Background Angiomatoid Fibrous Histiocytoma mimicking Systemic JIA via mutation-driven IL-6 production: Angiomatoid Fibrous Histiocytoma (AFH) is a rare tumour associated with mutation-driven production of Interleukin-6 (IL-6) which causes a systemic inflammatory picture similar to Systemic Juvenile Idiopathic Arthritis (sJIA).

Objectives A previously well 6-year old girl was referred with 6 weeks of abdominal pain, nausea, weight loss, night sweats, & lethargy.

Examination was unremarkable apart from a 2cm lump in the right popliteal fossa. This had been reported on USS 2 months earlier, at an external hospital, to be a Sebaceous cyst. There was no rash, organomegaly, lymphadenopathy, or synovitis.

She had persistent recurrent fevers of >39C, but not in the classical quotidian pattern of sJIA.

Methods Bloods showed persistent Hb <70, platelets >600, ESR >100, & CRP >200.

Autoantibody & full infection screens were negative.

Urine HMMA:creatinine ratio was minimally raised at 7.2 (normal 1.8 - 5)

Faecal calprotectin, upper & lower GI endoscopy were normal.

Bone-Marrow Aspiration was reported as being highly reactive but with no malignancy seen.

Whole-body STIR MRI was reported as normal, but repeat localised USS &MRI of the knee showed a 27x18x21mm well circumscribed, mixed cystic/solid lesion with marked vascularity. The lesion was then biopsied, and subsequently excised

Plasma IL-6 levels were significantly elevated at 46.7pg/ml (normal range: 0-2), but normalised after excision. TNF and IL1b levels were normal

Results Initial biopsy and FISH analysis confirmed the diagnosis of AFH with an abnormal EWSR1 signal pattern and classical EWSR1-CREB1 fusion. She went on to have a full excision, and staging investigations were negative.

AFH is rare (<0.3% of all soft-tissue tumours) and arises in the deep dermis/subcutis of the extremities of children & young adults. It has been regularly described in the axilla & popliteal fossa. It has a high (15%) local recurrence rate but rarely metastasises.

In >90% of cases AFH is associated with a characteristic translocation: t(2:22) (q33:q12). This forms the fusion gene EWSR1-CREB1 which in turn leads to continuous activation of CREB1. The promoter region of IL-6 has a CREB1 binding site thus causing IL-6 over-production and leading to the paraneoplastic syndrome.

Conclusion Paraneoplastic immune dysregulation is a rare, but important cause of symptoms often otherwise associated with rheumatic diseases. Careful physical examination, and liaison with oncology teams, is needed, particularly before treatment with steroids or IL-6 inhibitors such as Tocilizumab are considered

Disclosure of Interests:  Mark Friswell: None declared, Stephen Owens Consultant for: paid a consultancy fee by Chimerix to act as an advisor on a study of adenovirus in transplant patients, Gail Halliday: None declared