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Needle Biopsy in the Diagnosis of Testicular Leukemia in Children
0022-534 7/89/1415-1169$2.00/0 Vol.141, May
THE JOURNAL OF UROLOGY
,
Copyright © 1989 by The Williams & Wilkins Co.
Printed in U.S.A.
NEEDLE BIOPSY IN THE DIAGNOSIS OF TESTICULAR LEUKEMIA IN CHILDREN BHAGWANT GILL, STANLEY KOGAN, BARRY ROSSMAN, MARIA SANTORINEOU, EVA RADEL, EDWARD REDA AND SELWYN LEVITT From the Departments of Urology and Pediatrics, The Jack D. Weiler Hospital of the Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, and Westchester Medical Center, Valhalla, New York
ABSTRACT
Aggressive chemotherapy in patients with acute lymphoblastic leukemia has resulted in a marked upsurge in patient survival. In the course of their management, testicular biopsy and rebiopsy have an important role. We evaluated the histological findings in 50 sets of open wedge and simultaneous needle core biopsy specimens from 44 testes of children with acute lymphoblastic leukemia to determine the accuracy of the needle biopsy technique in the evaluation of testis involvement in acute lymphoblastic leukemia. We conclude that needle biopsy of the testis in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional open wedge biopsy, and it may have a role in the management of children with acute lymphoblastic leukemia. (J. Urol., 141: 1169-1171, 1989)
With the advent of aggressive chemotherapy in the treatment of acute lymphoblastic leukemia, there has been a dramatic upsurge in patient survival. However, extramedullary relapse continues to be a major obstacle to the adequate control of this disease. With routine central nervous system prophylaxis using intrathecal chemotherapy with or without radiation, initial ~]j complete remission has been achieved in 97 per cent of these i:1 children and continuous complete remission in 61 per cent, o, with a 5-year survival rate exceeding 50 per cent.1•2 In children who have extramedullary leukemic relapse the testis not only ~'2.·,· is a site for harboring occult leukemic infiltrates and one that •• . is most resistant to treatment3 •4 but it may also be the site :,J responsible for later systemic relapse. 6- 9 Stoffel and associates ,•1 in 1975 reported overt testicular involvement in 13 of 163 ~ patients (8 per cent) with acute lymphoblastic leukemia. 5 The ~~ ,;: frequency of occult testicular infiltration reported recently was [_(_:_(,: 6.5 per cent (3 of 46 children). 10 At autopsy of patients with - acute lymphoblastic leukemia microscopic evidence of testicular involvement has varied between 27 and 92 per cent. 4• 7 • 11• 12 Givler found microscopic testicular infiltration at autopsy in 64.3 per cent of 140 male patients with acute lymphoblastic leukemia, 7 and Stoffel and associates reported similar involvement in 70 per cent of their autopsies. 6 Therefore, testicular leukemia has been considered an ominous prognostic sign. Stoffel and associates reported the testis as the first site of relapse in 8 of 13 patients (62 per cent). 5 Therefore, early detection of testicular involvement and prompt therapy are important. This has prompted most oncologists currently to refer patients routinely for testicular biopsies at the conclusion of chemotherapy to exclude occult testicular involvement. Furthermore, with better survival and chemotherapy sometimes repeat testicular biopsies have been indicated. The established means to diagnose testicular leukemia has been open wedge testicular biopsy. Needle biopsy is being used in the diagnosis of almost all types of neoplastic lesions and it seems a simple means to rebiopsy such lesions. We evaluated the histological findings in 50 sets of biopsies in 22 boys with acute lymphoblastic leukemia between 2 and 21 years old (mean age 10.5 years) to determine the accuracy of the needle biopsy technique in the evaluation of testicular involvement with acute lymphoblastic leukemia. Biopsies were performed by open peripheral wedge excision and by a simultaneous core needle
biopsy technique. Histological results were compared to determine the accuracy of each method. MATERIALS AND METHODS
Between 1978 and 1986, 22 boys with acute lymphoblastic leukemia were referred to the pediatric urology service for testicular biopsies to exclude leukemic testicular involvement. Repeat biopsies were taken from 4 boys during followup. Patient age ranged from 2 to 21 years, with a mean age of 10.5 years. Fifty sets of wedge and core biopsies were performed in 44 testes and are the subject of this study. After the diagnosis of acute lymphoblastic leukemia was established, remission was induced by varying chemotherapy regimens. In addition, most children received 1,800 to 2,400 rad of radiotherapy to the cranium along with 6 to 7 doses of intrathecal methotrexate for central nervous system prophylaxis. More recent patients with good prognosis did not receive cranial radiotherapy. Testicular biopsies to detect possible occult leukemic infiltrates were performed before discontinuation of m:aintainence chemotherapy after 2 or 3 years of continuous complete remission. In 2 boys with the leukemia-lymphoma syndrome biopsies were performed at 4 to 5 months after diagnosis while in hematological remission. Testicular biopsies were repeated in 4 boys at the first sign of testicular enlargement or if the enlargement persisted after further treatment for testicular leukemia. In each case after the testis was explored a conventional peripheral wedge biopsy and a Tru-Cut* needle core biopsy were performed bilaterally. A total of 50 sets of biopsies was available for pathological evaluation to correlate the accuracy of each technique. RESULTS
Among the 38 testes that were normal bilaterally on initial clinical examination, the wedge and the core biopsies showed no evidence of leukemic infiltration in 36 sets of biopsies. In 1 instance the needle core biopsy was insufficient for adequate analysis. In 1 patient the core biopsy of the right testis showed leukemic infiltration but the wedge biopsy of both testes and the core biopsy of the left testis were normal. Review of these slides by another pathologist indicated a crush artifact and, thus, the patient did not receive further treatment. Within 2 years this patient had unilateral testicular enlargement, and * Travenol Laboratories, Inc., Deerfield, Illinois.
Accepted for publication November 23, 1988. 1169
1170
GILL AND ASSOCIATES
repeat wedge and core biopsies from both testes showed leukemic infiltration (case 1). Of the 3 boys who initially presented with unilateral testicular enlargement 2 had testicular relapse while still on the initial maintenance chemotherapy. One patient presented initially with normal testes bilaterally and later had testicular involvement during remission while off chemotherapy (see table). CASE REPORTS
Case 1. C. A. was diagnosed to have acute lymphoblastic leukemia when he was 9 years old. Bilateral wedge and the left core needle biopsies of the clinically benign testes when he was 11 years old were normal. However, the right core biopsy showed focal leukemic infiltrate. Controversy existed whether the histological finding was a crush artifact and no treatment was instituted. However, 18 months later left testicular enlargement developed, and the wedge and core biopsies of the left testis showed diffuse leukemic infiltration, while similar biopsies from the right testis showed focal leukemic infiltrate. Radiotherapy (2,400 rad) to the gonads and reinduction of chemotherapy resulted in normalization of testis size and a normal wedge biopsy 18 months later. The patient was in complete remission 3 years later. Case 2. D. P. was diagnosed to have acute lymphoblastic leukemia when he was 3 years old. Right testicular enlargement developed 1 year after discontinuation of chemotherapy. The left testis was clinically normal. Open wedge and core needle biopsies of the right testis showed diffuse infiltration, while the wedge biopsy of the left testis was normal and the core biopsy of the left normal-sized testis was considered insufficient for adequate analysis. After reinduction of chemotherapy and 2,000 rad radiotherapy to the testis, the testicular enlargement persisted, and repeat biopsies still remained positive on the right side and negative on the left side. Right orchiectomy confirmed diffuse testicular involvement with paratesticular infiltration. Despite an intra-abdominal recurrence, with intense chemotherapy and local radiotherapy to the abdomen the patient was in remission 2 years later while off treatment, with a clinically normal left testis. Case 3. E. B. was diagnosed to have acute lymphoblastic leukemia when he was 6 years old. Left testicular firmness developed 14 months later while on maintenance chemotherapy. The right testis was clinically benign and of normal size. Bilateral open wedge and core needle biopsies all showed diffuse leukemic infiltration in both testes. Despite further chemotherapy and local radiation therapy to both testes, left orchiectomy became necessary due to persistant leukemic infiltration at the repeat biopsy. The wedge and core biopsies of the right testis at this time were negative and he had a clinically normal testis. However, the patient died of sepsis 1 year later. No postmortem examination was obtained. Case 4. F. K. had acute lymphoblastic leukemia when he was 8 years old. Two years later, while in hematological remission on maintenance chemotherapy, left testicular enlargement developed. Wedge and core biopsies of the left testis showed diffuse leukemic infiltration, while similar biopsies from the right testis were normal. Subsequent central nervous system and bone marrow relapse responded to intense chemotherapy
and he recently underwent bone marrow transplantation 4 years after initial testis relapse. DISCUSSION
Histological examination of biopsy specimens in patients with leukemic involvement of the testes classically reveals massive diffuse interstitial cell infiltration with variable degrees of invasion and destruction of the seminiferous tubules. At times cellular infiltration may involve the tunica albuginea and the paratesticular tissue. False negative biopsies are reported in 10 per cent of the cases. 1 This results from difficulty encountered in identifying some light interstitial infiltrates as true blast cells and to occasional focal distribution of leukemic infiltrates in some patients. False positive biopsies can result from crushing of the biopsy specimen causing damage to germ cells, which may mimic blast cells histologically. This was noted in 1 of our wedge biopsy specimens. A second wedge biopsy and the core needle biopsy from the same testis in this patient were normal. In our series of 22 boys with acute lymphoblastic leukemia who underwent open wedge and needle core biopsies both techniques were reliable. All 50 wedge biopsies were adequate for pathological examination. Of the 50 core needle biopsies only 2 were considered insufficient for accurate pathological evaluation. In both instances these biopsies were from smaller than normal-sized testes. The large size of the biopsy needle caused the difficulty in obtaining an adequate specimen. All core biopsies from normal-sized and enlarged testes were adequate for histological examination. In all 4 instances of enlarged testes the open wedge and needle core biopsies showed diffuse leukemic infiltration in the ipsilateral testis. Of the specimens from the contralateral normal-sized testis both biopsies in 1 instance showed focal infiltration and in the other 3 patients both sets of contralateral biopsies were normal. Therefore, in patients with unilaterally enlarged testes the 2 biopsy techniques correlated not only on the ipsilateral enlarged side but also on the contralateral normal side. In children with clinically normal-sized testes bilaterally, when the wedge biopsy was normal so was the core biopsy in all but 1 instance. In this patient with clinically normal testes bilaterally only the core needle biopsy showed evidence of focal leukemic infiltration. This child had overt testicular leukemia 18 months later. We conclude that core needle biopsy of the testes in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional wedge biopsy. Layfield and associates previously reported a similar review of 11 boys with acute lymphoblastic leukemia who underwent percutaneous fine needle aspiration biopsy and simultaneous open wedge biopsy of the testes. 13 In each instance the aspiration cytology diagnosis corresponded to the histological diagnosis, attesting to the reliability of this procedure. Their results and ours suggest that needle biopsy findings accurately reflect the findings encountered in conventional open wedge biopsy and that a false negative biopsy due to a sampling error is unlikely to occur. Although our study was done to validate the safety and efficacy of the needle biopsy technique in preparation for adoption of a percutaneous technique, fine needle biopsy appears to be more
Results
Normal testis bilat.: Subsequent unilat. testis enlargement Unilat. testis enlargement: Persistent testis enlargement
No. Pts.
Sets Biopsies
19
38
1
2
3
6
2
4
Biopsy Results 1 needle biopsy insufficient, 1 pos. (?) core, neg. wedge unilat. Pos. needle, pos. wedge bilat. Wedge and needle correlated in 5 biopsies, 1 needle biopsy insufficient on normal side Wedge and needle biopsies correlated in all cases
NEEDLE BIOPSY IN DIAGNOSIS OF TESTICULAR LEUKEMIA IN CHILDREN
attractive and may allow for ambulatory biopsy in children without using general anesthesia.
REFERENCES
1. Ortega, J. J., Javier, G. and Toran N.: Testicular infiltrates in children with acute lymphoblastic leukemia: a prospective study. Med. Ped. Oncol., 12: 386, 1984. 2. Simone, J.: Acute lymphocytic leukemia in childhood. Sem. Hematol., 11: 25, 1974. 3. Fernandez, C. H. and Sutow, W. W.: Irradiation and chemotherapy in pediatric tumors. In: Textbook of Radiotherapy, 2nd ed. Edited by G. H. Fletcher. Philadelphia: Lea & Febiger, chapt. 8, p. 561, 1973. 4. Finkelstein, J. Z., Dyment, P. G. and Hammond, G. D.: Leukemic infiltration of the testes during bone marrow remission. Pediatrics, 43: 1042, 1969. 5. Stoffel, T. J., Nesbit, M. E. and Levitt, S. H.: Extramedullary involvement of the testes in childhood leukemia. Cancer, 35: 1203, 1975. 6. Sharp, H. L., Nesbit, M. E., D' Angio, G. J. and Krivit, W.: Addition of local radiation after bone marrow remission in acute leukemia in children. Cancer, 20: 1403, 1967. 7. Givler, R. L.: Testicular involvement in leukemia and lymphoma.
Cancer, 23: 1290, 1969. 8. Mathe, G., Schwarzenberg, L., Mery, A. M., Cattan, A., Schneider, M., Amie!, J. L., Schlumberger, J. R., Poisson, J. and Wajcner, G.: Extensive histological and cytological survey of patients with acute leukemia in "complete remission". Brit. Med. J., 1: 640, 1966. 9. Nies, B. A., Bodey, G. P., Thomas, L.B., Brecher, G. and Freireich, E. J.: The persistence of extramedullary leukemic infiltrates during bone marrow remission of acute leukemia. Blood, 26: 133, 1965. 10. Ise, T., Kishi, K., lmashuku, S., Tsukada, M., Tsukimoto, I., Tsujino, G., Bessho, F., Tanaka, H., Miyazaki, S., Sakurai, M., Taguchi, N. and Muchi, M.: Testicular histology and function following long-term chemotherapy of acute leukemia in children and outcome of the patients who received testicular biopsy. Amer. J. Ped. Hemat. Oncol., 8: 288, 1986. 11. Haggar, R. A., MacMillan, A. B. and Thompson, D. C.: Leukemic infiltration of testis. Canad. J. Surg., 12: 197, 1969. 12. Sullivan, M. P. and Hrgovcic, M.: Extramedullary leukemia. In: Clinical Pediatric Oncology. Edited by W.W. Sutow, T. J. Vietti and D. J. Fernbach. St. Louis: The C. V. Mosby Co., p. 227, 1973. 13. Layfield, L. J., Hilborne, L. H., Ljung, B.-M., Feig, S. and Ehrlich, R. M.: Use of fine needle aspiration cytology for the diagnosis of testicular relapse in patients with acute lymphoblastic leukemia. J. Urol., 139: 1020, 1988.
THE JOURNAL OF UROLOGY
,
Copyright © 1989 by The Williams & Wilkins Co.
Printed in U.S.A.
NEEDLE BIOPSY IN THE DIAGNOSIS OF TESTICULAR LEUKEMIA IN CHILDREN BHAGWANT GILL, STANLEY KOGAN, BARRY ROSSMAN, MARIA SANTORINEOU, EVA RADEL, EDWARD REDA AND SELWYN LEVITT From the Departments of Urology and Pediatrics, The Jack D. Weiler Hospital of the Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, and Westchester Medical Center, Valhalla, New York
ABSTRACT
Aggressive chemotherapy in patients with acute lymphoblastic leukemia has resulted in a marked upsurge in patient survival. In the course of their management, testicular biopsy and rebiopsy have an important role. We evaluated the histological findings in 50 sets of open wedge and simultaneous needle core biopsy specimens from 44 testes of children with acute lymphoblastic leukemia to determine the accuracy of the needle biopsy technique in the evaluation of testis involvement in acute lymphoblastic leukemia. We conclude that needle biopsy of the testis in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional open wedge biopsy, and it may have a role in the management of children with acute lymphoblastic leukemia. (J. Urol., 141: 1169-1171, 1989)
With the advent of aggressive chemotherapy in the treatment of acute lymphoblastic leukemia, there has been a dramatic upsurge in patient survival. However, extramedullary relapse continues to be a major obstacle to the adequate control of this disease. With routine central nervous system prophylaxis using intrathecal chemotherapy with or without radiation, initial ~]j complete remission has been achieved in 97 per cent of these i:1 children and continuous complete remission in 61 per cent, o, with a 5-year survival rate exceeding 50 per cent.1•2 In children who have extramedullary leukemic relapse the testis not only ~'2.·,· is a site for harboring occult leukemic infiltrates and one that •• . is most resistant to treatment3 •4 but it may also be the site :,J responsible for later systemic relapse. 6- 9 Stoffel and associates ,•1 in 1975 reported overt testicular involvement in 13 of 163 ~ patients (8 per cent) with acute lymphoblastic leukemia. 5 The ~~ ,;: frequency of occult testicular infiltration reported recently was [_(_:_(,: 6.5 per cent (3 of 46 children). 10 At autopsy of patients with - acute lymphoblastic leukemia microscopic evidence of testicular involvement has varied between 27 and 92 per cent. 4• 7 • 11• 12 Givler found microscopic testicular infiltration at autopsy in 64.3 per cent of 140 male patients with acute lymphoblastic leukemia, 7 and Stoffel and associates reported similar involvement in 70 per cent of their autopsies. 6 Therefore, testicular leukemia has been considered an ominous prognostic sign. Stoffel and associates reported the testis as the first site of relapse in 8 of 13 patients (62 per cent). 5 Therefore, early detection of testicular involvement and prompt therapy are important. This has prompted most oncologists currently to refer patients routinely for testicular biopsies at the conclusion of chemotherapy to exclude occult testicular involvement. Furthermore, with better survival and chemotherapy sometimes repeat testicular biopsies have been indicated. The established means to diagnose testicular leukemia has been open wedge testicular biopsy. Needle biopsy is being used in the diagnosis of almost all types of neoplastic lesions and it seems a simple means to rebiopsy such lesions. We evaluated the histological findings in 50 sets of biopsies in 22 boys with acute lymphoblastic leukemia between 2 and 21 years old (mean age 10.5 years) to determine the accuracy of the needle biopsy technique in the evaluation of testicular involvement with acute lymphoblastic leukemia. Biopsies were performed by open peripheral wedge excision and by a simultaneous core needle
biopsy technique. Histological results were compared to determine the accuracy of each method. MATERIALS AND METHODS
Between 1978 and 1986, 22 boys with acute lymphoblastic leukemia were referred to the pediatric urology service for testicular biopsies to exclude leukemic testicular involvement. Repeat biopsies were taken from 4 boys during followup. Patient age ranged from 2 to 21 years, with a mean age of 10.5 years. Fifty sets of wedge and core biopsies were performed in 44 testes and are the subject of this study. After the diagnosis of acute lymphoblastic leukemia was established, remission was induced by varying chemotherapy regimens. In addition, most children received 1,800 to 2,400 rad of radiotherapy to the cranium along with 6 to 7 doses of intrathecal methotrexate for central nervous system prophylaxis. More recent patients with good prognosis did not receive cranial radiotherapy. Testicular biopsies to detect possible occult leukemic infiltrates were performed before discontinuation of m:aintainence chemotherapy after 2 or 3 years of continuous complete remission. In 2 boys with the leukemia-lymphoma syndrome biopsies were performed at 4 to 5 months after diagnosis while in hematological remission. Testicular biopsies were repeated in 4 boys at the first sign of testicular enlargement or if the enlargement persisted after further treatment for testicular leukemia. In each case after the testis was explored a conventional peripheral wedge biopsy and a Tru-Cut* needle core biopsy were performed bilaterally. A total of 50 sets of biopsies was available for pathological evaluation to correlate the accuracy of each technique. RESULTS
Among the 38 testes that were normal bilaterally on initial clinical examination, the wedge and the core biopsies showed no evidence of leukemic infiltration in 36 sets of biopsies. In 1 instance the needle core biopsy was insufficient for adequate analysis. In 1 patient the core biopsy of the right testis showed leukemic infiltration but the wedge biopsy of both testes and the core biopsy of the left testis were normal. Review of these slides by another pathologist indicated a crush artifact and, thus, the patient did not receive further treatment. Within 2 years this patient had unilateral testicular enlargement, and * Travenol Laboratories, Inc., Deerfield, Illinois.
Accepted for publication November 23, 1988. 1169
1170
GILL AND ASSOCIATES
repeat wedge and core biopsies from both testes showed leukemic infiltration (case 1). Of the 3 boys who initially presented with unilateral testicular enlargement 2 had testicular relapse while still on the initial maintenance chemotherapy. One patient presented initially with normal testes bilaterally and later had testicular involvement during remission while off chemotherapy (see table). CASE REPORTS
Case 1. C. A. was diagnosed to have acute lymphoblastic leukemia when he was 9 years old. Bilateral wedge and the left core needle biopsies of the clinically benign testes when he was 11 years old were normal. However, the right core biopsy showed focal leukemic infiltrate. Controversy existed whether the histological finding was a crush artifact and no treatment was instituted. However, 18 months later left testicular enlargement developed, and the wedge and core biopsies of the left testis showed diffuse leukemic infiltration, while similar biopsies from the right testis showed focal leukemic infiltrate. Radiotherapy (2,400 rad) to the gonads and reinduction of chemotherapy resulted in normalization of testis size and a normal wedge biopsy 18 months later. The patient was in complete remission 3 years later. Case 2. D. P. was diagnosed to have acute lymphoblastic leukemia when he was 3 years old. Right testicular enlargement developed 1 year after discontinuation of chemotherapy. The left testis was clinically normal. Open wedge and core needle biopsies of the right testis showed diffuse infiltration, while the wedge biopsy of the left testis was normal and the core biopsy of the left normal-sized testis was considered insufficient for adequate analysis. After reinduction of chemotherapy and 2,000 rad radiotherapy to the testis, the testicular enlargement persisted, and repeat biopsies still remained positive on the right side and negative on the left side. Right orchiectomy confirmed diffuse testicular involvement with paratesticular infiltration. Despite an intra-abdominal recurrence, with intense chemotherapy and local radiotherapy to the abdomen the patient was in remission 2 years later while off treatment, with a clinically normal left testis. Case 3. E. B. was diagnosed to have acute lymphoblastic leukemia when he was 6 years old. Left testicular firmness developed 14 months later while on maintenance chemotherapy. The right testis was clinically benign and of normal size. Bilateral open wedge and core needle biopsies all showed diffuse leukemic infiltration in both testes. Despite further chemotherapy and local radiation therapy to both testes, left orchiectomy became necessary due to persistant leukemic infiltration at the repeat biopsy. The wedge and core biopsies of the right testis at this time were negative and he had a clinically normal testis. However, the patient died of sepsis 1 year later. No postmortem examination was obtained. Case 4. F. K. had acute lymphoblastic leukemia when he was 8 years old. Two years later, while in hematological remission on maintenance chemotherapy, left testicular enlargement developed. Wedge and core biopsies of the left testis showed diffuse leukemic infiltration, while similar biopsies from the right testis were normal. Subsequent central nervous system and bone marrow relapse responded to intense chemotherapy
and he recently underwent bone marrow transplantation 4 years after initial testis relapse. DISCUSSION
Histological examination of biopsy specimens in patients with leukemic involvement of the testes classically reveals massive diffuse interstitial cell infiltration with variable degrees of invasion and destruction of the seminiferous tubules. At times cellular infiltration may involve the tunica albuginea and the paratesticular tissue. False negative biopsies are reported in 10 per cent of the cases. 1 This results from difficulty encountered in identifying some light interstitial infiltrates as true blast cells and to occasional focal distribution of leukemic infiltrates in some patients. False positive biopsies can result from crushing of the biopsy specimen causing damage to germ cells, which may mimic blast cells histologically. This was noted in 1 of our wedge biopsy specimens. A second wedge biopsy and the core needle biopsy from the same testis in this patient were normal. In our series of 22 boys with acute lymphoblastic leukemia who underwent open wedge and needle core biopsies both techniques were reliable. All 50 wedge biopsies were adequate for pathological examination. Of the 50 core needle biopsies only 2 were considered insufficient for accurate pathological evaluation. In both instances these biopsies were from smaller than normal-sized testes. The large size of the biopsy needle caused the difficulty in obtaining an adequate specimen. All core biopsies from normal-sized and enlarged testes were adequate for histological examination. In all 4 instances of enlarged testes the open wedge and needle core biopsies showed diffuse leukemic infiltration in the ipsilateral testis. Of the specimens from the contralateral normal-sized testis both biopsies in 1 instance showed focal infiltration and in the other 3 patients both sets of contralateral biopsies were normal. Therefore, in patients with unilaterally enlarged testes the 2 biopsy techniques correlated not only on the ipsilateral enlarged side but also on the contralateral normal side. In children with clinically normal-sized testes bilaterally, when the wedge biopsy was normal so was the core biopsy in all but 1 instance. In this patient with clinically normal testes bilaterally only the core needle biopsy showed evidence of focal leukemic infiltration. This child had overt testicular leukemia 18 months later. We conclude that core needle biopsy of the testes in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional wedge biopsy. Layfield and associates previously reported a similar review of 11 boys with acute lymphoblastic leukemia who underwent percutaneous fine needle aspiration biopsy and simultaneous open wedge biopsy of the testes. 13 In each instance the aspiration cytology diagnosis corresponded to the histological diagnosis, attesting to the reliability of this procedure. Their results and ours suggest that needle biopsy findings accurately reflect the findings encountered in conventional open wedge biopsy and that a false negative biopsy due to a sampling error is unlikely to occur. Although our study was done to validate the safety and efficacy of the needle biopsy technique in preparation for adoption of a percutaneous technique, fine needle biopsy appears to be more
Results
Normal testis bilat.: Subsequent unilat. testis enlargement Unilat. testis enlargement: Persistent testis enlargement
No. Pts.
Sets Biopsies
19
38
1
2
3
6
2
4
Biopsy Results 1 needle biopsy insufficient, 1 pos. (?) core, neg. wedge unilat. Pos. needle, pos. wedge bilat. Wedge and needle correlated in 5 biopsies, 1 needle biopsy insufficient on normal side Wedge and needle biopsies correlated in all cases
NEEDLE BIOPSY IN DIAGNOSIS OF TESTICULAR LEUKEMIA IN CHILDREN
attractive and may allow for ambulatory biopsy in children without using general anesthesia.
REFERENCES
1. Ortega, J. J., Javier, G. and Toran N.: Testicular infiltrates in children with acute lymphoblastic leukemia: a prospective study. Med. Ped. Oncol., 12: 386, 1984. 2. Simone, J.: Acute lymphocytic leukemia in childhood. Sem. Hematol., 11: 25, 1974. 3. Fernandez, C. H. and Sutow, W. W.: Irradiation and chemotherapy in pediatric tumors. In: Textbook of Radiotherapy, 2nd ed. Edited by G. H. Fletcher. Philadelphia: Lea & Febiger, chapt. 8, p. 561, 1973. 4. Finkelstein, J. Z., Dyment, P. G. and Hammond, G. D.: Leukemic infiltration of the testes during bone marrow remission. Pediatrics, 43: 1042, 1969. 5. Stoffel, T. J., Nesbit, M. E. and Levitt, S. H.: Extramedullary involvement of the testes in childhood leukemia. Cancer, 35: 1203, 1975. 6. Sharp, H. L., Nesbit, M. E., D' Angio, G. J. and Krivit, W.: Addition of local radiation after bone marrow remission in acute leukemia in children. Cancer, 20: 1403, 1967. 7. Givler, R. L.: Testicular involvement in leukemia and lymphoma.
Cancer, 23: 1290, 1969. 8. Mathe, G., Schwarzenberg, L., Mery, A. M., Cattan, A., Schneider, M., Amie!, J. L., Schlumberger, J. R., Poisson, J. and Wajcner, G.: Extensive histological and cytological survey of patients with acute leukemia in "complete remission". Brit. Med. J., 1: 640, 1966. 9. Nies, B. A., Bodey, G. P., Thomas, L.B., Brecher, G. and Freireich, E. J.: The persistence of extramedullary leukemic infiltrates during bone marrow remission of acute leukemia. Blood, 26: 133, 1965. 10. Ise, T., Kishi, K., lmashuku, S., Tsukada, M., Tsukimoto, I., Tsujino, G., Bessho, F., Tanaka, H., Miyazaki, S., Sakurai, M., Taguchi, N. and Muchi, M.: Testicular histology and function following long-term chemotherapy of acute leukemia in children and outcome of the patients who received testicular biopsy. Amer. J. Ped. Hemat. Oncol., 8: 288, 1986. 11. Haggar, R. A., MacMillan, A. B. and Thompson, D. C.: Leukemic infiltration of testis. Canad. J. Surg., 12: 197, 1969. 12. Sullivan, M. P. and Hrgovcic, M.: Extramedullary leukemia. In: Clinical Pediatric Oncology. Edited by W.W. Sutow, T. J. Vietti and D. J. Fernbach. St. Louis: The C. V. Mosby Co., p. 227, 1973. 13. Layfield, L. J., Hilborne, L. H., Ljung, B.-M., Feig, S. and Ehrlich, R. M.: Use of fine needle aspiration cytology for the diagnosis of testicular relapse in patients with acute lymphoblastic leukemia. J. Urol., 139: 1020, 1988.