Changing testicular histology in AIDS: its implication for sexual transmission of HIV.

OBJECTIVES: The understanding of testicular histology in acquired immunodeficiency syndrome (AIDS) is essential, because the sexual route is one of the main means of transmission of the human immunodeficiency virus, which is localized primarily in the germ cells of the testes. It is important to determine whether any changes have occurred in the testicular histologic patterns in the course of the AIDS epidemic. METHODS: One hundred forty testicular specimens were available from AIDS autopsies during the AIDS epidemic (1981 to 1998). The epidemic was divided into pre-zidovudine (pre-AZT) therapy (1981 to 1987) and antiviral therapy (1988 to 1998) periods; the latter period was further subdivided on the basis of the particular treatment used. Testicular histology was evaluated and correlated with patient age, CD4 T-cell counts, and pathologic findings in other parts of the body. RESULTS: Testicular histologic findings were categorized into three groups: hypospermatogenesis (group S), spermatogenic arrest (group A), and Sertoli cell only (group O). The percentage of AIDS patients with group S histologic findings remained constant throughout the study period: 26% in the pre-AZT and 28% in the antiviral therapy periods. However, there was a reversal in the percentages of patients in groups A and O: group A decreased from 48% (pre-AZT) to 28% (antiviral) and group O increased from 26% (pre-AZT) to 44% (antiviral). There was no correlation between testicular histologic results and patient age or CD4 count. Opportunistic infections and testicular neoplasms were also identified. CONCLUSIONS: This study demonstrates that current therapy and prolongation of survival in AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. However, 28% of patients still show significant spermatogenesis at the time of death from AIDS and this subgroup cannot be identified by age or CD4 T-cell counts. The presence of large numbers of residual germ cells in these patients suggests that they may continue to be infectious throughout their disease course.

HIV in testis: quantitative histology and HIV localization in germ cells.

The testes of AIDS patients invariably show decreased spermatogenesis and are atrophic. These testicular changes can be grouped into three categories: (1) spermatogenesis present, but decreased; (2) spermatogenic arrest at primary spermatocyte stage; and (3) Sertoli only (or almost Sertoli only). The purpose of this study is 2-fold: firstly, to quantitate the numbers and types of germ cells in these three groups as compared with normals. In addition the presence of HIV-1 DNA positive germ cells was quantitated by PCR in situ hybridization. HIV-1 was identified in 14 of 15 testes from HIV infected adults, and was present in 25-33% of residual germ cells. There was an average of 18.9 HIV infected germs cells/tubule in the spermatogenesis group, 6.3 HIV infected germs cells in the spermatogenic arrest group, and 0.25 HIV infected germ cells in the almost Sertoli only group. HIV-1 DNA was absent in three of the three preadolescent boys testes (HIV acquired in utero). This study quantitates the degree of germ cell loss in AIDS patients and quantitates the degree of HIV positivity of the residual germ cells, thus shedding more light on the testicular HIV burden, with its possible repercussions for sexual transmission of HIV.

bcl-2 and p53 in endometrial adenocarcinoma.

bcl-2 protein is expressed in normal endometrium and seems to be under hormonal control. Its role in endometrial carcinoma (EC) is largely unknown. EC can serve as a good model to investigate the role of bcl-2 in hormone-dependent neoplasia, because EC shows a spectrum of hormonally induced changes in which bcl-2 might have a potential role. p53, a tumor suppressor gene, is the most commonly mutated gene in human cancer and is a frequent abnormality in advanced EC. There is interaction between p53 and bcl-2 proteins in the regulation of physiological programmed cell death and in malignant processes. In this study, we performed immunohistochemical investigations of the expression of bcl-2 and p53 in 57 ECs, along with estrogen and progesterone receptors (ERs, PRs), to correlate the expression patterns of bcl-2 and p53 in different grades of EC with relation to clinicopathologic parameters. The average age of the patients was 61 years. Among 57 ECs, there were 13 noninvasive ECs and 44 ECs with various depths of invasion. p53 was positive in 21 of 57 cases, and bcl-2 was positive in 42 of 57. ER and PR were positive in 24 of 57 cases; PR and ER alone were positive in 15 and 2 cases, respectively. bcl-2 expression is present in ECs, and its expression is related to grade and stage. bcl-2 expression is strongly associated with PR, whereas p53 is associated with higher grade and is inversely related to PR positivity.

Metastatic breast carcinoma presenting as endometrial cancer. A case report.

BACKGROUND: Breast cancer is the most common cancer in women in the United States and second leading cause of cancer death in women. Primary breast carcinoma frequently metastasizes to the pelvic organs. CASE: A 63-year-old, post-menopausal woman with a history of breast carcinoma presented with post-menopausal vaginal bleeding. Diagnostic studies were consistent with a fibroid uterus and notably normal ovaries bilaterally. Dilatation and curettage revealed poorly differentiated adenocarcinoma thought to be primary endometrial cancer. A total abdominal hysterectomy and bilateral salpingooophorectomy were performed, and final pathology revealed metastatic breast carcinoma. Neoplastic cells were strongly positive for both carcinoembryonic antigen and gross cystic disease fluid protein, a marker of breast carcinoma. CONCLUSION: Breast carcinoma may metastasize to unusual sites, such as the endometrium and uterine leiomyomata, and mimic primary uterine malignancies. Immunohistochemistry is useful in reaching the diagnosis in difficult cases when a patient has a history of breast carcinoma.

Detection of HIV-related protein in testes and prostates of patients with AIDS.

The testes and prostates of 14 patients with acquired immune deficiency syndrome (AIDS) for whom autopsies were performed were examined for the presence of human immunodeficiency virus (HIV) and the pathologic alterations seen in AIDS. Histologically, the testes contained peritubular fibrosis and variable spermatogenic arrest, which were inconsistent with the young age of these patients. There were also numerous foci of germ cell degeneration and occasional germ cell loss. The Leydig cells were atrophic and decreased in number. The prostates contained increased numbers of concretions. Sections of testis and prostate were stained with an anti-HIV P17 monoclonal antibody with the use of the avidin-biotin technique. Small scattered foci of positive staining were identified in 8 of 14 testes (57%). They were located over one or several degenerating germ cells and the surrounding Sertoli cells. In addition, in 9 of 14 prostates (64%) there were a few minute foci of positive staining in several adjacent glandular epithelial cells. In one case the testis was positive and the prostate was negative, whereas in two cases the testes were negative and the prostate positive. In contrast, 22 testes and 22 prostates of control non-AIDS patients, read double-blind, were negative. The positive controls were HIV-infected tissue culture HUT 78 lymphoma cells in which there were many scattered positive cells. The results indicate the presence of focal HIV-associated protein in the testes and prostates of patients with AIDS, particularly within the foci of germ cell degeneration. The present observations are in accordance with previous research demonstrating the presence of HIV in the seminal fluid of patients with AIDS and appears to indicate the presence of an infection of the male genital tract by the HIV virus.

Acid phosphatase localization in prostatic carcinoma. A comparison of monoclonal antibody to heteroantisera.

A series of 39 prostatic carcinomas was characterized in terms of grade, stage, histologic pattern, and serum acid phosphatase values. These cases were studied immunohistochemically with two different heteroantisera, a goat and rabbit antiserum, and with a monoclonal antibody to prostatic acid phosphatase (PAP). Eighty-three percent of carcinomas had some degree of PAP positivity when stained by the goat anti-PAP. Seventy percent were positive with the rabbit antiserum, and 59% showed positivity with the monoclonal antibody. Microacinar patterns were consistently the most positive for PAP, followed by cribriform patterns. The least positivity was observed in the undifferentiated, single-file and sheet-like patterns. Likewise, there was more PAP positivity in the lower Gleason and Mostofi grades. When the serum PAP positivity (done by counterimmunoelectrophoresis [CIEP]) was compared with tissue positivity (using the same goat antiserum), 37% were positive in both serum and tissue; 48% were negative in serum, but positive in tissue; and in only 9% the tissue sample was negative when the serum was positive. Based on these data, conclusions are drawn about the significance of the serum acid phosphatase elevations and the role of monoclonal antibodies and heteroantisera in clinical-diagnostic and research work.

DNA content of condyloma acuminatum.

Female genital condylomata acuminata were examined for DNA content. Diploid and polyploid DNA distributions, including tetraploidy and octaploidy, were found. These findings are in clear counter-distinction to squamous intraepithelial lesions, which have been found to be aneuploid. DNA quantitation, therefore, can be used in difficult cases to distinguish between condylomatous and neoplastic epithelium.

Muscle phosphofructokinase deficiency: abnormal polysaccharide in a case of late-onset myopathy.

A 61-year-old woman with muscle phosphofructokinase (PFK) deficiency had mild limb weakness all her life but no cramps or myoglobinuria. For 5 years the limb weakness progressed. In muscle, PFK activity was 1% of normal and glycogen concentration was elevated (2.13%). By light microscopy, a minor component of the accumulated glycogen appeared as PAS-positive, diastase-resistant inclusions in 10% of muscle fibers. The inclusions had a filamentous fine structure that resembled the abnormal long-chain glycogen of brancher enzyme deficiency. Iodine absorption spectra of both the inclusions and a diastase-resistant fraction of isolated glycogen resembled amylopectin. The abnormal polysaccharide in PFK deficiency may be related to greatly elevated concentration of muscle glucose-6-phosphate, an activator of the chain-elongating enzyme glycogen synthase.

Clear cell carcinoma of the ovary: a clinicopathologic study with review of the literature.

The pathologic and clinical aspects of 21 cases of pure, clear cell carcinoma of the ovary are discussed. The literature is reviewed with particular reference to histogenesis and to the problems related to defining this tumor as a separate clinicopathologic entity. It is suggested that clear cell carcinoma represents a histologic variant of endometrioid carcinoma rather than constituting a separate entity.

Carcinoembryonic antigen localization in benign and malignant transitional epithelium.

Transitional epithelium from 30 cases, including transitional cell carcinoma of various grades and stages, carcinoma in situ, cystitis cystica, and glandularis, as well as normal bladder epithelium, was studied for carcinoembryonic antigen (CEA) content by the immunoperoxidase technique. The results indicate that CEA is present in normal transitional epithelium and that its level frequently decreases in transitional cell carcinoma. These results are related to the findings in studies of urinary CEA excretion.

Histogenesis of Brenner tumors, II: histochemistry and CEA.

The histochemical characteristics of 21 benign Brenner tumors were studied. The mucins associated with these tumors are of transitional cell origin and do not represent a secondary metaplasia of transitional to intestinal-type epithelium. The goblet and ciliated columnar cells associated with the proliferative Brenner tumor are thought to represent a parallel mucinous metaplasia from celomic epithelium. Thirteen of the 16 benign Brenner tumors and the one proliferative Brenner tumor were found to contain carcinoembyronic antigen (CEA), indicating an additional antigenic similarity to transitional epithelium.

Histogenesis of Brenner tumors, I: histology and ultrastructure.

The histology of 36 benign and four proliferative Brenner tumors is reviewed, and the ultrastructural features of benign Brenner tumors are described. Evidence is presented for the origin of these tumors from celomic inclusion cysts through transitional metaplasia of the cyst lining and progressive growth of branching cords of transitional epithelium. Ovarian lesions associated with the Brenner tumor are described, particularly those containing mucinous epithelia, and their significance is discussed.

Malignant mixed tumor of the vagina probably arising in mesonephric rests.

An exceedingly rare tumor arising in the upper lateral vagina is described histologically, histochemically, and ultrastructurally. It is compared to the lesion reported by Okagaki et al. which is considered to represent the same type of tumor. Comparison with synovial sarcomas indicates that the lesion is similar, but the reasons why it should not be so classified are discussed. Evidence is presented for the origin of these tumors in mesonephric rests (Gartner's duct).