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Myeloid sarcoma of the prostate as first clinical manifestation of acute myeloid leukaemia
Case report Myeloid sarcoma of the prostate as first clinical manifestation of acute myeloid leukaemia Sebastian Spethmann, Roman Heuer, Helmut Hopfer, and Gert Tuinmann Lancet Oncol 2004; 5: 62–63
A 32-year-old white male patient was admitted to the Department of Urology at our hospital with dysuria. The patient reported that he had experienced nightly sweats for 6 weeks and had experienced weight-loss of about 11 pounds over 4 weeks. Before these symptoms started to occur his medical history was unremarkable. A physical examination showed no pathological findings except for a large nodulous prostate. Laboratory analyses of haematological and biochemical parameters showed no abnormalities. In particular, concentrations of prostatespecific antigen were within normal range. However, abdominal MRI and CT identified a mass in the prostate that was infiltrating the lower bladder and seminal vesicles. No enlarged lymph nodes were seen. The histology of needle biopsies taken from the prostate showed the tumour to be highly proliferative, malignant, and consisting of atypical cells arranged in nests and cords without glandular differentiation. Most of the neoplastic cells had vacuolated cytoplasm, moderately polymorphic nuclei, and were mitotic or apoptotic. The stroma contained a dense inflammatory infiltrate with numerous eosinophilic granulocytes. Immunohistochemically, the tumour cells stained strongly for vimentin and weakly for neuron-specific enolase and CD31, an endothelial marker. Results indicating the presence of cytokeratins, desmin, prostate-specific antigen, placental alkaline phosphatase, neuroendocrine markers, thyrosine hydroxylase, and lymphocytic and lymphoma markers, were all negative. An initial diagnosis of an undifferentiated malignant tumour was made with a strong suggestion that it might be a sarcoma. Since the disease had progressed rapidly, a radical cystoprostatectomy with regional lymphadenectomy and construction of an ileum neobladder was done. Pathological examination of the resected tissue showed infiltration of the prostate, both seminal vesicles, the urinary bladder, the adjacent soft tissue, and regional lymph-nodes with positive resection margins. Histologically, tissue sections containing preserved tumour morphology consisted of undifferentiated blastic cells and differentiated myeloid cells with nongranulated cytoplasm (figure 1). Tumour cells did not stain for myeloperoxidase but they were positive for lysozyme (figure 1, inset), CD34, and CD117 (c-kit), leading to a final diagnosis of a myeloid sarcoma of the prostate. The patient developed postoperative acute peritonitis due to a rectal perforation, and needed a re-laparotomy and construction of an artificial anus. 3 weeks after the original operation, haematological findings were: haemoglobin concentration, 9·2 g/dL; number of white blood-cells, 13·9⫻109/mL; number of platelets, 189⫻109/mL.
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Figure 1. Histology of a well-preserved section of tumour from the prostatectomy specimen showing myeloid blasts and eosinophil precursors. Inset: Immunohistochemical reaction against lysozyme showing positive tumour cells and negative prostatic-duct cells.
A differential blood smear showed no abnormalities. In addition, a bone-marrow aspirate and biopsy were also done. Highly abnormal blast cells with non-granulated, vacuolated cytoplasm containing phagocytosed erythrocytes and unusually shaped nuclei were found (figure 2). Erythropoiesis and megakaryopoiesis were severely reduced. A cytogenetic study of 25 metaphasic chromosomes from the bone-marrow aspirate showed nine normal male karyotypes and 16 hyperdiploid karyotypes with numeric and structural
Figure 2. Bone-marrow differential blood smear showing abnormal blast cells with non-granulated, highly vacuolated cytoplasm containing phagocytosed erythrocytes.
THE LANCET Oncology Vol 5 January 2004
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For personal use. Only reproduce with permission from The Lancet.
Case report aberrations including a probable duplication of the long arm of chromosome 11 (dup(11)(q13q23)), leading to a tandem duplication of the MLL gene. Cytochemistry showed the blast cells were negative for myeloperoxidase and positive (21%) for napthol-ASDchloroacetate esterase. Immunophenotyping showed blast cells were positive for CD11b (86%), CD11c (13%), CD13 (97%), CD14 (18%), CD15 (15%), CD33 (88%), CD36 (11%), and CDw65 (11%). These findings were consistent with a diagnosis of acute myeloid leukaemia, subtype M5 according to the French–American–British (FAB) classification. The patient was treated with a combination of cytosine arabinoside at a dose of 100 mg/m2 on days 1–7 and daunorubicin at a dose of 60 mg/m2 on days 1, 3, and 5. After two cycles of chemotherapy, a second bone-marrow biopsy showed a 70% infiltration of blast cells. The patient died 3 months after diagnosis. Myeloid sarcoma of the prostate is a very rare finding. To our knowledge, this is only the third time that myeloid sarcoma, as the first clinical sign of acute myeloid leukaemia, has been reported.1,7 In addition, seven cases of prostatic myeloid sarcoma secondary to leukemia,2,3,8–12 and one case secondary to myelodysplasia,1 have also been published. This unusual type of tumour is associated with either the initial extramedullar manifestation of a myeloid leukaemia or in the context of a known disease, such as leukaemia or myelodysplastic syndrome. In post mortem examinations, the frequency of patients who had acute myelogenous leukaemia presenting with myeloid sarcoma is reported to vary between 3·1% and 9·1%. Moreover, patients who present with myeloid sarcoma without any evidence of leukaemia often develop acute myeloid leukaemia within 1 year of being diagnosed. Tissue sites most commonly affected are bone, periosteum, soft tissues, lymph nodes, and skin, and in general, more than one tissue is involved.4,5 About 75% of patients with myeloid sarcoma, but without concomitant symptoms of leukaemia, are initially misdiagnosed.5 The case presented here illustrates this problem very well. Originally, we did not diagnose a haematological tumour because of its rarity and the needle biopsies produced only small quantities of tumour and did not contain areas of tissue with adequately preserved morphology to facilitate an accurate diagnosis. And moreover, immunohistochemical staining of the tumour cells for myeloperoxidase—a primary marker widely used to identify myelogenous cells—was negative. Local treatments for myeloid sarcoma, such as radiation therapy or surgical resection, are less effective than chemotherapy at improving the disease-free interval or disease-free survival. A review of 74 cases of non-leukaemic myeloid sarcoma concluded that the chemotherapy regimen used for acute non-lymphoblastic leukaemia was more effective than local treatment modalities specifically directed at myeloid sarcoma.6 One other treatment option has also shown promise. One case, published in 2002, showed complete resolution of disseminated myeloid sarcoma in response to an allogeneic peripheral-blood stem-cell transplant.13 The transplant in this THE LANCET Oncology Vol 5 January 2004
case was done 3 months after a limited response to combination chemotherapy had been seen, which in turn had been given after local surgery and radiotherapy. In addition, a further case of primary myeloid sarcoma treated with autologous bone-marrow transplantation secondary to radical surgery, chemotherapy, and local prophylactic irradiation, has also been reported to have a long period of disease-free survival.14 The occurrence of myeloid sarcoma in a patient with acute myeloid leukaemia does not alter the prognosis; the course of disease simply depends on the clinical context in which the myeloid sarcoma is found. Conversely, however, for patients with known myeloproliferative disorders, the development of myeloid sarcoma is a strongly negative prognostic factor because it indicates a high propensity for acute myeloid leukaemia or blast crisis.4 Conflicts of interest
None declared References
1 Frame R, Head D, Lee R, et al. Granulocytic sarcoma of the prostate. Two cases causing urinary obstruction. Cancer 1987; 59: 142–46. 2 Thalhammer F, Gisslinger H, Chott A, et al. Granulocytic sarcoma of the prostate as the first manifestation of a late relapse of acute myelogenous leukemia. Ann Hematol 1994; 68: 97–99. 3 Chan YF. Granulocytic sarcoma (chloroma) of the kidney and prostate. Br J Urol 1990; 65: 655–56. 4 Neiman RS, Barcos M, Berard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981; 48: 1426–37. 5 Meis JM, Butler JJ, Osborne BM, Manning JT. Granulocytic sarcoma in non-leukemic patients. Cancer 1986; 58: 2697–709. 6 Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002; 94: 1739–46. 7 Quien ET, Wallach B, Sandhaus L, et al. Primary extramedullary leukemia of the prostate: case report and review of the literature. Am J Hematol 1996; 53: 267–71. 8 Buchanan GR, Boyett JM, Pollock BH, et al. Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study. Cancer 1991; 68: 48–55. 9 Lubin EN, Fetter TR, Erf LA. Subacute monocytic leukemia presenting symptoms of prostatism: a case report. J Urol 1947; 58: 272–76. 10 Mitch WE Jr, Serpick AA. Leukemic infiltration of the prostate: a reversible form of urinary obstruction. Cancer 1970; 26: 1361–65. 11 Tighe JR. Leukaemic infiltration of the prostate. Br J Surg 1960; 47: 658–60. 12 Muss HB, Moloney WC. Chloroma and other myeloblastic tumors. Blood 1973; 42: 721–28. 13 Stevenson WS, Vincent PC, Iland HJ. Disseminated granulocytic sarcoma treated with allogeneic peripheral blood stem-cell transplantation. Leuk Lymphoma 2002; 43: 2221–24. 14 Huter O, Brezinka C, Nachbaur D, et al. Successful treatment of primary extramedullary leukemia (EML) of the uterus with radical surgery, chemotherapy, autologous bone marrow transplantation (BMT) and prophylactic local irradiation. Bone Marrow Transplant 1996; 18: 663–64. SS and RH are students, and GT is a medical assistant, all in the Department of Oncology and Haematology, Universitätsklinikum Hamburg-Eppendorf, Germany. HH is a medical assistant at the Pathology Institute, Universitätsklinikum Hamburg-Eppendorf, Germany. Correspondence: Dr Gert Tuinmann, Medizinische Klinik II, Onkologie und Hämatologie Martinistr 52, 20246 Hamburg, Germany. Tel : +49 40 42803 2960. Fax: +49 40 42803 8054. Email: [email protected]
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
63
A 32-year-old white male patient was admitted to the Department of Urology at our hospital with dysuria. The patient reported that he had experienced nightly sweats for 6 weeks and had experienced weight-loss of about 11 pounds over 4 weeks. Before these symptoms started to occur his medical history was unremarkable. A physical examination showed no pathological findings except for a large nodulous prostate. Laboratory analyses of haematological and biochemical parameters showed no abnormalities. In particular, concentrations of prostatespecific antigen were within normal range. However, abdominal MRI and CT identified a mass in the prostate that was infiltrating the lower bladder and seminal vesicles. No enlarged lymph nodes were seen. The histology of needle biopsies taken from the prostate showed the tumour to be highly proliferative, malignant, and consisting of atypical cells arranged in nests and cords without glandular differentiation. Most of the neoplastic cells had vacuolated cytoplasm, moderately polymorphic nuclei, and were mitotic or apoptotic. The stroma contained a dense inflammatory infiltrate with numerous eosinophilic granulocytes. Immunohistochemically, the tumour cells stained strongly for vimentin and weakly for neuron-specific enolase and CD31, an endothelial marker. Results indicating the presence of cytokeratins, desmin, prostate-specific antigen, placental alkaline phosphatase, neuroendocrine markers, thyrosine hydroxylase, and lymphocytic and lymphoma markers, were all negative. An initial diagnosis of an undifferentiated malignant tumour was made with a strong suggestion that it might be a sarcoma. Since the disease had progressed rapidly, a radical cystoprostatectomy with regional lymphadenectomy and construction of an ileum neobladder was done. Pathological examination of the resected tissue showed infiltration of the prostate, both seminal vesicles, the urinary bladder, the adjacent soft tissue, and regional lymph-nodes with positive resection margins. Histologically, tissue sections containing preserved tumour morphology consisted of undifferentiated blastic cells and differentiated myeloid cells with nongranulated cytoplasm (figure 1). Tumour cells did not stain for myeloperoxidase but they were positive for lysozyme (figure 1, inset), CD34, and CD117 (c-kit), leading to a final diagnosis of a myeloid sarcoma of the prostate. The patient developed postoperative acute peritonitis due to a rectal perforation, and needed a re-laparotomy and construction of an artificial anus. 3 weeks after the original operation, haematological findings were: haemoglobin concentration, 9·2 g/dL; number of white blood-cells, 13·9⫻109/mL; number of platelets, 189⫻109/mL.
62
Figure 1. Histology of a well-preserved section of tumour from the prostatectomy specimen showing myeloid blasts and eosinophil precursors. Inset: Immunohistochemical reaction against lysozyme showing positive tumour cells and negative prostatic-duct cells.
A differential blood smear showed no abnormalities. In addition, a bone-marrow aspirate and biopsy were also done. Highly abnormal blast cells with non-granulated, vacuolated cytoplasm containing phagocytosed erythrocytes and unusually shaped nuclei were found (figure 2). Erythropoiesis and megakaryopoiesis were severely reduced. A cytogenetic study of 25 metaphasic chromosomes from the bone-marrow aspirate showed nine normal male karyotypes and 16 hyperdiploid karyotypes with numeric and structural
Figure 2. Bone-marrow differential blood smear showing abnormal blast cells with non-granulated, highly vacuolated cytoplasm containing phagocytosed erythrocytes.
THE LANCET Oncology Vol 5 January 2004
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
Case report aberrations including a probable duplication of the long arm of chromosome 11 (dup(11)(q13q23)), leading to a tandem duplication of the MLL gene. Cytochemistry showed the blast cells were negative for myeloperoxidase and positive (21%) for napthol-ASDchloroacetate esterase. Immunophenotyping showed blast cells were positive for CD11b (86%), CD11c (13%), CD13 (97%), CD14 (18%), CD15 (15%), CD33 (88%), CD36 (11%), and CDw65 (11%). These findings were consistent with a diagnosis of acute myeloid leukaemia, subtype M5 according to the French–American–British (FAB) classification. The patient was treated with a combination of cytosine arabinoside at a dose of 100 mg/m2 on days 1–7 and daunorubicin at a dose of 60 mg/m2 on days 1, 3, and 5. After two cycles of chemotherapy, a second bone-marrow biopsy showed a 70% infiltration of blast cells. The patient died 3 months after diagnosis. Myeloid sarcoma of the prostate is a very rare finding. To our knowledge, this is only the third time that myeloid sarcoma, as the first clinical sign of acute myeloid leukaemia, has been reported.1,7 In addition, seven cases of prostatic myeloid sarcoma secondary to leukemia,2,3,8–12 and one case secondary to myelodysplasia,1 have also been published. This unusual type of tumour is associated with either the initial extramedullar manifestation of a myeloid leukaemia or in the context of a known disease, such as leukaemia or myelodysplastic syndrome. In post mortem examinations, the frequency of patients who had acute myelogenous leukaemia presenting with myeloid sarcoma is reported to vary between 3·1% and 9·1%. Moreover, patients who present with myeloid sarcoma without any evidence of leukaemia often develop acute myeloid leukaemia within 1 year of being diagnosed. Tissue sites most commonly affected are bone, periosteum, soft tissues, lymph nodes, and skin, and in general, more than one tissue is involved.4,5 About 75% of patients with myeloid sarcoma, but without concomitant symptoms of leukaemia, are initially misdiagnosed.5 The case presented here illustrates this problem very well. Originally, we did not diagnose a haematological tumour because of its rarity and the needle biopsies produced only small quantities of tumour and did not contain areas of tissue with adequately preserved morphology to facilitate an accurate diagnosis. And moreover, immunohistochemical staining of the tumour cells for myeloperoxidase—a primary marker widely used to identify myelogenous cells—was negative. Local treatments for myeloid sarcoma, such as radiation therapy or surgical resection, are less effective than chemotherapy at improving the disease-free interval or disease-free survival. A review of 74 cases of non-leukaemic myeloid sarcoma concluded that the chemotherapy regimen used for acute non-lymphoblastic leukaemia was more effective than local treatment modalities specifically directed at myeloid sarcoma.6 One other treatment option has also shown promise. One case, published in 2002, showed complete resolution of disseminated myeloid sarcoma in response to an allogeneic peripheral-blood stem-cell transplant.13 The transplant in this THE LANCET Oncology Vol 5 January 2004
case was done 3 months after a limited response to combination chemotherapy had been seen, which in turn had been given after local surgery and radiotherapy. In addition, a further case of primary myeloid sarcoma treated with autologous bone-marrow transplantation secondary to radical surgery, chemotherapy, and local prophylactic irradiation, has also been reported to have a long period of disease-free survival.14 The occurrence of myeloid sarcoma in a patient with acute myeloid leukaemia does not alter the prognosis; the course of disease simply depends on the clinical context in which the myeloid sarcoma is found. Conversely, however, for patients with known myeloproliferative disorders, the development of myeloid sarcoma is a strongly negative prognostic factor because it indicates a high propensity for acute myeloid leukaemia or blast crisis.4 Conflicts of interest
None declared References
1 Frame R, Head D, Lee R, et al. Granulocytic sarcoma of the prostate. Two cases causing urinary obstruction. Cancer 1987; 59: 142–46. 2 Thalhammer F, Gisslinger H, Chott A, et al. Granulocytic sarcoma of the prostate as the first manifestation of a late relapse of acute myelogenous leukemia. Ann Hematol 1994; 68: 97–99. 3 Chan YF. Granulocytic sarcoma (chloroma) of the kidney and prostate. Br J Urol 1990; 65: 655–56. 4 Neiman RS, Barcos M, Berard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981; 48: 1426–37. 5 Meis JM, Butler JJ, Osborne BM, Manning JT. Granulocytic sarcoma in non-leukemic patients. Cancer 1986; 58: 2697–709. 6 Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002; 94: 1739–46. 7 Quien ET, Wallach B, Sandhaus L, et al. Primary extramedullary leukemia of the prostate: case report and review of the literature. Am J Hematol 1996; 53: 267–71. 8 Buchanan GR, Boyett JM, Pollock BH, et al. Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study. Cancer 1991; 68: 48–55. 9 Lubin EN, Fetter TR, Erf LA. Subacute monocytic leukemia presenting symptoms of prostatism: a case report. J Urol 1947; 58: 272–76. 10 Mitch WE Jr, Serpick AA. Leukemic infiltration of the prostate: a reversible form of urinary obstruction. Cancer 1970; 26: 1361–65. 11 Tighe JR. Leukaemic infiltration of the prostate. Br J Surg 1960; 47: 658–60. 12 Muss HB, Moloney WC. Chloroma and other myeloblastic tumors. Blood 1973; 42: 721–28. 13 Stevenson WS, Vincent PC, Iland HJ. Disseminated granulocytic sarcoma treated with allogeneic peripheral blood stem-cell transplantation. Leuk Lymphoma 2002; 43: 2221–24. 14 Huter O, Brezinka C, Nachbaur D, et al. Successful treatment of primary extramedullary leukemia (EML) of the uterus with radical surgery, chemotherapy, autologous bone marrow transplantation (BMT) and prophylactic local irradiation. Bone Marrow Transplant 1996; 18: 663–64. SS and RH are students, and GT is a medical assistant, all in the Department of Oncology and Haematology, Universitätsklinikum Hamburg-Eppendorf, Germany. HH is a medical assistant at the Pathology Institute, Universitätsklinikum Hamburg-Eppendorf, Germany. Correspondence: Dr Gert Tuinmann, Medizinische Klinik II, Onkologie und Hämatologie Martinistr 52, 20246 Hamburg, Germany. Tel : +49 40 42803 2960. Fax: +49 40 42803 8054. Email: [email protected]
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
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