Fine-Needle Aspiration Cytology of Localized Fibrous Tumor of Pleura David Dusenbery, M.D., Margaret M. Grimes, M.D., and William J. Frable, M.D.
Fine-needle aspiration (FNA) biopsy findings are presented in three cases of localized fibrous tumor of pleura (LFTP). Clinically, two of the tumors behaved benignly, although one showed frequent mitoses and foci of necrosis. The third tumor exhibited local aggressiveness us evidenced by rib destruction. Cytologically, these tum0r.s exhibited a wide range of cellularity, composed mainly of .small, bland oval to spindle cells with moderate numbers of stripped nuclei. Small bits of collagen were seen in the smears. In all cases, cell blocks were instrumental in making the diagnosis. Previous cytologic descriptions of the tumor ure briefly reviewed and the cytologic differential diagnosis is discussed. The peripheral location of this uncommon tumor makes it an ideal target for FNA biopsy. Diagn Cytopathol 1992;8:444-450. @ 1992 Wiley-Liss, Inc.
Key Words: Localized mesothelioma; Needle biopsy
Localized fibrous tumor of serosal surfaces (localized fibrous mesothelioma) is a histologically distinctive, uncommon tumor that has received recent attention in the surgical pathology literature. A histologically similar neoplasm has been described within the lung and in the mediastinum. l o , ' ' It usually has a pleural location and is most frequently benign, although it is potentially aggressive locally and rarely possesses metastatic potential. I ,6.9,12-14 The debate has centered primarily on the histogenesis of the tumor-mesothelial origin 5,8,15-17 versus submesothelial connective tissue origin. 14,6,7,9.12,18,19 This controversy is reflected in the myriad of names given to this neoplasm: localized fibrous mesothelioma, fibroma of pleura, submesothelioma, benign mesothelioma, subpleural fibroma, and others. Most recent studies support a submesothelial connective tissue origin, thus the cur1,7,9312
Received June 21, 1991. Accepted December 18, 1991. From the Division of Surgical and Cytopathology, Department of Pathology, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA. Address reprint requests to Dr. Margaret M. Grimes, Department of Pathology, Medical College of Virginia/Virginia Commonwealth University, Box 662, MCV Station, Richmond, VA 23298-0662.
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rently favored term is localized or solitary fibrous tumor. 1-4,6,7,9,19 Less has been written about the cytology of this tumor. The pleural fluid from patients with localized fibrous tumor of pleura (LFTP) is much less likely to contain exfoliated cells than the pleural fluid from patients with diffuse epithelial mesothelioma; patients with localized tumors are less prone to develop pleural effusions to begin with. 20-23 However, the peripheral location of this pleuralbased tumor lends itself well to the fine-needle aspiration (FNA) biopsy technique. Relatively few detailed descriptions of the FNA cytology of LFTP have been published. 1y,21,22,24,25 Herein, we describe the FNA cytologic findings in three cases of LFTP.
Case 1 A 76-yr-old female was admitted for resection of a large mass in the left hemithorax. The tumor was first identified on chest x-ray 15 yr previously, at which time it was smaller and noted to be near the diaphragm. On clinical follow-up, the asymptomatic lesion slowly increased in size. At admission, chest x-ray showed replacement of the lower two-thirds of the left hemithorax by tumor. Past medical history was unremarkable, and physical examination revealed no other abnormalities. Bronchoscopic examination was normal except for external compression. FNA biopsy was performed, followed by thoracotomy. At exploration, the lesion was found to be attached to the basilar portion of the lower lobe of the lung. It was loosely adherent to the parietal pleura, but there was no gross evidence of invasion into adjacent structures. After dissection at the point of attachment to the lung, the tumor was easily removed from the chest. Gross pathologic examination revealed a 1,589-g, 18.5 X 15.0 x 9.5 cm solid tumor with foci of hemorrhage and necrosis. Microscopically, it was a spindle cell neoplasm with varying degrees of cellularity and of collagenization (Fig. 1). In areas of high cellularity, up to 7
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mitoses per 10 high-power fields were evident, as well as focal necrosis. The tumor was diploid by flow cytometry. The patient is well, without evidence of disease, 1 yr after surgery.
During clinical evaluation for an episode of gross hematuria, a 49-yr-old white female was found to have both a mass in the left kidney and a large tumor that initially appeared to be located posterior to the right lobe of the liver. Chest x-ray was remarkable for a calcified nodule that was felt to represent an old granuloma; PPD skin test was negative. The patient had a history of cervical carcinoma 20 yr previously, treated by hysterectomy and complete left and partial right salpingo-oophorectomy, and was taking replacement estrogen and progesterone. She was a moderate cigarette smoker. Physical examination was unremarkable. CT-guided needle biopsy of the lesion behind the liver was inter-
preted as consistent with a benign fibrous tumor. Subsequently, a left radical nephrectomy was performed; the renal tumor was a stage 1, mixed clear and granular cell carcinoma. Since review of C T scans suggested the possibility that the second lesion probably originated from the pleura, diagnostic pneumoperitoneum was performed 6 wk after nephrectomy. This demonstrated the supradiaphragmatic location of the tumor. Flexible bronchoscopic examination was normal. At thoracotomy, the mass was found to be attached via a pedicle to the visceral pleura of the posterior basilar segment of the right lower lobe. The tumor and pedicle were easily resected. Pathologic examination revealed a 13.0 X 12.0 x 4.6 cm solid, well-circumscribed tumor with no grossly evident hemorrhage or necrosis. Microscopically, the tumor was a heavily collagenized spindle cell neoplasm without nuclear atypia, necrosis, or significant mitotic activity (Fig. 2). The tumor was aneuploid by flow cytometry. The patient is well 5 months after thoracotomy.
Fig. 1. Densely collagenized area o f tumor adjacent to a highly cellular region, case 1 (H&E, x 148).
Fig. 2. Relatively hypocellular spindle cell neoplasm with haphazard arrangement of coarse collagen, case 2 (H&E, x 184).
Case 2
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Case 3 A 61-yr-old woman who presented with low-grade fever, dyspnea, right chest pain, and pleural effusion was found to have a large mass in the right lower hemithorax extending into the chest wall. Past medical history was unremarkable. Physical examination revealed right chest wall tenderness and diminished breath sounds on the right side. CT scan suggested involvement of the right lung by the tumor. FNA biopsy and subsequent open biopsy were followed by en bloc resection of the right lung, the pleuralbased mass, segments of five ribs, and soft tissue and skin of the chest wall. The tumor, which measured 11.5 X 9.8 X 8.5 cm, had a broad base of attachment to the parietal pleura and was adherent to the visceral pleura. No invasion of lung parenchyma was grossly evident. The cut surface of the tumor was white and whorled, with focal hemorrhage. Microscopically, the tumor displayed variable patterns, ranging from paucicellular and densely hyalinized, to extremely cellular (Fig. 3). Focal necrosis was present. The tumor cell nuclei were ovoid to spindle in shape, with mild pleomorphism. Mitotic activity ranged from 0 to 7 mitoses per 10 high-power fields. Immunohistochemical staining for cytokeratin was negative. The tumor infiltrated adjacent soft tissues and rib. The patient is well kith no evidence of recurrence approximately 2 mo after thoracotomy.
Cytologic Findings The aspirates from cases 1 and 2 are similar enough to be described together. Overall, both aspirates were hypocellular, however, in each case occasional smears showed moderate numbers of small, bland, oval naked nuclei reminiscent of those seen in aspirates of benign breast tissue (Fig. 4). In case 2, these cells were partly obscured by blood and could very likely have been overlooked as representing mononuclear inflammatory cells. A few metachromatically staining (Diff-Quick-stained smears) stroma1 fragments containing nuclei were present in each case; in case 2, a rare fragment showed a transition from cellular to hypocellular areas within a single stromal fragment (Fig. 5). Cell blocks from both cases showed dense, “wire-like’’ collagen arranged, for the most part, haphazardly, but focally, in a lamellar pattern (Fig. 6). Spindle cell nuclei were present in cell blocks from both cases. In case 1, densely cellular areas were juxtaposed with collagenous hypocellular areas. In case 2, the spindle cells were mainly situated between hyalinized collagen bundles. Mitotic figures were not identified. Immunoperoxidase staining for cytokeratin, vimentin, epithelial membrane antigen, and leukocyte common antigen of cell block preparations of case 1 were negative. This 446
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Fig. 3. Juxtaposed cellular and hypocellular areas in histologic section, case 3 (H&E, K 184).
case was diagnosed cytologically as “malignant spindle cell tumor, favor malignant fibrous mesothelioma,” based on the presence of highly cellular areas. Case 2 was diagnosed cytologically as suggestive of solitary fibrous tumor. Aspirates from case 3 were highly cellular. Small spindle cells were present singly and in loose aggregates with haphazard overlap and lack of uniform polarity. Some cellular tissue fragments too thick to permit closer scrutiny were present. Some “DNA streaming artifact” was present, but this may have been due to excessive pressure in making the smears. The nuclei were predominantly oval, with some round, and the chromatin was finely granular, for the most part, with occasional chromocenters, but no true nucleoli. Rare areas of the smears contained larger nuclei with a coarser chromatin pattern (Fig. 7). Cytoplasm was mostly stripped, but where present, was fairly abundant. Small bits of stroma were identified in the smears. The cell block in this case once again showed dense hyalinized fibrous areas with focal lamination alternating
FNA CYTOLOGY OF LOCALIZED FIBROUS TUMOR OF PLEURA
Fig. 4. Moderate numbers of oval, naked nuclei similar to those seen in aspirates from benign breast tissue, case 1 (Diff-Quik, ~ 4 1 4 ) .
Fig. 5. Mesenchymal fragment showing transition from hypocellular to highly cellular areas recapitulating the pattern seen histologically, case 2 (Diff-Quik, ~ 2 2 9 ) .
with focally cellular areas. Cellularity varied markedly within single tissue fragments. Small, dark, oval to spindle-shaped nuclei were wedged between collagen bundles. This case was interpreted cytologically as poorly differentiated sarcoma versus fibrosarcoma versus fibrosarcomatous mesothelioma.
the general lack of tendency of the tumor to shed cells. 2023 This fact further supports FNA biopsy as the logical procedure of choice to diagnose this tumor preoperatively. Relatively few descriptions of the FNA cytology of LFTP have been published. Orell et al. commented on the surprising cellularity of the one example that they had aspirated. Their aspirate yielded large numbers of spindleshaped cells with moderately pleomorphic nuclei and some chromatin clumping, small collagen fibers, and some epithelial-like cells, which they interpreted as entrapped bronchiolar epithelium.24 Tao reported on a series of mesot heliomas which were aspirated. Included were seven cases of benign fibrous mesothelioma (LFTP). The aspirates contained bundles and loose groupings of spindleshaped cells with uniform, regular nuclei with finely granular chromatin, usually without nucleoli. No comment concerning the cellularity of the smears is offered. 2 ' Two of the 13 fibrous tumors of pleura in the immunohistochemical study of Rayburn and Godwin were subjected to
Discussion Despite the controversy regarding its histogenesis, LFTP is a clinicopathologically well-defined, histologically distinctive neoplasm. The tumor is frequently asymptomatic when diagnosed, probably as a result of the widespread use of chest radiographs as screening examinations. The tumor most commonly arises from the visceral pleura and, therefore, occupies a peripheral location in the lung field, offering an ideal target for FNA diagnosis. Pleural fluid cytology, a useful examination in diffuse mesotheliomas, is of little or no help in diagnosing LFTP because of the frequent lack of an associated effusion and ',639,'2
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Fig. 6. Cell block showing a heavily collagenized spindle cell neoplasm with focal lamellar drpo\ition of collagen, case I (H&E, X 184).
Fig. 7. Area of aspirate that showed a slightly coarser chromatin pattern, case 3 (Papanicolaou, X 576).
F N A biopsy. The authors briefly describe the cytologic yield as cytologically benign oval to spindle cells. As this was primarily an immunohistochemical study, the cytologic findings are not described in more detail.I9 In a review of the cytologic diagnosis of mesothelioma that centers on findings in serous effusions, Ehya states that in needle aspirates, in addition to single cells and tissue fragments, many naked nuclei may be seen.’* Our cases exhibited a wide range in cellularity of the aspirates. The cellularity of the clinically benign tumors (cases 1 and 2 ) was relatively low; however, case 3, the clinically malignant tumor, was extremely cellular. This seems intuitive; however, Orell et al. have described surprisingly high cellularity in an aspirate of a benign fibrous tumor of pleura. 24 This range of cellularity should not be surprising when one considers the corresponding variability of cellularity seen in histologic sections of LFTP. The juxtaposition of cellular areas with hyalinized, hypocellular areas is one of the histologic hallmarks of this tu-
1,6,%9,12,l3 and was present in both clinically benign and invasive tumors in this study. The value of preparing a cell block from aspirates of these tumors cannot be overemphasized. In all three of our cases, the cell block preparation was instrumental in formulating a diagnosis. All three were similar in showing the characteristic “wire-like’’ desmoplastic (sometimes lamellar) collagen pattern. Also obvious was the juxtaposition of both the cellular and the hypocellular hyalinized areas within single tissue fragments. Small bits of stroma were seen in smears from all cases; these stained metachromatically and were therefore more obvious on Diff-Quick-stained smears. Another feature worthy of note on the Diff-Quik-stained material in both cases in which smears were stained by this method was the presence of moderate numbers of small, oval naked nuclei in the background of the smears. This finding has previously been mentioned by Ehya. 2 2 The appearance of these cells is reminiscent of that seen in smears from benign
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breast aspirates, notably fibroadenomas. In breast, the origin of these cells is believed by some authors to be myoepithelial.26 Although no such origin is implied for LFTP, the similarity in appearance is noted. The cytological differential diagnosis of LFTP mirrors the histologic differential diagnosis. Among the spindlecell lesions most difficult to distinguish from LFTP would be fibrosarcoma of the chest wall. Some might see this distinction as arbitrary. l 3 Spindle-cell squamous carcinomas are far more important to distinguish from LFTP because of the marked difference in prognosis. These tumors are usually not peripheral in location, 27 and cytokeratin should identify them in smears or cell block material. Sarcomatoid renal carcinoma might present a similar diagnostic difficulty. As illustrated by our case 2, C T scan cannot always definitively separate inferiorly located pleural masses from subdiaphragmatic masses. The problem of delineating the diaphragmatic interface has been noted previously. Diagnostic pneumoperitoneum was useful in our case; sonography has also been offered as a procedure to resolve this question.29 Once again, imrnunocytochemistry would offer a solution to the cytologic differential diagnosis with LFTP failing to stain for cytokeratin. Diffuse sarcomatous or desmoplastic mesothelioma might well present significant problems in the cytologic differential diagnosis of LFTP, if it were not for the radiologically circumscribed, localized nature of the latter tumor. Although diffuse mesotheliomas may rarely present as an apparently localized mass lesion, there is usually radiographic evidence of associated diffuse pleural thickening. The possible cytologic similarity could be further compounded by cell block material, if obtained, because it is not unusual for diffuse desmoplastic mesothelioma to show a very similar, if not identical, “wire-like” collagen pattern. I 2 Thus, the radiologic correlation is of utmost importance when considering this differential diagnosis. The tumor cells of diffuse sarcomatous or desmoplastic mesothelioma express cytokeratin, which differentiates this process from LFTP.” Neurogenic tumors of the posterior mediastinurn present a possible difficulty in differential diagnosis, especially since localized fibrous tumors have recently been reported to arise primarily in the mediastinurn. I ’ The dernonstration of nuclear palisading or Verocay bodies would be a useful differentiating feature, but these structures are not universally present in aspirates from neurogenic tumors. In addition to the spindled cells, which LFTP and neurogenic tumors share in common, oval naked nuclei, which were noted in our aspirates of LFTP, are very commonly seen in aspirates from schwannoma and neurofibroma, further enhancing their cytologic similarity. 31 Probably
’*
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most useful in the distinction would be cell block material, since the pattern of collagen deposition and hyalinization in LFTP is quite different from the stroma usually encountered in neurogenic tumors. A neurofibroma with hyalinization might be exceedingly difficult to distinguish from LFTP on aspiration or small biopsy material without resorting to immunohistochemical staining. LFTP are negative with staining for S-100 protein. l9 Predicting tumor behavior on the basis of the FNA findings would seem to be tenuous at best, since even in histologic material, biologic behavior cannot be predicted with certainty. We were able to predict a probable malignant behavior from the aspirate in case 3 based on the high cellularity along with the clinical findings, but it should be remembered that benign tumors may have areas of high cellularity that may be represented in the aspirate. Conversely, collagenized areas with relatively low cellularity may be present in malignant tumors and sampled on FNA. Most of these tumors will behave in a benign fashion especially if the tumor is pedunculated and completely resectable at initial surgery. Our case 3 , in which tumor invaded rib and chest wall, could be classified as a fibrosarcoma of pleura. When the cytologic features described in this report are observed in the proper clinical and radiologic setting, the diagnosis of LFTP should be considered. Preoperative diagnosis by FNA may obviate the need for an open biopsy and may help direct surgical treatment.
‘
Acknowledgment The authors wish to thank Dr. James Brooks, Professor of Surgery, Medical College of Virginia, for clinical information in cases 1 and 2; and Dr. Patricia Allen, Michael P. Hurley, Bob Carter, and John R. Esther of Joplin, Missouri for contributing case 3 and providing follow-up information. We also acknowledge Ms. Rhonda C . Jackson for typing the manuscript. This article was written while Dr. Dusenbery was a fellow in surgical and cytopathology at the Medical College of Virginia. The views expressed in this article are those of the authors and do not reflect the offical policy or position of the Department of the Navy, Department of Defense, or of the U S . government.
References I . Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer 1981;47:2678-89. 2. Dervan PA, Tobin B, OConnor M. Solitary (localized) fibrous mesothelioma: evidence against mesothelial cell origin. Histopathology 198610:867-75. 3. Said JW, Nash G, Banks-Schlegel S, Sassoon AF, Shintaku IP. Localized fibrous mesothelioma: an immunohintochemical and clectron microscopic study. Hum Pathol 1984;15:440-3.
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DUSENBERY ET AL. 4. Al-lzzi M, Thurlow NP, Corrin B. Pleural mesothelioma ofconnective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison. J Pathol 1989;158:414. 5. Doucet J, Dardick I, Srigley JR, van Nostrand AWP, Bell MA, Kahn HJ. Localized fibrous tumour of serosal surfaces. Immunohistochemical and ultrastructural evidence for a type of mesothelioma. Virchow Arch [A] 1986;409:349-63. 6. Dalton WT, Zolliker AS, McCaughey WTE, Jacques J, Kannerstein M. Localized primary tumors of the pleura: an analysis of 40 cases. Cancer 1979;44:1465-75. 7. Hernandez FJ, Fernandez BB. Localized fibrous tumors of pleura: a light and electron microscopic study. Cancer 1974;34:1667-74. 8. Kuwai T, Mikata A, Torikata C, Yakumaru K , Kageyama K, Shimosato Y. Solitary (localized) pleural mesothelioma: a light and electron microscopic study. Am J Surg Pathol 1978;2(4):365-75. 9. Scharifker D, Kaneko M. Localized fibrous "mesothelioma" of pleura (submesothelial fibroma): a clinicopathologic study of 18 cases. Cancer 1979;43:627-35. 10. Yousem SA, Flynn SD. Intrapulmonary localized fibrous tumor. Am J Clin Pathol 1988;89:365-9. 11. Witkin GB, Rosai J. Solitary fibrous tumor of the mediastinum: a report of 14 cases. Am J Surg Pathol 1989;13:547-57. 12. McCaughey WTE, Kannerstein M, Churg J. Tumors and pseudotumors of the serous membranes. Armed Forces Institute of Pathology, Atlas of Tumor Pathology, Second Series, Fascicle 20, Washington, DC, 1985. 13. Roggli VL, Kolbeck J, Sanfilippo F, Shelburne JD. Pathology of human mesothelioma: etiologic and diagnostic considerations. In: Rosen PP, Fechner RE, eds. Pathology annual, Vol 22 (part 2). E. Norwalk, Connecticut: Appleton & Lange, 1987:91-131. 14. Obers VJ, Leiman G, Girdwood RW, Spiro FI. Primary malignant pleural tumors (mesotheliomas) presenting as localized masses: fine needle aspiration cytologic findings, clinical and radiologic features and review of the literature. Acta Cytol 1988;32:567-75. 15. Stout AP, Murray MR. Localized pleural mesothelioma: investigation of its characteristics and histogenesis by the method of tissue culture. Arch Pathol 1942;34:951-64.
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16. Foster EA, Ackerman LV. Localized mesotheliomas of the pleura: the pathologic evaluation of 18 cases. Am J Clin Pathol 1960;34: 349-64. 17. Kay S, Silverberg SG. Ultrastructural studies of a malignant fibrous mesothelioma of the pleura. Arch Pathol 1971;92:449-55. 18. Klemperer P, Rabin CB. Primary neoplasms of the pleura: a report of five cases. Arch Pathol 1931; 11:385-412. 19, Rayburn JL, Godwin TA. Fibrous tumor of the pleura: An immunohistochemical study. Lab Invest 1988;58:76A (abst). 20. Tao L-C. The cytopathology of mesothelioma. Acta Cytol 1979;23: 209-13. 21. Tao L-C. Aspiration biopsy cytology of mesothelioma. Diagn Cytopathol 19893: 19-2 1. 22. Ehya H. The cytologic diagnosis of mesothelioma. Semin Diagn Pathol 1986;3:196-203. 23. Ratzer ER, Pool JL, Melamed MR. Pleural mesotheliomas: clinical experiences with thirty-seven patients. AJR 1967;99:863-80. 24. Orell SR, Sterrett GF, Walters MN-I, Whitaker D. Manual and atlas of fine needle aspiration cytology. Edinburgh: Churchill Livingstone, 1986:142-3. 25. Suen KC. Atlas and text of aspiration biopsy cytology. Baltimore: Williams & Wilkins, 1990:159. 26. Frable WJ. Thin-needle aspiration biopsy. Philadelphla: WB Saunders, 1983:21. 27. Carter D, Eggleston JC. Tumors of the lower respiratory tract. Armed Forces Institute of Pathology, Atlas of tumor pathology, Second Series, Fascicle 17, Washington, DC, 1980. 28. Dedrick CG, McLoud TC, Shepard JO, Shipley RT. Computed tomography of localized pleural mesothelioma. AJR 1985;144:27580. 29. Doust BD, Baum JK. Maklad NF, Doust VL. Ultrasonic evaluation of pleural opacities. Radiology 1975;114:13540. 30. Battifora H. The pleura. In: Sternberg SS, ed. Diagnostic surgical pathology. New York: Raven Press, 1989:83846. 31. Willems J-S. Aspiration biopsy cytology of soft-tissue tumors. In: Linsk JA, Franzen S, eds. Clinical aspiration cytology. Philadelphia: JB Lippincott, 1983:337-8.
Fine-needle aspiration (FNA) biopsy findings are presented in three cases of localized fibrous tumor of pleura (LFTP). Clinically, two of the tumors behaved benignly, although one showed frequent mitoses and foci of necrosis. The third tumor exhibited local aggressiveness us evidenced by rib destruction. Cytologically, these tum0r.s exhibited a wide range of cellularity, composed mainly of .small, bland oval to spindle cells with moderate numbers of stripped nuclei. Small bits of collagen were seen in the smears. In all cases, cell blocks were instrumental in making the diagnosis. Previous cytologic descriptions of the tumor ure briefly reviewed and the cytologic differential diagnosis is discussed. The peripheral location of this uncommon tumor makes it an ideal target for FNA biopsy. Diagn Cytopathol 1992;8:444-450. @ 1992 Wiley-Liss, Inc.
Key Words: Localized mesothelioma; Needle biopsy
Localized fibrous tumor of serosal surfaces (localized fibrous mesothelioma) is a histologically distinctive, uncommon tumor that has received recent attention in the surgical pathology literature. A histologically similar neoplasm has been described within the lung and in the mediastinum. l o , ' ' It usually has a pleural location and is most frequently benign, although it is potentially aggressive locally and rarely possesses metastatic potential. I ,6.9,12-14 The debate has centered primarily on the histogenesis of the tumor-mesothelial origin 5,8,15-17 versus submesothelial connective tissue origin. 14,6,7,9.12,18,19 This controversy is reflected in the myriad of names given to this neoplasm: localized fibrous mesothelioma, fibroma of pleura, submesothelioma, benign mesothelioma, subpleural fibroma, and others. Most recent studies support a submesothelial connective tissue origin, thus the cur1,7,9312
Received June 21, 1991. Accepted December 18, 1991. From the Division of Surgical and Cytopathology, Department of Pathology, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA. Address reprint requests to Dr. Margaret M. Grimes, Department of Pathology, Medical College of Virginia/Virginia Commonwealth University, Box 662, MCV Station, Richmond, VA 23298-0662.
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rently favored term is localized or solitary fibrous tumor. 1-4,6,7,9,19 Less has been written about the cytology of this tumor. The pleural fluid from patients with localized fibrous tumor of pleura (LFTP) is much less likely to contain exfoliated cells than the pleural fluid from patients with diffuse epithelial mesothelioma; patients with localized tumors are less prone to develop pleural effusions to begin with. 20-23 However, the peripheral location of this pleuralbased tumor lends itself well to the fine-needle aspiration (FNA) biopsy technique. Relatively few detailed descriptions of the FNA cytology of LFTP have been published. 1y,21,22,24,25 Herein, we describe the FNA cytologic findings in three cases of LFTP.
Case 1 A 76-yr-old female was admitted for resection of a large mass in the left hemithorax. The tumor was first identified on chest x-ray 15 yr previously, at which time it was smaller and noted to be near the diaphragm. On clinical follow-up, the asymptomatic lesion slowly increased in size. At admission, chest x-ray showed replacement of the lower two-thirds of the left hemithorax by tumor. Past medical history was unremarkable, and physical examination revealed no other abnormalities. Bronchoscopic examination was normal except for external compression. FNA biopsy was performed, followed by thoracotomy. At exploration, the lesion was found to be attached to the basilar portion of the lower lobe of the lung. It was loosely adherent to the parietal pleura, but there was no gross evidence of invasion into adjacent structures. After dissection at the point of attachment to the lung, the tumor was easily removed from the chest. Gross pathologic examination revealed a 1,589-g, 18.5 X 15.0 x 9.5 cm solid tumor with foci of hemorrhage and necrosis. Microscopically, it was a spindle cell neoplasm with varying degrees of cellularity and of collagenization (Fig. 1). In areas of high cellularity, up to 7
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mitoses per 10 high-power fields were evident, as well as focal necrosis. The tumor was diploid by flow cytometry. The patient is well, without evidence of disease, 1 yr after surgery.
During clinical evaluation for an episode of gross hematuria, a 49-yr-old white female was found to have both a mass in the left kidney and a large tumor that initially appeared to be located posterior to the right lobe of the liver. Chest x-ray was remarkable for a calcified nodule that was felt to represent an old granuloma; PPD skin test was negative. The patient had a history of cervical carcinoma 20 yr previously, treated by hysterectomy and complete left and partial right salpingo-oophorectomy, and was taking replacement estrogen and progesterone. She was a moderate cigarette smoker. Physical examination was unremarkable. CT-guided needle biopsy of the lesion behind the liver was inter-
preted as consistent with a benign fibrous tumor. Subsequently, a left radical nephrectomy was performed; the renal tumor was a stage 1, mixed clear and granular cell carcinoma. Since review of C T scans suggested the possibility that the second lesion probably originated from the pleura, diagnostic pneumoperitoneum was performed 6 wk after nephrectomy. This demonstrated the supradiaphragmatic location of the tumor. Flexible bronchoscopic examination was normal. At thoracotomy, the mass was found to be attached via a pedicle to the visceral pleura of the posterior basilar segment of the right lower lobe. The tumor and pedicle were easily resected. Pathologic examination revealed a 13.0 X 12.0 x 4.6 cm solid, well-circumscribed tumor with no grossly evident hemorrhage or necrosis. Microscopically, the tumor was a heavily collagenized spindle cell neoplasm without nuclear atypia, necrosis, or significant mitotic activity (Fig. 2). The tumor was aneuploid by flow cytometry. The patient is well 5 months after thoracotomy.
Fig. 1. Densely collagenized area o f tumor adjacent to a highly cellular region, case 1 (H&E, x 148).
Fig. 2. Relatively hypocellular spindle cell neoplasm with haphazard arrangement of coarse collagen, case 2 (H&E, x 184).
Case 2
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Case 3 A 61-yr-old woman who presented with low-grade fever, dyspnea, right chest pain, and pleural effusion was found to have a large mass in the right lower hemithorax extending into the chest wall. Past medical history was unremarkable. Physical examination revealed right chest wall tenderness and diminished breath sounds on the right side. CT scan suggested involvement of the right lung by the tumor. FNA biopsy and subsequent open biopsy were followed by en bloc resection of the right lung, the pleuralbased mass, segments of five ribs, and soft tissue and skin of the chest wall. The tumor, which measured 11.5 X 9.8 X 8.5 cm, had a broad base of attachment to the parietal pleura and was adherent to the visceral pleura. No invasion of lung parenchyma was grossly evident. The cut surface of the tumor was white and whorled, with focal hemorrhage. Microscopically, the tumor displayed variable patterns, ranging from paucicellular and densely hyalinized, to extremely cellular (Fig. 3). Focal necrosis was present. The tumor cell nuclei were ovoid to spindle in shape, with mild pleomorphism. Mitotic activity ranged from 0 to 7 mitoses per 10 high-power fields. Immunohistochemical staining for cytokeratin was negative. The tumor infiltrated adjacent soft tissues and rib. The patient is well kith no evidence of recurrence approximately 2 mo after thoracotomy.
Cytologic Findings The aspirates from cases 1 and 2 are similar enough to be described together. Overall, both aspirates were hypocellular, however, in each case occasional smears showed moderate numbers of small, bland, oval naked nuclei reminiscent of those seen in aspirates of benign breast tissue (Fig. 4). In case 2, these cells were partly obscured by blood and could very likely have been overlooked as representing mononuclear inflammatory cells. A few metachromatically staining (Diff-Quick-stained smears) stroma1 fragments containing nuclei were present in each case; in case 2, a rare fragment showed a transition from cellular to hypocellular areas within a single stromal fragment (Fig. 5). Cell blocks from both cases showed dense, “wire-like’’ collagen arranged, for the most part, haphazardly, but focally, in a lamellar pattern (Fig. 6). Spindle cell nuclei were present in cell blocks from both cases. In case 1, densely cellular areas were juxtaposed with collagenous hypocellular areas. In case 2, the spindle cells were mainly situated between hyalinized collagen bundles. Mitotic figures were not identified. Immunoperoxidase staining for cytokeratin, vimentin, epithelial membrane antigen, and leukocyte common antigen of cell block preparations of case 1 were negative. This 446
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Fig. 3. Juxtaposed cellular and hypocellular areas in histologic section, case 3 (H&E, K 184).
case was diagnosed cytologically as “malignant spindle cell tumor, favor malignant fibrous mesothelioma,” based on the presence of highly cellular areas. Case 2 was diagnosed cytologically as suggestive of solitary fibrous tumor. Aspirates from case 3 were highly cellular. Small spindle cells were present singly and in loose aggregates with haphazard overlap and lack of uniform polarity. Some cellular tissue fragments too thick to permit closer scrutiny were present. Some “DNA streaming artifact” was present, but this may have been due to excessive pressure in making the smears. The nuclei were predominantly oval, with some round, and the chromatin was finely granular, for the most part, with occasional chromocenters, but no true nucleoli. Rare areas of the smears contained larger nuclei with a coarser chromatin pattern (Fig. 7). Cytoplasm was mostly stripped, but where present, was fairly abundant. Small bits of stroma were identified in the smears. The cell block in this case once again showed dense hyalinized fibrous areas with focal lamination alternating
FNA CYTOLOGY OF LOCALIZED FIBROUS TUMOR OF PLEURA
Fig. 4. Moderate numbers of oval, naked nuclei similar to those seen in aspirates from benign breast tissue, case 1 (Diff-Quik, ~ 4 1 4 ) .
Fig. 5. Mesenchymal fragment showing transition from hypocellular to highly cellular areas recapitulating the pattern seen histologically, case 2 (Diff-Quik, ~ 2 2 9 ) .
with focally cellular areas. Cellularity varied markedly within single tissue fragments. Small, dark, oval to spindle-shaped nuclei were wedged between collagen bundles. This case was interpreted cytologically as poorly differentiated sarcoma versus fibrosarcoma versus fibrosarcomatous mesothelioma.
the general lack of tendency of the tumor to shed cells. 2023 This fact further supports FNA biopsy as the logical procedure of choice to diagnose this tumor preoperatively. Relatively few descriptions of the FNA cytology of LFTP have been published. Orell et al. commented on the surprising cellularity of the one example that they had aspirated. Their aspirate yielded large numbers of spindleshaped cells with moderately pleomorphic nuclei and some chromatin clumping, small collagen fibers, and some epithelial-like cells, which they interpreted as entrapped bronchiolar epithelium.24 Tao reported on a series of mesot heliomas which were aspirated. Included were seven cases of benign fibrous mesothelioma (LFTP). The aspirates contained bundles and loose groupings of spindleshaped cells with uniform, regular nuclei with finely granular chromatin, usually without nucleoli. No comment concerning the cellularity of the smears is offered. 2 ' Two of the 13 fibrous tumors of pleura in the immunohistochemical study of Rayburn and Godwin were subjected to
Discussion Despite the controversy regarding its histogenesis, LFTP is a clinicopathologically well-defined, histologically distinctive neoplasm. The tumor is frequently asymptomatic when diagnosed, probably as a result of the widespread use of chest radiographs as screening examinations. The tumor most commonly arises from the visceral pleura and, therefore, occupies a peripheral location in the lung field, offering an ideal target for FNA diagnosis. Pleural fluid cytology, a useful examination in diffuse mesotheliomas, is of little or no help in diagnosing LFTP because of the frequent lack of an associated effusion and ',639,'2
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Fig. 6. Cell block showing a heavily collagenized spindle cell neoplasm with focal lamellar drpo\ition of collagen, case I (H&E, X 184).
Fig. 7. Area of aspirate that showed a slightly coarser chromatin pattern, case 3 (Papanicolaou, X 576).
F N A biopsy. The authors briefly describe the cytologic yield as cytologically benign oval to spindle cells. As this was primarily an immunohistochemical study, the cytologic findings are not described in more detail.I9 In a review of the cytologic diagnosis of mesothelioma that centers on findings in serous effusions, Ehya states that in needle aspirates, in addition to single cells and tissue fragments, many naked nuclei may be seen.’* Our cases exhibited a wide range in cellularity of the aspirates. The cellularity of the clinically benign tumors (cases 1 and 2 ) was relatively low; however, case 3, the clinically malignant tumor, was extremely cellular. This seems intuitive; however, Orell et al. have described surprisingly high cellularity in an aspirate of a benign fibrous tumor of pleura. 24 This range of cellularity should not be surprising when one considers the corresponding variability of cellularity seen in histologic sections of LFTP. The juxtaposition of cellular areas with hyalinized, hypocellular areas is one of the histologic hallmarks of this tu-
1,6,%9,12,l3 and was present in both clinically benign and invasive tumors in this study. The value of preparing a cell block from aspirates of these tumors cannot be overemphasized. In all three of our cases, the cell block preparation was instrumental in formulating a diagnosis. All three were similar in showing the characteristic “wire-like’’ desmoplastic (sometimes lamellar) collagen pattern. Also obvious was the juxtaposition of both the cellular and the hypocellular hyalinized areas within single tissue fragments. Small bits of stroma were seen in smears from all cases; these stained metachromatically and were therefore more obvious on Diff-Quick-stained smears. Another feature worthy of note on the Diff-Quik-stained material in both cases in which smears were stained by this method was the presence of moderate numbers of small, oval naked nuclei in the background of the smears. This finding has previously been mentioned by Ehya. 2 2 The appearance of these cells is reminiscent of that seen in smears from benign
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breast aspirates, notably fibroadenomas. In breast, the origin of these cells is believed by some authors to be myoepithelial.26 Although no such origin is implied for LFTP, the similarity in appearance is noted. The cytological differential diagnosis of LFTP mirrors the histologic differential diagnosis. Among the spindlecell lesions most difficult to distinguish from LFTP would be fibrosarcoma of the chest wall. Some might see this distinction as arbitrary. l 3 Spindle-cell squamous carcinomas are far more important to distinguish from LFTP because of the marked difference in prognosis. These tumors are usually not peripheral in location, 27 and cytokeratin should identify them in smears or cell block material. Sarcomatoid renal carcinoma might present a similar diagnostic difficulty. As illustrated by our case 2, C T scan cannot always definitively separate inferiorly located pleural masses from subdiaphragmatic masses. The problem of delineating the diaphragmatic interface has been noted previously. Diagnostic pneumoperitoneum was useful in our case; sonography has also been offered as a procedure to resolve this question.29 Once again, imrnunocytochemistry would offer a solution to the cytologic differential diagnosis with LFTP failing to stain for cytokeratin. Diffuse sarcomatous or desmoplastic mesothelioma might well present significant problems in the cytologic differential diagnosis of LFTP, if it were not for the radiologically circumscribed, localized nature of the latter tumor. Although diffuse mesotheliomas may rarely present as an apparently localized mass lesion, there is usually radiographic evidence of associated diffuse pleural thickening. The possible cytologic similarity could be further compounded by cell block material, if obtained, because it is not unusual for diffuse desmoplastic mesothelioma to show a very similar, if not identical, “wire-like” collagen pattern. I 2 Thus, the radiologic correlation is of utmost importance when considering this differential diagnosis. The tumor cells of diffuse sarcomatous or desmoplastic mesothelioma express cytokeratin, which differentiates this process from LFTP.” Neurogenic tumors of the posterior mediastinurn present a possible difficulty in differential diagnosis, especially since localized fibrous tumors have recently been reported to arise primarily in the mediastinurn. I ’ The dernonstration of nuclear palisading or Verocay bodies would be a useful differentiating feature, but these structures are not universally present in aspirates from neurogenic tumors. In addition to the spindled cells, which LFTP and neurogenic tumors share in common, oval naked nuclei, which were noted in our aspirates of LFTP, are very commonly seen in aspirates from schwannoma and neurofibroma, further enhancing their cytologic similarity. 31 Probably
’*
233,4319
most useful in the distinction would be cell block material, since the pattern of collagen deposition and hyalinization in LFTP is quite different from the stroma usually encountered in neurogenic tumors. A neurofibroma with hyalinization might be exceedingly difficult to distinguish from LFTP on aspiration or small biopsy material without resorting to immunohistochemical staining. LFTP are negative with staining for S-100 protein. l9 Predicting tumor behavior on the basis of the FNA findings would seem to be tenuous at best, since even in histologic material, biologic behavior cannot be predicted with certainty. We were able to predict a probable malignant behavior from the aspirate in case 3 based on the high cellularity along with the clinical findings, but it should be remembered that benign tumors may have areas of high cellularity that may be represented in the aspirate. Conversely, collagenized areas with relatively low cellularity may be present in malignant tumors and sampled on FNA. Most of these tumors will behave in a benign fashion especially if the tumor is pedunculated and completely resectable at initial surgery. Our case 3 , in which tumor invaded rib and chest wall, could be classified as a fibrosarcoma of pleura. When the cytologic features described in this report are observed in the proper clinical and radiologic setting, the diagnosis of LFTP should be considered. Preoperative diagnosis by FNA may obviate the need for an open biopsy and may help direct surgical treatment.
‘
Acknowledgment The authors wish to thank Dr. James Brooks, Professor of Surgery, Medical College of Virginia, for clinical information in cases 1 and 2; and Dr. Patricia Allen, Michael P. Hurley, Bob Carter, and John R. Esther of Joplin, Missouri for contributing case 3 and providing follow-up information. We also acknowledge Ms. Rhonda C . Jackson for typing the manuscript. This article was written while Dr. Dusenbery was a fellow in surgical and cytopathology at the Medical College of Virginia. The views expressed in this article are those of the authors and do not reflect the offical policy or position of the Department of the Navy, Department of Defense, or of the U S . government.
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