Micropapillary urothelial carcinoma of the ureter.

Micropapillary urothelial carcinoma (MPUC) is a rare aggressive variant of urothelial carcinoma, associated with advanced tumor stage, high tendency to invade lymphovascular spaces, and metastasize to lymph nodes and other organs. Therefore, it has a poor prognosis. One of the most prominent histological features is the presence of small, round empty spaces surrounding infiltrating tumor nests. If detected, even a small focus of micropapillary pattern may be therapeutically significant; the higher proportion of micropapillary component, the worse the prognosis. Radical nephroureterectomy is the treatment of choice even in the setting of superficially invasive disease. Although, MPUC has been well studied in urinary bladder, only a few cases of MPUC in upper urinary tract have been described. We are describing a case of a 79-year old woman with micropapillary urothelial carcinoma involving ureter and review the literature of this rare entity.

Prognostic value of galectin-3 in primary cutaneous melanoma.

BACKGROUND: Galectin-3, one of the ß-galactoside-binding lectins, has been suggested as a marker of disease progression in melanoma patients because of its overexpression observed in recent studies. However, prognostic value of galectin-3 in primary cutaneous melanoma (PCM) has not been clearly defined. OBJECTIVES: The aim of the study was to analyse whether the intensity of galectin-3 expression can predict survival in patients with PMC. METHODS: Galectin-3 expression was evaluated using immunohistochemistry in 104 PCM samples, including 71 (68.2%) superficial spreading (SSM) and 33 (31.8%) nodular melanomas (NM). RESULTS: Significant difference of galectin-3 expression between SSM and NM was determined (P < 0.001). Increased galectin-3 expression was positively correlated with tumour thickness (P < 0.001), Clark (P < 0.001) and Breslow (P < 0.001) stage, mitotic rate (P < 0.001), presence of tumour ulceration (P < 0.001), lymphatic invasion (P = 0.018), positive sentinel lymph node (P < 0.022) and distant metastases (P < 0.001). Kaplan-Meier analysis showed an association between increased galectin-3 expression and reduced recurrence-free survival (RFS) (P = 0.001) and reduced disease-specific survival (DSS) (P = 0.015). In Cox proportional hazards regression analysis, significant predictors of reduced RFS were positive sentinel lymph node (P = 0.025) and lymphovascular invasion (P = 0.021), whereas predictors of DSS were tumour thickness (P = 0.012), lymphovascular invasion (P = 0.047), Clark stage (P = 0.029) and location of tumour on upper extremities (P = 0.024). CONCLUSIONS: Our results support the potential role of galectin-3 in PCM development, progression and metastasis. Moreover, galectin-3 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression and metastasis in patients with PMC.

Renal artery changes in patients with primary renal cell carcinoma.

Arterial fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic, occlusive condition of the systemic arteries, most frequently affecting renal arteries. Renal cell carcinoma (RCC) might be associated with arterial hypertension; however, there are no data in the literature regarding the relationship between RCC and associated renal artery changes. We analyzed a consecutive series of 57 (35 male and 22 female) patients aging from 35 to 79 years (mean 58.9 years) who underwent nephrectomy due to RCC in the year 2003. The patients had RCC measuring from 2 to 16 cm (mean 7.1 cm). Specimens were routinely fixed, embedded in paraffin, cut, and stained with hematoxylin and eosin, Mallory trichrome method, and orcein. Renal arteries of 26 patients (20 male, 6 female) showed no changes. In these patients, RCC measured 2.5-11 cm in largest diameter (mean 6.6 cm). In 24 patients (10 male, 14 female), renal arteries showed FMD. RCCs in these patients measured between 2 and 16 cm (mean 8.0 cm). Seven patients had atherosclerotic changes in renal arteries. In this series, FMD was found in a significant proportion of patients with RCC, mainly in women. The cause of such changes and their relationship with RCC and systemic hypertension should be further analyzed.

Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate adenocarcinoma.

The aim of this study was to analyse relationship between changes of the stroma and expression of tenascin-C (TN-C) and laminin in prostate carcinoma. Tenascin-C immunostaining was increased, and laminin decreased in carcinomas compared with peritumoral tissue and benign prostate hyperplasia (P<0.05). Statistical analysis confirmed connection between stromal changes and TN-C expression in prostate carcinoma (P<0.05). Gleason pattern 3 carcinomas showed more pronounced stromal reaction and TN-C expression compared with Gleason pattern 4 carcinomas (P<0.05). The main cells in prostate cancer stroma are myofibroblasts that are also responsible for tenascin production. Degradation of laminin was not connected with myofibroblastic stromal changes.

Ultrastructural analysis and TUNEL demonstrate motor neuron apoptosis in Werdnig-Hoffmann disease.

Werdnig-Hoffmann disease (WHD) is the most severe clinical type of spinal muscular atrophy characterized by loss of lower motor neurons and paralysis. We examined the hypothesis that disease pathogenesis is based on an inappropriate persistence of normally occurring motor neuron programmed cell death. The diagnosis of WHD was made on the basis of clinical findings, electromyoneurography, and biopsy, and further confirmed by mutation analysis of the survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes using PCR. We used ultrastructural analysis as well as TUNEL and ISEL methods to assess DNA fragmentation, and immunocytochemistry to identify expression of the apoptosis-related proteins bcl-2 and p53. A significant number of motor neurons in the spinal cord of children with WHD were shown to die by apoptosis. As revealed by TUNEL, dying neurons in WHD patients comprised 0.2%-6.4% of the neuron numbers counted. This finding contradicts earlier studies that failed to find such evidence and suggests that early blockade of prolonged motor neuron apoptosis may be a potential therapeutic strategy for WHD.

Parachordoma: a case report.

Parachordoma is a very rare soft tissue tumor with histological features similar to chordoma and chondrosarcoma. It should be distinguished from metastatic chordoma and extraskeletal myxoid chondrosarcoma because of its different treatment and prognosis. In this paper we report one case of parachordoma in a 20-year-old female patient. The tumor occurred in the subcutaneous tissue of the left hand as a painless, fixed, slow-growing mass. Pathologic analysis revealed a tumor composed of lobules of cells with variably vacuolated cytoplasm (physaliphorous cells) separated by fibrous septa, predominantly arranged in peculiar small or large alveolar structures. Immunohistochemistry showed positive staining of the tumor cells with cytokeratin 8/18, S-100 protein and vimentin. The patient is well and without recurrence 20 months after surgery.

Salivary duct carcinoma metastasizing to the small bowel.

We report a case of salivary duct carcinoma in a 47-year-old woman. The patient presented with symptoms simulating acute appendicitis. Surgery revealed metastatic tumor in the wall of the small bowel. Two months later, a tumor of the right parotid gland was resected, and histologic analysis revealed a salivary duct carcinoma. To our knowledge, this is the first case of salivary duct carcinoma metastasizing to the small bowel with manifestations of metastatic disease as the prominent symptom.

Calcified leiomyoma of the lateral pterygoid muscle in an 8-year-old boy.

Deep soft tissue leiomyomas are extremely rare benign tumors in childhood. An unusual case of benign calcified leiomyoma of the pterygoid muscle in an 8-year old boy is presented. Clinical manifestations and radiographic and histologicpathologic findings, as well as the differential diagnosis and possible histogenesis of this rare tumor, are discussed.

Correlation between vimentin expression and morphological features of renal cell carcinoma.

The aim of this study was to analyze the correlation between the expression of vimentin and morphological features of renal cell carcinoma (RCC). We analyzed tumor tissue of 20 patients with RCC. There were 13 female and 7 male patients with RCC confined to the kidney (pT1, pT2). They were ranging in age from 36 to 80 years (mean age 60.6 years). Thirteen tumors measured > 5 cm and 7 tumors < 5 cm in diameter. Two tumors were papillary and 18 tumors showed a non-papillary pattern. Six tumors were composed of granular cells and 14 tumors of clear cells. Formalin fixed, paraffin-embedded tumor tissue was cut at 5 microns, deparaffinized, and stained with a monoclonal antibody to vimentin (Dako, Denmark). There were 4 tumors with nuclear grade I, 3 with grade II, 11 with grade III, and 2 with grade IV. Histopathologic examination showed vimentin expression in eight cases (40%), while 12 tumors (60%) were negative. Positive reaction for vimentin was observed in all four grade I tumors, none of three grade II tumors, four of 11 grade III tumors and in none of 2 nuclear grade IV tumors. In our study, there was no statistically significant difference between the expression of vimentin and morphologic features of RCC. Our study showed the lack of correlation between the expression of vimentin and nuclear grade, cell type and histologic pattern of RCC. Further studies on a larger series of tumors as well as follow-up of patients are obviously needed.

Congenital anomalies of the central nervous system at autopsy in Croatia in the period before and after the Chernobyl accident.

In this study, we analyzed the frequency, type and sex distribution of congenital anomalies of the central nervous system (CNS) at autopsy in the period prior to and after the Chernobyl accident in northwest Croatia, one of the areas with the highest exposure to nuclear contamination from Chernobyl. All autopsies in both periods were performed by the same technique, i.e. dissection of the trunk and head, and inspection of the extremities. There were 53 infants with congenital anomalies of the CNS in the period prior to, and 99 in the period after the Chernobyl accident. Our results showed a statistically significant increase in the incidence of CNS anomalies in general (chi 2 = 4,719, p < 0.05, D. F. = 1) and of neural tube defects (chi 2 = 5.380, p < 0.05, D. F. = 1) in the period after the Chernobyl accident. Differences in the incidence of various CNS anomalies, in all types of anomalies, and in sex distribution were not statistically significant. Studies of the association between the Chernobyl accident and congenital anomalies showed no clear changes in the prevalence of anomalies at birth which might have been associated with the accident. This study provided some additional data on the frequency of CNS anomalies in the period after the Chernobyl accident in one of the areas with the highest exposure to the nuclear contamination from Chernobyl. We suggest that the frequency of all anomalies, including CNS, in the period after the Chernobyl accident should be carefully monitored.

[Primary malignant melanoma of the female urethra]. / Primarni maligni melanom zenske uretre.

Primary malignant melanoma of the genitourinary tract is rare and accounts for less than 1 per cent of all melanomas. The most frequent locations in male are penis and urethra. The most frequent site in female is urethra and it most commonly affects meatus and the distal urethra. The prognosis is poor. We report a patient with primary malignant melanoma of the female urethra. Clinicopathologic features and treatment of this tumor are discussed.

[Carcinoma of the urinary bladder resembling lymphoepithelioma]. / Karcinom mokracnog mjehura slican limfoepiteliomu.

Lymphoepithelioma-like carcinoma of the bladder is rare and has only recently been described at this site. We report a case of lymphoepithelioma-like carcinoma of the urinary bladder in a 70-years old male patient who presented with painless hematuria lasting for one month. The patient underwent transurethral resection two times. Histopathologic diagnosis was transitional cell carcinoma. Histopathologic examination of the third biopsy showed tumor tissue with typical syncitial growth pattern of atypical, large, epitheloid cells with ill-defined cytoplasmic borders, prominent nucleoli and numerous mitoses. A prominent lymphocytic infiltrate was found as a component of the tumor. Immunohistochemistry showed positive reaction for cytokeratin and epithelial membrane antigen, and negative results for leukocyte common antigen, CD3, CD20, CD30, CD68 and PSA. The lymphoid infiltrate was an admixture of T and B cells. The tumor invaded the muscle wall. After last surgery the patient underwent chemotherapy by local application of Adriablastine. At present the patient is without recurrence 10 months after the last surgery.

[Pathohistologic procedures in encapsulated follicular tumors of the thyroid gland]. / Osobitosti pathohistoloske obrade ocahurenih folikularnih tumora stitne zlijezde.

Determination of pathohistologic diagnosis of encapsulated thyroid tumors, particularly follicular carcinoma, is sometimes very difficult, even for well-experienced pathologists. The analysis of intraoperative biopsies could be even more difficult. The importance of proper handling of bioptic material for correct interpretation of pathohistologic findings is not adequately stressed in our literature. In this article, we point out necessity of serial sections of encapsulated follicular tumors for correct diagnosis.

[Congenital anomalies of the central nervous system 1990-1993]. / Kongenitalne anomalije sredisnjega zivcanog sustava u razdoblju od 1990. do 1993. godine.

We have analyzed all available data including birth certificates, maternity records, pediatric records, and pathology reports of spontaneous and induced abortions and newborn deaths to determine the frequency of congenital anomalies of the central nervous system. We found 76 infants (34 males, 39 females and 3 of undetermined sex) with CNS anomalies during the 1990-93 period. In the same period there were 23,425 births. The frequency of CNS anomalies in this period was 32,4/10,000 births. These results are at variance with conclusions of previously published and incomprehensive studies in Croatia. Therefore, a systematic follow-up of the autopsy findings of induced and spontaneous abortions and newborn deaths in the epidemiology of CNS anomalies is clearly needed.

[Relation between grades of histologic differentiation and hormone receptors in breast cancer]. / Odnos izmedu stupnja histoloske diferenciranosti i hormonskih receptora kod raka dojke.

The relationship between the grade of histologic differentiation of the tumor and estrogen (ER) and progesterone (PgR) receptor values was analyzed in 261 patients with breast cancer of the invasive duct type. There was a statistically significant difference in concentration and incidence of positive and negative ER and PgR with regard to histologic grade. The concentration and number of positive hormone receptors increased with better differentiation of the tumor. A statistically significant correlation between histologic grade, hormone receptor values and axillary nodal involvement was obtained only in patients with no metastases to axillary lymph nodes.

[Prognostic value of determination of the presence and histologic grade of the intraductal component in invasive ductal carcinoma of the breast after conservative treatment]. / Prognosticka vrijednost odredivanja prisutnosti i histoloskog stupnja intraduktalne komponente invazivnog duktalnog karcinoma dojke nakon postednog lijecenja.

In recent years, breast-conserving therapy and radiation therapy have become an important treatment option for patients with stage I and II invasive breast cancer. The results of long-term retrospective studies have demonstrated that this treatment can provide a high level of local tumor control with satisfactory cosmetic results. Numerous studies have shown that the presence of extensive intraductal component (prominent intraductal carcinoma) is highly associated with subsequent local recurrence. In this article we have stressed the value of the determination of the presence and the histologic grade of prominent intraductal component of invasive ductal breast carcinoma in the determination of the extent of surgery. We also point out the possibility of determination of prominent DCIS on frozen sections.

TGF-ß1 expression in chromophobe renal cell carcinoma and renal oncocytoma.

Distinguishing renal oncocytoma (RO) from the eosinophilic variant of chromophobe renal cell carcinoma (ChRCC) under the light microscope is a common diagnostic problem. Our recent research has shown significant difference between the presence of tumor fibrous capsule in ChRCCs and ROs. Transforming growth factor beta 1 (TGF-ß1) is a potent cytokine involved in regulating a number of cellular processes. Two main purposes of this research were to investigate whether the TGF-ß1 staining could be related to the presence of tumor fibrous capsule and if it could be used in the differential diagnosis between ChRCC and RO. We investigated 34 cases: 16 ChRCCs (8 eosinophilic and 8 classic) and 18 ROs. All available slides of each tumor, routinely stained with hematoxylin and eosin (H&E) were first analyzed to note the presence of tumor fibrous capsule. One paraffin embedded tissue block matching the representative H&E slide was selected for the immunohistochemical analysis. TGF-ß1 expression was analyzed semiquantitatively in the tumor tissue, the tumor fibrous capsule, if present and the peritumoral renal parenchyma. Intensity of TGF-ß1 expression was weaker in ChRCCs than the one observed in ROs (P<0.05). The type of reaction in ChRCCs was predominantly membranous unlike in ROs, which exhibited a predominantly cytoplasmic reaction (P<0.05). Moreover, none of the ROs showed membranous type of reaction for TGF-ß1. In the group of ChRCCs, tumors with capsule had statistically significant higher quantity of TGF-ß1 expression in tumor tissue and in peritumoral renal parenchyma compared to the tumors without capsule (P<0.05). Our results showed different types of TGF-ß1 expression in ChRCCs and ROs: ChRCCs had predominantly membranous type of reaction, and ROs predominantly cytoplasmic. Furthermore, ChRCCs with capsule had statistically significant higher quantity of TGF-ß1 expression in tumor tissue and in peritumoral renal parenchyma compared to the tumors without capsule. Based on these findings we can speculate that it could be possible that TGF-ß1 plays a role in the formation of fibrous capsule in ChRCCs.

MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma.

In the present study we analyzed immunohistochemical expression of MAGE-A 3/4 and NY-ESO-1 in 55 samples of esophageal squamous cell carcinomas (ESCC) and their respective lymph node metastases. To our knowledge this is the first study to assess and compare the expression of these antigens in ESCC lymph node metastases. Fifty (90.9%) primary ESCC were positive for MAGE-A 3/4 and 53 (96.6%) were positive for NY-ESO-1. MAGE-A 3/4 was expressed in all lymph node metastases and the intensity of expression was high in a majority of cases. NY-ESO-1 was negative in 2 (7.1%) lymph nodes metastases, while the reaction was predominantly moderate in the positive group. In primary tumors MAGE-A 3/4 showed a significantly higher intensity of expression compared to NY-ESO-1 (P=0.047), while in lymph node metastases the intensity of expression was not significantly different (P=0.387). Primary tumors with and without lymph node metastases showed no significant differences in MAGE-A 3/4 (P=0.672) and NY-ESO-1 (P=0.444) expression. Intensity of MAGE-A 3/4 (P=0.461) and NY-ESO-1 (P=0.414) expression in primary tumors was not significantly different compared to the expression in their respective lymph nodes metastases. Expression of MAGE-A 3/4 in primary tumors showed significant positive correlation with primary tumor expression of NY-ESO-1 (P=0.021) but no significant correlation with the expression of MAGE-A 3/4 in lymph node metastases (P=0.056). Expression of NY-ESO-1 in primary tumors showed significant positive correlation with the expression of NY-ESO-1 in lymph node metastases (P=0.001) and significant negative correlation with patients’ age (P<0.001). Expression of MAGE-A 3/4 and NY-ESO-1 in primary tumors and lymph node metastases showed no significant correlation with prognostic parameters such as tumor grade and TNM stage (P>0.05). We have shown different levels of MAGE-A 3/4 and NY-ESO-1 expression in almost all specimens of primary tumor and lymph node metastases, suggesting that ESCC may be possible target of immunotherapy and anti-tumor vaccination. High levels of expression in lymph node metastases indicate possible clinical benefit of postoperative vaccine with MAGE-A3 and NY-ESO-1 in advanced stage of disease.

Expression and prognostic role of syndecan-2 in prostate cancer.

Syndecans are a four-member family of transmembrane heparan sulphate proteoglycans that have different functions in cell signalling, adhesion, cytoskeleton organization, migration, proliferation, and angiogenesis. Several studies investigated the role of syndecan-2 (SDC2) in different carcinomas; however, only one being focused on SDC2 in prostate cancer. SDC2 expression and relationship with established prognostic features were assessed in a cohort of 86 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. SDC2 expression was present in the majority of prostate cancers and absent in only 11.6% of cases. SDC2 expression was also recorded in cells of prostatic intraepithelial neoplasia, whereas normal prostatic epithelial tissue and stroma did not express SDC2. SDC2 overexpression in prostate cancer was significantly associated with established features indicative of worse prognosis such as higher preoperative PSA (P=0.011), higher Gleason score (P<0.001), positive surgical margins (P<0.003), and extraprostatic extension of disease (P<0.003). Moreover, expression of SDC2 was also associated with biochemical disease progression on univariate analysis (P<0.001). Study results supported the potential role of SDC2 in prostatic carcinogenesis and cancer progression. Moreover, SDC2 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression in patients with prostate cancer.