Stanford School of Medicine
Surgical Pathology Criteria
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Inflammatory Myofibroblastic Tumor

Definition

  • Tumor composed of cytologically bland spindled myofibroblasts with admixed inflammatory cells, predominantly occurring in infants and children

Alternate / Historical Names

  • Inflammatory fibrosarcoma
  • Inflammatory myofibrohistiocytic proliferation
  • Inflammatory pseudotumor
  • Omental-mesenteric myxoid hamartoma
  • Plasma cell granuloma
  • Plasma cell pseudotumor

Diagnostic Criteria

  • Virtually all patients under 30 years
    • Most under 14
  • Grossly circumscribed
    • Microscopically usually infiltrative
    • May be multinodular
    • May have associated reactive lymphadenopathy
  • Composed of spindled myofibroblasts and inflammatory cells
    • Spindle or stellate cells bland to mildly atypical
      • Large vesicular oval nuclei
        • No hyperchromasia
        • Small nucleoli
      • Variable amounts of pale eosinophilic cytoplasm
      • Mitotic figures variable
        • May be numerous but not atypical
    • Ganglion-like cells may be seen
      • Abundant eosinophilic to amphophilic cytoplasm
      • Prominent large nucleoli
      • May be numerous
    • Prominent inflammatory cells, predominantly lymphocytes and plasma cells
      • May include neutrophils and eosinophils
      • May form germinal centers
      • Foamy histiocytes occasionally present
  • Three patterns of cell mixtures described:
    • Patterns may vary within the same tumor
    • Pattern 1:  Loose or myxoid stroma with prominent vascularity
    • Pattern 2:  Compact spindle cells
    • Pattern 3:  Densely collagenous with fewer spindle cells and inflammatory cells
  • The following have been proposed as predictors of malignant behavior
    • Aneuploidy by flow cytometry
    • Frequent ganglion like cells
    • p53 positivity by immunohistochemistry
    • The utility of such grading has not been confirmed
  • Rare reports of transformation to high grade malignant pattern
    • Increased cellularity, atypical mitotic figures, necrosis
  • Calcifying fibrous pseudotumor has been proposed to represent a sclerosing stage of inflammatory myofibroblastic tumor
  • Richard L Kempson MD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting: May 15, 2008
    Last update: June 15, 2008

 

Supplemental studies

Immunohistology

Smooth muscle actin >90% positive
Vimentin >90% positive
Factor XIIIa positive, extensive
Desmin 10-70%
Keratin 30-77%
ALK 35-60%
CD68 variable
CD34 variable
p53 8%
bcl2 37%
MDM2 100%
HHV8 negative

 

In situ hybridization

  • ALK rearrangements 47%
  • EBV negative

Cytogenetics

  • Complex clonal chromosomal aberrations involving 2p23-24 seen in most cases tested

Laboratory Studies

  • Abnormalities may be seen in some cases
    • Erythrocyte sedimentation rate elevation
    • Thrombocytosis
    • Polyclonal hypergammaglobulinemia
    • Microcytic anemia

Differential diagnosis

Sclerosing Inflammatory Lesions (Retroperitonitis, Mesenteritis, Mediastinitis, Cholangitis, Pancreatitis) Inflammatory Myofibroblastic Tumor
Diffuse, typically no distinct mass Circumscribed mass lesion
Rare in children Usually in children
IgG4 serum levels and plasma cells increased No association with IgG4

 

Inflammatory Myofibroblastic Tumor Nodular Fasciitis
Frequently over 5 cm Rarely over 5 cm
Usually in children Rare in children
Frequently involves abdominal cavity Does not involve abdominal cavity
Variable patterns Usually loose pattern throughout
Prominent inflammatory cells Only scattered inflammatory cells

 

Inflammatory Myofibroblastic Tumor Infantile Fibromatosis
Frequent in abdomen Rare in abdomen
Usually age 0-14 years Age <5 years
Prominent inflammation Variable, peripheral inflammation
Variable locations Centered in muscle

 

Fibromatosis, Abdominal Desmoid, Extra-abdominal Desmoid, Mesenteric, Retroperitoneal and Pelvic Inflammatory Myofibroblastic Tumor
Rare <12 years of age Age usually <14, rare >30
Inflammation not prominent Prominent inflammation, particularly plasma cells
Alk1 negative Alk1 frequently positive
Beta catenin 80-90% Beta catenin negative

 

Inflammatory Myofibroblastic Tumor Gastrointestinal Stromal Tumor
Usually in children Rare in children
Frequently associated with systemic signs and symptoms Not associated with systemic signs and symptoms
Prominent inflammatory cells Usually only scattered inflammatory cells
Frequently positive for desmin, keratin and ALK Desmin, keratin and ALK negative
CD117, DOG1, CD34 negative CD117 74-95%, DOG1 87-95%, CD34 70%

 

Inflammatory Fibroid Polyp Inflammatory Myofibroblastic Tumor
Systemic signs and symptoms absent Systemic signs and symptoms frequent
Infrequent involvement of muscularis propria Frequent involvement of muscularis propria
Eosinophils predominate Plasma cells usually predominate
Concentric onion skin like pattern around vessels and glands is frequent Lacks concentric onion skin pattern
Not associated with lymphadenopathy May have reactive regional lymphadenopathy

 

Inflammatory Myofibroblastic Tumor Leiomyosarcoma of Soft Tissue
Usually <14 years, rare >30 years Rare under 12 years
Chronic inflammation usual Infrequent inflammation
Rare inflammatory leiomyosarcoma exhibits a regular fascicular pattern

 

Inflammatory Malignant Fibrous Histiocytoma Inflammatory Myofibroblastic Tumor
Mean age 50, wide range Usually <14 years, rare >30 years
Sheets of neutrophils Mixed or lymphocyte predominant inflammation
Marked cytologic atypia Absent or mild atypia

 

Myofibroma Inflammatory Myofibroblastic Tumor
90% <2 years Usually age 0-14 years
Biphasic nodules with immature cells No immature cells
Hemangiopericytomatous vessels No HPC like vessels
Rare in abdomen Frequent in abdomen

 

Dedifferentiated Liposarcoma Inflammatory Myofibroblastic Tumor
High grade nonlipogenic comoponent present Lacks significant cytologic atypia
Atypical lipomatous tumor component present Lacks lipomatous component

 

Inflammatory Myofibroblastic Tumor Inflammatory Pseudotumor of Lymph Node and Spleen
ALK positive 35-60% ALK negative
EBV negative EBV may be positive
Rare in lymph node and spleen Occurs in lymph node and spleen

 

In the GU tract some consider the following to be separate entities while others consider them to be the same lesion
Inflammatory Myofibroblastic Tumor Pseudosarcomatous Myofibroblastic Proliferation of GU Tract
Prominent lymphoplasmacytic infiltrate Lacks prominent plasma cells
Frequent storiform and fibrous areas Lacks storiform and fibrous areas
Pale eosinophilic cytoplasm on spindle cells Intensely eosinophilic cytoplasm on spindle cells
Both may be postive for actin, desmin, keratin, ALK and both are benign at this site

 

Inflammatory Myofibroblastic Tumor Follicular Dendritic Cell Neoplasm
Rarely involves lymph node or spleen Frequently involves lymph node and spleen
ALK positive 35-60% ALK negative
CD21, CD23, CD35 negative CD21, CD23 or CD35 positive
EBV negative EBV positive by in situ hybridization

 

Inflammatory Myofibroblastic Tumor Interdigitating Dendritic Cell Sarcoma
ALK positive 35-60% ALK negative
S100 negative S100 positive

 

Clinical

  • Primarily affects infants and children
    • Age range 2 months to 46 years
    • Virtually all under age 30
    • Mean age 6-10 years
    • Higher ages reported for cases involving the gastrointestinal and genitourinary tracts
  • May cause systemic signs and symptoms
    • Fever, weight loss, pain, malaise, night sweats
    • Anemia, thrombocytosis, polyclonal hypergammaglobulinemia, elevated erythrocyte sedimentation rate
    • May resolve following resection
  • Most involve abdomen, mesentery and lung
    • Also reported in extremities, head and neck, brain
    • Bladder involvement is controversial
      • Some consider pseudosarcomatous myofibroblastic proliferations of the bladder to be a separate entity
  • May be multifocal
  • Size 1-20 cm
  • Up to half may recur
    • Recurrence rare if resection is complete
  • Metastases occur in <5-10%
    • Most often to lung, brain, liver, bone

Bibliography

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  • Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors, 5th edition, 2008
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  • Meis-Kindblom JM, Kjellstrom C, Kindblom LG.  Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in the spectrum of inflammatory myofibroblastic tumors.  Semin Diagn Pathol 1998 May;15(2):133-43
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