Sarcomatoid carcinoma of lung

Definition

Poorly differentiated non-small cell carcinoma with a sarcoma or sarcoma-like component^0,9. Loss of heterozygocity studies indicate that both epithelial and mesenchymal components are derived from the same clone¹².

Epidemiology

Up to 1.3% of all lung carcinomas are of sarcomatoid type. It is four times more common in men than in women^{1,10,13,14,16,19,21,22}. There is a strong association with smoking^10,13,21,22.

Histopathology

• Pleomorphic carcinoma: a non-small cell carcinoma with a spindle or giant cell component. In order to be classified as a pleomorphic carcinoma, at least 10% of the tumour should consist of spindle and/or giant cells.

• Spindle cell carcinoma is a carcinoma consisting only of spindle-shaped tumour cells¹⁸. There may be a lymphoplasmacytic infiltrate, which may cause a resemblance to inflammatory myofibroblastic tumour.

• Giant cell carcinoma is a tumour consisting only of highly pleomorphic multi- or mono-nucleated tumour giant cells. There is frequently an inflammatory component, often predominantly of neutrophils.

• Carcinosarcoma is a malignant tumour having a mixture of carcinoma and sarcoma containing heterologous elements such as malignant cartilage, bone or skeletal muscle¹⁶. The sarcomatous component may predominate and may be composed predominantly of undifferentiated spindle cells. The carcinomatous element is most often squamous (45-70% of cases), less often adenocarcinomatous (20-30% of cases ) or large cell (10% of cases)¹⁶. If it resembles high grade fetal adenocarcinoma (as it does in 20% of cases), there should not be a blastematous stromal component. Metastases may be biphasic or may consist of only the carcinomatous or only the sarcomatous component.

• Pulmonary blastoma²³: a biphasic tumour containing a primitive epithelial component resembling well-differentiated fetal adenocarcinoma and a primitive mesenchymal component with occasional foci of osteosarcoma, chondrosarcoma or rhabdomyosarcoma¹⁷. Combination with a yolk sac tumour has been reported²⁴. The epithelial component may include squamous morules. The stromal component shows condensations around the epithelial component.

Immunohistochemistry

Expression of epithelial markers by the spindle or giant cell component is not a requirement, provided that an overtly epithelial component is present. If negative for cytokeratins, differentiation of pure spindle cell carcinoma from sarcoma is problematic. There is often co-expression of cytokeratins, vimentin, CEA and SMA.

	Cytokeratins	Variable4, reduced compared to better differentiated carcinomas5, 37/37 (sarcomatous component positive in all cases)19, 18/21 (results are for cytokeratin and/or EMA in the sarcomatous component)20, positive (in epithelial component of blastomas)28
	AE1	10/10 (strong diffuse positivity)11
	AE3	10/10 (two cases only focally positive)11
	Cam5.2	10/10 (weaker and less extensive than AE1/AE3)11
	EMA	Reduced compared to better differentiated carcinomas5, positive (in epithelial component of blastomas)28
	MAb A80 (binds a mucinous glycoprotein associated with exocrine function)	10/10 (staining strong but of variable extent)11
	CEA	positive (in epithelial component of blastomas)28
	Vimentin	Often strong paranuclear in giant cell carcinoma5, 9/10 (extensive intense positivity)11
	beta-human chorionic gonadotrophin	May be positive in giant cell carcinoma6. Positive in 21% of squamous carcinomas, 60% of adenocarcinomas and 93% of large cell carcinomas, showing no association with tumour giant cells8.
	hPL	Positive in 28% of squamous carcinomas, 10% of adenocarcinomas and 56% of large cell carcinomas, showing no association with tumour giant cells8.
	pregnancy-specific beta-1 glycoprotein	Positive in 64% of squamous carcinomas, 80% of adenocarcinomas and 93% of large cell carcinomas, showing no association with tumour giant cells8.
	Collagen IV	positive in the sarcomatous component26.

specific components present are shown in brackets	TTF-1		CK7
	epithelial	sarcomatous	epithelial	sarcomatous
pure spindle cell carcinoma		4/101		7/10
pure giant cell carcinoma		2/3 (the positive cases included one choriocarcinoma-like giant cell tumour)1		2/3 (the positive cases included one choriocarcinoma-like giant cell tumour)
pleomorphic carcinoma (giant cell carcinoma/spindle cell carcinoma)		5/71		5/71
Pleomorphic carcinoma (adenocarcinoma)	12/141	11/141	14/141	12/141
Pleomorphic carcinoma (squamous cell carcinoma)	0/121	0/121	5/121	2/121
Pleomorphic carcinoma (large cell carcinoma)	13/181	7/181	14/181	13/181
Pleomorphic carcinoma(adenocarcinoma/large cell carcinoma)	4/51	3/51	5/51	4/51
Pleomorphic carcinoma(squamous cell carcinoma/adenocarcinoma)	1/21	1/21	1/21	1/21
Carcinosarcoma	1/31	0/31	1/31	0/31
Pulmonary blastoma	1/11, 1/13	0/11, 0/13	1/11	0/11
Overall	58%1	55%1	76%1	63%1

CK20 was negative in all components in all the above tumours. Surfactant protein A showed a low sensitivity (39% for epithelial component, 6% for sarcomatoid component).

Carcinosarcoma: the epithelial component is positive for cytokeratins; any chondrosarcomatous component is positive for S-100 and any rhabdomyosarcomatous component is positive for muscle markers.

Pulmonary blastoma: the epithelial component is positive for cytokeratins, EMA and CEA, variably for neuroendocrine markers and specific hormones. Staining for alpha-fetoprotein is rare. The stromal component is positive for vimentin and muscle-specific actin. Any striated muscle is positive for desmin and any cartilage for S-100. Although usually segregated, sometimes the epithelium is positive for vimentin and the stroma for cytokeratins.

The correlation in the level of p53 expression in the epithelial and sarcomatoid components of biphasic tumours argues that the two components share a common pathway of tumourogenesis².

Ultrastructure

There may be dense paranuclear aggregation of intermediate filaments in giant cell carcinoma⁵. Spindle cell squamous carcinomas show intercellular junctions and thick bundles of tonofilaments²⁵.

Differential diagnosis

• If an inflammatory component is prominent and the neoplastic component is deceptively bland (inflammatory sarcomatoid carcinoma), the differential includes reactive / inflammatory processes (inflammatory pseudotumour, bronchiolitis obliterans / organising pneumonia)²⁷. The presence of focally moderate nuclear pleomorphism and of vascular invasion is helpful, as are positivity for cytokeratins and EMA²⁷ .

• In the absence of an obvious epithelial element; sarcomata, including fibrosarcoma, pleomorphic malignant fibrous histiocytoma, leiomyosarcoma, follicular dendritic cell sarcoma, angiosarcoma and synovial sarcoma.

• Giant cell carcinoma: pleomorphic rhabdomyosarcoma, metastatic adrenocortical carcinoma, choriocarcinoma and other pleomorphic tumours. b-HCG is commonly positive in non-small cell carcinoma and does not indicate a diagnosis of choriocarcinoma. Non-small cell carcinomas may contain osteoclast-like giant cell tumours⁷ but should not be mistaken for giant cell carcinoma.

• Carcinosarcoma: metastases from the genital tract, carcinosarcomas and teratomas

• Pulmonary blastoma: fetal adenocarcinoma, pleuropulmonary blastoma, metastatic synovial sarcoma sarcoma (primary pulmonary synovial sarcoma is not usually biphasic).

Prognosis

These are generally considered highly aggressive tumours^{13,14,16,17,21,23,26}, which may metastasis to unusual sites¹⁰. Others have found no difference in prognosis from non-sarcomatoid carcinomas¹⁹. There may be a higher rate of gastrointestinal tract involvement than for other non-small cell carcinomas¹⁵. Giant cells constituting less than 10% of the tumour may be found in squamous cell carcinomas and adenocarcinomas and do not worsen the prognosis⁶.

References

⁰Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

¹Rossi, G., Cavazza, A., Sturm, N., Migaldi, M., Facciolongo, N., Longo, L., Maiorana, A. and Brambilla, E. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol 2003;27:311-24.

²Ansari-Lari, M. A., M. O. Hoque, et al. (2002). "Immunohistochemical p53 expression patterns in sarcomatoid carcinomas of the upper respiratory tract." Am J Surg Pathol 26(8): 1024-31.

³Garcia-Escudero, A., R. Gonzalez-Campora, et al. (2004). "Thyroid transcription factor-1 expression in pulmonary blastoma." Histopathology 44(5): 507-8.

⁴Addis BJ,Corrin B Pulmonary blastoma, carcinosarcoma and spindle-cell carcinoma: an immunohistochemical study of keratin intermediate filaments. J Pathol 1985; 147:291-301

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⁶Attanoos RL, Papagiannis A, Suttinont P, et al. Pulmonary giant cell carcinoma: pathological entity or morphological phenotype? Histopathology 1998; 32:225-31

⁷Bocklage TJ, Dail D,Colby TV Primary lung tumors infiltrated by osteoclast-like giant cells. Ann Diagn Pathol 1998; 2:229-40

⁸Boucher LD,Yoneda K The expression of trophoblastic cell markers by lung carcinomas. Hum Pathol 1995; 26:1201-6

⁹Brambilla E, Travis WD, Colby TV, et al. The new World Health Organization classification of lung tumours. Eur Respir J 2001; 18:1059-68

¹⁰Chang YL, Lee YC, Shih JY, et al. Pulmonary pleomorphic (spindle) cell carcinoma: peculiar clinicopathologic manifestations different from ordinary non-small cell carcinoma. Lung Cancer 2001; 34:91-7

¹¹Chejfec G, Candel A, Jansson DS, et al. Immunohistochemical features of giant cell carcinoma of the lung: patterns of expression of cytokeratins, vimentin, and the mucinous glycoprotein recognized by monoclonal antibody A-80. Ultrastruct Pathol 1991; 15:131-8

¹²Dacic S, Finkelstein SD, Sasatomi E, et al. Molecular pathogenesis of pulmonary carcinosarcoma as determined by microdissection-based allelotyping. Am J Surg Pathol 2002; 26:510-6

¹³Davis MP, Eagan RT, Weiland LH, et al. Carcinosarcoma of the lung: Mayo Clinic experience and response to chemotherapy. Mayo Clin Proc 1984; 59:598-603

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¹⁵Ginsberg SS, Buzaid AC, Stern H, et al. Giant cell carcinoma of the lung. Cancer 1992; 70:606-10

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¹⁷Koss MN, Hochholzer L,O'Leary T Pulmonary blastomas. Cancer 1991; 67:2368-81

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¹⁹Nakajima M, Kasai T, Hashimoto H, et al. Sarcomatoid carcinoma of the lung: a clinicopathologic study of 37 cases. Cancer 1999; 86:608-16

²⁰Nappi O, Glasner SD, Swanson PE, et al. Biphasic and monophasic sarcomatoid carcinomas of the lung. A reappraisal of 'carcinosarcomas' and 'spindle-cell carcinomas'. Am J Clin Pathol 1994; 102:331-40

²¹Nappi O,Wick MR Sarcomatoid neoplasms of the respiratory tract. Semin Diagn Pathol 1993; 10:137-47

²²Ro JY, Chen JL, Lee JS, et al. Sarcomatoid carcinoma of the lung. Immunohistochemical and ultrastructural studies of 14 cases. Cancer 1992; 69:376-86

²³Robert J, Pache JC, Seium Y, et al. Pulmonary blastoma: report of five cases and identification of clinical features suggestive of the disease. Eur J Cardiothorac Surg 2002; 22:708-11

²⁴Siegel RJ, Bueso-Ramos C, Cohen C, et al. Pulmonary blastoma with germ cell (yolk sac) differentiation: report of two cases. Mod Pathol 1991; 4:566-70

²⁵Suster S, Huszar M,Herczeg E Spindle cell squamous carcinoma of the lung. Immunocytochemical and ultrastructural study of a case. Histopathology 1987; 11:871-8

²⁶Wick MR, Ritter JH,Humphrey PA Sarcomatoid carcinomas of the lung: a clinicopathologic review. Am J Clin Pathol 1997; 108:40-53

²⁷Wick MR, Ritter JH,Nappi O. Inflammatory sarcomatoid carcinoma of the lung: report of three cases and clinicopathologic comparison with inflammatory pseudotumors in adult patients. Hum Pathol 1995; 26:1014-21

²⁸Yousem SA, Wick MR, Randhawa P, et al. Pulmonary blastoma. An immunohistochemical analysis with comparison with fetal lung in its pseudoglandular stage. Am J Clin Pathol 1990; 93:167-75

This page last revised 18.4.2005.

©SMUHT/PW Bishop