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Hypernephroid carcinoma of the ovary
Hypernephroid carcinoma of the ovary Case report
J. W. WELCH, M.D. C.
A.
HELLWIG,
M.D.
Halstead, Kansas
H Y P E R N E P H R o I D carcinoma or clear cell adenocarcinoma of the ovary is a rare disease entity. Just how rare it is is difficult to determine from the literature but only two small series, 1 • ~ in addition to a few isolated case reports, have come to our attention. This is the only case recorded in the files of the Hertzler Clinic in the last 20 years, during which time approximately 8,000 pelvic laparotomies have been performed, nearly 500 of them for ovarian pathology. The hypernephroid carcinoma of the ovary is a bright yellow, nonmasculinizing, malignant tumor which differs histologically and symptomatically from either the luteoma or the hypernephroma of the ovary. According to Saphir and Lackner 1 the tumor is believed to take origin from persistent tubular structures of intraovarian mesonephric origin and is in most respects similar to the hypernephroid carcinoma of the kidney. The latter neoplasm. endocrinologically inert, is also a yellowish malignant tumor but arises within the kidney and is believed to originate from kidney tubules and not from suprarenal structures. Since the histologic architecture of the clear cell adenocarcinoma of the ovary resembles suprarenal tissue but the cells do not arise from suprarenal cells, it is called hypernephroid ( resembling suprarenal cortical structures) carcinoma rather than hypernephroma.
A detailed case report of one such plasm follows:
neo~
Mrs. E. D., a 65-year-old white woman, complained of painless swelling of the abdomen for 6 weeks prior to admission to the Hertzler Clinic. She was referred by her local physician with the diagnosis of fibroid tumor of the uterus, with a recommendation for operation. Her previous medical history revealed a late marriage with no pregnancies, no previous operations, and only 2 medical illnesses requiring hospitalization. One of these admissions was concerned with asthma and bronchiectasis and the other with glaucoma and diverticulosis of the colon. The patient had had an uneventful menopause at 52 years of age and had experienced no vaginal bleeding or discharge since. Physical examination revealed an alert white woman in apparently good health, with a normal pulse rate, respiration, and temperature; shP had a mild degree of hypertension. The positivP physical findings consisted of moist rales in the right lung base, hypertension, and a grapefruitsized cystic but firm midline pelvic mass felt both abdominally and by bimanual examination. A provisional diagnosis of ovarian cyst, bronchiectasis, glaucoma, and benign hypertension was made. There was no evidence of virilism. The following laboratory tests were within normal limits: complete blood count, urinalysis, serology, transaminase, blood urea nitrogen, fasting blood sugar, protein-bound iodine, gastric analysis, bleeding time. coagulation time, platelet count, total protein and albumin-globulin ratio, cholesterol, intravenous pyelogram, gall bladder visualization, barium meal, and electrocardiogram. The pyelogram, while normal, revealed a mass the size of a large grapefruit in the
From the Hertzler Research Foundation and the Hertzler Clinic.
426
Volume 80
NumhC'r 3
pelvis; x-ray examination of the chest showed a lobulated diaphragm; barium enema confirmed a previous diagnosis of multiple diverticula scattered throughout the sigmoid and descending colon. On cystoscopic examination a large extrinsic noninvasive mass was seen to be pressing in upon the bladder. The diagnostic impression after completion of the examination remained benign hypertension, glaucoma, bronchiectasis, and a pelvic mass. Exploratory operation was advised and accepted. At operation a large 13.5 by 11 by 7 em. bluish left ovarian cyst with attached tube was encountered and removed intact along with the uterus and the contralateral tube and ovary. Expl oration of adjacent lym ph nodes proved them benign. Exploration of the remainder of the abdomen revealed a walled-off perforated diverticulum. This was removed and the patient's abdomen was closed in a routine manner. She had an uneventful recovery and left the hospital in 10 days. She has been seen several times in the past year on routine postoperative foll ow-up visits and remains well. Gross pathology. The ovarian tumor, measuring 13.5 by 11 by 7 em. and weighing 360 grams, had a glistening bluish gray lobulated surface. An II em. long tube was stretched out over the surface of the tumor. In one area yellow nodules protruded from the wall without: perforating the capsule (Fig. 1, A). The cyst contained about 100 c.c. of clear, straw-colored fluid. On cross-section the wall of the cyst was thin, measuring between 1 mm. and 2 mm. with two large tumors firmly attached (Fig. 1, B). These two tumors filled out three fourths of the cavity of the cyst. One tumor measured 7 by 5 em., had a deep yellow color, and was completely solid. There was no hemorrhage or necrosis visible. The other tumor, measuring 8.5 by 6 em., consisted of many small cystic spaces filled with clear, straw-colored fluid. This second tumor appeared to be a separate tumor and touched the yellow tumor in only one area. On cut section the wall of the second cyst varied between 1 mm. and 1 em. in thickness, and the tissue was grayish brown in color. Microscopic pathology. Section of the thin cyst wall (Fig. 2) showed fibrous tissue which was quite cellular near the lumen. The epithelial lining was in a single layer and consisted of cuboid cells of varying sizes. The nuclei did not protrude over the surface of the cells, some of which had a clear cytoplasm. No cilia were
Hypernephroid carcinoma of ovary
427
A
B Fig. 1. Hypernephroid carcinoma of the ovary. A, Photograph of gross specimen. B, Cross-section of the tumor.
seen on the internal surface of the cells. Section of the yellowish tumor (Fig. 3) showed the typical structure of hypernephroma. The tumor cells were clear and had a very distinct cytoplasm. The nuclei, which were found in the center of the cells, were dark stained and varied markedly in size. Most of the cells were arranged in small glandular spaces while others formed papillae with a very thin fibrous stalk. The stroma was very scanty and consisted only of blood vessels with fibrous tissue. The other tumor (Fig. 4) consisted of a great many glandular spaces which varied in size and had the appearance of mesonephroma. The lining cells had protruding nuclei which varied in size. The cytoplasm was either light stained or granular. Occasional tufts which originated from the wall were 3een protruding into the lumen. These tufts were covered with hobnail epithelium and contained few blood vessels. The tumor apparently invaded the stroma.
428
Sept ClliO
Welch and Hellwig
Am .
J. Oost.
&
Gruec .
and
There is another rare yellow malignant tumor which masculinizes and which is thought by some to arise from misplaced suprarenal cortical cells within the ovary, hence, hypernephroma. This tumor is a lso called a lu tcoma or lutein cell blastoma since others believe that the tumor arises from luteinized granu losa cells rather than from misplaced suprarenal cells. The tumor, regardless of origin, produces masculinizing characteristics sttch as amenorrhea, , -nice changes, hirstttisrn, and hypertrophy of 1he clitoris indistinguishable from simila r disturbances in st'x characteristics produced by the arrhenoblastomas. Schiller'' It a ~ introdu ced still another tcm i. .;rnesonephroma,'' for malignant ovarian tumors of mesonephric origin. Novak and Woodruff ' ~lllmnarin·d Schilln's reasoning on mesonephric origin thus: ( 1) a semblance of the tumor cells to the endothelium of the glomeru lus ; ( 2) a generalized tubular pattern histologically resembling the mesonephric tubules; (3) isolated tufts and buds of tumor cel ls mindful of glomeruli; and p) a tendency to involve not only the ovary but other areas compatible with a mesonephric origin, such as th e broad ligament. They stated in a re\-it:'w of 35 cases of mesonephroma uf the ovary from the Ovarian Tumor Registry of the American Gynecological Society that the ovarian tumors formerly spoken of as hypernephroicl
It is highly important, of course, to determine whenever possible that such malignant growths as these are not really metastatic in nature. As far as can be determined, the case under discussion is that of a primary lesion. The opinion from our departments of urology and radiology, following complete examination preoperatively and postoperatively and including intravenous and retrograde pyelography, is that the kidneys are innocent. It is admitted that this is not proof positive but it is the best evidence obtainable under the circumstances.
Fig. 4. Mesonephroma of the ovary; in one lumen are glomerulus-like protrusions. Glandular spaces are lined with hobnail epithelium.
Fig. 2. Hypernephroid carcinoma of the ovary. Wall of large cyst; cuboid epithelium without cilia.
Fig. 3. Hypernephroid 'arcinoma of the ovary; clear cells with distinct cell border.
Diagnosis. Hypernephroid carcinoma mesonephroma in an ovarian cyst. Comment
Volume 80 Number 3
were actually mesonephric in origin. Stowe5 concurs in this view. In an earlier paper, Novak, Woodrlliff, and Novak 6 pointed out that there is a certain group of tumors derived from the Wolffian or mesonephric duct remnants that may arise at any level of the genital tract where the Wolffian duct has previously been present. They have found that the so-called Schiller type of mesonephroma is probably of mesonephric duct origin and is characterized by a glomerulus-like architecture with a tubular pattern featuring a low cuboidal lining epithelium with a frequent peglike budding into the lumen. They believe it is a frequent associate of the clear cell hypernephroid tumor as reported by Saphir and Lackner and that it probably takes origin from the mesonephric duct remnant in the ovary. Novak and Novak 7 state that their cases show various admixtures of these two tumors, frequently in the same section. Our case, which showed coexistence of a hypernephroid carcinoma 1 and a mesonephroma 8 in the same cyst cavity, strongly supports the view held by Novak and co-workers that both types of
Hypernephroid carcinoma of ovary
429
tumor have the same ongm, i.e., from the Wolffian (mesonephric) duct. Selye8 classified all of these tumors in one category~lipid cell tumors. He states that the possibility that they are morphogenetically heterogenous cannot be excluded but, until better methods are available to determine origin, all may be combined into one group. From the preceding discussion it becomes readily apparent that at present there is no general agreement on the origin or on the nomenclature of this group of ovarian neoplasms. Yet, they comprise a group of tumors with distinct characteristics histologically related. It is to be hoped that clarification and a standardized nomenclature will soon emerge.
Summary
A detailed case report of a rare disease entity, a hypernephroid carcinoma of the ovary, is presented along with a discussion of the problems of uniformity in classification and terminology of this and related tumors.
REFERENCES
1. Saphir, 0., and Lackner, J. E.: Surg. Gynec. & Obst. 79: 539, 1934.
2. Turner, J. C., Jr., ReMine, W. H., and Dockerty, M. B.: Surg. Gynec. & Obst. 109: 198, 1959. 3. Schiller, W. A.: Am. ]. Cancer 25: 1, 1939. 4. Novak, E. R., and Woodruff, J. D.: AM. J. 0BST. & GYNEC. 77: 632, 1959. 5. Stowe, L.: Cancer 8: 446, 1955.
6. Novak, E., Woodruff,
J.
D., and Novak, E. R.: 68: 1222, 1954. 7. Novak, Emil, and Novak, Edmund R.: Gynecologic and Obstetric Pathology, ed. 4, Philadelphia, 1958, W. B. Saunders Company, p. 295. 8. Selye, Hans: In Encyclopedia of Endocrinology, Montreal, Canada, 1945, Richardson, Bone & Wright, Vol. 7-A, Sect. 4, p. 69. AM.
J.
0BST.
&
GYNEC.
J. W. WELCH, M.D. C.
A.
HELLWIG,
M.D.
Halstead, Kansas
H Y P E R N E P H R o I D carcinoma or clear cell adenocarcinoma of the ovary is a rare disease entity. Just how rare it is is difficult to determine from the literature but only two small series, 1 • ~ in addition to a few isolated case reports, have come to our attention. This is the only case recorded in the files of the Hertzler Clinic in the last 20 years, during which time approximately 8,000 pelvic laparotomies have been performed, nearly 500 of them for ovarian pathology. The hypernephroid carcinoma of the ovary is a bright yellow, nonmasculinizing, malignant tumor which differs histologically and symptomatically from either the luteoma or the hypernephroma of the ovary. According to Saphir and Lackner 1 the tumor is believed to take origin from persistent tubular structures of intraovarian mesonephric origin and is in most respects similar to the hypernephroid carcinoma of the kidney. The latter neoplasm. endocrinologically inert, is also a yellowish malignant tumor but arises within the kidney and is believed to originate from kidney tubules and not from suprarenal structures. Since the histologic architecture of the clear cell adenocarcinoma of the ovary resembles suprarenal tissue but the cells do not arise from suprarenal cells, it is called hypernephroid ( resembling suprarenal cortical structures) carcinoma rather than hypernephroma.
A detailed case report of one such plasm follows:
neo~
Mrs. E. D., a 65-year-old white woman, complained of painless swelling of the abdomen for 6 weeks prior to admission to the Hertzler Clinic. She was referred by her local physician with the diagnosis of fibroid tumor of the uterus, with a recommendation for operation. Her previous medical history revealed a late marriage with no pregnancies, no previous operations, and only 2 medical illnesses requiring hospitalization. One of these admissions was concerned with asthma and bronchiectasis and the other with glaucoma and diverticulosis of the colon. The patient had had an uneventful menopause at 52 years of age and had experienced no vaginal bleeding or discharge since. Physical examination revealed an alert white woman in apparently good health, with a normal pulse rate, respiration, and temperature; shP had a mild degree of hypertension. The positivP physical findings consisted of moist rales in the right lung base, hypertension, and a grapefruitsized cystic but firm midline pelvic mass felt both abdominally and by bimanual examination. A provisional diagnosis of ovarian cyst, bronchiectasis, glaucoma, and benign hypertension was made. There was no evidence of virilism. The following laboratory tests were within normal limits: complete blood count, urinalysis, serology, transaminase, blood urea nitrogen, fasting blood sugar, protein-bound iodine, gastric analysis, bleeding time. coagulation time, platelet count, total protein and albumin-globulin ratio, cholesterol, intravenous pyelogram, gall bladder visualization, barium meal, and electrocardiogram. The pyelogram, while normal, revealed a mass the size of a large grapefruit in the
From the Hertzler Research Foundation and the Hertzler Clinic.
426
Volume 80
NumhC'r 3
pelvis; x-ray examination of the chest showed a lobulated diaphragm; barium enema confirmed a previous diagnosis of multiple diverticula scattered throughout the sigmoid and descending colon. On cystoscopic examination a large extrinsic noninvasive mass was seen to be pressing in upon the bladder. The diagnostic impression after completion of the examination remained benign hypertension, glaucoma, bronchiectasis, and a pelvic mass. Exploratory operation was advised and accepted. At operation a large 13.5 by 11 by 7 em. bluish left ovarian cyst with attached tube was encountered and removed intact along with the uterus and the contralateral tube and ovary. Expl oration of adjacent lym ph nodes proved them benign. Exploration of the remainder of the abdomen revealed a walled-off perforated diverticulum. This was removed and the patient's abdomen was closed in a routine manner. She had an uneventful recovery and left the hospital in 10 days. She has been seen several times in the past year on routine postoperative foll ow-up visits and remains well. Gross pathology. The ovarian tumor, measuring 13.5 by 11 by 7 em. and weighing 360 grams, had a glistening bluish gray lobulated surface. An II em. long tube was stretched out over the surface of the tumor. In one area yellow nodules protruded from the wall without: perforating the capsule (Fig. 1, A). The cyst contained about 100 c.c. of clear, straw-colored fluid. On cross-section the wall of the cyst was thin, measuring between 1 mm. and 2 mm. with two large tumors firmly attached (Fig. 1, B). These two tumors filled out three fourths of the cavity of the cyst. One tumor measured 7 by 5 em., had a deep yellow color, and was completely solid. There was no hemorrhage or necrosis visible. The other tumor, measuring 8.5 by 6 em., consisted of many small cystic spaces filled with clear, straw-colored fluid. This second tumor appeared to be a separate tumor and touched the yellow tumor in only one area. On cut section the wall of the second cyst varied between 1 mm. and 1 em. in thickness, and the tissue was grayish brown in color. Microscopic pathology. Section of the thin cyst wall (Fig. 2) showed fibrous tissue which was quite cellular near the lumen. The epithelial lining was in a single layer and consisted of cuboid cells of varying sizes. The nuclei did not protrude over the surface of the cells, some of which had a clear cytoplasm. No cilia were
Hypernephroid carcinoma of ovary
427
A
B Fig. 1. Hypernephroid carcinoma of the ovary. A, Photograph of gross specimen. B, Cross-section of the tumor.
seen on the internal surface of the cells. Section of the yellowish tumor (Fig. 3) showed the typical structure of hypernephroma. The tumor cells were clear and had a very distinct cytoplasm. The nuclei, which were found in the center of the cells, were dark stained and varied markedly in size. Most of the cells were arranged in small glandular spaces while others formed papillae with a very thin fibrous stalk. The stroma was very scanty and consisted only of blood vessels with fibrous tissue. The other tumor (Fig. 4) consisted of a great many glandular spaces which varied in size and had the appearance of mesonephroma. The lining cells had protruding nuclei which varied in size. The cytoplasm was either light stained or granular. Occasional tufts which originated from the wall were 3een protruding into the lumen. These tufts were covered with hobnail epithelium and contained few blood vessels. The tumor apparently invaded the stroma.
428
Sept ClliO
Welch and Hellwig
Am .
J. Oost.
&
Gruec .
and
There is another rare yellow malignant tumor which masculinizes and which is thought by some to arise from misplaced suprarenal cortical cells within the ovary, hence, hypernephroma. This tumor is a lso called a lu tcoma or lutein cell blastoma since others believe that the tumor arises from luteinized granu losa cells rather than from misplaced suprarenal cells. The tumor, regardless of origin, produces masculinizing characteristics sttch as amenorrhea, , -nice changes, hirstttisrn, and hypertrophy of 1he clitoris indistinguishable from simila r disturbances in st'x characteristics produced by the arrhenoblastomas. Schiller'' It a ~ introdu ced still another tcm i. .;rnesonephroma,'' for malignant ovarian tumors of mesonephric origin. Novak and Woodruff ' ~lllmnarin·d Schilln's reasoning on mesonephric origin thus: ( 1) a semblance of the tumor cells to the endothelium of the glomeru lus ; ( 2) a generalized tubular pattern histologically resembling the mesonephric tubules; (3) isolated tufts and buds of tumor cel ls mindful of glomeruli; and p) a tendency to involve not only the ovary but other areas compatible with a mesonephric origin, such as th e broad ligament. They stated in a re\-it:'w of 35 cases of mesonephroma uf the ovary from the Ovarian Tumor Registry of the American Gynecological Society that the ovarian tumors formerly spoken of as hypernephroicl
It is highly important, of course, to determine whenever possible that such malignant growths as these are not really metastatic in nature. As far as can be determined, the case under discussion is that of a primary lesion. The opinion from our departments of urology and radiology, following complete examination preoperatively and postoperatively and including intravenous and retrograde pyelography, is that the kidneys are innocent. It is admitted that this is not proof positive but it is the best evidence obtainable under the circumstances.
Fig. 4. Mesonephroma of the ovary; in one lumen are glomerulus-like protrusions. Glandular spaces are lined with hobnail epithelium.
Fig. 2. Hypernephroid carcinoma of the ovary. Wall of large cyst; cuboid epithelium without cilia.
Fig. 3. Hypernephroid 'arcinoma of the ovary; clear cells with distinct cell border.
Diagnosis. Hypernephroid carcinoma mesonephroma in an ovarian cyst. Comment
Volume 80 Number 3
were actually mesonephric in origin. Stowe5 concurs in this view. In an earlier paper, Novak, Woodrlliff, and Novak 6 pointed out that there is a certain group of tumors derived from the Wolffian or mesonephric duct remnants that may arise at any level of the genital tract where the Wolffian duct has previously been present. They have found that the so-called Schiller type of mesonephroma is probably of mesonephric duct origin and is characterized by a glomerulus-like architecture with a tubular pattern featuring a low cuboidal lining epithelium with a frequent peglike budding into the lumen. They believe it is a frequent associate of the clear cell hypernephroid tumor as reported by Saphir and Lackner and that it probably takes origin from the mesonephric duct remnant in the ovary. Novak and Novak 7 state that their cases show various admixtures of these two tumors, frequently in the same section. Our case, which showed coexistence of a hypernephroid carcinoma 1 and a mesonephroma 8 in the same cyst cavity, strongly supports the view held by Novak and co-workers that both types of
Hypernephroid carcinoma of ovary
429
tumor have the same ongm, i.e., from the Wolffian (mesonephric) duct. Selye8 classified all of these tumors in one category~lipid cell tumors. He states that the possibility that they are morphogenetically heterogenous cannot be excluded but, until better methods are available to determine origin, all may be combined into one group. From the preceding discussion it becomes readily apparent that at present there is no general agreement on the origin or on the nomenclature of this group of ovarian neoplasms. Yet, they comprise a group of tumors with distinct characteristics histologically related. It is to be hoped that clarification and a standardized nomenclature will soon emerge.
Summary
A detailed case report of a rare disease entity, a hypernephroid carcinoma of the ovary, is presented along with a discussion of the problems of uniformity in classification and terminology of this and related tumors.
REFERENCES
1. Saphir, 0., and Lackner, J. E.: Surg. Gynec. & Obst. 79: 539, 1934.
2. Turner, J. C., Jr., ReMine, W. H., and Dockerty, M. B.: Surg. Gynec. & Obst. 109: 198, 1959. 3. Schiller, W. A.: Am. ]. Cancer 25: 1, 1939. 4. Novak, E. R., and Woodruff, J. D.: AM. J. 0BST. & GYNEC. 77: 632, 1959. 5. Stowe, L.: Cancer 8: 446, 1955.
6. Novak, E., Woodruff,
J.
D., and Novak, E. R.: 68: 1222, 1954. 7. Novak, Emil, and Novak, Edmund R.: Gynecologic and Obstetric Pathology, ed. 4, Philadelphia, 1958, W. B. Saunders Company, p. 295. 8. Selye, Hans: In Encyclopedia of Endocrinology, Montreal, Canada, 1945, Richardson, Bone & Wright, Vol. 7-A, Sect. 4, p. 69. AM.
J.
0BST.
&
GYNEC.