Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment.

The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment.

Fibroepithelioma of Pinkus.

Basal cell carcinoma (BCC) is recently the most common cancer in humans characterized by several histopathological subtypes. Fibroepithelioma of Pinkus (FEP) is traditionally classified as a very rare variant of BCC, however, it manifests clinical and morphological differences that distinguish it from most other types BCCs. This study was performed to evaluate the incidence of FEP and clinical-pathological characteristics of patients diagnosed with this tumor. Four cases of primary FEP (3 females, 1 male, mean age 53.4 y) were analyzed retrospectively. The prevalence of FEP was 0.7 % of all diagnosed BCCs. Topographically, tumors were localized on the right brachium, right gluteal region, left mesogastrium, and right side of the abdomen. Histological examination showed typical anastomosing cords of basaloid cells extending from the overlying epidermis into the loose fibrous stroma in the dermis. Mitotic activity or significant cellular atypia, as well as sign of solar dermatosis were absent. Mean horizontal and vertical diameter of the lesions were 7.7 and 2.8 mm, retrospectively. We did not observe infiltration of deeper skin structures. All lesions were removed completely and classified as pathological stage pT1. Three cases manifested typical picture of a "pure" FEP, one lesion had partially a feature of nodular type BCC, too. Although FEP is conventionally considered as indolent BCC variant with a favorable clinical outcome, recent evidences also favors its classification as a form of trichoblastoma. This is appropriate example how some types of cutaneous tumors can overlap in terms of dignity and clinical-morphological characteristics. This should be taken into account in differential diagnosis and in predicting of biological behaviour of the individual tumors of the skin (Tab. 2, Fig. 3, Ref. 26).

Comparision of histological types of primary and subsequent relapsing basal cell carcinomas of the skin.

BACKGROUND: Basal cell carcinoma (BCC) recurrences are relatively frequent event in a routine dermatologic practice. One of the most important factor which impacts risk of their development is a histomorphological appearance of tumor. DESIGN: The purpose of our study was to compare histological types of primary and corresponding relapsing BCCs of the skin. MATERIAL AND METHODS: The study included 36 cases of BCC recurrences from 34 patients, 17 women and 17 men. The patients ranged in age from 32 to 97 years, with a mean age of 67.1 years at the time of (the first) recurrence. RESULTS: Both tumor groups generally exhibited the same proportion of indolent and aggressive histological phenotype. In 21 cases (58.4%), we found an identical histological BCC type in primary and subsequent relapsing lesion. In 3 cases (8.3%), primary lesion showed indolent histological features without aggressive--growth component, while recurrent tumor already manifested it. Conversely, in next 3 cases (8.3%) primary tumor exhibited focal infiltrative-growth features and corresponding relapsing lesion did not. Of the remaining 9 cases (25%), histomorphological phenotype was not identical, but it showed the same prognostic histological tumor variant. CONCLUSION: Based on the results of our study it can be assumed that a BCC recurrence is a dynamic histogenetic process, during which the phenotypic transformation and the changes in histomorphological picture of lesions occur, probably as a result of the interactions between cancer cells and re-modulated surrounding stroma.

[Solitary distal femoral osteosarcoma in 89-year-old woman. Case report]. / Solitárny osteosarkóm distálneho femuru diagnostikovaný u 89-rocnej zeny.

The authors describe the case of an 89-year-old patient with a one-month history of pain in the right knee and a pathological fracture of the distal femur. Excisional biopsy showed a classical osteogenic sarcoma. The patient died after six months of palliative surgical and oncological therapy; her primary disease generalised and progressed with numerous metastases. The authors discuss the possibilities of histological diagnostics of osteogenic sarcoma and its differential diagnosis. They draw attention to a possible occurrence of this type of sarcoma also in elderly patients, and not only in adolescents.

[Giant cutaneous basal cell carcinoma of the head with intracranial propagation--a case report]. / "Gigantický" bazocelulárny karcinóm koze hlavy s intrakraniálnou propagáciou--kazuistika.

Basal cell carcinoma (BCC) of the skin is generally characterised by a favourable clinical outcome. The slow and mostly local character of growth helps in its early recognition, thus the vast majority of cases are diagnosed in the early phase of disease. However, in cases of long-term neglect of clinical symptoms, certain cancers may reach huge proportions and may significantly destroy surrounding tissue. BCCs larger than 5 cm are called giant BCCs. The authors of the article present a case report of woman suffering from a giant BCC of the head with a history of 15 years of lasting growth, during which she had refused a medical examination. Finally, she was forced to go into hospital due to episodes of unconsciousness and convulsions. Clinical investigations revealed a huge ulcerating tumour in the fronto-parietal region infiltrating the skull and penetrating into the cranial cavity with compression of the brain. A surgical extirpation of the tumor-affected soft tissue and the calva was performed with plastic reconstruction of dura mater and skin. Microscopic examination of biopsy specimens confirmed a diagnosis of mixed BCC with nodular, infiltrative and metatypical features, which had completely infiltrated calva and dura mater. It was not possible to surgically remove a part of the tumour-affected bones of the left orbita, thus the patient is going to undergo local radiotherapy. This case report emphasizes the fact that BCC, in spite of its usually "benign" biological behaviour, should never be underestimated because it may progress to the advanced stage of the disease, for which treatment is much more difficult with a larger negative impact and a significantly worse prognosis for the patient.

[Basal cell carcinoma of the skin--biological behaviour of the tumor and a review of the most important molecular predictors of disease progression in pathological practice]. / Bazocelulárny karcinóm koze--biologické správanie nádoru a prehl'ad najvýznamnejsích molekulových ukazovatel'ov progresie ochorenia v praxi patológa.

Basal cell carcinoma of the skin is currently the most frequent malignancy in human population. Basal cell carcinoma represents a heterogeneous group of tumors with a variable clinical and morphological picture. Based on its biological behaviour, we generally differentiate between indolent (superficial and nodular) and aggressive type (infiltrative, micronodular, and metatypical) of basal cell carcinoma. Because of the different biological characteristics of these tumors, it is questionable whether they are a part of a continuous spectrum of carcinogenesis, starting with indolent and ending with aggressive forms, or they represent separate developmental lines. In the current clinical practice, there is an increasing demand for identification of tumors that are prognostically more adverse and their impact on the overall health status of patients is more serious. Recent advances in pathology and molecular medicine allow identification of various biomarkers from tumor tissue that are significantly involved in the mechanisms of malignant cell transformation. Detection of these biomarkers is of great importance in predicting further clinical behaviour of the cancer. The authors of the paper present basic information about biological behaviour of cutaneous basal cell carcinoma and provide an overview of the most important biomarkers that influence the clinical outcome and disease progression and are detectable through a routine biopsy tissue examination. It is now necessary to search for novel histological and molecular parameters that, in the future, could have a prognostic value in diagnostic and therapeutic process of this disorder.

Congenital polycystic kidney disease in one of the twins.

Cystic renal disorders generally comprise a heterogeneous group of conditions. The most common genetic form is a polycystic kidney disease. This nosologic entity can be inherited as either an autosomal recessive or autosomal dominant trait. Among all cystic renal disorders, autosomal recessive polycystic kidney disease is the most frequent heritable disease manifesting in infancy and childhood and is among those that come to clinical attention early. The characteristic pathologic changes occur in the kidneys and the liver, however, several other organ systems can be affected secondarily. Both kidneys are enlarged because of multiple progressive cystic dilatation of the renal tubules that results to renal failure. The liver is characterized by periportal fibrosis with bile ducts abnormalities. The renal and hepatic manifestations are more or less inversely proportional in individual patients. Therefore, the morphological features and clinical presentation of this disorder can vary substantially. Moreover, there is also a great variability in the severity and manifestations even between individuals from the same family who carry the identical mutations. The authors present a case report of a fatal clinical course of the perinatal congenital polycystic kidney disease in one of the twins (Fig. 4, Ref. 19).

Side effects of anastrozole in the experimental pre-menopausal mammary carcinogenesis.

UNLABELLED: The aim of this study was to assess side effects of aromatase inhibitor anastrozole in the prevention of N-methyl-N-nitrosourea - induced pre-menopausal mammary carcinogenesis in female Sprague-Dawley rats. This model mimicked situation in healthy, but from the point of view of the development of breast cancer, high-risk pre-menopausal women.

Aromatase inhibitor anastrozole was used as a chemopreventive agent taken by the animals in the food during the whole period of time of the experiment. Group 1 - the control group had taken food without anastrozole, the groups 2 and 3 with anastrozole in various concentrations - 0.05 mg/1 kg of food (ANA 0.05) and 0.5 mg/1 kg of food (ANA 0.5).

In anastrozole-treated animals in comparison with untreated animals, macroscopic changes of uterus and vagina were not found. The values of absolute and relative wet weight of uterus and vagina in the groups ANA 0.05 and ANA 0.5 were comparable with the control. Histological examination did not show atrophic changes in endometrium of uterus and in epithelium of vagina in anastrozole-treated animals. In the group ANA 0.5 myometrium was significantly grosser than in the group ANA 0.05 (P<0.05). Anastrozole neither affects parameters of plasma lipid metabolism (triacylglycerols, total cholesterol, low - density lipoprotein cholesterol and high - density lipoprotein cholesterol) nor serum levels of sex hormones (estradiol, testosterone, dehydroepiandrosterone). Compact bone thickness in the groups with anastrozole was significantly increased in comparison with untreated animals (P<0.001). A significant increase in body weight was found in the group ANA 0.5 compared with the control group (P<0.01). The significant increase in body weight gain was not attended by the significant increase in food intake.

The side effects of aromatase inhibitor anastrozole in the prevention of N-methyl-N-nitrosourea - induced pre-menopausal mammary carcinogenesis in female Sprague-Dawley rats on myometrium, compact bone thickness and body weight gain were observed.

Effects of flavin7 on allergen induced hyperreactivity of airways.

Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4), and interleukin 5 (IL-5) in bronchoalveolar lavage fluid (BALF). Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

[Perforating folliculitis. Case report and differential diagnosis]. / Folliculitis perforans kazuistický prípad a diferenciálna diagnostika choroby.

A 26-year-old woman suddenly noticed an onset of disseminated papular exanthema during her institutional treatment for alcohol abuse. After 9 weeks of slowly progressive course a dermatologist was consulted, who suggested a diagnosis of pityriasis lichenoides. Skin biopsy revealed cystical enlargement of hair follicles that were filled up with keratinous and parakeratotic masses interspersed with particles of fragmented collagen. Numerous inflammatory cells were present within the lesion. Many focal perforations of infundibular epithelium draining a cellular debris were prominent. Severely disturbed follicles were engulfed by giant cell inflammatory infitrate containing remnants of collagen and elastic fibers. Considering all the histopathologic findings and clinical course, the case was finally diagnosed as perforating folliculitis, a distinct type from the family of perforating dermatoses.

Gorlin-Goltz syndrome.

BACKGROUND: Gorlin-Goltz syndrome is an autosomal dominant inherited disorder characterized by a predisposition to various cancers. Clinicopathological findings of syndrome are very diverse and many symptoms begin to manifest in a certain period of life. CASE: The authors describe a case report of a man who, at the age of 34 years, presented to a dermatologist with multiple tumor lesions of the skin. The lesions started to develop when he was 30 years old and thereafter increased in number. Histology revealed superficial, superficial-nodular and nodular basal cell carcinomas. A total of 11 basal cell carcinomas were surgically removed and microscopically investigated. The others were treated locally with imiquimod cream and cryotherapy. In addition, he was found to have multiple odontogenic keratocysts in the jaw and mandible, as well as supernumerary and retinated teeth. Stomatologic and maxillofacial surgery interventions were performed. Further clinical and imaging examinations confirmed macrocephaly, hypertelorism, calcification of falx cerebri, and abnormalities of the cervical vertebrae. The spectrum of pathological findings met the diagnostic criteria of Gorlin-Goltz syndrome. CONCLUSION: Although Gorlin-Goltz syndrome is very rare in routine practice, it usually represents a serious disease with multiple organ system involvement. From a prognostic point of view, early diagnosis with adequate therapy is critical. If a diagnosis is confirmed, lifetime dispensary care with interdisciplinary medical cooperation is necessary. The authors would like to thank all physicians who participated in the diagnostics and therapy of the presented patient. The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 30. 8. 2018 Accepted: 8. 1. 2019.

[Bloch-Sulzberg syndrome in pathology]. / Blochov-Sulzbergov syndróm v patológii.

The authors present some pathological findings in the skin and hair of the child affected by rather rare Bloch-Sulzberg syndrome manifested in incontinentia pigmenti, followed for 10 years. In this work are presented also some recent data about pathogenesis of the disease with X-chromosome dominant heredity, primary of neuroectodermal origincaused by mutation of nuclear factor kappa-B of essential modulator (NEMO) of the gene (chromosomal locus Xq28).

[Diagnostic procedures in skin adnexal tumours]. / Diagnostika adnexálnych tumorov koze.

From histogenetic, morphologic and immunohistochemical point of view the authors try to make possible algorithms that can be employed in a routine diagnosis of adnexal skin tumours. They stress the importance of knowledge of clinical data necessary for orientation classification of tumour skin lesions after biopsies. The authors translated their obtained data into survey tables to be used as guidelines in a routine bioptic practice.

[Massive localized lymphedema in an extremely obese patient]. / Massives lokalisiertes Lymphödem einer extrem fettleibigen Patientin.

Soft tissue tumors are commonly encountered in all surgical departments. The authors present a case of a very rare large tumor lesion, with macroscopic signs of liposarcoma.

[Does short-term high-frequency jet ventilation damage the tracheobronchial mucosa?]. / Poskodzuje krátkodobá vysokofrekvencná trysková ventilácia tracheobronchiálnu sliznicu?

In anesthetized rabbits, the occurrence of histopathological changes was studied above below and the level of the endotracheal tube opening after one-hour high-frequency jet ventilation (f = 150.min-1,Pin = 70-90 kPa, Ti = 0.5) with nonhumidified air and oxygen mixture (FiO2 = 0.6). The findings were compared with those obtained in intact rabbits and in rabbits which were inhaling nonhumidified air from the environment spontaneously via the endotracheal tube. Mechanical obstruction of the airways by mucus or necrosis of the mucous membrane was not observed. The major histopathological changes characteristic of inflammation and mechanical damage of the mucosa were recorded above the opening of the endotracheal tube. Towards the main bronchi the degree of the injury was decreasing. (Tab. 2, Fig. 2, Ref. 11.)

[Antioxidants in the respiratory system]. / Antioxidanty v respiracnom systéme.

BACKGROUND: Reactive oxygen species can participate in the airways reactivity changes after oxidants. The authors have observed an increase in airways reactivity after an exposure to toluene in guinea-pigs and cats in previous experiments. There literature data provide information on the prevention or the delay of free radical damage by antioxidants. MAIN PURPOSE: The aim of our study was to evaluate the effect of nonenzymatic antioxidants--vitamin C and vitamin E on the airways reactivity changes after the exposure to toluene vapours. METHODS: After a one-month-lasting pretreatment with 500 mg/kg/day vitamin C and 50 mg/kg/day vitamin E the guinea-pigs were exposed to toluene for 3 days 2 hours. Then the reactivity of trachea and lung strip smooth muscle to histamine was evaluated. RESULTS: The pretreatment with vitamin C did not evoke statistical significant changes of trachea and lung strip smooth muscles reactivity when compared with the control group. The pretreatment with vitamin E produced a statistically non-significant decrease in trachea smooth muscle reactivity, but an increase in contraction amplitude of lung strip smooth muscle. Trachea was without expressive histological changes. The lung showed granulomatous inflammation with lymphocytes and eosinophils. SUMMARY: Antioxidants in used doses did not prevent the reactivity changes evoked by toluene exposure. (Fig. 2, Tab. 4, Ref. 14.)

[Mechanisms of the effect of oxidants on the respiratory system]. / K mechanizmu pôsobenia oxidantov na dýchací systém.

BACKGROUND: It is known that oxidants may evoke changes of respiratory tract functions. The precise mechanisms of these changes are yet unknown. MAIN PURPOSE: In this study possible participation of eicosanoids, cytochrome P-450 and reactive oxygen species in the changes of airways reactivity evoked by toluene exposure as the source of free radicals was followed up by an indirect method. METHODS: Used drugs--naproxen (50 mg/kg b.w.), cimetidine (50 mg/kg b.w.) and N-acetylcysteine (300 mg/kg b.w.) were administered in two doses (first 30 minutes before exposure to toluene, second six hours after first dose). After exposure to toluene (2 hours in each of 3 consecutive days) was followed up reactivity of tracheal and lung smooth muscle to histamine in "in vitro" conditions. The studied substances were not administered in the control group of animals. RESULTS: In pretreated animals exposed to toluene the administration of naproxen, cimetidine and N-acetylcysteine does not provoke pronounced changes of tracheal smooth muscle reactivity compared to control group. More pronounced effect of these drugs with decrease contraction amplitude was detected on lung smooth muscle reactivity. CONCLUSION: According to our results it is not possible to determine the precise mechanisms which participate in changes of airways reactivity. There are probably multifactorial in nature.

[Deep soft-tissue leiomyoma]. / Leiomyóm hlbokých mäkkých tkanív.

Deep soft tissue leiomyomas (DSTL) are very rare. For this reason they are neither histologically, nor clinically reliably characterized, especially regarding their dignity. The authors present two cases of leiomyomas which grew from the deep soft tissue in the region of the head and perineum. Both cases involved women 43 and 63 years of age. Characteristically morphological traits, as e.g. good borderline of lesion, the presence of fibrous pseudocapsule, and classical morphologic appearance of leiomyoma were present in both cases. While in the first case the foci of dystrophic calcification within regressively altered foci of the tumour were found, the second case involved the presence of foci of myxohyalin degeneration of stroma. The first tumour contained also parts with a palisade arrangement of nuclei which gives a hint of resemblance to that of neurilemmoma. Mitoses did not exceed the HPF index of 2/10 in neither of the cases. Both cases were S-100 immunohistochemically negative, actin and human muscle actin were significantly positive, desmin was weakly or mediately positive, and vimentin significantly or mediately positive. The first case involved a clinical recurrence of a histologically verified leiomyoma after 5 years in the same location with MI being of zero value. Regarding the presented characteristics, the authors classify the described leiomyomas as DSTL. These tumours with an uncertain prognosis can metastatize despite their benign morphology. (Tab. 2, Fig. 4, Ref. 19.)

[Pathologic interpretation and clinical aspects of invasive basalioma]. / Invazívny bazalióm v interpretácii patológa a klinika.

Bioptic evaluations of basaliomas require from pathologists to perform histogenetic classification, type ascertainment, TNM system classification, as well as detection of the presence or absence of tumor elements on the margins and base of excisions. The systems of histologic type classification of basaliomas utilized by pathologists are inconsistent with the terminology used by clinicians. The presented work is aimed at correlation of the current terminology of invasive basaliomas from the view of dermatologists and pathologists. The method of retrospective study was used, namely in a 100 cases of histologically verified basaliomas followed by comparisons with clinical diagnoses and catamnestic data. Average age in male patients was 66.4 year, and 67.6 year in female patients. 11 cases of histologically ascertained types of basaliomas included two cases of invasive biological characteristics detected at control examinations after 3 months, while the margins and base of the former excisions were without tumor elements. In none of the 9 cases of clinically judged invasive basaliomas the histologic picture yielded signs of tumor invasiveness. The results imply that the clinical diagnosis of a variant of basalioma may represent information of its presupposed characteristics. An important task of a pathologist is however to notify by means of accurate ascertainment of the histologic variant in cases of morpheaphorm and fibroepithelial basalioma the possible invasive character of the particular tumor. (Tab. 4, Ref. 14.)

[Juvenile hyaline fibromatosis]. / Juvenilná hyalínová fibromatóza.

BACKGROUND: Juvenile hyaline fibromatosis is a sporadic hereditary disease with autosomal recessive mode of inheritance, characterized by the presence of nodules and tumours in the skin and soft tissues and gingival hyperplasia. The majority of patients are growth retarded, suffer from joint disorders, contractures, osteolytic lesions and have a positive family history. The disease most frequently occurs in children, but may be diagnosed also in adults. Since 1873, when the disease was described by Murray, only a few cases were introduced in the literature. THE AIM AND THE BASIS OF THE STUDY: To present the clinical pattern of a patient diagnosed at the age of 28 and describe also the histopathological, immunohistological and electron-microscopic findings of excisions from the lesions. METHODS: The pathologist in cooperation with clinicians from several disciplines established the diagnosis on the basis of typical histopathological picture and additional immunohistological tests not yet introduced in the literature. RESULTS: Tumorous lesions contained hyaline structureless matrix often with chondroid or even osteoid metaplasia, calcium salts. The matrix contained numerous fibroblastoid-like cells with eosinophilic cytoplasm, oval nucleus and often pericytoplasmic halo. ELMI investigation revealed dilated cisternae of rough endoplasmic reticulum and hypertrophic Golgi apparatus. Sporadically were particles with calcium salts density detected. Immunohistochemical tests revealed the expression of vimentin, alfa1-antitrypsin and alfa1-antichymotripsin by the tumorous cells. CONCLUSION: The authors presented an extremely sporadic childhood disease in an adult. The results are in accordance with the data from the literature. Immunohistochemical picture of "cementicles" has not yet been introduced in the available literature. (Fig. 12, Ref. 25.)