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Hilus-Cell Tumor of the Ovary
Case Reports, New Instruments and Methods HILUS-CELL TUMOR OF THE OVARY Report of a Case s. w. BERKHEISER, M.D.,"' SAYRE, PA. (From the Department of Pathology at the (}uthrie Cz.inio and Robert Packe1· Hospital)
tumors derived from the ovarian hilus cells are rare the following SINCE case is reported. H. F., a 50·year·old unmarried white woman, was admitted to the hospital beeau~0 of hypertension and an excess growth of hair. Twenty·five years previously she had begun to develop an increase in facial and body hair, which gradually became exceHsive. During the eight years prior to admission she began to lose scalp hair. Her voke gradually changed, became deeper, and more masculine. She also noticed occasional episodes of palpitation and dyspnea. Hypertension was discovered three years prior 10 admission. This was not severe and was relieved by rest. Past history disclosed that menses had started at the age of 13 years. Her periods were regular but profuse, generally lasting a week. Nineteen years previously she underwent exploratory laparotomy, and extensive pelvic endometriosis was discovered. This requir~d resection of a portion of small intestine, and an incidental appendeetomy was also performed. Two ,\·ears later she received a course of radium therapy (a total of 1~ bourg). Her nHm~Ps then gradually decreased, and finally ceased entirely. Physical Examination.-The temperature on admission was 98° F.; pulse rate 80; respirations 24; and blood pressure 162/100. She was a slightly obese white woman with a deep, low voice. She complained of fatigue and was noticeably apprehensive. Th(•re was marked increase in hair over the face, chest, and back. A typical masculine distril>u· tion was noted over the lower abdomen and extremities. The scalp line was receding. The skin was dry and coarse. Slight exophthalmos was noted. The heart and lungs wPre not remarkable. There was a well·healed lower abdominal scar. The clitoris and labia were enlarged and hypertrophied. Vaginal examination disclosed a small, freely movable cervix. The uterus was small and considered infantile. There was a suggestion of a mass in the left adnexal region. Laboratory Data.-The blood cholesterol was 368 mg. per 100 ml. Other studies including blood count, urinalysis, and blood chemistry determinations were within norlllal limits. Roentgenograms of the skull, long bones, pelvis, and chest were unrevealing. Several days after admission a hysterectomy and bilateral oophorectomy were performed by Dr. W. C. Beck. She did well postoperatively and was discharged within n week. Pathology.-The uterus was small, being' 3.5 by 2.8 by 2.0 em. in dimensions. There were several subserosa! fibromyomas, the largest 5.0 em. in diameter. Within the endo· metrial cavity was a benign polyp, 1.2 em. in length. The right ovary was enlarged, and *:Present address, Harrisburg Polyclinic Hospital, Barri13burg, :Pa.
429
430
BERKHEJSER
Am.]. Obst. & Gynec. February , 1957
measured 4.8 by 3.5 by 2.5 em. Near one pole was a poorly defined nodule, 2.0 em. in diameter (Fig. 1). There was no definite capsule, and the cut surface was gray brown and focally hemorrhagic. The left ovary and tube showed no unusual changes. Microscopic sections of the right ovary disclosed a tumor composed of broad sheets of uniform polygonal cells. Most of these cells had oval, centrally placed nuclei, and abundant eosinophilic, but slightly granular cytoplasm (Fig. 2). No cytoplasmic inclu· sions or crystalloids were observed. In some regions the cells were closely associated with small bundles of unmyelinated nerves (Fig. 3 ). Sections stained with sudan IV disclosed the presence of sudanophilic material within the cytoplasm of these cells. The initial impression was that this represented a masculinizing ovarian tumor, of perhaps the adrenal-cell-rest type. Representative sections and material from this tumor were submitted to Dr. Emil Novak. Both hel and Dr. Robert L. Faulkner agreed that this was a tumor of the hilus or interstitial-cell type. The patient was examined 8 months after operation. She felt much stronger, and her skin was softer and warm. She thought that there was increased growth of scalp hair, and that the hirsutism of the extremities, trunk, and abdomen was less accentuated.
Fig. 1.-:-Gross photograph showing the poorly defined hilus-cell tumor of the right ovary.
Comment The studies of Sternberg 2 have shown that the hilus of the human ovary contains nests of cells morphologically identical with the interstitial or Leydig cells of the testis. These cells are present in at least 80 per cent of adult ovaries. There is a constant relationship of these cells to the nonmyelinated nerves of the hilus. This relationship is also maintained in tumors derived from the hilus cells. According to Novak 3 a total of 6 tumors derived from the ovarian hilus cells are recorded in the literature. It is difficult to determine the actual number, since differentiation of hyperplasia from tumor has not always been made clear. Typical examples of hilus-cell hyperplasia have been reported by Langley, 4 Taliaferro/ Sternberg/ and others. Although the latter also have masculinizing signs, bilateral ovarian involvement has occurred in almost all cases. The true hilus-cell tumors, with one exception, have been unilateral. Table I summarizes the cases of hilus-cell tumors reported to date. Approximately half the patients showed some degree of hypertension prior to removal of the tumor. Clinically and pathologically the hilus-cell tumors should be differentiated from the more common arrhenoblastomas, and the ra1·e "virilizing lipoid-cell
l•'ig. 2.-Photomicrograph showing the typical large, polygonal hilus cells. eosin: X360; reduced \.'.. J
(Hematoxylin and
Fig. 3.-The close association of the hilus cells to a nonmyelinated nerve bun•lle ie d<·arly shown. (Hematoxylin and eosin; Xl60).
BERKHEISER
432
Am.
1. Obst. & Gynec. February, 1957
tumors,'' or adrenal tumors of the ovary. Godsick 10 found 21 tumors of the latter type in tho literature up to 1954. The adrenal tumors of the ovary are most common in the 20 to 30 year age group, with only two cases reported occurring after the menopause. Sternberg 2 has shown that the adrenal tumors are yellow, spherical nodules, encapsulated, and usually 1 to 3 mm. in diameter. They duplicate normal adrenal cortex, and have a definite organoid structure. '!'he arrhenoblastomas include a broad spectrum with a variable pattern, usually with tubular structure and sometimes a sarcoma-like picture, depending upon the degree of differentiation. In a recent publication Langley 4 tends to regard the hilus-cell tumors as a variant of the arrhenoblastomas. The variable structure of the arrhenoblastomas, however, is in direct contrast to the uniform, single cell type of the hilus-cell tumors. A summary of the main features of these three masculinizing ovarian tumors is given in Table II. TABLE I. SUMMARY OF REPORTED CASES OF OVARIAN HILUS-CELL 'I.'UMORS
menses +
Hypertension, 17 ketosteroid normal
+
+
17 ketosteroid normal
Not stated
+
+
17 ketosteroid increased
47
1.8 em.
+
+
Hypertension, 17 ketosteroid normal. Ectopic adrenal rest (incidental)
27
Not stated
+
Not stated
2.0 em.
+
Absent
Sternberg2
86
1.0, 1.2 em.
Sternberg2
64
1.0 em.
Waugh7
46
Sachss
Youngo .Present case
50
+
Pregnancy
TABLE II. SUMMARY OF CLINICAL AND PATHOLOGIC FEATURES OF ARRHENOBLASTOMAS, ADRENALCELL-REST AND HILUS-CELT, TUMORS
TUMOR Arrhenoblastoma
I
AGE
GROUP 20-30
I
CELL TYPE Varied
I
I
I
I
I
ORGANOID BIUNISTRUCCAPSULE LATERAL LATERAL 17 KETOSTEROID TURE Normal, or slightly Present Usually + elevated present
Adrenal cell rest
20-30
Single cell
Present Present
+
Hilus cell
.Postmeno-
Single cell
Absent Usually absent
+
+
Elevated
Rarely Usually normal
Summary
A case of rare hilus-cell tumor occurring in a 50-year-old woman is recorded. Some of the current concepts with respect to the clinical and pathologic features are briefly discussed.
Volume 73 Number 2
HILUS-CELL TUMOR OF OVARY
4:3:3
References 1. 2. 3. 4. 5.
Novak, E.: Personal communication, May, 1955. Sternberg, W. H.: Am. J. Path. 25: 493, 1949. Novak, E.: Obst. & Gynec. 1: 3, 1953. Langley, F. A.: J. Olin. Path. 7: 10, 1954. Taliaferro, I., Wells, E. J., Kay, S., and Hoge, R H.:
675, 1953. 6. Be:rger, L.! Quoted by Sternberg.z
A. M. A. Arch. Int. Med. 91:
7. Waugh, D., Venning, E. H., and McEachern, D.: J. Olin. Endocrinol. 9: 486, 1\14\l. 8. Sachs, B. A., and Spiro, D.: J. Olin. Endoc1·inol. 11: 878, ltl5.1. 9. Young, W. R.: Illinois M. J. 100: 263, 1951. 10. Godsick, W. H., and Baydoun, A. B.: Obst. & Gynec. 4: 54~. U-l:'i4.
tumors derived from the ovarian hilus cells are rare the following SINCE case is reported. H. F., a 50·year·old unmarried white woman, was admitted to the hospital beeau~0 of hypertension and an excess growth of hair. Twenty·five years previously she had begun to develop an increase in facial and body hair, which gradually became exceHsive. During the eight years prior to admission she began to lose scalp hair. Her voke gradually changed, became deeper, and more masculine. She also noticed occasional episodes of palpitation and dyspnea. Hypertension was discovered three years prior 10 admission. This was not severe and was relieved by rest. Past history disclosed that menses had started at the age of 13 years. Her periods were regular but profuse, generally lasting a week. Nineteen years previously she underwent exploratory laparotomy, and extensive pelvic endometriosis was discovered. This requir~d resection of a portion of small intestine, and an incidental appendeetomy was also performed. Two ,\·ears later she received a course of radium therapy (a total of 1~ bourg). Her nHm~Ps then gradually decreased, and finally ceased entirely. Physical Examination.-The temperature on admission was 98° F.; pulse rate 80; respirations 24; and blood pressure 162/100. She was a slightly obese white woman with a deep, low voice. She complained of fatigue and was noticeably apprehensive. Th(•re was marked increase in hair over the face, chest, and back. A typical masculine distril>u· tion was noted over the lower abdomen and extremities. The scalp line was receding. The skin was dry and coarse. Slight exophthalmos was noted. The heart and lungs wPre not remarkable. There was a well·healed lower abdominal scar. The clitoris and labia were enlarged and hypertrophied. Vaginal examination disclosed a small, freely movable cervix. The uterus was small and considered infantile. There was a suggestion of a mass in the left adnexal region. Laboratory Data.-The blood cholesterol was 368 mg. per 100 ml. Other studies including blood count, urinalysis, and blood chemistry determinations were within norlllal limits. Roentgenograms of the skull, long bones, pelvis, and chest were unrevealing. Several days after admission a hysterectomy and bilateral oophorectomy were performed by Dr. W. C. Beck. She did well postoperatively and was discharged within n week. Pathology.-The uterus was small, being' 3.5 by 2.8 by 2.0 em. in dimensions. There were several subserosa! fibromyomas, the largest 5.0 em. in diameter. Within the endo· metrial cavity was a benign polyp, 1.2 em. in length. The right ovary was enlarged, and *:Present address, Harrisburg Polyclinic Hospital, Barri13burg, :Pa.
429
430
BERKHEJSER
Am.]. Obst. & Gynec. February , 1957
measured 4.8 by 3.5 by 2.5 em. Near one pole was a poorly defined nodule, 2.0 em. in diameter (Fig. 1). There was no definite capsule, and the cut surface was gray brown and focally hemorrhagic. The left ovary and tube showed no unusual changes. Microscopic sections of the right ovary disclosed a tumor composed of broad sheets of uniform polygonal cells. Most of these cells had oval, centrally placed nuclei, and abundant eosinophilic, but slightly granular cytoplasm (Fig. 2). No cytoplasmic inclu· sions or crystalloids were observed. In some regions the cells were closely associated with small bundles of unmyelinated nerves (Fig. 3 ). Sections stained with sudan IV disclosed the presence of sudanophilic material within the cytoplasm of these cells. The initial impression was that this represented a masculinizing ovarian tumor, of perhaps the adrenal-cell-rest type. Representative sections and material from this tumor were submitted to Dr. Emil Novak. Both hel and Dr. Robert L. Faulkner agreed that this was a tumor of the hilus or interstitial-cell type. The patient was examined 8 months after operation. She felt much stronger, and her skin was softer and warm. She thought that there was increased growth of scalp hair, and that the hirsutism of the extremities, trunk, and abdomen was less accentuated.
Fig. 1.-:-Gross photograph showing the poorly defined hilus-cell tumor of the right ovary.
Comment The studies of Sternberg 2 have shown that the hilus of the human ovary contains nests of cells morphologically identical with the interstitial or Leydig cells of the testis. These cells are present in at least 80 per cent of adult ovaries. There is a constant relationship of these cells to the nonmyelinated nerves of the hilus. This relationship is also maintained in tumors derived from the hilus cells. According to Novak 3 a total of 6 tumors derived from the ovarian hilus cells are recorded in the literature. It is difficult to determine the actual number, since differentiation of hyperplasia from tumor has not always been made clear. Typical examples of hilus-cell hyperplasia have been reported by Langley, 4 Taliaferro/ Sternberg/ and others. Although the latter also have masculinizing signs, bilateral ovarian involvement has occurred in almost all cases. The true hilus-cell tumors, with one exception, have been unilateral. Table I summarizes the cases of hilus-cell tumors reported to date. Approximately half the patients showed some degree of hypertension prior to removal of the tumor. Clinically and pathologically the hilus-cell tumors should be differentiated from the more common arrhenoblastomas, and the ra1·e "virilizing lipoid-cell
l•'ig. 2.-Photomicrograph showing the typical large, polygonal hilus cells. eosin: X360; reduced \.'.. J
(Hematoxylin and
Fig. 3.-The close association of the hilus cells to a nonmyelinated nerve bun•lle ie d<·arly shown. (Hematoxylin and eosin; Xl60).
BERKHEISER
432
Am.
1. Obst. & Gynec. February, 1957
tumors,'' or adrenal tumors of the ovary. Godsick 10 found 21 tumors of the latter type in tho literature up to 1954. The adrenal tumors of the ovary are most common in the 20 to 30 year age group, with only two cases reported occurring after the menopause. Sternberg 2 has shown that the adrenal tumors are yellow, spherical nodules, encapsulated, and usually 1 to 3 mm. in diameter. They duplicate normal adrenal cortex, and have a definite organoid structure. '!'he arrhenoblastomas include a broad spectrum with a variable pattern, usually with tubular structure and sometimes a sarcoma-like picture, depending upon the degree of differentiation. In a recent publication Langley 4 tends to regard the hilus-cell tumors as a variant of the arrhenoblastomas. The variable structure of the arrhenoblastomas, however, is in direct contrast to the uniform, single cell type of the hilus-cell tumors. A summary of the main features of these three masculinizing ovarian tumors is given in Table II. TABLE I. SUMMARY OF REPORTED CASES OF OVARIAN HILUS-CELL 'I.'UMORS
menses +
Hypertension, 17 ketosteroid normal
+
+
17 ketosteroid normal
Not stated
+
+
17 ketosteroid increased
47
1.8 em.
+
+
Hypertension, 17 ketosteroid normal. Ectopic adrenal rest (incidental)
27
Not stated
+
Not stated
2.0 em.
+
Absent
Sternberg2
86
1.0, 1.2 em.
Sternberg2
64
1.0 em.
Waugh7
46
Sachss
Youngo .Present case
50
+
Pregnancy
TABLE II. SUMMARY OF CLINICAL AND PATHOLOGIC FEATURES OF ARRHENOBLASTOMAS, ADRENALCELL-REST AND HILUS-CELT, TUMORS
TUMOR Arrhenoblastoma
I
AGE
GROUP 20-30
I
CELL TYPE Varied
I
I
I
I
I
ORGANOID BIUNISTRUCCAPSULE LATERAL LATERAL 17 KETOSTEROID TURE Normal, or slightly Present Usually + elevated present
Adrenal cell rest
20-30
Single cell
Present Present
+
Hilus cell
.Postmeno-
Single cell
Absent Usually absent
+
+
Elevated
Rarely Usually normal
Summary
A case of rare hilus-cell tumor occurring in a 50-year-old woman is recorded. Some of the current concepts with respect to the clinical and pathologic features are briefly discussed.
Volume 73 Number 2
HILUS-CELL TUMOR OF OVARY
4:3:3
References 1. 2. 3. 4. 5.
Novak, E.: Personal communication, May, 1955. Sternberg, W. H.: Am. J. Path. 25: 493, 1949. Novak, E.: Obst. & Gynec. 1: 3, 1953. Langley, F. A.: J. Olin. Path. 7: 10, 1954. Taliaferro, I., Wells, E. J., Kay, S., and Hoge, R H.:
675, 1953. 6. Be:rger, L.! Quoted by Sternberg.z
A. M. A. Arch. Int. Med. 91:
7. Waugh, D., Venning, E. H., and McEachern, D.: J. Olin. Endocrinol. 9: 486, 1\14\l. 8. Sachs, B. A., and Spiro, D.: J. Olin. Endoc1·inol. 11: 878, ltl5.1. 9. Young, W. R.: Illinois M. J. 100: 263, 1951. 10. Godsick, W. H., and Baydoun, A. B.: Obst. & Gynec. 4: 54~. U-l:'i4.