Ctibor Povýšil

Division of Lymphatic Vessels at Varicocelectomy Leads to Testicular Oedema and Decline in Testicular Function According to the LH-RH Analogue Stimulation Test

OBJECTIVES To study the andrological outcome of the division of testicular lymphatic vessels at varicocelectomy in children and adolescents. METHODS Testicular size and basal and stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) values were determined prospectively in 86 patients with left unilateral varicocele grades II-III. 22 patients underwent lymphatic non-sparing surgery (LNS group), 10 of them with artery sparing (LNS/AS) and 12 without artery sparing (LNS/ANS), 23 patients underwent lymphatic sparing repair (LS group) and 41 patients were treated conservatively (NT group). RESULTS The LNS group demonstrated significantly greater left testicular enlargement at six weeks and one year following repair, left testicular hypertrophy developed in 31.8% and hydrocele in 22.7% of patients. Marked oedema of intertubular tissue and a varying degree of tubular injury was observed in boys surgically treated for hydrocele. In the LS group, neither hypertrophy nor hydrocele developed postoperatively, the LH stimulated values were lower than in LNS/ANS group (p<0.05) and the NT group (p<0.04), the FSH stimulated values were lower than in the LNS/ANS group (p<0.001). CONCLUSIONS Division of lymphatic vessels at varicocelectomy is associated with an excessive increase in testicular volume due to oedema, and with a reduced testicular function according to higher LH and FSH stimulated values. Preservation of lymphatics is strongly advised in varicocelectomy in adolescents to ensure better andrological outcome.

Ultrastructure of Ewing's tumour

Tumour tissue surgically excised from 10 patients bearing Ewings tumour of bones was examined electron microscopically and histoenzymologically. In all cases the tumour was composed of polygonal cells with cytoplasm poor in organelles but with conspicuous aggregates of glycogen particles. There were numerous intercellular connections of desmosomal type and a distinct cell membrane bound positivity for alkaline phosphatase activity. In two cases in which there was a negative reaction for alkaline phosphatase, the lack of enzyme activity might have been related to cytotoxic treatment carried out for several months immediately before excision of the tissue used for histoenzymological studies. The problem of histogenesis of Ewings tumour remains unresolved although some of the present findings support a haemangiogenic origin of the tumour.

A comparative ultrastructural study of chondrosarcoma, chordoid sarcoma, chordoma and chordoma periphericum.

The present study is based on electron microscopical examinations of 15 conventional chondrosarcomas, 1 clear cell chondrosarcoma, 3 mesenchymal chondrosarcomas, 2 so-called chordoid sarcomas (extraskeletal myxoid chondrosarcoma), 4 sacrococcygeal chordomas, 2 ecchordoses and 1 neoplasm of tibia with features of a true peripheral chordoma (parachordoma). The neoplastic cells from various types of chondrosarcoma shared a number of features with nonneoplastic chondrocytes as e.g. a well-developed rough endoplasmic reticulum and microvillous cytoplasmic processes. In clear-cell chondrosarcoma, glycogen accumulation in the tumour cells was a prominent feature. The cells of mesenchymal chondrosarcoma usually showed the characteristics of immature mesenchymal cells. In contrast, chordomas commonly contained physaliferous cells with two types of vacuoles in their cytoplasm. The first type can be most adequately characterized as intracytoplasmic pseudoinclusions of intercellular substance, whereas the other type, glycogen-containing, single membrane-bound vacuoles most probably correspond to autophagosomes (cytolysosomes). Only vacuoles of the first type were recorded in the so-called chordoid sarcoma. They were also seen in chondrosarcomas. In contrast, both types of vacuoles were identified in the above-mentioned tibial tumour which, in addition, showed even other cytological characteristics of chordoma. The findings presented here have demonstrated distinct structural relationships between chordoid sarcoma and chondrogenic tumours. On the other hand, our observation of the uncommon tibial neoplasm indicates the possibility that tumours identical with chordoma may occur at sites other than the axial skeleton.

Large cell neuroendocrine carcinoma of the urinary bladder with lymphoepithelioma-like features.

The group of undifferentiated carcinomas of the urinary bladder encompasses small cell undifferentiated carcinoma, giant cell carcinoma, lymphoepithelioma-like carcinoma (LELC), and large cell neuroendocrine carcinoma (LCNEC). These tumors are either pure or can be associated with other components, such as transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. We report a case of LCNEC of the urinary bladder in a 54-year-old woman. Histologically, the tumor showed features of LELC; immunohistochemically, the tumor cells reacted to chromogranin A, NSE, and synaptophysin. In addition to these neuroendocrine markers, tumor cells were positive for cytokeratin CAM 5.2 and AE1/AE3, and there was focal positivity for vimentin. In situ hybridization for the detection of Epstein-Barr virus was negative. Despite radical cystourethrectomy and six courses of chemotherapy, the patient developed metastases invading the left inguinal lymph nodes 11 months postoperatively. Currently, 16 months postoperatively, the patient has developed metastases spreading into the lymph nodes of the right ischiorectal fossa; therefore, she is receiving a new cyclus of chemotherapy. There are only three previously reported cases of LCNEC of the urinary bladder, and the significance of neuroendocrine differentiation in non-small cell carcinomas at this location remains to be established. However, LELC appears to be a separate clinicopathological entity with sensitivity to chemotherapy and a relatively favorable prognosis. The differentiation between LELC and LCNEC with prominent inflammatory reaction could be of therapeutic relevance. However, in our case, this was possible using immunohistochemistry only.

Muscle-specific actin expression in chondroblastomas.

Chondroblastomas are unusual cartilage benign lesions of bone that have well-characterized histological features. We reviewed and immunohistochemically examined the paraffin block material of 20 cases, and in seven tumors of this collection we found distinct cytoplasmic muscle-specific actin positivity of some tumor chondroblasts and chondrocytes. Muscle-specific actin-positive cells had the histological and ultrastructural features typical of chondroblasts. Moreover, in their cytoplasm they contained bundles of microfilaments with focal densities, as is typical of myofilaments. We did not observe any basal lamina around these cells, which were surrounded by intercellular matrix of the cartilage tissue type. Therefore, we suppose that muscle-specific actin-positive cells occurring in some chondroblastomas do not represent an admixture of myofibroblasts but chondroblasts with actin expression. The unusual immunophenotype of some chondroblasts might be the result of aberrant actin expression or of the plasticity of their phenotype modulated by microenvironmental stimuli. It is a question of whether, analogously to the terminology of myofibroblasts, such cells could be designated as myochondroblasts.

Primary pure large-cell neuroendocrine carcinoma of the ovary.

We report a case of a 73-year-old female with a rare simultaneous occurrence of three tumors: ovarian carcinoma, endometrial carcinoma, and breast carcinoma. The ovarian tumor was a primary pure large-cell neuroendocrine carcinoma. Grossly, the left ovary was enlarged by a solid tumor that measured 9 x 7 x 7 cm. Histologically, the tumor consisted of large cells with irregular hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was cribriform and solid-alveolar, with palisaded tumor cells located peripherally. The tumor cells showed multiple mitotic figures (up to 43 mitoses/10 HPF). Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for EMA, synaptophysin, chromogranin, CD56, and CEA. Cytokeratin 20 was positive focally. Primary large-cell neuroendocrine carcinoma of the ovary is a rare tumor. To the best of our knowledge, only 4 cases of a pure tumor of this type have been reported to date.

Pigmented composite paraganglioma-ganglioneuroma of the urinary bladder

We report a case of a pigmented composite paraganglioma-ganglioneuroma of the urinary bladder in a 70-year-old female. Grossly, the tumor measured 6.5 cm in diameter and had arisen from the base of the urinary bladder. Histologically, the tumor was composed of approximately equal components of paraganglioma and ganglioneuroma, which were partly separated and partly mixed, and intermingled with each other. There were foci of ample dark brown pigmentation in the cytoplasm of chromaffin paraganglioma cells. The pigment was Masson-Fontana-positive and had been bleached by hydrogen peroxide (H2O2). Electron microscopy showed large, abundant, pleomorphic electron-dense granules consistent with neuromelanin. In addition, there were numerous electron-dense neurosecretory-type granules. Neuromelanin, melanin or lipofuscin are occasionally observed in paragangliomas, although the occurrence of these pigments has never been described in a composite tumor originating from either adrenal medulla or extraadrenal paraganglia. To the best of our knowledge, our report represents the first case of pigmented composite paraganglioma-ganglioneuroma and expands the morphological spectrum of these unusual tumors.

Comparison of the IHC, FISH, SISH and qPCR methods for the molecular diagnosis of breast cancer.

Her2 proto-oncogene amplification and protein overexpression is observed in 20-40% of patients with breast cancer and plays a crucial role in invasive breast cancer and its treatment. In the present study, we investigated samples from 131 patients with invasive breast carcinoma. In all cases, the overexpression/amplification level of Her2 was determined using manual immunohistochemistry (IHC) and/or automatic IHC, fluorescence in situ hybridization (FISH), silver in situ hybridization (SISH) and quantitative polymerase chain reaction (qPCR). Using various methods, we demonstrated candidate methods for Her2 detection and their dependability. Our results demonstrate that these methods are highly comparable for the detection of Her2 overexpression/amplification. It was also revealed that qPCR is a valuable tool for the evaluation of Her2 gene overexpression/amplification. The results from pPCR analysis positively correlated with the results from IHC and FISH analysis. Moreover, in contrast to IHC or SISH/FISH, the results obtained by qPCR were not encumbered with any subjective error on the part of the evaluator.

Ultrastructure of adamantinoma of long bones

Electron microscopic examination of three adamantinomas of long bones revealed structures usually observed in both mesenchymal and epithelial tumours. Tumour cells showing high alkaline phosphatase activity frequently tended to line clefts in connective tissue, resembling endothelial cells. The long processes of such cells showed fenestration. In areas showing fibre production the tumour cells were in close relationship to collagen fibrils. The latter were found, together with microfibrils, between the processes and above the basement membranes. The tumour cells were interconnected by desmosomes with tonofilaments and contained numerous bundles of microfilaments. All three cases revealed tiny intracytoplasmic inclusions resembling Weibel-Palade endothelial bodies. In addition, some of the structures in the lumena contained definite acid mucosubstances. A squamous cell pattern was present in only one of the three specimens. The coincidence of divergent structures in a single specimen has led us to the conclusion that the so-called adamantinoma of long bone might be possibly related to tumours of mesodermal or mesectodermal origin.

Granular cell basal cell carcinoma

A 69‐year‐old woman presented with a 2‐year history of a slowly growing tumour on the nose. The clinical diagnosis was basal cell carcinoma (BCC) and a complete excision was performed. Histologically, the tumour had the general features of a BCC but with sheets and nests of cells with granular cytoplasmic changes in the centre of the lesion. A pathological diagnosis of granular cell BCC was made. On immunohistochemical examination, the tumour cells were Ber‐EP4, cytokeratin AE1/AE3 and cytokeratin CAM 5.2 positive but S100 protein negative. Only the granular cells were CD68 antigen (monoclonal antibody KP1) positive.