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Biomedical subjects

F Rilke

Publications and source records attributed to F Rilke.

At least 19 recordsLinked to original sources

Well-differentiated neuroendocrine carcinoma of the lung: a clinicopathologic and ultrastructural study of 10 cases.

The clinico-pathologic characteristics of 10 resected pulmonary tumors, which proved to be well-differentiated neuroendocrine carcinomas (WDNC) on the basis of light microscopic, immunocytochemical, ultrastructural and immunoelectron microscopic investigations, were evaluated. The tumors showed a wide spectrum of histologic features that could be referred to three basic patterns: 1) a carcinoid-like pattern; 2) an organoid pattern characterized by palisading cells at the edge of cellular areas, and 3) a prevalent adenocarcinoma-like pattern. The second pattern was the most distinct even though it often mimicked the small cell/large cell subtype of small cell carcinoma (SCC) owing to its association with marked atypia and poor differentiation. All but one of the patients were males and smokers. The mean age was 58 years. Half of the tumors were centrally located including those showing the adenocarcinoma-like pattern. Disease-free and overall survival and type of tumor dissemination in four patients were similar to those of SCC. Five evaluable patients were alive and disease-free after a mean follow-up of 74 months. Two of these were initially diagnosed as SCC. We conclude that, because of its impact on prognosis, the diagnosis of WDNC appears to be relevant although other factors able to adversely affect the clinical course remain undefined.

Adenocarcinoma

Primary non-Hodgkin's lymphomas of the female breast.

The charts of 35 women with primary malignant non-Hodgkin's lymphomas (NHL) of the breast were retrieved from the files of the Istituto Nazionale Tumori, Milan, over a 30-year period (1957 to 1986). These cases represented 0.1% of the more than 25,000 primary malignant tumors of the breast treated during the same period. The median age of these patients was 57 years (range, 28 to 81 years). In most cases, the clinical diagnosis was carcinoma. The tumors were either Stage IE(48%) or IIE(52%) at presentation, and only two patients had B symptoms. The right breast was involved in 17 patients, the left breast in 14, and both breasts in two. According to the updated Kiel classification and the Working Formulation (WF) for Clinical Usage, three cases were lymphoplasmacytoid (immunocytoma) NHL (WF, A); three, centroblastic-centrocytic, follicular NHL (WF, B); four, centroblastic-centrocytic, diffuse NHL (WF, F); 17 centroblastic NHL (WF, G); three immunoblastic NHL (WF, H); two B-lymphoblastic NHL (WF, I); and one, a Burkitt-like NHL (WF, J). Treatment consisted either of a combination of surgery, radiation therapy, and chemotherapy or radiation therapy and chemotherapy. The follow-up period for 32 patients ranged from 6 to 161 months (mean, 45 months); 17 patients died of their disease. The prognosis appeared to be related to the histologic type and stage of the disease. Median survival periods were 63, 52, 42, and 47 months for centroblastic-centrocytic follicular, centroblastic-centrocytic diffuse, centroblastic, and immunoblastic NHL, respectively. The overall 5-year survival rate was 43%; the 5-year survival rate and the probability of freedom from progression at 5 years were, respectively, 61% and 50% for Stage I and 27% and 26% for Stage II disease.

Breast Neoplasms

Simultaneous in situ hybridization for DNA and RNA reveals the presence of HPV in the majority of cervical cancer cells.

Thirteen cases of invasive squamous cell carcinoma of the uterine cervix containing HPV types 16 or 18 DNA sequences, as detected by Southern blot analysis, were investigated by in situ hybridization on routine paraffin sections, using 35S nick-translated DNA probes. Simultaneous in situ hybridization for DNA and RNA showed that in ten out of 13 cases (77%) the percentage of tumor cells containing HPV 16 or 18 varied from 75 to 100%. In one case, harboring both in situ and invasive carcinoma, the same type of HPV DNA was detected in both components. This finding suggests that neoplastic cells retained the viral genome during progression to invasiveness.

Carcinoma, Squamous Cell

HPV DNA in intraepithelial neoplasia and carcinoma of the vulva and penis.

Surgical specimens of 15 patients with early and 12 patients with advanced squamous cell carcinoma of the vulva and the penis were examined for the presence of human papillomavirus (HPV) type 6, 11, 16, and 18 DNA by Southern blotting (SB) and polymerase chain reaction (PCR) analysis. By SB, HPV type 16 DNA was detected in all early carcinomas and 2 of 12 cases of advanced squamous cell carcinoma (ISCC) of the vulva and penis. PCR revealed HPV DNA in four additional cases of vulvar and penile ISCC negative by SB. Three cases contained HPV16 and one HPV18. Two cases of vulvar and penile Buschke-Löwenstein (BL) tumor with malignancy and one case of vulvar verrucous carcinoma were also examined by both techniques. While BL tumors were associated with DNA of HPV6 or 11, no HPV association was found for verrucous carcinoma. Our results confirm that the detection rate of HPV DNA in early vulvar and penile carcinomas is much higher than in invasive carcinomas. In addition, we have shown that in the lower genital tract, 50% of cases of ISCC are HPV16 correlated. The absence of HPV DNA (types 6, 11, 16, and 18) in the remaining 50% of cases of ISCC thus suggests that vulvar and penile ISCC may have more than one pathogenetic pathway.

Base Sequence

Comparison of Southern blot analysis with isotopic and nonisotopic in situ hybridization for the detection of human papillomavirus sequences in invasive carcinoma of the uterine cervix.

To compare the efficiency of hybridization methods for the detection of HPV genome, 22 cases of invasive squamous cell carcinoma of the uterine cervix were analyzed by Southern blot analysis and in situ hybridization carried out with 35S- and biotin-labeled probes. These cases contained from less than one to as many as 50 copies per cell of HPV 16 and 18 types. To increase the sensitivity of biotinylated probes, a silver enhancement procedure of the peroxidase reaction product was applied. Results showed that in situ hybridization performed with isotopic probes is as sensitive as Southern blot analysis and is more sensitive than that performed with biotin-labeled probe. However, the application of the silver enhancement procedure increases the percentage of HPV-positive cases from 27 to 50%.

Base Sequence

Human papillomavirus genomes in male urethral cells.

Sixty-four samples of urethral cells from male sexual partners of women with genital human papillomavirus (HPV) infection were analyzed for the presence of HPV types 6, 11, 16, and 18 by polymerase chain reaction (PCR) followed by slot blot hybridization. Additional samples from 37 of these subjects were analyzed for the presence of viral cytopathic effects by conventional cytology. By PCR, HPV DNA was detected in 21% (14/64) of samples. By cytology, 16% (6/37) of the samples showed cellular changes consistent with HPV infection. Polymerase chain reaction and cytology results were concordant for presence and absence of HPV in 5 and 28 cases, respectively. Three additional HPV-positive cases were obtained with PCR in the cytologically negative samples. The cytologic abnormalities were found to be associated with the presence of both low-risk HPV types and meatal acetoreactivity. On the contrary, HPV DNA positivity by PCR was unrelated to viral type and peniscopic findings. Urethral HPV infection was detected by PCR in 30% of males with visible penile lesions and in 18% of those without. These results indicate that PCR analysis of urethral samples is a helpful adjunct to cytology for the detection of HPV DNA in absence of cytologic evidence of infection.

Base Sequence

Estrogen and progesterone receptors in breast cancer. Immunohistochemical assay on scraping material.

In order to demonstrate the reliability of immunocytochemical results on cytologic specimens for receptor analysis, the expression of estrogen and progesterone receptors was investigated using immunohistochemistry on frozen sections and on scraping material from the same samples of 50 breast carcinomas. The level of agreement between the two procedures was evaluated by the kappa statistic, as was that between each immunohistochemical procedure and the dextran-coated-charcoal assay since the latter is still the assay employed most frequently for steroid receptor determination and is used for official reports. Statistical results revealed very good agreement regarding the estrogen receptor analysis, with kappa values of .910 and .952 for the comparison of the dextran-coated-charcoal assay with immunocytochemistry on frozen sections and on scrapes, respectively, and .950 for the comparison between the two immunocytochemical procedures. As to progesterone receptors, the kappa values were .795 and .712 for the comparison between the biochemical and immunocytochemical results and .915 for agreement evaluation between the two immunocytochemical procedures. The study showed that the scraping procedure is a valuable tool for the immunocytochemical assessment of steroid receptors in small mammary tumors; it yields representative cellular samples, thus permitting the investigation of heterogeneously distributed substances in tissues.

Adult

Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors.

Archival surgical specimens from 1,210 female breast cancer patients treated between 1968 and 1971 and with a 19-year follow-up were reanalyzed with special reference to several parameters, such as size of the primary tumor, axillary nodal involvement, histologic grade, degree of inflammatory infiltrate (LPI) of the tumor and expression of the neu oncoprotein (p185) as detected by immunohistochemistry. In a multifactorial analysis the 4 former factors were found to be independent prognostic parameters. Over-expression of p185 was found to be related to tumor size and grade and to LPI but not to pathologic nodal status. Over-expression of p185 showed a negative impact upon survival in node-positive but not in node-negative patients. However, in the subset of node-negative patients without LPI, p185 over-expression showed the same correlation with a poor prognosis as in node-positive patients. In contrast, in node-negative and LPI-positive patients, p185 over-expression correlated with a good prognosis. Also, the prognosis of patients with positive nodes, presence of LPI and no p185 over-expression was similar to that of patients with negative nodes, absence of LPI and p185 over-expression.

Age Factors

Comparison of long-term survival of 1986 consecutive patients with breast cancer treated at the National Cancer Institute of Milano, Italy (1971 to 1972 and 1977 to 1978).

Long-term survival of 1986 consecutive patients with infiltrating duct carcinoma of the breast treated at the National Cancer Institute of Milano (Italy) in two periods of time (1971 to 1972 and 1977 to 1978) was comparatively evaluated to verify if the evolving concepts in the management of breast cancer had an impact on survival. The authors found that 10-year survival of our patients increased from 59.4% of the first period of time to 65% of the second (P = 0.005). Both node-negative (N-) and node-positive (N+) patients had an improvement of survival rates at 10 years of the same magnitude: 6.8% and 5.9% respectively. Taking into consideration both the maximum diameter of the primary tumor and the status of axillary nodes it was found that in (1) both N- and N+ patients with a primary tumor of no more than 2 cm in greatest diameter, the improvement of survival was not statistically significant; and (2) both N- and N+ patients with a primary greater than 2 cm in maximum diameter had a better chance of survival in the second time period.

Aged

Genital human papilloma virus infection in males. A clinico-pathologic study.

From March 1987 to December 1988, 402 male sexual partners of 317 women with human papilloma virus (HPV) infection of the lower genital tract and 85 with HPV-associated cervical and/or vulvar intraepithelial neoplasia (CIN and/or VIN) were submitted to clinical examination and peniscopy. The latter was performed at a 6-15 X magnification after a 3 min exposure to 5% acetic acid solution. Visible lesions were biopsied. Thirty-one patients had clinical evidence of HPV infection in the glans, penile shaft or urethra, and 222 had peniscopic evidence of subclinical aceto-white lesions. Of 31 patients with clinical lesions, 11 showed also aceto-white subclinical lesions. Of 253 peniscopically positive males, 237 were biopsied and 191 of these were histologically ascertained. Three patients had penile intraepithelial neoplasia, one with clinical appearance of a Buschke-Löwenstein tumor. The incidence of HPV infection in male sexual partners of women affected by HPV infection of the lower genital tract associated or not with intraepithelial neoplasia is lower than expected. However, clinically negative males should not be considered disease free; in fact, 12 patients, negative at the first examination, showed histological evidence of HPV infection at subsequent controls. Therefore, follow-up of at least 6 months should be allowed to identify HPV bearing males. The reported low frequency of HPV infection may be due to the fact that the males may harbour the virus in the urethra, prostate or seminal vesicles or penis without any clinical evidence of disease. Although research for HPV-DNA in intraurethral and penile scraping material might be useful for diagnosis, peniscopy with a 5% acetic acid application remains the clinical test for evaluating HPV infection in males. The importance of peniscopy should be viewed with respect to the prevention of infection or reinfection of the female sexual partners, in addition to the specific diagnostic purpose in male patients.

Adolescent

Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme.

Dysplastic nevi are an important indicator of risk of cutaneous malignant melanoma. The study of and, particularly, international communication regarding this group of lesions have been hindered by a lack of precision in diagnosis. In an effort to broaden understanding, a panel of pathologists agreed upon a set of criteria for the diagnosis of dysplastic melanocytic nevi. Two major and four minor criteria were defined. The major criteria are (1) basilar proliferation of atypical nevomelanocytes (extending at least three rete ridges or "pegs" beyond any dermal nevo-cellular component), and (2) organization of this proliferation in a lentiginous or epithelioid-cell pattern. Minor criteria are (1) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (2) neovascularization, (3) inflammatory response, and (4) fusion of rete ridges. Diagnosis required presence of both major criteria and at least two minor criteria. One hundred fourteen histologic specimens of benign acquired nevi, dysplastic nevi, and radial-growth-phase melanomas were examined by the members of this panel; their diagnoses were compared to determine degree of concordance. The established criteria yielded 92% mean concordance overall.

Diagnosis, Differential

Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I).

Argyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I)-immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered.

Adult

Distinct morphophenotypic features of chronic B-cell leukaemias identified with CD1c and CD23 antibodies.

Morphological criteria usually applied to diagnose various subtypes of B-cell chronic lymphoid leukaemia are largely subjective. Immunophenotyping of 61 relevant cases using a selected panel of monoclonal antibodies (mAb), showed that CD1c and CD23 mAb were able to separate B-cell chronic lymphocytic leukaemia (B-CLL) from other chronic B-cell lymphoproliferative diseases. Lymphocytes of B-CLL were CD1c-, CD23+, whereas those of other types of chronic B-cell leukaemia were CD1c+/-, CD23-, and CD38/-. Non-B-CLL cases had a significantly higher amount of large peroxidase-negative (unstained) cells analyzed with an automated blood cell counter (Technicon H6000). This type of volumetric assessment allowed a separation between typical and "atypical" B-CLL, which otherwise were both CD1c-, and CD23+. These combinations of phenotypic markers corresponded to well-defined haematopathologic entities, conventionally diagnosed on peripheral blood (PB) and bone marrow smears, and on histologic sections of lymph nodes and spleen.

Antibodies, Monoclonal

Silver enhancement of nickel-diaminobenzidine as applied to single and double immunoperoxidase staining.

A reliable and practical method is proposed for increasing sensitivity and detection efficiency of immunocytochemical techniques, based on silver enhancement of the nickel-diaminobenzidine product of the peroxidase reaction. The procedure produces a strong signal at the site of the end product of the peroxidase reaction which is visible as black grains at the light microscopic level. The method has been used to detect peroxidase labeled probes in immunocytochemical tissue preparations and blotting assays and is ideal for the purposes of double staining and photographic documentation.

3,3'-Diaminobenzidine

C-cell hyperplasia accompanying thyroid diseases other than medullary carcinoma: an immunocytochemical study by means of antibodies to calcitonin and somatostatin.

Eighteen normal thyroid glands and unaffected thyroid tissue adjacent to 37 follicular cell-derived benign and malignant tumors and to ten thyroid metastases were studied immunocytochemically with calcitonin (CT) and prosomatostatin/somatostatin (SMS) antibodies. CT- and SMS-immunoreactive cells were found in 100% of cases, though with ample variations in number. Most but not all SMS-immunoreactive cells also contained CT. Diffuse and/or nodular C-cell hyperplasia was seen in 30% of pathological thyroid glands; in concomitance with follicular adenomas, the mean C-cell number more than doubled that found in normal glands. Furthermore the proportion of SMS-immunoreactive C-cells increased from about 1% of CT-immunoreactive cells in normal adult thyroid glands to 2.5% in follicular adenomas, 3% in follicular carcinomas, 4.6% in papillary carcinomas, and 5.7% in metastases. The findings suggest that C-cell hyperplasia may be causally related to pathologic disorders affecting follicular cells. Furthermore, the demonstration that the intrathyroidal SMS cell mass is readily affected by alterations of the follicular structure of the gland suggests a possible regulatory role of SMS in the thyroidal microenvironment.

Adenocarcinoma

Expression of two antigens defined by monoclonal antibodies in normal, benign and malignant human mammary tissues.

We examined the reactivity of two monoclonal antibodies (MAbs), MBrI and MBr8, on sections from normal breast tissues, benign lesions, primary infiltrating carcinomas and distant breast cancer metastases and compared the expression of the recognized antigens (CaMBr1 and CaMBr8 respectively) in these different normal and pathologic conditions. The expression of both antigens was found to significantly decrease in the neoplastic tissues, in comparison to normal breast tissue (34% vs 61% for MBr1 and 52% vs 86% for MBr8; p less than 0.001 for both). Atypical epithelial hyperplasia was found to be reactive on the same level (31%) of the tumors when tested with MBr1, whereas its reactivity was similar to that of normal tissues (78%) when MBr8 was used. Nonatypical epithelial hyperplasia showed the same reactivity with both MAbs (positive staining on about 50% of the cells). 65% of the "in situ" ductal carcinoma cases was MBr1-positive, whereas 50% was MBr8-positive; these values, when compared with the reactivity on normal glands, were significantly lower for MBr8, but not for MBr1. When testing sections from premenopausal women who had biopsies performed on different days during their menstrual cycle a correlation was found between the expression of CaMBr1 in normal breast epithelial cells and the stimulatory phase of the cycle. These findings suggest that both antigens are typical of normal breast and their expression could possibly decrease in pathologic tissues.

Antibodies, Monoclonal