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July 1995, Volume 45, Issue 7

Case Reports

Case of Pelvic Relapse in a Child Suffering from Acute Lymphoblastic Leukemia

Karim Qamruddin  ( Department of Pathology, The Aga Khan University Hospital, Karachi. )
Sheema Hassan  ( Department of Pathology, The Aga Khan University Hospital, Karachi. )
Mohammad Khurshid  ( Departments of Pathology, The Aga Khan University Hospital, Karachi. )

Abstract

We describe here a case of an eight years old child suffering from acute lymphoblastic leukemia. She developed pelvic infiltration of leukemic cells while in bone marrow remission and receiving maintenance chemotherapy: She also developed leukemic infiltration of Central Nervous System and died of complications resulting from massive pelvic relapse. With greater number of children in bone marrow and CNS remission, the issue ofpossible greater predisposition to extramedullary relapse has been discussed. The need for greater vigilance towards pelvic surveillance has been stressed.

Introduction

Since the advent of combination chemotherapy and Central Nervous System (CNS) prophylaxis the prognosis of acute lymphoblastic leukemia has improved considerably. With more children in bone marrow and CNS remission the infiltration of leukemic cells into other extramedullary sites is becoming a cause of increasing concern. The testicles have become the most common site of extramedullary relapse in boys, occurring most often during periods of bone marrow remission1. At autopsy leukemic infiltration of ovary has been reported in 32.-36% of the girls who have died with acute leukemia2. Pelvic leukemic relapse in young girls who are in clinical remission is however, a rare phenomena3. Recently we came across an eight years old child who developed a pelvic relapse of lymphoblastic leukemia while she was in clinical remission and still on maintenance chemotherapy.

Case Report

This 8 years old female child presented to us in May, 1991 with one month history of fever and bone pains. She was to have a WBC count of 56,900 with 90% blast cells. Bone marrow examination confirmed diagnosis of acute lymphoblastic leukemia (Li type). She was started onchemo­therapy comprising of Daunorubicin, Vincristine, Pred­msolone and intrathecal Methotrexate for CNS prophylaxis. Bone marrow remission was documented after 4 weeks of therapy and she underwent reintensification therapy with Vincristine, Daunorubicin, Cytosine Arabinoside, Etoposide, Predmsolone and intrathecal Methotrexate. She remained in remission for 2 years during which she was continued on maintenance therapy with Vincristine, oral Methotrexate and 6-mercaptopurine and intrathecal Methotrexate. In July, 1993 she presented with complaints of urinary retention and examination revealed firm lobulated mass which bled on touch arising from upper 2/3 Of vagina. Biopsy revealed leukemic cell infiltrate (Figures 1 and 2).


She received radiotherapy over lower abdomen, her urine retention was relieved and she received reintensification therapy and was started on mainte­nance therapy for leukemia as before. In January, 1994 she presented with complaints of headache and was found to be hypertensive. CSF examination showed atypical lymphoid cells suggesting CNS relapse. She received another course of reintensification therapy with weekly intrathecal Methotrexate, Cytosine and Hydrocorti­sonefor6 weeks. While barely recovered from the reintensifi­cation therapy and still on monthly injections of intrathecal Methotrexate, she presented with gross hematuria and flank pain. She had a palpable mass in the pelvis and ultrasound examination showed large mass in the lower abdomen displacing and distorting bladder anatomy. The mass was pressing onbothureters and causing bilateral hydronephrosis. It was evaluated as being inoperable and bilateral nephns­tomes were introduced. She was started on a UKALL relapse protocol compnsing of Epirubicin, L-asparaginase, Vin­cristine and Dexainethasone. The tumor sluunk in size and nephmstomes could be removed. She however, developed severe pancytopenia and died of overwhelming sepsis in July, 1994.

Discussion

Hams and Scully4 studied 27 cases of malignant lymphomas and granulocytic sarcoma involving the pelvic cavity. Twenty-one of these tumors appeared to originate from cervix, 4 in vagina and 2 in endometrium. Zutter and Gersell5 subsequently described a case of 36 years old woman known to be. suffering from acute leukemia which was tenninal deoxynbonucleotidyl transferase positive and involved the bone marrow and peripheral blood. Their patient developed relapse of the disease in uterus and cervix after remaining disease free for 2 years following induction therapy. Apart from few such case reports, involvement of female genital tract by hematologic ncoplasms is infrequent. Marcello et al6 studied ovarianbiopsy specimen from 10 girls who had undergone antiblastic treatment for acute lymphoblastic leukemia and were in complete remission. Apart from cortical fibrosis, variable reduction of follicular component and impairment of maturation, they found no evidence of leukemic infiltrate. Still leukemic infiltration of the ovary has been found in 3.2-36% of girls at autopsy who died of acute leukemia compared to 29-92% incidence of testicular leukemic infiltration2 . In his report of 4 young girls with pelvic relapse of acute leukemia, Cecalupo3 found 3 to be arising from ovaries and forth had pre-sacral mass without ovarian disease. The unique features of these cases was that diagnosis was made antemortem, onset of relapse and presumably the growth of the mass were extremely rapid and no marrow involvement was present. One arguable explana­tion for such behaviour of leukemia is that testis or ovary constitute sanctuary areas7. These sites represent areas in which nests of leukemic cells have been present as metastatic spread from the time of initial malignant transformation and asymptomatic state during the course of ALL does not imply the complete absence of leukemia. Why is itthenthat testicular relapses are far more frequent than ovarian relapse? The explanation is either ovaries and testis are not equally favourable soil for leukernic cells or that chemotherapy is better at preventing or eradicating subclinical leukemic ovarian involvement than at preventing testicular involve­ment. Other hypothesis for such a difference in incidence is the temperature difference between the ovary and testis. In a leukemic patient with unilateral cryptorchidism, testicular relapse occurred only in the nonnally descended testis8. The effect of chemotherapy on malignant tissue has been shown to be more efficient at higher temperature3. The patient described here had extremely aggressive behaviour of leukemia. She first developed a vaginal mass, then a CNS relapse and later went on to develop massive recurrence in the ovaries. The frequency of relapse in female genital tract may increase with longer survival rates expected from new treatment protocols. This may necessitate a more vigilant attention to pelvic surveillance during the course of acute lymphoblastic leukemia in girls.

References

1. Kuo, 1., Tschang. T. and Yih-Chu, J. Testicular relapse in childhood acute lymphoblastic leukemia during bone-marrow remission. Cancer, 1976;38:2604-261 2.
2. Jeh-Yih, C., Cradock, f V., Danis, R. K. eta!. Ovarian tumor as manifestation of relapse in acute lymphoblastic leukemia. Cancer, 1981;48:377.79.
3. Cecapalupo, A. J., Frankel, L. S. and Sullivan, M. P. Pelvic and ovarian extramedullary leukemic relapse in young girls. Cancer, 1982;50:587-93.
4. Harris, N. L. and Scully, R. B. Malignant lymphoma and gs-anulocytic sarcoma of the uterus and vagina. Cancer, 1984;53 :2530-2545.
5. Zutter, M. M. and Gersell, D. J. Acute lymphoblastic leukemia. An unusual case of primary relapse in the uterine cervix. Cancer, 1990;66: 1002-1004.
6. Marcello, M. F., Nuciforo, G., Romeo, R. et al. Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Cancer, 1990;66:2099:21-24.
7. Mathe, G., Schwarzenberg, L., Mary, A. M. et a!. Extensive histological and cytological survey of patients with acute leukemia in complete remission. Br. Med. J., 1986;1:640-42.
8. Van-Eys, J. and Sullivan, M. P. Testicular leukemia and temperature. Lancet, 1976;2:256-57.

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