Inflammatory pseudotumor
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1 Inflammatory pseudotumor
2 Inflammatory pseudotumor (IPT) Heterogeneous group of lesions of obscure etiology On physical and radiographic examination often confused with malignancy
3 Synonyms Plasma cell granuloma Inflammatory myofibroblastic tumor (IMT) Inflammatory myofibrohistiocytic proliferation Omental-mesenteric myxoid hamartoma Inflammatory fibrosarcoma Inflammatory myofibroblastic sarcoma Xanthofibroma/-granuloma
4 Location Soft tissue and viscera 1. Mesentery, omentum, retroperitoneum, pelvis, abdominal soft tissue 2. Lung, mediastinum, head and neck 3. Unuasual: Liver, GIT, uterus, bladder, pancreas, spleen, kidney, lymph nodes, CNS, Nerve
5 Epidemiology Primary children and young adults Most frequent in the first 3 decades of life Slight female predominance
6 Exact pathogenesis unknown: Autoimmune? Acute infectious? Postinflammatory reparative? Trauma? Neoplasia?
7 ALK, Virus Rearrangement (Chromosome 2p23) of the anaplastic lymphoma kinase (ALK) gene in 50-70% -> Suggests neoplasia in a subset of cases Rare association with Epstein-Barr virus (EBV) and HHV8 positivity
8 Symptoms Chest pain, dyspnoea Gastrointestinal obstruction Fever, malaise, weight loss, anaemia, thrombocytosis, elevated erythrocyte sedimentation, elevated CRP ->Cytokine mediated???
9 Macroscopy Nodular circumscribed or multinodular mass. Fleshy or myxoid cut surface. Hemorrhagia, necrosis, calcification
10 Histology Fibroblasticmyofibroblastic cells Inflammatory cells Collagen Vascular proliferation Few mitoses, should not be marked Necrosis uncommon
11 3 histological patterns 1. Myxoid vascular pattern Loosely arranged myofibroblasts in oedematous or myxoid background Abundant blood vessels
12 3 histological patterns 2. Compact spindled cell pattern Compact fascicular spindle cell proliferation Pronounced inflammatory infiltrate, aggregates Ganglion - like myofibroblasts
13 3 histological patterns 3. Hypocellular fibrous pattern Lower cellularity Sparse inflammatory infiltrate Calcification, osseous metaplasia
14 Fibrohistiocytic variant Round epitheloid or histiocytoid cells Associated with RANBP2-ALK gene rearrangement More agressive clinical behaviour
15 Immunphenotype SMA, Desmin+ Fokal keratin expression (30%) CD68+ (histocytic-appearing cells) ALK+: 50-70% CD34-
16 Differential diagnosis Inflammatory fibroid polyp Submucosa of Gastric antrum Proliferating cells around prominent capillary vessels Eosinophils CD34+, SMA, PDGFRA
17 Differential diagnosis GIST Usually muscularis propria of stomach Spindle or epitheloid cells Sparse inflammation CD34+, CD117+, Dog1+, S100- KIT or PDGFRA mutations
18 Differential diagnosis Inflammatory liposarcoma Retroperitoneum of older adults Prominent inflammatory infiltrate Atypical hyperchromatic nuclei Zones of well differentiated liposarcoma MDM2 and CDK4+
19 Differential diagnosis Inflammatory Leiomyosarcoma Deep soft tissues of older adults Dense inflammation Nuclear atypia Areas of classic leyomyosarcoma Actin+, desmin+, ALK-
20 Differential diagnosis Desmoid tumor/fibromatosis Usually in small bowel mesentery Sparse inflammation Fascicles of myofibroblasts with interspersed collagen Beta-catenin+
21 Inflammatory Pseudotumor of the nerve
22 Inflammatory pseudotumor of the nerve 9 cases have been reported years Men: women: 1:1 Fibrosis with large epineurial perivascular inflammatory infiltrates near nerve fascicles
23 IPT of the nerve
24 Involved peripheral nerves Sciatic nerve Facial, greater auricular, trigeminal, mandibular nerve Radial, ulnar, median nerve Peroneal nerve
25 Clinical presentation Weakness, paresis Paresthesia, sensory loss Neuropathic pain
26 Serological markers Sedimentation rate, angiotensin-converting enzyme (ACE), anti-neutrophil cytoplasmic antibodies, antinuclear antibody, rheumatoid factor, hepatitis panel, HIV, and paraneoplastic antibodies...normal
27 IPT of sciatic nerve 61 year old women Irregular, mass lesion that involves and surrounds the nerve with heterogeneous signal characteristics
28 Intraoperative, sciatic nerve
29 Histology Chronic inflammatory, with histiocytes, plasma cells, eosinophils and fibroblasts, hemosiderin-laden macrophages
30 Increased microvessels Histology
31 Histology Focal atrophy, axonal degeneration, edema, decreased density of myelin Compressed and atrophic nerve fibers with edema
32 Histology Increased collagen of the perineurium and epineurium Increase in epineurial lipocytes Fibrosis and lipocytes
33 Histology Rare non-caseating granulomas and multi-nucleated giant cells in the epineurium
34 Immunhistochemistry CD68+ Ham 56+ CD45+ S100, CD1a and EMA- Histiocytes expressing CD68
35 Differential diagnosis Leprosy M. leprae and M. lepromatosis Fite positive acid fast organisms Linear Perivascular, periadnexal and neurotropic lymphohistiocytic infiltrate Granulomas Foamy macrophages
36 Differential diagnosis Neurofibroma Angulated, wavy nuclei Myxoid or collagenous matrix Collagen bundels No inflammation S100+
37 Differential diagnosis Perineurioma Neoplastic perineural cells surround nerve fibers Onion skin formation No atypia Rare mitoses EMA+, S100-
38 Differential diagnosis Malignant peripheral nerve sheath tumor Mostly high grade sarcoma Hypercellular, storiform Spindle cell Necrosis, high mitotic rate Heterologous differentiation S100+
39 Differential diagnosis Epithelioid sarcoma Multinodular Epitheloid cells, spindled at periphery Mildly atypical nuclei Central necrosis Epithelial markers+ Vimentin+ INI1- S100-
40 Therapy Nerve sparing resection Improvement in pain, weakness, reduction in lesion size with intravenous steroids
41 Immune component? Systemic process? One patient with history of excessive lacrimation which required monthly intraocular steroid injections -> with removal of the IPT symptoms resolved Response to treatment with steroids Further studies are needed
42 AJNR September 2011
43 Case report 59-year-old woman with IPT of the trigeminal nerve with abundant IgG4 plasma cell infiltrates
44 IgG4 related IPT In recent years, the relationship between some populations of IPT and IgG4 has been suggested Some IPTs of the liver and lung have been reported with IgG4-related sclerosing disease
45 Prognosis Approximately 25% recurrence Metastasis <2% Metastasis may be associated with specific ALK fusion partners (RANBP2) and round cell morphology (fibrohistiocytic variant)
46 Conclusions Increasingly recognized Should be considered in the differential diagnosis of peripheral nerve nodular mass lesions Can mimic neoplastic nerve sheath tumors Recognition is important to avoid overaggressive surgery
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