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PubMed1993

[Role of bronchial resection-anastomosis in conservative surgery of lung cancer. Apropos of 34 cases].

We report our 20 year experience with bronchial sleeve resection for endobronchial neoplasms. Among 832 patients who underwent resection procedures, thirty-four underwent a bronchial sleeve resection (4.1%): 27 bronchogenic carcinomas out of 780 (3.5%) and 7 carcinoids tumors out of 52 (13.4%). Bronchial sleeve resection is an appropriate treatment for neoplasms with low grade malignant potential and selected cases of bronchogenic carcinoma (tumor invading the adjacent main-stem bronchus without large hilar extension), especially for patients with compromised pulmonary function. There were no operative deaths; but minor complications occurred in 20% of patients without any major complications. Sleeve resection is a safe and adequate resection therapy for tumors with low-grade malignant potential and for selected cases of carcinoma.

Adolescent↗

PubMed2006

Should bladder biopsies be performed routinely after bacillus Calmette-Guérin treatment for high-risk superficial transitional cell cancer of the bladder?

OBJECTIVE: After endoscopic resection of high-grade superficial urothelial neoplasms (Ta, T1 or Tis), adjuvant bacillus Calmette-Guérin (BCG) therapy is performed routinely to avoid recurrence and/or progression. Vesical biopsies often are performed to assess the efficacy of treatment. The aim of our study was to evaluate the usefulness of these biopsies. MATERIALS AND METHODS: During this retrospective bi-centre study, 130 patients who had undergone vesical high-grade tumour resection were included. There were 40 Ta associated with Tis in three cases, 87 T1 associated with Tis in 13 cases, and three isolated Tis. After BCG treatment, the following parameters were studied: cytoscopic findings, urine cytology and the histologic results of systematised biopsies. RESULTS: Urine cytology was positive (high-grade) for 26 patients and negative (normal or low-grade) for 104 patients. For the 26 patients with positive cytology, vesical flexible cystoscopy findings were considered suspicious in 18 patients and normal in eight patients. As for the 104 patients who presented negative cytology, cystoscopic findings were considered negative in 76 patients and suspicious in 28 patients. In the present study, the sensitivity of cytology and cystoscopy in the detection of recurrence after BCG treatment was 56% and 87.5%, respectively; specificity was 56% and 81.6%, respectively. When the two examinations were combined, sensitivity was 100%, and specificity was 76%. CONCLUSIONS: After BCG therapy, the association of negative flexible cystoscopy findings and normal urine cytology made it possible to avoid routine biopsies. Patients could therefore avoid the morbidity of this procedure.

BCG Vaccine↗

PubMed1999

Co-expression of Fas and Fas ligand in human non-astrocytic glial tumors.

The study of Fas (APO-1/CD95) and Fas ligand (FasL) expression in human glial neoplasms has been primarily restricted to astrocytomas. Using immunohistochemistry, we analyzed 35 non-astrocytic glial neoplasms (12 WHO grade II ependymomas, 15 grade II oligodendrogliomas, and 8 grade III oligodendrogliomas) for these factors. A significant correlation was found between Fas and FasL expression within the same tumors (P = 0.001). Western blotting was used to corroborate these findings in 7 of these tumors (3 ependymomas and 4 oligodendrogliomas). Theoretically, the co-expression of Fas and FasL should render gliomas susceptible to suicidal and fratricidal elimination. Their progressive nature, however, suggests that gliomas have acquired mechanisms to prevent Fas-mediated apoptosis. Expression of the anti-apoptotic protooncogene bcl-2 is one potential way in which Fas/FasL-bearing gliomas can escape this fate. Although expression of Bcl-2 protein was found in 6 of 12 (50%) grade II ependymomas, 5 of 15 (33%) grade II oligodendrogliomas, and 6 of 8 (75%) grade III oligodendrogliomas, no correlation between Fas/FasL co-expression and Bcl-2 production could be demonstrated, indicating that protection from Fas-mediated apoptosis probably involves other mechanisms.

Blotting, Western↗

PubMed1998

Needle aspiration cytology of metastatic high-grade transitional-cell carcinomas of the urinary tract.

We reviewed 4 cases of high-grade transitional-cell carcinoma (TCC) of the urinary tract with solitary pulmonary metastases that were studied by transthoracic needle aspiration biopsy cytology. There were two grade II and two grade III TCCs. The two grade II tumors yielded, in needle aspirates, syncytial tumor-cell clusters showing ill-defined, granular cytoplasm and slightly pleomorphic nuclei with inconspicuous nucleoli. In one case the tumor-cell cluster showed a focal acinar arrangement, mimicking cells of an adenocarcinoma. In both cases the electron microscopy (EM) study of aspirated tumor cells revealed epithelial cells with well-formed cell junctions, intracytoplasmic vesicles, apical short microvilli, and focal interdigitation of lateral cell membranes, suggesting a urothelial neoplasm. The two grade III TCCs yielded, in needle aspirates, pleomorphic malignant cells singly and in small clusters, showing well-defined, granular cytoplasm and pleomorphic nuclei containing prominent nucleoli, suggesting a poorly differentiated adenocarcinoma or an anaplastic large-cell carcinoma. By EM examination the aspirated tumor cells from one case revealed well-formed cell junctions, intracytoplasmic vesicles, poorly formed microvilli, and focal interdigitation of lateral cell membranes, suggesting a urothelial differentiation. In the other case the tumor cells were pleomorphic cells with occasional cell junctions and no ultrastructural features as seen in the other 3 cases of TCC. The tumor cells from the two grade II TCCs showed strong immunopositive reaction with keratin 7 antibody and weakly positive reaction with carcinoembryonic antigen antibody (CEAA), while those of the two grade III TCCs displayed only a weak and focal immunopositive staining with keratin 7 antibody and strong reaction with CEAA.

Aged↗

PubMed2005

Determination of human papillomavirus (HPV) load and type in high-grade cervical lesions surgically resected from HIV-infected women during follow-up of HPV infection.

BACKGROUND: The role of human papillomavirus (HPV) load and the importance of multiple-strain HPV infections as biomarkers for the development of cervical disease were evaluated in human immunodeficiency virus (HIV)-positive women. METHODS: A total of 108 samples were analyzed, 64 of which were obtained from 16 HIV-positive women who underwent surgical resection of the cervical cone for treatment of a histologically confirmed high-grade cervical intraepithelial neoplasm (cases) and 44 of which were obtained from 22 HIV-positive women who had high-risk HPV but a negative colposcopy result (controls). Each patient underwent periodic examinations at 6-12-month intervals that included colposcopy, Papanicolaou testing, biopsy (if indicated), and cervical brushing for HPV testing. Viral typing was performed by reverse dot-blot hybridization and quantification of viral load by in-house real-time PCR and commercial assays. RESULTS: Analysis of the cervical-brush samples collected when high-grade squamous intraepithelial lesions were diagnosed revealed that all cases had HPV loads that were significantly higher than those of controls (P=.0004 and P=.0003, by PCR and the Hybrid Capture 2 index [Digene], respectively). Decreasing concentrations of HPV load were observed when comparing samples obtained before and after treatment (P<.0001). The number and type of HPV strains that were detected were not statistically different between cases and controls. CONCLUSIONS: The significantly higher HPV load detected in women with high-grade cervical dysplasia, as well as the dramatic decrease in the load after surgical removal of the lesion, suggest that HPV load is a possible prognostic marker of high-grade SIL.

Adult↗

PubMed1998

[Adrenal carcinoma. Clinical and anatomopathological prognostic factors].

We performed on 9 patients with adrenal cortical carcinoma a retrospective study during 1967-1995 to evaluate the most important prognostic factors. Four patients were males and five females (mean age: 40.3 years). Five patients had endocrine symptoms (55%) and four had "non-functioning" tumors (45%). The tumor involved the left adrenal gland in 5 cases and the right in 4. The mean diameter of the neoplasm was 9.5 cm, with a mean weight of 411 g. The average duration of symptoms before diagnosis was 7.3 months. One patient had invasion of the inferior vena cava with liver metastases. Eight patients underwent curative surgery, the median survival time was 13.7 months, only 1 patient is alive after 18 months from surgical resection. We concluded that adrenal carcinomas have poor prognosis; staging and grading of the neoplasm, and age of the patient at diagnosis are predictors of survival.

Adolescent↗

PubMed2007

Carcinoma cuniculatum: a distinctive variant of penile squamous cell carcinoma: report of 7 cases.

We are reporting a peculiar variant of penile squamous cell carcinoma (SCC) characterized by its peculiar deeply penetrating and burrowing pattern of growth. This low grade, verruciform penile neoplasm is similar to the plantar epithelioma cuniculatum originally described by Ayrd in 1954. Clinical and pathologic features of 7 patients are presented. There were 7 partial penectomies and 4 bilateral inguinal node dissections. The mean patient's age was 77 years. Grossly, the tumors were white to gray, exo-endophytic, and papillomatous with a cobblestone or spiky appearance. All cases affected the glans and extended to coronal sulcus and foreskin (average size was 6.3 cm). The hallmark of the lesion was noted on cut surface where there were deep tumoral invaginations forming irregular, narrow, and elongated neoplastic sinus tracts connecting the surface of the neoplasm to deep anatomic structures. The neoplasm invaded through lamina propria and corpus spongiosum and grew along the loose connective tissue of Buck fascia to involve the tunica albuginea and corpora cavernosa (average depth was 32 mm). Deeply invasive keratin filled cysts or crypts, on serial sections, showed to be connected to the surface tumor. Fistulization to the skin was also noted. Microscopically, the lesions corresponded to well-differentiated carcinomas with bulbous front of invasion. There were focal areas of higher histologic grade and more infiltrative and jagged borders in 4 cases. Inguinal nodes were negative in 4 patients in which groin dissection was performed. Carcinoma cuniculatum is a variant of penile SCC with distinctive growth pattern and should be distinguished from other verruciform tumors such as the verrucous, papillary, and warty carcinomas. Unlike most subtypes of penile SCCs and despite the deep invasion, none of the tumors showed groin or systemic dissemination at time of diagnosis.

Aged↗

PubMed1995

"Cercariform" cells: a clue to the cytodiagnosis of transitional cell origin of metastatic neoplasms?

The "cercariform" cell is described as a distinct cytomorphologic clue that may be helpful in the diagnosis of metastatic transitional cell neoplasms, particularly low grade. This cell has a nucleated globular body and a cytoplasmic process with a nontapering, flattened, bulbous or fishtail-like end. The cercariform cell corresponds to intermediate cells in histologic and ultrastructural preparations of normal urothelium. The cercariform appearance is the result of pseudostratification of both normal and low-grade neoplastic urothelium. The unique features of cercariform cells make them readily distinguishable from neoplastic squamous cells as well as spindle cells of mesenchymal origin.

Adult↗

PubMed2004

Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding.

Hypoxia is known to be an important prognostic marker in many human cancers. We report the use of two oxygen measurement techniques in human brain tumors and compare these data with semiquantitative histological end points. Oxygenation was measured using the Eppendorf needle electrode and/or EF5 binding in 28 brain tumors. These data were compared with necrosis, mitosis, and endothelial proliferation. In some tumors, absolute EF5 binding was converted to tissue pO(2) based on in vitro calibrations. Eppendorf electrode readings could not be used to identify WHO grade 1/2 versus WHO grade 3/4 tumors, they could not differentiate grade 3 versus grade 4 glial-derived neoplasms, nor did they correlate with necrosis or endothelial proliferation scores. EF5 binding increased as the tumor grade increased and was significantly associated with necrosis and endothelial proliferation. There was no statistically significant correlation between the two hypoxia detection techniques, although both methods indicated similar absolute ranges of tissue pO(2). There was substantial inter- and intratumoral heterogeneity of EF5 binding in WHO grade 4 glial neoplasms. The majority of cells in glial-derived tumor had levels of hypoxia that were mild to moderate (defined herein as 10% to 0.5% pO(2)) rather than severe (defined as approximately 0.1% pO(2)). Immunohistochemical detection of EF5 binding tracks histological parameters in adult brain tumors, with increased binding associated with increasing necrosis and endothelial proliferation. The proportion of moderately to severely hypoxic cells is relatively low, even in the high-grade tumors. Human brain tumors are dominated by oxic to moderately hypoxic cells.

Adult↗

PubMed1993

Papillary cystic tumours of the pancreas: an analysis by nuclear morphometry.

Papillary cystic tumour (PCT) is a rare, low-grade malignant pancreatic neoplasm, in which the histological criteria for malignancy are still uncertain. We performed a histological examination of 3 metastasizing PCTs, while comparing them with 18 non-metastasizing PCTs, using a computed image analyser. The mean maximum nuclear diameter, the mean standard deviation (SD) of the nuclear diameter, the mean nuclear area and the nuclear-nonnuclear (N/NN) ratio obtained by the image analyser of the metastasizing PCTs (7.23 microns, 2.21 microns, 30.45 microns2, 36.41%) were all significantly larger than those of the non-metastasizing PCT (6.34 microns, 1.59 microns, 23.66 microns2, 23.74%; P < 0.005, P < 0.005, P < 0.005, P < 0.001 respectively). However, there were no statistical differences in either the nuclear ellipsoidity or nuclear regularity. These results suggested that nuclear morphometry might be a useful parameter to define metastatic potential, in addition to histological variables such as venous invasion, nuclear grade and mitotic rate.

Adolescent↗

PubMedDate not supplied

[Cell proliferation in salivary gland tumors].

Previous studies on cell proliferation in salivary gland tumors have shown the utility of immunostain with MIB1 in the differential diagnosis and prognosis of these neoplasms. We have carried out a study of 39 salivary gland tumors (17 benign), from different histological lineages. The immunocytochemical method used was the streptavidin--biotin--peroxidase complex which used the MIB1 monoclonal antibody. Benign tumors showed a low cell proliferation rates, below 5% with an overall average of 1.9%. The malignant tumors presented higher rates, with a middle value of 17.85%. Epidermoid carcinomas had the higher cell proliferation rates, with an average of 43%. In adenoid cystic carcinomas, we have observed that proliferation was greater at the peripheral level of tumor nests and cell surrounding the cystic structures. Neoplasms of low grade of malignancy presented lower cell proliferation rates. The MIB1 immunostain allowed to reach a differential diagnosis between pleomorphic adenoma and adenoid cystic carcinoma, specially in those cases in which there could be any doubt.

Cell Division↗

PubMed2002

[The new WHO classification of tumors of the nervous system 2000. Pathology and genetics].

New developments in neuro-oncology have prompted an update of the World Health Organization (WHO) classification of tumors of the nervous system. Major changes include the addition of new entities and the refinement of criteria for the diagnosis and grading of various neoplasms, in particular the meningiomas. As novel clinico-pathological entities, the chordoid glioma of the third ventricle, the atypical teratoid/rhabdoid tumor (AT/RT), the solitary fibrous tumor, and the perineurioma have been listed. The former lipomatous medulloblastoma of the cerebellum, previously incorporated in the family of embryonal tumors, is now classified as cerebellar liponeurocytoma. The term mixed pineocytoma/pineoblastoma has been replaced by pineal parenchymal tumor of intermediate differentiation. Furthermore, the large cell medulloblastoma and the tanycytic ependymoma were established as novel tumor variants. A separate chapter on the peripheral neuroblastic tumors has now been included in the classification. Substantial revisions were introduced in the meningioma chapter. For both atypical meningioma WHO grade II and anaplastic meningioma WHO grade III, histopathological criteria are now precisely defined. An important new addition to the WHO 2000 classification of nervous system tumors is the inclusion of molecular pathology findings. With this combination of pathology and genetics it has set the stage for a new format of the WHO tumor classification series.

Astrocytoma↗

PubMed1983

Glial and divergent cells in primate central nervous system tumors induced by JC virus isolated from human progressive multifocal leukoencephalopathy (PML).

Immunofluorescent stains for fibronectin (FN) and glial fibrillary acidic protein (GFAP) were used in conjunction with routine histologic stains to study tumors induced in squirrel and owl monkeys by JC virus from progressive multifocal leukoencephalopathy (PML). Three varieties of glioma were identified. The first and most common variety was a neoplasm similar to grade 4 astrocytoma in humans. The second had thin, normal-appearing FN-positive vessel walls and a vastly expanded neuroectodermal parenchyma which could not be characterized by routine histologic stains. Anti-GFAP revealed the glial nature of the parenchyma. Isolating glial parenchymal cells from divergent FN-positive cells has become important to neurooncology. This type of tumor may be of particular interest for such isolations due to its high ratio of glial cells to divergent cells. The third variety was not a homogeneous neoplasm. It occurred as focal regions within tumors of the first type, and consisted of giant cells with huge nuclei. These cells resemble the cells of a human giant cell glioblastoma and bear a slight similarity to the bizarre glial cells seen in PML. The rare human giant cell glioblastoma might have an association with JC virus or with PML.

Animals↗

PubMed2001

Pancreatic neuroendocrine neoplasms: a current summary of diagnostic, prognostic, and differential diagnostic information.

Pancreatic endocrine tumors (PETs) continue to be challenging diagnostic and prognostic lesions in surgical pathology and clinical medicine. These neoplasms can be graded into 1 of 3 tiers, based on histologic characteristics in likeness to epithelial neuroendocrine tumors in other anatomic sites. However, grade 1 tumors are by far the most common and are the most difficult to prognosticate. The most helpful features by which to gauge the behavior of such lesions include size (3 cm or larger); mitotic activity (2 or more mitoses per 10 high-power [x400] microscopic fields); marked nuclear atypia, especially with atypical mitoticfigures; predominant tumor synthesis of gastrin, vasoactive intestinal polypeptide, somatostatin, glucagon, calcitonin, or adrenocorticotropic hormone; complete nonfunctionality of the tumor at an immunohistochemical level; or invasion of blood vessels, nerves, or adjacent organs by the neoplasm. Differential diagnosis of PETs includes lesions such as solid-pseudopapillary neoplasms, acinar carcinomas, metastatic neuroendocrine tumors, and plasmacytomas.

Cell Nucleus↗

PubMed2003

[Comparative study of P 53, Bcl-2, and C-erbB-2 expression in low-grade papillary bladder tumors].

OBJECTIVE: To study the prognostic value of p53, bcl-2 and c-erbB-2 immunoexpression in predicting tumor relapses in low-grade papillary bladder neoplasms. METHODS: In all patients a complete transurethral resection of the lesion was performed. All the material was formalin-fixed and paraffin-embedded. At the immunohistochemical level, the following monoclonal antibodies were utilized: p53 (clone DO7), bcl-2 (clone 124) and c-erbB-2 (clone CB11). In order to predict tumor relapses during follow-up, a study of specificity, sensitivity and predictive positive value (PVP) and negative was designed. In univariate statistical studies, the following tests were utilized: Chi-square, Kaplan-Meier estimates and Cox logistic regression. RESULTS: Mean follow-up was 76.6 months (38 to 168). In recurrence prediction, p53 expression showed a high specificity (99%) as well as a high PPV (96%). Regarding bcl-2 and c-erbB-2 immunoexpression, both specificity (65% and 72%) and PPV (61% and 72%) were also high, although these percentages were lower than those obtained for p53 expression. The combined analysis of p53 and bcl-2 indicated that bcl-2 immunoexpression in non-basal cells of the urothelium could be independent of p53, although the number of cases showing this particular expression pattern is not high enough to perform an accurate statistical analysis. Otherwise, histologic grade demonstrated higher sensitivity (64%) and lower specificity (40%) than the immunohistochemical markers. In univariate studies, p53 showed an intense statistical correlation with relapse-free interval (RFI) and prediction of tumor recurrences during follow-up (p < 0.001), whereas the expression of bcl-2 (p = 0.065) was nearly correlated with RFI (p = 0.065). In contrast, expression of c-erbB-2 did not show statistical correlation (p = 0.112). CONCLUSIONS: In our study, individual and combined analysis of p53 and bcl-2 immunoexpression have demonstrated to be useful in predicting tumor recurrences and RFI in low-grade bladder lesions.

Antibodies, Monoclonal↗

PubMed2001

[Fluorescence cytology of the urinary bladder].

5-aminolevulinic acid induced fluorescence cystoscopy is invaluable for diagnosing urinary bladder carcinoma and its precursors. Because neoplastic cells of the urinary bladder possess striking fluorescent properties due to protoporphyrin IX, we initiated a study to evaluate the use of fluorescence microscopy in urinary sediments. In 27 patients suspected of having bladder carcinomas, we instilled 5-aminolevulinic acid into their urinary bladders before transurethral therapy and compared thereafter our studies of standard cytological sediments with those made under fluorescence microscopy. The results of fluorescence cystoscopy and those using urinary sediments for neoplastic cells under fluorescence microscopy correlated extremely well. In this pilot study using fluorescence microscopy, we found that we could diagnose with precision urinary neoplasms of different grades of differentiation. Accordingly, we regard fluorescence microscopy as a valuable complement for standard urinary cytology, especially since with fluorescence microscopy we can readily recognize fluorescing cells of highly differentiated urinary tumors and flat premalignant dysplasias.

Aminolevulinic Acid↗

PubMedDate not supplied

Relationship between Ki-67 positive cells, growth rate and histological type of human intracranial tumors.

The proliferation rate of 40 intracranial neoplasms (30 gliomas, 1 hemangioblastoma, 3 meningiomas, 1 neurinoma and 5 brain metastases) was investigated using the monoclonal antibody Ki-67. In eleven of the gliomas recurrences could be observed, and two of them recurred for second time. In total the Ki-67 labelling indices of 53 specimens were investigated. The Ki-67 nuclear antigen was demonstrated in frozen sections by application of the appropriate monoclonal antibodies according to a modified alkaline phosphatase-antialkaline phosphatase (APAAP) technique. The proliferation rate was evaluated by cell count calculation of the staining index. Ki-67-labelled glioma cells varied from 0.2 percent in one meningioma (WHO-grade I) to 9.1 percent in one glioblastoma. In ten glioma recurrences, higher Ki-67 staining indices could be observed than in their primaries, even when the histological grading did not change substantially. In a cerebellar hemangioblastoma, a trigeminal neurinoma and two endotheliomatous meningiomas the fraction of stained nuclei was less than one percent; however, one recurrent transitional meningioma without any histological sign of malignancy showed a staining index of 2.4 percent. The staining indices of five brain metastases of different malignancies ranged from 1.5 percent in a malignant melanoma to 6.1 percent in bronchial carcinoma. In the majority of the cases examined, the percentage of Ki-67 labelled cells was in accordance with the histologic grade of the neoplasm. In general, there was a direct relationship between the number of stained nuclei and the frequency of mitoses (mitotic index) evaluated in hematoxylin-eosin stained frozen sections. Interestingly, the frequency of mitosis and stained nuclei were higher in tumor recurrences than in the primaries. The results of this study imply that immunohistological labelling of the proliferating cell fraction should become an important additional criterion to predict the biological behaviour of human nervous system neoplasms.

Adult↗

PubMed2005

Fine-needle aspiration cytology of intraductal papillary-mucinous tumors: a retrospective analysis.

Intraductal papillary-mucinous tumor (IPMT) of the pancreas has become the accepted terminology for a group of mucin-producing epithelial proliferations lying within ectatic segments of the main pancreatic duct or its large branches. These neoplasms generally are associated with an indolent course, characteristic endoscopic ultrasonographic (EUS) findings, and a variable histo- and cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens obtained by endoscopic ultrasound-guided or percutaneous fine-needle aspiration (FNA) are characterized by a background containing abundant mucin in which are entrapped single or loosely cohesive clusters of neoplastic cells characteristically showing a goblet-cell morphology. The degree of nuclear atypia, cell crowding, and cell shape varies between smears within a single case and between cases. Cytomorphological examination, when coupled with EUS features, is accurate for the diagnosis of these lesions but often it underdiagnoses the grade of the neoplasm.

Adenocarcinoma, Mucinous↗