Initial accurate diagnosis critical for rare tumors

New York - Atypical fibroxanthoma (AFX) and undifferentiated pleomorphic sarcoma (UPS) share a similar histological picture. But unlike AFX, UPS can have an aggressive clinical course, underscoring the importance of initial accurate diagnosis of these tumors, and the implementation of appropriate therapy.

Undifferentiated pleomorphic sarcoma was previously known as malignant fibrous histiocytoma (MFH), but in 2002, the World Health Organization (WHO) set out to reclassify UPS as such because MFH too often became a diagnosis of exclusion and was used for many tumors that could not be classified into other specialized tumors.

“Advances in immunohistochemistry and electron microscopy helped to clarify the diagnosis and reclassify tumors that were previously diagnosed as MFH,” says Allison Hanlon, M.D., Ph.D., assistant professor of dermatology, Yale School of Medicine, Section of Dermatologic Surgery and Cutaneous Oncology, New Haven, Conn.

Diagnosis difficulties

Both AFX and UPS are currently distinguished by the depth of local invasion in the skin, Dr. Hanlon says. While UPS is much more aggressive - invading much deeper into the subcutaneous tissue - AFX typically remains localized in the dermis with minimal subcutaneous involvement and can be successfully treated with surgery alone with a very small risk of recurrence or metastasis.

“Appropriately diagnosing these tumors can sometimes be very challenging because if you have a partial biopsy, you could misdiagnose one or the other tumor, which can have far reaching implications in terms of initiating appropriate therapy,” she says. “Using more precise diagnostic techniques is key in more accurately distinguishing these two tumor types.”

In a 1997 study conducted by Lazova et al, researchers attempted to establish diagnostic criteria to help better distinguish MFX and UPS (then still termed MFH), and looked at varying sarcomas staining them with LN-2, an antigen that is expressed by B cells, macrophages and Reed-Sternberg cells. They found that 90 percent of the undifferentiated pleomorphic sarcomas stained positive whereas the AFX tumors stained negative (Lazova R, Moynes R, May D, Scott G. Cancer. 1997;79(11):2115-2124).

Recent results

A more recent study, however, conducted by Hollmig et al was not able to reproduce these results, Dr. Hanlon says. It found that LN-2 was not a sensitive or specific marker for UPS, or indicative in the prognosis for AFX (Hollmig ST, Rieger KE, Henderson MT. Am J Dermatopathol. 2013;35(2):176-179).

“These two studies indicate the extreme difficulty in trying to differentiate between AFX and UPS, beyond just the similar histologic pictures of the lesions,” she says. “More research needs to be done to help find a sensitive and specific marker to help the clinician arrive at a more precise diagnosis.”

Currently, Dr. Hanlon and her colleagues are performing genetic studies looking at full exome sequencing of AFX - specifically in primary AFX tumors that have been successfully treated with surgery and AFX tumors that have recurred or metastasized - and comparing them to UPS, in hopes of finding a specific genetic marker for these tumors.

“We are hopeful that we may be able to find specific markers for both AFX and UPS using the whole genome sequencing technique. Until then however, an initial accurate diagnosis remains crucial to help distinguish between these tumors, requiring a heightened vigilance by both the dermatologist as well as dermatopathologist,” Dr. Hanlon says.

Disclosures: Dr. Hanlon reports no relevant financial interests.