General Thoracic Surgery (General Thoracic Surgery (Shields)) [2 VOLUME SET]
Editors: Shields, Thomas W.; LoCicero, Joseph; Ponn, Ronald B.; Rusch, Valerie W.
Title: General Thoracic Surgery, 6th Edition
Copyright 2005 Lippincott Williams & Wilkins
> Table of Contents > Volume I - The Lung, Pleura, Diaphragm, and Chest Wall > Section XI - The Pleura > Chapter 67 - Uncommon Tumors of the Pleura
Chapter 67
Uncommon Tumors of the Pleura
Thomas W. Shields
Anjana V. Yeldandi
RARE PRIMARY BENIGN TUMORS OF THE PLEURA
Calcifying Fibrous Pseudotumor of the Pleura
Pinkard and associates (1996) described the occurrence of a benign, pleural-based tumor in three young adults. The pleural lesions were identified on standard chest radiography and did not reveal any calcification. Computed tomography (CT), however, revealed calcification within the masses; Erasmus and colleagues (1996) published the significant radiographic and CT features in these three patients. On resection, the masses were found to be unencapsulated and were seen to arise from either the parietal or visceral pleural surface. In two of the patients, the lesions were solitary, whereas in the other, multiple lesions were seen. Histologically, the tumors were composed of hyalinized collagenous fibrotic tissue interspersed with lymphoplasmacytic infiltrates and calcification; many of these had psammomatous features. No evidence of malignancy existed in these tumors. Surgical resection appears to be curative.
Adenomatoid Tumor
The adenomatoid tumors are small nodular pleural lesions that are found incidentally at the time of a thoracotomy or on examination of a resected lung specimen. They have been found in the visceral pleura as well as in a pulmonary ligament. These lesions, according to Kaplan and co-workers (1996), are made up of epithelial cells with mesothelial differentiation of areas of vacuoles and tubular spaces present in a fibrous stroma. The epithelial nature is confirmed by the cells' positivity for the presence of keratin on immunohistologic tissue staining. These rare tumors are benign, and their only importance is to differentiate them from pleural metastatic disease in patients with malignancy.
Sclerosing Hemangioma
Sclerosing hemangioma is almost always a benign epithelial tumor primarily found in the lungs, and approximately 200 cases have been recorded. In the report of 100 cases by Devouassoux-Shisheboran and associates (2000), four sclerosing hemangiomas were identified as arising in the pleura. The details concerning the cellular origin, pathology, clinical features, and treatment are presented in Chapter 118. The treatment of the pleural-based tumors is surgical resection, and the prognosis should be excellent.
RARE PRIMARY MALIGNANT TUMORS OF THE PLEURA
Except for a few rare primary malignant tumors of the pleura, most malignant lesions involving the pleura are either diffuse malignant mesotheliomas, metastatic lesions involving the pleural surface, or direct invasion of adjacent tumors from the lung or chest wall. Many of the metastatic and invasive lesions mimic a diffuse malignant mesothelioma in both their pathologic features and clinical course. The metastatic lesions include adenocarcinomas from various sites, primarily the lung, including the so-called pseudomesotheliomatous adenocarcinoma of the lung, which was initially described by Harwood and colleagues (1976) and further defined by Dessy and Pietra (1991) and Koss (1992) and Freidman (1993) and their associates. Falconieri and colleagues (1995) reported four cases of small cell carcinoma simulating pleural mesothelioma as confirmed by autopsy examination. Melanomas, thymomas, and metastatic epithelioid sarcomas, as well as tumors from other sites of origin, have also been described. These secondary tumors must be differentiated from true diffuse mesotheliomas by ultrastructural and immunohistochemical features, the discussion of which is not germane to this chapter. However, the few rare primary malignant pleural lesions deserve further comment.
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Biphasic Synovial Sarcoma of the Pleura
Battifora (1994) reported one case and Gaertner and associates (1996) reported five cases of biphasic tumors that were interpreted as synovial sarcomas arising from the pleura. These tumors resembled the synovial (biphasic) tumors of the mediastinum reported by Witkin and colleagues (1989) (see Chapter 192). In 2002, Colwell and co-workers reported two monophasic and one biphasic synovial sarcomas arising from the pleura. In the monophasic type, the tumor was composed of plump, spindle-shaped cells arranged in short fascicles. In the biphasic tumor, glandular epithelium was interspersed among the aforementioned spindle-shaped cells. Immunohistochemical studies were positive for pankeratin and epithelial membrane antigen in all these tumors and all were negative for S-100 protein. Translocation t(x:18) was positive in one case. These tumors occur in young adults and are generally rapidly fatal, although the use of a multimodality approach of surgery and chemotherapy may prolong survival, multiple recurrences are seen. Many chemotherapeutic agents have been used, but the best regimen has yet to be determined. Henderson and associates (1997) stress that it is necessary to separate this tumor from a primary malignant mesothelioma so that the most appropriate therapy may be used in the management of either tumor type.
Epithelioid Hemangioendothelioma Involving the Pleura
Dail (1988) and Battifora (1993) reported the occurrence of an epithelioid hemangioendothelioma involving the pleura. Lin and associates (1996) reported seven similar cases. These tumors markedly resemble malignant mesotheliomas but can be differentiated by labeling the tumor with antibodies to von Willebrand's factor (factor VIII) and to other monoclonal antibodies of epithelioid vascular endothelial-derived cells (CD34, UEA-I, QBEND10, and CD31). Furthermore, these tumors are negative to or have low reactivity to low-molecular-weight cytokeratin. The clinical outlook of these patients is grave; the tumor responds poorly to treatment, and early death is the result of disseminated disease.
Angiosarcoma of the Pleura
A few cases of angiosarcoma of the pleura have been recorded. McCaughey and colleagues (1983) reported one case, and Hammar (1995) noted the observation of one case. Although this tumor, when it occurs in the pleura, may resemble a diffuse malignant mesothelioma, its true nature may be suggested by the presence of vascular-appearing spaces by light microscopy. The presence of Weibel-Palade bodies and the tumor's positive reaction to vimentin and factor VIII related antigen plus its negative reaction to cytokeratin antigens establishes the vascular origin of the tumor. The clinical course of the patient is poor.
Primary Smooth Muscle Tumors of the Pleura
Moran and colleagues (1995) described five cases of primary smooth muscle tumors of the pleura. These tumors are extremely rare and should be distinguished from other spindle cell neoplasms. These tumors test positive for muscle markers, such as smooth muscle action and desmin, by immunohistochemistry. It should be noted that Gibbs (1995) is not convinced that these tumors represent a true entity.
Pseudomesotheliomatous (Epithelioid) Angiosarcoma
This rare tumor is associated with pleural thickening and hemorrhagic effusion, and is readily confused as being a malignant mesothelioma. The tumor is made up of large endothelial cells, and the histologic features range from those of an epithelioid hemangioendothelioma to a frank epithelioid angiosarcoma. Immunohistochemical studies by Falconieri and associates (1997) revealed the tumor cells to be strongly positive for vimentin and to show weak focal positivity for keratin. Also, at least two or more of the common endothelial markers (CD31, CD34, factor VIII related antigen, and Ulex europaeus agglutination-I) are present. The tumor is very aggressive in its malignant behavior, and death of the patients usually occurs within a few months of diagnosis.
Primary Pleural Liposarcoma
Liposarcomas of the pleura are exceedingly rare. Only a small number of cases of primary pleural liposarcomas have been reported. Wong and associates (1994), in their report of a single case, also review eight other cases reported in the literature. Histologically, three were myxoid liposarcomas, one was a well-differentiated liposarcoma, and four liposarcomas were not subtyped. Patients were symptomatic only when the tumors reached a large size. The most common symptom was dyspnea. Iqbal and colleagues (2000) reported a lymphocyte-rich pleural liposarcoma mimicking a right-sided pericardial cyst. This subtype of liposarcoma was initially described by Argani and co-workers in 1997, none of which originated in the pleura. The relationship between this subtype of liposarcoma and the well-differentiated inflammatory liposarcoma described by Krauss and associates (1997) is undetermined.
The treatment of pleural liposarcoma is complete surgical resection with care taken to ensure a wide surgical margin
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and to prevent any rupture of the capsule of the tumor. Complete removal may be curative, but often postoperative irradiation is added to the therapeutic regimen.
Primary Extraskeletal Myxoid Chondrosarcoma of the Pleura
Only a few primary extraskeletal myxoid chondrosarcomas of the pleura have been reported. Thompson and Entin (1969) reported a case arising in conjunction with an extrapleural lucite ball plombage so that its origin from the pleura per se may be questioned. However, Bailey and Head (1990) reported a 70-year-old patient who had multiple pleural lesions excised in early 1976 that were diagnosed as typical chondrosarcomas. No recurrence was noted at the time of the 1990 report, and in a subsequent update, Head (2001) stated that the patient had remained free of disease for 24 years after the initial resection. Goetz and associates (1992) reported an additional case of chondrosarcoma of the pleura that clinically mimicked a malignant mesothelioma. This tumor was seen in a patient with a 15-year history of exposure to asbestos. The tumor encased the lung and grossly was nodular with a gelatinous texture. Histologically, the tumor had typical features of myxoid chondrosarcoma. Immunochemically, only vimentin was expressed. Many ferruginous bodies also were seen in histologic sections. A metastatic sarcoma from a distant primary site was excluded clinically. A sarcomatoid mesothelioma was excluded by lack of keratin expression and by the presence of microtubular aggregates with rough endoplasmic reticulum by ultrastructural examination.
Primary Pleural Thymomas
Most cases reported in the literature as pleural thymomas have been shown, as noted by Moran and co-workers (1992), to be an extension to the pleural surfaces of an underlying malignant thymoma originating in the thymus gland in the mediastinum. Such was the case in the report of Fukayama and colleagues (1988). However, some cases of thymomas have involved the pleura, but in none of these was evidence of involvement of the thymus gland found, and these cases have been regarded as primary pleural lesions. Moran and associates (1992) described eight cases of thymomas presenting as pleural tumors. Histologically, six cases were indistinguishable from mediastinal thymomas. The tumors had lobular architecture with lymphocytic and epithelial components. Radiologically, four cases had diffuse pleural thickening mimicking mesothelioma. Whether these tumors represent thymomas arising from ectopic thymic tissue or invasive thymomas from an occult mediastinal primary is unclear.
Localized Malignant Mesothelioma
Crotty and associates (1994) described six cases of localized malignant mesotheliomas of the pleura. In four patients, the tumors presented as sessile broad-based pleural tumors and two were pedunculated. Histologically, three were purely epithelioid and three were biphasic. Immunohistochemically and ultrastructurally, these tumors had a malignant mesothelioma phenotype. An aneuploud population was present in 80% of cases on flow cytometry. Three patients had recurrences and died of their disease, and three were free of disease after surgical resection. A more recent report by G mez-Rom n and colleagues (2002) stated that these authors knew of only 10 reliable pleurally localized malignant mesotheliomas that had been reported in the literature. In their own case they noted only small areas of vimentin positivity and found on flow cytometry an aneuploud population with a DNA index of 1.20 (Table 67-1).
Primary Squamous Cell Carcinoma of the Pleura
Willen and associates (1976) reported the occurrence of a squamous cell carcinoma arising from the pleural surface in six patients who had been treated over long periods by a pneumothorax to maintain an extrapleural pneumolysis for the management of pulmonary tuberculosis. In four other patients treated in the same manner, they identified areas of squamous metaplasia of the pleural surface. They suggested that such areas of metaplasia could become the site of origin of squamous cell carcinomas they identified. Ruttner and Heinzl (1977)
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described a similar case and noted an earlier case reported by Ender (1966). Watanabe and colleagues (1999) reported an additional case of a squamous cell carcinoma arising in a chronic empyema space and noted 13 other cases reported in the Japanese literature, seven of which arose from the pleural surface. Treatment is complete resection, if possible. The role of irradiation is unknown. Other squamous cell carcinomas have been described that have originated in pleurocutaneous fistulae, but these are not true pleural lesions. The occurrence of squamous cell carcinoma in chronic sinus and fistulous tracts is a well-known entity.Table 67-1. Differential Characteristics of Malignant Localized Mesothelioma, Malignant Diffuse Mesothelioma, and Solitary Fibrous Tumor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adenosquamous Cell Carcinoma of the Pleura
Hammar (1995) mentions one patient who had a squamous cell carcinoma of the pleura. Some of the cells in this tumor stained for the presence of mucicarmine, thus suggesting the diagnosis of adenosquamous cell carcinoma. Kwee and colleagues (1981) reported the presence of an adenosquamous mesothelioma of the pleura. Again, whether this is a rare primary pleural tumor or only a variant of a diffuse mesothelioma remains conjecture.
Primary Melanoma of the Pleura
According to Dail (1995), only one case of probable primary pleural melanoma has been reported. This case was presented by Smith and Opipari (1978), and no evidence of a reported primary site of a melanoma was uncovered by the history or autopsy performed 3 weeks after biopsy of a large pleural-based melanoma. Their major criteria for a primary lung melanoma were met, equally applicable to primary pleural melanoma as espoused by Jensen and Egedorf (1967): (a) no previously removed skin tumor, (b) no ocular tumor, (c) a solitary specimen, and (d) autopsy proof of no other organ involvement.
Malignant Peripheral Nerve Sheath Tumor
Ord ez and Tornos (1997) described a single case of primary malignant peripheral nerve sheath tumor of the pleura in a 57-year-old man that clinically mimicked a malignant mesothelioma. Histologically, the tumor had features of epithelioid malignant peripheral nerve sheath tumor. In this case, rhabdomyoblasts were seen in addition to spindle and epithelioid cells. The immunohistochemical features of this tumor were as follows: the spindle and epithelioid cells expressed S-100 protein; the epithelioid cells had local reaction to heavy keratins; and the rhabdomyoblasts were positive for desmin and myoglobin and negative for S-100 protein. No reactivity occurred for muscle actin, synaptophysin, chromogranin, or antimelanoma monoclonal antibody (HMB45). The patient had a fatal course and died from the disease.
Other Primary Malignant Tumors
Malignant solitary localized fibrous tumors of the pleura are generally readily differentiated from other malignant tumors involving the pleura. As noted in Chapter 64, these tumors do not express cytokeratin, whereas they label positive for CD34.
Other malignant sarcomas, because of their site of origin and lack of expression for cytokeratin reactivity, are usually not confused as being diffuse malignant mesotheliomas. In rare instances, diagnostic (as a rule purely academic) dilemmas do occur.
REFERENCES
Argani P, et al: Lymphocyte-rich well-differentiated liposarcoma: report of nine cases. Am J Surg Pathol 21:884, 1997.
Bailey SC, Head HD: Pleural chondrosarcoma. Ann Thorac Surg 49:996, 1990.
Battifora H: Case six biphasic synovial sarcoma invading the pleura. In Short Course of Tumors and Tumor-Like Lesions of Serosal Membranes. Presented at the XXth International Congress of the International Academy of Pathology, Hong Kong, 1994.
Battifora H: Epithelioid hemangioendothelioma imitating mesothelioma. Appl Immunohistochem 1:220, 1993.
Colwell AS, et al: Synovial sarcoma of the pleura: a clinical and pathologic study of three cases. J Thorac Cardiovasc Surg 124:828, 2002.
Crotty TB, et al: Localized malignant mesothelioma: a clinicopathologic and flow cytometric study. Am J Surg Pathol 18:357, 1994.
Dail DH: Uncommon tumors. In Dail DH, Hammar SP (eds): Pulmonary Pathology. New York: Springer-Verlag, 1988, p. 847.
Dail DH: Uncommon tumors. In Dail DH, Hammar SP, Colby TV (eds): Pulmonary Pathology Tumors. New York: Springer-Verlag, 1995, p. 157.
Dessy E, Pietra GG: Pseudomesotheliomatous carcinoma of the lung. An immunohistochemical and ultrastructural study of three cases. Cancer 68:1747, 1991.
Devouassoux-Shisheboran M, et al: A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies: TTF-1 is expressed in both round and surface cells, suggesting an origin from primitive respiratory epithelium. Am J Surg Pathol 24:906, 2000.
Ender A: Ein Beitrag zum primaren pflasterzellkarzinom der Pleura nach extrapleuralem Pneumothoraax [Thesis]. University of Zurich, Juris-Verlag, 1966.
Erasmus JJ, et al: Calcifying fibrous pseudotumor of pleura: radiographic features in three cases. J Comput Assist Tomogr 20:763, 1996.
Falconieri G, et al: Small cell carcinoma of the lung simulating pleural mesothelioma. Report of 4 cases with autopsy confirmation. Pathol Res Pract 191:1147, 1995.
Falconieri G, et al: Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma. Histopathology 30:419, 1997.
Freidman HD, Litovsky SH, Abraham JL: Mucin-positive epithelial mesothelioma and pseudomesotheliomatous adenocarcinoma. Arch Pathol Lab Med 117:967, 1993.
Fukayama M, et al: Pulmonary and pleural thymoma. Diagnostic application of lymphocyte markers to the thymoma of unusual site. Am J Clin Pathol 89:617, 1988.
Gaertner E, et al: Biphasic synovial sarcomas arising in the pleural cavity: a clinicopathologic study of five cases. Am J Surg Pathol 20:36, 1996.
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Gibbs AR: Smooth muscle tumors of the pleura. Histopathology 27:295, 1995.
Goetz SP, Robinson RA, Landas SK: Extraskeletal myxoid chondrosarcoma of the pleura: report of a case clinically simulating mesothelioma. Am J Clin Pathol 97:498, 1992.
G mez-Rom n JJ, et al: Flow cytometric analysis of localized malignant mesothelioma. Ann Thorac Surg 73:1292, 2002.
Hammar SP: Pleural diseases. In Dail DH, Hammar SP, Colby TV (eds): Pulmonary Pathology Tumors. New York: Springer-Verlag, 1995, p. 405.
Harwood TR, Gracey DR, Yokoo H: Pseudomesotheliomatous carcinoma of the lung: a variant of peripheral lung cancer. Am J Clin Pathol 65: 159, 1976.
Head HD: Pleural chondrosarcoma. Updated in 2001. Ann Thorac Surg 71:1396, 2001.
Henderson DW, et al: Malignant mesothelioma of the pleura: current surgical pathology. In Corrin B (ed): Pathology of Lung Tumors. New York: Churchill Livingstone, 1997, p. 241.
Iqbal M, et al: Lymphocyte-rich pleural liposarcoma mimicking pericardial cyst. J Thorac Cardiovasc Surg 120:610, 2000.
Jensen QA, Egedorf J: Primary melanoma of the lung. Scand J Respir Dis 48:127, 1967.
Kaplan MA, et al: Adenomatoid tumors of the pleura. Am J Surg Pathol 20:1219, 1996.
Koss M, et al: Pseudomesotheliomatous adenocarcinoma: a reappraisal. Semin Diagn Pathol 9:117, 1992.
Krauss M, Guillou L, Fletcher CD: Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked variant of a common sarcoma. Am J Surg Pathol 21:518, 1997.
Kwee WS, et al: Primary adenosquamous mesothelioma of the pleura. Virchows Arch [A] 393:353, 1981.
Lin BT, et al: Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases. Am J Surg Pathol 20:1431, 1996.
McCaughey WTE, Dardick I, Barr JR: Angiosarcoma of serous membranes. Arch Pathol Lab Med 107:304, 1983.
Moran CA, et al: Thymomas presenting as pleural tumors. Report of eight cases. Am J Surg Pathol 16:138, 1992.
Moran CA, Suster S, Koss MN: Smooth muscle tumours presenting as pleural neoplasms. Histopathology 27:227, 1995.
Ord ez NG, Tornos C: Malignant peripheral nerve sheath tumor of the pleura with epithelial and rhabdomyoblastic differentiation: report of a case clinically simulating mesothelioma. Am J Surg Pathol 20:1515, 1997.
Pinkard NB, et al: Calcifying fibrous pseudotumor of pleura. A report of three cases of a newly described entity involving the pleura. Am J Clin Pathol 105:189, 1996.
Ruttner JR, Heinzl S: Squamous-cell carcinoma of the pleura. Thorax 32:497, 1977.
Smith S, Opipari MI: Primary pleural melanoma. A first reported case and literature review. J Thorac Cardiovasc Surg 75:827, 1978.
Thompson JR, Entin D: Primary extraskeletal chondrosarcoma. Report of a case arising in conjunction with extrapleural lucite ball plombage. Cancer 23:936, 1969.
Watanabe S, et al: Squamous cell carcinoma in chronic empyema cavity case report with review of the literature. J Jpn Assoc Chest Surg 13:42, 1999.
Willen R, et al: Squamous epithelial cancer in metaplastic pleura following extrapleural pneumothorax for pulmonary tuberculosis. Virchows Arch [A] 370:225, 1976.
Witkin GB, Miettinen M, Rosai J: A biphasic tumor of the mediastinum with features of synovial sarcoma. A report of four cases. Am J Surg Pathol 13:490, 1989.
Wong WW, et al: Liposarcoma of the pleura. Mayo Clin Proc 69:882, 1994.