Final Diagnosis -- Angiomatoid Fibrous Histiocytoma



Angiomatoid fibrous histiocytoma (AFH) is a rare slow-growing tumor of the deep dermis and subcutaneous tissue predominately affecting children and young adults. AFH comprises only 0.3% of all soft tissue tumors, and is classified by the WHO as a tumor of uncertain differentiation. This classification reflects the current opinion that a normal cellular counterpart has not been identified and the cell type of origin is unknown. AFH was originally described as angiomatoid "malignant" fibrous histiocytoma in 1979 by Enzinger, but has since been renamed due to its very infrequent malignant behavior (1).

The extremities are the most common site of involvement, followed by the trunk and head and neck. Sixty-six percent occur in areas where lymph nodes are normally found, such as the popliteal, axillary, inguinal, supraclavicular, and cervical regions (3). Occasionally, patients report antecedent trauma to the area although the lesion is painless. A minority of cases present with constitutional symptoms or polyclonal gammopathy.

Grossly, AFH may resemble a lymph node with its firm consistency and circumscribed appearance. The lesion can also be mistaken for a hematoma or vascular neoplasm clinically, as hemorrhage within cystic spaces is frequent. The key histologic feature of AFH is a proliferation of histiocytoid or myoid cells in sheets, nodules, whorls, or storiform pattern. The cells can be spindled or epithelioid and are generally uniform with ovoid vesicular nuclei and scant mitotic activity. Other features which may be seen microscopically in varying proportions include pseudoangiomatoid spaces, a thick fibrous pseudocapsule, and a cuff of lymphoplasmacytic infiltrate with occasional germinal centers. The pseudoangiomatoid spaces, from which the name is derived, are unlined cysts or spaces filled with red blood cells. Nuclear pleomorphism and mitotic activity are occasionally present in the spindled tumors (>5 mitoses/hpf), but these findings do not correlate with recurrence or metastasis. (1, 3)

Immunohistochemical staining of AFH typically shows positivity for histiocytic and muscle markers (CD68, desmin), although strong evidence for either histiocytic, smooth muscle, or skeletal muscle origin has not been presented to date. EMA and CD99 are also frequently positive, further adding to the uncertain lineage of this tumor. Tumor cells are uniformly negative for keratin, vascular markers (CD34, CD31, and Factor VIII), dendritic cell markers (CD21, CD35), neural markers (S100), and melanocytes (HMB45). Although translocation t(12;16)(q13;p11), leading to fusion of ATF1 and FUS genes, has been reported in one case, chromosomal or molecular aberrations characteristic of AFH have not been confirmed. (3, 6)

AFH is an indolent tumor with metastasis occurring in less than 1% of cases, which is generally non-fatal to regional lymph nodes. Local recurrence occurs in up to 11% of cases. It is therefore clinically important to accurately diagnose this entity so that wide local excision may be performed and patients may be appropriately monitored. There are no known clinical, morphologic, or genetic factors that correlate with metastasis or recurrence. (3)

In this case, although the patient had a history of neurofibromatosis, the histologic findings are characteristic of an angiomatoid fibrous histiocytoma. The clinically suspected neurofibroma or malignant peripheral nerve sheath tumor are excluded by morphology and the negative S-100 stain. AFH has not been specifically described in association with neurofibromatosis. However, other fibrohistiocytic lesions have been reported in patients with NF1, including malignant fibrous histiocytoma and juvenile xanthogranuloma (2, 5). Juvenile xanthogranuloma has been known to occur in children with NF1, and the triple association between NF1, juvenile xanthogranuloma, and chronic myeloid leukemia is well documented (2, 4).


  1. Athanasou NA (ed.). Colour Atlas of Bone, Joint, and Soft Tissue Pathology. Oxford University Press: New York 1999.
  2. Cambiaghi S, Restano L, and Caputo R. Juvenile xanthogranuloma associated with neurofibromatosis 1: 14 patients without evidence of hematologic malignancies. Pediatric Dermatology 2004;21(2):97-101.
  3. Fletcher CDM, Unni KK, and Mertens F (eds.). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. IARCPress: Lyon 2002.
  4. Gutmann DH, Gurney JG, and Shannon KM. Juvenile xanthogranuloma, neurofibromatosis 1, and juvenile chronic myeloid leukemia. Arch Dermatol 1996 Nov;132(11):1390-1.
  5. Johnson PS, Katz DA, Pester J, and Penn R. Malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis: a case report and a literature review. J Surg Oncol 1979;12(2):97-105.
  6. Miettinen M (ed.). Diagnostic Soft Tissue Pathology. Churchill Livingstone: Philadelphia 2003.

Contributed by Teresa LaCaria, MD and John Ozolek, MD

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