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Four additional examples of theca-cell tumors of the ovary have been reported, three being removed surgically, one having been discovered incidental to autopsy. All the tumors were benign. One very large tumor occurred in a 17-year-old girl, producing no menstrual irregularities. One tumor associated with a fibroma of the opposite ovary showed infarction due to torsion of its pedicle. Convalescence and follow-up of the three cases have been uneventful. A complete summary of the literature has been presented.

The anatomic and histologic characteristics of theca cell tumors are described, together with their distinctive clinical and hormonal features. Descriptions are given of six cases illustrating variations from the more benign fibroma type to the highly cellular and malignant type. A correlation is made between the presence of hormonal changes and the presence of intracellular, doubly refractile fat containing cholesterol and cholesterol esters. It is suggested that some of the ovarian neoplasms previously diagnosed as fibromas or fibrosarcomas may on further investigation prove to be of theca cell origin.

Thirty ovarian tumors belonging to the granulosa and theca cell group of neoplasms are reported. They correspond in age incidence, clinical manifestations, and in gross and microscopic appearance with other reported cases. They differ in one major respect, that of malignancy. Only one tumor has proved to be malignant despite a follow-up record of four years or longer in 14 cases. By means of Laidlaw's silver stain granulosa-like cells were identified in all theca cell tumors and thecalike cells in a number of granulosa cell neoplasms. While our results are similar to those reported by Traut and Marchetti, we are not yet completely satisfied in regard to the recognition of these two types of cells by this method. Tumors of the theca cell group, however, had a later age incidence and presented sufficiently well-marked pathologic differences to warrant their continued recognition as a particular type of estrogen-secreting tumor. Two of the granulosa cell tumors were completely luteinized and one of these was of the unusual adenomatous type. The occurrence of 5 cases of carcinoma of the endometrium and 10 cases of uterine fibroids suggests a direct relationship between the ovarian neoplasm and the uterine tumors but does not warrant a definite conclusion in this regard.

Ovaries from normal adult dairy cows were obtained at all days of the estrous cycle. The largest Graafian follicle and corpus luteum were excised, prepared for light microscopy, examined morphologically, and quantitations of nuclear sizes were made using a planimetric technique.

IN A PREVIOUS COMMUNICATION, the experimental production of biologically active ovarian tumors in mice by roentgen irradiation was reported (I). Granulosa and theca cell neoplasms with varying degrees of luteinisation were found to occur in a number of mice during periods of 10 to 15 months following irradiation. Histogenetically, these tumors appeared to have been derived from undifferentiated ovarian parenchyma. Their estrogenic hormonal activity was expressed in proliferative changes within the endometrial and vaginal mucosa. Since these tumors were comparable in structure and function to the granulosa cell neoplasm, its excessively luteinised variety, the Lecene tumor, and the theca cell tumor of the human ovary, an analogous derivation from ovarian parenchyma was postulated. In the course of this study, animals were killed at frequent intervals during the many months prior to tumor development, permitting a correlation between the histopathology of the ovary, the uterine endometrium and the vaginal m...

The association of ovarian theca cell tumors with endometrial glandular hyperplasia and neoplasia is well established. A recognized association of these tumors with endometrial stromal neoplasia does not, however, appear to have emerged. The coexistence, on two occasions, of endometrial stromal neoplasia with theca cell tumors is herewith reported. Although no conclusion can be drawn from but two instances, the phenomenon is regarded as worthy of documentation in the event that further accumulation of similar evidence may permit of a definitive statement in the future.

A relationship of tumor cytology (anaplasia) and clinical course has not been established for the granulosa-theca cell tumor group. Granulosa-theca cell tumor cytology and clinical information from a single institution has been independently studied. A relationship of tumor cytology and clinical course does exist.

Theca-cell tumors are discussed relative to their histogenesis, clinical manifestations, pathology, and treatment. A small series of eleven cases from the Montreal General and Royal Victoria Hospitals is reported. These cases are representative of the problems involved in the investigation and management of theca-cell tumors generally. The ages of patients ranged from 21 to 69 years, with an average of 50 years. Seven of the patients were postmenopausal, only two of whom presented bleeding as a symptom. One of these showed hyperplasia, and one an adenocarcinoma of the endometrium. Three other patients demonstrated bleeding as a symptom, two at the menopausal age, and one earlier; all three of these had a hyperplasia of the endometrium. The one remaining patient exhibited amenorrhea as the principal symptom, and, after surgical removal of the thecoma, the menses returned to regularity. Three of the patients in the series had been previously radiated. Theca-cell tumors accounted for 1.8 per cent of all ovarian tumors during the ten years under review.

A case of malignant thecoma has been presented. Five previously reported cases have been reviewed and only three of these have criteria acceptable for malignant tumors. The incidence of malignancy in theca-cell tumors is approximately 3 per cent.

The clinical and pathologic data on 10 so-called theca cell tumors have been presented. These tumors occur most frequently following the menopause. They resemble granulosa cell tumors clinically, but pathologically possess certain distinguishing features which probably justify their consideration as an entity.

1. 1. One hundred and thirty-two cases of combined feminizing tumors of the ovary and carcinoma of the uterus were reviewed from the literature. 2. 2. Twenty-eight new cases of feminizing mesenchymoma of the ovary were reported. Eight cases of combined carcinoma and granulosa cell tumor were presented and evaluated. 3. 3. Evidence is offered that granulosa cell tumors, as well as thecomas, present a clinical and pathologic picture of hyperestrogenism. 4. 4. The relationship of estrogen to carcinogenesis in certain target or “receptor” tissues is discussed.

A case of a theca cell tumor removed at the sixteenth week of pregnancy which subsequently proceeded to term has been described. Only 7 cases of thecoma and 20 cases of granulosa cell tumor occurring with pregnancy have previously been reported. These cases have been reviewed.

Certain ovarian tumors exert hormonal effects, and of the feminizing type there are two, the granulosa cell tumors and the theca cell tumors. Theca cell tumors have only recently been recognized. Two such cases are reported. They produced hyperplasia of the myometrium and endometrium, and postclimacteric bleeding. In one case the bleeding was periodic, resembling the normal menstrual cycle. The tumors are composed of cells which have the histologic characteristics of theca interna cells. Apparently these tumors secreted theelin. This conclusion is supported by much experimental and deductive evidence from the literature that the theca cells secrete the estrogenic hormone. Unfortunately, the tumors were formalin fixed before implantation experiments could be made, and no blood or urine tests for hormone were made, but perhaps future investigators may be able to do this, for diagnosis as well as for investigation. In this connection we reiterate an admonition made in a previous communication, 37 namely, if in a woman past the menopause who is bleeding, nothing of an etiologic nature is found in the systemic or local examination, and curettage proves barren, one should perform a colpotomy and visualize the ovaries, in order that guilty ovarian tumors be not overlooked.

In connection with systematic studies of steroid and peptide hormone interactions during follicular growth, we have measured ovarian weight responses to graded doses of highly purified human chorionic gonadotropin (hCG), human interstitial cell stimulating hormone (hICSH)in hypophysectomized immature female rats (HIFR) treated with diethylstilbestrol in silastic capules (desc) implanted subcutaneously. Our results are consistent with earlier reports of enhancement of ovarian weight responses to hCG and FSH. Contrary to results of similar experiments reported by others, we have found that estrogen treatment of HIFR enhanced ovarian weight response to ICSH. In addition, we report for the first time that small doses of hCG and hICSH inhibit ovarian weight responses to estrogen in HIFR. Our observations on effects of small doses of hCG and hICSH and the long-known fact that ovarian interstitial cells are stimulated in HIFR given similar doses of these hormones lead us to hypothesize that ovarian interstitial cell stimulation is involved in the control of follicular maturation.

It has been shown in the past that labelling of human chorionic gonadotropin (HCG) with 1 – 2 atoms of radioactive iodine does not affect the biological, immunological and physicochemical behaviour of the hormone. (1). Furthermore, it has been established that the ovary, more than any other organ, has a capacity to concentrate HCG, and this is specific for the gonadotropic hormone. Labelled albumin or iodide were not concentrated by the ovary even when the animals were stimulated simultaneously with unlabelled HCG (1, 2).

After the implantation of ovarian tissue into the spleen of gonadectomized female Sprague-Dawley rats (splenic ovary), luteomata and later benign granulosa or granulosa-theca cell tumours develop. Treatment of these rats with 7,12 dimethylbenz(a)anthracene (DMBA), given intravenously, 2 mg/kg body weight weekly, total dosage 40 mg/kg, immediately and especially 25 weeks after implantation of ovarian tissue into the spleen, led to malignant, partially metastasizing granulosa, and in one case theca cell tumours, 16-46 weeks after beginning the carcinogen treatment. No malignant neoplastic growth was seen when diethylnitrosamine (DEN), 20 mg/kg once weekly for life, was injected subcutaneously immediately or 25 weeks after implanting ovarian tissue. Since the normal, non-implanted rat ovary was not affected by DMBA treatment the malignant transformation of splenic ovaries in the respective experimental groups may be related to the increased stimulation by pituitary gonadotrophins and formation of luteomata or beginning granulosa and theca cell proliferations. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9

Solid ovarian tumors, especially those producing endocrine changes, have been the subject of much discussion and investigation both by the pathologist and by the gynecologist during the past few years. Robert Meyer's 1 work, reported in 1931, was probably the spark that first aroused interest in America. In this publication he described the dysgerminoma ovarii, the granulosa cell tumor and the arrhenoblastoma. Later numerous reports of these tumor types appeared in the literature at frequent intervals, as did also reports of Brenner cell tumors; Bland and Goldstein 2 reviewed the literature and collected sixty cases of the latter type of tumor in 1935. Loeffler and Priesel 3 in 1932 recorded six cases of ovarian tumors, which they termed "fibroma theca cellulari xanthomatodes ovarii," and in 1934 the same authors 4 reported four additional cases of this type. In the same year Melnick and Kanter 5 reported two similar cases, the

Summary: 1 Eleven patients with theca cell tumours of the ovary have been presented. 2 The pertinent literature has been reviewed.

Tumors of the ovary that cause symptoms related to the endocrine system include arrhenoblastoma, masculinovoblastoma, often called the adrenal rest tumor, and luteinized tumors, variously called luteomas, luteinomas, and luteinized granulosa cell or theca cell tumors. The two that result in symptoms of masculinization are arrhenoblastoma and masculinovoblastoma. Arrhenoblastomas are somewhat commoner, 94 having been reported in 1947 by Iverson.1Masculinovoblastomas are rarer. Iverson limited the reported cases to 15 definitely established, after excluding six cases in which the patients did not have complete masculinization associated with a lipoid cell tumor of the ovary. The origin of lipoid cell tumors is disputed, some authors believing that they arise from adrenal rests and some believing that they arise from undifferentiated cells in the ovary, while still others believe that both modes of origin are possible. Histologically, these tumors resemble adrenal cortical tissue. According to Curtis,2this group of tumors

A malignant theca-cell tumor has been reported. The patient is living and well eight years after removal of only a portion of the neoplasm. Postoperative radiation therapy resulted in the disappearance of clinical evidence of the growth. Approximately 3 per cent of all theca-cell tumors are malignant. Criteria for the histologic diagnosis of malignancy in theca-cell tumors have been outlined and discussed.

Autoradiographic studies showed a specific uptake of 125I-LH in the corpus luteum of pregnancy and in the theca cell layer of the follicle in the rat and murine ovary. Both autoradiographic and quantitative studies indicated that the luteal receptor(s) for LH can be blocked by unlabeled LH, HCG and anti-LH serum, but not with FSH. The luteal LH-receptor was found in the particle preparation, presumably in the plasma membrane fraction. Intact luteal cells also showed specific binding of LH. After sonication of the membrane fraction the LH-receptor complex could be separated from the free hormone by gel filtration and DEAE-cellulose chromatography. Also the proximal tubule of the kidney markedly concentrated both 125I-LH and 125I-FSH and may actively participate in the metabolism and excretion of these hormones. The Kupffer cells of the liver were also active in the hormone uptake especially when bound to the specific antibody. In both tissues the labeled hormones were not, however, bound to any particulate...

I N A P R E v I 0 u s study of the stromal theta cell1 a peculiar accumulation of lipid was noted in the stromal spindle cells (the ovarian “fibroblasts”) forming a band just below the surface of the ovary. The distribution and location were different from those of the polygonal stromal theta cells, called luteinized stromal cells by Scully,” and there was no connection with the follicular apparatus. In the same study,l evidence was presented that a spindle form of the stromal theta cell was an early stage in the development of the polygonal form. Since the presence of lipid in the ovary appeared to be intimately connected with the synthesis of the steroid hormones, it was thought appropriate to compare the stromal spindle cells forming the lipid band with the stromal theta cells and the theta interna cells which are also derived from morphologically similar stromal spindle cells. Methods ap