Prediction of additional lymph node involvement in breast cancer patients with positive sentinel lymph nodes.

Axillary lymph node dissection (ALND) has traditionally been the principal method for evaluating axillary lymph node status in breast cancer patients. In the past decades sentinel lymph nodes biopsy after lymphatic mapping has been used to stage the disease. The majority of sentinel lymph nodes (SLN) positive patients do not have additional metastases in non-sentinel nodes (non-SLN) after additional ALND. These patients are exposed to the morbidity of ALND without any benefit from additional axillary clearence. In the present study we would like to asses the criteria for selecting those patients, who have high risk for non-SLN metastases in the axilla in cases of positive SLN. In this retrospective analysis, clinical and pathologic data from 163 patients who underwent SLN biopsy followed by ALND were collected. Following clinical and pathological characteristics were analyzed to predict the likehood of non-SLN metastases: age, staging, histologic type and grading of the tumors, hormonal receptor status, HER-2 receptor status and Ki-67 protein, angioinvasion, metastases in SLN and non-SLN. Relative frequencies of individual characteristics between sample groups were statistically tested by Chi-square test at significance level p=0.5, when sample sizes in groups were small (≤5) by Fisher´s exact test. Metastasis in SLN were present in 67 (41%) of patients, 48 patients (29,4%) had metastasis also in non-SLN. The ratio between non-SLN positive / non-SLN negative lymph nodes in patients with positive SLN increases with the stage of the disease, the difference between values for the pT1c and pT2 stadium was statistically significant (p = 0.0296). The same applies to grading, but the differences were not significant (p>0.05). We could not find significant differences for angioinvasion of the tumor, probably for small number of patients with angioinvasion (p>0.05).Only the stage of the tumor was shown to be significant in predicting the metastasis in non-SLN in our group of breast cancer patients with positive SLN Nearly 80% of the patients of 70 years and older displayed no benefit from axillary staging, because of negative SLN as well as non-SLN, although thanks to the small sample size this was not a statistically significant result. Furthermore, current recommendations for axillary staging in breast cancer patients are discussed.

Current possibilities of cervical precancerous lesions screening in Slovakia: prevalence of high risk human papillomavirus in patients with cytological diagnoses of atypical squamous cells of unknown significance.

INTRODUCTION: It has been confirmed, that there is a causal relationship between persistent infection of high risk human papillomavirus (HR-HPV) and the development of cervical cancer. In population of women older than 30 years HPV infection becomes a significant etiological factor of precancerous lesion of the cervix, but HPV infection may spontaneously regress in the majority of the cases. PATIENTS AND METHODS: The analysed study group consisted of 397 samples with cytological diagnosis of atypical squamous cells of unknown significance (ASCUS). All cases underwent HPV DNA testing using the Hybrid Capture 2 (HC2) assay. We analysed prevalence of HR-HPV and a viral load expressed as relative light units/cut off ratio (RLU/CO) in different age groups with cytological diagnoses of ASCUS. RESULTS: The prevalence of HR-HPV with cytological diagnoses of ASCUS was detected in 44 %. The prevalence of HR-HPV between patients aged 17-29 and between patients aged 30-40 was 55 % and 48 % respectively and we detected significant reduction of prevalence (28 %) in patients older than 41 years. CONCLUSION: Based on the results of presented study we assumed that age the 40 and over is crucial for the development of serious precancerous lesions in Slovakia, thus this age group is the most suitable for HPV triage of ASCUS. As a refinement of that type of ASCUS triage we recommend to add to the algorithm quantitative measurement of viral load in the specimens in the form of RLU/CO ratio (Fig. 3, Ref. 27).

COX-2, p16 and Ki67 expression in DCIS, microinvasive and early invasive breast carcinoma with extensive intraductal component.

BACKGROUND: Recent studies have showed a significant association between the combination of COX-2, p16 and Ki67 overexpression and incidence of subsequent invasive carcinoma in a subgroup of treated ductal carcinoma in situ (DCIS) and the indicated prognostic value of COX-2, p16 and Ki67 in early breast cancer. Based on the continual model of carcinogenesis and the mentioned results, we hypothesize, that if COX-2, p16 and Ki67 expression is prognostic for DCIS future behaviour, the expression level of the markers correlates also with different stages of breast carcinomas such as DCIS, microinvasive cancer and early invasive cancer with an extensive intraductal compound. The aim of this study was to compare the expression of COX-2, p16 and Ki67 in different stages of breast carcinoma such as pure DCIS, microinvasive cancer (T1mic) and invasive ductal carcinoma with an extensive intraductal component (IDC with EIC). The expression was assessed only in in situ component of the three subgroups (DCIS, T1mic, EIC) in order to show a possible correlation of COX-2, p16 and Ki67 with different stages of carcinogenesis. METHODS: We carried out a retrospective study using immunohistochemical staining to evaluate the expression of the markers COX-2, p16 and Ki67 in in situ lesions within three subgroups of tumors with the rising extant of invasive compound: in pure DCIS, microinvasive carcinoma (T1mic) and invasive carcinoma with extensive in situ component (IDC with EIC). Additionally, we performed a correlation analysis between the tumor subgroups and patients history data (age, parity, age of menarche, family and personal cancer history, breast feeding lengths, contraception intake, chest irradiation) as well as some of the tumor characteristics (tumor grade, multicentricity, necrosis). RESULTS: Distribution of p16 expression differed significantly among the three diagnoses. P16 score 1 was highest in the DCIS group whereas the lowest proportion was in IDC and p16 overexpression (score 2, 3) maintained this tendency (overexpression proportion in DCIS < T1mic < IDC), though this was not significant. The frequency of COX-2 and p16 overexpression (phenotype COX-2+p16+) was higher in EIC within invasive carcinoma in comparison to DCIS and T1mic and was rising gradually with the severity of the diagnosis (proportion in DCIS < T1mic < IDC). CONCLUSION: This is the first published study ever assessing the expression of COX-2, p16 and Ki67 markers in different breast tumors containing DCIS compound. Our results showed an increasing expression pattern of COX-2 and p16 with the rising severity of the diagnosis (expression was measured exclusively in in situ lesions within tumors containing different extant of invasiveness). The same relationship was showed for p16 marker alone. These data support different expression pattern of COX-2 and p16 markers in combination and p16 marker alone in "in situ lesions" according to the stage of carcinogenesis. This fact might be useful in the evaluation of further behaviour of early breast tumors (Tab. 3, Fig. 8, Ref. 29).

Renal oncocytoma with invasive histopathologic features -  case report.

BACKGROUND: Renal oncocytoma is an uncommon tumor, classified as a benign renal neoplasm in the World Health Organisation classification of renal tumours. Despite it there were described several reports with invasive histopathologic features. CASE REPORT: We describe a case of renal oncocytoma with bizzare cells and invasion of renal sinus fat tissue. We performed immunohistochemical analysis of the case and a review of relevant literature. CONCLUSION: In order to set up the right dia-gnosis the perfect co- operation of clinicians and pathologists is necessary. In our opinion, in accordance with other authors, the renal oncocytomas should be considered as having a very low rather than no malignant potential, in spite of clinically benign behavior, supplementing a hypothesis, whether renal oncocytomas may be considered as a precancerous lesion of chromophobe carcinoma.

Mediastinal ganglioneuroma with perineural cell differentiation. Report of a case.

An unusual case of ganglioneuroma with perineural cell differentiation is presented. The tumor was removed from the mediastinum in a 34-year-old male patient. Histologically, it contained neuroid bundles of bland spindle cells, scattered ganglion cells, and some foci of adipocytic metaplasia. Immunohistochemically, the tumor showed expected expressions of S100 protein, neurofilament protein and calretinin. In addition, many spindle cells were positive for perineural cell markers EMA, claudin-1, and GLUT-1. These cells were often arranged in an organoid fashion around the schwannoid bundles. This case indicates that the cells of ganglioneuroma can mature simultaneously towards both Schwann cell and perineural cell phenotypes.

Perineural cell differentiation in ganglioneuromas. Report of 8 cases with immunohistochemical expression of perineural cell markers.

Eight cases of ganglioneuroma were examined for a presence of perineural cell differentiation, using the immunohistochemical markers epithelial membrane antigen (EMA), claudin-1 and GLUT-1. The mean age of the patients was 42.3 years (range 26-68 years), six patients were females and two were males. Five tumors were located in the adrenal gland and 3 tumors in the retroperitoneum. Morphology of the tumors was typical, i.e., they were composed of neuroid spindle cell population and scattered mature appearing ganglion cells. Spindle cells positive for perineural cell markers claudin-1 and GLUT-1 were found in all lesions, at least focally. EMA+ cells were seen in 2 of 8 tumors. These perineural-type cells were often arranged in organoid fashion around the schwannoid bundles or around the vessels. Our findings indicate that perineural cell differentiation is commonly present in ganglioneuromas.

[Acute cholestasis following treatment with nimesulide and oral contraception: case report and review]. / Akútna cholestáza po uzívaní nimesulidu a kontraceptív: kazuistika a prehl'ad literatúry.

Our case report of acute cholestatic liver injury highlights the potential hepatotoxicity of nimesulide treatment in combination with oral contraception. Rarely occuring histological findings of "pure" cholestasis without any inflammatory or necrotic changes with favourable outcome following ursodeoxycholic acid administration are described. It was not possible to distinguish the separate role of any of these two drugs on hepatotoxicity according to the available information. Based on the known similarities in hepatotoxic profile of nimesulide and oral contraceptives, it can be assumed that their interaction could increase the risk of liver damage, although the precise mechanisms are not ellucidated yet. Nimesulide toxicity however is often reported in cases taking several potentially hepatotoxic drugs. It is therefore prudent to reconsider any concommitant treatment and closely monitor liver function tests in patients requiring nimesulide treatment.

[Intraductal papillary proliferation of brest. Actual review and clinicopathological corelation]. / Intraduktální papilární proliferace prsu. Aktuální prehled problematiky a klinicko-patologické korelace.

OBJECTIVE: Complex summary addressing current view of the intraductal papillary lesions of breast, especially focused on morphology, exact terminology and clinicopathological aspects of effective therapy. DESIGN: Review article. SETTING: Biopsy Lab s.r.o. and Sikl's Department of Pathology, Charles University and Faculty Hospital, Pilsen. METHODS: Summarized recent data, diagnostic principals and clinicopathological recommendations of papillary breast lesions created comprehensive guide for daily diagnostic and therapeutic practice. RESULTS: The group of papillary tumors of the breast includes various lesions with different biologic potential. They are all presenting as pure intraductal lesions, but in case of multiple peripheral distribution imply possible risk for aggressive behavior. The reason is frequent occurrence of atypical ductal hyperplasia/intraductal (in situ) carcinoma in the adjacent tissue. Spectrum of secondary changes further complicates the diagnosis of papillary tumors, especially in core needle biopsy. Atypical papilloma is still very controversial issue and it essentially means situation when atypical ductal hyperplasia/conventional ductal in situ carcinoma arises in preexisting papillomas or extends to it from neighborhood. Generally, papillary lesions are suitable for effective conservative treatment in the case of proper clear resection margin. Finding of benign papilloma in core biopsy remains unsolved question yet.

[Giant retroperitoneal liposarcomas]. / Obrovské liposarkómy retroperitonea.

According to literature liposarcomas account to less than 0.1% of all human tumors, 13% of which are localiced retroperitoneally. Authors describe two cases of giant retroperitoneal liposarcoms treated in their department. CT findings and the course of the disease discussed. Conlusively authors remark of high probability of microscopical residual disease with need of patients' follow up with eventual reoperation and adjuvant radiotherapy.

Malignant tumors and embolizing paraneoplastic endocarditis.

A group of 4495 autopsied patients was evaluated. In 1011 (22.5%) of them various malignancies were found. In 20 of these cancer patients (2%) also a nonbacterial verrucous endocarditis was observed. The most serious complication of this paraneoplastic syndrome was central arterial embolization resulting in cerebral and myocardial infarctions. In our group this was observed in 12 patients (60%), in 9 cases of them infarction was the immediate cause of death. Fatal complications due to central embolization were seen also in 3 patients who had a malignant disease without symptoms of generalization. The most frequent tumors observed among the autopsied patients were adenocarcinomas of the digestive tract (40%). In the group of revealed tumors adenocarcinomas clearly prevailed (70%) in 10 cases (50%) also mucin production could be detected.

The etiology of underlying liver lesions in 70 autopsied cases of hepatocellular carcinoma.

In 70 patients with hepatocellular carcinoma without history of antineoplastic chemotherapeutic drugs, anabolic and contraceptive steroids, representative sections of nonneoplastic liver tissue were examined for the presence of etiological markers. Hepatitis B surface antigen-positive hepatocytes were found in 16 (22.8%), alpha-1-antitrypsin globules in 3 (4.2%), Mallory bodies in 9 (12.8%), acicular inclusions in 1 (1.4%), diffuse giant mitochondria in 2 (2.8%), copper-binding protein in 25 (35.7%), greater amount of hemosiderin in 9 (12.8%) cases. Thorotrast was not detected. One or more markers were seen in 38 (54.3%) cases, most frequently in association with liver cell dysplasia and alcoholism. The presence of hepatitis B surface antigen in livers with dysplastic foci was highly significant as compared to organs showing no dysplasia. Only the mentioned antigen and the alpha-1-antitrypsin globules were found to indicate the etiology of the underlying liver lesion. The value of the other markers was found inconsistent in etiological diagnosis.

Polythelia is not a mere aesthetic issue.

Anomalies in breast development include an increase in the number of breast (polymastia), nipples (polythelia), areolas (polythelia areolaris) and the tissue of the breast gland. Of the many forms, the most common is an accessory nipple, polythelia. It commonly develops along the embryonic "milk line" (Fig. 1). It constitutes a diagnostic problem only sporadically. Excision is indicated for diagnostic, treatment or cosmetic reasons. In the literature, the evidence of these anomalies suggests that they could be markers for others, most notably urologic malformations and malignancies.

[Pathology of the uterine cervix. Infectious lesions of the endocervix and exocervix]. / Patológia cervixu maternice. Infekcné lézie endocervixu a exocervixu.

Bioptic findings from the region of the endo- and exocervix of the uterus were analyzed in a retrospective study covering the years 1988-1990. The series studied consisted of 366 women. Infectious processes in the cervix were evaluated in this first part of the study. Over the period investigated, 155 cases of cervicitis were established. Of these 56 (36.2 %) were acute bacterial, 17 (10.9 %) were lympho-plasmocytic (chlamydial), and 4 (2.5 %) were herpetic. The largest group of 78 (50.3 %) patients had HPV induced lesions. Koilocytic dysplasia was grouped into three grades according to severity. Mild dysplasia occurred in 16 patients (22 %), intermediate in 19 patients (26 %) and severe dysplasia in 37 patients (52 %). (Fig. 6, Ref. 15.).

[Precancerous and malignant tumors of the uterine cervix]. / Prekancerózy a malígne nádory cervixu maternice.

Bioptic findings recorded in 366 women with lesions of the endocervix and exocervix were analyzed in a retrospective study covering the years 1988 to 1990. The series represented 24.5% of the total number of 1495 gynecological precancerous and tumorous changes. Severe dysplastic changes and malignant tumors of the endocervix were seen in 31 patients (19.4%). Concurrence of endocervical and exocervical lesions was recorded in 66 patients (18.0%). In the studied series 35% of the women were below the age of 40 years. Signs of koilocystic dysplasia were recorded in 72 women (37%) with precancerous and tumorous lesions. (Fig. 4, Ref. 15.)

[Pathologic findings in the uterine cervix--diagnostic aspects]. / Patologické nálezy na cervixe maternice--diagnostické aspekty.

The study presents results of routine bioptic diagnoses. 651 lesions of cervix uteri have been diagnosed during a five-year period. The presented number represented a summary of 26% of the absolute number of 2513 registered neoplastic and precancerous lesions of the female genital. The group of patients yielded dominance of precancerous lesions of exo and endocervix, namely in 445 cases, i.e. 68%. Malign tumours of exo and endocervix uteri constituted a group of 185 cases, i.e. 28%. The study proves the world's trends of the development of pathological changes in cervix uteri where HPV infection represents one of the most significant factors. The two-year lasting evaluation of 27,093 cytologically examined patients revealed HPV infection in 748 female patients, i.e. in 2.8%. Summarization of the findings detected on the basis of cytologic and bioptic examinations proved the histologic correlation of HPV infection in 124 patients out of 467 patients afflicted with dysplastic or malign lesion of exocervix. (Tab. 1, Fig. 3, Ref. 13.)

[Retrorectal and presacral tumors]. / Retrorektálne a presakrálne tumory.

The group of patients with retrorectal and presacral tumours is presented. Their clinical picture, CT examination, results of biopsy and surgery treatment are analysed. The authors present the recent procedures of diagnosis and therapy of tumors in this location.

[Morphologic findings in models of acute experimental pancreatitis]. / Morfologické nálezy pri niektorých modeloch akútnej experimentálnej pankreatitídy.

Morphological changes found in two models of acute experimental pancreatitis are presented. Acute pancreatitis was induced in rats by the method of ligation of the lateral pancreatic ducts and by the method of the blind duodenal loop. After four hours the animals were sacrificed and processed for light and electron microscopic examination. Changes indicative of edematous and necrotizing pancreatitis were recorded. In the electron microscopic picture the predominant findings were disintegration of organelles of acinar cells and the appearance of numerous vacuoles and autophagosomes. The presented models of pancreatitis are considered to be suitable for further research into the pathogenesis and therapeutic intervention of acute pancreatitis in rats. (Fig. 15, Ref. 8.)

[Microscopic diagnosis of mixed and mesenchymal tumors of the mucosa and uterine body]. / Mikroskopická diagnostika zmiesaných a mezenchýmových nádorov sliznice a tela maternice.

A series of 452 with 831 precancerous and tumorous lesions of the corpus uteri is presented. The series was obtained by analyzing the authors' own series of bioptic findings covering the period of two years. Some problems arising at the evaluation of proliferating myogenic and stromal precancerous and tumorous lesions are pointed out. "Classical" types of leiomyomas were found to be predominant, amounting to 78.5% of tumors recorded at the studied site. Of the total number of tumors of the corpus uteri, malignant tumors constituted only 8.5%. On evaluating the series of malignant tumors of the corpus uteri epithelial malignant tumors (94.3%) were overwhelmingly prevailing over sarcomatous tumors. Attention is called to problems of histological evaluation of prognosis of mesenchymal and mixed tumors. Literary data as well as the authors' own observations indicate the necessity of exact and particularly of differentiated histological evaluation of the described tumors.

Mixed hepatoblastoma in the adult: morphological and immunohistochemical findings.

A case of mixed hepatoblastoma in a 66-year-old man is discussed. Assessment of malignant mesenchymal and malignant epithelial elements yields the diagnosis. In the reported case, the epithelial area consisted of fetal hepatocytes. Distinct ductal differentiation, chondroid and even asteoid metaplasia were recorded. The morphological and immunohistochemical findings observed in the given patient are compared with data published in the world literature.