Nontrophoblastic pathology of the female genital tract and peritoneum associated with pregnancy

This report reviews the clinical and pathological features of nontrophoblastic lesions that involve the female genital tract and peritoneum and are typically or exclusively associated with pregnancy or the puerperium. The majority of them are nonneoplastic lesions that may be confused with a neoplasm on clinical or pathological examination. Pregnancy-related changes within gynecological tumors that may create problems in histological interpretation also are discussed briefly.     

Xanthogranulomatous inflammation of the female genital tract

We describe three cases of xanthogranulomatous inflammation in the female genital tract--one affecting endometrium, tube and ovary, one affecting tube, ovary and parametrium and one confined to the endometrium. To date, xanthogranulomatous inflammation in the female genital tract has been reported in a total of 19 cases including the present three. The inflammation most often affects the endometrium but involvement of the vagina, cervix, fallopian tube and ovary may also occur.     

Selenium deficiency is associated with shedding of HIV-1--infected cells in the female genital tract

OBJECTIVE: To assess the relation between selenium deficiency and vaginal or cervical shedding of HIV-1-infected cells. DESIGN: Cross-sectional study of 318 HIV-1 seropositive women in Mombasa, Kenya. METHODS: Vaginal and cervical swab specimens were tested for the presence of HIV-1 DNA by polymerase chain reaction. Multivariate logistic regression models, adjusting for CD4 count and vitamin A deficiency, were used. RESULTS: Selenium deficiency (defined as levels <85 microg/L) was observed in 11% of the study population. In unstratified multivariate analyses, there was no significant association between selenium deficiency and vaginal or cervical shedding. In stratified analyses, however, significant associations became apparent after excluding women with predictors of shedding with strong local effects on the genital tract mucosa. Among women who did not use oral contraceptives and who did not have vaginal candidiasis, selenium deficiency was significantly associated with vaginal shedding (adjusted odds ratio [AOR] 2.9, 95% confidence interval [CI] 1.0--8.8, p =.05). Effect modification was also observed in the relation between selenium deficiency and cervical shedding, with a significant association seen among those women who were not using oral contraceptive pills or depot medroxyprogesterone acetate and who did not have Neisseria gonorrhoeae infection (AOR 2.8, 95% CI 1.1--7.0, p =.02). CONCLUSIONS: We found selenium deficiency to be associated with a nearly threefold higher likelihood of genital mucosal shedding of HIV-1--infected cells, suggesting that deficiency may increase the infectiousness of women with HIV-1. Nutritional interventions to prevent HIV-1 transmission warrant investigation.     

Multifocal PEComa (PEComatosis) of the female genital tract associated with endometriosis, diffuse adenomyosis, and endometrial atypical hyperplasia

The authors describe a case of multifocal perivascular epithelioid cell tumor (PEComa) arising in the pelvis of a 39-year-old woman affected by tuberous sclerosis. The tumor presented in the form of multiple fascicular, focally cystic nodules involving the uterine corpus, both ovaries, and the omentum. Microscopically, the nodules were composed of foci of adenomyosis and endometriosis (with focal atypical complex hyperplasia) associated with a stromal spindle cell population immunoreactive for HMB-45, smooth muscle actin, and estrogen and progesterone receptors. We interpret these foci as the result of a widespread proliferation of perivascular epithelioid cells (PEC). Because of the diffuse quality of the process, the designation of PEComatosis seems warranted.     

Clinical syndromes associated with tumors of the female genital tract.

Tumors of the female genital tract may be associated with a variety of unusual clinical manifestations. Uncommon endocrine and paraendocrine syndromes include production of human chorionic gonadotropin by tumors other than those of germ cell origin, hyperthyroidism associated with struma ovarii and gestational trophoblastic disease, the carcinoid syndrome, the Zollinger-Ellison syndrome, hypercalcemia, Cushing's syndrome, hypoglycemia, hypertension related to renin or aldosterone production, hyperprolactinemia, inappropriate secretion of antidiuretic hormone, and virilization associated with Nelson's syndrome and placental site trophoblastic tumor. Paraneoplastic syndromes associated with gynecological tumors include disorders of the nervous system, connective tissue, and skin, as well as hematologic abnormalities and the nephrotic syndrome. Heritable and other congenital syndromes associated with these tumors are the Peutz-Jeghers syndrome, the nevoid basal-cell carcinoma syndrome, Ollier's disease and Maffucci's syndrome, hereditary leiomyomatosis, ataxia-telangiectasia, von Hippel-Lindau's disease, thyroid abnormalities associated with Sertoli-Leydig cell tumors, and Carney's complex. Other syndromes associated with tumors of the female genital tract include Meigs' syndrome, hyperamylasemia, uveal melanocytic lesions, and pyrexia.     

Oxyphilic proliferations of the respiratory tract and paranasal sinuses.

Neoplasms of the upper respiratory comprised primarily of eosinophilic cells are, in general, rare, and they include a diverse group of lesions. Low-grade oncocytic neuroendocrine neoplasms (so-called oncocytic carcinoids) can be encountered in several locations throughout the respiratory tract. The oncocytoma and related entities, lesions that presumably arise from minor gland tissue, can likewise be seen from the nasal cavity to the lung; differences in clinical significance may relate to the location of such lesions, and are discussed herein. Granular cell tumor is another entity that can involve both the upper respiratory tract and lungs, and specific features of this lesion in different anatomic sites are highlighted. The oncocytic variant of Schneiderian papilloma is an important nasal lesion to recognize, because of important therapeutic and prognostic implications of that diagnosis. Finally, unique oncocytic variants of glomus tumor and pulmonary alveolar adenoma are discussed, as well as eosinophilic varieties of pulmonary carcinomas and mesotheliomas.     

Fungal disease of the nose and paranasal sinuses

Fungal infections of the nose and paranasal sinuses represent a spectrum of diseases ranging from colonization to invasive rhinosinusitis. Clinical manifestations are largely dependent on the immune status of the host, and given the ubiquitous nature of these organisms, exposure is unavoidable. Noninvasive disease includes asymptomatic fungal colonization, fungus balls, and allergic fungal rhinosinusitis. Invasive disease includes indolent chronic rhinosinusitis, granulomatous fungal sinusitis, and acute fulminant fungal rhinosinusitis. A?differentiation of these somewhat overlapping syndromes and the disparate treatment regimens required for effective management are the focus of this review.     

Colonization of the female genital tract with Staphylococcus saprophyticus.

The prevalence of colonization by Staphylococcus saprophyticus of the urogenital tracts of 276 women from an outpatient gynecology practice was determined by using selective and enrichment culture techniques. Nineteen subjects (6.9%) were found to be colonized by S. saprophyticus. The rectum was the most frequent site of colonization and was responsible for 40% of the isolates; this was followed in decreasing order by the urethra, urine, and cervix. Women colonized by S. saprophyticus were more likely to have experienced a urinary tract infection in the previous 12 months (P = 0.058; odds ratio, 2.844; 95% confidence interval, 1.054 to 7.671). Patients colonized by S. saprophyticus tended to have had their menstrual periods more recently (P = 0.066), experienced sexual intercourse more recently (P = 0.168), and had a recent or concurrent diagnosis of vaginal candidiasis (P = 0.111; odds ratio, 2.393; 95% confidence interval, 0.877 to 6.528). A seasonal variation in colonization was observed, with colonization most likely occurring during the summer and fall. Follow-up for an average of 6.75 months failed to document any colonized woman progressing to symptomatic urinary tract infection. In addition, 21 women colonized by non-S. saprophyticus, novobiocin-resistant, coagulase-negative staphylococci were identified and characterized.     

Paget's disease with extensive involvement of the female genital tract initially detected by cervical cytosmear

A 78-year-old woman with extramammary Paget's disease presented with vaginal bleeding and vulvar pruritus. Paget's cells were demonstrated initially in a cervical cytosmear and, subsequently, in the epithelia of the vagina and cervix, in addition to those of the vulva, periurethral area, and perineum. Such extensive intraepithelial spread of Paget's disease in the genital tract has rarely been reported previously. This is the first case, to our knowledge, in which the cells of cervicovaginal Paget's disease were detected by Papanicolaou smear.     

Undifferentiated and dedifferentiated neoplasms of the female genital tract

Undifferentiated neoplasms in the female gynecologic tract comprise two main groups—undifferentiated carcinoma, most common in the endometrium and ovary, and undifferentiated uterine sarcoma, although tumors with an undifferentiated appearance may occur in all gynecologic organs. Their differential diagnosis is broad and generous sampling, careful morphological evaluation, judicious use of immunohistochemistry, and in many cases, molecular testing is often essential in the diagnostic work-up. As some of these neoplasms fail to respond to conventional chemotherapy regimens and/or radiation therapy, targeted therapy may be valuable in treating these highly aggressive tumors, thus the importance of precise diagnosis. In this review we discuss the clinicopathological features of undifferentiated carcinoma, dedifferentiated carcinoma, and undifferentiated uterine sarcoma, followed by a comprehensive analysis of morphological mimickers. Finally, we briefly review ovarian and lower genital tract tumors with an undifferentiated histological appearance.     

Inherited plasminogen deficiency presenting as ligneous vaginitis: a case report with molecular correlation and review of the literature

Type 1 plasminogen deficiency is an inherited and potentially life-threatening systemic disease in which patients develop pseudomembranous lesions of mucosal surfaces exposed to minor trauma. It is most commonly clinically encountered as ligneous conjunctivitis. We report the case of a 39-year-old woman with extensive involvement of the female genital tract. Microscopically, the vagina, cervix, endometrium, ovaries, and parametrial tissues showed innumerable deposits of paucicellular hyaline material with adjacent inflammation. Histochemical, immunofluorescent, and electron microscopic analyses revealed the amorphous material to be fibrin and collagen. In the plasma, functional plasminogen and plasminogen antigen levels were markedly decreased. Sequencing showed the patient to be a compound heterozygote for a missense and nonsense mutation in the plasminogen gene. Histologically, deposits in ligneous vaginitis are easily confused with amyloid or fibrinous debris. Recently, replacement therapy with plasminogen has been shown to significantly improve systemic symptoms, making ligneous mucositis a serious but treatable condition.     

Endometriosis associated with defective handling of apoptotic cells in the female genital tract is a major cause of autoimmune disease in women

Several autoimmune diseases are far more common in women than men. The reasons are unknown. Recent studies have shown that many autoimmune diseases which predominantly affect females are characterized by the production of autoantibodies against components of apoptotic cells. Furthermore, in experimental animals, defective clearance of apoptotic cells in a pro-oxidant inflammatory environment can trigger the production of these autoantibodies and related autoimmune disease. Endometriosis is characterized by defective clearance of apoptotic endometrial cells in a pro-oxidant inflammatory environment. It is proposed that this combination of abnormalities triggers autoantibody production in women affected by endometriosis. A proportion of these women will be genetically predisposed to develop overt autoimmune disease. As endometriosis affects at least 4% of the female population of reproductive age, this phenomenon will have a major effect on the gender prevalence of several related autoimmune syndromes. The hypothesis is supported by epidemiological studies which show a strong association between endometriosis and female-predominant autoimmune disorders.     

Generation of female genital tract antibody responses by local or central (common) mucosal immunization

Genital antibody responses were compared in female mice immunized intravaginally (i.vag.) or intranasally (i.n.) with a bacterial protein antigen (AgI/II of Streptococcus mutans) coupled to the B subunit of cholera toxin. Serum and salivary antibodies were also evaluated as measures of disseminated mucosal and systemic responses. Although i.vag. immunization induced local vaginal immunoglobulin A (IgA) and IgG antibody responses, these were not disseminated to a remote secretion, the saliva, and only modest levels of serum antibodies were generated. In contrast, i.n. immunization was substantially more effective at inducing IgA and IgG antibody responses in the genital tract and in the circulation, as well as at inducing IgA antibodies in the saliva. Moreover, mucosal and systemic antibodies induced by i.n. immunization persisted for at least 12 months. Analysis of the molecular form of genital IgA indicated that the majority of both total IgA and specific IgA antibody was polymeric, and likely derived from the common mucosal immune system.     

Teratogenic effects of clomiphene, tamoxifen, and diethylstilbestrol on the developing human female genital tract

The potential estrogenicity and teratogenicity of triphenylethylene antiestrogens were examined in 54 genital tracts isolated from 4- to 19-week-old human female fetuses and grown for 1 to 2 months in untreated athymic nude mice or host mice treated by subcutaneous pellet with the antiestrogens clomiphene and tamoxifen or the synthetic estrogen diethylstilbestrol (DES). In specimens grown to a gestational age equivalent of 15 weeks or less, the vagina and urogenital sinus were lined by an immature squamous epithelium, which were similar in both drug-treated and untreated specimens. Proliferation and maturation of the squamous vaginal epithelium were observed in specimens treated with clomiphene, tamoxifen, or DES only when grown to a gestational age equivalent of 16 weeks or more. Formation of endometrial and cervical glands proceeded in 87 per cent (13 of 15) of control specimens grown to a gestational age equivalent of 13 weeks or more in untreated hosts. By contrast, age-matched drug-treated specimens contained glands in only 44 per cent (12 of 27) of specimens. In the developing uterine corpus of untreated controls, the uterine mesenchyme segregated into inner (endometrial stroma) and outer (myometrial) layers; whereas in drug-treated specimens, condensation and segregation of the mesenchyme were greatly impaired. The fallopian tube was also affected by clomiphene and tamoxifen (and to a lesser extent by DES) in that its epithelium was hyperplastic and disorganized. The complex mucosal plications characteristic of the fallopian tube were also distorted in drug-treated specimens. These results emphasize the heretofore unrecognized estrogenicity and potential teratogenicity of triphenylethylene antiestrogens on the developing human genital tract and emphasize the need for caution to prevent inadvertent exposure of the developing fetus to these compounds.