Atypical Fibroxanthoma 

Updated: Oct 30, 2018
Author: Forrest C Brown, MD; Chief Editor: William D James, MD 

Overview

Background

Atypical fibroxanthoma (AFX) is a tumor that occurs primarily in older individuals after the skin of the head and neck has been damaged significantly by sun exposure and/or therapeutic radiation. Clinically, lesions usually are suggestive of malignancy because they arise rapidly (over just a few weeks or months) in skin in which other skin cancers have been found and treated. When this clinical impression is combined with highly anaplastic pathology, misdiagnosis can result in unnecessary and extensive surgery and radiation. The image below demonstrates the typical clinical presentation of an atypical fibroxanthoma.

Red, beefy, sessile nodule typical of clinical pre Red, beefy, sessile nodule typical of clinical presentation of atypical fibroxanthoma. Note the markedly sun-damaged skin with solar telangiectasias. Courtesy of Capt James Steger, MC, USN, US Naval Hospital, San Diego.

Histologically, lesions show a highly atypical and pleomorphic cellular appearance, but they typically respond to simple excision. Clinicopathologic correlation is essential. Factors important to consider are lesion location, patient age, histopathologic appearance, and the observation that the tumor arises from the dermis, not the fat. Many AFX tumors may represent a superficial form of malignant fibrous histiocytoma (MFH) with a much better prognosis. Some cases may represent primary squamous cell carcinoma (SCC) that fails to express keratin.

Etiology

Sun exposure and/or therapeutic radiation that have caused significant skin damage are associated with the development of atypical fibroxanthoma (AFX). The tumor primarily occurs on the head or neck of older individuals.

Epidemiology

Sex

Male-to-female ratio is equal.

Age

In one study, age ranged from 13-95 years with a mean age of 69 years.

 

Presentation

History

Typically, the patient presenting with atypical fibroxanthoma (AFX) is an older individual (mean age 69 y) with sun-damaged or radiation-damaged skin of the head, neck, and scalp.

Physical Examination

Nodules are red, juicy, and dome shaped and they may be ulcerated, as in the image below. Lesions are usually located on skin that is red, thin, and telangiectatic, indicating previous significant sun or radiation damage. Some nodules are dark enough, due to deposits of hemosiderin, to be confused with a nodular melanoma.

Red, beefy, sessile nodule typical of clinical pre Red, beefy, sessile nodule typical of clinical presentation of atypical fibroxanthoma. Note the markedly sun-damaged skin with solar telangiectasias. Courtesy of Capt James Steger, MC, USN, US Naval Hospital, San Diego.

Nodules primarily are located on the head and neck and in sun-exposed areas. In addition, lesions have been reported to occur on the trunk, extremities, and in sun-protected areas. The ratio of lesions that occur on the head and neck to lesions that occur in other areas is approximately 4:1.

Tumor size increases proportionately with duration of existence but rarely exceeds 3 cm in diameter. Lesion growth typically is rapid, and patients usually seek medical advice within 6 months of onset.

In adult cases, the skin underlying developing atypical fibroxanthoma (AFX) lesions may be considered locally immunosuppressed. Reports have shown an increased incidence of AFX in patients with AIDS and in patients who are immunosuppressed because of organ transplantation.

One case of localized cutaneous metastases has been reported after excision of the primary lesion. This is extremely rare.

 

DDx

Diagnostic Considerations

Also consider the following:

  • Spindle cell squamous cell carcinoma
  • Spindle cell malignant melanoma
  • Superficial portion of a malignant fibrous histiocytoma
  • Leiomyosarcoma [1]

Differential Diagnoses

 

Workup

Laboratory Studies

The following laboratory tests may be needed:

  • Panels of antibodies

  • Electron microscopy

  • DNA content quantification

Other Tests

Dermoscopy may be helpful (see Histologic Findings).

Histologic Findings

The pathologic appearance of atypical fibroxanthoma (AFX) belies the usually excellent prognosis. As shown in the image below, this nonencapsulated dermal tumor is composed of large, fibrocytic, spindle-shaped and anaplastic cells arranged in a haphazard fashion, occasionally in fascicles, and usually with an increased number of mitotic figures. Large histiocytic cells may form bizarre multinucleated giant cells that frequently contain lipid, contributing to the tumor's name. Phagocytosis of erythrocytes has been demonstrated, resulting in hemosiderin pigmentation within a lesion and causing clinical confusion with malignant melanoma.[2] Granular and clear cell variants have been reported.[3, 4, 5, 6]

Microscopic view of atypical fibroxanthoma. Note t Microscopic view of atypical fibroxanthoma. Note the large abnormal-appearing cells in a field of spindle cells. Courtesy of Capt James Steger, MC, USN, US Naval Hospital, San Diego.

Electron microscopy[7]

Electron microscopy suggests a fibrohistiocytic nature in the tumor. A transition from fibroblast to large giant cells can be seen, with intermediate forms that exhibit features of both cell types. Pathologic findings in AFX appear to be more related to MFH than to either dermatofibroma or dermatofibrosarcoma protuberans (DFSP). Delicate cytoplasmic fibrils were seen in one case studied with electron microscopy, but these fibrils were not considered to arise from myofibroblasts and findings did not support a muscle origin for AFX.

Immunohistochemistry

Panels of specific antibodies together with the tumor's histologic pattern help differentiate AFX from other types of spindle cell skin lesions.[8] Specific and critical differences of antibody reactivity (R) and nonreactivity (N) are demonstrated in the Table.

Table. Antibody Panels in Tumors (Open Table in a new window)

Antibody

AFX

MFH

SCC

DFSP

Spindle

MM*

Leiomyosarcoma

Vimentin

R

R

N

R

R

R

Cytokeratin

N

N

R

N

N

N

S-100

N

N

N

N

R

N

Desmin or smooth muscle actin

N

N

N

N

N

R

*Spindle cell malignant melanoma

 SCC, spindle cell MM, and leiomyosarcoma usually are differentiated using immunocytochemistry. No reliable consistent immunocytochemistry method is specific for AFX, and the diagnosis is based on typical histologic findings and the absence of immunomarker positivity for melanocytes, keratin, and smooth muscle actin.

DNA content quantification[9, 10]

Diploid or euploid cells have pairs or multiple pairs of chromosomes and usually are considered benign. Aneuploid cells have single or multiple single sets of chromosomes and are more common in malignant neoplasms.

Attempts to evaluate chromatin content in AFX have resulted in much confusion because of the methods of evaluation. The average picture produced with flow cytometry suggests that AFX is diploid. Using individual cell analysis, aneuploidy was found in giant cells, while diploidy has been found in smaller spindle-shaped cells. This picture is similar to MFH and does not allow nuclear cytometry to differentiate between MFH and AFX.

Dermoscopic features

A diagnosis of AFX is often not suspected clinically. The histologic findings of the biopsy specimen may cause great consternation, bringing to mind serious and possibly life-threatening diagnoses. Only by combining the clinical presentation with specific staining panels to eliminate other suspected diagnoses is the correct one determined. Although dermatoscopic features of the tumor have been reported, they are not specific. Bugatti and Filosa found white areas and an atypical polymorphous vascular pattern characterized by linear, dotted, hairpin and arborescent vessels irregularly distributed over the surface of the tumor.[11]

Histologic variants

Nonpleomorphic AFX (spindle cell AFX) was reported by Calonje et al in a series of cases of sun-damaged skin of the head and neck in older individuals.[12] The immunocytochemistry findings and the tumors' benign clinical course supported the diagnosis of AFX. Pathologically, lesions were monomorphic, spindle-celled, fascicular variants without pleomorphic cells. All lesions were vimentin positive with approximately 50% showing focal actin activity. Desmin, keratin, and S-100 protein were negative in all cases. Other variants with clear cells, osteoclastic-type cells, and granular cells have been reported.

 

Treatment

Surgical Care

In the past, many lesions were diagnosed clinically as pyogenic granuloma and removed by shave and curettage, without recurrence, which has prompted physicians to treat atypical fibroxanthoma (AFX) conservatively. Local recurrence and spread to lymph nodes may occur.[13, 14] This suggests that complete tumor removal is required. Simple excision with a margin of normal skin or Mohs micrographic surgery may be appropriate.

Mohs micrographic surgery, with its high reliability of complete tumor removal and tissue-conserving property, is an excellent choice for AFX on the head and neck.[15, 16, 17, 18]

Prevention

Instruct patients to avoid excessive sun exposure.

 

Questions & Answers