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Background: Hormonal factors may play a more prominent role in cervical adenocarcinoma than squamous cell carcinoma. The authors evaluated whether obesity, which can influence hormone levels, was associated with adenocarcinoma and squamous cell carcinoma., Methods: This case-control study included 124 patients with adenocarcinoma, 139 matched patients with squamous cell carcinoma, and 307 matched community control participants. All participants completed interviews and provided cervicovaginal samples for human papillomavirus (HPV) testing. Polytomous logistic regression-generated odds ratios (ORs) and 95% confidence intervals (95% CIs) for self-reported height and weight, body mass index (BMI; kg/m(2)), and measured waist-to-hip ratio (WHR) for both histologic types were adjusted and stratified for HPV and other confounders., Results: Height, weight, BMI, and WHR were positively associated with adenocarcinoma. BMI >or= 30 kg/m(2) (vs. BMI < 25 kg/m(2); OR, 2.1 and 95% CI, 1.1-3.8) and WHR in the highest tertile (vs. the lowest tertile; OR, 1.8 and 95% CI, 0.97-3.3) were associated with adenocarcinoma. Neither height nor weight was found to be associated with squamous cell carcinoma, and associations for BMI >or= 30 kg/m(2) (OR, 1.6) and WHR in the highest tertile (OR, 1.6) were weaker and were not statistically significant. Analyses using only HPV positive controls showed similar associations. The data were adjusted for and stratified by screening, but higher BMI and WHR were associated with higher disease stage at diagnosis, even among recently and frequently screened patients with adenocarcinoma. Thus, residual confounding by screening could not be excluded as an explanation for the associations., Conclusions: Obesity and body fat distribution were associated more strongly with adenocarcinoma than with squamous cell carcinoma. Although questions about screening remain, obesity may have a particular influence on the risk of glandular cervical carcinoma.

Background: Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms., Methods: To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing., Results: Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there., Conclusions: International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions.

Background: Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by disseminated intraperitoneal mucinous tumors, often with mucinous ascites. The term PMP has been applied historically as a pathologic diagnostic term to both benign and malignant mucinous neoplasms that produce abundant extracellular mucin, resulting in a variable and poorly predictable prognosis. A recent study reported a pathologic classification that separated patients into prognostically distinct groups, but the follow-up was relatively short., Methods: Long-term follow-up data were analyzed for a previously reported series of 109 patients with PMP to examine the prognostic utility of a pathologic classification system that divided patients into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). Patients whose tumors were classified 25 DPAM (n = 65 patients) had disease that was characterized by histologically bland to low-grade adenomatous mucinous epithelium associated with abundant extracellular mucin and fibrosis, often with an identifiable appendiceal mucinous adenoma that was the source of the peritoneal lesions. Patients whose tumors were classified 25 PMCA (n = 30 patients) had disease that was characterized by peritoneal lesions that displayed the cytologic and architectural features of mucinous carcinoma associated with extracellular mucin, often with an identifiable invasive mucinous adenocarcinoma of the gastrointestinal tract. Patients whose tumors were classified 25 PMCA-I (n = 11 patients) had peritoneal lesions that combined the features of DPAM and PMCA derived from well differentiated mucinous adenocarcinomas associated with adenomas. Patients whose tumors were classified 25 PMCA-D (n = 3 patients) had markedly atypical appendiceal adenomas associated with peritoneal lesions similar to PMCA., Results: Patients with DPAM had 5-year and 10-year survival rates of 75% and 68%, respectively (mean follow-up, 96 months; median follow-up, 104 months). Patients with PMCA and PMCA-I/D had a significantly worse prognosis, with 5-year and 10-year survival rates, respectively, of 50% and 21% for PMCA-I/D (mean follow-up, 58 months; median follow-up, 51 months) and 14% and 3% for PMCA (mean follow-up, 27 months; median follow-up, 16 months; P = 0.0001)., Conclusions: The term PMP should be used only as a clinical descriptor for patients who have the syndrome of mucinous ascites accompanied by a characteristic distribution of peritoneal mucinous tumors with the pathologic features of DPAM. DPAM should be used as a pathologic diagnostic term for patients with the bland peritoneal mucinous tumors associated with ruptured appendiceal mucinous adenomas and PMP. These patients should not be diagnosed with carcinoma, because they have disease that is distinct pathologically and prognostically from PMCA., (Copyright 2001 American Cancer Society.)

Background: Fatty acid synthase (FAS), a biosynthetic enzyme, normally functions in the liver to convert dietary carbohydrate to fat, but it is minimally expressed in most other normal adult tissues. FAS is expressed at markedly elevated levels in subsets of human breast, ovarian, and prostate carcinomas that are associated with poor prognoses. During the menstrual cycle, the expression of FAS in the human endometrium is closely linked to the expression of the proliferation antigen Ki-67, estrogen receptor (ER), and progesterone receptor (PR)., Methods: This study reports the expression patterns of these antigens in 35 endometrial carcinomas as determined by immunohistochemical analysis., Results: All cases demonstrated a close direct correlation between FAS and Ki-67 expression. Average FAS expression levels were correlated with tumor grade. Twenty-five carcinomas that were positive for ER and PR showed close correlation in expression of FAS, Ki-67, and hormone receptors. Individual tumors displayed varying degrees of heterogeneity of expression. A few well-differentiated carcinomas showed very low expression of all four antigens, similar to the antigenic profile of secretory endometrium. Nine high grade carcinomas that were negative for ER and PR also showed close correlation in expression of FAS and Ki-67 with uniformly high expression., Conclusions: These data suggest the following hypothesis: In hormone-dependent endometrial cells, FAS expression is part of the estrogen-driven cellular response that leads to proliferation; however, its linkage to proliferation is such that FAS expression is maintained in proliferating cells in endometrial carcinomas that acquire hormone independence. The use of these four antibodies as a panel may increase the diagnostic utility of ER and PR immunohistochemistry for tumor classification and prediction of the responsiveness of tumors to hormonal therapy.

Background: Numerous pathologic factors have been identified as important in predicting outcome for women with endometrial adenocarcinoma. However, most patients have a mixture of good and bad factors. For these women, the prognosis is uncertain, and it is often unclear whether postoperative therapy is indicated., Methods: Using univariate and multivariate analysis, we investigated the pathologic factors commonly reported to be of prognostic significance, using data from 819 patients with clinical Stages I and II endometrial adenocarcinoma from a Gynecologic Oncology Group study. Since the clinical stage frequently underestimated the surgical stage, models that designate the relative risk associated with each of the variables were created for both clinical and surgical Stage I and 11 patients., Results: We confirmed the importance of age, depth of myometrial invasion, and to a lesser degree, histologic grade, and cell type, as independent prognostic variables., Conclusions: The relative risk of death can be determined using a simple multiplicative calculation, and the absolute risk can be estimated by inspection of the accompanying figures. These data can be used to provide patients with prognostic information and to help determine the need for postoperative adjuvant therapy.

Background: The histologic grade of endometrial adenocarcinoma is related to the aggressiveness of the tumor and probability of death from disease. However, the ideal system for assignment of histologic grade remains controversial. In 1988, the International Federation of Gynecology and Obstetrics (FIGO) revised its recommendations for grading typical endometrial adenocarcinoma, such that grade is determined primarily by the architecture of the tumor and secondarily modified in the presence of "notable nuclear atypia"; this phrase, however, has never been defined, and therefore the prognostic validity of this system is unknown., Methods: Seven hundred and fifteen women with clinical Stage I and occult Stage II endometrial adenocarcinomas (excluding serous or clear cell type) entered on a Gynecologic Oncology Group protocol, and those treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and selective pelvic and para-aortic lymph node sampling formed the study population. All cases were centrally reviewed and assigned an architectural grade and a nuclear grade using specific criteria. The FIGO grade was then determined. The various grading methods were examined based on ability to stratify patients into groups with differing rates of disease progression and relative survival at five years., Results: The architectural grade, nuclear grade, and FIGO grade of tumors each were used to separate patients into groups with statistically significant different rates of progression of disease and relative survival. The FIGO modification of architectural grade resulted in the reassignment of 44 patients into a higher grade. The outcome for these 44 was worse than for the remaining patients in the initial grade but was similar to the group into which they were moved., Conclusions: If clearly specified criteria for architectural and nuclear grading are used and "notable nuclear atypia" is defined as grade 3 nuclei, the 1988 FIGO grading system has prognostic utility. The authors recommend this system as the standard method for the grading of typical endometrial adenocarcinoma.

Background: Diagnostic and consistent chromosomal abnormalities have been reported in several soft tissue sarcomas, but few studies have reported the frequency of chromosomal abnormalities in uterine sarcomas., Methods: Cytogenetic studies were performed on specimens of uterine sarcoma from 14 patients. The specimens included five of leiomyosarcoma (LMS), four of endometrial stroma sarcoma (ESS), and five of malignant mixed mesodermal tumor (MMMT)., Results: Chromosomal abnormalities were detected in 10 of 14 (71%) patients. Chromosome 1 was involved in 7 of 13 (54%) of the patients, chromosome 11 in 6 of 13 (46%), and chromosome 7 in 6 of 13 (46%). A site-specific chromosomal abnormality, del(11)(q22) was found in two patients with LMS and three patients with MMMT, and 7q31 also was involved frequently. Marked genomic instability characterized the MMMT studied., Conclusions: These findings suggest that abnormalities of chromosomes 1, 7, and 11 may play a role in tumor initiation or progression in uterine sarcomas. Genomic alterations in the region 11q22 may be specific for malignant smooth muscle tumors of the uterus.

The prognostic significance of vascular invasion as compared with other pathologic features was evaluated in 102 cases of endometrioid adenocarcinoma confined to the uterus (Stage I) treated by hysterectomy. By univariate analysis, survival most closely correlated with patient age, architectural grade, depth of myometrial invasion, vascular invasion, and the presence of perivascular lymphocytic infiltrates. Among these, vascular invasion and the presence of perivascular lymphocytic infiltrates were the best indicators of prognosis. In contrast to perivascular lymphocytic infiltrates, the presence of a lymphocytic infiltrate at the tumor-myometrial junction was not related to outcome. The presence of vascular invasion was found to be associated closely with perivascular lymphocytic infiltrates. These two features may be related biologically and were designated "vascular invasion-associated changes." By multivariate analysis with the Cox proportional hazards model, the depth of myometrial invasion and the presence of vascular invasion-associated changes were found to provide a highly reliable model for predicting outcome. The highly predictive value of vascular invasion as a prognostic factor in Stage I endometrial carcinoma suggests that it is the mechanism by which occult metastasis develops in patients whose disease progresses after hysterectomy. It is likely that other variables correlating with recurrence, such as the presence of deep myometrial invasion and high tumor grade, may act by increasing the probability of vascular invasion and subsequent metastasis.

A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the beta-globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a "condylomatous" appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus-16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV-positive women were younger than HPV-negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles.

The clinical and pathologic features of 15 examples of a hitherto undescribed germ cell tumor of the ovary are delineated. This tumor resembles the embryonal carcinoma of the adult testis and may be distinguished from the endodermal sinus tumor on the basis of its histologic and immunohistochemical characteristics. An indirect immunoperoxidase method for the localization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was done on formalin-fixed paraffin-embedded tissue from 10 neoplasms; HCG was present in all 10 neoplasms, and AFP was found in seven. HCG was indentified only in cells resembling syncytiotrophoblast, whereas AFP was present only in mononuclear embryonal cells, indicating that the two protein antigens were localized in different cell types. Abnormal hormonal manifestations, consisting of precocious puberty, irregular bleeding, amenorrhea, or hirsutism, were present in nine (60%) of the patients. The actuarial survival for the entire group was 39%; for those with stage I tumors, 50%. We are proposing the term "embryonal carcinoma" for this neoplasm in order to distinuish it from the more common endodermal sinus tumor of the ovary and to emphasize the histologic similarity to embryonal carcinoma of the adult testis.

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotropho-blastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.

Eleven granulosa-theca tumors (seven pure granulosa and four with associated theca elements) were examined for the presence of estradiol, progesterone and testosterone using an indirect immunoperoxidase technique on formalin-fixed paraffin embedded tissue. In ten patients the endometrium was studied histologically and significant endometrial hyperplasia consistent with estrogen production by the tumors was found. Estradiol was localized in granulosa cells (nonluteinized) in all 11 cases and in luteinized theca cells in three of the four cases in which theca elements are present. In contrast, progesterone was always detected in luteinized theca cells and in granulosa cells in over one half the cases. Testosterone was also present in granulosa cells in just over half the cases but tended to be only weakly positive. The nonluteinized stromal cells were negative for all steroids. These results are compatible with the concept that in granulosa-theca tumors, both granulosa and theca cells can produce a wide range of steroid hormones but that the predominant steroid present in granulosa cells is estradiol, while progesterone is the predominant steroid in luteinized theca cells.

Endometrial curettings from 204 patients containing severe forms of atypical hyperplasia, carcinoma in situ, and well-differentiated carcinoma were compared with subsequent hysterectomy specimens to evaluate and identify the most useful histologic criteria for predicting the presence of invasive carcinoma. Endometrial stromal invasion, increased degrees of nuclear atypism, mitotic activity, cellular stratification, and epithelial necrosis in curettings were associated with a greater likelihood of carcinoma in the uterus. Of these, stromal invasion was the most significant feature. When stromal invasion was absent, carcinoma was present in the uterus in only 17%, and the carcinomas were well differentiated and confined to the endometrium or only superficially invasive. When stromal invasion was present in curettings, residual carcinoma was present in the uterus in half, and of these, one third were moderately or poorly undifferentiated and a quarter invaded deeply into the myometrium. The criteria for invasion are 1) an irregular infiltration of glands associated with an altered fibroblastic stroma or desmoplastic response; 2) a confluent glandular pattern in which individual glands are uninterrupted by stroma and merge to form a cribriform pattern of stromal replacement; 3) an extensive papillary pattern; and 4) replacement of stroma by masses of squamous epithelium. To qualify as invasion, 2, 3, and 4 must occupy at least one half (2.1 mm) of low power field 4.2 mm in diameter. Because of the important role of stromal invasion in predicting prognosis, future classifications of endometrial neoplasia should utilize this feature in distinguishing atypical hyperplasia from well differentiated adenocarcinoma.

Twenty-one cases of clear cell carcinoma of the endometrium are analysed in an effort to characterize the histologic features and biologic behavior of this type of neoplasm in the uterus and thereby to shed further light on the histogenesis of clear cell carcinoma in the female genital tract. The clinical profile of the patients closely paralleled that of women with the usual types of carcinoma of the endometrium. Fifteen (71%) were stage I, five were stage II, and one was stage IV at diagnosis. An assessment of the clinical stage and depth of myometrial invasion are useful in predicting the prognosis. The actuarial survival for all stages is 55.3% at 5 years, which is somewhat lower than that of adenocarcinoma of the endometrium in general. Operation alone or combined with radiation therapy is the treatment of choice for stage 1 clear cell carcinoma of the endometrium. The most cogent evidence for a müllerian rather than a mesonephric origin for clear cell carcinoma in the female genital tract is its presence in the endometrium, a Müllerian derivative. More specific points that support this concept are the findings of clear cell carcinoma confined to an otherwise benign endometrial polyp in two instances, the initimate admixture of clear cell and typical adenocarcinoma in three other instances, and the absence of mesonephric remnants in any of the 21 cases.

Twelve cases of a hitherto unrecognized pseudotumorous trophoblastic invasion of the myometrium are analyzed. Human chorionic gonadotropin (HCG) was identified by an immunoenzyme technique in the cytoplasm of the invasive cells. The lesion may be localized and only superficially invasive or deeply invasive and have a gross appearance suggesting a neoplasm in the excised uterus. In either case, this process has been confused with various types of malignant tumors, most often choriocarcinoma, from which it may be distinguished by an absence of the characteristic dimorphic population of cytotrophoblast and cyncytiotrophoblast. Most of the patients, who ranged in age from 19 to 41 years, presented with amenorrhea uterine enlargement and were thought to be pregnant, although only four of them had positive pregnancy tests. The most serious complication was uterine perforation, which occurred spontaneously in one patient and during curettage in five others. One patient died as a result, but the other 11 are alive without evidence of disase 6 months to 12 years after the diagnosis. Of the 11 surviving patients, four received no treatment other than curettage. Because this trophoblastic lesion is likely benign and simulates a malignant tumor on pathologic examination, the term "trophoblastic pseudotumor" has been chosen to designate it.

The clinical and pathologic features of 71 endodermal sinus tumors of the ovary were studied in an effort to delineate the histogenesis and biologic behavior of this neoplasm and to evaluate the efficacy of different forms of treatment. Alpha-fetoprotein (AFP) was identified in hyaline droplets, cell cytoplasm, and intercellular spaces of all 15 tumors examined by an immunoperoxidase technique; this supports the view that the neoplasm simulates yolk sac endoderm. There were only nine survivors among 65 patients on whom follow-up information was available; the actuarial survival was 13% at 3 years. Of the neoplasms that recurred, 93% did so within 1 year, and of those patients who died, 93% did so within 2 years. The size and stage of the tumor had prognostic significance, but the patient's age, the mitotic activity, and histologic pattern did not. Although 71% of the patients had Stage I tumors at the time of diagnosis, subclinical metastasis was present in 84% of Stage I patients. Triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide (VAC)) employed after unilateral salpingo-oophorectomy in four patients with Stage I tumors resultivors among 12 Stage I patients treated with combined surgery and radiation. The finding of AFP in all tumors in which this was evaluated suggests that serum radioimmunoassay might be useful to monitor response to therapy.

Endometrial curettings from 170 patients with all grades of endometrial hyperplasia, who did not undergo a hysterectomy for at least 1 year were evaluated in order to correlate the histopathologic features with behavior. Follow-up ranged from 1 to 26.7 years (mean, 13.4 years). Cytologic and architectural alterations were analyzed separately in order to assess their respective roles in predicting the likelihood of progression to carcinoma. Classification of proliferative lesions based solely on the presence of cytologic atypia revealed that atypia was a discriminant factor. Proliferations lacking cytologic atypia were designated hyperplasia and those displaying atypia were designated atypical hyperplasia. Only 2 (1.6%) of 122 patients with hyperplasia progressed to carcinoma compared with 11 (23%) of women with atypical hyperplasia (P = 0.001). Subclassification of the two forms of hyperplasia (those with cytologic atypia and those without) was performed using the degree of architectural abnormalities. Hyperplasia and atypical hyperplasia displaying marked glandular complexity and crowding producing a back-to-back appearance were designated complex hyperplasia (CH) and complex atypical hyperplasia (CAH), respectively. Hyperplasia and atypical hyperplasia with lesser degrees of glandular complexity and crowding were designated simple hyperplasia (SH) and simple atypical hyperplasia (SAH), respectively. Progression to carcinoma occurred in 1 (1%) of 93 patients with SH, in 1 (3%) of 29 patients with CH, in 1 (8%) of the patients with SAH, and in 10 (29%) of the patients with CAH. The differences between the four subgroups suggest a trend but are not statistically significant. The findings in this study provide a rationale for classifying noninvasive endometrial proliferations primarily on the basis of cytologic atypia since this is the most useful criterion in predicting the likelihood of progression to carcinoma. In addition, the presence of concommitant architectural alterations appears to identify a particularly high-risk subgroup.

Paraffin-embedded tissues from 15 women with breast or endometrial carcinomas were analyzed in a study designed to explore the possible value and validity of an immunoperoxidase method for the detection of estrogen receptor in formalin-fixed paraffin-embedded tissue. Results were compared with biochemical assays for estrogen receptor performed on cytosols of fresh tissue from the same patients. There was complete correlation in nine of 15 (60%) of the tumors analyzed. Four cases (26.7%) were judged positive for estrogen binding sites by immunoperoxidase but were negative for estrogen receptor by biochemical assays; in two cases the converse was observed. The immunohistologic technique is relatively rapid and utilizes fixed paraffin sections of the same tissue that is used for standard histologic diagnosis. The provision of a permanent record that can be kept for future reference provides an advantage over immunofluorescence methods that have been advanced for the detection of estrogen receptors. The excellent morphology achieved permits an assessment of the staining of individual cells in relation to the usual histologic criteria employed in the diagnosis of breast and endometrial cancer. This stands in contrast to biochemical cytosol-based assays that take no account of variations in receptor expression by the tumor cells or variations in the proportion of the assayed material that is in fact neoplastic as distinct from supporting stroma and connective tissue.

Twenty-six cases of atypical smooth muscle tumors of the uterus, including leiomyoblastoma, epithelioid leiomyoma, clear-cell leiomyoma, and plexiform tumorlet, are presented. The characteristic microscopic feature serving as the basis for inclusion in this study is the rounded to polygonal shape of the majority of cells instead of the elongated blunt-ended shape of smooth muscle cells seen in the typical leiomyoma. Mixtures of epithelioid, clear-cell, and plexiform patterns occurred with sufficient frequency to indicate that such patterns are variants of a single entity. A transition to typical smooth muscle cells was found in most instances, confirming the smooth muscle origin of these tumors. Features related to a favorable prognosis include the presence of clear cells, an expansile tumor margin, extensive hyalinization, and absence of extensive necrosis as seen microscopically. Until additional evidence has been accumulated it is proposed that neoplasms having five or more mitotic figures per ten high-power fields (HPF) be tentatively termed epithelioid leiomyosarcoma or leiomyosarcoma with epithelioid features and those with less than five mitotic figures per ten HPF, epithelioid leiomyoma.

Nine ovarian Sertoli-Leydig tumors, showing varying degrees of differentiation, one pure ovarian Sertoli cell tumor, and one poorly differentiated stromal tumor of the testis, were examined for the presence of testosterone, estradiol and progesterone with an indirect immunoperoxidase method on formalin fixed paraffin embedded tissue. Clinically all nine patients with Sertoli-Leydig tumors had evidence of increased androgen production, manifested by either hirsutism or virilization; elevated serum testosterone was found in all four patients in whom it was measured. The patients with the pure ovarian Sertoli cell and testicular tumors were asymptomatic except for the presence of a mass. Testosterone was identified in Leydig cells in nine instances, in Sertoli cells in six, and in poorly differentiated spindle cells resembling the mesenchyme of the embryonic gonad in two. Cells with vacuolated cytoplasm, both Sertoli and Leydig cells, though positive for lipid were consistently negative for testosterone. Estradiol was present in Leydig cells in nine instances, in Sertoli cells in five, and in primitive gonadal stomal cells in two. The pattern of distribution was similar to that of testosterone but the intensity of the reaction for estradiol was generally less than that for testosterone. Progesterone was identified in Sertoli cells in one instance and was weakly positive in Leydig cells in three instances. The presence of testosterone and estradiol in both Sertoli and Leydig cells as well as in primitive spindle cells resembling those found in the embryonic gonad suggests that the latter cell is the precursor for both Sertoli and Leydig cells.