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Biomedical subjects

J Macák

Publications and source records attributed to J Macák.

At least 19 recordsLinked to original sources

[Melanoma simulating malignant soft tissue tumour].

The authors presented the case of an 82-year-old man with primary nodular melanoma of the skin on the back (Breslow 3 mm) which repeatedly metastasized five times to the cervical lymph nodes. Metastases were excised. The aim of this report was to demonstrate changes in the phenotype and immunophenotype during tumour progression. Originally round and oval melanoblasts had a characteristic immunophenotype. They were S100 protein, HMB45, Malan A, MITF positive. From the second biopsy the immunophenotype began to change, and the amount of positive cells declined. In the succeeding biopsies the morphology was also changed. There were spindle cells which formed mutually intermingled bundles in places with large multinucleate cells. The histological pattern assembled malignant mesenchymal tumour - type malignant fibrous histiocytoma. The immunophenotype was also changed. The second to fifth metastases in the cervical region were only S100 protein positive. The other above-mentioned melanoma markers were negative. Differential diagnosis includes neurotropic-desmoplastic malignant melanoma, Bednár tumour (pigmented dermatofibrosarcoma protuberans; storiform neurofibroma), malignant peripheral nerve sheath tumour (neurogenic sarcoma) and malignant fibrous histiocytoma.

Aged, 80 and over↗

[Immunohistological and molecular genetic findings in GIST of the stomach].

The authors described immunohistological and molecular genetic findings in series of 21 tumours with spindle and epithelioid cells histology of the stomach. In 18 cases the tumours were KIT (CD117) positive and the diagnosis of gastrointestinal stromal tumour (GIST) was confirmed. Three cases were KIT (CD117) negative. According to additional immunohistological markers (desmin and smooth muscle actin positivity) two of them were categorized as leiomyomas. The immunohistological profile of the third case showed that the tumour could be classified as a transitional form between leiomyoma and GIST. All but one KIT (CD117) positive tumours were also CD34 positive. In other three KIT (CD117) positive cases up to 10% of CD34 positive cells were found. Desmin was negative in KIT (CD117) positive cases. S100 protein was positive in three KIT (CD117) positive cases ranging from single cells to 10% of cells. Nine tumours were NSE positive. In our study the connection between proliferation factors (Ki67 and PCNA) and the mitotic index was not established. Risk factors were identified based on the size of the tumours and the mitotic index. Very low and low risk of aggressive behaviour included 12 cases, intermediate risk category 5 cases, high risk category 4 cases. For molecular genetic examination, DNA was extracted from formalin-fixed, paraffin-embedded tissues. Exon 11 was analyzed by SSCP (single-strand conformational polymorphism analysis) with following sequencing. Deletion was found in 7 cases, point mutation in one case, silent point mutation in one case and in two cases the examination could not be detected. In 10 cases (47%) a "wild type" was found. We suggest that other exons, e.g. 9, 13, 17, (which were not examined) and genes than KIT gene could also trigger tyrosine-kinase activity.

Aged↗

[Intra-abdominal desmoplastic small-cell tumor of the peritoneum].

The authors described three cases of intraabdominal desmoplastic small round cell tumour of the peritoneum (IDSRT). In one case the patient was a woman, and in the other two men. The age ranged from 20-29 years. Common of all the cases was a rapid onset of clinical symptoms during the period of twelve to eighteen months. In one case, a 22-year-old woman presented with a symptomless course of disease documented by medical examination one month ago. Intensive chemotherapy was applied but two patients died of generalisation. The 22-year-old woman is alive but with clinical evidence of generalisation in the abdominal cavity. The "classical" type of IDSRT was found in all the cases. Sharply demarcated groups of tumour cells of different size were surrounded by dense fibrous stroma. In some regions desmoplastic areas prevailed. In one case the tumour consisted of round and oval cells resembling a lymphoma. In the other two cases, the slightly elongated cells were present. Immunohistologically, the small round cells were positive for cytokeratins with antibody AE1-AE3. Membrane and dot-like paranuclear positivity were found. In 2 cases the reaction to desmin was seen in a dot-like paranuclear distribution, whereas the reaction to smooth muscle actin (MSA) was negative. In all the cases positivity to vimentin and neuron specific enolase (NSE) were apparent. Negative reactions were found for WT-1 antibody in all three cases. In one of the cases the RT PCR reaction for chimeric gene EWS/WT1 was performed, and found to be negative. Many different tumour types, such as lymphoma, Ewing sarcoma/PNET, neuroblastoma, alveolar rhabdomyosarcoma, malignant mesothelioma must be excluded. Cytogenetic examination should be performed on tumours with a "non-typical" histological pattern and uncommon immunohistological examinations.

Abdomen↗

[Diagnosis of lymphoproliferative diseases from bone marrow biopsies].

The cytological, histological and immunophenotypical markers of lymphoproliferative diseases are evaluated in the collection of 950 trepanobiopsies, and correlated with types of extramedullary malignant lymphoma. The diagnostic significance of tumor infiltrates topography and basic rules of the differential diagnoses of malignant lymphomas in the bone marrow biopsies are discussed.

Biopsy, Needle↗

[Adenoleiomyomatous hamartoma of the lung] ].

The author described an adenoleiomyomatous hamartoma of the lung. The hamartoma was well circumscribed and measured 2.5 x 3.0 x 3.0 cm. This type of hamartoma is a rare lesion in literature described only in single cases, and without performed immunohistochemistry. In our case, the hamartoma was formed by slit or irregular glandular-like spaces lined by cuboid or columnar epithelial cells. Located around these spaces, fascicles and bundles of smooth muscle tissue with a positive antibody reaction to desmin, smooth muscle actin, and calponin, were found. Reaction with CD34 and S100 protein antibodies was negative. In the discussion, the author draws attention to disunity of terms and nomenclature of similar lesions. After three years of post-operative clinical follow-up, the patient is asymptomatic and without any signs of lung disorder.

Female↗

[Simultaneous occurrence of papillary carcinoma, oncocytic carcinoma and malignant lymphoma of the thyroid gland in a female patient with Hashimoto's disease].

A 51-year-old woman was admitted for a painless enlargement of the thyroid lasting over 6 months. Hashimoto's thyreoiditis was diagnosed and three tumors were found: oncocytic carcinoma, malignant lymphoma and papillary carcinoma. In the right lobe, oncocytic carcinoma and high grade malignant lymphoma composed of cells with irregular, lobulated nuclei were found. The lymphoma was confined to the thyroid gland. The oncocytic carcinoma invaded the capsule and the surrounding tissues. In the left lobe, there was a papillary carcinoma.

Adenocarcinoma↗

[Morphometric parameters of nuclei in EBV-positive and EBV-negative Hodgkin's lymphoma].

Five morphometric parameters of nuclei of EBV-positive and EBV-negative Hodgkin's lymphoma cells were assessed for length, width, area, circumference, and circularity. For the measurement of the nuclei of the tumor cells (Hodgkin, Reed-Sternberg cells) the system of image analysis "Lucie" was used. In comparison with EBV-positive Reed-Sternberg cells, the nuclei of the EBV-negative Reed-Sternberg cells had significantly larger circumference, area and width. The nuclei of the Hodgkin cells in EBV-negative Hodgkin's lymphomas had significantly larger width and circularity. The authors assume that the altered morphometric parameters are related to a latent EBV infection.

Adolescent↗

[Mummified Hodgkin and Reed-Sternberg cells in EBV positive and EBV negative Hodgkin's lymphomas, Bcl-2 positivity and evaluation of survival].

Mummified tumour cells in Hodgkin's lymphoma (HL) are a special type of programmed cellular death, which differs from apoptosis in several respects. The common feature with apoptosis is the death of individual tumour cells. The number of mummified cells is many times higher than the number of cells in apoptosis. The authors examined a group of 24 cases of EBV positive and 24 cases of EBV negative HL and assessed the so-called mummification index. The value of the mummification index was 10.4 in EBV positive and 8.2 in EBV negative HL. The difference of values was not marked and therefore it may be concluded that latent EBV infection does not influence the numbers of mummified cells. Using statistical methods (the log-rank test) the authors evaluated survival and differences between groups of EBV positive and EBV negative HL. In the course of 16.6 years no statistically significant difference was found between the two groups of HL. By means of the chi2 individual stages of the disease were compared and no significant differences between groups were recorded. Expression of Bcl-2 protein in tumour cells in HL was small and positivity was not found in mummifying cells. Bcl-2 protein was assessed in 24 EBV positive HL and 37 cases of EBV negative HL. In the first group the authors recorded positive findings in six cases, in the second group in five cases.

Adolescent↗

[T and NK cell peripheral tumors].

Peripheral T lymphomas are formed by cells with CD3 antigen which contain TCR alpha/beta. A minor part of the non-tumourous population contains TCR gamma/delta. The position is similar in T cell tumours. In the tumours however TCR may be lacking .NK ("natural killer") cells are CDR3 negative, rearrangement of the gene TCR does not occur and they are TCR alpha/beta and TCR gamma/delta negative. Contrary to T cells they contain antigen CD56 ("NK-associated antigen"). In these cells and in tumours cytotoxic proteins are usually present: TIA-1, granzyme-B, perforin. There is a continuous transition between T and NK cells. The prognosis of T cell tumours cannot be assessed from the cell size. T/NK small cell lymphomas are highly aggressive tumours. The prognosis of patients is very bad. From the morphological aspect they can resemble very much non-tumorous lymphocytes. Conversely, large cell T lymphomas of the skin which are CD30 positive take a very mild course and their prognosis is favourable. The author mentions also some more recent entities of extra-nodular T lymphomas: angiocentric NK/T lymphoma of the nose (and other regions), malignant T cell lymphoma in enteropathies, T cell lymphoma resembling subcutaneous panniculitis, hepatosplenic gamma/delta T lymphoma. These tumours are rare in this country and some, e.g. T/NK lymphoma of the nose, are found usually only in certain regions of the world. They may be however encountered also in Europe, in particular in immunosuppressed subjects and patients after organ transplantation.

CD3 Complex↗

Detection of Epstein-Barr virus in Hodgkin's lymphoma (patients in the Czech Republic).

The frequency of EBV demonstrated in patients with Hodgkin's lymphoma (HL) shows geographical variability. In the present study, we investigated the frequency of EBV in HL patients in the Czech Republic. The presence of EBV was determined by immunohistochemistry (IHC) with anti LMP-1 antibody and by in situ hybridization (ISH) method for EBERs. We studied 142 cases with HL. The age of patients ranged from 4 to 82 years. The male to female ratio was 1.2 (males 55.6%). In the series of 142 patients 47 (33%) positive cases were found. The incidence of EBV-positive results was significantly, higher in males than in females (70.2 vs. 29.7%, p = 0.023). Five patients were found in the age group below 10 years. They were positive with LMP-1 antibody and for EBERs in ISH method. The same results were discovered in two patients above the age of eighty. The most frequent histologic types of HL were nodular sclerosis (64 cases) and mixed cellularity (62 cases), respectively. The former type contained 16 EBV-positive cases (25%) and the latter 24 (38%) positive cases. The lymphocyte depletion type 2 (67%); lymphocyte rich type 5 (38%). EBV-positivity examined by ISH and IHC methods determined not only diagnostic Hodgkin cells and Reed-Sternberg cells but also small lymphocytes. In IHC method were small lymphocytes positive in 11 cases, more sensitive ISH revealed 32 positive cases.

Adolescent↗

[Latent membrane protein LMP-1 in Hodgkin's lymphoma].

The authors examined using the antibody against latent membrane protein (LMP-1) a group of 169 patients with Hodgkin's lymphoma (age 2 to 82 years). From the total number of 169 patients 48 (28%) patients were positive when tested with this antibody. In the whole group the following histological types were represented most frequently: type II (nodular sclerosis) 83 (49%) patients, and type III (mixed cellularity) 70 (41%) patients. Type I (lymphocytic predominance) was not represented. In type IV (lymphocyte depletion) there were three cases (1.7%). Type V (lymphocyte rich) was represented by 13 patients (7.6%). The frequency of positive cases was in these histological types as follows: type II 14 cases (17% of 83 cases), type III 28 cases (40% of 70 cases), type IV 2 cases (66% of 3 cases). type V 4 cases (30% of 13 cases). Distribution of positive cases by age: in children under 10 years a positive finding was recorded in 80%. In old people above the age of 80 years there was a 100% positivity (only two patients were examined). The smallest number of positive cases was in the third decade (of 26 patients 4% were positive). LMP-1 positivity was most frequent in male patients--in 37 (of 96 examined patients) and in 11 female patients (of 73 examined) The frequency of LMP-1 in Hodgkin's lymphoma is consistent with similar studies in economically developed countries. A markedly higher incidence of positive cases in the lowest and highest age groups and gender differences are striking and so far there is no unequivocal explanation for them.

Adolescent↗

[EBV-positive Hodgkin's lymphoma in children under 10 years].

The number of EBV-positive child patients with HL varies in different countries and regions. In developing countries the number of child patients with this disease is higher than in the patient population of economically advanced countries. The authors examined 24 patients under 10 years with Hodgkin's lymphoma. Twenty patients were males, four females. In ten cases according to histological examination type II of HL was involved--nodular sclerosis (7 boys, 3 girls). In 14 instances the authors detected the mixed cellularity type (13 boys and 1 girl). EBV positivity was assessed immunohistologically by means of the antibody against LMP-1 and EBER-1 by the method of in situ hybridization. In 20 EBV positive HL 18 boys and 2 girls were affected. EBV positivity was proved in 83%. The marked intersexual difference in different EBV positive HL has not been explained unequivocally so far. The authors proved, that 14 EBV positive HL were type III--mixed cellularity. In 6 cases the type of nodular sclerosis was involved. The authors assume that marked positivity of child patients is associated with the initial massive EBV infection. EBV positive tumour cells are to a considerable extent removed by the immune apparatus and thus in the second and third decade EBV negative patients predominate.

Child↗

Lex glycosphingolipids-mediated cell aggregation.

Glycoconjugates bearing oligosaccharide Lex, Galbeta1-->4(Fucalpha1-->3)GlcNAcbeta1-->3R, are found on the surface of several cell types. Although recent studies have indicated that Lexon both glycosphingolipids (GSL) and polylactosaminoglycans can mediate under certain experimental conditions Lex-Lexinteractions, cell-cell interactions based exclusively on LexGSLs have not been demonstrated. In this study we show that preincubation of nonaggregating rat basophilic leukemia (RBL) cells with purified LexGSLs resulted in incorporation of the GSLs into plasma membrane, as determined by immunostaining, and formation of aggregates in the presence of Ca2+; no aggregates were formed after preincubation of the cells with globoside or sphingomyelin. Lex-mediated aggregation was inhibited by removal of Ca2+or by addition of lactofucopentaose III but not by lactose or lacto-N-fucopentaose II. In a mixture of Lex-positive and Lex-negative RBL cells most of the aggregates were composed exclusively of Lex-positive cells. The combined data suggest that interactions between LexGSL on opposite cell surfaces are strong enough to allow formation of stable cell-cell contacts.

Animals↗

[Hodgkin's disease with epithelioid granulomatous reaction].

Hodgkin's disease with a conspicuous presence of epithelioid-histiocytic elements was described as a particular subvariant of mixed type Hodgkin's disease. The authors presented four new cases. An additional increase of Langerhan's and interdigitating cells was observed in two cases, sarcoidosis-like granulomas with epithelioid and big multinucleated cells in the third. This female died and granulomas were found in several other organs. A prognostic relevance of this conspicuous reaction has not been clear for the time being. The mentioned patient deceased one year after the diagnosis had been settled, other three patients have been clinically well surviving 2-5 years.

Adult↗

Melanoma of the stomach: reality or fiction?

Malignant melanoma of the stomach is a very rare tumour. In all publications the authors express their suspicion of metastases to the gastric wall which must be carefully excluded. In our case of a 75-year-old man, the diagnosis of a large gastric melanoma (diameter 10 cm) was established by explorative laparotomy. Clinically extensive exploration for a primary tumour of the skin, the anal region, the nose, the eyes was not successful. One month later the patient died. Autopsy revealed brown-black metastases in the liver, the perigastric lymph nodes, the brain, and the cerebellum. Microscopically the stomach tumour was composed of nests and sheets of epithelioid cells with typical solid alveolar pattern. In the tumour cells both argentaffin and argyrophil granules were present. Immunohistochemistry revealed a positive reaction with S100 protein and HMB45 antibodies. Histogenesis of primary melanoma of the stomach and oesophagus is discussed.

Aged↗

[Molecular biology aspects of Hodgkin's disease].

Immunohistological methods did not elucidate the etiology and pathogenesis of Hodgkin's disease. In "classical" cases the immunophenotype is based on evidence of three markers: CD30+, CD15+, CD20-. Despite the use of more recent methodical approaches a considerable percentage of Hodgkin and RS cells with CD15 antibody is negative. The Epstein-Barr virus (EBV) plays an important part in the development of malignant disease and at the same time a number of nuclear antigens can be detected: EBNA-1, EBNA-2, EBNA-3a,-3b,-3c,LP. Also latent membrane proteins LMP-1, -2a, -2b and two small ribonucleic acids described as EBER-1, EBER-2. Bcl-2 protein was detected in the majority of malignant lymphomas which reduces its value in differential diagnostic reflections. In Hodgkin and RS cells its positivity is not due to translocation or other disorders of the cell genoma. In these cells the expression of mRNA for bcl-2 is much more constant. Most probably there is no cooperation of bcl-2 and p53. Co-expression of the two genes was found only in a small percentage of patients with m.Hodgkin. The varied morphological picture in particular in the mixed type of m. Hodgkin is most probably associated with the formation and release of cytokines, factors which stimulate cell colonies (IL-3, GM-CSF, G-CSF, M-CSF). Non-tumourous cells chemotactically attracted to sites of tumour cells release further cytokines e.g. TGF-beta, IL-1, Il-2, which participate in the overall morphological appearance of the lesion.

Hodgkin Disease↗

[Malignant lymphoma with epithelioid cells].

Authors studied a group of 6 cases of malignant lymphomas with epithelioid cells. Their additional common features were a variegated cell population, big admixture of T lymphocytes and rare elements reminding of Reed-Sternberg cells. The seventh case serving as a standard was Hodgkin's disease with a high content of epithelioid cells. According to phenotyping the group consisted of 3 peripheral T cell lymphomas of the type of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and single cases of centroblastic ML, T-rich B-cell lymphoma and Hodgkin's disease. The latter diagnosis was settled after revision of a T-rich B-cell lymphoma. Some large cells were CD 20 and CD 30 positive. The classification was proved by autopsy. Authors tried to be more precise when classifying ML but they may be inapparent transitions among single types (e.g. between peripheral type of T cell lymphoma AILD type and AILD or between T-rich B-cell lymphoma and Hodgkin's disease with lymphocytic predominance). The patients were followed for a relatively short period. Four of them died in several months after diagnostic excision, two showed a conspicuous generalization at autopsy. The presence of epithelioid cells in ML may not be connected with a more moderate behaviour and better prognosis.

Adult↗