Dr. Charlene Lam discusses atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma, (PDS), including nomenclature changes, distinguishing features, and the importance of strict margin control.
Charlene Lam, MD, MPH, Mohs surgeon and Associate Professor of Dermatology, Penn State University, Hershey, Pennsylvania
“During our session on rare tumors, I focused on atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), with 3 main objectives: recognizing the change in nomenclature of pleomorphic dermal sarcomas; identifying distinguishing features between [AFX] versus [PDS]; and appreciating the importance of strict margin control when treating these tumors,” said Charlene Lam, MD, MPH, who presented during the “Rare Non-melanoma Skin Cancers: Diagnosis, Management and Treatment,” session at the 2023 AAD Innovation Academy in Tampa, Florida.
AFX and PDS can be confusing terms, and nomenclature changes in recent decades have only added to the confusion in dermatologists’ understanding of these tumors, said Dr. Lam.
“I like to think of them as primary cutaneous sarcomas of fibrohistiocytic etiology.”
For many years dermatologists and others used AFX interchangeably with malignant fibrous histiocytoma (MFH), said Dr. Lam.
“Around 2002, the World Health Organization reclassified these tumors, replacing the term ‘malignant fibrous histiocytoma’ with ‘undifferentiated pleomorphic sarcoma’. With some of the contemporary histologic techniques, they found that tumors deemed as [MFH] should have been characterized as other tumors, altogether.”
But there was a problem with replacing MFH with undifferentiated pleomorphic sarcoma, she said.
“Undifferentiated pleomorphic sarcoma represents a diverse, heterogeneous cohort of malignant soft tissue neoplasms, including those in the retroperitoneum. The term lacks any specificity towards tumors derived from the skin. So, in 2012, Dr. Christopher Fletcher coined the term ‘pleomorphic dermal sarcoma’ for the cutaneous neoplasm that virtually resembles an [AFX], except being more clinically and histologically aggressive.”1
Moving forward, the goal is to think about the terms “atypical fibroxanthoma” and “pleomorphic dermal sarcoma” as one entity on a disease spectrum, said Dr. Lam.
Distinguishing Features
AFX and PDS share many clinical etiologies and histological features. They typically occur on sun damaged skin of elderly men. Other risk factors include immunosuppression as well as areas that have been previously radiated, said Dr. Lam.
“AFX tends to be more superficial in the skin and overall can be very nonspecific in appearance. The overall prevalence is probably less than 1%; however, the true prevalence is unknown because of the nomenclature change.”
Given the nonspecific clinical findings, AFX and PDS diagnoses are based on histology, said Dr. Lam.
“It’s a diagnosis of exclusion in histology.”
These tumors present as unencapsulated dermal tumors with a mix of atypical spindle cells and epithelial cells, mixed with some multinucleated giant cells with mitotic figures, said Dr. Lam.
“We need immunohistochemical staining in order to rule out different spindle cells. AFX and PDS do have a positive CD10.”
The differentiating features between an AFX and PDS determine the prognosis.
“You cannot distinguish an AFX from a PDS with a superficial biopsy.”
Classically, AFX is more well-defined and more limited to the dermis, while PDS is less clearly demarcated and a more aggressive infiltrating neoplasm that invades the subcutaneous skeletal muscle and fascia, said Dr. Lam.
“Within the [PDS] tumor there is necrosis [and] lymphovascular and peripheral perineural invasion.”
Different studies have shown that size, depth, and lymphovascular invasion leads to a poorer prognosis. This includes a recent SEER database study showing an increase in tumor size and presentation increased the odds of metastasis, said Dr. Lam.2
For large tumors, dermatologists should not only consider imaging but also a multidisciplinary tumor board to determine treatment, she said.
Tumor Treatment
“The mainstay of treatment for both AFX and PDS is surgical excision with clear margins.”
Optimal margins, however, are poorly defined.
“In a recent metanalysis of AFX they found that Mohs micrographic surgery has a lower recurrence than conventional wide excision.”3
When performing Mohs surgery, dermatologists should do a debulk to determine the depth of invasion and aggressive histologic features, said Dr. Lam.
“The data is more limited for PDS because of the nomenclature changes and developing diagnostic criteria. Specific margins are undefined. Most recommendations for PDS are based on broad margins with comprehensive margin control. In the case of these aggressive PDSs, the priority is on margin control over tissue conservation. Single cell spread can occur with PDS because of the unencapsulated etiology of that tumor.”
Dr. Murad Alam and coauthors recently published a mathematic model based on historic controls with known margins and recurrences to determine appropriate surgical margins for these cutaneous sarcomas, said Dr. Lam.4
“They found that margin control really matters, and the size of the tumor will determine the amount of margins necessary to clear the tumor. We’ve also seen that those tumors that are incompletely excised are the ones that come back and can present with metastasis.”
For advanced, aggressive tumors, multidisciplinary tumor boards are important to determine further treatment, said Dr. Lam.
“Radiotherapy can be considered judiciously for those aggressive tumors. However, traditional chemotherapy has not been shown to be that effective for large PDSs. Some genetic investigations have noted that tumor burden mutations in PDSs have found that off-label uses of checkpoint inhibitors, such as anti-PD1s, have been useful in some cases.”
Prognosis is dependent on the depth of infiltration, as well as lymphatic and perineural invasion, she said.
“The current literature has not seen any metastasis with AFX. With PDS, local recurrence is approximately 5% to 28% within the first 2 years of excision. Often it is due to incomplete excisions.”
Metastases can occur in the skin, lymph nodes, and lungs, said Dr. Lam.
“In terms of surveillance and follow-up, it’s recommended for AFXs to follow up every 6 months for at least 2 years. With PDSs, the follow-up is every 3 to 6 months for the first 2 years and then regional lymph node examination with imaging if necessary.”
References:
- McCalmont TH. Correction and clarification regarding AFX and pleomorphic dermal sarcoma. J Cutan Pathol. 2012;39(1):8. doi:10.1111/j.1600-0560.2011.01851.x.
- Perez AN, Dashti NK, Cates JMM. Prognostic factors for pleomorphic dermal sarcoma: analysis of 1911 cases from the SEER database. J Clin Pathol. 2023;76(6):424-428. doi:10.1136/jcp-2022-208570.
- Tolkachjov SN, Kelley BF, Alahdab F, et al. Atypical fibroxanthoma: Systematic review and meta-analysis of treatment with Mohs micrographic surgery or excision. J Am Acad Dermatol. 2018;79(5):929-934.e6. doi:10.1016/j.jaad.2018.06.048.
- Jibbe A, Worley B, Miller CH, et al. Surgical excision margins for fibrohistiocytic tumors, including atypical fibroxanthoma and undifferentiated pleomorphic sarcoma: A probability model based on a systematic review. J Am Acad Dermatol. 2022;87(4):833-840doi:10.1016/j.jaad.2021.09.036