Biomedical subjects
Publications and source records attributed to B Ghiringhello.
A study of 80 cases of dysplasia of the uterine cervix showed the coexistence of HPV infections in 52 cases. This association (65%) shows the important role played by the human papilloma virus in the genesis of cancer of the cervix.
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Material from 111 invasive primary vulvar carcinomas was reviewed in order to study the histopathologic changes adjacent to the neoplasia. The histopathologic characteristics of the adjacent tissue were divided into categories. Dystrophic lesions were adjacent to invasive cancer in 57.6% of the cases, carcinoma in situ (CIS) in 21.6% and epithelial changes suggestive of human papillomavirus infection in 18.9%. A spectrum of epithelial changes, ranging from hyperplastic dystrophy without atypia to CIS, was found adjacent to nine cases of invasive carcinoma (8.1%). In 40.5% of the vulvar carcinomas there were no specific alterations surrounding the neoplasia. These data show that dystrophies and CIS were adjacent to invasive carcinomas in nearly 60% and 20% of cases, respectively.
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We studied the frequency and distribution of cellular atypia in 448 cases of vulvar dystrophy. The total frequency was 9.4%. Atypia was found almost exclusively in hyperplastic areas. Epithelial changes suggestive of human papillomavirus infection were found in 14.2% of the atypical dystrophies. During the follow-up of 78 patients with typical dystrophy, mild atypia developed in three cases, but with the continuation of medical treatment it disappeared in two cases. Eleven cases of atypical dystrophy were followed for 3-48 months; three patients with severe atypia underwent surgical treatment, and eight with mild atypia underwent medical treatment. Among the last patients, six showed regression and two, progression of the atypia.
Eighty-six cases of vulvar dystrophy in young and premenopausal women (age range, 6-53 years) were studied clinically and histopathologically. The most frequent symptom was pruritus associated with burning. Clinical examination showed the presence of white areas in 73% of the patients, red areas in 9% and other signs (such as melanosis) in 18%. Hyperplastic dystrophy was the most frequent type of dystrophy in these patients and was observed in 63% of cases. Cellular atypia was observed in 9.8% of the cases and was found almost exclusively in hyperplastic dystrophy. Epithelial changes suggestive of human papillomavirus infection were found in 4 of the 86 cases of dystrophy, and they were observed only in atypical dystrophies.
Argyrophilia in breast carcinomas is of uncertain significance. We tested a series of 20 cases of Grimelius-positive carcinomas with immunocytochemical markers of endocrine or exocrine differentiation. Fifty per cent of these tumors were positive, in a variable percentage of the neoplastic cells, with monoclonal antibodies against chromogranin, a specific marker of neuroendocrine differentiation. All cases were positive for neuron-specific enolase, but the significance and specificity of the reaction remain doubtful. The apparent positivity for alpha-lactalbumin, as found also by Clayton and coworkers, was found to be related to a contaminant, which is in fact also an endocrine marker. As with other types of breast carcinoma, all our cases were positive for epithelial membrane antigen, evidence that argyrophilic breast carcinomas, and specifically the chromogranin-positive subgroup, should be interpreted as endocrine neoplasms displaying multidirectional differentiation.
Papillomavirus common internal capsid antigen (PV-Ag) was demonstrated using an immunoperoxidase technique in 74 out of 239 (31.0%) cases of cervical condylomata diagnosed histologically. All the positive cases but 2 (72/74) had nuclear changes compatible with dysplasia or cervical intraepithelial neoplasia (CIN). Immunocytochemically determined PV-Ag positivity was found in 54 out of 92 CIN I (58.7%), in 14 out of 32 CIN II (43.8%) and in 4 out of 18 CIN III (22.2%). The extent of koilocytosis in the epithelium had a direct correlation with the PV-Ag positivity: when koilocytosis extended to more than two thirds of the epithelium thickness, 24/41 cases (63.4%) were positive; when between one third and two thirds, 32/105 cases (30.5%) were positive; when present in less than one third 16/93 cases (17.2%) were positive. The positivity was 41.8% under 30 years of age and 20.5% over 30. Out of 16 positive cases followed with multiple biopsies for 6-20 months, 9 remained positive without change in CIN degree and 7 became negative, with CIN regression in 4 cases and progression to CIN III with disappearance of koilocytosis in 3 cases. More specific methods than histocytopathology alone are needed for epidemiologic and follow-up studies, especially in the cases in which the disappearance of antigenic and morphological expression of PV infection is not followed by dysplasia regression.
Protein-thiol groups that react with dihydroxydinaphthyl disulphide during a 7 h incubation (so-called reactive protein thiols, PSHr) have been quantitatively measured on sections of human uterine cervix by microcytospectrophotometry. Measurements were made on areas (1 micron 2) of epithelium and adjoining stroma in samples of normal cervix, and in samples obtained from patients with dysplasia, carcinoma-in-situ and invasive cancer. The ratio of PSHr in epithelium to stroma is substantially reduced in the pathological conditions compared with normal and in apparently normal adjacent areas. Such changes in PSHr are discussed in relation to the redox balance of the tissue, and free radical disturbances previously described.
Estrogen receptors (ER) were evaluated in 634 breast cancer patients by the dextran-coated charcoal method (DCC). In 206, ER and progesterone receptors (PR) were also tested by cytochemistry (Lee method), and in 124 ER were tested by immunofluorescence (Pertschuk method). The median follow-up is 3.7 years. Comparisons have been made between receptor content and: anatomical and clinical features, disease-free survival (DFS), and survival. The following conclusions can be drawn: there is no correlation between ER determinations by DCC and by immunofluorescence or cytochemical methods; there is no evidence of association between ER and PR determined by Lee's method and anatomical and clinical features; a highly significant positive association was found between ER rich specimens and age, post-menopausal status, lobular and tubular histologic types; there is no association between ER values and TNM stage, WHO grading, pathologic prognostic factors of primary tumor and of lymph nodes; and the DFS was not affected by ER status, except for tumors with more than 50 fmol/mg protein.
The production of PGI2 (determined by bioassay) and TXB2 (determined by radioimmunoassay) was studied in the supernatant solutions obtained after incubation of vessel rings prepared from veins draining and not draining benign and malignant tumours of the breast. A significant increase (p less than 0.01) was found in the production of PGI2 by vessels draining the malignant tumours as compared to those not draining such tumours or vessels draining benign tumours. The changes in PGI2, and the tendency for TXB2 to be higher in vessels draining malignant tumours, were in the same direction so that they balanced out when the ratio PGI2/TXB2 was calculated: in consequence no significant changes in this ratio were found in malignant tumours as compared to the benign. A significant difference (p less than 0.01) was observed in the ratios of vessels draining tumours:vessels not draining tumours between malignant and benign tumours in relation to the production of PGI2. The present data demonstrate that the production of PGI2 by vessels draining malignant tumours of the breast is different to that obtained with vessels from patients with benign tumours, although the mechanism responsible for this difference is not known.
Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in a single pathology laboratory were checked against the final pathological report. In 4284 cases (96.57%) there was no difference between the FSD and the definitive diagnosis. There were 74 (1.66%) false negative reports and no false positive diagnoses. The diagnosis was deferred to paraffin sections in 78 cases (1.75% of biopsies). The predictive value for positive results was 100% and for negative results 97.5%; the specificity was 100%, the sensitivity 94.6% and the accuracy 98.3%. Minimal breast cancer, in situ (CIS) especially, was the main source of false negative reports. In non minimal invasive cancers (NMIC) FSD was correct in 99.42%. In minimal invasive cancers (MIC) FSD was correct in 80.21%, false negatives and deferred diagnosis increased to 8.79% and 10.98%. In CIS false negatives increased to 76.82% and deferred diagnoses to 12.19%. The sensitivity of fine needle aspiration, performed before biopsy in a portion of the patients, was lower than FSD in NMIC (71.39% versus 99.21%) and in MIC (41.66% versus 80.55%), identical to FSD in CIS (7.40% versus 7.40%). The value of cytodiagnosis in addressing surgery is discussed.
To identify histological preneoplastic lesions and early neoplastic foci, a histological and immunohistochemical study has been conducted on a series of 18 cases with the rare association of multiple intraductal papillomas and in situ breast carcinoma. The pathological and clinical data of these cases have been collated. A close anatomical and spatial association between the benign papillomas and areas of in situ carcinoma (mostly of the cribriform type) was a frequent finding. In agreement with the results of our previous investigations, cytoplasmic CEA has been found to be a marker of intraductal carcinomas, while staining for actin has been found useful to identify the myoepithelial cells present in benign papillomas as opposed to carcinomas. The immunohistochemical procedures for these two markers have been conducted on parallel sections; alternatively, an immunoperoxidase/immuno-galactosidase sequence has been applied on the same section. The results indicate that, in cases with multiple papillomas, CEA-positive, myoepithelial cell-free carcinomatous areas can be anatomically associated with and even present inside the benign-looking papillary lesions. These findings can be interpreted as evidence of a malignant transformation of intraductal papillomas, or, less likely, of their 'cancerization' by ductal carcinoma.
Hamartomas of the breast are rare lesions that may grossly simulate carcinomas: up till now fibrous, adipose and glandular tissues have been recognized within them. Here we report and discuss a case with the typical features of hamartomas, but displaying a marked smooth muscle component. The structure and localization of this tumour, and that of the few similar lesions reported in the literature, suggest that this peculiar type of hamartoma originates in the subareolar tissue.
A case of juvenile secretory carcinoma of the breast is reported. The tumor occurred in a 19 yr-old nulliparous woman and was treated by local resection; it recurred 7 years later. Slight infiltration of the pectoral muscle, metastatic involvement of one lymph node and multifocal areas of carcinoma were found at radical mastectomy. No further recurrence has been detected after 1 year. This case confirms the slow evolution of this neoplasm but stresses that its behavior is not always as indolent as previously believed. We have used histochemical techniques for mucins (PAS, Alcian Blue) and immunoperoxidase methods for milk proteins (MFGM, beta-Casein, alpha-lactalbumin), for myoepithelial cells (actin) and for oncofetal antigens (CEA). Our results suggest that: Immunoperoxidase methods for milk proteins are a more specific and reliable marker than PAS staining in characterizing the secretory activity of juvenile carcinoma. The absence of myoepithelial cells in infiltrative areas detected by immunoperoxidase methods for actin confirms the low degree of organization in this well differentiated carcinoma of limited aggressiveness which secretes milk proteins.
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