Stuart C. Lauchlan

The secondary müllerian system revisited.

The peritoneum is the matrix where benign and malignant proliferation of secondary müllerian epithelium occur. Endometriosis, endosalpingiosis, and endocervicosis are benign peritoneal neoplasms corresponding to endometrioid, serous, and mucinous carcinomas. These latter are concentrated predominantly, although not exclusively in the ovary, and reasons for this localization are discussed. Exposure to talc, or perhaps to the asbestos that often contaminates it, occurs in the process of powdering during infancy and may be the major initiating factor in benign and malignant disorders of the secondary müllerian system. It can be anticipated that the incidence both of endometriosis and of ovarian tumors will be reduced in those women powdered with starch instead of talc during infancy, as well as by the continued use of ovulation-suppressing agents such as contraceptive steroids.

Clinical characteristics of placental site trophoblastic tumor (PSTT)

Placental site trophoblastic tumor (PSTT) has been demonstrated to be a rare variant of gestational trophoblastic disease, with only 43 cases of this disorder having been reported in the English language literature since 1976. It is associated with a 20% mortality rate, occurs in young women, is very resistant to standard trophoblastic disease chemotherapy, and is generally treated by hysterectomy. This report describes an additional 5 cases of PSTT, two of whom died of their disease. It aims to clarify the varied clinical characteristics of the condition through a comparative analysis of these patients with those previously reported. Specific factors in the analysis include age, mitotic count, presence of marker hormones, preceding gestational situation, cause of death, survival time from diagnosis, tumor karyotype, and treatment. The study suggests that a preceding term pregnancy, a high mitotic ratio, and an older age group may be associated with a higher mortality rate. It also supports the premise that some patients, with a low mitotic ratio and other favorable histologic features, may be treated conservatively with curettage and very careful follow-up monitoring if they wish to preserve reproductive potential.

α and β subunits of inhibin/activin as sex cord-stromal differentiation markers

Inhibins (α and β heterodimers) and activins (β homodimers) are related peptides with opposing biologic action on gonadotropin regulation. They serve as components of the pituitary-gonadal feedback system. Although sexcord stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. A total of 28 sex cord-stromal tumors of the ovary and 43 non-sex cord-stromal tumors were immunohistochemically evaluated for the presence of α and β subunits of inhibin and activin. For comparison, 10 normal adult gonads including seven ovaries with hilar regions and three testes also were examined. Immunoreactivity for both α and β subunits of inhibin/activin was identified in both non-neoplastic and neoplastic granulosa, Sertoli, Leydig, hilar and luteinized theca cells, with the strongest immunoreactivity in Leydig and hilar cells. One of three Sertoli-Leydig cell tumors that showed a sarcomatoid growth pattern and one sex-cord tumor with annular tubules also were immunoreactive for both subunits. For non-sex cord stromal-derived ovarian tumors, α subunit immunoreactivity was negative in all but two of five ovarian mucinous tumors. Weak immunoreactivity for β subunit was found in most ovarian surface epithelial carcinomas, two of four colonic, and one of three pancreatic carcinomas. No immunostaining was found in nonspecialized gonadal stromal or interstitial cells, thecal cells, germ cells, ovarian small cell carcinomas, carcinoid tumors, dysgerminomas, or leiomyosarcomas. Immunostaining of α subunit (inhibin α), but not of β subunit could serve as a sex cord-stromal differentiation marker because α subunit alone is largely confined to sex cord-stromal lesions with the exception of some ovarian mucinous tumors. Further studies are needed to define the usefulness of this sex cord-stromal differentiation marker in the practice of surgical pathology. Coexpression of α and β subunits in sex cord-stromal elements suggests that dimeric inhibin is expressed in these cells.

Quantitative analysis of follicle-stimulating hormone receptor in ovarian epithelial tumors: A novel approach to explain the field effect of ovarian cancer development in secondary mullerian systems

The role of FSHR expression in ovarian cancer development is not clear. We examined quantitative expression of FSHR in different types of OET, presumed precursor lesions and peritoneal implants and further discussed FSH as a key growth‐promotion factor for the process of ovarian epithelial tumorigenesis. Thirty‐five primary OET specimens, including 5 serous cystadenomas, 4 papillary serous cystadenomas, 9 SBTs and 17 serous carcinomas, were examined for quantitative FSHR expression. Ten paired samples (3 benign cystadenomas, 5 SBTs and 2 carcinomas) were obtained from several morphologically different areas, including benign‐looking, borderline and cancerous areas in the same OETs, and from the remaining ovarian tissue and contralateral ovaries. Competitive RT‐PCR was performed to measure the quantitative expression of FSHR in each tissue sample. FSHR expression levels were compared among nonpaired samples and within paired samples. We found that OSE had the lowest FSHR expression, whereas antral follicles had the highest level. Within benign OETs, papillary serous cystadenomas have 4.9‐fold higher FSHR levels than nonpapillary serous cystadenomas. SBTs had the highest level of FSHR expression, which was 12.8‐fold, 2.7‐fold and 2.4‐fold higher than that of serous cystadenomas, papillary serous cystadenomas and grade 1 carcinomas, respectively. A similarly high level of FSHR mRNA was found in peritoneal implants, which were associated with SBTs. FSHR levels among serous carcinomas decreased with an increase in carcinoma grade. Grade 3 carcinomas had the lowest FSHR level, which was similar to that of serous cystadenomas, while grade 1 carcinomas had 6.5‐fold higher FSHR levels than those in serous cystadenomas. Our results suggest that not only serum FSH but also FSHR in ovarian epithelium may play important roles in ovarian OET development. Both the receptor and ligand may act in a synergistic way to promote tumor growth. The observation that high FSHR levels are present in peritoneal implants suggests that FSH may also play a similar role in the development of peritoneal serous tumors. From this perspective, circulating FSH may be considered a driving force in the field effect theory for the development of both ovarian neoplasms and their associated peritoneal implants. However, the exact role of FSH and/or FSHR in the development of epithelial tumors arising in both the ovary and peritoneum needs further investigation.

Non-invasive ovarian carcinoma.

Summary:The subset of ovarian epithelial tumors that is morphologically carcinoma, but has not yet shown any stromal invasion, is discussed. It is emphasized that metastasis is a function of invasive tumors, and that the spread of a noninvasive lesion cannot be explained by the usual concepts of metastasis. The multicentricity of peritoneal origin of ovarian epithelial tumors is a far more likely reason for morbidity and mortality, and is inescapable when the ovaries contain no lesion, when they contain a lesion that is noninvasive, or when the ovaries have been surgically removed.