Sarcomatoid carcinoma of lung

Definition

Poorly differentiated non-small cell carcinoma with a sarcoma or sarcoma-like component0,9. 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 women1,10,13,14,16,19,21,22. There is a strong association with smoking10,13,21,22.

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. This entity should not be confused with pleuropulmonary blastoma.

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, 37/3719, 18/2120, positive28
	AE1/AE3	15/1930
	AE1	10/10(strong diffuse positivity)11
	AE3	10/10(two cases only focally positive)11
	Cam5.2	10/1011
	CK20	0/2129
	EMA	Reduced compared to better differentiated carcinomas5, positive28 , 13/1930
	MAb A80	10/1011
	CEA	positive28
	TTF-1	5/1930
	p63	10/2030
	MOC-31	8/1930
	Vimentin	Often strong paranuclear in giant cell carcinoma5, 9/10(extensive intense positivity)11
	CD99	18/2129
	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.

The immunoreactivity of the sarcomatous component is often determined by the nature of the coexistent epithelial component:

specific components present are shown in brackets	TTF-1		CK7
specific components present are shown in brackets	epithelial	sarcomatous	epithelial	sarcomatous
pure spindle cell carcinoma		4/101		7/10
pure giant cell carcinoma		2/31, 0/329		2/31, 2/329
pleomorphic carcinoma (giant cell carcinoma/spindle cell carcinoma)		5/71, 1/329		5/71, 1/329
Pleomorphic carcinoma (adenocarcinoma)	12/141, 3/429	11/141, 1/429	14/141, 3/429	12/141, 2/429
Pleomorphic carcinoma (squamous cell carcinoma)	0/121, 0/329	0/121, 0/229	5/121	2/121, 1/3(spindle cell component)29
Pleomorphic carcinoma (large cell carcinoma)	13/181, 2/829	7/181, 0/629	14/181, 6/829	13/181, 6/829
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 cells7 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 tumours13,14,16,17,21,23,26, 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.

1 Rossi, 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.

2 Ansari-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.

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

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

5 Addis BJ, Dewar A,Thurlow NP Giant cell carcinoma of the lung--immunohistochemical and ultrastructural evidence of dedifferentiation. J Pathol 1988; 155:231-40

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

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

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

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

10 Chang 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