The prominent lymphoid cuff present in many AFHs can lead to diagnostic confusion as metastatic tumor deposits within lymph nodes.
Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate (rarely metastasizing) biologic potential and uncertain differentiation, which predominantly arises superficially in the deep dermis and subcutis of the extremities of children and young adults.
Most patients present in the first 3 decades of life, although the age distribution is wide, and AFH can occur in infants (including congenitally) (5) and adults to the eighth and ninth decades.
(12) Reports of its occurrence as a second neoplasm in other malignancies are rare and include a supraclavicular AFH occurring in a 27-year-old man 16 months after chemotherapy for disseminated testicular cancer, (13) an inguinal mass in a child with stage III retroperitoneal neuroblastoma, (14) and in an 18-year-old woman with a 4-year history of treatment for Hodgkin lymphoma.
The etiology and differentiation of AFH remain unclear, and its constituent ovoid and spindle cells do not wholly phenotypically resemble any mature cell type.
Pluripotent mesenchymal stem cells have been postulated as potential originating cells for several sarcoma types, (26-31) and the same suggestion was made for AFH by some authors in the 1980s.
EWSR1-CREB1 is the most frequently described gene fusion to date, having been described in more than 90% of cases, (43,44) although EWSR1-ATF1 appears to be more common in AFH occurring in extrasomatic soft tissue sites.
While FUS-ATF1 fusions have so far not been detected in other neoplasms, EWSR1-CREB1 and EWSR1-ATF1 fusions are not unique to AFH and have been consistently described in a number of different tumor groups that are clinically and usually histopathologically distinct from AFH.
(57) EWSR1 rearrangements in AFH have not been shown to cause the downstream activation of the MiTF pathway and melanogenesis seen in CCS, (23,36,37) and MiTFM and SOX10 expressed in CCS with EWSR1-ATF1 are not detectable in AFH with this fusion.
The differential diagnosis of AFH is wide, encompassing reactive lesions such as granulomas to both benign and malignant neoplasms.
A reticular pattern is now well documented in AFH, (40) including those occurring endobronchially, (80) which can lead to diagnostic confusion with PPMS, especially because the latter also shows patchy, predominantly lymphoplasmacytic chronic inflammation.