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angiomatoid fibrous histiocytoma

Tuesday 14 October 2003

Definition: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of low malignant potential and uncertain differentiation.



Angiomatoid "malignant" fibrous histiocytoma is considered to be a low-grade sarcoma of childhood, and, with its fibrous pseudocapsule, angiomatoid change, dense lymphoplasmacytic response, and proliferation of spindled or round cells, has been classified as a fibrohistiocytic neoplasm.

Angiomatoid fibrous histiocytoma clearly represents a clinically and morphologically distinct entity, the precise line of differentiation of which remains unknown.

These tumours, which are commonest in the subcutis of children and young adults, are notably associated with a prominent lymphoplasmacytic infiltrate in many cases and, by immunohistochemistry, show positivity for desmin and/or epithelial membrane antigen (EMA) in approximately 40–50% of cases.

These lesions, which are in no way related to aneurysmal fibrous histiocytoma of skin, are speculated to show either fibroblastic reticulum cell or perhaps some type of myoid differentiation.


- gender ratio of 1.3 females: males (10571514)
- age range of 2 to 71 years (10571514)
- distribution: extremities > trunk > head and neck, with 66% lesions occurring in areas of normal lymphoid tissue (10571514)


- median size of 2.0 cm (10571514)
- well-circumscribed (10571514)


- 18% of cases had some degree of lymphoplasmacytic infiltration (10571514)
- 50% cases had pseudovascular spaces filled with blood (10571514)
- 52% had predominantly round cell morphology;
48% had a predominantly spindle cell pattern (10571514)


The resemblance of these lesions to lymph nodes, clinically and morphologically, the finding of similar desmin positive cells in the adjacent lymphoid infiltrate, and the fact that 66% cases were found in sites of normal lymphoid tissue raise the possibility that some of these lesions may arise from or be related to myoid cells of lymphoid tissue.

Differential diagnosis

The predominantly round cell, CD99-positive and desmin positive AMFH cases, respectively, should not be confused with:

- Ewing’s sarcoma/PNET
- rhabdomyosarcoma


Desmin positivity was noted in 51% cases and occurred in both predominantly round cell and spindle cell tumors. Most of the desmin-positive cases with adjacent lymphoid infiltrate (67%) showed scattered similar, desmin-positive cells in the surrounding lymphoid infiltrate, adjacent to the tumor.

Muscle-specific and smooth-muscle actins were seen in 14% cases.

Heavy-caldesmon was strongly positive in 3%, and calponin was focally positive in 73% and extensively positive in 12% cases.

MyoD1, myoglobin, and myogenin (myf4) were negative in all tumors studied. Forty-five percent of cases were positive for CD99; 52% of these had round cell morphology. Fifteen percent of cases were positive for KP-1.

All tumors were positive for vimentin and negative for CD21, CD35, S100 protein, CD34, keratins 8/18, and lysozyme.

Clinical follow-up on 86 patients indicated that only 1 patient was alive with a local nodal metastasis (1% frequency of metastasis) within 1 year, and 2 others had local recurrence, all over a mean follow-up period of 6 years.

The myoid, primarily myofibroblastic, phenotype of these lesions is supported by desmin, calponin, and occasional actin positivity.

The occasional heavy-caldesmon and smooth muscle actin additionally suggest rare smooth muscle phenotype; however, lack of skeletal muscle markers indicate no relationship of AMFH to skeletal muscle tumors.

- vimentin +
- calponin +
- CD99 +
- desmin +/-

Molecular biology

- ATF1-FUS fusion gene by t(12;16)(q13;p11) (ATF1 at 12q13 and FUS at 16p11) (12218455, 11063792)

- ATF1-EWSR1 fusion gene by t(12;22)(q13;q12) (ATF1 at 12q13 and EWSR1 at 22q12) (15884099, 18300800)

- CREB1-EWSR1 fusion gene by t(2;22)(q33;q12) (17724745)


AMFH has an almost invariably benign behavior, but the 1% metastatic rate warrants its classification as low-grade "malignant." (10571514)


- Dunham C, Hussong J, Seiff M, Pfeifer J, Perry A. Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes. Am J Surg Pathol. 2008 Mar;32(3):478-84. PMID: 18300800

- Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, Ladanyi M. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007 Aug 20; PMID: 17724745

- Hallor KH, Micci F, Meis-Kindblom JM, Kindblom LG, Bacchini P, Mandahl N, Mertens F, Panagopoulos I. Fusion genes in angiomatoid fibrous histiocytoma. Cancer Lett. 2007 Jun 18;251(1):158-63. PMID: 17188428

- Hallor KH, Mertens F, Jin Y, Meis-Kindblom JM, Kindblom LG, Behrendtz M, Kalen A, Mandahl N, Panagopoulos I. Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2005 Sep;44(1):97-102. PMID: 15884099

- Waters BL, Panagopoulos I, Allen EF. Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11. Cancer Genet Cytogenet. 2000 Sep;121(2):109-16. PMID: 11063792