Malignant Fibrous Histiocytoma (undifferentiated pleomorphic sarcoma, not otherwise specified)

Table I.

Storiform (pleomorphic) – most frequent

Giant Cell

Myxoid

Inflammatory

Figure 2.

Figure 3.

Who is at Risk for Developing this Disease?

MFH affects males slightly more than females. It is most common in the 6th to 8th decade of life, and is rarely seen in individuals less than 20 years of age.

What is the Cause of the Disease?

Etiology

The etiology is unknown.

Pathophysiology

The pathophysiology is likewise unknown.

Systemic Implications and Complications

Recurrence in up to one-third of cases, typically in the first 1-2 years. Systemic implications/complications include metastasis and death.

Treatment Options

–Surgery

–Radiation

–Chemotherapy

The first-line treatment is based on surgical resection aiming at microscopically tumor-free excisional margins (R0 resection). In dermatology, this technique is called Mohs’ micrographic surgery (then conventionally referring to the fresh frozen technique that uses “instant” cryostat sections) or “Slow Mohs,” applying the micrographic technique on formalin-fixed and paraffin-embedded slides that require at least 1 day delay until reading.

The term “3D-histological evaluation of surgery” coined by the Tübingen group lumps all micrographic excisional techniques together. The Tübingen group and the Zürich group agree that formalin-fixed and paraffin-embedded sections are more suitable for diagnosing excisional margins of cutaneous soft tissue tumors, particularly when deep anatomical structures or scar tissue have to be distinguished from fine strands of tumor extensions.

The old surgical dogma proposes to use wide surgical margins to treat cutaneous soft tissue tumors, ie, wide excision with 2-cm or 3-cm lateral margins measured from the macroscopically visible or palpable tumor delineation. It has been shown by several authors that recurrence rates after wide excision tend to be higher than with micrographic surgery. This has been explained by long, unidirectional tumor protrusions that may exceed the empirically chosen “wide” surgical margin.

The technique of 3D-histological evaluation of surgery to treat MFH of the skin is explained in the comprehensive paper by Häfner et al. They resect the tumor with lateral margins of 6-10 mm, including the subcutis to the underlying anatomical layer, commonly the fascia. The specimen is prepared and encapsuled by the surgeon himself, and after a formalin fixation at 60°C the specimens can be processed using paraffin sections that are ready 20 hours after the first excision.

They continue to reexcise tumor-positive margins until they reach R0 margins in all directions. An R0 resection is mandatory before repair, even if the excisional procedure may extend over multiple steps on several consecutive days.

Häfner et al treated 31 patients with cutaneous MFH, amongst whom 26% had recurrent tumors. They were able to achieve R0-resections in 90% of patients. At 5 years follow-up they observed eight recurrences (26%). All three patients (10%) with a noncompletely resectable MFH had died after an observational period of 5 years.

The effectiveness of adjuvant radiotherapy in the treatment of MFH is not yet completely clarified. In the French study, postoperative radiotherapy decreased the local relapse risk (p = 0.002). It should probably be reserved for patients with a more serious prognosis based on the risk factors at initial presentation. In other words, patients with a superficial type of MFH with a diameter less than 5 cm that can be totally removed (R0-resection) can avoid postoperative radiotherapy.

The effectiveness of adjuvant chemotherapy is unknown. In both the French study and the Memorial Sloan-Kettering Cancer Center study a fraction of patients (9% and 23%, respectively) had postoperative chemotherapy. The decision for adjuvant chemotherapy was made by a multidisciplinary tumor board. A variety of regimens that usually contained doxorubicine were applied.

It is likely that both studies reserved adjuvant chemotherapy for patients with a high-risk profile at study entry. It was not used in a controlled study setting and therefore it is hardly possible to draw any conclusions on its effectiveness.

Optimal Therapeutic Approach for this Disease

In summary,, MFH of the skin should be first treated with micrographic surgery. It should be emphasized that the use of “wide surgical margins” (2 cm or 3 cm) leads to higher recurrence rates than the use of the more tissue-sparing micrographic (“3D-histologically evaluated”) surgical techniques. It is probably advisable to use formalin-fixed and paraffin-embedded sections instead of cryostat sections to control the surgical margins. Patients presenting with a superficial MFH of less than 5-cm diameter who can be treated with a R0 resection can expect a 10-year survival rate of almost 100%, and do not require adjuvant radiotherapy or adjuvant chemotherapy.

Patient Management

The French, Memorial Sloan-Kettering Cancer Center, and Tübingen studies are summarised in Table II, Table III, and Table IV, respectively.