. The extracellular staining by anti-CC(1-30) partially resembles that seen with an antibody to fibronectin, suggesting that extracellular TGF-beta may be bound to matrix proteins. The intracellular staining by anti-LC(1-30) is similar to that seen with two other antibodies raised to peptides corresponding to either amino acids 266-278 of the TGF-beta 1 precursor sequence or to amino acids 50-75 of mature TGF-beta 1, suggesting that anti-LC(1-30) stains sites of TGF-beta synthesis. Results from RIA and ELISAs indicate that anti-LC(1-30) and anti-CC(1-30) recognize different epitopes of this peptide and of TGF-beta 1 itself.

In situ hybridization and immunohistochemical study of human papillomavirus infection in adult laryngeal papillomas.

Routinely processed paraffin sections from 20 patients with adult laryngeal papillomas were examined for the presence of human papillomavirus type 11 (HPV-11) DNA and its specific mRNA by in situ hybridization methods using 35S-labeled RNA probes. Immunohistochemical techniques were also used to identify papillomavirus genus-specific common antigen (pgs-antigen). HPV-11 DNA signals and/or papillomavirus genus-specific common antigen were detected in all eight samples of multiple laryngeal papilloma. On the other hand, in 12 samples of single laryngeal papilloma, neither papillomavirus genus-specific common antigen nor HPV-11 DNA were detected. Four patients were positive for both HPV-11 DNA and pgs-antigen. In three of these four patients, HPV-11 mRNA signals were also detected. These results provided direct evidence of the association of HPV and adult multiple laryngeal papilloma.

Correlation of the histologic appearance of intraepithelial neoplasia of the cervix with human papillomavirus types. Emphasis on low grade lesions including so-called flat condyloma.

Cervical condylomas and intraepithelial neoplasia (CIN) were correlated with human papillomavirus (HPV) types and analyzed for the presence of abnormal mitotic figures. Colposcopically directed cervical biopsies were divided in half and processed for routine microscopy and Southern blot hybridization. Of 83 specimens from 71 patients, 70 (84%) contained HPV-DNA sequences. The HPV distribution was as follows: HPV 16 in 6/25 flat condylomas (FC), 2/8 CIN I, 8/18 CIN II, 12/14 CIN III; HPV 18 in 1/25 FC; HPV 31 in 3/25 FC, 3/18 CIN II, and 1/14 CIN III; HPV 6/11 in 12/18 exophytic condylomas (EC), 5/25 FC, 2/8 CIN I, and 3/18 CIN II. Uncharacterized HPVs were identified in 4/18 EC, 5/25 FC, 2/8 CIN I, and 1/18 CIN II. A similar heterogeneous distribution of HPV types was found in flat condylomas and CIN I. A more homogeneous distribution was noted in the exophytic condylomas and high grade CIN lesions, with HPV 6/11 found in the former and predominantly HPV 16 in the latter. Abnormal mitotic figures were predominantly seen in the high grade CIN lesions. Based on our findings, we would recommend that the term flat condyloma be abandoned and that low grade flat lesions of the cervix be graded according to CIN criteria.

Temperature-induced alterations in protein composition of newt papilloma cells.

Protein patterns of Japanese newt papilloma in vivo at low (4 degrees C), normal (10 degrees C, control) and elevated (30 degrees C) temperature were investigated by two-dimensional gel electrophoresis. There were nine protein spots in normal skin (skin specific spots: SSS) which did not exist in papillomas. At 10 degrees C, the papillomas possessed three specific protein spots (papilloma specific spots: PSS) which did not appear in normal skin. At the reduced environmental temperature, eight of the nine missing proteins in papillomas had reappeared by 12 weeks exposure. Differential responses in reappearance of SSS in papillomas varied with environmental temperature. The PSS generally were unchanged by environmental temperature modulation, although one specific protein disappeared at 12 weeks at 4 degrees C. Reappearance of normal SSS in papillomas occurred early in treatment and reflected only minor variations in high versus low temperature exposures. These data suggest that temperature-induced tumor regression may be associated with changes in protein composition.

Tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenzaanthracene

The incidence of tumor and the time of expression, cellular localization and the molecular weight of tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) with or without 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were studied. The time of the development of skin tumors in 0.1% DMBA-TPA treated rats was significantly shorter than that in rats which were treated with DMBA alone. In the complete carcinogenesis case, papillomas developed more slowly and were less common and also squamous cell carcinomas appeared much later. From the analysis of the proteins of each experimental group by SDS-PAGE and two dimensional gel electrophoresis, at least three tumor associated proteins were identified (54kd, pl = 5.66; 27kd, pl = 5.85; 11kd, pl = 4.90). Also these proteins were found in rat dorsal skin from 14 days gestation to 21 days postpartum, and disappeared after 28 days. In conclusions, two stage skin carcinogenesis could be successfully demonstrated in Sprague-Dawley rats and abnormal proteins were produced in DMBA or DMBA-TPA induced skin tumor. The tumor associated proteins of skin tumor induced by DMBA or DMBA-TPA were appeared at the late initiation stage or early promotion stage, and they were localized in plasma membrane and were glycoproteins that are thought to be related to the epidermal differentiation process.

Tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenzaanthracene

The incidence of tumor and the time of expression, cellular localization and the molecular weight of tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) with or without 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were studied. The time of the development of skin tumors in 0.1% DMBA-TPA treated rats was significantly shorter than that in rats which were treated with DMBA alone. In the complete carcinogenesis case, papillomas developed more slowly and were less common and also squamous cell carcinomas appeared much later. From the analysis of the proteins of each experimental group by SDS-PAGE and two dimensional gel electrophoresis, at least three tumor associated proteins were identified (54kd, pl = 5.66; 27kd, pl = 5.85; 11kd, pl = 4.90). Also these proteins were found in rat dorsal skin from 14 days gestation to 21 days postpartum, and disappeared after 28 days. In conclusions, two stage skin carcinogenesis could be successfully demonstrated in Sprague-Dawley rats and abnormal proteins were produced in DMBA or DMBA-TPA induced skin tumor. The tumor associated proteins of skin tumor induced by DMBA or DMBA-TPA were appeared at the late initiation stage or early promotion stage, and they were localized in plasma membrane and were glycoproteins that are thought to be related to the epidermal differentiation process.

Expression of epidermal growth factor receptor on oral squamous cell carcinoma.

The expression of the receptor for epidermal growth factor (EGF) in normal oral mucosa, papillomas and squamous cell carcinoma (SCC) has been determined by immunohistology and autophophorylation studies. Immunoreactive receptor was localised using two antibodies which recognise the receptor; EGFR1 which reacts with sequences in the external domain of the receptor and F4 which recognises sequences in the internal domain. EGFR was present on basal, suprabasal and some spinous cells of normal oral mucosa. Regional variation in the distribution of receptor was apparent. A similar pattern of receptor expression was seen on oral papillomas. The distribution and intensity of epidermal growth factor receptor (EGFR) expression varied between 20 patients with oral SCC. The staining patterns seen with the two antibodies were similar on all tissue types. The protein tyrosine-kinase activity of the receptor present on eight oral SCC was also examined by immunoprecipitation and autophosphorylation studies. This procedure also demonstrated variations in the amount of functional EGFR in these tumours. There was no significant correlation between the level of EGFR expression and tumour behaviour.

[Papillomavirus and cancer].

Papillomaviruses are causative agents of benign tumor (papilloma) and are widely distributed in most of animals. The papillomaviruses are small DNA viruses grouped in the papovavirus family. The genomes of all papillomaviruses pce double stranded circular DNA of approximately 8 K. base pairs. Classification of the viruses is presently based on the host range and relatedness of the nucleic acids. In the case of human papillomavirus (HPV), more than 50 types have been isolated. The amount of information about the HPV has grown considerably in the last few years, and at present it has been considered that the specific types of HPV are involved in the development of human genital cancer and the skin cancer developed in the patients with EV (epidermodysplasia verruciformis). The reasons are; i) Epidemiological evidence distinctly indicates that cervical carcinoma and other high-grade lesions of female and male genital tracts derive from a sexually transmitted disease. ii) Many cervical carcinomas, most cell lines derived from the carcinoma and almost all skin tumors of EV patient contain specific types of HPV DNA (genital tumors; HPV-16, 18, 31, 33 and 25, skin tumor of EV patient; HPV-5, 8, 17 and 20). Moreover, genetic information of the viruses can be detected in the cancer cells. iii) Follow-up studies of HPV carriers suggested that HPV-16, 18 have high oncogenic potential. iv) Oncogenic functions (transformation and immortalization) can be detected in the early genetic region of HPV-16 DNA. v) Cottontail rabbit papillomavirus (CRPV) induces tumor in rabbit (and that almost all of these tumors contain CRPV DNA. When rabbits are infected with CRPV, benign papillomas are induced in 100% of the rabbits and the lesion are progressed to skin cancer at the frequency of 40-60%). In human cases, however, the presence of specific types of HPV does not seem to be sufficient to assure the development of benign tumors into carcinomas, since only a part of all such cases progress after latent period of several to several ten years. This emphasizes that other etiological agents or cofactors must be involved.

Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues.

A mouse monoclonal antibody (MAb) recognizing alpha-smooth-muscle actin has been used to study smooth-muscle differentiation features in the stromal cells of desmoplastic reactions accompanying mammary tumors. We have studied, by the same immunohistochemical technique, a series of malignant and non-malignant human breast tissues. Cells composing the desmoplastic reaction were found to express alpha-smooth-muscle actin in all the 11 breast carcinomas examined, whereas no immunostain was demonstrated in the stromal cells of 7 breast tissue samples histologically defined as normal. Three of 9 cases of fibrocystic disease showed a minority of positively stained stromal cells, generally in association with epithelial hyperplasia. All the 7 cases of sclerosing adenosis, 3 of 4 cases of diffuse papillomatosis and all 3 intraductal papillomas exhibited a majority of immunoreactive stromal cells. Numerous stromal cells in 3 of 11 circumscribed fibroadenomas analyzed expressed low amounts of alpha-smooth-muscle actin. The factor(s) responsible for smooth-muscle differentiation in stromal cells are presently unknown, but the detection of this previously unsuspected stromal cell phenotype in nonmalignant mammary tissues might help in characterizing the variant morphological aspects designated under the label "fibrocystic disease" and in understanding the biology of premalignant or early malignant lesions of the breast.

Ependymal and choroid plexus tumors. Cytokeratin and GFAP expression.

Twenty-six ependymal and 15 choroid plexus tumors were examined with monoclonal antibody against cytokeratin using the avidin-biotin-peroxidase complex (ABC) technique. Serial sections were examined with antisera to glial fibrillary acidic protein (GFAP). In five ependymal tumors (one ependymoma, two papillary ependymomas, and two primitive neuroectodermal tumors [PNET] with ependymal cells), a variable number of cytokeratin-positive cells were present. Most tumor cells (except two PNET) were positive with GFAP antisera. Many cytokeratin-positive cells were present in all choroid plexus tumors. GFAP-positive cells were present focally in six of 11 papillomas and in one of four carcinomas. Although their staining patterns and distribution were clearly different, focal coexistence of cytokeratin and GFAP was observed in six papillomas and two ependymal tumors. Thus, some ependymal tumors (especially papillary ependymomas and occasional PNET) and many choroid plexus tumors have demonstrable positivity with antibody to cytokeratin, suggesting a transitional cell type with features of both ependyma and choroid plexus.