Case Study
Malignant transformation in solitary fibrous tumor of the pleura
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(8) 981–983 ß The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313498090 aan.sagepub.com
Ming-Ko Law1, Yung-Wei Tung1,2 and Jong-Shiaw Jinc3
Abstract A 55-year-old man with a solitary fibrous tumor of the pleura on the left side underwent resection, but 2 recurrent tumors were found 3 years later. The recurrent tumors were reported to have undergone malignant transformation. Recurrent solitary fibrous tumor of the pleura with malignant progression is rare. Solitary fibrous tumor of the pleura often has an indolent clinical course, and may be asymptomatic for several years, so postoperative surveillance may necessitate long-term follow-up because of the potentially malignant transformative biological behavior of this type of tumor.
Keywords Neoplasm recurrence, local, Pleural neoplasms. Solitary fibrous tumor, pleural
Introduction Solitary fibrous tumor of the pleura (SFTP) is a rare neoplasm of the pleura, which accounts for less than 5% of all pleural tumors. Most are benign, but 10%–20% of those reported in the literature were malignant.1,2 Localized pleural tumors have been known by a variety of terms (localized fibrous tumor of the pleura, localized mesothelioma, localized fibrous mesothelioma, localized benign fibroma, or submesothelial fibroma). More recently, immunohistochemical techniques, flow cytometric studies, and electron microscopic analysis have demonstrated that these neoplasms do not originate from the mesothelial layer but from the submesothelial mesenchymal layer.3 The first large collected review series of SFTP cases describing the clinicopathologic features of the neoplasm appeared in 1981 by Briselli and colleagues4 (368 cases) and in 1989 by England and colleagues2 (223 cases). Subsequent series have refined our understanding of the clinical behavior of this somewhat unpredictable tumor. In a 2002 publication by the WHO, titled ‘‘Pathology & Genetics of Tumors of Soft Tissue and Bone’’, SFTP is defined as a mesenchymal tumor that may have fibroblastic characteristics and clear peripheral vascular tumor-like branching blood vessels.5 Those classified as fibroblastic or myofibroblastic tumors may represent an intermediate type
(i.e., occasionally malignancy.
metastatic)
and
intermediate
Case report The patient was a 55-year-old man with no particular medical history. However, a tumor was discovered incidentally in the left chest cavity during his health examination. Chest radiography and computed tomography showed a 17 9 9-cm lobulated lesion in the left pleural cavity (Figure 1). The physical examination and laboratory test findings were otherwise noncontributory. We performed a left thoracotomy for removal of the tumor, combined with a partial wedge resection of the lingual segment to removal the pedicle. The surgical margin of the specimen was free of tumor. Immunopathological findings revealed intervascular 1 Division of Thoracic Surgery, Department of Surgery, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan 2 Taipei Medicine University,Taipei, Taiwan 3 Department of Pathology, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan
Corresponding author: Yung-Wei Tung, MD, Division of Thoracic Surgery, Tungs’ Taichung MetroHarbor Hospital, No. 699, Sec. B, Taiwan Blvd., Wuqi Dist., Taichung City 43503, Taiwan, R.O.C. Email: [email protected]
982 and perivascular proliferation of pericyte-like cells with relatively uniform round and oval nuclei; no necrosis or mitosis was noted. The cells stained positive for CD34 and bcl-2, and negative for S-100 protein. The final diagnosis was a benign SFTP. The patient was lost to follow-up but was readmitted to our clinic with the complaint of cough 3 years after the surgery. Two recurrent tumors were noted at the left major fissure (smaller tumor: 2.5 2 2 cm) and the medial aspect of the left basal lung (large tumor: 11 11 4.5 cm; Figure 2). The patient underwent surgical resection of the recurrent tumors. The tumors were found to be firm encapsulated lobular masses (Figure 3). Histologic evidence to support malignant transformation of SFTP includes high cellularity with pleomorphism and increased mitotic activity (>4 mitotic figures per 10 high-power fields) accompanied by local necrosis (Figure 4). The specimens stained positive for vimentin, CD99, and Ki67 by immunohistochemistry, and negative for cytokeratin and calretinin.
Figure 1. A well-defined lobular solitary mass, approximately 17 cm, in the left chest wall (arrow).
Asian Cardiovascular & Thoracic Annals 22(8)
Discussion More than 50% of patients with SFTP are asymptomatic, and the tumor is frequently an incidental finding on a standard chest radiograph. There is no apparent genetic predisposition for this tumor, and no relationship to exposure to asbestos, tobacco, or any other environmental agent. Paraneoplastic syndromes are also seen in patients with SFTP. Hypertrophic pulmonary osteoarthropathy (Pierre Marie-Bamberger syndrome) has been described in 10% to 20% of cases, and refractory hypoglycemia (Doege-Potter syndrome) has been reported in up to 5% of cases. According to the review by de Perrot and colleagues,6 approximately 800 cases of SFTP were reported in the literature before July 2002, and an additional 960 cases of SFTP were collected by Cardillo and colleagues3 between 2002 and 2012, for a total of approximately 1760 reported cases. SFTP are rare neoplasms and commonly benign in up to 80% of cases. The reported incidence of malignant SFTP varies from 7% to 60%, a variation attributed to slight differences in institutional pathologic criteria.
Figure 3. A larger tumor with pedicle (arrow) at the lower margin of the left lower lobe.
Figure 2. (a) A smaller tumor is seen at the left major fissure, and (b) a larger well-defined mass at the medial aspect of the left basal lung with a pedicle from the visceral pleura.
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Figure 4. (a) Histopathological examinations of the tumors showed tumor cells with hypercellularity and mitosis (arrow) in the tumor relapse 3 years after the initial resection. Hematoxylin and eosin stain, original magnification 200. (b) Local necrosis (arrow) indicating malignancy. Hematoxylin and eosin stain, original magnification 100.
England and colleagues2 defined the criteria of malignancy, including high cellularity, increased mitotic activity, pleomorphism, hemorrhage, and necrosis, in a large study. The most important predictors of outcome are morphological and histological indicators. The prognosis for patients with SFTP is generally favorable. Survival in the group with malignant SFTP was lower, mainly because of local and general recurrences, with a 5-year survival rate of 68%.6 Complete en-bloc surgical resection is the mainstay of therapy for all benign and malignant SFTP. A distance of 1 to 2 cm from the tumor into healthy tissue is usually recommended; however, pedunculated tumors can be safely resected with a wedge resection of the lung. After complete surgical resection, plain radiography or computed tomography should be used to monitor for recurrence every 6 months for the first 2 years, and then yearly. All SFTP need long-term follow-up, which may extend to 15–20 years due to the possibility of late recurrence. We have described an unusual case of SFTP with malignant transformation. This is an extremely rare phenomenon and only a few cases have been reported in the literature.7 SFTP remains an enigmatic tumor. Malignant transformation is unpredictable and may not always correlate with histologic findings.8 Some authors suggested that these tumors derive from longlived ‘‘fibroblastic’’ stem cells, and that successive mutations may lead to the malignant form.6 Complete surgical resection remains the treatment of choice for benign and malignant SFTP. Radiation therapy is used routinely in patients with malignant SFTP if resection is not feasible or incomplete, but the role of adjuvant therapy remains controversial. Our patient received complete resection with a safe margin, and we suggested regular follow-up without adjuvant therapy.
Conflict of interest statement None declared.
Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
References 1. Robinson LA. Solitary fibrous tumors of the pleura. Cancer Control 2006; 13: 264–269. 2. England DM, Hochholzer L and McCarthy MJ. Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol 1989; 13: 640–658. 3. Cardillo G, Lococo F, Carleo F and Martelli M. Solitary fibrous tumors of the pleura. Wolters Kluwer Health/ Lippincott Williams & Wilkins, 2012. 4. Briselli M, Mark EJ and Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer 1981; 47: 2678–2689. 5. Folpe AL. Neoplasms with perivascular epithelioid cell differentiation (PEComas). In: Fletcher CM, Unni KK, Mertens F (eds) World Health Organization Classification of Tumors. Pathology and genetics of tumors of soft tissue and bone. Lyon: IARC Press, 2002. 6. de Perrot M, Fischer S, Bru¨ndler MA, Sekine Y and Keshavjee S. Solitary fibrous tumors of the pleura. Ann Thorac Surg 2002; 74: 285–293. 7. Kanthan R and Torkian B. Recurrent solitary fibrous tumor of the pleura with malignant transformation. Arch Pathol Lab Med 2004; 128: 460–462. 8. Agarwal VK, Plotkin BE, Dumani D, French SW, Becker R and Lee P. Solitary fibrous tumor of pleura: a case report and review of clinical, radiographic and histologic findings. J Radiol Case Rep 2009; 3: 16–20.
Malignant transformation in solitary fibrous tumor of the pleura
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(8) 981–983 ß The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313498090 aan.sagepub.com
Ming-Ko Law1, Yung-Wei Tung1,2 and Jong-Shiaw Jinc3
Abstract A 55-year-old man with a solitary fibrous tumor of the pleura on the left side underwent resection, but 2 recurrent tumors were found 3 years later. The recurrent tumors were reported to have undergone malignant transformation. Recurrent solitary fibrous tumor of the pleura with malignant progression is rare. Solitary fibrous tumor of the pleura often has an indolent clinical course, and may be asymptomatic for several years, so postoperative surveillance may necessitate long-term follow-up because of the potentially malignant transformative biological behavior of this type of tumor.
Keywords Neoplasm recurrence, local, Pleural neoplasms. Solitary fibrous tumor, pleural
Introduction Solitary fibrous tumor of the pleura (SFTP) is a rare neoplasm of the pleura, which accounts for less than 5% of all pleural tumors. Most are benign, but 10%–20% of those reported in the literature were malignant.1,2 Localized pleural tumors have been known by a variety of terms (localized fibrous tumor of the pleura, localized mesothelioma, localized fibrous mesothelioma, localized benign fibroma, or submesothelial fibroma). More recently, immunohistochemical techniques, flow cytometric studies, and electron microscopic analysis have demonstrated that these neoplasms do not originate from the mesothelial layer but from the submesothelial mesenchymal layer.3 The first large collected review series of SFTP cases describing the clinicopathologic features of the neoplasm appeared in 1981 by Briselli and colleagues4 (368 cases) and in 1989 by England and colleagues2 (223 cases). Subsequent series have refined our understanding of the clinical behavior of this somewhat unpredictable tumor. In a 2002 publication by the WHO, titled ‘‘Pathology & Genetics of Tumors of Soft Tissue and Bone’’, SFTP is defined as a mesenchymal tumor that may have fibroblastic characteristics and clear peripheral vascular tumor-like branching blood vessels.5 Those classified as fibroblastic or myofibroblastic tumors may represent an intermediate type
(i.e., occasionally malignancy.
metastatic)
and
intermediate
Case report The patient was a 55-year-old man with no particular medical history. However, a tumor was discovered incidentally in the left chest cavity during his health examination. Chest radiography and computed tomography showed a 17 9 9-cm lobulated lesion in the left pleural cavity (Figure 1). The physical examination and laboratory test findings were otherwise noncontributory. We performed a left thoracotomy for removal of the tumor, combined with a partial wedge resection of the lingual segment to removal the pedicle. The surgical margin of the specimen was free of tumor. Immunopathological findings revealed intervascular 1 Division of Thoracic Surgery, Department of Surgery, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan 2 Taipei Medicine University,Taipei, Taiwan 3 Department of Pathology, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan
Corresponding author: Yung-Wei Tung, MD, Division of Thoracic Surgery, Tungs’ Taichung MetroHarbor Hospital, No. 699, Sec. B, Taiwan Blvd., Wuqi Dist., Taichung City 43503, Taiwan, R.O.C. Email: [email protected]
982 and perivascular proliferation of pericyte-like cells with relatively uniform round and oval nuclei; no necrosis or mitosis was noted. The cells stained positive for CD34 and bcl-2, and negative for S-100 protein. The final diagnosis was a benign SFTP. The patient was lost to follow-up but was readmitted to our clinic with the complaint of cough 3 years after the surgery. Two recurrent tumors were noted at the left major fissure (smaller tumor: 2.5 2 2 cm) and the medial aspect of the left basal lung (large tumor: 11 11 4.5 cm; Figure 2). The patient underwent surgical resection of the recurrent tumors. The tumors were found to be firm encapsulated lobular masses (Figure 3). Histologic evidence to support malignant transformation of SFTP includes high cellularity with pleomorphism and increased mitotic activity (>4 mitotic figures per 10 high-power fields) accompanied by local necrosis (Figure 4). The specimens stained positive for vimentin, CD99, and Ki67 by immunohistochemistry, and negative for cytokeratin and calretinin.
Figure 1. A well-defined lobular solitary mass, approximately 17 cm, in the left chest wall (arrow).
Asian Cardiovascular & Thoracic Annals 22(8)
Discussion More than 50% of patients with SFTP are asymptomatic, and the tumor is frequently an incidental finding on a standard chest radiograph. There is no apparent genetic predisposition for this tumor, and no relationship to exposure to asbestos, tobacco, or any other environmental agent. Paraneoplastic syndromes are also seen in patients with SFTP. Hypertrophic pulmonary osteoarthropathy (Pierre Marie-Bamberger syndrome) has been described in 10% to 20% of cases, and refractory hypoglycemia (Doege-Potter syndrome) has been reported in up to 5% of cases. According to the review by de Perrot and colleagues,6 approximately 800 cases of SFTP were reported in the literature before July 2002, and an additional 960 cases of SFTP were collected by Cardillo and colleagues3 between 2002 and 2012, for a total of approximately 1760 reported cases. SFTP are rare neoplasms and commonly benign in up to 80% of cases. The reported incidence of malignant SFTP varies from 7% to 60%, a variation attributed to slight differences in institutional pathologic criteria.
Figure 3. A larger tumor with pedicle (arrow) at the lower margin of the left lower lobe.
Figure 2. (a) A smaller tumor is seen at the left major fissure, and (b) a larger well-defined mass at the medial aspect of the left basal lung with a pedicle from the visceral pleura.
Law et al.
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Figure 4. (a) Histopathological examinations of the tumors showed tumor cells with hypercellularity and mitosis (arrow) in the tumor relapse 3 years after the initial resection. Hematoxylin and eosin stain, original magnification 200. (b) Local necrosis (arrow) indicating malignancy. Hematoxylin and eosin stain, original magnification 100.
England and colleagues2 defined the criteria of malignancy, including high cellularity, increased mitotic activity, pleomorphism, hemorrhage, and necrosis, in a large study. The most important predictors of outcome are morphological and histological indicators. The prognosis for patients with SFTP is generally favorable. Survival in the group with malignant SFTP was lower, mainly because of local and general recurrences, with a 5-year survival rate of 68%.6 Complete en-bloc surgical resection is the mainstay of therapy for all benign and malignant SFTP. A distance of 1 to 2 cm from the tumor into healthy tissue is usually recommended; however, pedunculated tumors can be safely resected with a wedge resection of the lung. After complete surgical resection, plain radiography or computed tomography should be used to monitor for recurrence every 6 months for the first 2 years, and then yearly. All SFTP need long-term follow-up, which may extend to 15–20 years due to the possibility of late recurrence. We have described an unusual case of SFTP with malignant transformation. This is an extremely rare phenomenon and only a few cases have been reported in the literature.7 SFTP remains an enigmatic tumor. Malignant transformation is unpredictable and may not always correlate with histologic findings.8 Some authors suggested that these tumors derive from longlived ‘‘fibroblastic’’ stem cells, and that successive mutations may lead to the malignant form.6 Complete surgical resection remains the treatment of choice for benign and malignant SFTP. Radiation therapy is used routinely in patients with malignant SFTP if resection is not feasible or incomplete, but the role of adjuvant therapy remains controversial. Our patient received complete resection with a safe margin, and we suggested regular follow-up without adjuvant therapy.
Conflict of interest statement None declared.
Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
References 1. Robinson LA. Solitary fibrous tumors of the pleura. Cancer Control 2006; 13: 264–269. 2. England DM, Hochholzer L and McCarthy MJ. Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol 1989; 13: 640–658. 3. Cardillo G, Lococo F, Carleo F and Martelli M. Solitary fibrous tumors of the pleura. Wolters Kluwer Health/ Lippincott Williams & Wilkins, 2012. 4. Briselli M, Mark EJ and Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer 1981; 47: 2678–2689. 5. Folpe AL. Neoplasms with perivascular epithelioid cell differentiation (PEComas). In: Fletcher CM, Unni KK, Mertens F (eds) World Health Organization Classification of Tumors. Pathology and genetics of tumors of soft tissue and bone. Lyon: IARC Press, 2002. 6. de Perrot M, Fischer S, Bru¨ndler MA, Sekine Y and Keshavjee S. Solitary fibrous tumors of the pleura. Ann Thorac Surg 2002; 74: 285–293. 7. Kanthan R and Torkian B. Recurrent solitary fibrous tumor of the pleura with malignant transformation. Arch Pathol Lab Med 2004; 128: 460–462. 8. Agarwal VK, Plotkin BE, Dumani D, French SW, Becker R and Lee P. Solitary fibrous tumor of pleura: a case report and review of clinical, radiographic and histologic findings. J Radiol Case Rep 2009; 3: 16–20.
