0 1992 Harwood Academic Publishers GmbH
Leukemia and Lymphoma, Vol. 7 , pp. 171-172 Reprints available directly from the publisher Photocopying permitted by license only
Printed in the United Kingdom
Letter
Leuk Lymphoma Downloaded from informahealthcare.com by McMaster University on 11/06/14 For personal use only.
Splenic Lymphoma in a Patient Treated with Interleukin-2 and Dacarbazine for Metastatic Melanoma EITAN SHILONI', KENNETH A. MACLENNAN', ELIMELECH OKON3 and AARON POLLIACK4 I
Department of Surgery, Hadassah University Hospital, Jerusalem, Israel.*Department of Histopathology, The Royal Marsden Hospital, London, U.K.3*4Departmentsof Pathology and Hematology, Hadassah University Hospital, Jerusalem, Israel. (Received 5 November 1991)
KEY WORDS:
Splenic lymphoma
interleukin 2
melanoma
We have recently encountered an unusual case which we would like to report. A 38 year old male underwent a wide excision of a primary cutaneous nodular malignant melanoma in June 1987 in the left flank (Breslow 1.5 mm). A palpable lymph node was detected in the left groin in November 1987 and left ileoinguinal dissection was performed. One of 15 lymph nodes was found to be involved by melanoma. Ten months later (September 1988) the patient presented with right inguinal lymphadenopathy and underwent superficial groin dissection. Three of the 11 excised nodes were infiltrated by melanoma. Subsequent CT scan and ultrasound performed in November 1988 revealed 2 filling defects in the spleen that were not evident in earlier studies. No attempt to achieve tissue diagnosis was made at that time and combined chemo-immuno therapy was started. Between December 1988 and April 1989 he received 4 courses of treatment, consisting of a single IV bolus injection of Dacarbazine (850 mg/m2) followed by 2 cycles of Interleukin-2 (IL-2) given continuouslly IV for 5 consecutive days each, (18 x lo6 IU/m2/24 h) with a rest period of 10 days between cycles. Reduction in the size of the splenic lesions was demonstrated after 2 courses of therapy and after 4 courses (May 1989), the patient achieved complete response. He was offered to continue on maintenance therapy but refused. In December 1989 he had a grand-ma1 seizure and CT and MRI of the brain
showed two adjacent small lesions in the left frontal lobe. Chest, abdomen and pelvic CT scans were normal. The 2 nodules were resected and histopathology confirmed metastatic melanoma. The post operative course was uneventful and the patient recovered completely. Seven months later (July 1990), a single splenic lesion (4 cm in diameter was detected in CT scan. Fine needle aspiration under ultrasound guidance failed to obtain a tissue diagnosis. The patient refused any systemic therapy and since there was no evidence of disease elsewhere he underwent explorative laparotomy and splenectomy. The spleen was found to be infiltrated by a solitary mass (4 x 5 cm) shown to be intermediate grade malignant lymphoma, follicular, large cell type. No melanoma was evident in the spleen. Immunophenotypic staining showed that tumor cells were negative for CD3 but were moderately positive for CD20 (B cell receptor). A small number of cells were found to express CD25 (IL-2 receptor). A follow up CT scan in December 1990 revealed a new 3.5 cm mass in the pelvis near the left common iliac artery which was resected and found to be a metastasis of melanoma in a lymph node. Five months later the CT scan showed a few new enlarged para-aortic lymph nodes. Combined therapy with alpha-interferon and dacarbazine was started recently. Dacarbazine (DTIC) is considered to be the most effective cytotoxic agent for melanoma although antitumor activity has been reported to be generally
171
Leuk Lymphoma Downloaded from informahealthcare.com by McMaster University on 11/06/14 For personal use only.
172
E. SHILONI et al.
dissapointing achieving responses of short duration only and virtually no prolongation of survival’. IL-2 administered alone or in conjunction with DTIC is a well recognised active agent in the management of both metastatic melanoma and Hodgkin’s and non-Hodgkin’s lymphoma24. There is, however, a theoretical possibility that IL-2, a T cell growth factor, may induce the development of a T cell or even a B cell lymphoma if the “activated” B lymphocytes bear IL-2 receptors. Until now there is only one report of this nature of Hodgkin’s disease which developed after 2 years of DTIC and IL-2 therapy for metastatic melanoma. However, no association between IL-2 therapy and the development of the lymphoma in this case, was proven’. It is unclear whether the patient we describe here suffered from two malignant disorders at the same time: one, an isolated splenic lymphoma which responded to melanoma-orientated therapy by complete tumor regression lasting 15 months but eventually recurring in the spleen, without involving any other lymphatic organ; and two: a metastatic melanoma appearing metachronously in various sites during a 3 year period. In retrospect this would seem to be an unusual course for two
neoplasias occuring simultaneously. A second possibility is that this patient developed the splenic lymphoma as a result of the combined chemoimmuno-therapeutic regime he received. We believe that one cannot exclude with complete certainty that the latter in fact correct and that the evolution of the lymphoma was related to IL-2 therapy.
REFERENCES 1. Luce, 1. K. (1972) Chemotherapy of malignant melanoma. Cancer 30,1604-1615. 2. Rosenberg S. A.,Lotze M. T., Yang J. C. ef al. (1989) Experience with the use of high dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 210, 474485. 3. Allison M. A., Jones S. E., and McGuffey P. (1989) Phase I1 trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia and selected solid tumors. J. Clin. Oncol. 7, 7S80. 4. Stoter G., Aamdal S., Rodenhuis S., et al: (1992) Sequential administration of recombinant human Interleukin-2 and Dacarbazine in metastatic melanoma. A multicenter phase I1 study. J. Clin. Oncol. (in press). 5. Flaherty L. E., Schwert R., and Redman B. G.(1990)Case report: Development of Hodgkin’s disease in patient receiving long-term administration of dacarabazine and a Interleukin-2 for metastatic melanoma. J. Natl. Cancer Inst. 82, 1360.
Leukemia and Lymphoma, Vol. 7 , pp. 171-172 Reprints available directly from the publisher Photocopying permitted by license only
Printed in the United Kingdom
Letter
Leuk Lymphoma Downloaded from informahealthcare.com by McMaster University on 11/06/14 For personal use only.
Splenic Lymphoma in a Patient Treated with Interleukin-2 and Dacarbazine for Metastatic Melanoma EITAN SHILONI', KENNETH A. MACLENNAN', ELIMELECH OKON3 and AARON POLLIACK4 I
Department of Surgery, Hadassah University Hospital, Jerusalem, Israel.*Department of Histopathology, The Royal Marsden Hospital, London, U.K.3*4Departmentsof Pathology and Hematology, Hadassah University Hospital, Jerusalem, Israel. (Received 5 November 1991)
KEY WORDS:
Splenic lymphoma
interleukin 2
melanoma
We have recently encountered an unusual case which we would like to report. A 38 year old male underwent a wide excision of a primary cutaneous nodular malignant melanoma in June 1987 in the left flank (Breslow 1.5 mm). A palpable lymph node was detected in the left groin in November 1987 and left ileoinguinal dissection was performed. One of 15 lymph nodes was found to be involved by melanoma. Ten months later (September 1988) the patient presented with right inguinal lymphadenopathy and underwent superficial groin dissection. Three of the 11 excised nodes were infiltrated by melanoma. Subsequent CT scan and ultrasound performed in November 1988 revealed 2 filling defects in the spleen that were not evident in earlier studies. No attempt to achieve tissue diagnosis was made at that time and combined chemo-immuno therapy was started. Between December 1988 and April 1989 he received 4 courses of treatment, consisting of a single IV bolus injection of Dacarbazine (850 mg/m2) followed by 2 cycles of Interleukin-2 (IL-2) given continuouslly IV for 5 consecutive days each, (18 x lo6 IU/m2/24 h) with a rest period of 10 days between cycles. Reduction in the size of the splenic lesions was demonstrated after 2 courses of therapy and after 4 courses (May 1989), the patient achieved complete response. He was offered to continue on maintenance therapy but refused. In December 1989 he had a grand-ma1 seizure and CT and MRI of the brain
showed two adjacent small lesions in the left frontal lobe. Chest, abdomen and pelvic CT scans were normal. The 2 nodules were resected and histopathology confirmed metastatic melanoma. The post operative course was uneventful and the patient recovered completely. Seven months later (July 1990), a single splenic lesion (4 cm in diameter was detected in CT scan. Fine needle aspiration under ultrasound guidance failed to obtain a tissue diagnosis. The patient refused any systemic therapy and since there was no evidence of disease elsewhere he underwent explorative laparotomy and splenectomy. The spleen was found to be infiltrated by a solitary mass (4 x 5 cm) shown to be intermediate grade malignant lymphoma, follicular, large cell type. No melanoma was evident in the spleen. Immunophenotypic staining showed that tumor cells were negative for CD3 but were moderately positive for CD20 (B cell receptor). A small number of cells were found to express CD25 (IL-2 receptor). A follow up CT scan in December 1990 revealed a new 3.5 cm mass in the pelvis near the left common iliac artery which was resected and found to be a metastasis of melanoma in a lymph node. Five months later the CT scan showed a few new enlarged para-aortic lymph nodes. Combined therapy with alpha-interferon and dacarbazine was started recently. Dacarbazine (DTIC) is considered to be the most effective cytotoxic agent for melanoma although antitumor activity has been reported to be generally
171
Leuk Lymphoma Downloaded from informahealthcare.com by McMaster University on 11/06/14 For personal use only.
172
E. SHILONI et al.
dissapointing achieving responses of short duration only and virtually no prolongation of survival’. IL-2 administered alone or in conjunction with DTIC is a well recognised active agent in the management of both metastatic melanoma and Hodgkin’s and non-Hodgkin’s lymphoma24. There is, however, a theoretical possibility that IL-2, a T cell growth factor, may induce the development of a T cell or even a B cell lymphoma if the “activated” B lymphocytes bear IL-2 receptors. Until now there is only one report of this nature of Hodgkin’s disease which developed after 2 years of DTIC and IL-2 therapy for metastatic melanoma. However, no association between IL-2 therapy and the development of the lymphoma in this case, was proven’. It is unclear whether the patient we describe here suffered from two malignant disorders at the same time: one, an isolated splenic lymphoma which responded to melanoma-orientated therapy by complete tumor regression lasting 15 months but eventually recurring in the spleen, without involving any other lymphatic organ; and two: a metastatic melanoma appearing metachronously in various sites during a 3 year period. In retrospect this would seem to be an unusual course for two
neoplasias occuring simultaneously. A second possibility is that this patient developed the splenic lymphoma as a result of the combined chemoimmuno-therapeutic regime he received. We believe that one cannot exclude with complete certainty that the latter in fact correct and that the evolution of the lymphoma was related to IL-2 therapy.
REFERENCES 1. Luce, 1. K. (1972) Chemotherapy of malignant melanoma. Cancer 30,1604-1615. 2. Rosenberg S. A.,Lotze M. T., Yang J. C. ef al. (1989) Experience with the use of high dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 210, 474485. 3. Allison M. A., Jones S. E., and McGuffey P. (1989) Phase I1 trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia and selected solid tumors. J. Clin. Oncol. 7, 7S80. 4. Stoter G., Aamdal S., Rodenhuis S., et al: (1992) Sequential administration of recombinant human Interleukin-2 and Dacarbazine in metastatic melanoma. A multicenter phase I1 study. J. Clin. Oncol. (in press). 5. Flaherty L. E., Schwert R., and Redman B. G.(1990)Case report: Development of Hodgkin’s disease in patient receiving long-term administration of dacarabazine and a Interleukin-2 for metastatic melanoma. J. Natl. Cancer Inst. 82, 1360.
