- Email: [email protected]
Patient presentations: Panel discussion
Patient presentations: Panel discussion*
hours (normal, up to 4). A 4 hour glucose tolerance test revealed a diabetic curve. The uterus was difficult to outline and no adnexal masses were palpated. Curettage was performed. Microscopically the specimen revealed diffuse adenocarcinoma of the endometrium (Fig. 1). Total abdominal hysterectomy and bilateral salpingooophorectomy were performed. The ovaries were sclerocystic, typical of Stein-Leventhal, being 4% cm. with a smooth, pale gray-blue discoloration with nodularity on the surfaces. The pathologic diagnosis was adenocarcinoma of the endometrium with bilateral ovaries showing cortical fibrosis and follicular cysts compatible with Stein-Leventhal syndrome. Case 2 (S-68-3732). This 34-year-old nulligravida patient, weight 260 pounds, complained of periods of amenorrhea and irregular menstrual periods since age 18, and hair growth necessitating shaving her upper lip and lower chin. Examination revealed a constitutional-type obesity with an 8 week size uterus and enlarged right ovary. She was not seen until 2 years later, when in October of 1968 she had 3 weeks of bleeding after intermittent spotting since July of 1968. The uterus was the size of a 12 week gestation organ. A curettage was performed. The specimen revealed atypical adenomatous and papillary hyperplasia of the endometrium. The slides were sent to New Orleans for review. The pathologist there diagnosed this adenocarcinoma whereas our pathologist had called it atypical endometrial hyperplasia. Abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The ovaries were typical of Stein-Leventhal syndrome with multiple subcapsular follicular cysts, absence of corpora lutea, and a very thick and fibrotic capsule. The uterus contained adenocarcinoma of the endometrium with superficial invasion of the myometrium (Fig. 2).
Adenocarcinoma of the endometrium associated with the Stein-Leventhal syndrome KENNETH Medical
J. Center,
PARHAM, Greenwo,od,
I N 1 9 5 7 Jackson and upon a group of 44 cases syndrome in which 17 women the endometrium.1 Dockerty,
M.D. South
Carolina
Dockerty reported of Stein-Leventhal had carcinoma of Lovelady, and
Fousts reported that approximately 20 per cent of women under 40 who developed carcinoma of the uterine fundus showed clinical evidence of the Stein-Leventhal syndrome. Novak and Rutledges called attention to certain atypical benign lesions of the endometrium, sometimes encountered in young women, which may simulate adenocarcinoma. In the light of their work one might naturally question whether the case reported herein is cancer of the endometrium. Case 1 (S-68-207). This 21-year-old white female complained of occasional periods of amenorrhea of 2 or 3 months’ duration, menstrual flow that lasted from 4 to 30 days, sterility for 4 years, obesity (196 pounds at age 13 and 245 pounds at age 17), headaches, dry skin, preference for cold weather, and marked decrease in libido. At age 17, after medical therapy had failed to control menstrual hemorrhage, a curettage was performed. The findings were glandular hyperplasia and dense stroma. The patient weighed 300 pounds and the fat distribution was of a constitutional type. She had a normal female distribution of fine hair and the breasts were normal. The blood pressure was 140/80. Skull x-rays were normal, Ts uptake 29 per cent (euthyroid result), intravenous pyelogram normal, 17-ketosteroids were 8.1 mg. per 24 hours (normal, 4.4 to 15.8), 17-ketogenic steroids 13.9 mg. per 24 hours (normal, 5 to 18)) l7-hydroxysteroids 5 mg. per 24 hours (normal, 0.8 to 9.7), and pregnanetriol 1.6 mg. per 24
These two cases fit into the category of SteinLeventhal syndrome. Stein4 Stern,5 and others% 6 have recommended that dilatation and curettage be performed on all patients with menometrorrhagia associated with this syndrome to rule out endometrial carcinoma. It has been said that the pathologist bears a heavy responsibility when he announces his decision. The clinician must assume his responsibility just as seriously, for the life of the patient, in the final analysis, is actually in his hands.7 Dockerty and Lovelady* stated that 7 of 36 patients with endometrial cancer exhibited features of the Stein-Leventhal syndrome and noted that carcinoma of the uterine corpus complicat-
*Presented by invitation at the Thirtyfirst Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Feb. 2-5, 1969.
113
114
Panel
discussion
Fig.
1. Adenocarcinoma
Fig.
2. Myometrial
of the
invasion
by
endometriurn
adenocarcinoma
ing this syndrome had not received sufficient emphasis. Gusburg commented upon the evidence of the association of estrogen producing ovarian tumors and corpus carcinoma. He closely studied 5 patients who had developed adenocarcinoma of the uterine corpus following prolonged estrogen administration. He also described
of the
endometrium.
a type of adenomatous endometrial hyperplasia as being a cancer precursor, a belief that has persisted in the minds of many of us. Hoffman and ScheffeylO called atypical endometrial hyperplasia carcinoid hyperplasia. Certain criteria have been elaborated in an attempt to distinguish microscopically this adenomatous hyperplasia
Volume 105 Number1
from adenocarcinoma of the endometrium. Novak and Rutledge3 stated that, in the nonmalignant hyperplasia, stratification of the epithelium is not ‘uncommon, but that not more than two layers of cells are seen in this stratification. Cellular polarity should be maintained in adenomatous hyperpIasia with the nuclei remaining uniform in size and shape. Certainly this is not the case in clear cut adenocarcinoma of the endometrium. Hertig and Somme& indicate cystic hyperplasia as a frequent, important, but remote forerunner of carcinoma, but feel that adenomatous hyperplasia appears to be a more immediate precursor of endometrial carcinoma. Adenomatous hyperplasia is not irreversible. Kistnerrz has shown that reversion of this advanced endometrial change can be effected with the use of estrogen antagonists. He has also reported treating a patient with in situ carcinoma of the endometrium with a progestin, resulting in regression of the anaplastic microscopic picture. Others have reported similar experiences.13 Andrews and Andrews14 presented a similar case to the :above mentioned in that the patient was 23 years old, showing adenocarcinoma of the endometrium with stromal invasion associated with Stein-Leventhal syndrome. Also Williamson15 has treated a 34-year-old patient with Stein-Leventhal syndrome with documented invasive carcinoma of the endometrium. Speertls reported a patient, aged 22, with irregular intermenstrual bleeding with endometrial hyperplasia at curettage. Three years later a second curettage revealed endometrial hyperplasia and Grade I: adenocarcinoma. A review of his original sections from the first curettage revealed a similar type cancer of the endometrium. Greenblattlr presented before this Association a report on a 28-year-old patient with Stein-Leventhal syndrome and adenoacanthoma of the endometrium, who had been treated prior to operation with cortisone because of elevated 17-ketosteroids. All of us are impressed that endometrial carcinoma developing in the young woman under 25 is extremely unusual, as for that matter is the Stein-Leventhal syndrome. Those for whom this syndrome has been named, Steinls and Leventhal,lD have not reported a case of this syndrome with associated carcinoma of the endometrium. Perhaps it has been well said that early diagnosis and treatment of the Stein-Leventhal syndrome represents a cancer prophylaxis.*0 Yet Dockerty, Lovelady, and Fousts reported that almost 20 per cent of women less than 40 years of age who had carcinoma of the uterus
Patient
presentations
115
gave clinical evidence of the Stein-LeventhaI syndrome. Perhaps it is true that carcinoma of the endometrium is a late complication of the unopposed estrogen stimulation to the endometrium found in the Stein-Leventhal syndrome. REFERENCES
Kaufman, Raymond H., Abbott, Jack P., and Wall, John A.: AM. .J. OBST. & GYNEC. 77: 1271, 1959. 2. Dockerty, M. B., Lovelady, S. B., and Foust, G. T., Jr.: AM. J. OBST. & GYNEC. 61: 966, 1951. 3. Novak, Emii, and Rutledge, Felix: AM. J. 1.
OBST.
& GYNEC.
55: 46, 1948.
Stein, I. F.: West. J. Surg. 63: 319, 1955. Stern, 0. N.: Delaware M. J. 28: 29, 1956. DeVere, R. D., and Dempstes, K. R.: J. Obst. & Gynaec. Brit. Emp. 60: 865, 1953. 7. Scheffey, Lewis C.: South. M. J. 42: 44, 1949. 8. Dockerty, M. B., Lovelady, S. B., and Foust, G. T.: AM. J. OBST. & GYNEC. 61: 966, 1951. 9. Gusburg, S. B.: Aol. J. OBST. & GYNEC. 54:
4. 5. 6.
905,
1947.
10. Hoffman, Jacob, and Scheffey, Lewis: AM. J. OBST. & GYNEC. 44: 925, 1942. 11. Hertig, Arthur T., and Sommers, Sheldon C.: Cancer 2: 946, 1949. 12. Kistner, R. W., and Smith, 0. W.: S. Forum 10: 725, 1960. 13. Kaufman, R. H., Abbott, J. P., and Wall; J. A.: AU. J. OBST. & GYNEC. 77: 1271, 1959. 14. Andrews, William C., and Andrews, Mason C.: AM. J. OBST. & GYNEC. 80: 632, 1960. 15. Williamson, H. Oliver: Personal communication. 16. Speert, Harold: Surg. Gynec. & Obst. 88: 332. 1949. 17. Greenblatt, Robert B.: Aan. J. OBST. & GYNEC.
66: 700,
1953.
Stein, I. F.: New England J. Med. 259: 420, 1958. 19. LiventhaI, M. L.: AM. J. OBST. & GYNEC. 76: 825. 1958. 20. Somme&, S. C., and Waldman, P. J.: AM. J. 18.
OBST.
& GYNEC.
72:
160,
1956.
Antepartum thrombophlebitis complicated by hyperuricemia, uremia, and polyhydramnios J.
B.
Jacksonville,
WILLIAMS,
JR.,
M.D.
Florida
THATTHROMBOEMBOLIC phenomenaare omnipresent in all disciplines of medicine is evident by the voluminous literature and extensive investigative studies done over the years. The in-
hours (normal, up to 4). A 4 hour glucose tolerance test revealed a diabetic curve. The uterus was difficult to outline and no adnexal masses were palpated. Curettage was performed. Microscopically the specimen revealed diffuse adenocarcinoma of the endometrium (Fig. 1). Total abdominal hysterectomy and bilateral salpingooophorectomy were performed. The ovaries were sclerocystic, typical of Stein-Leventhal, being 4% cm. with a smooth, pale gray-blue discoloration with nodularity on the surfaces. The pathologic diagnosis was adenocarcinoma of the endometrium with bilateral ovaries showing cortical fibrosis and follicular cysts compatible with Stein-Leventhal syndrome. Case 2 (S-68-3732). This 34-year-old nulligravida patient, weight 260 pounds, complained of periods of amenorrhea and irregular menstrual periods since age 18, and hair growth necessitating shaving her upper lip and lower chin. Examination revealed a constitutional-type obesity with an 8 week size uterus and enlarged right ovary. She was not seen until 2 years later, when in October of 1968 she had 3 weeks of bleeding after intermittent spotting since July of 1968. The uterus was the size of a 12 week gestation organ. A curettage was performed. The specimen revealed atypical adenomatous and papillary hyperplasia of the endometrium. The slides were sent to New Orleans for review. The pathologist there diagnosed this adenocarcinoma whereas our pathologist had called it atypical endometrial hyperplasia. Abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The ovaries were typical of Stein-Leventhal syndrome with multiple subcapsular follicular cysts, absence of corpora lutea, and a very thick and fibrotic capsule. The uterus contained adenocarcinoma of the endometrium with superficial invasion of the myometrium (Fig. 2).
Adenocarcinoma of the endometrium associated with the Stein-Leventhal syndrome KENNETH Medical
J. Center,
PARHAM, Greenwo,od,
I N 1 9 5 7 Jackson and upon a group of 44 cases syndrome in which 17 women the endometrium.1 Dockerty,
M.D. South
Carolina
Dockerty reported of Stein-Leventhal had carcinoma of Lovelady, and
Fousts reported that approximately 20 per cent of women under 40 who developed carcinoma of the uterine fundus showed clinical evidence of the Stein-Leventhal syndrome. Novak and Rutledges called attention to certain atypical benign lesions of the endometrium, sometimes encountered in young women, which may simulate adenocarcinoma. In the light of their work one might naturally question whether the case reported herein is cancer of the endometrium. Case 1 (S-68-207). This 21-year-old white female complained of occasional periods of amenorrhea of 2 or 3 months’ duration, menstrual flow that lasted from 4 to 30 days, sterility for 4 years, obesity (196 pounds at age 13 and 245 pounds at age 17), headaches, dry skin, preference for cold weather, and marked decrease in libido. At age 17, after medical therapy had failed to control menstrual hemorrhage, a curettage was performed. The findings were glandular hyperplasia and dense stroma. The patient weighed 300 pounds and the fat distribution was of a constitutional type. She had a normal female distribution of fine hair and the breasts were normal. The blood pressure was 140/80. Skull x-rays were normal, Ts uptake 29 per cent (euthyroid result), intravenous pyelogram normal, 17-ketosteroids were 8.1 mg. per 24 hours (normal, 4.4 to 15.8), 17-ketogenic steroids 13.9 mg. per 24 hours (normal, 5 to 18)) l7-hydroxysteroids 5 mg. per 24 hours (normal, 0.8 to 9.7), and pregnanetriol 1.6 mg. per 24
These two cases fit into the category of SteinLeventhal syndrome. Stein4 Stern,5 and others% 6 have recommended that dilatation and curettage be performed on all patients with menometrorrhagia associated with this syndrome to rule out endometrial carcinoma. It has been said that the pathologist bears a heavy responsibility when he announces his decision. The clinician must assume his responsibility just as seriously, for the life of the patient, in the final analysis, is actually in his hands.7 Dockerty and Lovelady* stated that 7 of 36 patients with endometrial cancer exhibited features of the Stein-Leventhal syndrome and noted that carcinoma of the uterine corpus complicat-
*Presented by invitation at the Thirtyfirst Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Feb. 2-5, 1969.
113
114
Panel
discussion
Fig.
1. Adenocarcinoma
Fig.
2. Myometrial
of the
invasion
by
endometriurn
adenocarcinoma
ing this syndrome had not received sufficient emphasis. Gusburg commented upon the evidence of the association of estrogen producing ovarian tumors and corpus carcinoma. He closely studied 5 patients who had developed adenocarcinoma of the uterine corpus following prolonged estrogen administration. He also described
of the
endometrium.
a type of adenomatous endometrial hyperplasia as being a cancer precursor, a belief that has persisted in the minds of many of us. Hoffman and ScheffeylO called atypical endometrial hyperplasia carcinoid hyperplasia. Certain criteria have been elaborated in an attempt to distinguish microscopically this adenomatous hyperplasia
Volume 105 Number1
from adenocarcinoma of the endometrium. Novak and Rutledge3 stated that, in the nonmalignant hyperplasia, stratification of the epithelium is not ‘uncommon, but that not more than two layers of cells are seen in this stratification. Cellular polarity should be maintained in adenomatous hyperpIasia with the nuclei remaining uniform in size and shape. Certainly this is not the case in clear cut adenocarcinoma of the endometrium. Hertig and Somme& indicate cystic hyperplasia as a frequent, important, but remote forerunner of carcinoma, but feel that adenomatous hyperplasia appears to be a more immediate precursor of endometrial carcinoma. Adenomatous hyperplasia is not irreversible. Kistnerrz has shown that reversion of this advanced endometrial change can be effected with the use of estrogen antagonists. He has also reported treating a patient with in situ carcinoma of the endometrium with a progestin, resulting in regression of the anaplastic microscopic picture. Others have reported similar experiences.13 Andrews and Andrews14 presented a similar case to the :above mentioned in that the patient was 23 years old, showing adenocarcinoma of the endometrium with stromal invasion associated with Stein-Leventhal syndrome. Also Williamson15 has treated a 34-year-old patient with Stein-Leventhal syndrome with documented invasive carcinoma of the endometrium. Speertls reported a patient, aged 22, with irregular intermenstrual bleeding with endometrial hyperplasia at curettage. Three years later a second curettage revealed endometrial hyperplasia and Grade I: adenocarcinoma. A review of his original sections from the first curettage revealed a similar type cancer of the endometrium. Greenblattlr presented before this Association a report on a 28-year-old patient with Stein-Leventhal syndrome and adenoacanthoma of the endometrium, who had been treated prior to operation with cortisone because of elevated 17-ketosteroids. All of us are impressed that endometrial carcinoma developing in the young woman under 25 is extremely unusual, as for that matter is the Stein-Leventhal syndrome. Those for whom this syndrome has been named, Steinls and Leventhal,lD have not reported a case of this syndrome with associated carcinoma of the endometrium. Perhaps it has been well said that early diagnosis and treatment of the Stein-Leventhal syndrome represents a cancer prophylaxis.*0 Yet Dockerty, Lovelady, and Fousts reported that almost 20 per cent of women less than 40 years of age who had carcinoma of the uterus
Patient
presentations
115
gave clinical evidence of the Stein-LeventhaI syndrome. Perhaps it is true that carcinoma of the endometrium is a late complication of the unopposed estrogen stimulation to the endometrium found in the Stein-Leventhal syndrome. REFERENCES
Kaufman, Raymond H., Abbott, Jack P., and Wall, John A.: AM. .J. OBST. & GYNEC. 77: 1271, 1959. 2. Dockerty, M. B., Lovelady, S. B., and Foust, G. T., Jr.: AM. J. OBST. & GYNEC. 61: 966, 1951. 3. Novak, Emii, and Rutledge, Felix: AM. J. 1.
OBST.
& GYNEC.
55: 46, 1948.
Stein, I. F.: West. J. Surg. 63: 319, 1955. Stern, 0. N.: Delaware M. J. 28: 29, 1956. DeVere, R. D., and Dempstes, K. R.: J. Obst. & Gynaec. Brit. Emp. 60: 865, 1953. 7. Scheffey, Lewis C.: South. M. J. 42: 44, 1949. 8. Dockerty, M. B., Lovelady, S. B., and Foust, G. T.: AM. J. OBST. & GYNEC. 61: 966, 1951. 9. Gusburg, S. B.: Aol. J. OBST. & GYNEC. 54:
4. 5. 6.
905,
1947.
10. Hoffman, Jacob, and Scheffey, Lewis: AM. J. OBST. & GYNEC. 44: 925, 1942. 11. Hertig, Arthur T., and Sommers, Sheldon C.: Cancer 2: 946, 1949. 12. Kistner, R. W., and Smith, 0. W.: S. Forum 10: 725, 1960. 13. Kaufman, R. H., Abbott, J. P., and Wall; J. A.: AU. J. OBST. & GYNEC. 77: 1271, 1959. 14. Andrews, William C., and Andrews, Mason C.: AM. J. OBST. & GYNEC. 80: 632, 1960. 15. Williamson, H. Oliver: Personal communication. 16. Speert, Harold: Surg. Gynec. & Obst. 88: 332. 1949. 17. Greenblatt, Robert B.: Aan. J. OBST. & GYNEC.
66: 700,
1953.
Stein, I. F.: New England J. Med. 259: 420, 1958. 19. LiventhaI, M. L.: AM. J. OBST. & GYNEC. 76: 825. 1958. 20. Somme&, S. C., and Waldman, P. J.: AM. J. 18.
OBST.
& GYNEC.
72:
160,
1956.
Antepartum thrombophlebitis complicated by hyperuricemia, uremia, and polyhydramnios J.
B.
Jacksonville,
WILLIAMS,
JR.,
M.D.
Florida
THATTHROMBOEMBOLIC phenomenaare omnipresent in all disciplines of medicine is evident by the voluminous literature and extensive investigative studies done over the years. The in-