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Primary paraganglioma of the lung
Primary Paraganglioma of the Lung Cheri L. Aubertine, MD, and Douglas B. Flieder, MD There are few reported cases of primary pulmonary paraganglioma in the pathology literature. Given the historical confusion surrounding bronchial tumors, widespread use of the term “chemodectoma” and classification of these lesions as paraganglioma in an outdated World Health Organization classification of lung tumors, the recognition of tumors arising from paraganglia within the lung has not been accepted by leading authorities. We present a well-documented case of a primary pulmonary paraganglioma with typical morphologic features and a supporting immunohistochemical profile. The 0.9 cm endobronchial tumor was submucosal and composed of nests of ovoid cells with abundant eosinophilic cytoplasm, cytoplasmic vacuoles, round to oval nuclei with speckled chromatin, and occasional conspicuous nucleoli. The nests of cells were surrounded by thin-walled vascular channels and stellate spindle cells. The ovoid cells showed strong diffuse staining for chromogranin A, synaptophysin, and faint staining for S-100; they were negative for cytokeratin AE1/AE3, Cam 5.2, and epithelial membrane antigen. The stellate spindle cells stained intensely positive for S-100 protein. A critical review of reported cases of pulmonary chemodectomas and paragangliomas in the English literature features few, if any, well-documented examples. While this exceedingly rare tumor should be discerned from carcinoid tumor, it remains unknown if primary pulmonary paragangliomas behave aggressively like intra-abdominal extraadrenal paragangliomas, or in a more indolent manner observed with extra-adrenal paragangliomas in other locations. Ann Diagn Pathol 8: 237-241, 2004. © 2004 Elsevier Inc. All rights reserved. Index Words: Pulmonary, paraganglioma, chemodectoma
E
XTRA-ADRENAL paragangliomas are uncommon tumors arising from neuroectodermal-derived paraganglionic tissue. While these low-grade malignant tumors most often occur in the superior or inferior para-aortic regions and have been reported in virtually every organ, the existence of paragangliomas as primary tumors of the lung is controversial. Taking into account varying terminology used to describe this lesion including glomus tumor, carotid body-like tumor, and chemodectoma, many examples reported as primary pulmonary paraganglioma (PPP) are not convincing. Complicating the matter is the fact that completely unrelated lesions currently classified as minute meningothelial
From the Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital–Weill Cornell Medical College, New York, NY. Address reprint requests to Cheri L. Aubertine, MD, Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital– Weill Cornell, Starr 1008, 525 E 68th St, New York, NY 10021. © 2004 Elsevier Inc. All rights reserved. 1092-9134/04/0804-0009$30.00/0 doi:10.1053/j.anndiagpath.2004.04.008
nodules were previously known as chemodectomas and classified as paragangliomas in the 1981 World Health Organization classification of lung tumors. Herein we present a bona fide case of a PPP and offer a critical review of published case reports. Case Report A 40-year-old man with no significant past medical history presented with recurrent obstructive pneumonia. A chest computed tomography demonstrated a left mainstem bronchus density adjacent to an irregular parenchymal infiltrate. The polypoid endobronchial nature of the tumor was confirmed on bronchoscopy. A transbronchial biopsy yielded a diagnosis of low-grade neuroendocrine tumor. The patient’s mediastinum, neck, and abdomen were without masses or appreciable lymphadenopathy on subsequent computed tomography scans and a left mainstem bronchial sleeve resection was performed. Although the patient’s immediate postoperative course was complicated by a persistent left pleural effusion, he recovered and remains well 12 months following surgery.
Annals of Diagnostic Pathology, Vol 8, No 4 (August), 2004: pp 237-241
237
238
Aubertine and Flieder
Materials and Methods The resection specimen was fixed in buffered formalin and embedded in paraffin. Sections were stained with hematoxylin-eosin. Immunohistochemistry was performed. Antibodies used include chromogranin A (Biogenex, San Ramon, CA), synaptophysin (DAKO, Carpinteria, CA), S-100 protein (DAKO), Pankeratin AE1/AE3 (Chemicon, Temecula, CA), low-molecular-weight keratin Cam 5.2 (BD, San Diego, CA), epithelial membrane antigen (DAKO), HMB-45 (Enzo, Farmingdale, NY), melan-A, A103 (DAKO), glial fibrillary acid protein (DAKO), CD68 (DAKO), vimentin (DAKO), and smooth muscle actin (DAKO).
Results The resected 0.9 cm tan-gray lobulated tumor was histologically similar to the preoperative biopsy. The well-circumscribed submucosal neoplasm encircled seromucinous glands and featured clusters of four to 10 ovoid tumor cells without discrete cytoplasmic borders surrounded by numerous vascular channels, scant connective tissue, and scattered slender stellate cells (Fig 1). The ovoid cells contained abundant eosinophilic cytoplasm with small vacuoles, round to oval nuclei with speckled chromatin, and occasional conspicuous nucleoli. The stellate cells had little cytoplasm, bland nuclei, and processes wrapping around nests and individual cells. Nuclear pleomorphism and mitoses were not identified. The overlying bronchial mucosa featured squamous metaplasia. Immunohistochemical studies performed on both the preoperative biopsy and resection specimen demonstrated the nests of cells reactive to antibodies directed against chromogranin A and synaptophysin antigens, but negative staining for AE1/AE3, Cam 5.2, (epithelial membrane antigen), HMB-45, and A103. Both the ovoid cells and stellate cells were immunoreactive for S-100 protein; however, the latter had a more intense pattern of staining (Fig 2). The stellate cells were additionally negative for glial fibrillary acid protein, CD68, vimentin, and smooth muscle actin. Discussion While the presence of paraganglionic tissue in the perivascular interstitium of fetal lungs was convincingly demonstrated by Blessing and Hora over 30 years ago.1 This case report stands as the first well-documented example of primary pul-
monary paraganglioma. The presented neoplasm meets the Armed Forces Institute of Pathology’s suggested morphologic criteria for the diagnosis of paraganglioma. These include: a diffuse zellballen pattern throughout the tumor, absence of classic carcinoid tumor architectural patterns such as trabecular, pseudoglandular or spindle cell, the presence of cytoplasmic vacuoles distinctive of paragangliomas, negative immunohistochemical staining for cytokeratin as well the exclusion of an extrapulmonary paraganglioma or pheochromocytoma.2 Previously reported cases3-17 (Table 1) suffer from a variety of incomplete or contradictory findings that do not allow them to be readily distinguished from a carcinoid tumor. Many of the early reports either illustrate tumors with morphologic patterns that are more typical of carcinoid tumor or lack photomicrographs altogether. Also, reticulin staining, once in vogue and used to highlight the nesting architectural pattern of the cells in support of the diagnosis, is now recognized as a nonspecific method that does not discern the two tumor types. Some previous case reports based their diagnoses on the presence of sustentacular cells because it was originally thought to be a specific diagnostic feature of paragangliomas. However, many studies have reported S-100 –positive stellate cells resembling sustentacular cells in bronchial carcinoids in up to 76% of cases.18-20 While there is some ongoing debate as to whether these S-100 –positive cells are mesenchymal or neuroectodermal in origin, it is generally agreed that they are not a distinguishing feature of paragangliomas. As the Armed Forces Institute of Pathology criteria suggest, cytokeratin can aid in the distinction between a PPP and a carcinoid tumor, but is not absolutely diagnostic. As expected, because of their epithelial origin, nearly 100% of bronchial carcinoids, despite their degree of differentiation, will be positive for cytokeratins.21,22 Inversely, with the exception of cauda equina paragangliomas, cytokeratin positivity has only been reported in three cases occurring in the head and neck region.23 Immunohistochemistry for cytokeratins was performed on only four of the previously reported cases of PPP.15-17 Three of these four cases reported positive staining for cytokeratin; therefore, they are more consistent with a carcinoid tumor. The one case that was reportedly negative for cyto-
Primary Paraganglioma of the Lung
239
Figure 1. Primary pulmonary paraganglioma. (A) The submucosal neoplasm splays seromucinous glands but respects bronchial cartilage. (B) Nests of ovoid tumor cells feature abundant cytoplasm and occasional nuclear atypia. Thin-walled vascular spaces abound.
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Figure 2.
S-100 protein immunohistochemical stain. Sustentacular cell processes are highlighted. Table 1. Documented Case Reports of Primary Pulmonary Paraganglioma
Study
Convincing Photomicrographs
Cytokeratin
S-100⫹ Sustentacular Cells
Heppleston (1958)3 Mostecky et al (1966)4 Fawcett and Husband (1967)5 Fawcett and Husband (1967)5 Laustela et al (1969)6 Goodman and Lafort (1972)7 Goodman and Lafort (1972)7 Lee and Hori (1972)8 deLuise et al (1977)9 Arom and Trinkle (1977)10 Singh et al (1977)11 Hangartner et al (1989)12 Lemonick et al (1999)13 Vuorela and Anttinen (1993)14 Skodt et al (1995)15 Skodt et al (1995)15 Saeki et al (1999)16 Kim et al (2001)17
No No Yes ND Yes Yes Yes No Yes ND No No No No Yes No Yes Yes
ND ND ND ND ND ND ND ND ND ND ND ND ND ND CK⫹ CK⫺ CK⫹ CK⫹(focal)
ND ND ND ND ND ND ND ND ND ND ND Yes ND ND Yes Yes Yes Yes
Abbreviation: ND, not done.
Primary Paraganglioma of the Lung
keratin did not include an accompanying photomicrograph of the tumor.15 If incomplete reports in the past muddied the existence of PPP, then shifting terminologies and classification nomenclature only confused the issue further. Not only did the 1981 World Health Organization classification of lung tumors classify minute meningothelial nodules as paragangliomas, but also standard lung pathology texts published as recently as 2000 refer to paragangliomas as chemodectomas.24,25 The most recent World Health Organization classification has corrected the confusion by defining meningothelial nodule and paraganglioma as entirely separate entities. In addition, the morphologically distinct gangliocytic paraganglioma should not be confused with a paraganglioma.26,27 Because the patient’s neoplasm was amenable to lung-sparing surgery and he remains well 12 months following excision, one can only speculate about the natural history and metastatic potential of PPP. Although intra-abdominal extra-adrenal paragangliomas are quite aggressive, with malignancy rates up to 50% and a 5-year survival rate of 36% in one series, paragangliomas in other locations (such as the bladder) have low metastatic rates with biologic behavior similar to that of a typical carcinoid tumor of the lung.28 Thus, while the distinction between PPP and carcinoid tumor may not have a clinical impact, this report of a PPP shows its existence, clarifies historically confusing nomenclature, and emphasizes that immunohistochemistry serves as an important adjunct to light microscopic morphologic features. References 1. Lack EE: Extra-adrenal paragangliomas of the sympathoadrenal neuroendocrine system. In: Atlas of Tumor Pathology: Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia. 3rd Series. Vol 19. Washington, DC, Armed Forces Institute of Pathology, 1997 2. Colby TV, Koss MN, Travis WD: Carcinoid and other neuroendocrine tumors. In: Atlas of Tumor Pathology: Tumors of the Lower Respiratory Tract. 3rd Series. Washington, DC, Armed Forces Institute of Pathology, 1994, pp 309-311 3. Heppleston AG: A carotid-body-like tumour in the lung. J Pathol Bact 1958;75:461-464 4. Mostecky H, Lichtenberg J, Kalus M: A non-chromaffin paraganglioma of the lung. Thorax 1966;21:205-208 5. Fawcett FJ, Husband EM: Chemodectoma of lung. J Clin Pathol 1967;20:260-262 6. Laustela E, Mattila S, Franssila K: Chemodectoma of the lung. Scand J Thorac Cardiovasc Surg 1969;3:59-62 7. Goodman ML, Lafort EG: Solitary primary chemodectomas of the lung. Chest 1972;61:48-50
241
8. Lee YN, Hori JM: Chemodectoma of the lung. J Surg Oncol 1972;4:33-36 9. deLuise VP, Holman CW, Gray GF: Primary pulmonary paraganglioma. NY State J Med 1977;77:2270-2271 10. Arom KV, Trinkle JK: Solitary pulmonary paraganglioma: Case report and literature review. Am Surg 1977;43:689-691 11. Singh G, Lee RE, Brooks DH: Primary pulmonary paraganglioma. Report of a cases and review of the literature. Cancer 1977;40:2286-2289 12. Hangartner JW, Loosemore TM, Burke M, et al: Malignant primary pulmonary paraganglioma. Thorax 1989;44:154156 13. Lemonick DM, Pai PB, Hines GL: Malignant primary pulmonary paraganglioma with hilar metastasis. J Thorac Cardiovasc Surg 1999;99:563-564 14. Vuorela AL, Anttinen J: Primary chemodectoma of the lung. AJR Am J Roentgenol 1993;161:1111-1112 15. Skodt V, Jacobsen GK, Helsted M: Primary paraganglioma of the lung. Report of two cases and review of the literature. APMIS 1995;103:597-603 16. Saeki T, Akiba T, Joh K, et al: An extremely large solitary primary paraganglioma of the lung: Report of a case. Jpn J Surg 1999;29:1195-1200 17. Kim MK, Park SH, Cho HD, et al: Fine needle aspiration cytology of primary pulmonary paraganglioma. Acta Cytologica 2001;45:459-464 18. Barbareschi M, Frigo B, Mosca L, et al: Bronchial carcinoids with S-100 positive sustentacular cells. Pathol Res Pract 1990;186:212-222 19. Gosney JR, Denley H, Resl M: Sustentacular cells in pulmonary neuroendocrine tumours. Histopathology 1999;34:211215 20. Nakajima T, Kameya T, Watanabe S, et al: An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am J Surg Pathol 2001;116:S65-S96 (suppl 1) 21. Cerilli LA, Ritter JH, Mills SE, et al: Neuroendocrine neoplasms of the lung. Am J Clin Pathol 2001;116:S65-S96 (suppl 1) 22. Gould VE, Lee I, Warren WH: Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung. Pathol Res Pract 1998;183:200-213 23. Chetty R, Pillay P, Jaichand V: Cytokeratin expression in adrenal pheochromocytomas and extra-adrenal paragangliomas. J Clin Pathol 1998;51:477-478 24. Corrin B: Rare pulmonary tumors. In: Corrin B (ed): Pathology of the Lungs. London, UK, Churchill Livingstone, 2000, pp 537-538 25. Dail DH: Uncommon tumors. In: Dail DH, Hammar SP (eds): Pulmonary Pathology. New York, NY, Springer Verlag, 1994, pp 1353-1354 26. Hironaka M, Fukayama M, Takayashiki N, et al: Pulmonary gangliocytic paraganglioma: Case report and comparative immunohistochemical study of related neuroendocrine neoplasms. Am J Surg Pathol 2001;25:688-693 27. Kee AR, Forrest CH, Brennan BA, et al: Gangliocytic paraganglioma of the bronchus: A case report with follow-up and ultrastructural assessment. Am J Surg Pathol 2003;27:1380-1385 28. Lack EE: Aorticopulmonary paraganglioma. In: Atlas of Tumor Pathology: Tumors of the Adrenal Gland and ExtraAdrenal Paraganglia. 3rd Series. Vol 19. Washington, DC, Armed Forces Institute of Pathology, 1997
E
XTRA-ADRENAL paragangliomas are uncommon tumors arising from neuroectodermal-derived paraganglionic tissue. While these low-grade malignant tumors most often occur in the superior or inferior para-aortic regions and have been reported in virtually every organ, the existence of paragangliomas as primary tumors of the lung is controversial. Taking into account varying terminology used to describe this lesion including glomus tumor, carotid body-like tumor, and chemodectoma, many examples reported as primary pulmonary paraganglioma (PPP) are not convincing. Complicating the matter is the fact that completely unrelated lesions currently classified as minute meningothelial
From the Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital–Weill Cornell Medical College, New York, NY. Address reprint requests to Cheri L. Aubertine, MD, Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital– Weill Cornell, Starr 1008, 525 E 68th St, New York, NY 10021. © 2004 Elsevier Inc. All rights reserved. 1092-9134/04/0804-0009$30.00/0 doi:10.1053/j.anndiagpath.2004.04.008
nodules were previously known as chemodectomas and classified as paragangliomas in the 1981 World Health Organization classification of lung tumors. Herein we present a bona fide case of a PPP and offer a critical review of published case reports. Case Report A 40-year-old man with no significant past medical history presented with recurrent obstructive pneumonia. A chest computed tomography demonstrated a left mainstem bronchus density adjacent to an irregular parenchymal infiltrate. The polypoid endobronchial nature of the tumor was confirmed on bronchoscopy. A transbronchial biopsy yielded a diagnosis of low-grade neuroendocrine tumor. The patient’s mediastinum, neck, and abdomen were without masses or appreciable lymphadenopathy on subsequent computed tomography scans and a left mainstem bronchial sleeve resection was performed. Although the patient’s immediate postoperative course was complicated by a persistent left pleural effusion, he recovered and remains well 12 months following surgery.
Annals of Diagnostic Pathology, Vol 8, No 4 (August), 2004: pp 237-241
237
238
Aubertine and Flieder
Materials and Methods The resection specimen was fixed in buffered formalin and embedded in paraffin. Sections were stained with hematoxylin-eosin. Immunohistochemistry was performed. Antibodies used include chromogranin A (Biogenex, San Ramon, CA), synaptophysin (DAKO, Carpinteria, CA), S-100 protein (DAKO), Pankeratin AE1/AE3 (Chemicon, Temecula, CA), low-molecular-weight keratin Cam 5.2 (BD, San Diego, CA), epithelial membrane antigen (DAKO), HMB-45 (Enzo, Farmingdale, NY), melan-A, A103 (DAKO), glial fibrillary acid protein (DAKO), CD68 (DAKO), vimentin (DAKO), and smooth muscle actin (DAKO).
Results The resected 0.9 cm tan-gray lobulated tumor was histologically similar to the preoperative biopsy. The well-circumscribed submucosal neoplasm encircled seromucinous glands and featured clusters of four to 10 ovoid tumor cells without discrete cytoplasmic borders surrounded by numerous vascular channels, scant connective tissue, and scattered slender stellate cells (Fig 1). The ovoid cells contained abundant eosinophilic cytoplasm with small vacuoles, round to oval nuclei with speckled chromatin, and occasional conspicuous nucleoli. The stellate cells had little cytoplasm, bland nuclei, and processes wrapping around nests and individual cells. Nuclear pleomorphism and mitoses were not identified. The overlying bronchial mucosa featured squamous metaplasia. Immunohistochemical studies performed on both the preoperative biopsy and resection specimen demonstrated the nests of cells reactive to antibodies directed against chromogranin A and synaptophysin antigens, but negative staining for AE1/AE3, Cam 5.2, (epithelial membrane antigen), HMB-45, and A103. Both the ovoid cells and stellate cells were immunoreactive for S-100 protein; however, the latter had a more intense pattern of staining (Fig 2). The stellate cells were additionally negative for glial fibrillary acid protein, CD68, vimentin, and smooth muscle actin. Discussion While the presence of paraganglionic tissue in the perivascular interstitium of fetal lungs was convincingly demonstrated by Blessing and Hora over 30 years ago.1 This case report stands as the first well-documented example of primary pul-
monary paraganglioma. The presented neoplasm meets the Armed Forces Institute of Pathology’s suggested morphologic criteria for the diagnosis of paraganglioma. These include: a diffuse zellballen pattern throughout the tumor, absence of classic carcinoid tumor architectural patterns such as trabecular, pseudoglandular or spindle cell, the presence of cytoplasmic vacuoles distinctive of paragangliomas, negative immunohistochemical staining for cytokeratin as well the exclusion of an extrapulmonary paraganglioma or pheochromocytoma.2 Previously reported cases3-17 (Table 1) suffer from a variety of incomplete or contradictory findings that do not allow them to be readily distinguished from a carcinoid tumor. Many of the early reports either illustrate tumors with morphologic patterns that are more typical of carcinoid tumor or lack photomicrographs altogether. Also, reticulin staining, once in vogue and used to highlight the nesting architectural pattern of the cells in support of the diagnosis, is now recognized as a nonspecific method that does not discern the two tumor types. Some previous case reports based their diagnoses on the presence of sustentacular cells because it was originally thought to be a specific diagnostic feature of paragangliomas. However, many studies have reported S-100 –positive stellate cells resembling sustentacular cells in bronchial carcinoids in up to 76% of cases.18-20 While there is some ongoing debate as to whether these S-100 –positive cells are mesenchymal or neuroectodermal in origin, it is generally agreed that they are not a distinguishing feature of paragangliomas. As the Armed Forces Institute of Pathology criteria suggest, cytokeratin can aid in the distinction between a PPP and a carcinoid tumor, but is not absolutely diagnostic. As expected, because of their epithelial origin, nearly 100% of bronchial carcinoids, despite their degree of differentiation, will be positive for cytokeratins.21,22 Inversely, with the exception of cauda equina paragangliomas, cytokeratin positivity has only been reported in three cases occurring in the head and neck region.23 Immunohistochemistry for cytokeratins was performed on only four of the previously reported cases of PPP.15-17 Three of these four cases reported positive staining for cytokeratin; therefore, they are more consistent with a carcinoid tumor. The one case that was reportedly negative for cyto-
Primary Paraganglioma of the Lung
239
Figure 1. Primary pulmonary paraganglioma. (A) The submucosal neoplasm splays seromucinous glands but respects bronchial cartilage. (B) Nests of ovoid tumor cells feature abundant cytoplasm and occasional nuclear atypia. Thin-walled vascular spaces abound.
240
Aubertine and Flieder
Figure 2.
S-100 protein immunohistochemical stain. Sustentacular cell processes are highlighted. Table 1. Documented Case Reports of Primary Pulmonary Paraganglioma
Study
Convincing Photomicrographs
Cytokeratin
S-100⫹ Sustentacular Cells
Heppleston (1958)3 Mostecky et al (1966)4 Fawcett and Husband (1967)5 Fawcett and Husband (1967)5 Laustela et al (1969)6 Goodman and Lafort (1972)7 Goodman and Lafort (1972)7 Lee and Hori (1972)8 deLuise et al (1977)9 Arom and Trinkle (1977)10 Singh et al (1977)11 Hangartner et al (1989)12 Lemonick et al (1999)13 Vuorela and Anttinen (1993)14 Skodt et al (1995)15 Skodt et al (1995)15 Saeki et al (1999)16 Kim et al (2001)17
No No Yes ND Yes Yes Yes No Yes ND No No No No Yes No Yes Yes
ND ND ND ND ND ND ND ND ND ND ND ND ND ND CK⫹ CK⫺ CK⫹ CK⫹(focal)
ND ND ND ND ND ND ND ND ND ND ND Yes ND ND Yes Yes Yes Yes
Abbreviation: ND, not done.
Primary Paraganglioma of the Lung
keratin did not include an accompanying photomicrograph of the tumor.15 If incomplete reports in the past muddied the existence of PPP, then shifting terminologies and classification nomenclature only confused the issue further. Not only did the 1981 World Health Organization classification of lung tumors classify minute meningothelial nodules as paragangliomas, but also standard lung pathology texts published as recently as 2000 refer to paragangliomas as chemodectomas.24,25 The most recent World Health Organization classification has corrected the confusion by defining meningothelial nodule and paraganglioma as entirely separate entities. In addition, the morphologically distinct gangliocytic paraganglioma should not be confused with a paraganglioma.26,27 Because the patient’s neoplasm was amenable to lung-sparing surgery and he remains well 12 months following excision, one can only speculate about the natural history and metastatic potential of PPP. Although intra-abdominal extra-adrenal paragangliomas are quite aggressive, with malignancy rates up to 50% and a 5-year survival rate of 36% in one series, paragangliomas in other locations (such as the bladder) have low metastatic rates with biologic behavior similar to that of a typical carcinoid tumor of the lung.28 Thus, while the distinction between PPP and carcinoid tumor may not have a clinical impact, this report of a PPP shows its existence, clarifies historically confusing nomenclature, and emphasizes that immunohistochemistry serves as an important adjunct to light microscopic morphologic features. References 1. Lack EE: Extra-adrenal paragangliomas of the sympathoadrenal neuroendocrine system. In: Atlas of Tumor Pathology: Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia. 3rd Series. Vol 19. Washington, DC, Armed Forces Institute of Pathology, 1997 2. Colby TV, Koss MN, Travis WD: Carcinoid and other neuroendocrine tumors. In: Atlas of Tumor Pathology: Tumors of the Lower Respiratory Tract. 3rd Series. Washington, DC, Armed Forces Institute of Pathology, 1994, pp 309-311 3. Heppleston AG: A carotid-body-like tumour in the lung. J Pathol Bact 1958;75:461-464 4. Mostecky H, Lichtenberg J, Kalus M: A non-chromaffin paraganglioma of the lung. Thorax 1966;21:205-208 5. Fawcett FJ, Husband EM: Chemodectoma of lung. J Clin Pathol 1967;20:260-262 6. Laustela E, Mattila S, Franssila K: Chemodectoma of the lung. Scand J Thorac Cardiovasc Surg 1969;3:59-62 7. Goodman ML, Lafort EG: Solitary primary chemodectomas of the lung. Chest 1972;61:48-50
241
8. Lee YN, Hori JM: Chemodectoma of the lung. J Surg Oncol 1972;4:33-36 9. deLuise VP, Holman CW, Gray GF: Primary pulmonary paraganglioma. NY State J Med 1977;77:2270-2271 10. Arom KV, Trinkle JK: Solitary pulmonary paraganglioma: Case report and literature review. Am Surg 1977;43:689-691 11. Singh G, Lee RE, Brooks DH: Primary pulmonary paraganglioma. Report of a cases and review of the literature. Cancer 1977;40:2286-2289 12. Hangartner JW, Loosemore TM, Burke M, et al: Malignant primary pulmonary paraganglioma. Thorax 1989;44:154156 13. Lemonick DM, Pai PB, Hines GL: Malignant primary pulmonary paraganglioma with hilar metastasis. J Thorac Cardiovasc Surg 1999;99:563-564 14. Vuorela AL, Anttinen J: Primary chemodectoma of the lung. AJR Am J Roentgenol 1993;161:1111-1112 15. Skodt V, Jacobsen GK, Helsted M: Primary paraganglioma of the lung. Report of two cases and review of the literature. APMIS 1995;103:597-603 16. Saeki T, Akiba T, Joh K, et al: An extremely large solitary primary paraganglioma of the lung: Report of a case. Jpn J Surg 1999;29:1195-1200 17. Kim MK, Park SH, Cho HD, et al: Fine needle aspiration cytology of primary pulmonary paraganglioma. Acta Cytologica 2001;45:459-464 18. Barbareschi M, Frigo B, Mosca L, et al: Bronchial carcinoids with S-100 positive sustentacular cells. Pathol Res Pract 1990;186:212-222 19. Gosney JR, Denley H, Resl M: Sustentacular cells in pulmonary neuroendocrine tumours. Histopathology 1999;34:211215 20. Nakajima T, Kameya T, Watanabe S, et al: An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am J Surg Pathol 2001;116:S65-S96 (suppl 1) 21. Cerilli LA, Ritter JH, Mills SE, et al: Neuroendocrine neoplasms of the lung. Am J Clin Pathol 2001;116:S65-S96 (suppl 1) 22. Gould VE, Lee I, Warren WH: Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung. Pathol Res Pract 1998;183:200-213 23. Chetty R, Pillay P, Jaichand V: Cytokeratin expression in adrenal pheochromocytomas and extra-adrenal paragangliomas. J Clin Pathol 1998;51:477-478 24. Corrin B: Rare pulmonary tumors. In: Corrin B (ed): Pathology of the Lungs. London, UK, Churchill Livingstone, 2000, pp 537-538 25. Dail DH: Uncommon tumors. In: Dail DH, Hammar SP (eds): Pulmonary Pathology. New York, NY, Springer Verlag, 1994, pp 1353-1354 26. Hironaka M, Fukayama M, Takayashiki N, et al: Pulmonary gangliocytic paraganglioma: Case report and comparative immunohistochemical study of related neuroendocrine neoplasms. Am J Surg Pathol 2001;25:688-693 27. Kee AR, Forrest CH, Brennan BA, et al: Gangliocytic paraganglioma of the bronchus: A case report with follow-up and ultrastructural assessment. Am J Surg Pathol 2003;27:1380-1385 28. Lack EE: Aorticopulmonary paraganglioma. In: Atlas of Tumor Pathology: Tumors of the Adrenal Gland and ExtraAdrenal Paraganglia. 3rd Series. Vol 19. Washington, DC, Armed Forces Institute of Pathology, 1997