Atypical fibroxanthoma (AFX)

Skin nonmelanocytic tumor
Fibrous, fibrohistiocytic and myofibroblastic neoplasms
Atypical fibroxanthoma (AFX)

Author: Hillary Rose Elwood, M.D.

Topic Completed: 1 November 2016

Revised: 30 October 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Atypical fibroxanthoma [title] skin

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Table of Contents

Cite this page: Elwood HR. Atypical fibroxanthoma (AFX). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumornonmelanocyticAFX.html. Accessed November 14th, 2019.

Definition / general

Dermal variant of undifferentiated pleomorphic sarcoma

Clinical features

Typically found on sun damaged skin of elderly patients, particularly head and neck
Rapidly growing, small, dome shaped or polypoid nodule, sometimes ulcerated
Size < 2 cm in diameter
Clinical appearance not distinctive and clinical differential diagnosis includes carcinoma

Case reports

21 year old woman with nasal nodule (Can J Plast Surg 2007;15:169)
81 year old woman with lower leg lesion (Dermatol Online J 2008;14:6)

Treatment

Wide local excision
Mohs micrographic surgery also effective (Dermatol Surg 2009;35:765)
Excellent prognosis after complete excision
Rarely recurs or metastasizes

Clinical images

Images hosted on other servers:

Irregular polypoid tumors

21 year old woman with nasal nodule

Solitary dome shaped nodule

Gross description

Papule to nodule, sometimes ulcerated; < 2 cm

Microscopic (histologic) description

Well circumscribed dermal nodule usually within skin showing solar damage (e.g. solar elastosis)
Tumor often abuts the epidermis but rarely may have a grenz zone of uninvolved dermis
Spindled to round or epithelioid tumor cells in haphazard or fascicular pattern
Bizarre multinucleated pleomorphic cells present
Frequent mitotic figures; many atypical mitotic figures
Resembles undifferentiated pleomorphic sarcoma but centered in dermis
The tumor should not extensively involve the subcutaneous tissue (if it does, the lesion may represent a pleomorphic dermal sarcoma)
No invasion of deeper structures (i.e. muscle or fascia) should be present (if it is, the lesion may represent a pleomorphic dermal sarcoma)
Histologic variants: angiomatoid, chondroid, clear cell (J Cutan Pathol 2006;33:343), granular cell (Am J Dermatopathol 2007;29:84), keloidal (J Cutan Pathol 2009;36:535), myxoid (J Cutan Pathol 2009;36:1177), osteoclastic, osteoid, pigmented (Actas Dermosifiliogr 2009;100:321)

Microscopic (histologic) images

Images hosted on PathOut servers:

Marked cellularity and pleomorphism

Characteristic bizarre cells

Spindle variant has less pleomorphism

Tumor is limited to dermis but otherwise
resembles MFH pleomorphic with marked
cellularity, prominent pleomorphism,
mitotic figures and clumped chromatin

CD68 (left), CD10 (middle) and AE1 / AE3 (right)
Above 6 images contributed by Dr. Angel Fernandez-Florez

Images hosted on other servers:

Ulcerated tumor

Spindle and epithelioid cells with atypia

Nodular spindle cell tumor

Fig 1: eyebrow primary
Fig 2 - 4: facial metastasis
(fig 4 is CD68)

Immunohistochemistry

Immunohistochemistry is imperative in excluding histologic mimics (see differential diagnosis)
The staining pattern of AFX is nonspecific and the diagnosis is largely one of exclusion based on negative staining for other markers
A typical immunohistochemical panel for AFX includes:
- High molecular cytokeratin, such as CK5 / CK6 and p63: Negative in AFX (helps to exclude a spindled squamous cell carcinoma)
- S100: negative in AFX (helps to exclude a spindled melanoma)
- Desmin: usually negative in AFX (helps to exclude a pleomorphic leiomyosarcoma)
- CD10: positive in AFX but nonspecific as this marker is widely expressed in other entities
  - If concerned for vascular proliferation, consider adding vascular marker to panel, such as ERG or CD31 (negative in AFX, helps to exclude spindled angiosarcoma)
Many other stains have been reported positive in AFX but none of these are helpful in differentiating from the histologic mimics
For completeness, positive stains reported include: CD68, alpha-1-antitrypsin, alpha-1-antichymotrypsin, Factor XIIIa (focal), CD117 (Am J Dermatopathol 2008;30:34), CD99 (73%, Am J Clin Pathol 2002;117:126), CD10 (Australas J Dermatol 2005;46:235), CD163, D2-40 (50%, J Cutan Pathol 2011;38:631), calponin (30%, Virchows Arch 2002;440:404), desmin (30%), smooth muscle actin (30%), CD31 (5%)

Electron microscopy description

Myofibroblasts, fibroblasts and primitive mesenchymal cells

Molecular / cytogenetics description

Diploid

Sample pathology report

Skin, biopsy:
- Superficially sampled pleomorphic dermal spindle cell neoplasm (see comment)
- Comment: The histologic differential for these findings includes an atypical fibroxanthoma or a pleomorphic dermal sarcoma. Complete re-excision is recommended along with close clinical followup. If the excision demonstrates this lesion to be superficial, then the findings are those of an atypical fibroxanthoma; however, if the re-excision demonstrates a large or more infiltrative tumor, a pleomorphic dermal sarcoma would be favored.

Differential diagnosis

The predominant histologic mimics are those atypical spindle cell neoplasms that abut the epidermis, sometimes referred to as the “SLAM” differential for ease of remembrance (spindled squamous cell carcinoma, leiomyosarcoma, AFX, spindled melanoma)
Angiosarcoma: spindle cell variant, prominent vascular spaces or blood, vascular markers+
Atypical fibrous histiocytoma
Leiomyosarcoma - pleomorphic type: usually more fascicular growth pattern, desmin+
Partial biopsy of Pleomorphic dermal sarcoma: superficial aspect of pleomorphic dermal sarcoma (PDS) can appear identical to AFX but on excision a PDS is a much larger and more deeply infiltrative lesion with a worse prognosis
Spindled or desmoplastic melanoma: S100+, may have associated atypical intraepidermal melanocytic proliferation (Am J Dermatopathol 2007;29:551)
Squamous cell carcinoma - spindle cell type: deep extension, p63+ and high molecular weight cytokeratin positive (J Cutan Pathol 2009;36:543)
Of note, the diagnosis of AFX should be avoided or made with caution on superficial biopsies as a superficially sampled pleomorphic dermal sarcoma could appear identical; if I don’t have the base on initial biopsy, I may diagnose as in sample pathology report