J Cutan Pathol 2011: 38: 8–13 doi: 10.1111/j.1600-0560.2010.01622.x John Wiley & Sons. Printed in Singapore Copyright  2010 John Wiley & Sons A/S Journal of Cutaneous Pathology Atypical fibroxanthoma with lymphomatoid reaction Background: Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun-damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30-positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. Methods: The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T-cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Results: Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S-100, cytokeratins and muscle mark- ers, thereby confirming the diagnosis of AFX. CD30 highlighted a signif- icant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. Conclusion: An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma. Zheng R, Ma L, Bichakjian CK, Lowe L, Fullen DR. Atypical fibroxanthoma with lymphomatoid reaction. J Cutan Pathol 2011; 38: 8 – 13.  2010 John Wiley & Sons A/S. Rui Zheng 1 , Linglei Ma 2,3 , Christopher K. Bichakjian 3 , Lori Lowe 2,3 and Douglas R. Fullen 2,3 1 Department of Dermatology, The First Hospital of Shanxi Medical University, Taiyuan, China, 2 Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA, and 3 Department of Dermatology, University of Michigan Medical Center, Ann Arbor, MI, USA Douglas R. Fullen, MD, Department of Pathology M3261 Medical Sciences I, 1301 Catherine Road, Ann Arbor, MI 48109, USA Tel: +1 734 764 4460 Fax: +1 734 764 4690 e-mail: dfullen@med.umich.edu Accepted for publication August 16, 2010 Atypical fibroxanthoma (AFX) represents a cuta- neous neoplasm that typically occurs on sun- damaged skin of elderly patients. It usually follows a non-metastatic course, presumably because of its superficial location, and is considered a superficial variant of pleomorphic sarcoma (formerly malignant fibrous histiocytoma 1 ). Microscopically, AFX is characterized by atyp- ical spindled cells arranged haphazardly or in a vaguely fascicular pattern. The tumor cells may be multinucleated and may exhibit nuclear pleomor- phism and frequent mitoses. 2 Several variants have been described, including spindled, 3 clear cell, 4–7 osteoid, 8 osteoclast-like giant cell, 9–12 chondroid, 9 pigmented, 13 granular cell 14 – 16 and myxoid types. 17 Herein, we present two cases of AFX accompanied by a prominent lymphoid infiltrate containing atypical lymphocytes. One case possessed many CD30-positive atypical large mononuclear cells and thus mimicked lymphomatoid papulosis (LyP) or anaplastic large-cell lymphoma. Case 1 A 91-year-old male with no previous history of skin cancer presented with a large, slightly exophytic growing lesion on the left parietal scalp for 6 months. The initial biopsy performed at an outside institution was interpreted as AFX. Two months later, the lesion had partially regressed, leaving a faintly pink and 8