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Non-Hodgkin lymphoma during pregnancy
European Journal of Obstetrics & Gynecology and Reproductive Biology 77 (1998) 249–251
Case report
Non-Hodgkin lymphoma during pregnancy a, a b ´ ´ Pereira-Leite a Pedro Tiago Silva *, Henrique M.N. de Almeida , Fernando Prıncipe , Luıs a
˜ , 4200 Porto, Portugal Department of Gynecology and Obstetrics, Hospital de S. Joao b ˜ , 4200 Porto, Portugal Service of Clinical Hematology, Hospital de S. Joao
Received 19 March 1997; received in revised form 9 September 1997; accepted 12 November 1997
Abstract The authors report a case of a pregnancy with a Non-Hodgkin lymphoma. A histological association of high-grade B-cell and a MALT type lymphoma was found which, to their best knowledge, is described for the first time in pregnancy. 1998 Elsevier Science Ireland Ltd. Keywords: Pregnancy; Lymphoma; MALT Lymphoma; Non-Hodgkin Lymphoma
1. Introduction Non-Hodgkin lymphoma (NHL) is rarely observed in pregnancy. In fact, in a review of the literature made in 1989, it was noted that only 75 cases had been reported by that time [1]. As a consequence of this scarcity, there is an absence of large series of cases and therefore most reports contain very few or single cases. In this report, a case of an high grade B cell NHL diagnosed in the second trimester of pregnancy and followed up for 24 months after delivery is described. Its association to a Mucosa Associated Lymphoid Tissue [MALT] type lymphoma was ascertained, which, to our best knowledge, is herein reported for the first time.
2. Case report A 32-year-old white gravida three, para two, was referred to our department in July 1995 with the diagnosis of 26 weeks gestation and high grade NHL of B cells. When the pregnancy was diagnosed, she began the usual *Corresponding author: Tel.: 1351 2 527 151; fax: 1351 2 550 5870.
surveillance with monthly visits to her family doctor, appropriate blood and urine testing and ultrasound dating. At 17 weeks she complained of dull epigastric pain without any other symptoms. During the examination, a hard, insensitive, fixed mass was felt in the left hypochondrium. An abdominal ultrasound confirmed the presence of an ill-defined tumor in the splenic angle of the colon; in a nuclear magnetic resonance performed at 19 weeks, there was evidence of an irregular mass close to the retroperitoneal portion of the duodenum, in the left of the midline, apparently without involvement of pancreas, liver, spleen, kidneys, adrenals, retroperitoneal ganglionar areas and vertebrae. An endoscopic study was then made and a duodenal biopsy obtained, which revealed a ‘low grade NHL, MALT type’. An exploratory laparotomy made at 21 weeks, showed that the tumor was not amenable for resection but a surgical biopsy of the tumor was obtained. The diagnosis of high grade NHL of B cells was established. At 26 weeks she was referred to our high risk pregnancy center for multidisciplinary management. The patient was pale and appeared underweighted, but had a normal performance status and B symptoms were absent. Due to uterine growth, the abdominal mass was not identified; the
0301-2115 / 98 / $19.00 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0301-2115( 97 )00261-3
250
P.T. Silva et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 77 (1998) 249 – 251
exam of the ganglionar areas did not disclose any adenomegaly. Blood tests revealed mild normocytic anemia but serum lactic dehydrogenase and b2-microglobulin were normal. Fetal well being assessed with cardiotocography, ultrasound and umbilical vessels Doppler fluxometry were also normal. Taking into account the patient’s request to postpone chemotherapy to the puerperium period, weekly surveillance continued on an outpatient basis. During this time she remained symptom free; regular ultrasound observation of the mass did not reveal an increase in its volume. At 32 weeks, she was admitted to hospital and received dexamethasone therapy for improvement of fetal lung maturity. A cesarean section was performed, which yielded an apparently healthy female infant, weighing 2075 g and with an Apgar score of 8–9 at 1 and 5 min. In the exam of the abdominal cavity, an irregular hard mass, 15 cm long, involving the small intestine and root of the mesentery was observed and biopsied; additional liver and bone biopsies were taken and tubal ligation was performed. The diagnosis of malignant high grade B NHL was confirmed (it was not possible to go further in the histological classification). The disease was considered in Stage II, bulky, with low intermediate risk, according to the International Prognostic Index, IPI [2]. In October, she began ambulatory chemotherapy with CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) which stopped in May 1996 with a total of eight cycles, in complete remission. In one of the cycles, she was admitted to hospital for parenteral nutrition because of severe vomiting and dehydration. A duodenal stenosis (D2) was diagnosed and biopsied. There was no evidence of disease, but the culture of one sample yielded colonies of Helicobacter pylori. At present, 24 months after starting chemotherapy, the patient is in complete remission.
3. Discussion The occurrence of NHL during pregnancy is rarely observed as a result of the higher incidence of the disease lately in life, generally beyond the reproductive age [1]. Due to the rarity of this association, the influence of pregnancy on the course of NHL is uncertain. Occasional observations of a postpartum deterioration of the disease [3,4], suggest that the progression of some types of lymphoma may be retarded by pregnancy although a lack of effect may also occur [1]. However, for the pregnant woman affected with NHL, the prognosis is generally poor and frequently leads to her death. In a review of 42 cases previously reported with sufficient detail [1] and in a paper presenting 20 other cases [5], only 20 women (32%) survived without evidence of the disease at the time of the study and 37 (60%) died. Considering the diagnosis at the second trimester as
is the present case, the prognosis worsened. In the same review, in a total of 16 cases diagnosed in the second trimester, only two patients (13%) had no evidence of disease and all the others (87%) had died [1]. The majority of extranodal lymphomas are B-cell lymphomas, usually of the diffuse large-cell type [6], and are frequently observed in the gastrointestinal tract [7]. MALT lymphoma is now recognized as a distinct clinicopathological entity and is the first type of malignant lymphoma for which a close epidemiological association with H. pylori was documented [8]. Typically presents as low-grade [6,9], but the observation that typical MALT lymphomas coexist with high-grade large-cell lymphomas led to the suggestion that these might result from the histological transformation of MALT lymphomas [10]. This point may explain the apparent discrepancy of findings between the endoscopic and surgical biopsies. In spite of the general poor prognosis of pregnant patients with NHL, the present case had a favorable evolution which is related to the Stage of the disease, a major prognostic determinant for the outcome [2] together with the histological type. The complete remission after CHOP treatment, also favors current opinion that it is the best treatment available for patients with high-grade NHL [11]. The use of chemotherapy in pregnancy complicated with NHL is a subject of great concern because of its potential teratogenic effect. Yet, reports of long-term follow-up of children born to women receiving chemotherapy during pregnancy failed to demonstrate teratogenic and other deleterious effects, despite the fact that some of them had been treated with CHOP even in the first trimester [5]. Notwithstanding the concerns about its use in pregnancy, treatment with CHOP for NHL should therefore be considered when it is decided to start chemotherapy before delivery.
References [1] Ward FT, Weiss RB. Lymphoma and pregnancy. Seminars in Oncology 1989;16:397–409. [2] The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Eng J Med 1993;329:987–94. [3] Steiner-Salz D, Yahalom J, Samuelov A, Polliack A. Non-Hodgkin lymphoma associated with pregnancy. A report of six cases, with a review of the literature. Cancer 1985;56:2087–91. [4] Kurtin PJ, Gaffey TA, Habermann TM. Peripheral T-cell lymphoma involving the placenta. Cancer 1992;70(12):2963–8. ´ A, Dıaz-Maqueo ´ [5] Aviles JC, Talavera A et al. Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol 1991;36(4):243–8. [6] Salhany KE, Pietra GG. Extranodal lymphoid disorders. Am J Clinical Pathol 1993;99:472–85. [7] Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972;29:252–60.
P.T. Silva et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 77 (1998) 249 – 251 [8] Zucca E, Roggero E. Biology and treatment of MALT lymphoma: The state-of-the-art in 1996. Ann Oncol 1996;7:787–92. [9] Isaacson PG, Spencer J. Malignant lymphoma of mucosa associated lymphoid tissue. Histopathology 1987;11:445–62. [10] Chan JKC, Ng CS, Isaacson PG. Relationship between high grade lymphoma and low grade B-cell mucosa associated lymphoid tissue
251
lymphoma (MALToma) of the stomach. Am J Pathol 1990;136:1153–64. [11] Fisher RI, Gaynor ER, Dahlberg S et al. Comparision of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Eng J Med 1993;328:1002–6.
Case report
Non-Hodgkin lymphoma during pregnancy a, a b ´ ´ Pereira-Leite a Pedro Tiago Silva *, Henrique M.N. de Almeida , Fernando Prıncipe , Luıs a
˜ , 4200 Porto, Portugal Department of Gynecology and Obstetrics, Hospital de S. Joao b ˜ , 4200 Porto, Portugal Service of Clinical Hematology, Hospital de S. Joao
Received 19 March 1997; received in revised form 9 September 1997; accepted 12 November 1997
Abstract The authors report a case of a pregnancy with a Non-Hodgkin lymphoma. A histological association of high-grade B-cell and a MALT type lymphoma was found which, to their best knowledge, is described for the first time in pregnancy. 1998 Elsevier Science Ireland Ltd. Keywords: Pregnancy; Lymphoma; MALT Lymphoma; Non-Hodgkin Lymphoma
1. Introduction Non-Hodgkin lymphoma (NHL) is rarely observed in pregnancy. In fact, in a review of the literature made in 1989, it was noted that only 75 cases had been reported by that time [1]. As a consequence of this scarcity, there is an absence of large series of cases and therefore most reports contain very few or single cases. In this report, a case of an high grade B cell NHL diagnosed in the second trimester of pregnancy and followed up for 24 months after delivery is described. Its association to a Mucosa Associated Lymphoid Tissue [MALT] type lymphoma was ascertained, which, to our best knowledge, is herein reported for the first time.
2. Case report A 32-year-old white gravida three, para two, was referred to our department in July 1995 with the diagnosis of 26 weeks gestation and high grade NHL of B cells. When the pregnancy was diagnosed, she began the usual *Corresponding author: Tel.: 1351 2 527 151; fax: 1351 2 550 5870.
surveillance with monthly visits to her family doctor, appropriate blood and urine testing and ultrasound dating. At 17 weeks she complained of dull epigastric pain without any other symptoms. During the examination, a hard, insensitive, fixed mass was felt in the left hypochondrium. An abdominal ultrasound confirmed the presence of an ill-defined tumor in the splenic angle of the colon; in a nuclear magnetic resonance performed at 19 weeks, there was evidence of an irregular mass close to the retroperitoneal portion of the duodenum, in the left of the midline, apparently without involvement of pancreas, liver, spleen, kidneys, adrenals, retroperitoneal ganglionar areas and vertebrae. An endoscopic study was then made and a duodenal biopsy obtained, which revealed a ‘low grade NHL, MALT type’. An exploratory laparotomy made at 21 weeks, showed that the tumor was not amenable for resection but a surgical biopsy of the tumor was obtained. The diagnosis of high grade NHL of B cells was established. At 26 weeks she was referred to our high risk pregnancy center for multidisciplinary management. The patient was pale and appeared underweighted, but had a normal performance status and B symptoms were absent. Due to uterine growth, the abdominal mass was not identified; the
0301-2115 / 98 / $19.00 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0301-2115( 97 )00261-3
250
P.T. Silva et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 77 (1998) 249 – 251
exam of the ganglionar areas did not disclose any adenomegaly. Blood tests revealed mild normocytic anemia but serum lactic dehydrogenase and b2-microglobulin were normal. Fetal well being assessed with cardiotocography, ultrasound and umbilical vessels Doppler fluxometry were also normal. Taking into account the patient’s request to postpone chemotherapy to the puerperium period, weekly surveillance continued on an outpatient basis. During this time she remained symptom free; regular ultrasound observation of the mass did not reveal an increase in its volume. At 32 weeks, she was admitted to hospital and received dexamethasone therapy for improvement of fetal lung maturity. A cesarean section was performed, which yielded an apparently healthy female infant, weighing 2075 g and with an Apgar score of 8–9 at 1 and 5 min. In the exam of the abdominal cavity, an irregular hard mass, 15 cm long, involving the small intestine and root of the mesentery was observed and biopsied; additional liver and bone biopsies were taken and tubal ligation was performed. The diagnosis of malignant high grade B NHL was confirmed (it was not possible to go further in the histological classification). The disease was considered in Stage II, bulky, with low intermediate risk, according to the International Prognostic Index, IPI [2]. In October, she began ambulatory chemotherapy with CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) which stopped in May 1996 with a total of eight cycles, in complete remission. In one of the cycles, she was admitted to hospital for parenteral nutrition because of severe vomiting and dehydration. A duodenal stenosis (D2) was diagnosed and biopsied. There was no evidence of disease, but the culture of one sample yielded colonies of Helicobacter pylori. At present, 24 months after starting chemotherapy, the patient is in complete remission.
3. Discussion The occurrence of NHL during pregnancy is rarely observed as a result of the higher incidence of the disease lately in life, generally beyond the reproductive age [1]. Due to the rarity of this association, the influence of pregnancy on the course of NHL is uncertain. Occasional observations of a postpartum deterioration of the disease [3,4], suggest that the progression of some types of lymphoma may be retarded by pregnancy although a lack of effect may also occur [1]. However, for the pregnant woman affected with NHL, the prognosis is generally poor and frequently leads to her death. In a review of 42 cases previously reported with sufficient detail [1] and in a paper presenting 20 other cases [5], only 20 women (32%) survived without evidence of the disease at the time of the study and 37 (60%) died. Considering the diagnosis at the second trimester as
is the present case, the prognosis worsened. In the same review, in a total of 16 cases diagnosed in the second trimester, only two patients (13%) had no evidence of disease and all the others (87%) had died [1]. The majority of extranodal lymphomas are B-cell lymphomas, usually of the diffuse large-cell type [6], and are frequently observed in the gastrointestinal tract [7]. MALT lymphoma is now recognized as a distinct clinicopathological entity and is the first type of malignant lymphoma for which a close epidemiological association with H. pylori was documented [8]. Typically presents as low-grade [6,9], but the observation that typical MALT lymphomas coexist with high-grade large-cell lymphomas led to the suggestion that these might result from the histological transformation of MALT lymphomas [10]. This point may explain the apparent discrepancy of findings between the endoscopic and surgical biopsies. In spite of the general poor prognosis of pregnant patients with NHL, the present case had a favorable evolution which is related to the Stage of the disease, a major prognostic determinant for the outcome [2] together with the histological type. The complete remission after CHOP treatment, also favors current opinion that it is the best treatment available for patients with high-grade NHL [11]. The use of chemotherapy in pregnancy complicated with NHL is a subject of great concern because of its potential teratogenic effect. Yet, reports of long-term follow-up of children born to women receiving chemotherapy during pregnancy failed to demonstrate teratogenic and other deleterious effects, despite the fact that some of them had been treated with CHOP even in the first trimester [5]. Notwithstanding the concerns about its use in pregnancy, treatment with CHOP for NHL should therefore be considered when it is decided to start chemotherapy before delivery.
References [1] Ward FT, Weiss RB. Lymphoma and pregnancy. Seminars in Oncology 1989;16:397–409. [2] The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Eng J Med 1993;329:987–94. [3] Steiner-Salz D, Yahalom J, Samuelov A, Polliack A. Non-Hodgkin lymphoma associated with pregnancy. A report of six cases, with a review of the literature. Cancer 1985;56:2087–91. [4] Kurtin PJ, Gaffey TA, Habermann TM. Peripheral T-cell lymphoma involving the placenta. Cancer 1992;70(12):2963–8. ´ A, Dıaz-Maqueo ´ [5] Aviles JC, Talavera A et al. Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol 1991;36(4):243–8. [6] Salhany KE, Pietra GG. Extranodal lymphoid disorders. Am J Clinical Pathol 1993;99:472–85. [7] Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972;29:252–60.
P.T. Silva et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 77 (1998) 249 – 251 [8] Zucca E, Roggero E. Biology and treatment of MALT lymphoma: The state-of-the-art in 1996. Ann Oncol 1996;7:787–92. [9] Isaacson PG, Spencer J. Malignant lymphoma of mucosa associated lymphoid tissue. Histopathology 1987;11:445–62. [10] Chan JKC, Ng CS, Isaacson PG. Relationship between high grade lymphoma and low grade B-cell mucosa associated lymphoid tissue
251
lymphoma (MALToma) of the stomach. Am J Pathol 1990;136:1153–64. [11] Fisher RI, Gaynor ER, Dahlberg S et al. Comparision of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Eng J Med 1993;328:1002–6.