Extracellular vesicle-mediated transfer of membranous components from the highly malignant T24 urinary carcinoma cell line to the non-malignant RT4 urinary papilloma cell line.

This communication reports the first experimental evidence that in the bladder cancer model, membranous components labelled with the DiO dye and the cholera toxin subunit B can be transported from highly malignant (T24) to non-malignant (RT4) cells by extracellular vesicles. Taking into account the presence of stable membranous nanostructures found by scanning electron microscopy, we suggest a possible uptake mechanism in recipient cells through fusion with highly curved membranous regions.

Intranuclear inclusions in epithelial cells of benign proliferative breast lesions.

AIM: To document and clarify the nature of intranuclear inclusions of luminal epithelium in benign proliferative breast lesions. METHODS AND RESULTS: Five benign breast lesions were selected which showed intranuclear inclusions within epithelial cells on light microscopy. Following confirmation of their luminal epithelial (non-myoepithelial) localisation by immunohistochemistry, ultrastructural examination was performed with the following observations: (1) presence of deep nuclear indentations occasionally verging on nuclear inclusions; (2) inclusions with features of helioid bodies; and (3) a morphological spectrum of helioid bodies and their focal coexistence. CONCLUSION: Intranuclear inclusions of breast epithelium are likely of cytoplasmic origin. Helioid bodies may be formed by a stepwise process, the nature of which needs further study.

Nasopharyngeal cylindrical cell papilloma.

INTRODUCTION: Cylindrical cell papillomas are rare tumours which usually arise in the sinonasal region. CASE REPORT: We report a case of a nasopharyngeal cylindrical cell papilloma in a 56-year-old man who presented with a four-month history of right-sided hearing loss, otalgia, vertigo and tinnitus. Investigation revealed a soft, nodular lesion obstructing the pharyngeal opening of the right eustachian tube; this was treated by wide endoscopic excision. CONCLUSION: Cylindrical cell papilloma is a possible cause of eustachian tube obstruction in adults. Effective treatment of these lesions usually requires wide endoscopic excision, in order not to miss coexistent carcinoma.

Etiology and pathology of epidermal papillomas in allogynogenetic crucian carp Carassius auratus gibelio (female) x Cyprinus carpio var. singuonensis (male).

Allogynogenetic crucian carp Carassius auratus gibelio (female) x Cyprinus carpio var. singuonensis (male) is one of the main freshwater aquaculture species in China. In recent years, epidermal papillomas have been observed on the scales, fins and opercula of adult fish in many fish farms in the Chongming county of Shanghai, China. The disease appears in the late autumn of the first year and becomes more severe in winter. It gradually regresses in the late spring or summer of the second year, as water temperature increases. Our study revealed that the disease pathogen was likely to be a herpes-like virus, as indicated by enveloped viral particles in the cytoplasm, empty capsids in the nucleus and a virus-like morphology of the pathogen. The size of the enveloped herpes-like virus was 118.18 +/- 10.53 (SD) nm (n = 22) and its nucleocapsid was 78.64 +/- 7.74 nm (n = 22) in diameter. Histopathological examination of tumours revealed that both epithelial and stromal cells proliferated to form papillomas. The nuclei of epithelial tumour cells were irregular in shape and in size. Most of the mucous cells were located in clusters near the middle of each papilloma. Cytoplasmic organelles were sparse in tumour cells. Numerous granulocytes and lymphocytes infiltrated into the tumour tissue. There were no inclusion bodies in the cytoplasm and nuclei of tumour cells. The lesions only occurred in adult allogynogenetic crucian carp, even though they were cultured together with other fish species. There was marked variation in incidence: in some ponds, only a few fish were affected, while the incidence was up to 90% in other ponds.

Bovine papillomavirus type 1 DNA and E5 oncoprotein expression in water buffalo fibropapillomas.

Papillomas and fibropapillomas may occur in the skin and in different organs in animals. Ten different genotypes of bovine papillomavirus (BPV) have been identified. BPV-1 through BPV-10 are all strictly species-specific, but BPV-1/2 may also infect other species such as equids, inducing fibroblastic tumors. BPV-1 and BPV-2 are associated with fibropapillomas in cattle; these tumors are formed by excessive proliferation of virus-infected dermal fibroblasts and epidermal keratinocytes. Nine water buffalo (Bubalus bubalis) were examined for the presence of multiple cutaneous and perivulvar tumors. Cutaneous and perivulvar fibropapillomatosis were confirmed histologically. Negative-stain transmission electron microscopic examination revealed papillomavirus-like particles in the fibropapillomas, and papillomaviral DNA was also detected by the polymerase chain reaction. The amplified long control region (LCR) DNA sequence was identical to that of BPV-1. The BPV-1 E5 oncoprotein was strongly expressed in the tumor cells thus confirming a causal role of the virus. This article represents the first report of cutaneous, perivulvar, and vulvar fibropapilloma associated with BPV-1 infection in the water buffalo and describes another example of cross-species infection by BPV-1.

Laryngeal papillomatosis: morphological study by light and electron microscopy of the HPV-6.

UNLABELLED: Laryngeal papillomatosis is the most frequent benign neoplasia in children. It is caused by HPV 6 and 11. The lesions are exophytic and highly recurrent, compromising the airway mucosa, mainly the larynx. Study design--clinical prospective. AIMS: To show morphologic alterations of the epithelium (light and electron microscopy) in the HPV-6 lesions. METHODS: Specimens of laryngeal lesions obtained during surgery of four children (1 male, 3 female) were submitted to HPV typing (PCR), light microscopy and electron microscopy. RESULTS: In all specimens, HPV type 6 was found. Epithelial projections were found by electron microscopy with superficial cells in desquamation. Light microscopy showed exophytic projections of the keratinized stratified squamous epithelium overlying a fibrovascular core. Koilocytes (vacuolated cells), suggesting the viral infection by HPV, were identified. No alterations were seen in the basement membrane and corion. Ultraestrutural analysis showed vacuolated cells with clear cytoplasmic inclusions, intercellular injuries and widening intercellular spaces. CONCLUSIONS: morphologic alterations of the epithelium in the HPV-6 lesions are superficial, and additional studies including the others HPV types are needed to show the more aggressive and extensive aspect of the disease.

Solitary peripheral ciliated glandular papillomas of the lung: a report of 3 cases.

We report 3 cases of solitary papillomas located in peripheral regions of the lung that are extremely rare in the literature. The patients were 75-year-old and 72-year-old men and a 53-year-old woman. One patient complained of recurrent hemoptysis. The other 2 had no symptoms, but abnormal nodular shadows were revealed by chest radiographs during a health check. The maximum diameters of the tumors were 1.0, 1.4, and 1.1 cm, respectively. The 3 tumors gave almost the same histologic findings. Papillomatous fronds lined by a stratified columnar epithelium were seen in the lumens of peripheral bronchi, bronchioles, or alveoli. The stratified columnar epithelium consisted of ciliated, mucous, and basal cells. The neoplastic epithelium extended to the alveolar region and showed a similar appearance to bronchioloalveolar or papillary type adenocarcinomas. For differential diagnosis, it is noteworthy that endobronchiolar papillomatous fronds constantly exist and spreading along alveolar walls is limited in adjacent alveoli in peripheral papillomas. The presence of ciliated cells and basal cells is considered an important finding to suggest benign character of the lesion.

Papilomatose laríngea: análise morfológica pela microscopia de luz e eletrônica do HPV-6 / Laryngeal papillomatosis: morphological study by light and electron microscopy of the HPV-6

Papilomatose laríngea é neoplasia benigna mais freqüente nas crianças, causada pelo HPV, principalmente subtipos 6 e 11 e caracteriza-se pela presença de lesões proliferativas exofíticas e recidivantes sobre a mucosa das vias aérea, em especial na laringe. Forma de Estudo: Clínico prospectivo. OBJETIVOS: Demonstrar alterações epiteliais morfológicas (pela microscopia de luz e eletrônica) em lesões papilíferas casadas pelo HPV-6. MATERIAL E MÉTODOS: Fragmentos de lesões de papilomatose laríngea, colhidos durante procedimento cirúrgico de quatro crianças (1 masculino, 3 femininas), foram submetidos à tipagem do HPV (por método de PCR), análise pela microscopia de luz e microscopia eletrônica (varredura e transmissão). RESULTADOS: Na tipagem, todos os papilomas eram do subtipo 6. A microscopia de varredura identificou projeções epiteliais de vários tamanhos, com células superficiais em descamação. A microscopia de luz demonstrou lesões exofíticas, revestidas por epitélio hiperplásico com coilócitos e binucleações, característicos do HPV. A membrana basal e o córion adjacente estavam íntegros. À microscopia eletrônica de transmissão identificou-se vacuolização perinuclear e alargamento das junções intercelulares. CONCLUSÕES: As alterações morfológicas apresentadas pelo HPV-6 demonstram o caráter não-invasivo da lesão, sendo necessário estudos morfológicos adicionais relacionando os outros tipos de HPV, considerados mais agressivos, com os achados ultra-estruturais.

Laryngeal papillomatosis is the most frequent benign neoplasia in children. It is caused by HPV 6 and 11. The lesions are exophytic and highly recurrent, compromising the airway mucosa, mainly the larynx. Study design - clinical prospective. AIMS: to show morphologic alterations of the epithelium (light and electron microscopy) in the HPV-6 lesions. METHODS: specimens of laryngeal lesions obtained during surgery of four children (1 male, 3 female) were submitted to HPV typing (PCR), light microscopy and electron microscopy. RESULTS: in all specimens, HPV type 6 was found. Epithelial projections were found by electron microscopy with superficial cells in desquamation. Light microscopy showed exophytic projections of the keratinized stratified squamous epithelium overlying a fibrovascular core. Koilocytes (vacuolated cells), suggesting the viral infection by HPV, were identified. No alterations were seen in the basement membrane and corion. Ultraestrutural analysis showed vacuolated cells with clear cytoplasmic inclusions, intercellular injuries and widening intercellular spaces. CONCLUSIONS: morphologic alterations of the epithelium in the HPV-6 lesions are superficial, and additional studies including the others HPV types are needed to show the more aggressive and extensive aspect of the disease.

Benign müllerian papilloma of childhood.

Benign müllerian papilloma of the female reproductive tract is a rare childhood tumor that can easily be mistaken by those unfamiliar with the entity for botryoid rhabdomyosarcoma. Ultrastructural findings have been mentioned only in two individual case reports, and these both were issued many years ago. The aim of this update is to familiarize the reader with the clinical, light, and electron microscopic features associated with this distinctive entity, and thereby hopefully preclude the risk of making a serious diagnostic error. Two cases are illustrated, one very typical in its presentation and the other less so.

Differentiation-dependent localisation of tissue-type plasminogen activator in human bladder urothelium.

Human bladder urothelium is able to secrete tissue-type plasminogen activator (tPA). The aim of our study was to analyse localisation of tPA antigen in comparison to differentiation state of cells in samples of histologically normal urothelium and non-invasive tumours of the human urinary bladder. Twenty-five samples of normal urothelium and 31 non-invasive papillary tumours from 36 patients were examined. The presence of tPA antigen was evaluated immunohistochemically. Differentiation of superficial cells was assessed by the presence of urothelial cell differentiation markers, uroplakins (UPs; immunohistochemistry) and cell's apical surface architecture (scanning electron microscopy). All tissue samples stained anti-tPA positive. In normal urothelium, the intensity of anti-tPA staining was the strongest in superficial cells, which were well-differentiated. In tumours, all cell layers stained anti-tPA positive. The intensity of anti-tPA positive reaction in the upper cell layer correlated with the percentage of anti-UP positive superficial cells. Superficial cells showed various differentiation states. The localisation of tPA antigen in human in vivo tissue is not confined to the well-differentiated superficial cells. Our results suggest a positive correlation between tPA secretion and cell differentiation.

AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

Quantitative assessment of bladder cancer by nuclear texture analysis using automated high resolution image cytometry.

The aim of this study was to investigate the possibility of identifying urothelial neoplasia by nuclear chromatin texture feature analysis using high resolution image cytometry to improve the diagnostic accuracy of cytologic examination in the detection and monitoring of bladder cancer. Touch imprints of transurethral resection material of 56 control group (CG) cases of nonmalignant urothelium and 94 tumor group (TG) cases of bladder cancer were analyzed. The specimen collection was divided randomly into a training set and a test set. Cells were stained specifically for DNA by the Feulgen method. Only diploid cell nuclei were analyzed from both groups. A discriminator comprised of three nuclear texture features was derived from the training set of cases to separate CG from TG cases. This discriminator was then applied to the independent test set. CG cases were separated from TG cases with a sensitivity of 97% and a specificity of 95% on the independent test set of cases. When dividing TG cases into high-risk and low-risk groups, sensitivity in the low-risk group was 93%. None of the high-risk cases was misclassified (sensitivity, 100%). This retrospective investigation demonstrates that by high-resolution image cytometry it is possible to distinguish between urothelial neoplasia and normal urothelium with high reliability when examining diploid cell nuclei only. This method is superior to DNA ploidy analysis using image or flow cytometry and may become clinically relevant as a supplement to conventional cytologic examination. These promising results should be confirmed on cytologic preparations derived from bladder washings or voided urine.

Actin inclusions in stromal cells of fibroepithelial tumor of breast: immunohistochemical and ultrastructural studies.

An uncommon occurrence of actin inclusions in the stromal cells of a benign fibroepithelial tumor of breast is reported. Histologically, many of the stromal cells contained round and eosinophilic intracytoplasmic inclusions identical to those seen in inclusion body fibromatosis. Ultrastructurally, these inclusions represented dense spherical clumps of microfilaments derived from rough endoplasmic reticulum. The literature was reviewed and follow-up data showed that the clinical course of these morphologically distinctive benign fibroepithelial tumors was relatively indolent if completely excised, in contrast to inclusion body fibromatosis, which commonly recurs. The pathogenesis may be related to abnormal production of truncated actin filaments or alteration in microenvironment.

Fine needle aspiration cytology of an intraductal papilloma originating in a sublingual gland. A case report.

BACKGROUND: Intraductal papilloma of the salivary gland is a very rare tumor; only eight cases have been reported to date. Only histopathology has been used to investigate this tumor to our knowledge. There has not been any reported case of this tumor in a sublingual gland. CASE: A 3-cm oral floor mass with a lanulalike lesion in a 72-year-old female was aspirated. The cytologic features included various cellular smears containing compact clusters of papillary, radial, palisading, trabecular, tubular and buddinglike projected patterns; monomorphic columnar cells with oval-to-spindle nuclei basally located; abundant, finely vacuolar cytoplasm; indistinct nucleoli; and no squamous differentiated cells. A sublingual glandectomy was performed. Cytology, histology, immunohistochemistry and electron microscopy were performed with standard methods. The intraductal papilloma seems to have arisen within an excretory duct and differentiated into acinar cells. CONCLUSION: The cytologic findings of intraductal papilloma are unique and may allow its specific diagnosis on fine needle aspiration.

[Prognostic significance of ultrastructural analysis of basal compartment disorder in recurrent transitional cell papilloma and in situ cancer of the bladder]. / Prognosticheskoe znachenie ul'trastrukturnogo analiza narushenii bazal'nogo kompartmenta pri retsidiviruiushchei perekhodnokletochnoi papillome i rake in situ mochevogo puzyria.

Four stages of the basal compartment disorders, not revealed while histological investigation and which may be used as an early differential-diagnostic, prognostic signs for the choice of the patients treatment tactics, were displayed during analysis of 20 observations of recurrent junction cell papilloma and 8 bladder cancer in situ.

[Ultrastructural pathologic research on the adult laryngeal papilloma].

In this paper, the ultrastructural features of laryngeal papillomas of 9 cases of adult patients were investigated by means of SEM. It showed that the polypoid surface of the papilloma is easily recognized; the surface cells are covered by microvilli of different size and shape; and the epithelium is bordered by an irregular and continuous basement membrane. In some areas, there is pseudopodium of basal cells stretching into connective tissue. The structure of interface between basement membrane and connective tissue varies with aggravation of tumor cell atypia. The significant variation of structural of basement membrane and semidesmosomes suggests the possibility of malignant change.

Atypical palatal papillomatosis treated by excision and full-thickness grafting.

Papillary lesions of the oral cavity are extremely common, and inflammatory palatal hyperplasia is well known to dental practitioners. Advanced sophistication in viral laboratory technologies makes it apparent that various forms of the human papilloma virus are often causative. However, this is not true for inflammatory palatal hyperplasia. This article describes a patient with anatomically well-demarcated, multiple squamous cell papillomas of the palate that could not be classified as inflammatory palatal hyperplasia, nor could a viral etiology be ascertained, despite exhaustive laboratory studies. The lesion recurred despite numerous surgical ablation attempts. Eradication was achieved only after applying free soft-tissue grafts over the areas of excision. The differential diagnosis of papillary lesions with an emphasis on viral etiology, laboratory studies associated with their identification, and a hypothesis that explains why grafting was the only successful means of treatment are also discussed.

Dose-dependent amplification by L-ascorbic acid of NaHCO3 promotion of rat urinary bladder carcinogenesis.

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which received basal diet (Oriental MF) containing AsA at 0, 1, 2, 3.5, or 5% plus 1.5% NaHCO3 for 32 wk. Relative urinary bladder weights in the 5% AsA group were significantly increased as compared to the 0 or 1% group values due to the development of tumors. Both the incidence and number of microscopic urinary bladder lesions (tumors and preneoplastic lesions) showed dose-dependent increases. Furthermore, the sizes of the urinary bladder tumors (carcinomas and papillomas) were significantly increased with the highest dose, 5-bromo-2'-deoxyuridine labeling indices showed slightly increased proliferation in preneoplastic lesions of the urinary bladder epithelium with 5% AsA treatment. In a separate experiment, scanning electron microscopic observation revealed that administration of 5% AsA plus 1.5% NaHCO3 for 8 wk, without BBN, altered the urinary bladder surface. Elevation of urinary bladder epithelium AsA content, as well as urinary AsA, was also noted. Ornithine decarboxylase (ODC) activity and ODC messenger RNA levels in urinary bladder epithelium of rats treated with 1.5% NaHCO3 plus 5% AsA for 8 wk showed no statistically significant differences as compared to the control group. The results indicate that AsA amplifies the rat urinary bladder carcinogenesis promotion activity of NaHCO3 and that its intensity of action depends on the dose, particularly at high dose.

[Prognostic value of initial ultrastructural changes in squamous cell metaplasia of junction cell papilloma of the bladder]. / Prognosticheskoe znachenie rannikh ul'trastrukturnykh priznakov ploskokletochnoi metaplazii perekhodnokletochnoi opukholi mochevogo puzyria.

In 48 patients with a junction cell papilloma, in 65--with a junction cell and in 20--with nondifferentiated bladder cancer the electron-microscopic studying of the squamous cell metaplasia signs was conducted. Great prognostic importance of an early and overt signs of squamous cell metaplasia was established.

[Prognostication of the clinical course of transitional cell papilloma of the bladder]. / Prognozirovanie klinicheskogo techeniia perekhodnokletochnoi papillomy mochevogo puzyria.

The dominance of nondifferentiated cells in tumor and the evidence of an early signs of metaplasia, the basal compartment disorder, accumulation in cytoplasm of tumoral cells of fibrillar protein (tonofilaments, tonofibrils), the increase of so-called "dark cells" quantity, determined as a result of ultrastructural investigation of 48 transition-cell papillomas, constitute the unfavourable prognostic factor for this disease.