Inflammatory pseudotumor
Inflammatory pseudotumor (IPT) Heterogeneous group of lesions of obscure etiology On physical and radiographic examination often confused with malignancy
Synonyms Plasma cell granuloma Inflammatory myofibroblastic tumor (IMT) Inflammatory myofibrohistiocytic proliferation Omental-mesenteric myxoid hamartoma Inflammatory fibrosarcoma Inflammatory myofibroblastic sarcoma Xanthofibroma/-granuloma
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
Epidemiology Primary children and young adults Most frequent in the first 3 decades of life Slight female predominance
Exact pathogenesis unknown: Autoimmune? Acute infectious? Postinflammatory reparative? Trauma? Neoplasia?
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
Symptoms Chest pain, dyspnoea Gastrointestinal obstruction Fever, malaise, weight loss, anaemia, thrombocytosis, elevated erythrocyte sedimentation, elevated CRP ->Cytokine mediated???
Macroscopy Nodular circumscribed or multinodular mass. Fleshy or myxoid cut surface. Hemorrhagia, necrosis, calcification
Histology Fibroblasticmyofibroblastic cells Inflammatory cells Collagen Vascular proliferation Few mitoses, should not be marked Necrosis uncommon
3 histological patterns 1. Myxoid vascular pattern Loosely arranged myofibroblasts in oedematous or myxoid background Abundant blood vessels
3 histological patterns 2. Compact spindled cell pattern Compact fascicular spindle cell proliferation Pronounced inflammatory infiltrate, aggregates Ganglion - like myofibroblasts
3 histological patterns 3. Hypocellular fibrous pattern Lower cellularity Sparse inflammatory infiltrate Calcification, osseous metaplasia
Fibrohistiocytic variant Round epitheloid or histiocytoid cells Associated with RANBP2-ALK gene rearrangement More agressive clinical behaviour
Immunphenotype SMA, Desmin+ Fokal keratin expression (30%) CD68+ (histocytic-appearing cells) ALK+: 50-70% CD34-
Differential diagnosis Inflammatory fibroid polyp Submucosa of Gastric antrum Proliferating cells around prominent capillary vessels Eosinophils CD34+, SMA, PDGFRA
Differential diagnosis GIST Usually muscularis propria of stomach Spindle or epitheloid cells Sparse inflammation CD34+, CD117+, Dog1+, S100- KIT or PDGFRA mutations
Differential diagnosis Inflammatory liposarcoma Retroperitoneum of older adults Prominent inflammatory infiltrate Atypical hyperchromatic nuclei Zones of well differentiated liposarcoma MDM2 and CDK4+
Differential diagnosis Inflammatory Leiomyosarcoma Deep soft tissues of older adults Dense inflammation Nuclear atypia Areas of classic leyomyosarcoma Actin+, desmin+, ALK-
Differential diagnosis Desmoid tumor/fibromatosis Usually in small bowel mesentery Sparse inflammation Fascicles of myofibroblasts with interspersed collagen Beta-catenin+
Inflammatory Pseudotumor of the nerve
Inflammatory pseudotumor of the nerve 9 cases have been reported 18-44 years Men: women: 1:1 Fibrosis with large epineurial perivascular inflammatory infiltrates near nerve fascicles
IPT of the nerve
Involved peripheral nerves Sciatic nerve Facial, greater auricular, trigeminal, mandibular nerve Radial, ulnar, median nerve Peroneal nerve
Clinical presentation Weakness, paresis Paresthesia, sensory loss Neuropathic pain
Serological markers Sedimentation rate, angiotensin-converting enzyme (ACE), anti-neutrophil cytoplasmic antibodies, antinuclear antibody, rheumatoid factor, hepatitis panel, HIV, and paraneoplastic antibodies...normal
IPT of sciatic nerve 61 year old women Irregular, mass lesion that involves and surrounds the nerve with heterogeneous signal characteristics
Intraoperative, sciatic nerve
Histology Chronic inflammatory, with histiocytes, plasma cells, eosinophils and fibroblasts, hemosiderin-laden macrophages
Increased microvessels Histology
Histology Focal atrophy, axonal degeneration, edema, decreased density of myelin Compressed and atrophic nerve fibers with edema
Histology Increased collagen of the perineurium and epineurium Increase in epineurial lipocytes Fibrosis and lipocytes
Histology Rare non-caseating granulomas and multi-nucleated giant cells in the epineurium
Immunhistochemistry CD68+ Ham 56+ CD45+ S100, CD1a and EMA- Histiocytes expressing CD68
Differential diagnosis Leprosy M. leprae and M. lepromatosis Fite positive acid fast organisms Linear Perivascular, periadnexal and neurotropic lymphohistiocytic infiltrate Granulomas Foamy macrophages
Differential diagnosis Neurofibroma Angulated, wavy nuclei Myxoid or collagenous matrix Collagen bundels No inflammation S100+
Differential diagnosis Perineurioma Neoplastic perineural cells surround nerve fibers Onion skin formation No atypia Rare mitoses EMA+, S100-
Differential diagnosis Malignant peripheral nerve sheath tumor Mostly high grade sarcoma Hypercellular, storiform Spindle cell Necrosis, high mitotic rate Heterologous differentiation S100+
Differential diagnosis Epithelioid sarcoma Multinodular Epitheloid cells, spindled at periphery Mildly atypical nuclei Central necrosis Epithelial markers+ Vimentin+ INI1- S100-
Therapy Nerve sparing resection Improvement in pain, weakness, reduction in lesion size with intravenous steroids
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
AJNR September 2011
Case report 59-year-old woman with IPT of the trigeminal nerve with abundant IgG4 plasma cell infiltrates
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
Prognosis Approximately 25% recurrence Metastasis <2% Metastasis may be associated with specific ALK fusion partners (RANBP2) and round cell morphology (fibrohistiocytic variant)
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