Soft Tissues: Angiomatoid fibrous histiocytoma

2005-10-01   Carolina Vicente-Dueñas , Isidro Sánchez-García 

Classification

Note

Angiomatoid fibrous histiocytoma is a rare soft tissue tumor of low-grade malignancy that usually occurs in children and young adults. Eighty-eight percent of patients are 30 years of age or younger. Enzinger in 1979 first designated the tumor as angiomatoid malignant fibrous histiocytoma. The tumour was later renamed angiomatoid fibrous histiocytoma because of its slow growth and rare metastasis.
This tumor forms solid, lobulated sheets of plump to spindled cells having histiocytic features adjacent to areas of haemorrhage.

Clinics and Pathology

Embryonic origin

Symptoms of anemia, weight loss, and fever are observed in a minority of cases; local symptoms, such as pain or tenderness, are extremely rare.

Clinics

Clinically, the tumor is often mistaken for hematoma or hemangioma. The diagnosis of angiomatoid fibrous histiocytoma is made on the basis of histopathology and immunohistochemical studies. Three microscopic findings are characteristic of AFH: (1) solid arrays or nests of histiocyte-like cells, (2) hemorrhagic cyst-like spaces, and (3) aggregates of chronic inflammatory cells. Multifocal recent and old hemorrhages are a striking feature in this tumor. These spaces resemble vascular spaces, but they are not lined by endothelium. Inflammatory cells present include lymphocytes and plasma cells. A thick pseudocapsule and occasional germinal centers give this tumor a resemblance to a lymph node.
Immunohistochemical studies are helpful in differential diagnosis of AFH. It was reported that the histiocytic marker CD68 was positive in 9 of 19 (47%) cases of angiomatoid fibrous histiocytoma. Immunopositivity for myoid or myofibroblastic markers in more than 50% of cases has also been reported.

Treatment

Local recurrence has been reported in 11% of patients and distant metastasis in 1%; wide excision is recommended as the treatment of angiomatoid fibrous histiocytoma. Local recurrence is attributed to the infiltrative margin and deep location of the tumour. Angiomatoid fibrous histiocytoma in the head and neck also can frequently recur, which may be a result of the difficulty of performing a wide local excision. If the tumor is unresectable or has metastasized, adjuvant chemotherapy may be helpful.

Note

This tumour typically affects children and young adults, presenting as a painless, slowly growing subcutaneous soft tissue mass that is usually located in the extremities and less commonly in the trunk, head, and neck. Only 18% of reported cases involved deep structures, such as skeletal muscle or periosteum.

Cytogenetics

Atlas Image
t(12;16)(q13; p11) G- banding - Courtesy G. Reza Hafez, Eric B.Johnson, and Sara Morrison-Delap,UW Cytogenetic Services

Cytogenetics molecular

  • FUS-ATF1 fusion gene in the t(12;16)(q13; p11).
  • EWSR1-ATF1 fusion gene in the t(12;22)(q13;q12)
  • Genes Involved and Proteins

    Gene name

    FUS (fusion involved in t (12;16) in malignant liposarcoma)

    Location

    16p11.2

    Dna rna description

    FUS gene consists of 15 exons located within 11 kb of genomic DNA.

    Protein description

    FUS protein, provisionally designated TLS (translocated in liposarcoma), and then called FUS, contains an RNA-recognition motif and is a component of nuclear riboprotein complexes. Lack of FUS in mice causes lethality into neonatal period, it influences lymphocyte development in a non-cell-intrinsic manner, it has an intrinsic role in the proliferative responses of B cells to specific mitogenic stimuli, and it is required for the maintenance of genomic stability. The involvement of a nuclear riboprotein in these processes in vivo indicates that FUS is important in genome maintenance.

    Somatic mutations

    FUS has been also shown a partner of gene fusions linked in other malignancies: fused to ERG in acute myeloid leukaemia with t(16;21) (p11;q22), fused to CREB3L2 in low-grade fibromyxoid sarcoma (LGFMS) by a translocation between chromosome bands 7q33-q34 (CREB3L2) and 16p11 (FUS), fused to ATF1 in histiocytoma or fused to CHOP gene in Myxoid Liposarcoma with t(13;16)(q13;p11).

    Gene name

    ATF1 (activating transcription factor 1)

    Location

    12q13.12

    Dna rna description

    816 bp mRNA

    Protein description

    ATF1 gene encodes a member of the CREB-ATF basic leucine-zipper (bZIP) family of transcription factors. This protein of 271 amino acids has a nuclear localization. Function: DNA binding protein, binds the consensus sequence: 5GTGACGT (A/C) (A/G)-3; cAMP-inducible transcription factor (cAMP-responsive enhancer-binding protein (CRE), like CREB. Is a member of the CREB protein family.

    Somatic mutations

    t(12;22)(q13;q12) in Angiomatoid Fibrous histiocytoma ATF1-EWSR1. It is also rearranged in clear cell sarcoma (CCS) with t(12;22) (q13;q12), creating an EWSR1-ATF1 fusion gene.

    Gene name

    EWSR1 (Ewing sarcoma breakpoint region 1)

    Location

    22q12.2

    Dna rna description

    DNA spans over 40 kb; open reading frame: 2.0 kb, 17 exons. Transcription 2.4 kb mRNA; centromere to telomere direction; differential splicing

    Protein description

    656 amino acids; serine-tyrosine tandem repeats. It has a wide expression and functions as a RNA binding.

    Somatic mutations

  • Ewing tumours with: t(11;22)(q24;q12) --> FLI1 - EWSR1. Ewing tumours: including Ewings Sarcoma and periphral primitive neuroectodermal tumour.
  • Ewing tumours with t(21; 22)(q21;q12) --> ERG - EWSR1. Ewing tumours (Ewings Sarcoma and peripheral primitive neuroectodermal tumour).
  • Ewing tumours with t(7;22)(p22;q12) --> ETV1 - EWSR1. Ewing tumours (Ewings Sarcoma and peripheral primitive neuroectodermal tumour).
  • Ewing tumours with t(17;22)(q12;q12) --> E1AF - EWSR1. Ewing tumours (Ewings Sarcoma and peripheral primitive neuroectodermal tumour).
  • t(11;22)(p13;q12) / Intra abdominal desmoplastic small round cell sarcoma (IADSRCT) --> WT1 - EWSR1.
  • t(12;22)(q13;q12) / Angiomatoid Fibrous Histiocytoma --> ATF1 - EWSR1.
  • t(9;22)(q22;q12) / Myxoid Chondrosarcoma --> TEC - EWSR1
  • Result of the chromosomal anomaly

    Description

  • EWSR1-ATF1 fusion gene t(12;22)(q13 ;q12)
  • Note

    FUS/ATF-1
    Atlas Image
    This fusion was generated by a translocation between chromosomal bands 16p11 and 12q 13, harbouring the FUS and ATF1 genes, respectively. FUS is interrupted at codon 175 (exon5) and fused to condon 110 (exon 5) of ATF1, resulting in an in-frame junction with a glycine to valina (GGT to GTT) transition.

    Description

    The normal ATF1 gene is transcribed from centromere to telomere, while the transcription of FUS seems to proceed in the opposite direction. Hence, the formation of FUS/ATF-1 is possible only if another genomic aberration, such as an inversion, occurs in addition to the chromosomal translocation. Such an event would be analogous to the formation of EWS/ERG in Ewing sarcoma and EWS/CHOP in myxoid liposarcoma.

    Bibliography

    Pubmed IDLast YearTitleAuthors
    114652072001Angiomatoid fibrous histiocytoma in mediastinum.Asakura S et al
    21746501990Angiomatoid malignant fibrous histiocytoma. A follow-up study of 108 cases with evaluation of possible histologic predictors of outcome.Costa MJ et al
    93069651997Additional evidence of a variant translocation t(12;22) with EWS/CHOP fusion in myxoid liposarcoma: clinicopathological features.Dal Cin P et al
    2288361979Angiomatoid malignant fibrous histiocytoma: a distinct fibrohistiocytic tumor of children and young adults simulating a vascular neoplasm.Enzinger FM et al
    105715141999Angiomatoid "malignant" fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype.Fanburg-Smith JC et al
    80403011994EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations.Giovannini M et al
    158840992005Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma.Hallor KH et al
    81870691994An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation.Ichikawa H et al
    108162412000Angiomatoid fibrous histiocytoma: a case report and review of the literature.Jacobs IA et al
    110155711999Molecular genetics of chromosome translocations involving EWS and related family members.Kim J et al
    160076692005Fine-needle aspiration cytology of angiomatoid malignant fibrous histiocytoma.Lemos MM et al
    152587042004MRI of angiomatoid fibrous histiocytoma.Li CS et al
    158268352005Understanding mesenchymal cancer: the liposarcoma-associated FUS-DDIT3 fusion gene as a model.Pérez-Mancera PA et al
    86377041996Fusion of the EWS and CHOP genes in myxoid liposarcoma.Panagopoulos I et al
    122184552002Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous histiocytoma.Raddaoui E et al
    129076332003FUS/ERG gene fusions in Ewing's tumors.Shing DC et al
    16768791991Evaluation of CD68 and other histiocytic antigens in angiomatoid malignant fibrous histiocytoma.Smith ME et al
    81620681994A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG.Sorensen PH et al
    107821742000Pathologic quiz case: a large cystic thigh mass in a 10-year-old boy.Wang H et al
    110637922000Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.Waters BL et al
    84015791993EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts.Zucman J et al
    82234581993Combinatorial generation of variable fusion proteins in the Ewing family of tumours.Zucman J et al

    External Links

    Citation

    Carolina Vicente-Dueñas ; Isidro Sánchez-García

    Soft Tissues: Angiomatoid fibrous histiocytoma

    Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5204/soft-tissues-angiomatoid-fibrous-histiocytoma