CASE REPORTS
Laparoscopic
Diagnosis of Ewing’s Sarcoma Metastatic Case Report and Review of the Literature
By Douglas J. Mackenzie,
Beverly James, Stephen A. Geller, and Jonathan Los Angeles, California
0 In this report we describe how a laparoscopic procedure confirmed a confusing and exceptional case of Ewing’s sarcoma metastatic to the liver. Copyright o 1992 by W.B. Saunders Company INDEX WORDS: Ewing’s sarcoma, laparoscopic
biopsy.
L
APAROSCOPY is becoming more entrenched as a valuable component of the diagnostic arsenal of the general surgeon. As modern medical and surgical therapy improves, patients who would have previously died earlier of their diseases are identified with some unusual manifestations of their disease. CASE REPORT
1
(January).
M. Sackier
lesions (Fig 2). Liver aspirate demonstrated a few cells consistent with malignancy, although there was not sufficient material for histochemical and immunologic studies. Laparoscopy was then performed and guided 14-gauge Trucut (Travenol Laboratories Inc. Deertield, IL) biopsy specimens were taken of several firm pale nodules of the liver (Fig 3). Although the patient was thrombocytopenic with a platelet count of 45,OOOimm’ after platelet transfusion, the initial brisk bleeding from the biopsy site was easily controlled with electrocautery. Frozen sections were interpreted as showing a malignant tumor and permanent sections showed densely packed anaplastic cells identical to the primary tumor (Fig 4). The entire abdomen was surveyed with the laparoscope and was otherwise grossly free of disease. The patient was discharged home and given supportive care until her death 3 weeks later.
DISCUSSION
A 16-year-old girl developed pain over her left iliac prominence and left pelvic area, with no constitutional symptoms. Physical examination showed an ill-defined 7 x 8 cm mass over the left iliac prominence, associated with local venous engorgement, tenderness, and warmth. Radiographs and computed tomography (CT) demonstrated a destructive lesion of the left iliac bone with soft tissue involvement and calcification. A needle biopsy of the anterior superior iliac crest was obtained. Hematoxylin and eosin stained sections showed extensive areas of hemorrhage and necrosis. The viable portion of the tumor showed satelliting around thick-walled blood vessels in a so-called peritheIiomatous pattern (Fig 1). The neoplasm was partially composed of cells with uniform round to ovoid nuclei with delicate, evenly dispersed chromatin. However, there was an abundance of larger more anaplastic forms with variable nuclei and multiple prominent nucleoli. The cytoplasm was multivacuolated and showed the presence of numerous glycogen granules that reacted with Periodic Acid Schiff (PAS). The tumor was high grade as evidenced by numerous mitotic figures (17110 HPF). Immunohistochemical stains were negative for S-100, epithelial membrane antigen, keratin, leukocyte common antigen, and vimentin. Electronmicroscopy showed multiple pools of cytoplasmic glycogen, a finding consistent with the diagnosis of Ewing’s sarcoma. An iliac bone marrow aspirate also contained atypical large cell Ewing’s sarcoma. Bone scan did not suggest extrailiac bony involvement at this time. Monthly courses of chemotherapy with ifosfamide, adriamycin, and VP16 were instituted with shrinkage of the iliac mass by serial CT scans. Bone marrow biopsy specimen 5 months after diagnosis was negative for tumor. Seven months after diagnosis, the patient was readmitted with fever. neutropenia, and symptoms of upper respiratory infection. Antibiotics were commenced empirically although all cultures were negative. During this admission the patient developed jaundice. elevated liver function tests, and an abdominal CT scan showed multiple hepatic and splenic lesions as well as lumbar and thoracic spine lesions. Percutaneous liver aspirate at this time did not demonstrate malignant cells. A repeat CT scan was obtained 1 week later, which showed a dramatic increase in the size of the hrpatic lesions and an increase in the size and number of splenic Journalof Pediatric Surgery, Vol 27, No
to the Liver:
1992: np 93-95
Ewing’s sarcoma is a highly malignant bone tumor that generally presents during the first two decades of life, often during the pubertal growth spurt. The tumor usually arises as a focus within the marrow cavity with long bones being the most common site followed by the pelvis. Ewing’s sarcoma may also arise in soft tissue.‘.’ The tumor is often quite large at presentation, and frequently has significant extension into the soft tissues. Histologically, the cells are typically undifferentiated small round cells with prominent nuclei. Cytoplasmic PAS-positive granules indicative of glycogen stores are distinctive for Ewing’s sarcoma, helping to distinguish the tumor from undifferentiated sarcoma, carcinoma, neuroblastoma, or bone lymphoma. The case presented represents a large cell (atypical) variant of Ewing’s sarcoma, which has been well described? Its clinical course mimics that of typical Ewing’s sarcoma with differentiation from large cell lymphoma or small cell osteosarcoma being its major point of diagnostic interest. Poor prognosis has been attributed to central location of tumor, systemic symptoms at diagnosis, presence of metastases at time of diagnosis, young age, and gross soft tissue extension of the primary From the Depatiments of SuQety and Patholo~ and L&orator?, Medicine, Cedars-Sinai Medical Center. Los Angle,. CA. Dute uccepted: September 3. 1991. Address reprint requests to Jonathan M. Sacker, MD, FRCS, Department of Sueety, Cedars-Sinai Medical Center. 8700 Be\ler!y Bhad. Los Angeles, CA 90048 Copyright II 1992 by W.B. Saunders Cornpurr) 0022-3468/9212701-0025$03.00l0
93
94
MACKENZIEETAL
Fig 2.
CT image showing hepatic and splenic metastases.
tumor.4.5 Metastases at the time of diagnosis are present in 25% of patients and most commonly involve other skeletal sites, lung, lymph nodes, and brain, although no sites have been spared.‘.“’ In an autopsy series of 26 cases of Ewing’s sarcoma arising in bone, liver metastases were noted in four cases and splenic metastases in three. The lung was the most common site of metastasis, being present in 85% of patients.h In one series of extraosseous Ewing’s sarcoma, lung was again the most common site for metastases, followed by liver (3/22 patients).” Bone metastases were not identified. In another series of extraosseous Ewing’s sarcoma, 4 of 21 patients had liver metastases, exceeded by lung (17 patients) and bone (10 patients).” None of the patients in these series presented with hepatic metastases. The present case illustrates the rare complication of early and fulminant hepatic and splenic metastases
Fig 1. (A) Iliac biopsy section showing extensive areas of hemorrhage and necrosis (tong arrow) with 8 peritheliomatous pattern (short arrows). (B) malignant cells with anaplastic nuclei. (H&E; original magnification [A] x100, [B] x400.) Fig 3.
L8p8roscopicphotograph of liver showing
tumor
nodule.
LAPAROSCOPIC
DIAGNOSIS
95
OF EWING’S SARCOMA
biopsy are also indicated when hepatic or peritoneal malignancy is suspected and imaging studies are negative or norma1.14 Although adult laparoscopy equipment was used in this 16-year-old girl, the value of laparoscopy in pediatrics has been appreciated since the development of the Hopkins rod lens optical system allowed miniaturization.‘5.” The value of laparoscopy has been defined in many other clinically puzzling situations” and its use in this case spared a sick young girl of the morbidity of laparotomy and enabled secure hemostasis in the presence of profound thrombocytopenia. As more patients have longer survival times with treated malignant disease, laparoscopy will be used more frequently to detect intraabdominal metastases in order to guide therapy appropriate to the patient’s clinical state and prognosis. REFERENCES
Fig 4. Liver biopsy section showing densely packed anaplastic cells replacing much of the normal hepatic parenchyma, with residual liver showing groups of malignant cells infiltrating hepatic sinusoids (H&E, original magnification x 100).
of a Ewing’s sarcoma despite an initially successful chemotherapy regimen. Serial CT scans of the liver and spleen lesions during the patient’s decline were more suggestive of a rapidly progressing infectious process and initial liver aspirate was nondiagnostic. Although repeat liver aspirate was suggestive of malignancy, diagnosis was confirmed only with laparoscopically guided Trucut biopsy. Further care appropriate to the patient’s terminal state could then proceed. Laparoscopy has the capability to solve diagnostic dilemmas when other diagnostic modalities have failed, and with proper use can avoid the performance of perhaps time-wasting and less definitive tests. Large-bore biopsy via laparoscopy has been previously shown to be useful for diagnosis in the setting of liver metastases.” Equivocal ultrasoundguided biopsies or impairments of coagulation demanding biopsy under direct vision are indications for laparoscopically guided biopsy.‘3 Laparoscopy and
1. Rud NP. Reiman HM, Pritchard DJ. et al: Extraosseous Ewing’s sarcoma. Cancer 64: 1548- 1553. 1S-3 2. O’Keeffe F, Lorigan JG, Wallace S: Radiological features of extraskeletal Ewing sarcoma. Br J Radio1 63:456-460, 1990 3. Nascimento AG, Cooper KL, Unni KK, et al: A clinicopathologic study of 20 cases of large cell (atypical) Ewing’s sarcoma of bone. Am J Surg Pathol4:29-36, 1980 4. Pomeroy TC, Johnson RE: Prognostic factors for survival in Ewing’s sarcoma. Am J Roentgen01 Rad Ther Nucl Med 123:598606, 1975 5. Mendenhall CM, Marcus RB, Enneking WF, et al: The prognostic significance of soft tissue extension in Ewing’s sarcoma. Cancer 51:913-917, 1983 6. Telles NC. Rabson AS, Pomeroy TC: Ewing’s sarcoma: An autopsy study. Cancer 41:2321-2329, 1978 7. Zidkova H, Drechslerova J. Matejovsky Z, et al: An extensive metastasis of Ewing’s sarcoma in the adrenal-renal area. Ceskosl Radio1 44:37-40, 1990 8. Simpson RK, Bruner JM. Leavens ME: Metastatic Ewing’s sarcoma to the brain: Case report and review of treatment. Surg Neural 31234-238. 1989 9. Young RH. Scully RE: Sarcomas metastatic to the ovary: A report of 21 cases. Int J Gynecol Path01 9:231-251, 1090 10. Hagay ZJ, Zirkin HJ. Moses M. et al: Ewing’s sarcoma metastatic to focal nodular hyperplasia of liver. J Surg Oncol 32:100-105, 1986 11. Angervall L, Enzinger FM: Extraskeletal neoplasm resembling Ewing’s sarcoma. Cancer 36:240-251. 1475 12. Fornai F. Rapaccini GL, Cavanna L. et al: Diagnosis of hepatic lesions: Ultrasonically guided tine needle biopsy or laparoscopy? Gastrointest Endosc 34:231-234. 198X 13. Gandolfi L, Muratori R, Solmi L, et al: Laparoscopy compared with ultrasonography in the diagnosis of hepatocellular carcinoma. Gastrointest Endosc 3550X-5 11, 1989 14. Brady PC, Peebles M. Goldschmid S: Role of laparoscopy in the evaluation of patients with suspected hepatic or peritoneal malignancy. Gastrointest Endosc 37:27-30. 1991 15. Gans SL, Berci G: Advances in endoscopy of infants and children. J Pediatr Surg 6:199-234, 1971 16. Cans SL, Berci G: Peritoneoscopy in infants and children. J Pediatr Surg 8399-405, I073 17. Sackier JM. Berci G: Diagnostic and interventional laparoscopy for the general surgeon. Contemp Surg 37:15-26, 1990
Laparoscopic
Diagnosis of Ewing’s Sarcoma Metastatic Case Report and Review of the Literature
By Douglas J. Mackenzie,
Beverly James, Stephen A. Geller, and Jonathan Los Angeles, California
0 In this report we describe how a laparoscopic procedure confirmed a confusing and exceptional case of Ewing’s sarcoma metastatic to the liver. Copyright o 1992 by W.B. Saunders Company INDEX WORDS: Ewing’s sarcoma, laparoscopic
biopsy.
L
APAROSCOPY is becoming more entrenched as a valuable component of the diagnostic arsenal of the general surgeon. As modern medical and surgical therapy improves, patients who would have previously died earlier of their diseases are identified with some unusual manifestations of their disease. CASE REPORT
1
(January).
M. Sackier
lesions (Fig 2). Liver aspirate demonstrated a few cells consistent with malignancy, although there was not sufficient material for histochemical and immunologic studies. Laparoscopy was then performed and guided 14-gauge Trucut (Travenol Laboratories Inc. Deertield, IL) biopsy specimens were taken of several firm pale nodules of the liver (Fig 3). Although the patient was thrombocytopenic with a platelet count of 45,OOOimm’ after platelet transfusion, the initial brisk bleeding from the biopsy site was easily controlled with electrocautery. Frozen sections were interpreted as showing a malignant tumor and permanent sections showed densely packed anaplastic cells identical to the primary tumor (Fig 4). The entire abdomen was surveyed with the laparoscope and was otherwise grossly free of disease. The patient was discharged home and given supportive care until her death 3 weeks later.
DISCUSSION
A 16-year-old girl developed pain over her left iliac prominence and left pelvic area, with no constitutional symptoms. Physical examination showed an ill-defined 7 x 8 cm mass over the left iliac prominence, associated with local venous engorgement, tenderness, and warmth. Radiographs and computed tomography (CT) demonstrated a destructive lesion of the left iliac bone with soft tissue involvement and calcification. A needle biopsy of the anterior superior iliac crest was obtained. Hematoxylin and eosin stained sections showed extensive areas of hemorrhage and necrosis. The viable portion of the tumor showed satelliting around thick-walled blood vessels in a so-called peritheIiomatous pattern (Fig 1). The neoplasm was partially composed of cells with uniform round to ovoid nuclei with delicate, evenly dispersed chromatin. However, there was an abundance of larger more anaplastic forms with variable nuclei and multiple prominent nucleoli. The cytoplasm was multivacuolated and showed the presence of numerous glycogen granules that reacted with Periodic Acid Schiff (PAS). The tumor was high grade as evidenced by numerous mitotic figures (17110 HPF). Immunohistochemical stains were negative for S-100, epithelial membrane antigen, keratin, leukocyte common antigen, and vimentin. Electronmicroscopy showed multiple pools of cytoplasmic glycogen, a finding consistent with the diagnosis of Ewing’s sarcoma. An iliac bone marrow aspirate also contained atypical large cell Ewing’s sarcoma. Bone scan did not suggest extrailiac bony involvement at this time. Monthly courses of chemotherapy with ifosfamide, adriamycin, and VP16 were instituted with shrinkage of the iliac mass by serial CT scans. Bone marrow biopsy specimen 5 months after diagnosis was negative for tumor. Seven months after diagnosis, the patient was readmitted with fever. neutropenia, and symptoms of upper respiratory infection. Antibiotics were commenced empirically although all cultures were negative. During this admission the patient developed jaundice. elevated liver function tests, and an abdominal CT scan showed multiple hepatic and splenic lesions as well as lumbar and thoracic spine lesions. Percutaneous liver aspirate at this time did not demonstrate malignant cells. A repeat CT scan was obtained 1 week later, which showed a dramatic increase in the size of the hrpatic lesions and an increase in the size and number of splenic Journalof Pediatric Surgery, Vol 27, No
to the Liver:
1992: np 93-95
Ewing’s sarcoma is a highly malignant bone tumor that generally presents during the first two decades of life, often during the pubertal growth spurt. The tumor usually arises as a focus within the marrow cavity with long bones being the most common site followed by the pelvis. Ewing’s sarcoma may also arise in soft tissue.‘.’ The tumor is often quite large at presentation, and frequently has significant extension into the soft tissues. Histologically, the cells are typically undifferentiated small round cells with prominent nuclei. Cytoplasmic PAS-positive granules indicative of glycogen stores are distinctive for Ewing’s sarcoma, helping to distinguish the tumor from undifferentiated sarcoma, carcinoma, neuroblastoma, or bone lymphoma. The case presented represents a large cell (atypical) variant of Ewing’s sarcoma, which has been well described? Its clinical course mimics that of typical Ewing’s sarcoma with differentiation from large cell lymphoma or small cell osteosarcoma being its major point of diagnostic interest. Poor prognosis has been attributed to central location of tumor, systemic symptoms at diagnosis, presence of metastases at time of diagnosis, young age, and gross soft tissue extension of the primary From the Depatiments of SuQety and Patholo~ and L&orator?, Medicine, Cedars-Sinai Medical Center. Los Angle,. CA. Dute uccepted: September 3. 1991. Address reprint requests to Jonathan M. Sacker, MD, FRCS, Department of Sueety, Cedars-Sinai Medical Center. 8700 Be\ler!y Bhad. Los Angeles, CA 90048 Copyright II 1992 by W.B. Saunders Cornpurr) 0022-3468/9212701-0025$03.00l0
93
94
MACKENZIEETAL
Fig 2.
CT image showing hepatic and splenic metastases.
tumor.4.5 Metastases at the time of diagnosis are present in 25% of patients and most commonly involve other skeletal sites, lung, lymph nodes, and brain, although no sites have been spared.‘.“’ In an autopsy series of 26 cases of Ewing’s sarcoma arising in bone, liver metastases were noted in four cases and splenic metastases in three. The lung was the most common site of metastasis, being present in 85% of patients.h In one series of extraosseous Ewing’s sarcoma, lung was again the most common site for metastases, followed by liver (3/22 patients).” Bone metastases were not identified. In another series of extraosseous Ewing’s sarcoma, 4 of 21 patients had liver metastases, exceeded by lung (17 patients) and bone (10 patients).” None of the patients in these series presented with hepatic metastases. The present case illustrates the rare complication of early and fulminant hepatic and splenic metastases
Fig 1. (A) Iliac biopsy section showing extensive areas of hemorrhage and necrosis (tong arrow) with 8 peritheliomatous pattern (short arrows). (B) malignant cells with anaplastic nuclei. (H&E; original magnification [A] x100, [B] x400.) Fig 3.
L8p8roscopicphotograph of liver showing
tumor
nodule.
LAPAROSCOPIC
DIAGNOSIS
95
OF EWING’S SARCOMA
biopsy are also indicated when hepatic or peritoneal malignancy is suspected and imaging studies are negative or norma1.14 Although adult laparoscopy equipment was used in this 16-year-old girl, the value of laparoscopy in pediatrics has been appreciated since the development of the Hopkins rod lens optical system allowed miniaturization.‘5.” The value of laparoscopy has been defined in many other clinically puzzling situations” and its use in this case spared a sick young girl of the morbidity of laparotomy and enabled secure hemostasis in the presence of profound thrombocytopenia. As more patients have longer survival times with treated malignant disease, laparoscopy will be used more frequently to detect intraabdominal metastases in order to guide therapy appropriate to the patient’s clinical state and prognosis. REFERENCES
Fig 4. Liver biopsy section showing densely packed anaplastic cells replacing much of the normal hepatic parenchyma, with residual liver showing groups of malignant cells infiltrating hepatic sinusoids (H&E, original magnification x 100).
of a Ewing’s sarcoma despite an initially successful chemotherapy regimen. Serial CT scans of the liver and spleen lesions during the patient’s decline were more suggestive of a rapidly progressing infectious process and initial liver aspirate was nondiagnostic. Although repeat liver aspirate was suggestive of malignancy, diagnosis was confirmed only with laparoscopically guided Trucut biopsy. Further care appropriate to the patient’s terminal state could then proceed. Laparoscopy has the capability to solve diagnostic dilemmas when other diagnostic modalities have failed, and with proper use can avoid the performance of perhaps time-wasting and less definitive tests. Large-bore biopsy via laparoscopy has been previously shown to be useful for diagnosis in the setting of liver metastases.” Equivocal ultrasoundguided biopsies or impairments of coagulation demanding biopsy under direct vision are indications for laparoscopically guided biopsy.‘3 Laparoscopy and
1. Rud NP. Reiman HM, Pritchard DJ. et al: Extraosseous Ewing’s sarcoma. Cancer 64: 1548- 1553. 1S-3 2. O’Keeffe F, Lorigan JG, Wallace S: Radiological features of extraskeletal Ewing sarcoma. Br J Radio1 63:456-460, 1990 3. Nascimento AG, Cooper KL, Unni KK, et al: A clinicopathologic study of 20 cases of large cell (atypical) Ewing’s sarcoma of bone. Am J Surg Pathol4:29-36, 1980 4. Pomeroy TC, Johnson RE: Prognostic factors for survival in Ewing’s sarcoma. Am J Roentgen01 Rad Ther Nucl Med 123:598606, 1975 5. Mendenhall CM, Marcus RB, Enneking WF, et al: The prognostic significance of soft tissue extension in Ewing’s sarcoma. Cancer 51:913-917, 1983 6. Telles NC. Rabson AS, Pomeroy TC: Ewing’s sarcoma: An autopsy study. Cancer 41:2321-2329, 1978 7. Zidkova H, Drechslerova J. Matejovsky Z, et al: An extensive metastasis of Ewing’s sarcoma in the adrenal-renal area. Ceskosl Radio1 44:37-40, 1990 8. Simpson RK, Bruner JM. Leavens ME: Metastatic Ewing’s sarcoma to the brain: Case report and review of treatment. Surg Neural 31234-238. 1989 9. Young RH. Scully RE: Sarcomas metastatic to the ovary: A report of 21 cases. Int J Gynecol Path01 9:231-251, 1090 10. Hagay ZJ, Zirkin HJ. Moses M. et al: Ewing’s sarcoma metastatic to focal nodular hyperplasia of liver. J Surg Oncol 32:100-105, 1986 11. Angervall L, Enzinger FM: Extraskeletal neoplasm resembling Ewing’s sarcoma. Cancer 36:240-251. 1475 12. Fornai F. Rapaccini GL, Cavanna L. et al: Diagnosis of hepatic lesions: Ultrasonically guided tine needle biopsy or laparoscopy? Gastrointest Endosc 34:231-234. 198X 13. Gandolfi L, Muratori R, Solmi L, et al: Laparoscopy compared with ultrasonography in the diagnosis of hepatocellular carcinoma. Gastrointest Endosc 3550X-5 11, 1989 14. Brady PC, Peebles M. Goldschmid S: Role of laparoscopy in the evaluation of patients with suspected hepatic or peritoneal malignancy. Gastrointest Endosc 37:27-30. 1991 15. Gans SL, Berci G: Advances in endoscopy of infants and children. J Pediatr Surg 6:199-234, 1971 16. Cans SL, Berci G: Peritoneoscopy in infants and children. J Pediatr Surg 8399-405, I073 17. Sackier JM. Berci G: Diagnostic and interventional laparoscopy for the general surgeon. Contemp Surg 37:15-26, 1990
