Fine-Needle Aspiration Cytology of an Unusual Primary Lung Tumor, Chondrosarcoma: Case Report Barbara L. Stanfield, M.D.,Celeste N. Powers, M.D.,Pm., Christopher E. Desch, M.D., James W. Brooks, M.D.,and William J. Frable, M.D.

A case of primary chondrosarcoma of the lung diagnosed byfineneedle aspiration biopsy (FNAB) cytology in a 78-yr-old male is presented. ‘4 mass detected on chest x-ray and defined by CTscan was subjected to a preoperative percutaneous fine-needle aspiration under fluoroscopic guidance. The distinctive cytologic features of pleomorphic cells nestled in lacunae surrounded by a chondromyxoid background resulted in a diagnosis of chondrosarcoma. The left upper lobectomy specimen confirmed the FNAB diagnosis and identified the tumor as arisingfrom the left upper lobe bronchus. Diagn Cytopathol 1991;7:423-426. Key Words: Lung; Immunohistochemistry;Pleomorphic cells

Fine-needle aspiration biopsy (FNAB) provides a safe and efficient method to diagnose a variety of lesions without the requirement of the traditional open surgical biopsy. Reports of FNA describing lung carcinomas appeared as early as 1886. With the aid of CT and fluoroscopic guidance, small lesions of the lung may be identified, aspirated directly, and a diagnosis rendered with an overall sensitivThe major indication for ity of approximately FNA of the lung is the diagnosis of suspected malignancy (i.e., small-cell vs. non-small-cell tumors) and/or lesions caused by infectious agents. To our knowledge, this is the first report of primary chondrosarcoma of the lung diagnosed by FNAB.



Received June 14, 1990. Accepted November 20, 1990. From the Section of Surgical and Cytopathology, Department of Pathology, Secl ion of Hematology/Oncology, Department of Internal Medicine, and Department of Surgery, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA. Address reprint requests to William J. Frable, M.D., Section of Surgical Pathology, Medical College of Virginia/VCU, Box 115, MCV Station, Richmond, VA 23298.

0 1991 WILEY-LISS, INC

Case Report A 78-yr-old black male presented to his primary physician with a 3-mo history of increasing dull pain in his left chest and shoulder. In January 1990, a chest x-ray showed a large left upper lobe lung mass involving the posterior mediastinum (Fig. 1). A CT scan noted a possible enlarged pericardial lymph node, but there was no obvious relationship between the mass and the rib or chest wall. Except for two suspicious areas in the humerus after a radionucleotide bone scan, no sites of metastasis were identified. The patient’s previous medical history was significant only for hypertension, which was controlled by medication, and a 40-pack/year history of smoking. The patient denied symptoms of shortness of breath, weight loss, cough, or hemoptysis. A percutaneous FNAB of the mass was performed under fluoroscopic guidance and a preliminary diagnosis of chondrosarcoma, possible mesenchymal type, was made. Subsequently, the patient underwent a left thoracotomy with resection of the left upper lobe of the lung, second and third ribs, and adjacent soft tissue. Postoperative recovery was normal, with a significant reduction in his cancer-related pain. No adjuvant therapy was recommended. Two months postoperatively, tumor was identified in a subclavian nodule of the chest wall adjacent to the surgical incision.

Pathology FNA Cytology From material obtained from a 22-gauge Chiba and Franseen needle, air-dried and 95% alcohol-fixed smears were stained with Diff-Quik and Papanicolaou methods, re-

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Fig. 1. Anterior-posterior chest radiograph demonstrating a large left upper lobe lung mass.

Fig. 3. Alcohol-fixed smear accentuating the finely fibrillar texture of the chondromyxoid ground substance and the evenly dispersed chromatin, prominent nucleolus, and binucleation (Papanicolaou, x 240).

Fig. 2. Air-dried smear showing neoplastic cells seen in clusters resembling the lacunar pattern of cartilage. Each cell has a distinct cell border and an ovoid nucleus with evenly dispersed chromatin and prominent macronucleolus. Occasional binucleated forms are present (Diff-Quik, x 240).

Fig. 4. Paraffin-embedded section of cell block shows neoplastic cells with similar architectural and cytological features seen with Papanicolaou or Diff-Quik stains. (H&E, X 240).

spectively. The aspirated material grossly appeared gelatinous. The Diff-Quik smear showed a conspicuous metachromatic chondromyxoid ground substance with a prominent finely fibrillar texture. However, distinct cellular features were somewhat obscured by the abundant ground substance (Fig. 2). Although the cell detail was poor, there were a few small sheets of undifferentiated appearing cells that initially raised the possible diagnosis of mesenchymal chondrosarcoma. The volume of metachromic stroma and the presence of differentiated cartilaginous cells made that diagnosis unlikely. The cytologic characteristics of the neoplastic cells were best demonstrated with alcohol-fixed, Papanicolaou-stained smears. The chondromyxoid background stained a pale lightgreen. Neoplastic cells were seen in isolation and in clusters, with the latter resembling a lacunar pattern (Fig. 3).

Each cell had pale eosinophilic cytoplasm with a distinct border. The pleomorphic, ovoid nuclei had an evenly dispersed chromatin, with the majority demonstrating a single macronucleolus. Binucleation was not uncommon. Identical cells were seen on Papanicolaou-stained bronchoscopy specimens obtained immediately prior to surgery. A cell block preparation was obtained by rinse of the Chiba and Franseen needles with 10% formalin and processed as a surgical specimen. Hematoxylin and eosin staining revealed a hyalin, pale-violet ground substance and identical neoplastic cells that were previously described on the Papanicolaou smear (Fig. 4). Immunocytochemical studies performed on cell blocks demonstrated immunoreactivity of tumor cells for Cytokeratin (MACK 6, Triton Bioscience) and no staining to S-100 (Biogenics).

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Extracellular mucin was demonstrated by a mucicarmine stain. However, Alcian blue G protein acid was not reactive.

Surgical Gross The thoracotomy specimen included a 175-gm left upper lobe of lung and portions of adjacent ribs and soft tissues as well as a separate tumor mass. The left upper lobe bronchus revealed a primary large, glistening, blue-gray, gelatinous, lobulated mass 2.5 cm from the bronchial margin. There was direct extension of the tumor into the adjacent lung parenchyma. The remainder of the pulmonary tissue revealed moderate emphysematous change and areas of consolidation. The separate tumor mass was grossly identical to the primary arising in the left upper lobe bronchus. Tumor was also identified in the soft tissue adjacent to the ribs, but without gross bone involvement.

Microscopic Feut u res The partially encapsulated tumor consisted of chondromyxoid stroma containing variably sized lacunae with pleomorphic and occasionally binucleated cartilage cells. The tumor cells had hyperchromatic nuclei, coarse chromatin, and macronucleoli (Fig. 5). The background of abundant chondromyxoid matrix was strongly positive with Toluidine blue stain. When stained with Alcian blue G protein acid, the background substance was unaffected with hyaluronidase. The mucicarmine stain showed positive background staining, but the tumor cells were unaffected. The neoplastic cells showed strong immunoreactivity for cytokeratin. From the gross and microscopic features it was concluded that this tumor represented a primary chondrosarcoma of the lung arising in the left upper lobe bronchus.

Discussion Primary chondrosarcomas of the lung were first reported in 1862 by Wilks.4 Such tumors arising de novo in the lung and not originally derived from a hamartoma are rare, with less than 12 well-documented cases. Patients with chondrosarcomas occurring within the tracheobronchial tree may present with cough, hemoptysis, or chest pain. These tumors are slow growing and if detected early are treated with local resection. Death from this tumor is usually due to intrathoracic spread. Although FNAB has been previously successful in diagnosing osseous and extraskeletal chondrosarcomas, this is the first case report of a primary chondrosarcoma of the lung diagnosed by FNAB. A designation of primary was later confirmed by demonstrating the tumor’s origin from the bronchial cartilage. The Diff-Quik, Papanicolaou, and cell block preparations utilized in FNAB are regarded as complementary. For this case, the Diff-Quik method provided a means of

Fig. 5. (A-C). Paraffin-embedded sections of the surgical specimen show neoplastic cells floating in an abundant chondromyxoid background arising from the left upper lobe bronchus. Dysplastic bronchial cartilage is adjacent to the tumor (A,C) (H&E: A, X60; B, ~ 2 4 0 C, ; X240).

rapid assessment of the pronounced metachromatic chondromyxoid ground substance and its lacunar structure containing neoplastic chondrocytes. The limited nuclear detail was compensated by the Papanicolaou stain, which de-emphasized the background matrix and highlighted Diagnostic Cytopathology, Vol 7, No 4

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nuclear abnormal features. The cell block was useful for confirming the unusual nature of this tumor and for application of special stains. The use of Toluidine blue and mucicarmine stains was helpful in distinguishing the extracellular background substance of this chondroid tumor from the mucin-positive chondrocytes within lacunae. Immunocytochemical stains in this case were not as useful as the previous reports seem to indicate. Although much of the literature supports the utility of S-100 staining as a positive marker for chondroid tumors, 13%-20% are negative as in this case. lo Although cytokeratin was positive, there was no morphologic evidence from numerous sections that this was a primary lung carcinoma with very extensive and in many areas differentiated cartilaginous metaplasia. Except in dedifferentiated chondrosarcomas, previous reports support the inability of chondrosarcomas to stain with cytokeratin. Interestingly, this particular case of a grade I1 chondrosarcoma shows strong individual cell positivity with cytokeratin antibody in both the aspiration and resected specimens. This is significant since cytokeratin had been previously used for distinguishing chordomas from chondrosarcomas. l 3 The variability of cytokeratin staining currently remains unexplained. Using clinical history, radiological studies, and careful evaluation of the FNAB, one may still separate most tumors in the differential diagnosis of chondrosarcoma, despite immunocytochemistry incongruences. Smears exhibiting vacuolated physaliphorous cells suggest chordoma. Electron microscopy is helpful in differentiating poorly defined chordoma, chondrosarcoma, and poorly differentiated epithelial tumors. 16,17 Toluidine blue and mucicarmine are helpful in distinguishing the latter two entities. FNAB may be limited in its ability to distinguish benign chondroma from a well-differentiated chondrosarcoma. In at least 25% of cases, the cytologic features of grade I chondrosarcoma are indistinguishable from its benign counterpart, chondroma. l8 Thus a formal biopsy is required for this differential diagnosis. This procedure is also unable to identify morphologically a metastatic from a primary chondrosarcoma. It is very rare that a primary chondrosarcoma of bone is so small that it is undetected clinically. In summary, this case report documents the use of FNAB in the diagnosis of primary chondrosarcoma of the lung. The diagnosis was based predominantly on radiographic findings in conjunction with cytologic features. Immunohistochemistry, despite the current literature re-

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ports, was not helpful. Careful gross and microscopic examination is still necessary to demonstrate conclusively the origin of a primary chondrosarcoma in the lung.

Acknowledgment This work was supported in part by the American Cancer Society, Clinical Oncology Fellowship 89-1 83 (to C.N. P.).

References 1. Menetrier P. Cancer primity du poumon. Bull SOCAnat 1886;61: 643-7. 2. Sterrett G, Whitaker D, Glancy J. Fine needle aspiration of lung, mediastinum and chest wall. Pathol Annu [Part 21 1982;17:197-228. 3. Johnston WW, Frable WJ. Diagnostic respiratory cytology. In: Johnston WW, ed. Masson monographs in cytology. New York: Masson, 1979:7-15. 4. Wilks S . Enchondroma of the lung. Trans Pathol SOC[Lond.] 1862; 13 :27-8. 5. Sun CJ, Kroll M, Miller JE. Primary chondrosarcoma of the lung. Cancer 1982;50:1864-6. 6. Olszewski W, Woyke S , Musiatowicz B. Fine needle aspiration biopsy cytology of chondrosarcoma. Acta Cytol 1983;27:345-9. 7. Xiaojing P, Xiangcheng Y. Cytodiagnosis of bone tumors by fine needle aspiration. Acta Cytol 1985;29:570-5. 8. Layfield LJ, Glasglow BJ, Anders KH, Mirra HM. Fine needle aspiration cytology of primary bone lesions. Acta Cytol 1987;31: 177-83. 9. Calafati SA, Wright AL, Rosen SE, Walowitz A, Koprowska I. Fine needle aspiration cytology of extraskeletal chondrosarcoma. Acta Cytol 1984;28:81-5. 10. Abenoza P, Sibley RK. Chordoma: An immunohistologic study. Hum Pathol 1986;17:744-7. I. Wick MR, Burgess JH, Manivel JC. A reassessment of “chordoid sarcoma”: Ultrastructural and immunohistochemical comparison with chordoma and skeletal myxoid chondrosarcoma. Mod Pathol 1988;1:433-43. 2. Salisbury JR, Isaacson PG. Demonstration of cytokeratin and an epithelial membrane antigen in chordomas and human fetal notochord. Am J Surg Pathol 1985;9:791-7. 3. Miettinen M, Lehto VP, Dahl D, Virtanen I. Differential diagnosis of chordoma, chondroid, and ependymal tumors as aided by antiintermediate filament antibodies. Am J Pathol 1983;112:160-9. 14. Dervan PA, Oloughlin J, Hurson BJ. Dedifferentiated chondrosarcoma with muscle and cytokeratin differentiation in the anaplastic component. Histopathology 1988;12:517-26. 15. Bouropoulou V, Bosse A, Roessner A, et al. Immunohistochemical investigation of chordomas: Histogenetic and differential diagnostic aspects. Curr Top Pathol 1989;80:183-203. 16. Fu Y, Kay S . A comparative ultrastructural study of mesenchymal chondrosarcoma and myxoid chondrosarcoma. Cancer 1974;33: 1531-42. 17. Johannessen JV, ed. Electron microscopy in human medicine. New York: McGraw-Hill International Book Company, 1981;4:75-9. 18. Mirra JM, Picci P, Gold RH. Bone tumors clinical, radiologic and pathologic correlations, Vol 1. Philadelphia: Lea & Febiger, 1989.

Fine-needle aspiration cytology of an unusual primary lung tumor, chondrosarcoma: case report.

A case of primary chondrosarcoma of the lung diagnosed by fine-needle aspiration biopsy (FNAB) cytology in a 78-yr-old male is presented. A mass detec...
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