Possible relationship between abnormal melanosome structure and cytotoxic phenomena in malignant melanoma.

Melanogenesis has been regarded as a hazard for pigment cells which are endangered by reactive quinones and semiquinones generated by this process. Normally the potentially cytotoxic species are confined to melanosomes by a limiting membrane and thus separated from the rest of the cell. Our electron microscopic investigation has demonstrated the presence of abnormal and incomplete melanosomes in human melanomas from epidermal and mucosal sites, in melanoma metastases, and in B16 mouse melanoma. We conclude that significant leakage of reactive melanin precursors including free radical species may occur from aberrant melanosomes in pigmented tumors. This would be expected to be reflected by fully extended physiological scavenging mechanisms, and by local and distant manifestations of cytotoxicity: Among these manifestations is free radical damage to the liver, detected by a thiobarbituric acid-reactive substances assay, in B16 melanoma-bearing mice. The efflux of toxic species from abnormal melanosomes may explain both the observed frequent occurrence of necrosis in melanomas and the therapeutic efficacy of tyrosinase substrates and may also be one of the factors influencing the extent of melanogenuria.

Benign hypergammaglobulinemic purpura in a patient with ulcerative colitis and peripheric arthritis.

A 32-year-old patient is described presenting with ulcerative colitis and oligoarthritis who later developed benign hypergammaglobulinemic purpura. This diagnosis was confirmed by clinical investigation, immunological findings as well as by histological and immunofluorescent examination. He was successfully treated with steroids and azathioprin. The relevant literature is reviewed.

Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2.

Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus, the proliferative potential of tumour cells is an important prognostic factor. However, evaluation of the prognostic significance of the expression of proteins involved in regulation of cell proliferation remains controversial. In the present study, expression of Ki-67, PCNA and cyclin D1 was estimated in a group of 89 surgically resected non-small cell lung carcinomas using immunohistochemistry. The results were compared with expression of bcl-2 and p53 and with clinicopathological parameters including patients' survival. Ki-67 and PCNA were found to be moderately and highly expressed in 39% and 44% of the tumours, respectively. There was a strong correlation between Ki67 and PCNA expression. Forty five of 88 tumours (51%) showed overexpression of cyclin D1. Surprisingly, cyclin D1 was mainly localized in the cytoplasm and only a small group of tumours (9/88, 10%) showed nuclear staining as well. Bcl-2 and p53 expression was observed in 69% and 30% of the tumours, respectively. All these markers were found to be independent of clinicopathological parameters, except for Ki-67 and bcl-2 expression, which was associated with squamous cell carcinomas. It is concluded that none of the markers that were studied can be used as an independent prognostic factor, whereas the following combinations of markers may have favourable prognostic value: p53 positivity and low Ki-67 expression, p53 positivity and lack of cyclin D1 expression, bcl-2 positivity and low Ki-67 expression, and lack of cyclin D1 expression and low Ki-67 expression.

[Soft tissue neoplasms arising from myofibroblasts]. / Nádory mekkých tkání z myofibroblastu.

A group of 14 mainly spindle-cell tumours caused some uncertainly during bioptic classification with diagnosis oscillating between proliferating fibroma, fasciitis, fibrosarcoma, mesenchymal tumour, leimyoma, fibromesothelioma or even polymorphocellular sarcoma. A common feature was seen in the presence of different proportions of myofibroblasts of largely variable appearance. The only justification for the term "tumours arising from myofibroblasts" is in the predominance of well defined myofibroblasts. In all other cases the presence of such elements is at least a prospective contribution to the assessment of histogenetic connections.

[Bronchial carcinoids with intracellular spherical clusters of microfilaments]. / Bronchiální karcinoidy s intracelulárními sférickými shluky mikrofilamentu.

Tumour cell plasma in 4 out of 8 bronchial carcinoids was found to contain sphere-shaped formations of microfilaments different in nature from tonofilaments, myofilaments or amyloid fibrils. The filamentous structures were closely related to agranular endoplasmic reticulum with the occassional inclusion of endocrine granules of type Pa cells. In the discussion prt, the author refers to similar structures in other tumours arising from cells of the diffuse endocrine system, and in some of the lung carcinomas.

[Cellular irregularities in nasal polyps]. / Bunecné nepravidelnosti v nosních polypech.

50 patients of different ages were found to have irregular multinuclear cells lodged in their inflammatory hyperplastic nasal mucosa. In only isolated cases were they numerous enough to give the tissue a sarcomatoid appearance. Most of those could clearly be described as proliferating endothelial cells. Mechanical irritation seemed to be the obvious explanation of their pathogenetic relationships.

[Unusual trabeculra material in the fine structure of intercellular matter in pulmonary hamartoma]. / Neobvyklý trabekulární materiál v jemné strukture mezibunecné hmoty plicních hamartomu.

Numerous fibrous structures stainable with resorcin--fuchsin were found by light microscopy in five pulmonary hamartomas. Their electronoptic correlates were granular dense trabecular formations reminiscent of oxytalan fibres whereas trabeculae typical of elastica were rare. The trabecular material orientation according to collagenous fibrils as well as its occasional transverse striation suggest a special form of collagen to be involved.

[Morphological typing of respiratory tract tumors]. / Morfologická typizace nádoru dýchacího ústrojí.

A group of 224 tumours of the respiratory tract was used to present experience with the standard histological classification, as proposed by WHO--incl. the revised version of pulmonary tumour classification which is under preparation. Electron microscopic facts from the authors' own material as well as from recent literature served in particular as a stimulus for the critical evaluation of some details of the standard classification. It served also as the basis for recommendations for rational modifications for its use in particular in Czech and Slovak speaking areas: 1. Prefer in respiratory pathways the term papilloma from respiratory epithelium to "transient" papilloma and not differentiate exophytic and inverted forms. 2. Respect the differentiation of bronchial adenomas and carcinoids, but identify atypical carcinoids with small-cell (oat-cell) carcinomas. 3. As to other carcinomas of the respiratory pathways to differentiate only between squamous carcinomas (spindle-cell and verrucal), glandular (in addition to adenoid cystic and mucoepidermoid) and undifferentiated. 4. In the section of pulmonary carcinomas to abandon completely large-cell carcinomas and to describe tumours which cannot be included in other groups as undifferentiated carcinomas. 5. Avoid in the other respect satisfactory classification pattern of pulmonary carcinomas subvariants (in particular in the group of glandular carcinomas) and include exceptional units in the group "others". 6. Arrange the group of malignant lymphomas according to the extrapulmonary classification pattern and include there from the group of tumourous lesions so-called lymphoproliferative processes, eosinophil granuloma and gangrenescent granuloma. 7. Use consistent with the nomenclature in the sphere of the nervous system the term olfactory neuroblastoma and omit its rare sub-variants.

[Genodermatoses in fetal skin biopsies]. / Genodermatózy v biopsii fetální kúze.

The risk of serious genodermatoses, i. e. mainly of bullous epidermolyses and keratinization lesions, can be verified only by a prenatal ultrastructural diagnosis. In a group of 23 biopsies of fetal skin the diagnosis of genodermatosis was proved in 10 cases and denied in 10 cases, 3 samples were useless. Discussion points out technological prerequisites of fetal skin biopsy and interpretation problems of ultrastructural diagnostic phenomena in genodermatoses.

[Intravascular sclerosing bronchoalveolar tumor--additional ultrastructural details]. / Intravaskulární sklerozující bronchioloalveolární nádor--dalsí ultrastrukturální podrobnosti.

A case of intravascular sclerosing bronchioloalveolar tumour was the 11th one studied by electron microscopy. Tumour cells were full of myofilaments with few and not quite typical Weibel-Palade bodies. It was an abundance of contractile proteins in cells that may have resulted in observed nemaline body-like structures, paracrystalline inclusions and a crystal combined with leptomeric fibrils.

[Ultrastructural analysis of breast carcinoma]. / Karcinomy mlécné zlázy v ultrastrukturální analýze.

An analysis of 117 cases of breast carcinoma of varied histological type stressed common ultrastructural features more than the importance of electron microscopy for classification. It called attention to a frequent discordance between the maturity of fine structure and biological behaviour of carcinoma but failed to verify any prognostic significance of myoepithelial differentiation of tumour cells.

[Ultrastructural evaluation of pulmonary adenocarcinoma. I. Cytologically homogeneous phenotypes]. / Ultrastrukturální hodnocení plicních adenokarcinomu. I. Cytologicky homogenní fenotypy.

A group of 102 lung carcinomas with an ultrastructural evidence of exocrine features comprised 88 adenocarcinomas and 2 adenosquamous carcinomas classified correctly according to the WHO histological typing as well as 12 other carcinomas which had to be re-classified after electron microscopy. Microvilli and secretory granules served as exocrine markers. The microvilli were more specific than granules because of being missing in 15 less differentiated tumours and granules in 45 cases. Microvilli were oriented into intercellular lumina in 65 tumours as well as into intracellular secretion slots in 16 cases, nonpolarized microvilli encirced the circumference of less differentiated cells in 22 tumours. Glycocalyceal bodies were identified not rarely and that was why they did not prove useful in distinguishing primary and secondary lung adenocarcinomas. Electron microscopical classification of adenocarcinomas, more reliable than the light microscopical one, was based on a phenotypical expression of various secretion granules in tumour cells. Phenotypical homogeneity characterized only 56 percent of tumours (57). The two most frequent phenotypes were together mucous cells (5) and dense granule microvillous elements (9) representing serous cells of bronchial glands; cells with apical dense granules but without microvilli (7) represented Clara cells in peripheral carcinomas; type II pneumocytes oftener were normal cells included in tumours (8) than proper tumour cells (2).

[Ultrastructural evaluation of pulmonary adenocarcinoma. II. Phenotype heterogeneity and classification]. / Ultrastrukturální hodnocení plicních adenokarcinomu. II. Fenotypická heterogenita a klasifikace.

A phenotypical heterogeneity was observed in 45 tumours (45 per cent) from a group of 102 carcinomas with ultrastructural features of exocrine differentiation. Double heterogeneity was found in 36 tumours and a triple one in 8 tumours; a case with quadruple heterogeneity was presented analogy of which has been lacking in literature. A combination of different exocrine phenotypes occurred in 12 tumours, exocrine and endocrine phenotypes combined in 18 tumours, exocrine cells and keratinocytes were found in 21 tumours. The exocrine phenotype was characterized usually (38 times) by secretion granules mostly of a serous type (19 times), cells with microvillous specialization without granules represented (15 times) a lower level of the exocrine phenotypical differentiation. A ciliary phenotype which could not produce homogenous population of dividing cells yet occurred (4 times) as a rudimentary accompaniment of an endocrine phenotype. The case of quadruple heterogeneity combined ciliary, serous, endocrine and keratinocytic phenotypes. The WHO histological typing scheme does not offer a proper category for heterogenous adenocarcinomas with one prevailing exocrine phenotype when compared with an analogous group of "combined" small cell carcinomas. Histological typing of such heterogenous adenocarcinomas is to be completed at least by an electron microscopical prevailing cytological characteristic in the same way as in phenotypically homogenous carcinomas. Heterogenous tumours without any phenotypical prevalence may form a group of mixed carcinomas which has been represented so far only by the histological types of adenosquamous and mucoepidermoid carcinoma.

[Histogenesis of benign pleomorphic mesenchymal tumors]. / Histogeneze benigních pleomorfních mezenchymových nádoru.

Benign pleomorphic mesenchymal tumours (lipoma, fibroblastoma) are defined by large cells which have multiple peripheral nuclei and thus remind of a flower. Similar cells were already previously detected by Mirejovský as a reactive change in polypous processes. We assume that these cells may occur not only in non-tumours but also in tumours where similar stromal conditions exist as in polyps. Therefore pleomorphic giant cells are of no value for assessment of the histogenesis of tumours. Nevertheless giant cell pleomorphic reactive changes may be mistaken for atypical tumours and therefore their knowledge is of practical importance.

[Sarcomatous hepatocellular carcinoma]. / Sarkomatoidní hepatocelulární karcinomy.

Atypical variants of liver carcinomas may represent diagnostic pitfalls when compared with classical types. We described two cases of unusual hepatocellular carcinoma with sarcomatoid pattern. Both were large tumors in elderly people. Their immunohistochemical investigation showed a coexpression of various epithelial and mesenchymal markers. There were positivities of antibodies against cytokeratin, actin and desmin in the first case, against cytokeratin, chromogranin and actin in the second case and against EMA and A1AT in both of them. Such a tumor was not found either in five year bioptic and four year necroptic archival material or in the Hlava Institute histopathological collection. The frequency of the tumor was about 4% of all hepatocellular carcinomas according to the literature.

[Lamellae annulatae and cisternae radiatae in human tumor cells]. / Lamellae annulatae a cisternae radiatae v lidských nádorových bunkách.

According to a literary survey supplemented with the authors' own observation, lamellae annulatae have already been referred to in a variety of 23 human tumours. Cisternae radiatae, more complicated than lamellae annulatae, have had two literary references; the present authors have found them in three cases: in malignant melanoma, in mammary gland carcinoma, and in pulmonary adenocarcinoma. A new interpretation of the structure of cisternae has been developed, based on three-dimensional projection of pores.

[Myxoma of the external nose]. / Myxom zevního nosu.

A male bus-driver aged 45 had a proboscoid mass on the tip of his nose removed after three year's duration of the disease. Microscopically, the tumour appeared to be a myxoma with marked mucus accumulation extending subepidermally and leading to the formation of lacunes lined with fibroblasts.

[The syndrome of multicystic dysplasia of the kidney, spleen and liver with multiple malformations]. / Syndrom multicystické dysplazie ledvin, slinivky a jater s mnohocetnými malformacemi.

A genealogic analysis carried out in a neonate suffering from multicystic dysplasia of kidneys, pancreas and liver indivated an autosomal recessive type of heredity. Associated malformations of extremities with heterotaxis were present in hitherto undescribed combinations.

[Electron microscopic classification of pulmonary carcinoma]. / Klasifikace plicních karcinomu z elektronmikroskopického hlediska.

In a selected group of 175 pulmonary carcinomas the authors demonstrated how electron microscopy renders it possible to respect in their classification more systematically cytological differentiation than when the revised version of the "Histological typisation of pulmonary tumours" published by WHO is used. After electron microscopic examination the group of so-called large cell carcinomas was divided into carcinomas with varying differentiation (small-cell from endocrine cells, pavement cells from keratinocytes, glandular from exocrine cells) and non-differentiated ones (from primitive cells). To the non-differentiated carcinomas those originally small-cell carcinomas were added which lacked ultrastructural differentiation. The uniform subtle structure of glandular carcinomas, however, did not support the importance of differentiation of their subgroups. It became particularly doubtful to have as a separate unit bronchioloalveolar carcinomas when in the group only two bronchiolar carcinomas (from Clara cells) were detected and no carcinoma from alveolar epithelium (from granular pneumonocytes). Double ultrastructural differentiation was found in 10-15% of the carcinomas; their group classification respected the predominating differentiation.

[Intravascular sclerosing bronchioloalveolar tumor and sclerosing hemangioma of the lung - differential diagnosis]. / Intravaskulární sklerózující bronchioloalveolární nádor a tzv. sklerózující hemangiom plic - diferenciální diagnóza.

Confrontation of typical cases of an intravascular sclerosing bronchioloalveolar tumour and a pulmonary sclerosing "haemangioma" was used for making easier histological typing. Both shared a bit different papillary structure and fibrosis as well as hyalinization. The first one grew in multiple slowly increasing foci where granular pneumocytes occurred but in spaces of original alveoli around protruding tumorous papillae; the tumour cells proper were alike vasoforming elements. The second one was a solitary benign tumour consisting of granular pneumocytes in spite of some angiomatoid and cavernomatoid structures.