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

• Fibroblastic-myofibroblastic 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

Facial, greater auricular, trigeminal, mandibular nerve

Sciatic 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

Histology

Increased microvessels

Histology

Compressed and atrophic nerve fibers with edema

Focal atrophy, axonal degeneration, edema, decreased density of myelin

Histology

Fibrosis and lipocytes

Increased collagen of the perineurium and epineurium Increase in epineurial 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