- Email: [email protected]
Granulocytic sarcoma: Three unusual patients
Granulocytic
Sarcoma: Three Unusual Patients
ROBERT G. GIITIN, M.D., WILLIAM B. SCHARFMAN, M.D., PETER T. BURKART, M.D. AUIXIY, New York
his report is comprised of three unusual patients. T Two patients had chronic granulocytic leukemia, and one was diagnosed as having a myelodysplastic syndrome. One patient presented with massive lymphadenopathy, the second with lytic bone lesions, and the third with diffuse skin involvement. In all three instances, biopsy examination showed that the lesions were composed of myeloblasts, and, subsequently, a diagnosis of granulocytic sarcoma (chloroma) was made. These casesillustrate that the diagnosis of granulocytic sarcoma should be considered when tumors or lytic lesions or skin involvement are encountered in patients with chronic granulocytic leukemia or acute granulocytic leukemia. In addition, this lesion needsto be considered in myelodysplastic syndromes. Historically, Burns [l] originally described this lesion in 1811. King [2] described chloroma as a green tumor, the color of which was due to myeloperoxidase in the cells. Dock [3] first noted the association of granulocytic sarcoma with acute leukemia in 1893. The term granulocytic sarcomawas first used by Rappaport [4] and is currently in use. Excellent reviews are presented by Neiman et al [5] and Eshghabadi and Shojanda [6]. Meis and co-workers [7] discuss the subject of granulocytic sarcoma in nonleukemic patients. Chabner et al [8] describe destructive bone lesions with granulocytic sarcoma. Long and Mihm [9] report those casespresenting with skin manifestations.
CASE REPORTS Patient 1 A Il-year-old man was admitted to Albany Medical Center Hospital on March 12,1984, for evaluation of a large left axillary mass.Physical findings included hepatosplenomegaly and a left axillary soft-tissue mass but no palpable lymph nodes. Computed tomographic (CT) scan of the chest and abdomen outlined a 6 X 6cm axillary mass aswell as multiple left-sided axillary lymph nodes and an enlarged spleen. The blood count showed a white cell count of 34,700/mm3 with 23% band forms, 45% polymorphonuclear leukocytes, 6% lymphocytes, 9% monocytes, 2% eosinophils, 7% myelocytes, and 1% promyelocytes. Findings on bone marrow examination were consistent with chronic granulocytic leukemia, and 100% of the mitoses contained a Philadelphia chromosome.A biopsy specimen was obtained from the axillary mass,and a diagnosisof granulocytic sarcoma was made after electron microsFrom the Division of Hematology, Department of Medicine, Albany Medical College, Albany, New York. Requests for reprints should be addressed to William E. Scharfman. M.D., Division of Hematology. Albany Medical ColCurrent address for D;. Gittin is Division of Hematology/Oncology, sity of North Carolina, Chapel Hill, North Carolina.
Univer-
copy and Leder’s staining (chloroacetate esterase granulocytic cell strain). Radiation therapy resolved the left axillary mass. Therapy with oral hydroxyurea was started to control the white blood cell count. Over the next six months, the patient developed enlarging right cervical, left supraventricular, and right axillary lymph nodes that were successfully treated with radiation therapy. On September 4,1984, the patient was admitted to the hospital with newly enlarging cervical and submandibular lymph nodes plus a right-sided axillary mass. His blood count revealed a white cell count of 15,800/mm3and bone marrow again was consistent with chronic granulocytic leukemia in the chronic phase. Chemotherapy was started with cytosine arabinoside 150 mg/m2 intravenously daily for four days followed by 200 mg subcutaneously twice weekly for six consecutive weeks. The lymphadenopathy and the axillary mass completely resolved. On October 27,1984, the patient had developed cervical, supraclavicular, inguinal, and right axillary lymphadenopathy, and he was again treated with intravenous cytosine arabinoside followed by subcutaneous cytosine arabinoside, and once again the lymphadenopathy completely resolved. On February 5,1985, the patient was readmitted to the hospital with newly enlarging inguinal, cervical, and supraclavicular lymph nodes. Chemotherapy was given with daunorubicin hydrochloride, cytosine arabinoside, and 6-thioguanine; once more, lymphadenopathy completely resolved. In May 1985, he was readmitted for the last time with abdominal pain and also a deep venous thrombosisand sepsis.CT scanning showed massive mediastinal lymphadenopathy as well asparenchymal lung infiltration and a chest wall mass.The white cell count was now 72,000/mm3 with 24% blasts, 2% promyelocytes, 17%myelocytes, 9% metamyelocytes, 20%banded forms, 25% polymorphonuclear leukocytes, 2% basophils, and 1% eosinophils. The hemoglobin was 11.4 g/dL, and the platelet count was 58,000/mm3. Bone marrow contained 35% blasts. The patient died of septicemia. Patient 2 A 49-year-old man was diagnosed as having chronic granulocytic leukemia in July 1982 when his white blood cell count was found to be 114,000/mm3.Findings from bone marrow aspiration and biopsy examination were consistent with chronic granulocytic leukemia in the chronic phase, and the Philadelphia chromosome was observed. Splenomegaly was present. He was treated successfully with oral busulfan. In December 1985, he was found to have an osteoblastic lesion of the left femur and was treated with radiation therapy to a total of 3,000 rads in 15 fractions with complete resolution by radiography. On February 1, 1986, he presented with a severe
September 1989 The American Journal of Medicine
Volume 87
345
GRANULOCYTIC
SARCOMA
/ GIllIN
ET AL
pain in the left leg. The radiograph showed a transverse pathologic fracture of the femur. The blood count showed a white cell count of 34,000/mm3 with 30% band forms, 48% segmented neutrophils, 9% lymphocytes, 5% monocytes, 2% eosinophils, 1% basophils, and 5% metamyelocytes. The platelet count was 192,000/mm3 and the level of hemoglobin was 14.6 g/ dL. On May 3, 1986, open reduction and internal fixation were performed. The biopsy specimen showed clusters of blast cells in the periosteum that stained positive with Leder’s stain. Hemorrhagic and infectious complications developed, and the patient’s course declined sharply because of supervening sepsis. Preterminally, the white cell count had risen to 167,000/mm3 with 35% myeloblasts in the peripheral blood. Bone marrow examination simultaneously showed 75% myeloblasts.
phocytes, and 2% basophils. Bone marrow examination showed 95% blasts, which were strongly positive for fluoride-inhibited nonspecific esterase. No treatment was given, and the patient died in a hospice. The skin lesions had not regressed.
346
87
COMMENTS
Granulocytic sarcoma is a localized tumor of immature myeloid cells. Although originally believed to be a rare lesion, it has been the subject of a number of reviews (Neiman et al [5] and Eshghabadi and Shojanda [6]). Granulocytic sarcoma has been described as a complication of acute granulocytic or chronic granulocytic leukemia, and it may occur without blood or bone marrow evidence of leukemia. In chronic granulocytic leukemia, the lesion implies a poor prognosis and usually predicts blast transformation, The incidence has been predicted to be 4.5% in chronic granulocytic leukemia and 2.5% in acute granulocytic leukePatient 3 A 79-year-old man had a history of chronic anemia mia (MUSS and Malony [lo]). Reports of chloroma preceding leukemia have since 1981. In October 1984, he presented to the Albastressed the poor prognosis associated with these tuny Medical Center Hospital with night sweats, prurimors in that virtually all patients eventually develop tus, and diffuse skin thickening associated with some leukemia within a mean of 10 months [5,6]. The clinidiscrete nodules on the upper extremities and trunk. cal spectrum of granulocytic sarcoma is broad and virThe rest of the physical examination was unremarkable. The white cell count was 24,900/mm3 with 3% tually any site can be involved, from the prostatic gland to the anterior chamber of the eye. The most metamyelocytes, 48% polymorphonuclear leukocytes, 9% band forms, 23% monocytes, 5% eosinophils, and commonly involved sites in order of occurrence are 11% lymphocytes. The platelet count was 244,000/ skin, lymph nodes, soft tissues overlying bone, bone mm3, and the hemoglobin level was 12.1 g/dL. Bone and periosteum, and finally viscera. Disease in the marrow examination revealed a hypercellular marrow epidural space with or without vertebral body involvewith a myeloid:erythroid ratio of 8:l. There were a few ment can cause spinal cord compression. Single lesions immature monocytic precursors in the marrow as well are the most common presentation, and in one large as slight eosinophilia, 4% myeloblasts, and megaloseries [5] (61 tumors in 50 patients), 42 patients had blastic red cell maturation. The megakaryocytes were only a single tumor. These lesions are sensitive to irranormal. There were no abnormal sideroblasts. Skin diation as well as to chemotherapy. Eshghabadi and biopsy examination showed myeloblastic infiltration. Shojanda [6] have recently described one patient with A diagnosis of myelodysplastic syndrome most consisisolated granulocytic sarcoma, reviewed 33 other cases tent with a chronic myelomonocytic leukemia was from the literature with this lesion, and identified five made at that time. The patient was treated with lowlong-term survivors. All patients received intensive dose cytosine arabinoside, but this regimen had no systemic chemotherapy. Meis et al [7] have recently effect on the skin lesions. reviewed the experience at the University of Texas The patient’s condition remained stable for many M.D. Anderson Hospital Cancer Center with 16 pamonths; however, on June 11,1985, he was admitted to tients seen over 25 years. Seven patients did not develthe hospital because of a 20-pound weight loss and op leukemia, with the longest follow-up 16 years. All progression of the skin lesions as well as an intense patients were given systemic chemotherapy. pruritus. Physical examination showed splenomegaly In the first case described, multiple chloromas apas well as enlarged right and left cervical lymph nodes. peared in the patient with chronic granulocytic leukeThe blood count showed a white cell count of 54,OOOl mia in the chronic phase, and yet this patient achieved mm3 with 8% blasts, 1% promyelocytes, 5% myeloa long survival. He presented with soft-tissue masses, cytes, 6% band forms, 30% polymorphonuclear leukoand a diagnosis of chloroma was unexpected until cytes, 14% monocytes, 5% eosinophils, 1% basophils, lymph node biopsy examination was done. Lymphadeand 30% lymphocytes. The hemoglobin level was 10.8 nopathy responded initially to local therapy and then g/dL and the platelet count was 250,00O/mms. Bone later to systemic therapy. He continued to show remarrow examination showed 25% myeloblasts. Theralapse even at a time when his leukemia was controlled py was initiated with cytosine arabinoside given as a in the chronic phase. Death occurred 14 months after continuous infusion of 20 mg/m*/day for 21 days. The presentation with blast transformation. In reviewing night sweats resolved, but the skin lesions only partialthe literature over the past 20 years, we encountered ly regressed. This was followed by a maintenance dose only a few cases that were similar to our case in that of 6-mercaptopurine given orally. multiple and/or recurring lesions were present and The patient did well for an additional six months, survival was prolonged. although the skin lesions did not regress. In January Wiernik and Serpick {ll] reported on one patient 1986, he began to lose weight again, and on January 22, with normal blood and bone marrow who developed 1986, he developed short-term mental confusion and multiple granulocytic sarcomas at bony sites. Our palethargy. At that time, the white blood cell count was tient, although not unique, was nonetheless unusual, 53,000/mm3 with 30% blasts, 9% myelocytes, 15% band with multiple sites of disease that were not associated forms, 16% polymorphonuclear leukocytes, 15% lymwith rapid progression to blastic crisis and that for a September
1989
The American
Journal
of Medicine
Volume
time were responsive and controllable by both radiation therapy and systemic chemotherapy. The second patient presented with granulocytic sarcoma of the bone within two months of developing blastic transformation, which is a more typical situation. Chabner et al [8], in an early review of the bone lesions in chronic granulocytic leukemia, found destructive lesions in six of 205 evaluable patients. One of these patients developed a pathologic fracture. Neiman et al [S] in grouping chronic granulocytic leukemia and acute granulocytic leukemia cases together encountered eight cases with lytic bone lesions. In Case 3, our patient was diagnosed with what is essentially considered leukemia cutis except that very early in the course of his disease nodular skin lesions could be seen. We describe him here because he seems to be unique, with extramedullary leukemia associated with preleukemic or myelodysplastic syndrome. The continuous administration of low-dose cytosine arabinoside did not convert his bone marrow to normal morphology or improve his skin lesions. With the increasing recognition of the myelodysplastic syndrome, it is likely that more associations may be recognized in the future.
SUM MARY This report describes three unusual patients with lesions due to myeloblasts. In one instance, the patient presented with massive adenopathy. The second patient had bone lesions and a pathologic fracture. The third patient, with myelodysplasia, had diffuse skin lesions infiltrated with myeloblasts. These cases fit the diagnostic category of granulocytic sarcoma. Granulocytic sarcoma is a tumor of immature myeloid cells that may involve any site in the body but that most commonly affects the skin, soft tissues, lymph nodes, bone, and periosteum. Lesions can predate leu-
kemia or occur late in an established chronic granulocytic leukemia or acute granulocytic leukemia. The most common presentation occurs late in the course of acute granulocytic leukemia or in chronic granulocytic leukemia as a herald to blastic transformation. Therapy for localized lesions is radiotherapy, which produces prompt shrinkage of the lesions but relapse occurs subsequently. Systemic chemotherapy also produces satisfactory clinical results. In all instances, therapy can only be considered palliative since virtually all patients have a short survival following the appearance of an extrarnedullary myeloblastic lesion. Recognition of this pathologic entity at an early stage may give us information on the best management for these patients.
REFERENCES 1. Burns A: Observations of surgical anatomy. In: Head and neck. London: Thomas Royce and Company, 1811; 364-366. 2 King A: A case of chloroma. Month J Med 1853; 17: 97-99. 3. Dock G: Chloroma and its relation to leukemia. Am J Med Sci 1893: 106: 152157. 4. Rappaport H: Tumors of the hematoooietic svstemn. In: Atlas of tumor oathology. section 3. fasicle 8. Washington, d.C.: Armed Forces Institute of Pathology. 1966: 241-243. 5. Neiman RS. Barcos M. Berard C. et al: Granulocytic sarcoma. A clinical pathologic study of 61 biopsy cases. Cancer 1981; 48: 1426-1437. 6. Eshghabadi M. Shojanda M: Isolated granulocytic sarcoma: report of a case and review of the literature. J Clin Oncol 1986: 4: 912-917. 7. Meis JM. Butler JJ, Osborne BM. Manning JT: Granulocytic sarcoma in nonleukemic patients. Cancer 1986; 58: 2697-2709. B.Chabnsr BA, Haskell CM. Canellos GP: Destructive bone lesions in chronic granulocytic leukemia. Medicine (Baltimore) 1969: 48: 4Ol-tlO. 9. Long LC, Mihm MC: Multiple granulocytic tumors of the skin: report of six cases with myelogenous leukemia with initial manifestations in the skin. Cancer 1977: 39: 2004-2016. 10. Muss HB. Maloney WC: Chloroma and other myeloblastic tumors. Blood 1973; 42: 721-728. 11. Wiernik PH. Serpick AA: Granulocytic sarcoma (chloroma). Blood 1970; 35: 361-369.
September
1989
The American
Journal
of Medicine
Volume 87
347
Sarcoma: Three Unusual Patients
ROBERT G. GIITIN, M.D., WILLIAM B. SCHARFMAN, M.D., PETER T. BURKART, M.D. AUIXIY, New York
his report is comprised of three unusual patients. T Two patients had chronic granulocytic leukemia, and one was diagnosed as having a myelodysplastic syndrome. One patient presented with massive lymphadenopathy, the second with lytic bone lesions, and the third with diffuse skin involvement. In all three instances, biopsy examination showed that the lesions were composed of myeloblasts, and, subsequently, a diagnosis of granulocytic sarcoma (chloroma) was made. These casesillustrate that the diagnosis of granulocytic sarcoma should be considered when tumors or lytic lesions or skin involvement are encountered in patients with chronic granulocytic leukemia or acute granulocytic leukemia. In addition, this lesion needsto be considered in myelodysplastic syndromes. Historically, Burns [l] originally described this lesion in 1811. King [2] described chloroma as a green tumor, the color of which was due to myeloperoxidase in the cells. Dock [3] first noted the association of granulocytic sarcoma with acute leukemia in 1893. The term granulocytic sarcomawas first used by Rappaport [4] and is currently in use. Excellent reviews are presented by Neiman et al [5] and Eshghabadi and Shojanda [6]. Meis and co-workers [7] discuss the subject of granulocytic sarcoma in nonleukemic patients. Chabner et al [8] describe destructive bone lesions with granulocytic sarcoma. Long and Mihm [9] report those casespresenting with skin manifestations.
CASE REPORTS Patient 1 A Il-year-old man was admitted to Albany Medical Center Hospital on March 12,1984, for evaluation of a large left axillary mass.Physical findings included hepatosplenomegaly and a left axillary soft-tissue mass but no palpable lymph nodes. Computed tomographic (CT) scan of the chest and abdomen outlined a 6 X 6cm axillary mass aswell as multiple left-sided axillary lymph nodes and an enlarged spleen. The blood count showed a white cell count of 34,700/mm3 with 23% band forms, 45% polymorphonuclear leukocytes, 6% lymphocytes, 9% monocytes, 2% eosinophils, 7% myelocytes, and 1% promyelocytes. Findings on bone marrow examination were consistent with chronic granulocytic leukemia, and 100% of the mitoses contained a Philadelphia chromosome.A biopsy specimen was obtained from the axillary mass,and a diagnosisof granulocytic sarcoma was made after electron microsFrom the Division of Hematology, Department of Medicine, Albany Medical College, Albany, New York. Requests for reprints should be addressed to William E. Scharfman. M.D., Division of Hematology. Albany Medical ColCurrent address for D;. Gittin is Division of Hematology/Oncology, sity of North Carolina, Chapel Hill, North Carolina.
Univer-
copy and Leder’s staining (chloroacetate esterase granulocytic cell strain). Radiation therapy resolved the left axillary mass. Therapy with oral hydroxyurea was started to control the white blood cell count. Over the next six months, the patient developed enlarging right cervical, left supraventricular, and right axillary lymph nodes that were successfully treated with radiation therapy. On September 4,1984, the patient was admitted to the hospital with newly enlarging cervical and submandibular lymph nodes plus a right-sided axillary mass. His blood count revealed a white cell count of 15,800/mm3and bone marrow again was consistent with chronic granulocytic leukemia in the chronic phase. Chemotherapy was started with cytosine arabinoside 150 mg/m2 intravenously daily for four days followed by 200 mg subcutaneously twice weekly for six consecutive weeks. The lymphadenopathy and the axillary mass completely resolved. On October 27,1984, the patient had developed cervical, supraclavicular, inguinal, and right axillary lymphadenopathy, and he was again treated with intravenous cytosine arabinoside followed by subcutaneous cytosine arabinoside, and once again the lymphadenopathy completely resolved. On February 5,1985, the patient was readmitted to the hospital with newly enlarging inguinal, cervical, and supraclavicular lymph nodes. Chemotherapy was given with daunorubicin hydrochloride, cytosine arabinoside, and 6-thioguanine; once more, lymphadenopathy completely resolved. In May 1985, he was readmitted for the last time with abdominal pain and also a deep venous thrombosisand sepsis.CT scanning showed massive mediastinal lymphadenopathy as well asparenchymal lung infiltration and a chest wall mass.The white cell count was now 72,000/mm3 with 24% blasts, 2% promyelocytes, 17%myelocytes, 9% metamyelocytes, 20%banded forms, 25% polymorphonuclear leukocytes, 2% basophils, and 1% eosinophils. The hemoglobin was 11.4 g/dL, and the platelet count was 58,000/mm3. Bone marrow contained 35% blasts. The patient died of septicemia. Patient 2 A 49-year-old man was diagnosed as having chronic granulocytic leukemia in July 1982 when his white blood cell count was found to be 114,000/mm3.Findings from bone marrow aspiration and biopsy examination were consistent with chronic granulocytic leukemia in the chronic phase, and the Philadelphia chromosome was observed. Splenomegaly was present. He was treated successfully with oral busulfan. In December 1985, he was found to have an osteoblastic lesion of the left femur and was treated with radiation therapy to a total of 3,000 rads in 15 fractions with complete resolution by radiography. On February 1, 1986, he presented with a severe
September 1989 The American Journal of Medicine
Volume 87
345
GRANULOCYTIC
SARCOMA
/ GIllIN
ET AL
pain in the left leg. The radiograph showed a transverse pathologic fracture of the femur. The blood count showed a white cell count of 34,000/mm3 with 30% band forms, 48% segmented neutrophils, 9% lymphocytes, 5% monocytes, 2% eosinophils, 1% basophils, and 5% metamyelocytes. The platelet count was 192,000/mm3 and the level of hemoglobin was 14.6 g/ dL. On May 3, 1986, open reduction and internal fixation were performed. The biopsy specimen showed clusters of blast cells in the periosteum that stained positive with Leder’s stain. Hemorrhagic and infectious complications developed, and the patient’s course declined sharply because of supervening sepsis. Preterminally, the white cell count had risen to 167,000/mm3 with 35% myeloblasts in the peripheral blood. Bone marrow examination simultaneously showed 75% myeloblasts.
phocytes, and 2% basophils. Bone marrow examination showed 95% blasts, which were strongly positive for fluoride-inhibited nonspecific esterase. No treatment was given, and the patient died in a hospice. The skin lesions had not regressed.
346
87
COMMENTS
Granulocytic sarcoma is a localized tumor of immature myeloid cells. Although originally believed to be a rare lesion, it has been the subject of a number of reviews (Neiman et al [5] and Eshghabadi and Shojanda [6]). Granulocytic sarcoma has been described as a complication of acute granulocytic or chronic granulocytic leukemia, and it may occur without blood or bone marrow evidence of leukemia. In chronic granulocytic leukemia, the lesion implies a poor prognosis and usually predicts blast transformation, The incidence has been predicted to be 4.5% in chronic granulocytic leukemia and 2.5% in acute granulocytic leukePatient 3 A 79-year-old man had a history of chronic anemia mia (MUSS and Malony [lo]). Reports of chloroma preceding leukemia have since 1981. In October 1984, he presented to the Albastressed the poor prognosis associated with these tuny Medical Center Hospital with night sweats, prurimors in that virtually all patients eventually develop tus, and diffuse skin thickening associated with some leukemia within a mean of 10 months [5,6]. The clinidiscrete nodules on the upper extremities and trunk. cal spectrum of granulocytic sarcoma is broad and virThe rest of the physical examination was unremarkable. The white cell count was 24,900/mm3 with 3% tually any site can be involved, from the prostatic gland to the anterior chamber of the eye. The most metamyelocytes, 48% polymorphonuclear leukocytes, 9% band forms, 23% monocytes, 5% eosinophils, and commonly involved sites in order of occurrence are 11% lymphocytes. The platelet count was 244,000/ skin, lymph nodes, soft tissues overlying bone, bone mm3, and the hemoglobin level was 12.1 g/dL. Bone and periosteum, and finally viscera. Disease in the marrow examination revealed a hypercellular marrow epidural space with or without vertebral body involvewith a myeloid:erythroid ratio of 8:l. There were a few ment can cause spinal cord compression. Single lesions immature monocytic precursors in the marrow as well are the most common presentation, and in one large as slight eosinophilia, 4% myeloblasts, and megaloseries [5] (61 tumors in 50 patients), 42 patients had blastic red cell maturation. The megakaryocytes were only a single tumor. These lesions are sensitive to irranormal. There were no abnormal sideroblasts. Skin diation as well as to chemotherapy. Eshghabadi and biopsy examination showed myeloblastic infiltration. Shojanda [6] have recently described one patient with A diagnosis of myelodysplastic syndrome most consisisolated granulocytic sarcoma, reviewed 33 other cases tent with a chronic myelomonocytic leukemia was from the literature with this lesion, and identified five made at that time. The patient was treated with lowlong-term survivors. All patients received intensive dose cytosine arabinoside, but this regimen had no systemic chemotherapy. Meis et al [7] have recently effect on the skin lesions. reviewed the experience at the University of Texas The patient’s condition remained stable for many M.D. Anderson Hospital Cancer Center with 16 pamonths; however, on June 11,1985, he was admitted to tients seen over 25 years. Seven patients did not develthe hospital because of a 20-pound weight loss and op leukemia, with the longest follow-up 16 years. All progression of the skin lesions as well as an intense patients were given systemic chemotherapy. pruritus. Physical examination showed splenomegaly In the first case described, multiple chloromas apas well as enlarged right and left cervical lymph nodes. peared in the patient with chronic granulocytic leukeThe blood count showed a white cell count of 54,OOOl mia in the chronic phase, and yet this patient achieved mm3 with 8% blasts, 1% promyelocytes, 5% myeloa long survival. He presented with soft-tissue masses, cytes, 6% band forms, 30% polymorphonuclear leukoand a diagnosis of chloroma was unexpected until cytes, 14% monocytes, 5% eosinophils, 1% basophils, lymph node biopsy examination was done. Lymphadeand 30% lymphocytes. The hemoglobin level was 10.8 nopathy responded initially to local therapy and then g/dL and the platelet count was 250,00O/mms. Bone later to systemic therapy. He continued to show remarrow examination showed 25% myeloblasts. Theralapse even at a time when his leukemia was controlled py was initiated with cytosine arabinoside given as a in the chronic phase. Death occurred 14 months after continuous infusion of 20 mg/m*/day for 21 days. The presentation with blast transformation. In reviewing night sweats resolved, but the skin lesions only partialthe literature over the past 20 years, we encountered ly regressed. This was followed by a maintenance dose only a few cases that were similar to our case in that of 6-mercaptopurine given orally. multiple and/or recurring lesions were present and The patient did well for an additional six months, survival was prolonged. although the skin lesions did not regress. In January Wiernik and Serpick {ll] reported on one patient 1986, he began to lose weight again, and on January 22, with normal blood and bone marrow who developed 1986, he developed short-term mental confusion and multiple granulocytic sarcomas at bony sites. Our palethargy. At that time, the white blood cell count was tient, although not unique, was nonetheless unusual, 53,000/mm3 with 30% blasts, 9% myelocytes, 15% band with multiple sites of disease that were not associated forms, 16% polymorphonuclear leukocytes, 15% lymwith rapid progression to blastic crisis and that for a September
1989
The American
Journal
of Medicine
Volume
time were responsive and controllable by both radiation therapy and systemic chemotherapy. The second patient presented with granulocytic sarcoma of the bone within two months of developing blastic transformation, which is a more typical situation. Chabner et al [8], in an early review of the bone lesions in chronic granulocytic leukemia, found destructive lesions in six of 205 evaluable patients. One of these patients developed a pathologic fracture. Neiman et al [S] in grouping chronic granulocytic leukemia and acute granulocytic leukemia cases together encountered eight cases with lytic bone lesions. In Case 3, our patient was diagnosed with what is essentially considered leukemia cutis except that very early in the course of his disease nodular skin lesions could be seen. We describe him here because he seems to be unique, with extramedullary leukemia associated with preleukemic or myelodysplastic syndrome. The continuous administration of low-dose cytosine arabinoside did not convert his bone marrow to normal morphology or improve his skin lesions. With the increasing recognition of the myelodysplastic syndrome, it is likely that more associations may be recognized in the future.
SUM MARY This report describes three unusual patients with lesions due to myeloblasts. In one instance, the patient presented with massive adenopathy. The second patient had bone lesions and a pathologic fracture. The third patient, with myelodysplasia, had diffuse skin lesions infiltrated with myeloblasts. These cases fit the diagnostic category of granulocytic sarcoma. Granulocytic sarcoma is a tumor of immature myeloid cells that may involve any site in the body but that most commonly affects the skin, soft tissues, lymph nodes, bone, and periosteum. Lesions can predate leu-
kemia or occur late in an established chronic granulocytic leukemia or acute granulocytic leukemia. The most common presentation occurs late in the course of acute granulocytic leukemia or in chronic granulocytic leukemia as a herald to blastic transformation. Therapy for localized lesions is radiotherapy, which produces prompt shrinkage of the lesions but relapse occurs subsequently. Systemic chemotherapy also produces satisfactory clinical results. In all instances, therapy can only be considered palliative since virtually all patients have a short survival following the appearance of an extrarnedullary myeloblastic lesion. Recognition of this pathologic entity at an early stage may give us information on the best management for these patients.
REFERENCES 1. Burns A: Observations of surgical anatomy. In: Head and neck. London: Thomas Royce and Company, 1811; 364-366. 2 King A: A case of chloroma. Month J Med 1853; 17: 97-99. 3. Dock G: Chloroma and its relation to leukemia. Am J Med Sci 1893: 106: 152157. 4. Rappaport H: Tumors of the hematoooietic svstemn. In: Atlas of tumor oathology. section 3. fasicle 8. Washington, d.C.: Armed Forces Institute of Pathology. 1966: 241-243. 5. Neiman RS. Barcos M. Berard C. et al: Granulocytic sarcoma. A clinical pathologic study of 61 biopsy cases. Cancer 1981; 48: 1426-1437. 6. Eshghabadi M. Shojanda M: Isolated granulocytic sarcoma: report of a case and review of the literature. J Clin Oncol 1986: 4: 912-917. 7. Meis JM. Butler JJ, Osborne BM. Manning JT: Granulocytic sarcoma in nonleukemic patients. Cancer 1986; 58: 2697-2709. B.Chabnsr BA, Haskell CM. Canellos GP: Destructive bone lesions in chronic granulocytic leukemia. Medicine (Baltimore) 1969: 48: 4Ol-tlO. 9. Long LC, Mihm MC: Multiple granulocytic tumors of the skin: report of six cases with myelogenous leukemia with initial manifestations in the skin. Cancer 1977: 39: 2004-2016. 10. Muss HB. Maloney WC: Chloroma and other myeloblastic tumors. Blood 1973; 42: 721-728. 11. Wiernik PH. Serpick AA: Granulocytic sarcoma (chloroma). Blood 1970; 35: 361-369.
September
1989
The American
Journal
of Medicine
Volume 87
347