malignant fibrous histiocytoma

Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation.

Genetic finding are similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas.

Nota bene: It is now recognized that so-called pleomorphic MFH is not a definable or reproducible entity. Instead, the large majority of lesions formerly so classified can be reproducibly categorized into other types of pleomorphic sarcoma, sarcomatoid carcinoma, melanoma or even lymphoma. Furthermore, there is now clear evidence that subclassification of pleomorphic sarcomas has clinical relevance, with those lesions showing myogenic differentiation (of any type) being especially aggressive.

In the current WHO Classification, the term pleomorphic MFH is now regarded as synonymous with undifferentiated pleomorphic sarcoma and essentially represents a diagnosis of exclusion, accounting for no more than approximately 5% of adult soft tissue sarcomas.

Most examples of so-called giant cell MFH can currently be reclassified as either giant cell-rich osteosarcomas, giant cell tumour (osteoclastoma) of soft tissue, leiomyosarcoma with an osteoclastic giant cell reaction or as giant cell-rich anaplastic carcinoma.

Similarly, the overwhelming majority of lesions formerly labelled inflammatory MFH are nowadays recognized to be dedifferentiated liposarcomas, in which the dedifferentiated component has a prominent stromal neutrophilic infiltrate.

Other tumours which may mimic the pattern of inflammatory MFH include anaplastic carcinomas and anaplastic large cell lymphoma.

Other important changes were that so-called myxoid MFH has been redesignated myxofibrosarcoma—being a malignant fibroblastic neoplasm associated with mucin deposition, which has been reallocated to the fibroblastic/myofibroblastic category.

Similarly, so-called angiomatoid fibrous histiocytoma (formerly known as angiomatoid MFH) has been reallocated to the category of tumours of uncertain differentiation. These two tumour types clearly represent distinct entities which are in no way associated with the category of pleomorphic sarcomas formerly known as pleomorphic MFH.

Cytogenetics

 amplifications of the 12q14-q15 chromosome region (20%)
 1p32 band amplification
 6q23 band amplification (amplification and overexpression of ASK1 or MAP3K5 gene)

 chromosome 13 deletion

• The RB1 gene is the target of chromosome 13 deletions in malignant fibrous histiocytoma. (11103795)

Molecular biology

 amplification and overexpression of ASK1 or MAP3K5 gene at 6q23 band (15034865)

Differential diagnosis

 dedifferentiated liposarcomas (15221942, 12640106)

References

 The evolving classification of soft tissue tumours: an update based on the new WHO classification. Fletcher CD. Histopathology. 2006 Jan;48(1):3-12. PMID: 16359532

 Chibon F, Mariani O, Derre J, Mairal A, Coindre JM, Guillou L, Sastre X, Pedeutour F, Aurias A. ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications. Genes Chromosomes Cancer. 2004 May;40(1):32-7. PMID: 15034865

 Chibon F, Mariani O, Derre J, Malinge S, Coindre JM, Guillou L, Lagace R, Aurias A. A subgroup of malignant fibrous histiocytomas is associated with genetic changes similar to those of well-differentiated liposarcomas. Cancer Genet Cytogenet. 2002 Nov;139(1):24-9. PMID: 12547153

 The RB1 gene is the target of chromosome 13 deletions in malignant fibrous histiocytoma. Chibon F, Mairal A, Fréneaux P, Terrier P, Coindre JM, Sastre X, Aurias A. Cancer Res. 2000 Nov 15;60(22):6339-45. PMID: 11103795