Role of cytoblock on pleural effusion for diagnosis of malignant disease.

BACKGROUND: Thoracocentesis of pleural effusion is a simple technique for pleural fluid examination through cytology. In addition to cytological examination to assess the nature of pleural fluid content, we can also perform more detailed examinations through cytoblocks of residual fluid. These paraffin-embedded cytoblock samples are important because we can perform examinations as in other bioptic samples. In these samples, immunohistochemical and molecular analyses can be performed. METHODS: Two hundred fifty-five cytological samples from patients with pleural effusion were examined. In cases in which the presence of malignant cells was identified in the cytological examination, as well as cases that were suspicious but not definitive for the presence of a malignant effusion, a cytoblock was prepared. Histological examination and immunohistochemical analysis were performed. RESULTS: Among 255 cases with pleural effusion, 152 had the presence of malignant cells and 6 cases were suspicious, but uncertain for the presence of malignant cells, while 86 cases had inflammatory pleural effusion or other pathologies but were not malignant. After histological analysis of the cytoblock and immunohistochemical analysis, we identified 82 malignant tumors of the lung, 8 malignant tumors of the gastrointestinal tract, 15 malignant tumors of the breast, and 6 malignant tumors of the female genital tract, as well as 24 tumors of undetermined origin. CONCLUSIONS: Cytoblocks are important for the diagnosis of the primary nature of malignant pleural effusions. The highest importance is primary lung tumors, as well as those tumors in which the primary site of the tumor cannot be determined clinically.

Lafora disease: a case report.

BACKGROUND: Lafora disease is a rare genetic disorder involving glycogen metabolism disorder. It is inherited by autosomal recessive pattern presenting as a progressive myoclonus epilepsy and neurologic deterioration beginning in adolescence. It is characterized by Lafora bodies in tissues such as brain, skin, muscle, and liver. CASE PRESENTATION: We report a rare case of Lafora disease in a 16-year-old Albanian girl who presented at a tertiary health care center with generalized tonic-clonic seizures, eyelid twitches, hallucinations, headache, and cognitive dysfunction. She was initially treated for generalized epilepsy and received an antiepileptic drug. However, owing to resistance of seizures to this antiepileptic drug, a second drug was introduced. However, seizures continued despite compliance with therapy, and general neurological status began to deteriorate. The child began to have hallucinations and decline of cognitive function. She developed dysarthria and unsteady gait. When admitted to the hospital, blood tests and imaging examinations were planned. The blood tests were unremarkable. There was no relevant family history and no consanguinity. Electroencephalography showed multifocal discharges in both hemispheres, and brain magnetic resonance imaging revealed no abnormality. Axillary skin biopsy revealed inclusion bodies in apocrine glands. Consequently, the child was referred to an advanced center for genetic testing, which also confirmed diagnosis of Lafora disease with a positive mutation on NHLRC1 gene. CONCLUSIONS:  Even though rare as a condition, Lafora disease should be considered on differential diagnosis in progressive and drug-refractory epilepsy in adolescents, especially when followed by cognitive decline.

The Prognostic Role of Vascular Endothelial Growth Factor-A Expression in Thyroid Carcinomas.

BACKGROUND: Thyroid carcinomas are the most common endocrine tumors - they account for 95% of all endocrine tumors. Thyroid carcinomas are more vascular than normal thyroid tissue. For the tumor to grow and subsequently metastasize it is crucial that it induces angiogenesis. This requires a change in the balance between certain angiogenic factors such as the vascular endothelial growth factor-A (VEGF-A) and the inhibitors of angiogenesis. The aim of this study was to evaluate the role of VEGF-A expression in thyroid carcinomas. MATERIALS AND METHODS: The present prospective study included 80 cases, of which 60 were patients with thyroid cancer including papillary, follicular, medullary and anaplastic carcinoma, and 20 patients (controls) with benign thyroid tissue (thyroid goiter). All cases were examined using the immunohistochemical staining for VEGF-A. RESULTS: VEGF-A expression in thyroid carcinoma was significantly higher than in benign thyroid tissues (p<0.001). VEGF-A expression values in thyroid carcinoma did not associate with tumor necrosis degree (p=1.000). Furthermore, VEGF-A expression values in thyroid carcinoma were not associated with other prognostic factors such as tumor hemorrhage, angioinvasion, atypical mitosis, and lymphatic invasion. CONCLUSION: Our data showed that the VEGF-A expression is upregulated in thyroid cancers compared with benign thyroid tissue. Therefore, it would be useful to perform IHC staining for VEGF-A expression as a valuable diagnostic tool in TC.

Prognostic Value of Vascular Endothelial Growth Factor A in the Prediction of the Tumor Aggressiveness in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most predominant renal tumour with unpredictable tumour behaviour. The aim of the study is to investigate the prognostic value of vascular endothelial growth factor A (VEGF-A) expression in CCRCC and to correlate it with other histological parameters as well as with patient's survival. MATERIAL AND METHODS: Tumour blocks were taken from 40 patients with histopathology diagnosis of CCRCC and tissue block from 20 normal kidneys as a control group were examined using the immuno-histochemical staining for VEGF-A. RESULTS: The VEGF A expression in CCRCC was significantly higher than in the normal kidney tissues (U' = 720, P < 0.0001). VEGF A expression values in CCRCC were positively correlated with Disease Free Survival (r = 0.335, P = 0.034) and the tumor necrosis degree (r = 0.181, P = 0.262). VEGF-A expression values in CCRCC did not correlate with CD 31 expression (r = -0.09, P = 0.549), and Progression Free Survival (r = -0.07, P = 0.838). VEGF A expression values in CCRCC were negatively correlated with the tumor nuclear grade (r = -0.161, P = 0.318); the pathological tumor stage (r = -0.371, P = 0.018); the tumor size (r = -0.361, P = 0.022); the degree of tumor hemorrhage (r = -0.235, P = 0.143); and Cancer Specific Survival (r = -0.207, P = 0.713). CONCLUSIONS: VEGF-A expression can be used to stratify advanced and metastatic CCRCC patients into low-benefit and high-benefit groups. Based on this study outcome it would be useful to perform IHC staining for VEGF-A expression in all patients with advanced and metastatic CCRCC.

Clinical Significance of VEGF-A and Microvessel Density in Diffuse Large B-Cell Lymphoma and Low-Grade Follicular Lymphoma.

Angiogenesis is essential for the development, growth and progression of tumors. Although vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor, its impact on lymphoma has not yet been fully clarified. The aim of this study was to evaluate VEGF-A -expression and microvessel density (MVD) in aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL), in indolent lymphomas such as low-grade follicular lymphoma (FL), and in lymph node reactive follicular hyperplasia (FH). In 80 prospective and retrospective cases (30 DLBCL, 30 FL and 20 FH), CD31 was analyzed by immunohistochemical staining assessing density of blood vessels, as well as the total number of CD31 positive endothelial cells. The results were compared with relevant clinical data. MVD was 85% in FH, followed by 60% in DLBCL and 43% in low-grade FL. VEGF-A was significantly higher in DLBCL than in low-grade FL and FH. A statistically significant association of MVD and VEGF-A with the International Prognostic Index (IPI) was found in DLBCL. High MVD and VEGF-A expression was observed in DLBCL patients with high IPI, while there was no statistically significant association between MVD and VEGF-A with the Follicular Lymphoma International Prognostic Index in low-grade FL. Our results suggested an important relationship between angiogenesis and high-grade lymphoma.

Atypical uterine leiomyoma: a case report and review of the literature.

BACKGROUND: Atypical uterine leiomyomas show benign behavior. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. We report a rare case of atypical uterine leiomyoma. We try to investigate potential immunohistochemical parameters that could be essential to distinguish cases of malignant smooth muscle tumors and those of uncertain or borderline histology. CASE PRESENTATION: A 56-year-old white ethnic Albanian woman from Kosovo presented with uterine bleeding because of uterine multiple leiomyomas. A hysterectomy with unilateral adnexectomy was performed. Her hysterectomy specimen contained multiple leiomyomas in submucosal, intramural and subserosal locations. The leiomyomas were well demarcated, firm and white with a whorled cut surface and one had foci of hemorrhage. Histology of most of the leiomyomas showed a whorled (fascicular) pattern of smooth muscle bundles separated by well-vascularized connective tissue. Smooth muscle cells were elongated with eosinophilic or occasional fibrillar cytoplasm and distinct cell membranes. Some of them developed areas of degeneration including hyaline change, with less than five mitotic figures per ten high power fields in most mitotically active areas, and no significant atypia. One leiomyoma was characterized by moderately to severely pleomorphic atypical tumor cells with low mitotic counts and no coagulative tumor cell necrosis. Immunohistochemistry showed strong immunoreactivity for vimentin, smooth muscle actin and desmin, while cyclin-dependent kinase inhibitor 2A (p16), and B-cell lymphoma 2 (bcl-2) showed focal immunoreactivity, estrogen and progesterone were positive, Ki-67 expressed a low proliferation index, whereas p21 and tumor suppressor gene p53 were negative. CONCLUSIONS: The combination of evaluation of conventional morphologic criteria with cyclin-dependent kinase inhibitor 2A (p16), p21, progesterone, B-cell lymphoma 2, tumor suppressor gene p53 and Ki-67 expression may be of great value in the assessment of uterine smooth muscle tumors of uncertain or borderline histology.

Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits.

BACKGROUND: The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding. Our purpose was to investigate the effects of 5-fluorouracil (5-FU) on tendon adhesions in partially divided profundus flexor tendons (flexor digitorum profundus [FDPs]) following surgical repair and in partially divided FDPs without surgical repair, and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions. METHODS: We used 32 adult male European rabbits (Oryctolagus cunniculus) weighing from 2.5 to 3.5 kg. The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits; thus, a total of 64 tendons were examined in this study. RESULTS: Based on the results achieved in our experimental study, the load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU. CONCLUSIONS: The load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU. Therefore, these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath, which in this case required greater traction force.

Clear cell variant of diffuse large B-cell lymphoma: a case report.

INTRODUCTION: Diffuse large B-cell lymphoma is a diffuse proliferation of large neoplastic B lymphoid cells with a nuclear size equal to or exceeding the normal macrophage nuclei. We report a case of a clear cell variant of diffuse large B-cell lymphoma involving a lymph node in the neck, which was clinically suspected of being metastatic carcinoma. CASE PRESENTATION: A 39-year-old Caucasian ethnic Albanian man from Kosovo presented with a rapidly enlarging lymph node in his neck, but he also disclosed B symptoms and fatigue. A cytological aspirate of the lymph node revealed pleomorphic features. Our patient underwent a cervical lymph node biopsy (large excision). The mass was homogeneously fish-flesh, pale white tissue replacing almost the whole structure of the lymph node. The lymph node biopsy showed a partial alveolar growth pattern, which raised clinical suspicion that it was an epithelial neoplasm. With regard to morphological and phenotypic features, we discovered large nodules in diffuse areas, comprising large cells with slightly irregular nuclei and clear cytoplasm admixed with a few mononuclear cells. In these areas, there was high mitotic activity, and in some areas there were macrophages with tangible bodies. Staining for cytokeratins was negative. These areas had the following phenotypes: cluster designation marker 20 (CD20) positive, B-cell lymphoma (Bcl)-2-positive, Bcl-6-, CD5-, CD3-, CD21+ (in alveolar patterns), prostate-specific antigen-negative, human melanoma black marker 45-negative, melanoma marker-negative, cytokeratin-7-negative and multiple myeloma marker 1-positive in about 30% of cells, and exhibited a high proliferation index marker (Ki-67, 80%). CONCLUSION: According to the immunohistochemical findings, we concluded that this patient has a clear cell variant of diffuse large B-cell lymphoma of activated cell type, post-germinal center cell origin. Our patient is undergoing R-CHOP chemotherapy treatment.

Hepatobiliary neuroendocrine carcinoma: a case report.

INTRODUCTION: Neuroendocrine carcinoma of the gallbladder is a rather uncommon disease. We report a case of a neuroendocrine tumor that was located in the wall of the gallbladder and that extended into the liver. CASE PRESENTATION: A 52-year-old Caucasian woman presented with right-sided abdominal pain, ascites and jaundice. An MRI scan revealed a tumor mass located in the gallbladder wall and involving the liver. A partial hepatectomy and cholecystectomy were performed. Histology revealed a neuroendocrine tumor, which showed scattered Grimelius positive cells and immuno-expressed epithelial and endocrine markers. Our patient is undergoing chemotherapy treatment. CONCLUSION: Gastroenteropancreatic neuroendocrine tumors need a multidisciplinary approach, involving immunohistochemistry and molecular-genetic techniques.

The study of volume density of tracheal ganglions in vitro in new born babies with respiratory distress syndrome.

Volume density of respiratory organs was studied in vitro in newborn babies at different age of gestation (abort, immature, premature and mature) using stereometric method. The total of 23 cases was subject to this study. The respiratory organs (trachea, lungs) were taken from autopsies of newborn babies exited from different causes. For this purpose the tissues were fixed in formalin (10%) solution, cut serially in 7micro and 10micro slabs. Volume density of the respiratory system was assessed stereometricaly using Universal testing system Weibel M 42. We observed that volume density of epithelia, musculature and glands were proportionally present in the tracheal tissue. Cellular interstitial tissue is consistently increasing and corresponds to the developmental stages of the newborn babies. The density of tracheal ganglions is greater in premature ages of immature and premature newborns (p<0,05). Decreased number of ganglion cells is observed in mature ages (p<0,05). This is caused by intensive ramification of ganglions from serosa to deeper layers of trachea right to epithelium. Medium diameter of tracheal ganglions is greater in mature newborn babies and corresponds to developmental ages of babies.