A patient with prostate cancer and multiple myeloma-diagnostics and possible association of both diseases.

In this report, we describe a case of a patient with prostate cancer and multiple myeloma as the second metachronous malignant disease. To our knowledge, synchronous occurrence of bone marrow prostate cancer metastases and multiple myeloma-as it was found in the clinical disease course of our patient-has not been documented in the literature. Among other diagnostic procedures, cytomorphology and immunocytochemistry analyses contribute to detection of metastases of epithelial cells and synchronous plasma cell proliferation in bone marrow. Occurrence of multiple myeloma and prostate cancer in our patient adds to other similar reports and points to possible association between both diseases and also to other factors involved in the development of a second malignant disease. Further studies are needed to confirm and clarify this association, because prostate cancer is a relatively common malignant disease.

Testicular germ cell tumor composed of placental site trophoblastic tumor and teratoma.

We present a case of a 24-year-old man with a right testicular mass, 2.5 cm in largest diameter. Before orchiectomy, the serum level of beta-human chorionic gonadotropin (hCG) was elevated, whereas that of alpha-fetoprotein was normal. Histologic examination showed a malignant germ cell tumor with a unique and hitherto unpublished combination of placental site trophoblastic tumor and teratoma. Testicular tubules adjacent to the tumor contained intratubular germ cell neoplasia. All cells of placental site trophoblastic tumor were immunohistochemically cytokeratin 7, 18, and pancytokeratin positive and cytokeratin 20, S-100 protein, alpha-fetoprotein, placental alkaline phosphatase, p63, OCT3/4, Nanog, and calretinin negative. Ten percent of the placental site trophoblastic tumor stained with hCG, 30% with epithelial membrane antigen and human placental lactogen, and 80% with inhibin antibodies. FISH study showed a gain on the short arm of chromosome 12 in the placental site trophoblastic tumor, proving that this component is of germ cell origin. The patient is alive and well 3 years after the orchiectomy without additional treatment.

E-cadherin and beta-catenin expression patterns in malignant melanoma assessed by image analysis.

BACKGROUND: We investigated the expression of E-cadherin and beta-catenin in melanoma. Both proteins are components of adherens junctions but also play signalling roles in the wnt signal transduction pathway. MATERIALS AND METHODS: Seventy malignant melanomas were analysed by immunohistochemistry and evaluated by image analysis as staining density, i.e. light permeability (LP). RESULTS: Comparison of mean values of relative LP for E-cadherin and beta-catenin in tumor tissue shows that levels of E-cadherin protein are significantly lower (259.67-116.23; t=22.7; p=0.000). The comparison of mean values of the relative LP of E-cadherin in melanoma to the LP in the adjacent normal skin also shows that the expression of E-cadherin in tumor is significantly lower (256.06-169.87; t=11.55, p=0.000). beta-catenin was observed in the cytoplasm in 30.6% of patients, in 24.2% in the cell membrane, in 21% in both the cytoplasm and membrane, in 1.6% in the membrane and nucleus and in 4.8% in the cytoplasm and nucleus, whereas in 17.7% of patients beta-catenin could not be observed. Patients with Clark 4 and 5 had significantly less beta-catenin than patients with Clark 2 and 3 (chi2=12.854; p=0.005). CONCLUSIONS: Changes in E-cadherin and beta-catenin levels have important roles in melanoma and could be used as molecular markers of disease progression.

Severe postoperative hypoglycemia in a patient with pheochromocytoma and preclinical Cushing's syndrome.

BACKGROUND: Postoperative hypoglycemia is not a common complication following the removal of a pheochromocytoma. Although the mechanism of hypoglycemia is not fully understood, it seems that it is caused by excessive rebound secretion of insulin after surgical resection of pheochromocytoma. CASE REPORT: We report a 43-year-old woman with a very rare association of pheochromocytoma and preclinical Cushing's syndrome (PCS) in the same adrenal gland who developed severe postoperative hypoglycemia. Pheochromocytoma was diagnosed by high serum and urine metanephrine and normetanephrine levels. PCS was characterized by blunted cortisol diurnal rhythm, low ACTH level, and failure of cortisol suppression by dexamethasone without any clinical signs of cortisol excess. In the early postoperative period after surgical removal of right adrenal gland, the patient lapsed into a stuporous state. The blood glucose level was 0.7 mmol/l. During the next 48 hours, normoglycemia was maintained with a continuous infusion of 20% glucose. On the third postoperative day, infusion was discontinued, oral feeds were introduced, and the plasma glucose level normalized. The patient did not have further episodes of hypoglycemia. Pathology revealed medullary pheochromocytoma and a cortical tumor of right adrenal gland. During the fifth postoperative day, plasma metanephrine and normetanephrine were 0.13 nmol/l and 0.30 nmol/l, respectively. Urinary metanephrine decreased to 0.5 pmol/24 h and normetanephrine to 2.8 micromol/24 h. CONCLUSIONS: This report indicates the importance of close monitoring of blood glucose level in a patient with pheochromocytoma after removal of an adrenal gland.

Immunohistochemical expression of tumor antigens MAGE-A1, MAGE-A3/4, and NY-ESO-1 in cancerous and benign prostatic tissue.

OBJECTIVE: To investigate immunohistochemical expression of MAGE-A and NY-ESO-1/LAGE-1, cancer testis antigens in prostate tissues showing evidence of malignant transformation or benign hyperplasia. METHODS: 112 prostate samples from patients undergoing surgery at the Urology Clinic at the Zagreb Clinical Hospital Center from 1995 to 2003 were investigated in this study. Of these, 92 carcinoma samples were obtained by radical prostatectomy, and 20 benign prostatic hyperplasia samples by transvesical prostatectomy. Three monoclonal antibodies were used for immunohistochemical staining: 77B for MAGE-A1, 57B for multi-MAGE-A and D8.38 for NY-ESO-1 expression. RESULTS: Expression of MAGE-A1 was observed in 10.8% of carcinoma samples, whereas multi-MAGE-A and NY-ESO-1/LAGE-1 stained 85.9% and 84.8% of samples. Immunohistochemical staining was only detectable in the cytoplasm. A significant heterogeneity could be observed within a same tissue sample where areas with strong positivities coexisted with cancer testis antigens negative areas. Interestingly, a majority of 57B positive cases were also found to be D8.38 positive (correlation coefficient r=0.727 (P<0.01)). Cancer testis antigens expression was neither significantly correlated with PSA values nor with Gleason score. In benign prostatic hyperplasia tissues MAGE-A1 expression was detected in 5%, while 57B and D8.38 staining was observed in 15% samples, and in all cases percentages of positive cells were always <10%. CONCLUSION: Our data underline the peculiar relevance of cancer testis antigens expression in prostate cancers, with potential implications regarding both diagnosis and therapy.

[New insights on genetics of malignant melanoma]. / Najnovije spoznaje o genskoj osnovi melanoma.

This review seeks to bring novel findings of genetic basis of melanoma. CDKN2A and CDK4 genes residing on chromosomes 9p21 and 12q14, as well as MC1R gene located at 16q24 are main candidates responsible for melanoma development and progression. These genes together with signal transduction pathways in which they are implied are primarily changed in hereditary melanoma. Moreover, changes of genes: BRAF, RAS, c-MET and PTEN characterize sporadic forms of melanoma. Today's knowledge on melanoma genetics is rather inconsistent and involves different genes and signalling pathways. Series of consecutive genetic events that lead to melanoma progression is a very dinamic scientific field in medicine.