Malignant fibrous histiocytoma, new name: undifferentiated pleomorphic sarcoma, is a soft tissue tumor, a sarcoma, that occurs in adulthood (ages 10-90, peaking at 50-70). It is the most common sarcoma in adults, accounting for 5-10% of all sarcomas. It usually occurs in the legs, especially the thigh, but can also arise in numerous other organs and even retroperitoneally. The tumor originates from primitive mesenchymal cells that do not differentiate in any specific direction and is often located in fascia or muscle. It occurs primarily in Caucasians; the male-to-female ratio is approximately 2:1. Clinically, it presents as a painless, slowly growing swelling of 5-10 cm, usually in the thigh. It is a dangerous tumor that can metastasize, especially to the lungs. The 5-year survival rate for tumors < 5 cm is around 80%, between 5 and 10 cm it is 65%, and for tumors > 10 cm it is around 45%.

There are two variants: superficial and deep. Superficial tumors are confined to the dermis and subcutaneous tissue, have a better prognosis, and metastasize less frequently. They may be provoked by damage of the skin (scars, ulcers, radiotherapy). These rare superficial variants are primarily seen in dermatology. Deep tumors are much more common (90%), are usually located in striated muscle tissue of the extremities, and have a poor prognosis. They can metastasize to the lungs, lymph nodes, bones, liver, and other organs.

Currently, most pathologists prefer the term pleiomorphic sarcoma to malignant fibrous histiocytoma because immunohistochemical analysis shows that these lesions can be several different pleiomorphic sarcomas, such as pleiomorphic liposarcoma, pleiomorphic leiomyosarcoma, and pleiomorphic rhabdomyosarcoma.




DD:
Other soft tissue sarcomas, pleomorphic dermal sarcoma (primary cutaneous localization of an undifferentiated pleomorphic sarcoma), atypical fibroxanthoma, dermatofibrosarcoma protuberans, leiomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, myxofibrosarcoma, osteosarcoma, malignant peripheral nerve sheath tumor, metastases, desmoplastisch melanoma, spindle-cell squamous cell carcinoma.

Therapy:
Wide surgical excision. Radiotherapy and chemotherapy may contribute to survival. Caution is advised when performing the excision; there is a case report in which the tumor was transferred to the surgeon through an incision during surgery.

Additional radiotherapy may be administered before or after surgical excision. Various chemotherapeutic agents are used, such as doxorubicin alone or in combination with ifosfamide, gemcitabine, docetaxel, and others. The effect is disappointing. Newer studies are underway combining chemotherapy with pembrolizumab or nivolumab. Patients are best referred to an oncology center with expertise in soft tissue tumors.




Nomenclature: Malignant fibrous histiocytoma, undifferentiated pleomorphic sarcoma, pleomorphic dermal sarcoma, or atypical fibroxanthoma?

An atypical fibroxanthoma is a tumor that often develops on the face of the elderly in sun-exposed areas. There are variants that are clinically and histologically difficult to distinguish from a superficial form of malignant fibrous histiocytoma / pleiomorphic sarcoma. There is debate about whether an atypical fibroxanthoma is a single entity or a superficial variant of a malignant fibrous histiocytoma / pleiomorphic sarcoma. Clinically, there are major differences, because atypical fibroxanthoma is a red, spherical, erosive tumor and the prognosis is good (recurrence after excision approximately 7%, low mortality) compared to MFH / pleiomorphic sarcoma (43% recurrence). Histologically, the distinction is difficult to make, even with immunohistochemical staining (perhaps CD74, which is strongly positive in MFH / pleomorphic sarcoma and weakly in atypical fibroxanthoma).

In newer classifications, the term superficial variant of malignant fibrous histiocytoma is no longer used; the new preferred term is undifferentiated pleomorphic sarcoma, or pleomorphic dermal sarcoma. The WHO (World Health Organization) also recommends deprecating the term malignant fibrous histiocytoma, because cytogenetic and molecular research has shown that it is not a single entity but rather a kind of catch-all group. In the past, various tumors, particularly different types of sarcomas, were classified as malignant fibrous histiocytoma, but these would now be called differently.

The WHO now distinguishes five different undifferentiated/unclassified sarcomas:

1.		Undifferentiated spindle cell sarcoma
2.		Undifferentiated pleomorphic sarcoma (previously classified as malignant fibrous histiocytoma)
3.		Undifferentiated round cell sarcoma
4.		Undifferentiated epithelioid sarcoma
5.		Undifferentiated sarcoma not otherwise specified

Dermatologists usually do not see the deep presentations of undifferentiated pleomorphic sarcoma, formerly known as malignant fibrous histiocytoma, in muscles, retroperitoneally, in bones, or in other organs. They see only the rare primary cutaneous presentations, pleomorphic dermal sarcoma, and its benign variant, atypical fibroxanthoma. Atypical fibroxanthoma is confined to the dermis and does not invade the depths or vessels. Pleomorphic dermal sarcoma does grow deeply into the subcutaneous tissue and can metastasize. Both occur in old age and are often found on the face.

Some authors (Cohen PR, 2020) argue that for these unusual cutaneous locations the terms pleomorphic dermal sarcoma and atypical fibroxanthoma should be retained and that the umbrella term undifferentiated pleomorphic sarcoma should not be used.




Author(s):
dr. Jan R. Mekkes. Dermatologist, Amsterdam UMC.