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Solitary Cyst of the Kidney with Adeno-Carcinoma in the Walls of the Cyst1
SOLITARY CYST OF THE KIDNEY WITH AD ENO-CARCINOMA IN THE WALLS OF THE CYST1 WILLIAM J. EZICKSON AND LLOYD B. GREENE Cysts of the kidney are not properly classified as tumors as they are considered to be the results of retention due to inflammatory changes or to congenital errors of development. Many theories concerning their formation have been proposed. The typical benign cyst is solitary and usually of considerable size. The contents may be clear and watery or mixed with blood. They can vary in size from a centimeter or two to a structure large enough to fill and distend the abdominal cavity. It may be located at any point on the surface of the kidney but most often on the convex border and at one of the poles. The cyst never communicates with the pelvis. It is lined with a delicate epithelium, either cuboidal or flat. There is no fibrous capsule in the serous cysts, the epithelium lying on a basement membrane of about the same thickness as that of a normal tubule and directly in contact with the parenchyma. In the hemorrhagic cysts there may be a thick wall or organized blood clot and adhesions to the surrounding organs may be more marked. The large cysts may press upon the other abdominal organs and produce symptoms. In other cases the cysts are multiple or simple cysts may be multilocular. The contents of serous cysts usually had a yellowish color and urea may be found in greater concentration than in the blood, suggesting that the lining epithelium has some relation to the secretory epithelium of the kidney. The investigations of Rienhoff are of especial interest in connection with speculations concerning renal cysts, polycystic kidneys and renal neoplasms. In tissue cultures taken from early embryos he saw convoluted tubules, glomeruli, vascular endothelium and connective tissue, all arising in situ from the undifferentiated mesenchymal cells of the primitive kidney. Thus any of these tissues might be represented in cystic or solid neoplasms or malformations of the kidney. Dr. John Douglas classifies cysts of kidney as: (1) degenerative; (2) perinephric; (3) retention; (4) simple or solitary; (5) hydatid and (6) 1
Presented before the Philadelphia Urological Society, February 1935. 153
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WILLIAM J. EZICKSON AND LLOYD B. GREENE
dermoid. Solitary cysts are of comparatively rare occurrence. Most frequently involve lower pole. Urine examination is usually negative unless secondary infection of the pelvis occurs but a differential functional test may show diminished renal function due to pressure on the kidney. In the same manner pressure may cause a distorted pyelogram. Origin of these solitary cysts is of interest and is still a matter of dispute. Wood writes; "In chronic diffuse nephritis of the atrophic form, a group of tubes may be dilated. Apparently one or more of the larger tubes in the pyramids are obstructed and this causes dilatation of a corresponding group of tubes. Such a dilatation may be moderate in size or it may form cysts visible to the naked eye." While this is an adequate explanation for the smaller cysts, often multiple, which are frequently found at autopsy, below the capsule, in atrophic kidneys, it hardly explains the large solitary cysts appearing in an otherwise normal appearing kidney. Ziegler states that these single cysts are due to retention of secretion from a glomerulus from which its tubules have been cut off and do not function, although the rest of the kidney may be normal. Aschoff quotes Ruchert that all cysts of the kidney are due to congenital tissue malformation. Most of the other writers on the subject also quote this opinion of Ruchert as does Berman, but the latter differs from him in his conclusion that all the solitary cysts of the kidney are congenital. Dr. Edwin Beer in remarks concerning a case reported by Douglas said that in a very extensive study of cysts of the kidney he had arrived at the conclusion from serial section of several hundred cysts that cysts of 3 distinct types occurred in the kidney. The smallest cysts, never much larger than the head of a pin, were almost always derived from Malpighi's corpuscles and frequently at some part of the cyst small glomerular tufts could be seen more or less atrophied. The contents of these cysts were usually colloidal material with more or less lime salts. The cysts which were next in size, growing as big as small peas, were usually of tubular origin, and in the walls of these cysts showed an endothelial lining with here and there in the walls accumulations of smooth muscle fibres. The largest cyst of this type that he had studied was about the size of a hen's egg. Otto F. Kampmeier in an exhaustive study writes on a hitherto unrecognized mode of origin of congenital renal cysts. The study was based on the microscopic examination and study of 26 human embryos and foetuses ranging in age from 6 weeks to 5 months of intra-uterine
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life; post-mortem examination of 10 babies and 36 cadavers in the dissecting room. He enumerates his observations as follows: (1) The existence of a vestigial primary generation of a uriniferous tubule; (2) the occasional cystic transformation of such vestigial tubules; (3) the early communication of the next order of uriniferous tubules with collecting ducts of the corresponding order, namely the second (4) the temporary attachment of most of these tubules from the secondary collecting ducts to their reunion with the ducts of the fourth and fifth orders (5) the later permanent separation of these uriniferous tubules from these ducts and the cystic transformation of most of them; in other words the apparently constant appearance of renal cysts at a certain period of fetal life. A review of voluminous isolated unilateral cysts of the kidney of serous type, 95 in all, reported in the literature from 1830 to 1922, did not reveal one case in which any malignant degeneration was reported as occurring within the walls of the cyst. T . J. Kirwin reported an interesting case of calcified renal cyst. H . Viethen reports an unusual case of solitary cyst in horseshoe kidney. H.B. Sweetsen reports a case of suppuration in solitary cyst. Two cases of solitary cysts associated with calculi have been reported. One by Arnsworth-Davis and Dunhill and one by D . R. Roberts. A. B. Hepler offers some observations on the pathogenesis of solitary cysts based on 7 personal and 249 collected cases; 216 serous; 40 hemorrhagic. He believes the large, usually solitary cysts are acquired. They are not a distinct entity with a common etiology but the mechanism is essentially the same. Recognized pathological conditions cause them, but only when so situated as to produce a combination of group tubular obstruction and anemic degeneration of the parenchyma from circulatory disturbances in the same segment of kidney. In some, an additional factor is repeated prolonged hemorrhages into the same area. This conception explains the variation in size, number, contents, cyst wall and associated renal conditions on the basis of variation of the direct etiologic factor, amount of group tubular obstruction of vessels involved. It also explains the apparent absence of a direct etiologic factor in some, for the original lesion may become so involved in the process that all evidence is eventually lost. Among the features of cysts which lend support to this hypothesis are: (1) the average age incidence of 45 years, when vascular lesions and acquired lesions, such as tumor, are common. (2) the rather frequent association of these cysts with lesions, which might produce the conditions
156
WILLIAM
J.
EZICKSON AND LLOYD B. GREENE
assumed to be necessary for their formation. (3) The frequent presence in the kidney containing a so-called solitary cyst, of small cysts similar in every detail except size and indistinguishable from nephritic cysts. (4) The presence in the sac wall of groups of atrophied glomeruli and tubules indicating its origin from parenchyma which has undergone compression atrophy with a connective tissue substitution. (5) The presence of remnants of neoplasm in the walls of many of the hemorrhagic cysts as the only indication that tumor was concerned in their formation. (6) In many, the sudden onset and rapid growth of cysts which can be easily understood in the light of experimental work in which enormous diverticula formed in a few days. Finally by creating experimentally the conditions assumed to be necessary for cyst formation, he has been able to reproduce a large solitary cyst similar in every detail to those in the human kidney. The solitary cyst, in a woman 37, operated on by J. S. Ritter, contained a hypernephroma. I herewith wish to present this unusual case of solitary cyst of the kidney with adeno-carcinoma in the walls of the cyst. Case report. F. C., a male, aged 31 years, a presser's helper, was seen March 21, 1934. He complained of intermittent hematuria, the last attack being March 20, 1934. His physician said the urine was the color of grape juice. In August, 1933, while the patient was spading very hard ground, he was seized with a sudden sharp pain, which lasted 5 to 10 minutes, in his lower back. Several days later he noticed blood-stained urine, which continued about two weeks. He lost his position and while not working there was no hematuria. In February, 1934 he went back to work and the hematuria returned. The bleeding occurred 2 to 3 (unes every 5 to 8 days and was associated with low sacral pain, urgency, frequency and dysuria. He had lost 11 pounds in 4 months. The family history was negative. General physical examination was essentially negative. No mass could be palpated in the abdomen. The hemoglobin was 15.8 grams. The red blood cells numbered 5,100,000, white blood cells 9,400, polymorphonuclears 68, small lymphocytes 24 and large lymphocytes 8. The blood Wassermann was negative. The urea nitrogen was 13 and the blood sugar 102. The phthalein test showed an output of 60 per cent the first hour, 9 per cent the second hour, 2-hour total 69 per cent. Cystoscopic examination disclosed no residual urine. There was a prominent interureteric ridge, and moderate trabeculation of the bladder. Number 5 catheters passed eaily up both ureters. Phthalein (1 cc.) injected intravenously appeared from the right kidney in 5 minutes and from the left kidney
SOLITARY CYST OF KIDNEY WITH ADENO-CARCINOMA
157
in 9 minutes. The output from the right kidney in 15 minutes was 17 .5 per cent, the left kidney 10 per cent. Left pyelogram (fig. 1) revealed a thinning of the middle calyx with some pressure on the upper calyx as well. This was highly suggestive of a hypernephroma involving the upper pole. There was no dilatation of the renal pelvis, which was of the intrarenal type, nor was there any disturbance of the uretero-pelvic junction. The kidney was not markedly enlarged and was more or less of the vertical type. There was no evidence of obstruction to the catheter.
FIG. 1 FIG. 4 FIG. 1. Preoperative left pyelogram showing thinning of middle calyx with some pressure on upper calyx, suggestive of hypemephroma involving upper pole. No dilatation of renal pelvis, which was of intra-renal type, nor was there any disturbance of the uretero-pelvic junction. FIG. 4. Postoperative left pyelogram showing irregular area between upper calyces. The uretero-pelvic juncture is normal and uppermost calyx negative.
Right pyelogram was normal. Bacteriologic study of the urine from the right kidney showed many epithelial cells, a few leucocytes and occasional red blood cells. Urine from the left kidney contained many epithelial cells and a great many red blood cells. On March 30 through a left lumbar incision the kidney was easily exposed. A solitary tumor-cyst was found in the mid-portion of the kidney. About 60 cc. muddy, serous fluid was aspirated from the cyst. The cyst was easily enucleated and did not connect with the pelvis. The halves of the kidney were sutured together, the wound closed in layers, and a large rubber drain inserted. The specimen (fig. 2) was a smooth, round mass measuring 6 cm. in diameter. On section the wall was firm and white, varying about 1 cm. in thickness and surrounding a cavity. The inner portion of the wall was broken and necrotic.
FIG. 2. Photograph of cyst removed from left kidney
FIG. 3. Photomicrograph of tissue from wall of cyst 158
SOLITARY CYST OF KIDNEY WITH ADENO-CARCINOMA
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Microscopic section (fig. 3) showed many small and large glandular elements. These were supported with a greater or less amount of fairly dense fibrous tissue. In some areas the growth took on a papillary form and in others it was found in solid masses. The cells were large and had large, light-staining nuclei. Few mitotic figures were found. The diagnosis was adeno-carcinoma. The convalescence was satisfactory and ten days after operation the patient was up in a chair. On April 13 a stereoscopic left pyelogram (fig. 4) revealed an irregular area between the upper calyces. The uretero-pelvic juncture was normal, and t he · uppermost calyx negative. An x-ray of the chest revealed a peribronchial thickening of the entire bronchial tree on the right side. This was distributed in irregular areas, but more or less uniform over the right bronchial tree. . The diaphragms were plainly visible and free from adhesions or fluid. There was no evidence of metastatic growths. The patient was discharged seventeen days after operation in excellent condition. Six months later he developed a persistent dry, hacking cough. An x-ray of the chest disclosed metastatic growths in the lungs. He was given several series of deep x-ray treatments to the chest and left kidney area, but this was of no avail and the patient died September 12, 1935.
2100 Walnut St., Philadelphia, Pa. Medical Arts Bldg., Philadelphia, Pa. REFERENCES AINSWORTH-DAVIS AND DUNHILL: Brit. Med. Jour., 1: 10, 1930. · DouGLAS: Ann. Surg., 76: 656, 1922. HEPLER: Surg., Gynec. and Obstet., 50: 668, 1930. KAMPMEIER: Surg., Gynec. and Obstet., 36: 208, 1923. KIRWIN: Jour. Urol., 15: 273, 1926. RIENHOFF: Johns Hop. Hosp. Bull., 33: 392, 1922. RITTER: Amer. Jour. Surg., 8: 1089, 1930. ROBERTS: Brit. Med. Jour., 2: 15, 1930. SWEETSEN: Minn. Med. Jour., 12: 786, 1929. VIETHEN: Ztschr. f. Chir., 53: 2655, 1926.
Presented before the Philadelphia Urological Society, February 1935. 153
154
WILLIAM J. EZICKSON AND LLOYD B. GREENE
dermoid. Solitary cysts are of comparatively rare occurrence. Most frequently involve lower pole. Urine examination is usually negative unless secondary infection of the pelvis occurs but a differential functional test may show diminished renal function due to pressure on the kidney. In the same manner pressure may cause a distorted pyelogram. Origin of these solitary cysts is of interest and is still a matter of dispute. Wood writes; "In chronic diffuse nephritis of the atrophic form, a group of tubes may be dilated. Apparently one or more of the larger tubes in the pyramids are obstructed and this causes dilatation of a corresponding group of tubes. Such a dilatation may be moderate in size or it may form cysts visible to the naked eye." While this is an adequate explanation for the smaller cysts, often multiple, which are frequently found at autopsy, below the capsule, in atrophic kidneys, it hardly explains the large solitary cysts appearing in an otherwise normal appearing kidney. Ziegler states that these single cysts are due to retention of secretion from a glomerulus from which its tubules have been cut off and do not function, although the rest of the kidney may be normal. Aschoff quotes Ruchert that all cysts of the kidney are due to congenital tissue malformation. Most of the other writers on the subject also quote this opinion of Ruchert as does Berman, but the latter differs from him in his conclusion that all the solitary cysts of the kidney are congenital. Dr. Edwin Beer in remarks concerning a case reported by Douglas said that in a very extensive study of cysts of the kidney he had arrived at the conclusion from serial section of several hundred cysts that cysts of 3 distinct types occurred in the kidney. The smallest cysts, never much larger than the head of a pin, were almost always derived from Malpighi's corpuscles and frequently at some part of the cyst small glomerular tufts could be seen more or less atrophied. The contents of these cysts were usually colloidal material with more or less lime salts. The cysts which were next in size, growing as big as small peas, were usually of tubular origin, and in the walls of these cysts showed an endothelial lining with here and there in the walls accumulations of smooth muscle fibres. The largest cyst of this type that he had studied was about the size of a hen's egg. Otto F. Kampmeier in an exhaustive study writes on a hitherto unrecognized mode of origin of congenital renal cysts. The study was based on the microscopic examination and study of 26 human embryos and foetuses ranging in age from 6 weeks to 5 months of intra-uterine
SOLITARY CYST OF KIDNEY WITH ADENO-CARCINOMA
155
life; post-mortem examination of 10 babies and 36 cadavers in the dissecting room. He enumerates his observations as follows: (1) The existence of a vestigial primary generation of a uriniferous tubule; (2) the occasional cystic transformation of such vestigial tubules; (3) the early communication of the next order of uriniferous tubules with collecting ducts of the corresponding order, namely the second (4) the temporary attachment of most of these tubules from the secondary collecting ducts to their reunion with the ducts of the fourth and fifth orders (5) the later permanent separation of these uriniferous tubules from these ducts and the cystic transformation of most of them; in other words the apparently constant appearance of renal cysts at a certain period of fetal life. A review of voluminous isolated unilateral cysts of the kidney of serous type, 95 in all, reported in the literature from 1830 to 1922, did not reveal one case in which any malignant degeneration was reported as occurring within the walls of the cyst. T . J. Kirwin reported an interesting case of calcified renal cyst. H . Viethen reports an unusual case of solitary cyst in horseshoe kidney. H.B. Sweetsen reports a case of suppuration in solitary cyst. Two cases of solitary cysts associated with calculi have been reported. One by Arnsworth-Davis and Dunhill and one by D . R. Roberts. A. B. Hepler offers some observations on the pathogenesis of solitary cysts based on 7 personal and 249 collected cases; 216 serous; 40 hemorrhagic. He believes the large, usually solitary cysts are acquired. They are not a distinct entity with a common etiology but the mechanism is essentially the same. Recognized pathological conditions cause them, but only when so situated as to produce a combination of group tubular obstruction and anemic degeneration of the parenchyma from circulatory disturbances in the same segment of kidney. In some, an additional factor is repeated prolonged hemorrhages into the same area. This conception explains the variation in size, number, contents, cyst wall and associated renal conditions on the basis of variation of the direct etiologic factor, amount of group tubular obstruction of vessels involved. It also explains the apparent absence of a direct etiologic factor in some, for the original lesion may become so involved in the process that all evidence is eventually lost. Among the features of cysts which lend support to this hypothesis are: (1) the average age incidence of 45 years, when vascular lesions and acquired lesions, such as tumor, are common. (2) the rather frequent association of these cysts with lesions, which might produce the conditions
156
WILLIAM
J.
EZICKSON AND LLOYD B. GREENE
assumed to be necessary for their formation. (3) The frequent presence in the kidney containing a so-called solitary cyst, of small cysts similar in every detail except size and indistinguishable from nephritic cysts. (4) The presence in the sac wall of groups of atrophied glomeruli and tubules indicating its origin from parenchyma which has undergone compression atrophy with a connective tissue substitution. (5) The presence of remnants of neoplasm in the walls of many of the hemorrhagic cysts as the only indication that tumor was concerned in their formation. (6) In many, the sudden onset and rapid growth of cysts which can be easily understood in the light of experimental work in which enormous diverticula formed in a few days. Finally by creating experimentally the conditions assumed to be necessary for cyst formation, he has been able to reproduce a large solitary cyst similar in every detail to those in the human kidney. The solitary cyst, in a woman 37, operated on by J. S. Ritter, contained a hypernephroma. I herewith wish to present this unusual case of solitary cyst of the kidney with adeno-carcinoma in the walls of the cyst. Case report. F. C., a male, aged 31 years, a presser's helper, was seen March 21, 1934. He complained of intermittent hematuria, the last attack being March 20, 1934. His physician said the urine was the color of grape juice. In August, 1933, while the patient was spading very hard ground, he was seized with a sudden sharp pain, which lasted 5 to 10 minutes, in his lower back. Several days later he noticed blood-stained urine, which continued about two weeks. He lost his position and while not working there was no hematuria. In February, 1934 he went back to work and the hematuria returned. The bleeding occurred 2 to 3 (unes every 5 to 8 days and was associated with low sacral pain, urgency, frequency and dysuria. He had lost 11 pounds in 4 months. The family history was negative. General physical examination was essentially negative. No mass could be palpated in the abdomen. The hemoglobin was 15.8 grams. The red blood cells numbered 5,100,000, white blood cells 9,400, polymorphonuclears 68, small lymphocytes 24 and large lymphocytes 8. The blood Wassermann was negative. The urea nitrogen was 13 and the blood sugar 102. The phthalein test showed an output of 60 per cent the first hour, 9 per cent the second hour, 2-hour total 69 per cent. Cystoscopic examination disclosed no residual urine. There was a prominent interureteric ridge, and moderate trabeculation of the bladder. Number 5 catheters passed eaily up both ureters. Phthalein (1 cc.) injected intravenously appeared from the right kidney in 5 minutes and from the left kidney
SOLITARY CYST OF KIDNEY WITH ADENO-CARCINOMA
157
in 9 minutes. The output from the right kidney in 15 minutes was 17 .5 per cent, the left kidney 10 per cent. Left pyelogram (fig. 1) revealed a thinning of the middle calyx with some pressure on the upper calyx as well. This was highly suggestive of a hypernephroma involving the upper pole. There was no dilatation of the renal pelvis, which was of the intrarenal type, nor was there any disturbance of the uretero-pelvic junction. The kidney was not markedly enlarged and was more or less of the vertical type. There was no evidence of obstruction to the catheter.
FIG. 1 FIG. 4 FIG. 1. Preoperative left pyelogram showing thinning of middle calyx with some pressure on upper calyx, suggestive of hypemephroma involving upper pole. No dilatation of renal pelvis, which was of intra-renal type, nor was there any disturbance of the uretero-pelvic junction. FIG. 4. Postoperative left pyelogram showing irregular area between upper calyces. The uretero-pelvic juncture is normal and uppermost calyx negative.
Right pyelogram was normal. Bacteriologic study of the urine from the right kidney showed many epithelial cells, a few leucocytes and occasional red blood cells. Urine from the left kidney contained many epithelial cells and a great many red blood cells. On March 30 through a left lumbar incision the kidney was easily exposed. A solitary tumor-cyst was found in the mid-portion of the kidney. About 60 cc. muddy, serous fluid was aspirated from the cyst. The cyst was easily enucleated and did not connect with the pelvis. The halves of the kidney were sutured together, the wound closed in layers, and a large rubber drain inserted. The specimen (fig. 2) was a smooth, round mass measuring 6 cm. in diameter. On section the wall was firm and white, varying about 1 cm. in thickness and surrounding a cavity. The inner portion of the wall was broken and necrotic.
FIG. 2. Photograph of cyst removed from left kidney
FIG. 3. Photomicrograph of tissue from wall of cyst 158
SOLITARY CYST OF KIDNEY WITH ADENO-CARCINOMA
159
Microscopic section (fig. 3) showed many small and large glandular elements. These were supported with a greater or less amount of fairly dense fibrous tissue. In some areas the growth took on a papillary form and in others it was found in solid masses. The cells were large and had large, light-staining nuclei. Few mitotic figures were found. The diagnosis was adeno-carcinoma. The convalescence was satisfactory and ten days after operation the patient was up in a chair. On April 13 a stereoscopic left pyelogram (fig. 4) revealed an irregular area between the upper calyces. The uretero-pelvic juncture was normal, and t he · uppermost calyx negative. An x-ray of the chest revealed a peribronchial thickening of the entire bronchial tree on the right side. This was distributed in irregular areas, but more or less uniform over the right bronchial tree. . The diaphragms were plainly visible and free from adhesions or fluid. There was no evidence of metastatic growths. The patient was discharged seventeen days after operation in excellent condition. Six months later he developed a persistent dry, hacking cough. An x-ray of the chest disclosed metastatic growths in the lungs. He was given several series of deep x-ray treatments to the chest and left kidney area, but this was of no avail and the patient died September 12, 1935.
2100 Walnut St., Philadelphia, Pa. Medical Arts Bldg., Philadelphia, Pa. REFERENCES AINSWORTH-DAVIS AND DUNHILL: Brit. Med. Jour., 1: 10, 1930. · DouGLAS: Ann. Surg., 76: 656, 1922. HEPLER: Surg., Gynec. and Obstet., 50: 668, 1930. KAMPMEIER: Surg., Gynec. and Obstet., 36: 208, 1923. KIRWIN: Jour. Urol., 15: 273, 1926. RIENHOFF: Johns Hop. Hosp. Bull., 33: 392, 1922. RITTER: Amer. Jour. Surg., 8: 1089, 1930. ROBERTS: Brit. Med. Jour., 2: 15, 1930. SWEETSEN: Minn. Med. Jour., 12: 786, 1929. VIETHEN: Ztschr. f. Chir., 53: 2655, 1926.