[Proliferative activity of stage I testicular neoplasms: evaluation by image analysis of immunoreactive MIB-1]. / L'attività proliferativa delle neoplasie del testicolo in stadio I: valutazione mediante analisi di immagine dell'immunoreattività MIB-1.

The proliferative activity has been evaluated in 55 cases of seminoma and 36 cases of non-seminomatous germ cell tumors of the testis (NSGCT) in clinical stage I from patients alive and well within 5 years, by a semi-quantitative image analysis method of determination of the percent MIB-1 positive nuclear areas, using a Leica Quantimet 500+ analyzer. Significant differences of growth fraction have been detected between classical seminomas and seminomas showing more than 3 mitoses/1HPF (anaplastic seminoma)-mean of MIB-1 positivity in classic seminoma 23.8%, versus 43.9% in anaplastic seminoma; confirming this value of cut-off in distinguishing two classes of cases with different growth fractions, but without any difference as far as prognosis is concerned. The non seminoma- germ cell tumours (NSGCT) in toto display a growth fraction significantly higher than that of seminomas (mean value of MIB-1 positivity: 26.3% in seminoma versus 40.4% in NSGCT), but absolute values of positivity as high as those obtained by others by subjective evaluation have not been observed. A higher growth fraction in NSGCT is positively correlated with an embryonal carcinoma component as high as 80% of the tumor mass and/or with vascular invasion, but not with different histotypes. The proliferative activity doesn't stratify subgroups with different prognosis within the two groups of germinal tumours of the testis (seminomas and NSGCT) in our cases of clinical stage I testicular tumours.

Cytologic features of 22 radial scar/complex sclerosing lesions of the breast, three of which associated with carcinoma: clinical, mammographic, and histologic correlation.

Radial scar/complex sclerosing lesion (RS/CSL) of the breast has become more frequently detected with the increasing performance of mammography as a screening test. The clinical, mammographic, and cytologic features of 22 cases of histologically proved breast RS/CSL, 3 of which associated with carcinoma arising at the periphery of the lesion, were reviewed. Clinical examination and mammography did not show specific features in differentiating RS/CSL from carcinoma of the breast. Cytology of RS/CSL without associated malignant changes was dominated by bland epithelial clusters and bipolar naked nuclei. Apocrine cells, papillary clusters, foam cells, and fibrillary elastoid material were also frequently seen. At the cytologic review, only one case of RS with apocrine adenosis, showing atypical cells, was diagnosed as suspicious. Two of the three cases of CSL with associated carcinoma in situ were cytologically characterized by the presence of single atypical cells. In the third case, characterized by a small tubular carcinoma near to CSL, fine-needle aspiration cytology revealed few tubular clusters without myoepithelial cells. Although cytology of RS/CSL without associated carcinoma does not seem characteristic, in most cases a diagnosis of benignancy can be performed correctly. The application of fine-needle aspiration cytology to mammographic lesions with features suggesting RS/CSL may permit a better planning of these lesions.

Morphometric analysis in prognostic evaluation of stage I thick cutaneous melanomas.

OBJECTIVE: To determine if morphometric analysis could be useful in distinguishing between good and adverse prognosis in thick melanomas. STUDY DESIGN: The study group consisted of 30 cutaneous melanomas (CM) (18 superficial spreading, 11 nodular and 1 acral lentiginous) measuring 1.5-14.8 mm in diameter. Area, perimeter, roundness and aspect ratio of 200 nuclei (100 in the superficial areas and 100 in the lower area) were morphometrically studied. After five years of follow-up, 18 patients were alive, and 12 had died of the tumor. The data were evaluated with univariate and multivariate (Cox's proportional hazard model) analysis. RESULTS: Univariate analysis showed that area and perimeter of superficial and deep nuclei were significantly larger in CM patients than in controls (10 acquired intradermal nevi). Regarding the prognostic role of the variables considered, aspect ratio of the deep nuclei (SD only) was significantly associated with prognosis. Otherwise, size factors (area and perimeter) had no prognostic value. CONCLUSION: Morphometric evaluation of nuclear shape factors in the subset of thick CM represents an additional prognostic tool with statistical significance.

Grading in superficial papillary bladder carcinoma, with an emphasis on nuclear orientation.

OBJECTIVE: To develop a computerized analysis method that could reflect not only cellular anaplasia but also the orientation (PV) of neoplastic elements and could allow the separation of low (grade G 1 and G 2a) and high (G 2b) grades of superficial papillary bladder tumors (SPBTs). STUDY DESIGN: Cellular anaplasia is based on classic morphometric parameters, such as mean and standard deviation of area, perimeter, roundness and aspect ratio (length/width ratio) of 50 papillary bladder tumors (16 G 1, 10 G 2a and 24 G 2b according to Pauwels). Orientation of the major axis of each nucleus with respect to the true basal membrane was calculated using the SD of valve distribution. RESULTS: No statistically significant differences were found between cases showing contiguous grades (G 1 versus G 2a or G 2a versus G 2b). PV, SD of the area and SD of the perimeter were the parameters that could significantly distinguish between G 1 and G 2b and between G 1 plus G 2a and G 2b (P < .05). When comparing G 1 with G 2a plus G 2b, only PV and SD of the area were statistically significant. CONCLUSION: Quantification of the irregularities in the orientation of nuclei with respect to the basal membrane may improve morphometric classification of low grade SPBTs.

Renal collecting duct carcinoma. Report of a case with urinary cytologic findings.

A case of collecting duct carcinoma of the kidney is presented with histologic and cytologic findings. Cytologic examination of voided urine showed glandlike clusters of large cells with granular cytoplasm and prominent nucleoli, along with normal transitional cells. Macroscopically the kidney had a pelvic tumor mass that, on microscopic examination, was consistent with renal collecting duct carcinoma. Urinary cytology is useful as a diagnostic procedure even in cases of rare entities, such as collecting duct carcinoma.

Evaluation of nucleolar organizer region-associated proteins in endometrial pathology.

In the current study the argyrophil staining technique for NOR proteins (Ag-NORs) has been performed on cases of different endometrial lesions, trying to find an aid in differentiating atypical hyperplasia from well differentiated carcinoma in biopsy specimens. We conclude that the Ag-NOR count, even though in endometrial carcinoma is significantly exceeding that of atypical hyperplastic endometrium, could be a misleading discriminator, because of a wide overlap of values in individual cases.

Histomorphometric and morphologic studies of the carotid body and aortic paragangliomas.

Morphometric and morphological parameters have been evaluated in tumours of carotid body paraganglia and of aorticopulmonary and aorticosympathetic paraganglia. Paragangliomas are characterized by a higher cell density and rounder nuclei (roundness factor) than non-neoplastic carotid body paraganglia. The nuclear area has similar mean values in tumours and normal paraganglia; however, the former group shows higher standard deviation values and coefficients of variation, reflecting the fact that paragangliomas have nuclei of variable size; the variation is more pronounced in aorticopulmonary and aortico-sympathetic paragangliomas. However, subgroups on the basis of morphological features (architectural patterns and degree of intensity of argyrophilia), site of origin, and clinical behaviour (metastases and recurrences) show no morphometric differences.

Neuroendocrine lung structures and tumours: immunohistochemical study by specific markers.

Out of 360 lungs or lobes surgically removed, 13 non neoplastic specimens and 16 neuroendocrine (NE) tumours are investigated with immunohistochemical methods, in order to evaluate the presence of NE structures in normal and pathological human lungs. The markers used are neuron specific enolase (NSE), chromogranin (CG) and the 80 kd antigen (80 kdAg) of NE secretory granules detected by the new monoclonal Phe-5 antibody. In non-neoplastic lung specimens, clearcut immunoreactivity for all three markers appears in NE cells, neuroepithelial bodies (NEB), NE cell-hyperplasias and dysplasias. In the same specimens 4 tumourlets with analogous clearcut immunoreactivities were also observed. The NE tumours show distinct immunoreactivity for all three antisera in the 8 well differentiated cases. The 8 poorly differentiated tumours are variably immunoreactive for NSE and present low to nil staining with antisera to CG and 80 kdAg. The immunohistochemical data are interpreted according to current views about a possible relationship between NE tumours and parent normal NE lung structures.

S-100 protein in human lung neuroendocrine neoplasms. Immunohistochemical study of 14 cases and review of the literature.

A group of lung neuroendocrine (NE) neoplasms are investigated in view of the possible presence of S-100 protein immunoreactivity in their cells. The selected tumours were classified according to Gould et al. (1983a) and Mosca et al. (1985). They comprise 5 carcinoids, 3 neuroendocrine carcinomas of the well-differentiated type, or peripheral carcinoids, 5 neuroendocrine carcinomas of the intermediate cell type, or intermediate-cell, poorly differentiated carcinomas, 3 neuroendocrine carcinomas of the microcytoma type, or small cell carcinomas-SCC and a nodal metastasis of microcytoma. All but 2 tumours were immunoreactive for neuron specific enolase (NSE). Few S-100 immunoreactive cells were detected in 4 out of 5 carcinoids, in 1 out of 3 peripheral carcinoids, in 4 out of 5 poorly differentiated carcinomas and in the 3 microcytomas examined. No S-100 positive cells were found in the SCC's nodal metastasis. The S-100 immunolabelled cells can be interpreted as dendritic reticulum cells migrating through the tumours. However, in one case of typical carcinoid, abundant S-100 positive cells were detected: their stellate morphology and their intimate relation with neoplastic cells suggest that they are part of the neoplasia as a sort of satellite cell.