CORRELATION OF EXPRESSION OF TGF- ß AND MMP2 BETWEEN PROSTATIC ADENOCARCINOMA AND ADJACENT UNAFFECTED PARENCHYMA.

In prostate adenocarcinoma, both tumorous stroma and epithelium have important role in tumor progression. Transforming growth factor beta (TGF- ß) is a promotor in advanced stages of prostate cancer. Matrix Metalloproteinase 2 (MMP2), the endopeptidase that degrades extracellular matrix is considered to be overexpressed in prostatic carcinoma related to its growth and aggressiveness. Therefore, the aim was to analyze the expression of proteins TGF- ß and MMP2 between both epithelium and stroma of prostatic adenocarcinoma and adjacent unaffected parenchyma. The intensity of TGF- ß and MMP2 expression in epithelium, tumorous stroma and adjacent unaffected parenchyma was analyzed in 62 specimens of prostatic adenocarcinoma by microarray-based immunohistochemistry. TGF- ß was more expressed in tumorous than in prostate stroma (p =0.000), while no statistical significance in case of MMP2 (p = 0.097) was found. MMP2 was more expressed in tumorous than in prostate epithelium (p =0.000), while no statistical significance in case of TGF- ß (p = 0.096) was observed. The study results indicate that both tumorous stroma and epithelium have a role in tumor progression and support potential role of TGF- ß and MMP2 in prostatic adenocarcinoma progression.

PATHOLOGICAL CHANGES OF RENAL ARTERIES IN PATIENTS WITH RENAL CELL CARCINOMA.

Renal cell carcinoma is the ninth most common cancer in the world. It may have a varied microscopic appear- ance, and the most common histopathological type is clear cell carcinoma. The most common pathological changes of renal arteries are atherosclerosis and fibromuscular dysplasia (FMD). During histopathological evaluation of a kidney specimen containing carcinoma, the renal vein is routinely analyzed, while the renal artery is usually given little attention. Our stud- ies have shown that pathological changes of renal arteries are significantly more frequent in the group of patients with renal cell carcinoma compared with the control group and the group of patients with non-tumor kidney diseases. These relations led us to the conclusion that the onset of renal artery changes is not prior to the carcinoma or non-tumor diseases and that they are formed simultaneously or as a consequence. Further studies should be aimed at determining the incidence of these changes in a larger number of samples and the detection of their possible correlation with renal cell carcinoma.

Surgical treatment for nasal polyposis: predictors of outcome.

Nasal polyps recur in approximately one-third of patients after surgical treatment. It would be beneficial to be able to predict the patients in whom we might expect recurrence and to predict the clinical outcome after surgery. The study included 30 patients operated for nasal polyps. Removed polyps were analyzed by immunohistochemical analysis for IL-5, IgE, vascular endothelial growth factor and eosinophilic infiltration. These parameters together with preoperative CT score were used as independent variables, and subjective score improvement after 2 years was used as a dependent variable in multiple linear regression analysis. Furthermore, the patients were divided into two groups: low and high polyp tissue immunoreactivity. The Chi-squared test was used to determine whether polyp immunoreactivity influences polyp recurrence and subjective score. Preoperative CT score had a slightly positive correlation with subjective score after 2 years. High eosinophil infiltration significantly predicted a higher risk for polyp recurrence. High IL-5 positivity was related to greater risk for polyp recurrence than low IL-5 reactivity but not significantly. IgE and VEGF reactivity in polyp specimens did not have any effect on polyp recurrence. High eosinophilic infiltration in polyps can predict worse outcome after surgical treatment of chronic rhinosinusitis with nasal polyposis. IgE and VEGF do not have prognostic significance to polyp recurrence after surgery. The preoperative extent of disease measured by CT score had a slightly positive correlation with worse outcome after surgery.

Pathological characteristics and clinical perspectives of papillary thyroid cancer: study of 714 patients.

Papillary thyroid cancer belongs to most commonly diagnosed well-differentiated malignant tumor of the thyroid gland, with only minority of cases being more aggressive, recurring locoregionally and developing distant metastatic foci. The aim of this study was to determine the clinical relationship between parameters of age, gender, size of primary tumor, intraglandular dissemination and regional metastatic spread and evaluate the importance of each parameter; analyze other major aggressive factors (tumor border, thyroid capsule invasion, perivascular, perilymphatic spread) on prevalence and extent of intraglandular dissemination and relation to metastatic spread in neck. This study is a retrospective analysis of clinical and pathological data from 714 patients with papillary thyroid cancer, presented and operated at the Department of ENT/Head and Neck surgery, Sisters of Charity University Hospital, Zagreb, in the period from 1980 to 2008. All patients were operated upon with total thyroidectomy and some type of neck lymphonode dissection (paratracheal or lateral). In results, we found 46.9% tumors were aggressive; 34.7% tumors were multicentric, with foci in the contralateral lobe nearly twice as often as in the ipsilateral lobe; 27.8% were regionally metastatic, with equal distribution between paratracheal and lateral regions. In conclusion, we revealed contralateral lobe multicentricity and male gender as independent risk factors for regional metastatic dissemination. Nodular goiter has been identified as a protective parameter.

Dedifferentiated Primary Parosteal Osteosarcoma of the Temporal Bone in a 19-Year-Old Patient: A Case Report.

Osteosarcoma is the most common primary malignant tumor affecting the bone but is a rare occurrence in the head and neck region. Complete surgical resection with wide surgical margins is currently the main treatment strategy for osteosarcoma but can be hard to achieve due to the complex anatomy of the head and neck. We report the first case of primary high-grade dedifferentiated parosteal osteosarcoma arising from the temporal bone in published literature. The 19-year-old patient presented with a left retroauricular lesion measuring 3 cm in diameter. Radiographic imaging and biopsy suggested the diagnosis of intermediate-grade chondrosarcoma, but definitive histopathology confirmed a diagnosis of dedifferentiated parosteal osteosarcoma. The tumor was resected with wide margins, removing the underlying temporal bone, periosteum and overlying soft tissue through a lateral temporal bone resection. The middle ear was reconstructed with cartilage grafting, and the dura of the posterior and middle cranial fossa was covered using temporal fascia grafts and local transpositional flaps. The patient is recurrence free 10 months after treatment. This report was assembled following CARE [The CARE guidelines (for Case Reports)] guidelines and describes clinical, histological, and radiological manifestations of our patient's rare clinical entity and may provide more data in treating patients with osteosarcoma affecting the anatomically complex head-and-neck region.

Prognostic value of Helicobacter pylori sinonasal colonization for efficacy of endoscopic sinus surgery.

Compared with rhinologic patients without chronic rhinosinusitis (CRS), a higher prevalence of sinonasal Helicobacter pylori (HP) in patients with CRS was found. This study investigated if HP sinonasal colonization has a prognostic value for efficacy of functional endoscopic sinus surgery (FESS). Nasal polyps of 40 patients with CRS, undergoing FESS, were analyzed for presence of HP using immunohistochemistry (IHC). Patients were categorized as to whether the IHC was positive (HP+ group) or negative (HP- group). HP+ group and HP- group were compared according to the nasal polyp eosinophil density, and to the improvement (difference between pre- and post-operative scores) of the subjective symptom scores, and the nasal endoscopic scores. Nasal polyps in 28 (70%) patients were positive for HP. There were no significant differences between HP+ group and HP- group comparing the eosinophils, and the improvement of the single symptom and the total symptom scores. HP+ group had significantly greater improvement of the nasal endoscopic scores (F[1.38] = 6.212; P = 0.017). There is no influence of sinonasal HP on tissue eosinophilia and on CRS symptoms. There is a prognostic value for endonasal findings: CRS patients with HP have statistically significant greater improvement of the postoperative endoscopic scores.

Giant congenital nevus with plexiform neurofibroma and malignant peripheral nerve sheath tumor.

A female patient with a giant congenital nevus associated with plexiform neurinoma and malignant peripheral nerve sheath tumor (MPNST) on head and neck is presented. We theoretically discuss possibilities of mutual origin all three entities, including the Boland theory of neurochristopaty. The clinical, surgical, and histologic aspects of the disease are discussed. Only one similar case in written literature was described.

Papillary thyroid microcarcinoma: clinical and pathological study of 321 cases.

The primary aim of the study was to investigate microcarcinoma characteristics of aggressivity, multicentricity and metastasis. Though its features are not significantly different from those of other papillary carcinomas, the optimal therapeutic approach continues to be an issue of controversy, most notably appropriate surgical approach and indications for neck dissection. The study is retrospective analysis of 321 microcarcinoma cases, operated upon with total thyroidectomy, with or without neck dissection. These cases were compared to larger papillary cancers. We found that 35.1% tumors were aggressive; 25.2% were multicentric, with foci in the contralateral lobe nearly twice as often as in the ipsilateral lobe; and 18.2% were metastatic. In comparison to groups of < or = 2 cm and < or = 3 cm, microcarcinomas were less aggressive, multicentric and metastatic. Male gender and age < 45 were unfavorable parameters. Multivariate analysis revealed contralateral lobe multicentricity and male gender as risk factors for metastasis. Although microcarcinoma demonstrated better characteristics than larger tumors, this subgroup behaves aggressively and should be approached cautiously.

[Carcinosarcoma of the sigmoid colon with micropapillary pattern: a case report]. / Karcinosarkom sigmoidnoga debelog crijeva s mikropapilarnom slikom: prikaz bolesnice.

Carcinosarcomas are very rare malignant tumors showing both mesenchymal and epithelial differentiation. They most commonly occur in the head and neck region. Few cases were described in the colon associated with very aggressive course. Micropapillary variant is also very rare in the colon and associated with poor prognosis. We report an unusual case of carcinosarcoma of the colon with micropapillary features and psammomatous calcification in an 83-year-old female patient. Tumor was located in the sygmoid colon and measured up to 3.8 cm in the largest diameter. Microscopically it was composed of glandular structures and micropapillary formations with psammomatous calcifications and solid areas built up of spindle cells with focal areas of cartilaginous differentiation. Glandular and micropapillary components immunohistochemically showed positive staining for cytokeratin and EMA while mesenchymal areas were positive for vimentin. The tumor was spreading through the whole thickness of the wall into adjacent fat tissue. Metastases in regional lymph nodes were composed entirely of glandular component. To the best of our knowledge, this is the first case of carcinosarcoma of the colon showing micropapillary features and psammomatous calcification.

Isolated cerebellar intraparenchymal Rosai-Dorfman disease--case report and review of literature.

BACKGROUND: Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) rarely affects intracranial structures without involvement of other sites. We herein review the tumour characteristics, differential diagnosis and treatment policy of this rare disease. METHOD: We conducted a PUBMED search using a combination of words 'Rosai-Dorfman disease', 'Central nervous system', and identified 42 cases of such a disease infecting exclusively central nervous system. Out of those cases only one case was reported to be purely intracerebellar making our case the second one in the literature. Clinical features, differential diagnosis, treatment details and follow-up were discussed. We also described the case of 41-year-old man presented with vertiginous symptoms and mild cerebellar ataxia who was diagnosed with a solitary lesion localised deep in the right cerebellar hemisphere. Immunohistological findings revealed Rosai-Dorfman disease. FINDINGS: The most common locations of the tumour were frontal and parietal region, but CNS lesions have commonly involved the skull base with a leptomeningeal component too. The median age at presentation was in the third decade, ranging from 3 to 78 years. There is a slight male predominance. The follow-up ranged from 1 month to 11 years. Recurrence was not observed in the cases where total surgical excision was performed. CONCLUSION: Though Rosai-Dorfman disease is a rarity, one should take it into a consideration when treating solitary intracerebellar lesion. Thorough preoperative evaluation is mandatory and biopsy should be done whenever feasible. Surgical treatment of this type of tumour is not always necessary, however, it is essential for postulating the right diagnosis. When total tumour removal is achieved, the outcome is generally better, with minimal risk of recurrence and with no need for further additional therapy.

C-myc expression in the microvessels of medulloblastoma.

The increased expression of c-myc is related to neoplastic transformation and angiogenesis. Therefore, the assessment of expression of c-myc in endothelial cells and neovascularization could help to determine the biological behavior of the tumor. We analyzed neovascularization and c-myc expression in 36 medulloblastoma specimens. The results were shown by determining immunohistochemical staining index (ISI), the sum of staining intensity (SI) and the percentage of positive cells (PPC) in the blood vessels endothelium of the tumor. We also performed the microvessel count (MVC) in 10 high-power fields (400X) with the most prominent vascularization and expressed it as microvessel density per mm2 (MVD). C-myc immunostaining intensity index in blood vessel endothelium is grouped into four groups, 0--no reaction, I-weak reaction (ISI = 1 or 2), II--moderate reaction (ISI = 3 or 4), III--strong reaction (ISI = 5 or 6). Statistically significant differences (p = 0.0214) have been found between groups 0 and 1 compared to groups 2 and 3. A higher percentage of positive cells has been found in male patients than in female ones (p = 0.0483). C-myc PPC 0 or 1 has on the average smaller density of blood vessels per mm2 than c-myc PPC 2 or 3, but the difference is not statistically significant. C-myc ISI 0 or 1 has, on the average, smaller density of blood vessels per mm2 than c-myc ISI 2 or 3, but the difference is not statistically significant. We concluded that c-myc staining intensity was associated with higher microvessels density.

Osteolytic skull metastasis with dural involvement from a papillary thyroid carcinoma.

Skull metastatic tumors are relatively rare medical entities and originate most often from the lungs, breast or prostate. We report a case of a 76-year-old woman who presented with a bulging, well-circumscribed mass on the right side of the forehead. Neuroimaging of the cranium detected an osteolytic lesion measuring 7 cm in the largest diameter while propagating outwards and intracranially. A thorough medical history revealed that patient had undergone surgery for invasive breast ductal carcinoma and also for a well-differentiated thyroid carcinoma 13 years ago. Considering patients medical history metastatic breast carcinoma was suspected. After a frontal craniotomy the tumour tissue was totally resected. Histological examination revealed metastatic papillary carcinoma characterized by ground-glass nuclei with intranuclear pseudo inclusion and nuclear grooves. We report clinical and neuroradiological features of this uncommon lesion and discussed the differential diagnosis of skull osteolytic lesion together with the treatment management.

Report on mutation in exon 15 of the APC gene in a case of brain metastasis.

The study analyzes exon 15 of the adenomatous polyposis coli gene (APC) in a 49-year-old male patient with brain metastasis. The primary site was lung carcinoma. PCR method and direct DNA sequencing of the metastasis and autologous lymphocyte samples identified the presence of a somatic mutation. The substitution was at position 5883 G-A in the metastasis tissue. The mutation was confirmed by RFLP analysis using Msp I endonuclease, since the mutation strikes the Msp I restriction site. Immunohistochemical analysis revealed the lack of protein expression of this tumor suppressor gene. The main molecular activator of the wnt pathway, beta-catenin, was expressed, and located in the nucleus. The mutation is a silent mutation that might have consequences in the creation of a new splice site. Different single-base substitutions in APC exons need not only be evaluated by the predicted change in amino acid sequence, but rather at the nucleotide level itself. In our opinion, such silent mutations should also be incorporated in mutation detection rate and validation.

Mixed Type Haemangioma of the Inferior Turbinate: A Rare Cause of Epistaxis.

Haemangiomas of the nasal cavity are rare benign tumours which usually arise in the Kiesselbach triangle of the septum. Mostly they are seen in young population with peak age 20 years. Epistaxis is the most common symptom in these patients. We present a case of a 62-year-old woman with recurrent epistaxis. On examination she had had an obstruction of both nasal cavities. Computed tomography imaging demonstrated a well-defined tumour originating from the posterior tip of the right inferior turbinate, passing into the nasopharynx. The tumour was managed via endoscopic endonasal approach. The histological analysis revealed a tumour tissue with the appearance of a cavernous haemangioma as well as capillary haemangioma. A focus of intravascular endothelial papillary hyperplasia was also observed. In patients with endonasal benign tumours choice of surgical approach depends on the exact location of the tumour and suspected pathology. The transnasal endoscopic approach and bipolar cautery resection enable adequate exposure and visualization of the tumour, control of bleeding and complete removal of the tumour.

Biological value of melanoma inhibitory activity serum concentration in patients with primary skin melanoma.

Melanoma inhibitory activity (MIA) protein was identified in significant quantities in primary and metastatic malignant melanomas, where it has an important role in promoting tumor development and progression. Our hypothesis was that MIA serum level will be elevated in patients with metastases or local spreading of the disease before any symptom of such progression is clinically apparent. We compared MIA serum levels in two groups of patients with primary melanoma; those with positive as opposed to those with negative sentinel lymph nodes. In addition, MIA serum levels were studied in two control groups; patients with dysplastic nevi and patients with basal cell carcinoma. A blood sample was obtained from each patient included in the study and MIA levels were assessed using standard enzyme-linked immunosorbent assay method. Patients with histologically positive sentinel lymph nodes, meaning that tumor cells were found in the lymph nodes, had much higher mean MIA values than any other patient group considered in this study. With mean value of 14.53 ng/ml, it was almost twice as high as mean MIA value in patients with histologically negative sentinel lymph nodes (7.32 ng/ml) and more than twice as high than any of the two control groups (P<0.001). However, neither the classification by Clarke nor the classification by Breslow could be used to distinguish patients with positive sentinel lymph nodes from those with negative sentinel lymph nodes. In our opinion, MIA serum level is the ideal test for screening the tumor spread to sentinel lymph nodes.

Thoracic intramedullary sarcoidosis mimicking an intramedullary tumor.

Sarcoidosis is a chronic, systemic granulomatous reticulosis of unknown origin, characterized by formation of hard tubercles and noncaseatinggranulomas. Since other infectious diseases such as berylliosis, mycobacterium and fungal infections may present with a noncaseating granulomas, histological diagnosis of sarcoidosis is made using the elimination method. Central nervous system manifestations of sarcoidosis may be present in 5-10% of the cases involving cranial nerves, leptomeninges and third ventricle respectively. Any part of the central nervous system can be affected. Involvement of spinal cord in sarcoidosis is extremely rare and presents with only 0.3-0.4% in patients with systemic sarcoidosis. Intramedullary sarcoidosis is a rare first manifestation of the disease and it can mimic an intramedullary tumor, which is often manifested with symptoms that initiate from spinal cord compression, resulting in paraparesis, sensory disorders and sphincter dysfunction. We present a case of intramedullary sarcoidosis that mimics a tumor of the thoracic spinal cord. Clinical features, neuroradiological, pathohistological findings, laboratory analysis and surgical treatment of such a rare entity are being discussed.

Periacinar retraction clefting in proliferative prostatic atrophy and prostatic adenocarcinoma.

AIMS: To evaluate the presence and extent of periacinar retraction clefting in proliferative prostatic atrophy and carcinoma in radical prostatectomy specimens. METHODS: Atrophic foci and neoplastic glands were analysed in specimens from 50 patients who underwent radical prostatectomy. Analysed atrophic glands were classified in two main groups, proliferative atrophy (PA) and proliferative inflammatory atrophy (PIA); each group was subclassified into simple atrophy (SA) and postatrophic hyperplasia (PAH). According to the presence and extent of periacinar retraction clefting, atrophic and neoplastic glands were classified as: group 1, glands without clefts or with clefts affecting 50% of the circumference in <50% of examined glands; and group 3, glands with clefts that affected >50% of the circumference in >or=50% of examined glands. RESULTS: Forty-four (88.0%) atrophic foci were without periacinar clefts or clefts were present in less than half of the gland circumference (group 1). In 6 (12.0%), atrophic foci clefts affected >50% of gland circumference (groups 2 and 3). Forty-five (90.0%) carcinomas were with clefts which affected more than 50% of gland circumference (groups 2 and 3); and in five carcinomas only, clefts were not found or affected <50% of gland circumference (group 1). CONCLUSION: Results indicate that periacinar retraction clefting represents a reliable criterion in differential diagnosis between proliferative atrophy and carcinoma.

An unusual pattern of pseudoepitheliomatous hyperplasia associated with cutaneous primary melanoma: report of two cases with analysis of p53 and bcl-2 immunoreactivity.

Pseudoepitheliomatous hyperplasia (PEH) is a benign, reactive epithelial proliferation. PEH is characterized by hyperplasia of the epidermis or adnexal epithelium into irregular squamous strands that extend deep down into the subjacent dermis. PEH occurs in response to underlying infections, inflammatory or neoplastic conditions. The presence of PEH overlying cutaneous melanoma is rare. The clinical and histological features of PEH can closely mimic squamous cell carcinoma and could be misinterpreted. We report two cases of cutaneous primary melanoma associated with PEH and discuss differential diagnoses and potential role of p53 and bcl-2 in the pathogenesis of PEH.

Periacinar Clefting and p63 Immunostaining in Prostatic Intraepithelial Neoplasia and Prostatic Carcinoma.

The aim of the present study was to correlate the presence and extent of retraction clefting and the expression of p63 in neoplastic glands and glands with prostatic intraepithelial neoplasia (PIN) in needle core biopsies. We analyzed needle core biopsies from 28 patients with PIN and 41 patients with adenocarcinoma. Neoplastic glands and those with PIN were analyzed on high power field (400x) and classified in three groups according to the extent of clefting. Immunohistochemical staining was performed following Microwave Streptavidin ImmunoPeroxidase (MSIP) protocol on DAKO TechMate Horizon automated immunostainer. Periacinar retraction clefting was significantly more prominent in prostatic carcinoma compared to PIN (p<0.0001) and nonneoplastic glands (p<0.0001). There was no difference between normal glands and PIN regarding clefting (p=0.8064). p63 was positive around the whole circumference in 12 out of 28 cases with PIN, and discontinuously positive in remaining 16 PIN cases suggesting initial disruption of the basal cell layer. p63 immunostaining was also positive in all nonneoplastic glands, and negative in all carcinomas. We conclude that retraction clefting was associated with cancer and lack of basal cells, but not with PIN. The relationship between clefting and p63 immunostaining in prostatic cancer should be further analyzed.

Histopathologic parameters as predictors of response to endoscopic sinus surgery in nonallergic patients with chronic rhinosinusitis.

OBJECTIVE: To estimate the predictable value of histopathologic parameters in chronic rhinosinusitis (CRS) for response to endoscopic sinus surgery (ESS). STUDY DESIGN: Symptomatology was rated in 100 patients prior to as well as 12 and 24 months after surgery. Specimens taken during the procedure were examined and scored for goblet cells, subepithelial thickening, mast cells, and eosinophils. Multiple regression analysis was performed to predict the total score of subjective symptoms before treatment by histopathologic parameters. The correlation between histopathologic parameters and postoperative symptoms was then evaluated. RESULTS: Goblet cells were the best predictor correlating with 5 symptoms. Subepithelial thickening correlated with 4 symptoms. Mast cell infiltration correlated with 3 symptoms. Eosinophilic infiltration correlated with only one symptom (P<0.05). CONCLUSION: Certain histopathologic parameters in CRS are predictive of favorable response to ESS. SIGNIFICANCE: Pathologic evaluation may help the ENT surgeon to predict the persistence of certain CRS symptoms after ESS, even in patients at low risk for surgical failure. EBM RATING: C-4.