ANATOMIC PATHOLOGY Single Case Report
Extraskeletal Myxoid Chondrosarcoma of the Pleura Report of a Case Clinically Simulating Mesothelioma STEVEN P. GOETZ, M.D., ROBERT A. ROBINSON, M.D., PH.D., AND STEVE K. LANDAS, M.D.
with the exposure history were found in the lung tissue sections and confirmed by energy-dispersive spectrometry. This case demonstrates an unusual pleural primary neoplasm associated with asbestos. (Key words: Extraskeletal myxoid chondrosarcoma; Pleura; Asbestos; Neoplasm) Am J Clin Pathol 1992;97: 498-502
were stained with hematoxylin and eosin, the periodic acid-Schiff reaction, with and without diastase digestion, Prussian blue for iron, Alcian blue with and without bovine testicular hyaluronidase (Sigma Chemical Co., St. Louis, MO) predigestion at pH 2.5, 1, and 0.4, and Alcian blue at pH 5.8 with increasing concentrations of magnesium chloride (a modification of the critical electrolyte concentration technique" described by Scott and Dorling12 and later applied as a diagnostic tool by Kindblom and Angervall13). Briefly, sections were stained with Alcian blue at pH 5.8 with 0.06, 0.3, 0.5, 0.7, and 0.9 mol/L concentrations of MgCl2. The critical electrolyte concentration is the highest MgCl2 concentration that still allows staining. Fresh tissue was fixed in buffered glutaraldehyde and processed routinely for electron microscopic examination. Formalin-fixed, paraffin-embedded tissue was stained by the immunoperoxidase avidin-biotin peroxidase complex MATERIALS AND METHODS method for keratin (Becton-Dickinson, San Jose, CA; Diagnostic Products Corporation, Los Angeles, CA), S-100 The tissue was received in saline, fixed in 10% buffered (DAKO Corp., Los Angeles, CA), vimentin (BioGenex formalin, and routinely processed to paraffin. Sections Laboratories, San Ramon, CA), neuron-specific enolase (BioGenex Laboratories), muscle-specific actin (ENZO From the Department of Pathology. University of Iowa Hospitals and Biochem, Inc., New York, NY), desmin (BioGenex LabClinics. Iowa City, Iowa. oratories), chromogranin (Boehringer-Mannheim Biochemicals, Indianapolis, IN), and Leu 7 (Becton-DickReceived April 26, 1991; received revised manuscript and accepted for publication June 24, 1991. inson). As a control, a normal serum was substituted for Address reprint requests to Dr. Robinson: Division of Surgical Pathe primary antibody. Lung tissue for energy-dispersive thology, Department of Pathology, 5239B RCP. University of Iowa Hosspectrometry was lifted directly from a hematoxylin-andpitals and Clinics, Iowa City, Iowa 52242. Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue neoplasm that was originally described by Stout and Verner' and the myxoid variety was later characterized in detail by Enzinger and Shiraki.2 Most occur deep in the extremities, especially in the thigh, popliteal fossa, or buttock, and are associated with a relatively favorable prognosis.2 Unusual locations include tongue,3 retroperitoneum,4-5 gastrocolic ligament,6 chest wall,7 testis,8 inguinal region,9 and synovium.10 We describe a case of extraskeletal myxoid chondrosarcoma of the pleura in a patient with a history of asbestos exposure that clinically simulated a malignant mesothelioma; however, characteristic results of histologic, histochemical, immunohistochemical, and electron microscopic examinations support the diagnosis of myxoid chondrosarcoma. To our knowledge, this is the first reported case of primary EMC of the pleura found in association with asbestos exposure.
498
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
A primary extraskeletal myxoid chondrosarcoma of the pleura that clinically mimicked a malignant mesothelioma in a 66-yearold man with a history of asbestos exposure is described. Although exceedingly rare in this location, the characteristic histologic features, immunohistochemical reactivities, and ultrastructural features support the diagnosis of extraskeletal myxoid chondrosarcoma. Many ferruginous (asbestos) bodies consistent
GOETZ, ROBINSON, AND LANDAS Extraskeletal Myxoid Chondrosarcoma of the Pleura
499
CASE REPORT
RESULTS FIG. 1. Chest radiograph with an encasing right pleural-based neoplasm tracking into the majorfissure(arrow).
eosin-stained slide and transferred to a copper grid. Analysis was performed using an Hitachi S-2700 scanning electron microscope equipped with a Kevex Delta I Energy Dispersive Spectrometer (Kevex Instruments, San Carlos, CA).
Grossly, the tissue was pale gray, soft, and nodular with a gelatinous texture. Scattered hemorrhagic foci were present. Microscopically, the tumor demonstrated characteristic features of myxoid chondrosarcoma, including a nodular architecture with separate discrete nests of small, oval- to spindle-shaped cells arranged in anastamosing cords surrounded by an abundant myxoid matrix and a very thin fibrous capsule (Fig. 3). Some of the nests contained areas
FlG. 2. CT scan confirming diffuse pleural involvement by the sarcoma on the right side, suggestive of malignant mesothelioma.
Vol. 97 • No. 4
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
A 66-year-old man was admitted to the Department of Veteran's Affairs Medical Center of Iowa City, Iowa complaining of a 6-week history of blood-tinged sputum, decreased appetite, and weight loss. The patient had a 15-year occupational history of asbestos exposure because he worked with furnaces. Physical examination revealed markedly decreased breath sounds in the right chest and thorough palpation failed to reveal any masses in the soft tissue of the extremities or pelvis. A chest x-ray (Fig. 1) and computed tomographic scan (Fig. 2) showed a large pleuralbased neoplasm encasing the right lung and extending into the major fissure, suggesting malignant mesothelioma. A bone scan was negative for other lesions. Bronchoscopic examination with biopsy, brushings, and washings was negative. Two transthoracic needle aspiration cytologic examinations were performed and a diagnosis of "spindle cell neoplasm consistent with sarcoma" was made. Subsequently the patient underwent a right thoracotomy with open biopsy of the mass, including pieces of pleura and peripheral lung. This operation revealed an encasing pleuralbased mass composed of multiple dark fluid-filled nodules. No resection was attempted. The patient refused further therapy and was discharged in stable condition.
500
ANATOMIC PATHOLOGY
Single Case Report
'£*
5s FIG. 3. Light photomicrograph of the neoplasm containing oval and spindle cells surrounded by a myxoid matrix characteristic of myxoid chondrosarcoma (hematoxylin and eosin, X400).
of hemorrhage, yet blood vessels were not prominent. The cells contained scant eosinophilic cytoplasm with periodic acid-Schiff-positive, diastase-sensitive material, presumably glycogen. Mitotic figures were rare and no giant cells, lipoblasts, or areas of well-differentiated chondrosarcoma were found. The myxoid matrix stained with Alcian blue at pH 2.5, 1.0, and 0.5, which was diminished but not abolished by pretreatment with hyaluronidase. The critical electrolyte concentration was 0.5 mol/L, indicating the presence of chondroitin 4- and 6-sulfate and possibly keratin sulfate. 7813 Microscopic examination revealed many ferruginous bodies with optically clear cores in the interstitium, often with a curved shape consistent with chrysotile. Elemental analysis using energy-dispersive spectrometry revealed silicon and magnesium in a proportion (Fig. 4) also suggestive of chrysotile.14 Immunoperoxidase studies demonstrated expression of only vimentin. S-100 and Leu 7 were negative, but internal tissue controls (nerve) also failed to stain. Electron microscopic examination revealed irregularly shaped cells of fairly uniform size surrounded by a finely granular amorphous matrix. The cells contained varying amounts of glycogen, oval mitochondria, dilated rough endoplasmic reticulum, indented nuclei with marginated chromatin, and thin delicate cell processes of varying lengths (Fig. 5). The remarkable ultrastructural feature was parallel aggregates of microtubules within rough endoplasmic reticulum, cut longitudinally and in cross-section (inset), a diagnostic feature of EMC. 415 " 18 DISCUSSION Myxoid sarcomas of the soft tissues include EMC, myxoid liposarcoma, myxoid malignant fibrous histio-
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FIG. 4. Energy-dispersive spectrometry analysis indicates magnesium and silicon in proportion consistent with chrysotile.
A.J.C.P.-April 1992
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
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cytoma, and embryonal rhabdomyosarcoma. 19 In the pleura, sarcomatoid mesothelioma and pleural sarcoma20 also must be considered as well as metastatic sarcoma. The diagnosis of EMC was based on characteristic histologic and histochemical findings, including glycogen positivity within cells, Alcian blue staining with and without hyaluronidase, appropriate Alcian blue critical electrolyte concentration results, the presence of microtubular aggregates within rough endoplasmic reticulum, and immunohistochemical negativity for cytokeratin and muscleassociated antigens. Although strong S-100 protein positivity in EMC has been described by some authors,7 others report weak or even negative staining.2'5'21 Leu 7 also has been reported as positive. 2223 In our case, S-100 and Leu 7 results (negative) were invalidated by failure of internal controls to stain. Primary EMC of the pleura is an exceedingly rare neoplasm. In their review of primary neoplasms of the pleura, Klemperer and Robin 24 cited three cases of diffuse pleural chondrosarcoma from the German literature by Busse,25 Schultze,26 and Fallscher,27 and speculated that the tumors arose from mesothelial cells because they behaved similarly to other diffuse pleural tumors in their mode of spread and had a similar gross appearance. To our knowledge, no other cases of primary EMC of the pleura have been described. Primary EMC arising from another mesothelial surface has been described in the synovial membrane of an ankle joint. 10 The authors suggested that the origin may be synovial intima cells. Metastatic sarcoma was a strong consideration in our case because spread of EMC to pleura from a distant site has been documented. 28 In that report, however, the clinical presentation was of multiple bilateral pleural-based nodules and not, as in this case, of a unilateral encasing lesion. Furthermore, careful clinical evaluation failed to reveal a distant primary lesion in our patient. More commonly, EMC metastasizes to the lung as multiple nodules,
501
GOETZ, ROBINSON, AND LANDAS Extraskeletal Myxoid Chondrosarcoma of the Pleura TT
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Extraskeletal Myxoid Chondrosarcoma of the Pleura Report of a Case Clinically Simulating Mesothelioma STEVEN P. GOETZ, M.D., ROBERT A. ROBINSON, M.D., PH.D., AND STEVE K. LANDAS, M.D.
with the exposure history were found in the lung tissue sections and confirmed by energy-dispersive spectrometry. This case demonstrates an unusual pleural primary neoplasm associated with asbestos. (Key words: Extraskeletal myxoid chondrosarcoma; Pleura; Asbestos; Neoplasm) Am J Clin Pathol 1992;97: 498-502
were stained with hematoxylin and eosin, the periodic acid-Schiff reaction, with and without diastase digestion, Prussian blue for iron, Alcian blue with and without bovine testicular hyaluronidase (Sigma Chemical Co., St. Louis, MO) predigestion at pH 2.5, 1, and 0.4, and Alcian blue at pH 5.8 with increasing concentrations of magnesium chloride (a modification of the critical electrolyte concentration technique" described by Scott and Dorling12 and later applied as a diagnostic tool by Kindblom and Angervall13). Briefly, sections were stained with Alcian blue at pH 5.8 with 0.06, 0.3, 0.5, 0.7, and 0.9 mol/L concentrations of MgCl2. The critical electrolyte concentration is the highest MgCl2 concentration that still allows staining. Fresh tissue was fixed in buffered glutaraldehyde and processed routinely for electron microscopic examination. Formalin-fixed, paraffin-embedded tissue was stained by the immunoperoxidase avidin-biotin peroxidase complex MATERIALS AND METHODS method for keratin (Becton-Dickinson, San Jose, CA; Diagnostic Products Corporation, Los Angeles, CA), S-100 The tissue was received in saline, fixed in 10% buffered (DAKO Corp., Los Angeles, CA), vimentin (BioGenex formalin, and routinely processed to paraffin. Sections Laboratories, San Ramon, CA), neuron-specific enolase (BioGenex Laboratories), muscle-specific actin (ENZO From the Department of Pathology. University of Iowa Hospitals and Biochem, Inc., New York, NY), desmin (BioGenex LabClinics. Iowa City, Iowa. oratories), chromogranin (Boehringer-Mannheim Biochemicals, Indianapolis, IN), and Leu 7 (Becton-DickReceived April 26, 1991; received revised manuscript and accepted for publication June 24, 1991. inson). As a control, a normal serum was substituted for Address reprint requests to Dr. Robinson: Division of Surgical Pathe primary antibody. Lung tissue for energy-dispersive thology, Department of Pathology, 5239B RCP. University of Iowa Hosspectrometry was lifted directly from a hematoxylin-andpitals and Clinics, Iowa City, Iowa 52242. Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue neoplasm that was originally described by Stout and Verner' and the myxoid variety was later characterized in detail by Enzinger and Shiraki.2 Most occur deep in the extremities, especially in the thigh, popliteal fossa, or buttock, and are associated with a relatively favorable prognosis.2 Unusual locations include tongue,3 retroperitoneum,4-5 gastrocolic ligament,6 chest wall,7 testis,8 inguinal region,9 and synovium.10 We describe a case of extraskeletal myxoid chondrosarcoma of the pleura in a patient with a history of asbestos exposure that clinically simulated a malignant mesothelioma; however, characteristic results of histologic, histochemical, immunohistochemical, and electron microscopic examinations support the diagnosis of myxoid chondrosarcoma. To our knowledge, this is the first reported case of primary EMC of the pleura found in association with asbestos exposure.
498
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
A primary extraskeletal myxoid chondrosarcoma of the pleura that clinically mimicked a malignant mesothelioma in a 66-yearold man with a history of asbestos exposure is described. Although exceedingly rare in this location, the characteristic histologic features, immunohistochemical reactivities, and ultrastructural features support the diagnosis of extraskeletal myxoid chondrosarcoma. Many ferruginous (asbestos) bodies consistent
GOETZ, ROBINSON, AND LANDAS Extraskeletal Myxoid Chondrosarcoma of the Pleura
499
CASE REPORT
RESULTS FIG. 1. Chest radiograph with an encasing right pleural-based neoplasm tracking into the majorfissure(arrow).
eosin-stained slide and transferred to a copper grid. Analysis was performed using an Hitachi S-2700 scanning electron microscope equipped with a Kevex Delta I Energy Dispersive Spectrometer (Kevex Instruments, San Carlos, CA).
Grossly, the tissue was pale gray, soft, and nodular with a gelatinous texture. Scattered hemorrhagic foci were present. Microscopically, the tumor demonstrated characteristic features of myxoid chondrosarcoma, including a nodular architecture with separate discrete nests of small, oval- to spindle-shaped cells arranged in anastamosing cords surrounded by an abundant myxoid matrix and a very thin fibrous capsule (Fig. 3). Some of the nests contained areas
FlG. 2. CT scan confirming diffuse pleural involvement by the sarcoma on the right side, suggestive of malignant mesothelioma.
Vol. 97 • No. 4
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
A 66-year-old man was admitted to the Department of Veteran's Affairs Medical Center of Iowa City, Iowa complaining of a 6-week history of blood-tinged sputum, decreased appetite, and weight loss. The patient had a 15-year occupational history of asbestos exposure because he worked with furnaces. Physical examination revealed markedly decreased breath sounds in the right chest and thorough palpation failed to reveal any masses in the soft tissue of the extremities or pelvis. A chest x-ray (Fig. 1) and computed tomographic scan (Fig. 2) showed a large pleuralbased neoplasm encasing the right lung and extending into the major fissure, suggesting malignant mesothelioma. A bone scan was negative for other lesions. Bronchoscopic examination with biopsy, brushings, and washings was negative. Two transthoracic needle aspiration cytologic examinations were performed and a diagnosis of "spindle cell neoplasm consistent with sarcoma" was made. Subsequently the patient underwent a right thoracotomy with open biopsy of the mass, including pieces of pleura and peripheral lung. This operation revealed an encasing pleuralbased mass composed of multiple dark fluid-filled nodules. No resection was attempted. The patient refused further therapy and was discharged in stable condition.
500
ANATOMIC PATHOLOGY
Single Case Report
'£*
5s FIG. 3. Light photomicrograph of the neoplasm containing oval and spindle cells surrounded by a myxoid matrix characteristic of myxoid chondrosarcoma (hematoxylin and eosin, X400).
of hemorrhage, yet blood vessels were not prominent. The cells contained scant eosinophilic cytoplasm with periodic acid-Schiff-positive, diastase-sensitive material, presumably glycogen. Mitotic figures were rare and no giant cells, lipoblasts, or areas of well-differentiated chondrosarcoma were found. The myxoid matrix stained with Alcian blue at pH 2.5, 1.0, and 0.5, which was diminished but not abolished by pretreatment with hyaluronidase. The critical electrolyte concentration was 0.5 mol/L, indicating the presence of chondroitin 4- and 6-sulfate and possibly keratin sulfate. 7813 Microscopic examination revealed many ferruginous bodies with optically clear cores in the interstitium, often with a curved shape consistent with chrysotile. Elemental analysis using energy-dispersive spectrometry revealed silicon and magnesium in a proportion (Fig. 4) also suggestive of chrysotile.14 Immunoperoxidase studies demonstrated expression of only vimentin. S-100 and Leu 7 were negative, but internal tissue controls (nerve) also failed to stain. Electron microscopic examination revealed irregularly shaped cells of fairly uniform size surrounded by a finely granular amorphous matrix. The cells contained varying amounts of glycogen, oval mitochondria, dilated rough endoplasmic reticulum, indented nuclei with marginated chromatin, and thin delicate cell processes of varying lengths (Fig. 5). The remarkable ultrastructural feature was parallel aggregates of microtubules within rough endoplasmic reticulum, cut longitudinally and in cross-section (inset), a diagnostic feature of EMC. 415 " 18 DISCUSSION Myxoid sarcomas of the soft tissues include EMC, myxoid liposarcoma, myxoid malignant fibrous histio-
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12
13
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Fe 1 7
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FIG. 4. Energy-dispersive spectrometry analysis indicates magnesium and silicon in proportion consistent with chrysotile.
A.J.C.P.-April 1992
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
>«£*'-.***
cytoma, and embryonal rhabdomyosarcoma. 19 In the pleura, sarcomatoid mesothelioma and pleural sarcoma20 also must be considered as well as metastatic sarcoma. The diagnosis of EMC was based on characteristic histologic and histochemical findings, including glycogen positivity within cells, Alcian blue staining with and without hyaluronidase, appropriate Alcian blue critical electrolyte concentration results, the presence of microtubular aggregates within rough endoplasmic reticulum, and immunohistochemical negativity for cytokeratin and muscleassociated antigens. Although strong S-100 protein positivity in EMC has been described by some authors,7 others report weak or even negative staining.2'5'21 Leu 7 also has been reported as positive. 2223 In our case, S-100 and Leu 7 results (negative) were invalidated by failure of internal controls to stain. Primary EMC of the pleura is an exceedingly rare neoplasm. In their review of primary neoplasms of the pleura, Klemperer and Robin 24 cited three cases of diffuse pleural chondrosarcoma from the German literature by Busse,25 Schultze,26 and Fallscher,27 and speculated that the tumors arose from mesothelial cells because they behaved similarly to other diffuse pleural tumors in their mode of spread and had a similar gross appearance. To our knowledge, no other cases of primary EMC of the pleura have been described. Primary EMC arising from another mesothelial surface has been described in the synovial membrane of an ankle joint. 10 The authors suggested that the origin may be synovial intima cells. Metastatic sarcoma was a strong consideration in our case because spread of EMC to pleura from a distant site has been documented. 28 In that report, however, the clinical presentation was of multiple bilateral pleural-based nodules and not, as in this case, of a unilateral encasing lesion. Furthermore, careful clinical evaluation failed to reveal a distant primary lesion in our patient. More commonly, EMC metastasizes to the lung as multiple nodules,
501
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