Thymic and upper respiratory tract carcinoma with t(15;19) translocation

Definition

A rare thymic undifferentiated carcinoma with a characteristic translocation, t(15;19)(q13;p13.1). This translocation appears to create a fusion product between a bromodomain gene, BRD4, on chromosome 19 regulating cell cycle progression and a putative oncogene on chromosome 15, NUT (Nuclear protein in Testis), normally only expressed in the testis^5,6.

Synonym

Lethal midline carcinoma.

Aetiology

There is no known association with EBV.

Epidemiology

This is a tumour of children and young adults, predominantly female.

Clinical features

Although most often arising in the thymus^1,3, this tumour has also been reported from the sinonasal region⁴, larynx⁴ and bladder. Widespread metastases are usual. There is commonly superior vena cava compression⁴.

Histopathology

In most cases, the tumours are morphologically undifferentiated, being composed of cells with relatively little cytoplasm, vesicular nuclei and prominent nucleoli forming syncytial sheets. There is extensive necrosis and a lymphoplasmacytic infiltrate. The mitoitc rate is high. There may be focal squamous differentiation⁴. In one case, the tumour showed mucoepidermoid differentiation⁴. Mucin stains are negative⁴.

Immunohistochemistry

	Cytokeratin	1/12, 2/24
	Vimentin	2/24
	CEA	1/12, 0/24
	EMA	1/2 (focal)4
	CD3	0/24
	CD20	0/24
	CD30	0/24
	CD45	0/24
	HMB-45	0/24
	PLAP	0/24
	AFP	0/24
	SMA	0/24
	MSA	0/24
	desmin	0/24
	S-100	0/24
	chromogranin	0/24

Ultrastructure

Electron microscopy shows rare intermediate junctions and basal lamina⁴.

Differential diagnosis

• Germ cell tumour

• Large cell lymphoma

• Lymphoepithelioma-like carcinoma

• poorly differentiated squamous cell carcinoma

• t(15;19)-negative undifferentiated carcinoma

Management

The tumours seem unresponsive to a range of modalities of treatment⁴.

Prognosis

This is a highly aggressive, lethal tumour⁴. Metastases occur to lymph nodes, lung, bone, skin and soft tissues.

References

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

¹ Kubonishi, I., N. Takehara, et al. (1991). "Novel t(15;19)(q15;p13) chromosome abnormality in a thymic carcinoma." Cancer Res 51(12): 3327-8.

² Kees, U. R., M. T. Mulcahy, et al. (1991). "Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19)." Am J Pediatr Hematol Oncol 13(4): 459-64.

³ Lee, A. C., Y. I. Kwong, et al. (1993). "Disseminated mediastinal carcinoma with chromosomal translocation (15;19). A distinctive clinicopathologic syndrome." Cancer 72(7): 2273-6.

⁴ Vargas, S. O., C. A. French, et al. (2001). "Upper respiratory tract carcinoma with chromosomal translocation 15;19: evidence for a distinct disease entity of young patients with a rapidly fatal course." Cancer 92(5): 1195-203.

⁵ French, C. A., I. Miyoshi, et al. (2001). "BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19)." Am J Pathol 159(6): 1987-92.

⁶ French, C. A., I. Miyoshi, et al. (2003). "BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma." Cancer Res 63(2): 304-7.

This page last revised 31.3.2004.

©SMUHT/PW Bishop