Primary Pulmonary Myxoid Sarcoma with EWSR1-CREB1 fusion

Definition

A single paper has been published which describes Primary Pulmonary Myxoid Sarcoma with EWSR1-CREB1 fusion as an extremely rare primary pulmonary sarcoma resembling extraskeletal myxoid chondrosarcoma, but with immunoreactivity limited to vimentin and EMA, and having a characteristic gene fusion.

Epidemiology

Patients are aged 27 to 67 with a mean of 45 years. There is a female predominance. There may be an association with cigarette smoking.

Clinical features

Presentation is with cough, haemoptysis or constitutional symptoms of fever and weight loss, or with the incidental finding of a thoracic mass.

Radiology

Macroscopic appearances

The tumours are predominantly endobronchial. They are well circumscribed with a glistening/gelatinous cut surface.

Histopathology

The tumour is in proximity to a bronchus but with infiltration of the lung parenchyma. There may be a peripheral fibrous pseudocapsule. A lobular architecture is apparent. The tumour cells are spindled, stellate or polygonal, forming cords or single or in small groups within the prominent lightly basophilic myxoid stroma. Cellular atypia is variable between cases. Focal necrosis is common. The mitotic rate varies from 0 to 32 / 10 HPF but is usually less than 5 / 10 HPF. There may be a lymphoplasmacytic inflammatory infiltrate with lymphoid follicles and some eosinophils. There is no chondroid deafferentation and lipoblasts are absent.

Immunohistochemistry

	Vimentin	5/5
	EMA	3/5(focal weak positivity)
	S100	1/9(very focal nuclear positivity)
	AE1/AE3	0/9
	CK5/6	0/2
	CK7	0/3
	CK20	0/2
	34bE12	0/2
	p63	0/2
	TTF-1	0/5
	HMB45	0/3
	Melan-A	0/2
	Desmin	0/9
	SMA	0/9
	CD34	0/9
	CD56	1/6(focal positivity)
	Chromogranin	1/6(focal positivity)
	Synaptophysin	1/6(focal positivity)
	Hyaluronidase sensitive Alcian Blue	5/5(Partially resistant in one case)

Ultrastructure

Molecular genetics

	RT-PCR EWSR1-CREB1 translocation	7/9
	FISH EWSR1 breakpoint	7/10
	NR4A3-EWSR	0/7
	NR4A3-TAF15	0/7

Differential diagnosis

Primary pulmonary extraskeletal myxoid chondrosarcoma has not been reported
Parachordoma: positive for cytokeratins and S100
Myoepithelioma: positive for cytokeratins and S100, variably for Calponin, EMA, GFAP and SMA. Rearrangements involve the EWSR1 gene with ZNF444, PBX1 and POU5F1 but not CREB1.
Primary chordoid meningioma: positive for Vimentin and EMA.
Pulmonary myxoma
Primary myxoid liposarcoma
Myxofibrosarcoma
Aggressive angiomyxoma
Microcystic fibromyxoma
EWSR1-CREB1 fusion is also seen in both angiomatoid fibrous histiocytoma and clear cell sarcoma-like tumour of the gastrointestinal tract (CCSLGT)/conventional soft tissue CCS.

Management

Prognosis

Two of ten patients developed metastases.

References

1 Thway K, Nicholson AG, Lawson K, Gonzalez D, Rice A, Balzer B, et al. Primary Pulmonary Myxoid Sarcoma With EWSR1-CREB1 Fusion: A New Tumor Entity. Am J Surg Pathol. 2011 Nov;35(11):1722-32.