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AN UNUSUAL SUBSET OF CRYPTORCHIDISM: POSSIBLE END ORGAN FAILURE
0022-5347/99/1623-0983/0
THEJOURNAL
Vol. 162,983-985. September 1999 Printed in U S A .
O F UROLOGY
Copyright 0 1999 by AMERICANUROLOGICAL ASSOCIATION, INC.
Testes AN UNUSUAL SUBSET OF CRYPTORCHIDISM: POSSIBLE END
ORGAN
FAILURE FARUK HADZISELIMOVIC, HOWARD M. SNYDER
AND
DALE S. HUFF
From the Kindertagesklinik, Liestal, Switzerland, and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
ABSTRACT
Purpose: A paucity of germ cells exists in the cryptorchid gonad that usually correlates with a similar finding in the contralateral descended testis. However, we have noted a small number of boys with cryptorchidism in whom there is a significant difference between the histological evaluation of the cryptorchid testis and the normal descended testis that may indicate a different etiology. Materials and Methods: From 1986 to 1991, 1,426 boys with unilateral cryptorchidism underwent orchiopexy, of whom 752 also underwent bilateral testicular biopsy. Testicular volume and position, and patency of the processus vaginalis were examined. Biopsies were fixed in 2% glutaraldehyde and embedded in Epon. Semithin tissue sections were analyzed by 2 independent investigators. The number of total germ cells, gonocytes, adult dark and pale spermatogonia, primary spermatocytes and Leydig cells was assessed. Results: Of the 1,426 boys the undescended testis was on the right side in 726 and on the left side in 658 (52 versus 48%,p = 0068). Of the 752 boys who underwent bilateral biopsy 42 (5.6%) 1.1 to 16 years old (mean age plus or minus standard deviation 0 5.2 2 3.65) had a poor fertility index of less than 0.2 germ cell per tubule in the cryptorchid gonad, although the germ cell count in the descended testis was normal. Of the 42 testes in this special group of boys 30 (71%) were on the right side (Fisher’s exact test p <0.23), including 16 (38%)in an intra-abdominal or high canalicular position. The processus vaginalis was patent in 86%of the intra-abdominal testes and in 100%of those located at the tubercle but in only 25%of those in a pre-scrota1 position. While average germ cell count in the cryptorchid testis was 0.06 per tubule with abnormal germ cell maturation, number was normal (greater than 2 germ cells per tubule) in the contralateral descended testis with a normal distribution of adult dark and pale spermatogonia, and primary spermatocytes. Average volume of the cryptorchid testis was significantly less than that of the descended testis (1.20 ? 0.35 versus 1.60 5 0.68 mm.3, p <0.0001). Conclusions: Based on the normal scrotal testis the fertility prognosis is good in this small subgroup of boys with cryptorchidism. Rather than the usual endocrinopathy of cryptorchi&sm, the undescended testis in these boys may be the result of end organ failure. These patients with favorable fertility potential may be recognized only if each testis is biopsied at unilateral orchiopeq. KEY WORDS:testis, abnormalities, cryptorchidism, fertility
The incidence of cryptorchidism is increasing, and cur- undescended testes but a normal contralateral testis that rently 1.8% of all boys are affected.* Common complications suggests an excellent prognosis for fertility later in life. associated with cryptorchidism are an increased risk of infertility and testicular malignancy. The typical testicular PATIENTS AND METHODS histopathology of unilateral undescended testis, including a From 1986 to 1991, 752 boys with unilateral cryptorchidism decreased number of germ cells and germ cell maturational underwent orchiopexy and bilateral testicular biopsy in Philadefects, is more pronounced in bilateral undescended tesdelphia. None of the patients had been treated previously with tes.”” These features are also found in the contralateral hormones to induce testicular descent preoperatively. Semithin descended testis in boys with a unilateral undescended tes- biopsy histological sections were fixed in 2% glutaraldehyde, ti^.^ Severity of the abnormalities is directly proportional to embedded in Epon and independently analyzed by 2 investigabut less severe than those in undescended t e ~ t i sreflecting ,~ tors. We counted the total number of germ cells, gonocytes, the recognized transient hypogonadotropic hypogonadism adult dark and pale spermatogonia, and primary spermatocytes endocrinopathy of c r y p t o r ~ h i d i s m . ~Therefore, -~ most boys in at least 50 tubular cross sections as well as the number of with unilateral cryptorchidism and severe germ cell deple- Leydig cells. In addition, we noted the side and position of the tion in the undescended testis have a marked decrease in undescended testis, patency of the processus vaginalis and tescells in the contralateral descended testis and a poor progno- ticular volume of each testis, as measured at surgery. To charsis for fertility. We identified a subset of boys with unilateral acterize better unilateral cryptorchidism an additional age cryptorchidism and a severe decrease in germ cells in the matched group of 679 boys 1 to 16 years old with unilateral 983
984
UNUSUAL SUBSET OF CRWTORCHIDISM
cryptorchidism in Basel, Switzerland was included in the study. Statistical analysis was performed using the Fisher exact, Wilcoxon and Mann-Whitney U tests.
100
90 80
F p < 0.0001
RESULTS
Of the 752 boys with unilateral cryptorchidism who under60 went bilateral biopsy 42 (5.2%)1.1 to 16 years old (mean age m 50 plus or minus standard deviation 5.2 2 3.65)had less than 0.02 germ cell per tubule (mean 0.06) with abnormal germ cell maturation in the undescended testis. In addition, they had a normal count of greater than 2 germ cells per tubule as well as normal germ cell maturation in the contralateral descended testis. Marked Leydig cell hyperplasia in the cryptorchid testis was more pronounced when the testis was intra-abdominal. Of the 42 patients in this special cryptorchidism subset the undescended testis was on the right side in 30 (71'701,while it was on Special Subset unilateral cryptorchidism the right side in 370 (52%)of the other 710 treated in Philadelphia. This incidence is comparable to the 356 of 674 boys (53%) FIG. 2. Marked difference in incidence of intra-abdominaltestis in with unilateral undescended testis in the Basel group in whom special subset of boys with unilateral cryptorchidism compared with the undescended testis was on the right side. This difference in that in others with cryptorchidism. the subset and the remainder of the patients was statistically significant (Fisher's exact test p c0.023, fig. 1). We noted an increased incidence of intra-abdominal testes. Of the 42 boys in this unusual cryptorchidism subset 17 (38%) had an intra-abdominal testis versus 60 of the other 1,055 (6%) in our series with unilateral cryptorchidism (fig. 2). In another 23 patients in this subset the testis was located at the tubercle and only 3 of the 42 testes were pre-scrotal. The processus vaginalis was patent in 86%of the intra-abdominal testes and in 100%of those at the tubercle but in only 33% of the testes at the scrota1 entrance. Average volume of the undescended testis was significantly less than that of the contralateral descended testis (1.20 2 0.35 versus 1.60 -t 0.68 mm.3, p <0.0001). DISCUSSION
This group of boys with cryptorchidism is rare and unique because the unilateral descended testis is histologically normal. This unusual circumstance should provide an excellent possibility for fertility later in life, although the undescended cryptorchid testis has less than 0.2 germ cell per tubule. This prospect contrasts with that in boys with the usual type of unilateral cryptorchidism, in whom an undescended testis with less than 0.2 germ cell per tubule is associated with a descended testis that also has a significantly decreased number of germ cells.4 The bilateral poor germ cell count portends a poor prognosis for fertility in life.4 In the majority of boys with cryptorchidism Leydig cells are in an atrophic state, which indicates hypogonadotropic hyp~gonadisrn.'-~ The histological condition of Leydig cells in the unilateral
A
descended
undescended testis points to the cause of primary testicular damage. The adverse environmental position effect, involving higher temperature and so forth, to which the undescended testis is subjected induces hyperplasia of these cells. It is similar to other patients in whom the testis has been subjected to a toxic influence, such as chemotherapy, or another pathological A more likely hypothesis of the condition, such as vari~ocele.~ cause of this rare form of unilateral cryptorchidism is that ab-
90
80 71
-?.
70 60
60
52
m
52
53
right lelt Philadelphia
right
c 0
50
Q
0
g
100
pc0.026
80
-
undescended
FIG. 3. Descended testis in boys in special unilateral cryptorchidism subset was significantly larger than undescended testis.
B
too
TESTES
40
40
30 20
20 10
C
0 right Special Subset
lelt
right
left
unilateral cryptorchidism
left
Basel
FIG. 1. Special subset of boys with unilateral cryptorchidism in Philadelphia and Basel. A, predominance of right testis. B , no significant difference in incidence of unilateral cryptorchidism.
UNUSUAL SUBSET OF CRYPTORCHIDISM
dominal wall failure similar to that in congenital Spigelian hernia and cryptorchidism induces an abnormal inguinal canal.73 In this rare subgroup with unilateral cryptorchidism and severely decreased germ cell counts in the undescended testis a normal testis has been noted in boys as old as 16 years with cryptorchidism. This fact negates the notion that an undescended testis induces severe pathological testicular damage in the contralateral testis. In conclusion, this fairly rare subset of boys with unilateral cryptorchidism and an excellent prognosis for fertility may be identified only if each testis is biopsied at unilateral orchiopexy. REFERENCES
1. Cryptorchidism: a prospective study of 7,500 consecutive male births. 1984-1988.John Radcliffe Hospital Cryptorchidism Study Group. Arch. Dis. Child., 67: 892, 1992.
985
2. Hadziselimovic, F., Herzog, B. and Seguchi, H.: Surgical correction of cryptmhidism at 2 years: electron microscopic and morphometric investigations. J. Ped. Surg., 10: 19, 1975. 3. Huff, D. S., Hadziselimovic, F., Snyder, H. M., Blyth, B. and Duckett, J. W.: Early postnatal testicular maldevelopment in cryptorchidism. J. Urol., 146: 624, 1991. 4. Hadziselimovic, F. and Herzog, B.: Hodenerkrankungen im Kindesalter. Stuttgart: Hippokrates Verlag, 1990. 5. Gendrel, D., Job, J. C. and Roger, M.: Reduced post-natal rise of testosterone in plasma of cryptorchid infants. Ada Endocrinol., 8 9 372, 1978. 6. Baker, B. A., Morley, R. and Lucas, A.: Plasma testosterone levels in pre-term infants with cryptorchidism. Arch Dis. Child., 63: 1198, 1988. 7. Silberstein, P. A,, Kern, I. B. and Shi, E. C.: Congenital Spigelian hernia with cryptorchidism. J. Ped. Surg., 31: 1208, 1996. 8. Ostlie, D. J. and Zerella, J. T.: Undescended testicle associated with Spigelian hernia. J. Ped. Surg., 3 3 1426, 1998.
THEJOURNAL
Vol. 162,983-985. September 1999 Printed in U S A .
O F UROLOGY
Copyright 0 1999 by AMERICANUROLOGICAL ASSOCIATION, INC.
Testes AN UNUSUAL SUBSET OF CRYPTORCHIDISM: POSSIBLE END
ORGAN
FAILURE FARUK HADZISELIMOVIC, HOWARD M. SNYDER
AND
DALE S. HUFF
From the Kindertagesklinik, Liestal, Switzerland, and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
ABSTRACT
Purpose: A paucity of germ cells exists in the cryptorchid gonad that usually correlates with a similar finding in the contralateral descended testis. However, we have noted a small number of boys with cryptorchidism in whom there is a significant difference between the histological evaluation of the cryptorchid testis and the normal descended testis that may indicate a different etiology. Materials and Methods: From 1986 to 1991, 1,426 boys with unilateral cryptorchidism underwent orchiopexy, of whom 752 also underwent bilateral testicular biopsy. Testicular volume and position, and patency of the processus vaginalis were examined. Biopsies were fixed in 2% glutaraldehyde and embedded in Epon. Semithin tissue sections were analyzed by 2 independent investigators. The number of total germ cells, gonocytes, adult dark and pale spermatogonia, primary spermatocytes and Leydig cells was assessed. Results: Of the 1,426 boys the undescended testis was on the right side in 726 and on the left side in 658 (52 versus 48%,p = 0068). Of the 752 boys who underwent bilateral biopsy 42 (5.6%) 1.1 to 16 years old (mean age plus or minus standard deviation 0 5.2 2 3.65) had a poor fertility index of less than 0.2 germ cell per tubule in the cryptorchid gonad, although the germ cell count in the descended testis was normal. Of the 42 testes in this special group of boys 30 (71%) were on the right side (Fisher’s exact test p <0.23), including 16 (38%)in an intra-abdominal or high canalicular position. The processus vaginalis was patent in 86%of the intra-abdominal testes and in 100%of those located at the tubercle but in only 25%of those in a pre-scrota1 position. While average germ cell count in the cryptorchid testis was 0.06 per tubule with abnormal germ cell maturation, number was normal (greater than 2 germ cells per tubule) in the contralateral descended testis with a normal distribution of adult dark and pale spermatogonia, and primary spermatocytes. Average volume of the cryptorchid testis was significantly less than that of the descended testis (1.20 ? 0.35 versus 1.60 5 0.68 mm.3, p <0.0001). Conclusions: Based on the normal scrotal testis the fertility prognosis is good in this small subgroup of boys with cryptorchidism. Rather than the usual endocrinopathy of cryptorchi&sm, the undescended testis in these boys may be the result of end organ failure. These patients with favorable fertility potential may be recognized only if each testis is biopsied at unilateral orchiopeq. KEY WORDS:testis, abnormalities, cryptorchidism, fertility
The incidence of cryptorchidism is increasing, and cur- undescended testes but a normal contralateral testis that rently 1.8% of all boys are affected.* Common complications suggests an excellent prognosis for fertility later in life. associated with cryptorchidism are an increased risk of infertility and testicular malignancy. The typical testicular PATIENTS AND METHODS histopathology of unilateral undescended testis, including a From 1986 to 1991, 752 boys with unilateral cryptorchidism decreased number of germ cells and germ cell maturational underwent orchiopexy and bilateral testicular biopsy in Philadefects, is more pronounced in bilateral undescended tesdelphia. None of the patients had been treated previously with tes.”” These features are also found in the contralateral hormones to induce testicular descent preoperatively. Semithin descended testis in boys with a unilateral undescended tes- biopsy histological sections were fixed in 2% glutaraldehyde, ti^.^ Severity of the abnormalities is directly proportional to embedded in Epon and independently analyzed by 2 investigabut less severe than those in undescended t e ~ t i sreflecting ,~ tors. We counted the total number of germ cells, gonocytes, the recognized transient hypogonadotropic hypogonadism adult dark and pale spermatogonia, and primary spermatocytes endocrinopathy of c r y p t o r ~ h i d i s m . ~Therefore, -~ most boys in at least 50 tubular cross sections as well as the number of with unilateral cryptorchidism and severe germ cell deple- Leydig cells. In addition, we noted the side and position of the tion in the undescended testis have a marked decrease in undescended testis, patency of the processus vaginalis and tescells in the contralateral descended testis and a poor progno- ticular volume of each testis, as measured at surgery. To charsis for fertility. We identified a subset of boys with unilateral acterize better unilateral cryptorchidism an additional age cryptorchidism and a severe decrease in germ cells in the matched group of 679 boys 1 to 16 years old with unilateral 983
984
UNUSUAL SUBSET OF CRWTORCHIDISM
cryptorchidism in Basel, Switzerland was included in the study. Statistical analysis was performed using the Fisher exact, Wilcoxon and Mann-Whitney U tests.
100
90 80
F p < 0.0001
RESULTS
Of the 752 boys with unilateral cryptorchidism who under60 went bilateral biopsy 42 (5.2%)1.1 to 16 years old (mean age m 50 plus or minus standard deviation 5.2 2 3.65)had less than 0.02 germ cell per tubule (mean 0.06) with abnormal germ cell maturation in the undescended testis. In addition, they had a normal count of greater than 2 germ cells per tubule as well as normal germ cell maturation in the contralateral descended testis. Marked Leydig cell hyperplasia in the cryptorchid testis was more pronounced when the testis was intra-abdominal. Of the 42 patients in this special cryptorchidism subset the undescended testis was on the right side in 30 (71'701,while it was on Special Subset unilateral cryptorchidism the right side in 370 (52%)of the other 710 treated in Philadelphia. This incidence is comparable to the 356 of 674 boys (53%) FIG. 2. Marked difference in incidence of intra-abdominaltestis in with unilateral undescended testis in the Basel group in whom special subset of boys with unilateral cryptorchidism compared with the undescended testis was on the right side. This difference in that in others with cryptorchidism. the subset and the remainder of the patients was statistically significant (Fisher's exact test p c0.023, fig. 1). We noted an increased incidence of intra-abdominal testes. Of the 42 boys in this unusual cryptorchidism subset 17 (38%) had an intra-abdominal testis versus 60 of the other 1,055 (6%) in our series with unilateral cryptorchidism (fig. 2). In another 23 patients in this subset the testis was located at the tubercle and only 3 of the 42 testes were pre-scrotal. The processus vaginalis was patent in 86%of the intra-abdominal testes and in 100%of those at the tubercle but in only 33% of the testes at the scrota1 entrance. Average volume of the undescended testis was significantly less than that of the contralateral descended testis (1.20 2 0.35 versus 1.60 -t 0.68 mm.3, p <0.0001). DISCUSSION
This group of boys with cryptorchidism is rare and unique because the unilateral descended testis is histologically normal. This unusual circumstance should provide an excellent possibility for fertility later in life, although the undescended cryptorchid testis has less than 0.2 germ cell per tubule. This prospect contrasts with that in boys with the usual type of unilateral cryptorchidism, in whom an undescended testis with less than 0.2 germ cell per tubule is associated with a descended testis that also has a significantly decreased number of germ cells.4 The bilateral poor germ cell count portends a poor prognosis for fertility in life.4 In the majority of boys with cryptorchidism Leydig cells are in an atrophic state, which indicates hypogonadotropic hyp~gonadisrn.'-~ The histological condition of Leydig cells in the unilateral
A
descended
undescended testis points to the cause of primary testicular damage. The adverse environmental position effect, involving higher temperature and so forth, to which the undescended testis is subjected induces hyperplasia of these cells. It is similar to other patients in whom the testis has been subjected to a toxic influence, such as chemotherapy, or another pathological A more likely hypothesis of the condition, such as vari~ocele.~ cause of this rare form of unilateral cryptorchidism is that ab-
90
80 71
-?.
70 60
60
52
m
52
53
right lelt Philadelphia
right
c 0
50
Q
0
g
100
pc0.026
80
-
undescended
FIG. 3. Descended testis in boys in special unilateral cryptorchidism subset was significantly larger than undescended testis.
B
too
TESTES
40
40
30 20
20 10
C
0 right Special Subset
lelt
right
left
unilateral cryptorchidism
left
Basel
FIG. 1. Special subset of boys with unilateral cryptorchidism in Philadelphia and Basel. A, predominance of right testis. B , no significant difference in incidence of unilateral cryptorchidism.
UNUSUAL SUBSET OF CRYPTORCHIDISM
dominal wall failure similar to that in congenital Spigelian hernia and cryptorchidism induces an abnormal inguinal canal.73 In this rare subgroup with unilateral cryptorchidism and severely decreased germ cell counts in the undescended testis a normal testis has been noted in boys as old as 16 years with cryptorchidism. This fact negates the notion that an undescended testis induces severe pathological testicular damage in the contralateral testis. In conclusion, this fairly rare subset of boys with unilateral cryptorchidism and an excellent prognosis for fertility may be identified only if each testis is biopsied at unilateral orchiopexy. REFERENCES
1. Cryptorchidism: a prospective study of 7,500 consecutive male births. 1984-1988.John Radcliffe Hospital Cryptorchidism Study Group. Arch. Dis. Child., 67: 892, 1992.
985
2. Hadziselimovic, F., Herzog, B. and Seguchi, H.: Surgical correction of cryptmhidism at 2 years: electron microscopic and morphometric investigations. J. Ped. Surg., 10: 19, 1975. 3. Huff, D. S., Hadziselimovic, F., Snyder, H. M., Blyth, B. and Duckett, J. W.: Early postnatal testicular maldevelopment in cryptorchidism. J. Urol., 146: 624, 1991. 4. Hadziselimovic, F. and Herzog, B.: Hodenerkrankungen im Kindesalter. Stuttgart: Hippokrates Verlag, 1990. 5. Gendrel, D., Job, J. C. and Roger, M.: Reduced post-natal rise of testosterone in plasma of cryptorchid infants. Ada Endocrinol., 8 9 372, 1978. 6. Baker, B. A., Morley, R. and Lucas, A.: Plasma testosterone levels in pre-term infants with cryptorchidism. Arch Dis. Child., 63: 1198, 1988. 7. Silberstein, P. A,, Kern, I. B. and Shi, E. C.: Congenital Spigelian hernia with cryptorchidism. J. Ped. Surg., 31: 1208, 1996. 8. Ostlie, D. J. and Zerella, J. T.: Undescended testicle associated with Spigelian hernia. J. Ped. Surg., 3 3 1426, 1998.