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"HORMONE SECRETION BY SO-CALLED FUNCTIONALLY INACTIVE OVARIAN TUMOURS"

(A Review)

by BHOLANATH BANERJI, * M.B. (Cal.), M.R.C.O.G. (Eng.), F.I.C.S.

There is definite evidence that tions have been recorded (Farrar et ovarian tumours, other than those al., 1960). Although most authori­ commonly regarded as hormonally ties are not impressed by any associa­ active, do, in fact, produce hormones. tion of Brenner tumours with endo­ In this category of tumours are crine changes, abnormal uterine cystadenomas, Brenner tumours and bleeding has been reported in 25 per certain ovarian carcinomas. Most of cent of cases in several series (Bland these new growths are not associated et al., 1935, Jondahl et al., 1950; with apparent endocrine effect in the Novak et al., 1939; Teoh 1953). Teoh vast majority of cases and, therefore, (1953) described abnormal bleeding they are regarded by most authori- in five out of a series of ten patients. ties as non-functionating. Occasional One of Teoh's cases had endometrial occurrence of endocrine changes is hyperplasia, and the stroma of the dismissed as strange coincidence. tumours contained lipoid and re­ The present paper is an attempt to sembled a . Endometrial review this group of ovarian neo- hyperplasia has been observed in ap­ plasms from the available current proximately 10 per cent by Biggert medical literature (including a et al., (1955), Jondahl et al., (1952) published case of the author). and Teoh (1953). Biggert and his colleagues (1955) reported three Brenner Tumour cases of uterine bleeding in his series This tumour is usually unassociat­ of 15 Brenner tumours and two of ed with endocrine anomalies. The these uterine bleedings were in post­ ----" view expressed by Novak and Novak menopausal women with endometrial ( 1958) that these tumours do not hyperplasia. Abnormal uterine have any hormonal influence is the bleeding, almost always postmeno­ one generally accepted. Occasional­ pausal, has also been noted in as­ ly, however, endocrine manifesta- sociation with Brenner tumours by others (Andujar et al., 1947; Eton et *Professor of Obstetrics & Gynaeco­ al., 1958; Mackinlay et al., 1956; logy, Bankura Sammilani Medical Col­ Ming et al., 1962; Morris and Scully lege, Bankura, West Bengal, India. 1958; Woodruff 1962). Some authors Received for publication on 13-11-64. (Biggert et al., 1955) attributed the 8 184 JOURNAL OF OBSTETRICS AND GYNAECOLOGY OF INDIA endometrial hyperplasia to hormones tumours have functionally active probably liberated by the thecoma- stromal element producing oestro­ like stroma (rich in doubly refractile.. gens. fat) of the Brenner tumour, as the thecoma-like stroma was conspicuous Krukenberg Tumour by its absence in cases of Brenner tumour unassociated with uterine Recently, there is some -eviden~e on bleeding. Postmenopausal enlarge­ Krukenberg tumours producing ment or tenderness of the breasts has hormones. Truenen (1955) reported been described (Gryzel et al., 1941; two cases of Krukenberg in post­ Marwill et al., 1942; Tighe, 1961). menopausal women, and claimed that Three patients of Tighe's series this is associated with endometrial (Tighe 1961) presented ipteresting hyperplasia and abnormal uterine features, possibly related to oestrogen bleeding more often than other stimulation. One woman stated that supposedly inactive ovarian tumours. she also had sickness of such severity The author attributes the uterine that she thought she was pregnant changes to the secretion by the 'theca­ (although she had postmenopausal like stroma' which is occasionally as­ amenorrhoea for 2 years). At laparo­ sociated with the Krukenberg tomy this woman was found to have tumour. an ovarian dermoid cyst as well as a Brenner tumour. Pseudo- Adeno-carcinoma of the endome­ Masson (1938) has demonstrated trium associated with Brenner that the majority of pseudo-mucinous tumour has also been reported (Eton cystadenoma contain argentiform et al., 1958; Farrar et al., 1960; cells providing opportunities for car­ Jondahl et al., 1950; Mackinlay et al., cinoid development. This, by liberat­ 1956; Ming et al., 1962; Shaaban et ing 5-hydroxy-tryptamine, produces al., 1960; Teoh 1953; Tighe 1961; the typical features of dyspnoea, Woodruff 1962, Shay and Janovski asthma, flushing and arterial hyper­ 1963); and a casual relationship of tension (Valsecchi 1954; Spies and with abnormal Stone 1952). Banerji ( 1964) report­ oestrogen production has been re­ ed a case of a pseudo-broad ligament cognised. Shaaban et al., (1960) cyst of the with the histological found increased urinary oestrogen picture of pseudo-mucinous cystade­ level in his reported case of Brenner noma associated with hypertension, tumour in a postmenopausal woman erythrocytosis and Meigs syndrome; with adenocarcinoma of the corpus these clinical features disappeared uteri, metropathia haemorrhagica, after removal of the tumour. He adenomyosis uteri and of the suggested that liberation of erythro­ uterus. poetin-like substance by the tumour was responsible for the erythrocytosis Sufficient evidence is, therefore. and probably tiny areas of argenti­ available to suggest strongly tpat a form cells were responsible for the certain percentage of Brenner clinical features of carcinoid tumours. "HORMONE SECRETION BY FUNCTIONALLY INACTIVE OVARIAN TUMOURS" 185

Dysgerminoma microscopic study either in ovarian mesenchyme or testicular . , supposedly arising from sexually unditterentiated me­ Fibro-thecoma of Ovary with Stromal senchymal cells of the early gonad, is Neoplasia believed to be hormonally inactive. However, there is a high association Willis ( 1960) has suggested that of these tumours with sexual under­ many if not all of the ovary development and pseudo-herma­ are really "fibrous theca cell phroditism. It has been suggested tumours". Sternberg and Gaskill that this tumour is capable of in- ( 195{)) recognised the association of ...._ hibiting normal feminine develop­ fibroma, thecoma and stromal hyper­ ment (Gough 1949), while others plasia. Daley and his colleagues state that it is inactive. Scully (1953) (1950) proposed a concept that this thinks that the absence of hormonal kind of fibrous tumours of ovary effect is in keeping with the neutral produces oestrogens; the association character of the undifferentiated cells of cystic endometrial hyperplasia particularly in its histogenic forma­ 'and ovarian cystfibro-adenoma tion. in a 61 year old patient with post- ' menopausal bleeding was in support In the majority of cases, no cause­ of this concept. Sharman and Suther­ effect relationship exists between land (1947) reported abnormal ovarian and sexual ab­ uterine bleeding in association with normalities with which they are often the lesions. associated. In a few instances pre­ Morrison and Woodruff ( 1964) cocious sexual development (Rain studied 104 ovarian tumours compos­ 1949) or masculinizing manifestations ed largely of stroma with or without (Gough 1949; Saegar 1938) have re­ cystic and adenomatous elements; and gressed after removal of the tumour. evaluated the endometria particular­ Some degree of virilism frequently ly in postmenopausal patients for accompanies "dysgerminoma". Giushi evidence of hormone stimulation. et al., ( 1962) reported a clinical, his­ Although correlation of active endo­ tological and hormonal study of metria with theca-like changes in .the ovarian dysgerminoma with precoci­ ovarian tumour was not always ac­ ous iso-sexual puberty followed by curate, there was enough evidence to virilization. suggest a definite relationship. __. The reported absence of hormonal Hughesdon (1963) described under ~ secretion is not a constant observa­ "Misfit tumours" one type associated tion. Elevated gonadotrophin levels with anomalous functional effects. have been reported (Burge 1949; This type of tumour is not normally Potter 1946; Moreton 1947; Santesdn hormonally active, but may be so if 1947). These are probably produced a theca-lutein reaction develops in by chorion-epitheliomatous elements the stroma. This is commonest in freauently present in dysgerminoma primary carcinoma but can occur in (Melicome, 1959) but this association a benign tumour and also in a second­ has not always been confirmed by ary carcinoma. Hughesdon gave a 186 JOURNAL OF OBSTETRICS AND GYNAECOLOGY OF INDIA

preliminary account in 1958. Out of in benign dermoid cyst (Mitchel and 81 primary ovarian carcinoma, 16 Diamond 1949) and in masculinizing showed marked stromal thecal reac­ arrhenoblastoma (Hartz 1945). The tion; and of the 9 uteri available for suggested possibility of producing ery­ study 7 showed cystic endometrial thropoetin-like substance (Banerji hyperplasia and proliferative phase 1964) deserves further critical study. (Hughesdon 1963). Virilizing effects The manifestation of harmonic effect were not seen by him but others re­ by Krukenberg (Truenen 1955), an ported about it. otherwise hormonally inactive Beck and Latour (1962) found 13.9 tumour, demands further observa­ per cent incidence of endometrial tion. Adeno-fibromas or fibro­ hyperplasia in the fibromas (as com­ require further search of -' pared to 15 per cent in routine endo­ hormone potentiality. It is in the metrial examination) ; and stressed study of this new group of tumours the fact that the fibromas are pro­ that a closer team work of gynaeco­ bably not functional and the excess logists, histologists, endocrinologist oestrogen stimulation of the endo­ and biochemists is so essential. metrium was from a source other than the co-existing fibroma. References 1. Andujar, J. J ., Enlse, G. R. and Comment Swift, W. B.: Texas State J. Med. The ovary contains the widest 43: 70, 1947. range of cellular material in the body. 2. Banerji, B. N.: J. Ind. Med. Ass. It is the seat of most primitive cells, 42: 177, 1964. -. the germ cells. Therefore, it 3. Beck, R. P. and Latour, J. P. A.: possesses the potentiality to develop Obst. & Gynec. 19: 228, 1962. into any of the tissue elements of the 4. Biggert, J . H. and Macafee, C. H. body. The possible endocrine effect G .: J. Obst. & Gynec. Brit. Emp. of Brenner tumours has aroused 62: 829, 1955. interest in recent years. In view of 5. Bland, P. B. and Goldstein, L.: Sur. this, it is probably important to in­ Gynec. & Obst. 61: 250, 1935. vestigate all patients with solid 6. Burge, E. S.: Am. J . Obst. & Gynec. ovarian tumours with abnorma·l 57: 1014, 1949. vaginal bleeding both by histological 7. Daley, D. , Harrison, C. V., Mjllar, and hormonal study, as it is thus that W. G.: J. Obst. & Gynec. Brit Emp. any hormonal (oestrogenic) effects 57: 408, 1950. may be proved. 8. Eton, B. and Parker, R. A.: J. Obst. In addition to the capacity to pro­ & Gynec. Brit. Emp. 65: 95, 1958. duce gonadal hormones such as oestrogen, androgen and gonadotro­ 9. Farrar, H. K. Jr., Elesh, R. and phins from diversely differentiated Libretti, J.: Obst. & Gynec. Survey. tissues, it 'is interesting that QVarian 15: 1, 1960. tumours may develop carcinoid fea­ 10. Giushi, G., Borg, A., Bigozzi., U., tures as in pseudo-mucinous cvsta­ Negri, L. and Toccafondi, R.: Obst. denomas (Banerji 1964; Mason 1938) , & Gynec. 20: 755, 1962. "HORMONE SECRETION BY FUNCTIONALLY INACTIVE OVARIAN TUMOURS" 187

11. Gough, A.: J. Obst. & Gynec. Brit. 27. Novak, E. and Jones, H. W.: Am. y Emp. 45: 1349, 1949. J. Obst. & Gynec. 38: 872, 1939. 12. Gryzel, D. M. and Friedman, H. H.: 28. Novak, E. and Novak, E. R.: Am\ J. Surg. 53: 509, 1941. Gynec. & Obst. Path. ed. 4, Phila­ 13. Hain, A. M.: J. Clin. Endocrinol. 9: delphia, 1958, p. 403, Saunders & 1349, 1949. Co. 14. Hartz, P. H.: Am. J. Path. 21: 1167, 29. Potter, E. B.: Am. J. Path. 22: 551, 1945. 1946. 15. Hughesdon, P. E.: J. Obst. & 30. Seeger, G. E.: Arch. Surg. 37: 697, Gynec. Brit. Emp. 65: 702, 1958. 1938. 16. Hughesdon, P. E.: Structure and 31. Santesson, L.: Acta. Radio!. 28: 644, Origin of Ovarian Tumour. Modern 1947. Trends in Gynaecology, edited by 32. Scully, R. E.: New England J. Med. R. J. Kellar, London, 1963, Butter­ 245: 905, 1951. worth & Co., p. 33. 33. Shaaban, A. H., Abdine, F. H. and 17. Jondahl, W. H., Dockerty, M. B. Youseff, A. F.: J. Obst. & Gynec. and Randall, L. M.: Am. J. Obst. Brit. Emp. 67: 138, 1960. & Gynec. 60: 160, 1950. 34. Sharman, A. and Sutherland, A. 18. Mackinlay, C. J.: J. Obst. & Gynec. M.: J. Obst. & Gynec. Brit. Emp. Brit. Emp. 63: 58, 1956. 54: 382, 1947. 19. Marwil, T. B. and Beaver, D. G.: 3.. Shay, M. D. and Janovski, N. A.: Am. J. Obst. & Gynec. 43: 99, 1942. Obst. & Gynec. 22: 246, 1963. 20. Mason, P. (1938): as quoted .bY 36. Spies, T. D. and Stone, R.I.: J. Am. Morris, J. M. and Scully, R. C.­ Med. Ass. 150: 1599, 1952. Endocrine of the Ovary, 3'7. Sternberg, W. 'H. and Geskile, C. St. Louis, 1958, C. V. Mosby Com­ J.: Am. J. Obst. & Gynec. 59: 575, pany, p. 73. 1950. 21. Melicome, M. M. and Uson, A. C.: 38. Teoh, T. B.: J. Path. & Bact. 66: Cancer. 12: 552, 1959. 441, 1953. 22. Mitchel, N. and Diamond, B.: 39. Tighe, J. R.: J. Obst. & Gynec. Cancer. 2: 799, 1949. Brit. Comm. 68: 292, 1961. 23. Ming, S. and Goldman, H.: Am. J. 40. Truenen, A.: Act Endocrinol, 20: Obst. & Gynec. 83: 666, 1962. 50, 1955. 24. Moreton, R. D. and Desjardens, A. 41. Valsecch.i, A. (1958): Abstract J. V.: Am. J. Roentgenol. 57: 84, 1947. Am. Med. Ass. 170: 744, 1954. 25. Morris, J. M. and Scully, R. E. 42. Willis, R. A.: Patholgoy of Endocrime Pathology of the Ovary, Tumours, London, 1960, Butter­ St. Louis, 1958, The C. V. Mosby worth & Co. Company, p. 132. 43. Woodruff, J.D. and Acosta, A. A.: 26. Morrison, C. W. and Woodruff, J. Am. J. Obst. & Gynec. 83: 657, D.: Obst. & Gynec. 23: 344, 1964. 1962.

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