Inflammatory Myofibroblastic Tumour

Inflammatory Fibrosarcoma

Inflammatory Pseudotumour

Plasma Cell Granuloma

Fibroxanthoma

Fibrous Histiocytoma

Pseudosarcomatous Myofibroblastic Tumour

Invasive Fibrous Tumour of the Tracheobronchial Tree

Epidemiology and Etiology:

• Children and young adults
• 10 y avg
• Most common endobronchial mesenchymal lesion in childhood
• Most occur in individuals < 40 y
• All ages
• M=F
• HHV8 associated in some

Common sites:

• Lung
• Mesentery
• Omentum
• Soft tissue
• Mediastinum
• GI tract
• Pancreas
• GU tract
• Oral cavity

Gross features:

• solitary or multinodular (30%)
• wide size range
• average 3.0 cm
• can be large (20-40 cm)
• firm
• white
• lobular
• rubbery
• solid (cavitation is rare)
• whorled fleshy or myxoid cut surface
• nonencapsulated
• infiltrative maybe
• lung:
• regular borders (80%)
• speculated maybe
• post-obstructive pneumonia and atelectasis maybe (if endobronchial)
• uncommonly hemorrhage, necrosis, and calcification

Histologic features:

• 3 patterns:
• fasciitis-like pattern:
• vascular, myxoid, and inflamed stroma
• plasma cells
• resembles granulation tissue or nodular fasciitis or other reactive process
• fascicular malignant fibrous histiocytoma or leiomyosarcoma-like spindle cell areas with inflammation
• compact fascicular spindle cell proliferation
• variable myxoid and collagnized regions
• distinctive inflammatory infiltrate
1. diffuse inflammation
2. small aggregates of plasma cells or lymphoid nodules
• resembles fibromatosis, fibrous histiocytoma, or a smooth muscle neoplasm
• myofibroblasts surround or bulge into vessels/vascular spaces maybe
• sclerosed desmoid-like areas with calcification
• resembles a scar or desmoid-type fibromatosis
• plate-like collagen
• lower cellularity
• relatively sparse inflammation with plasma cells and eosinophils
• coarse or psammomatous calcifications and osseous metaplasia maybe
• myofibroblasts and fibroblasts in fascicles or whorls or storiform
• oval nuclei
• inconspicuous nucleoli
• abundant bipolar lightly eosinophilic cytoplasm
• histiocytoid cells
• moderate pleomorphism
• atypia is not obvious
• main criteria for calling “inflammatory fibrosarcoma” rather than IMT
• rarely may see highly atypical polygonal cells with oval vesicular nuclei, prominent nucleoli, and variable mitoses, including atypical forms
• associated with malignant transformation
• large ganglion-like cells
• Reed-Sternberg-like cells
• mitoses infrequent
• often marked inflammatory infiltrate
• plasma cells predominant
• lymphocytes, occasionally neutrophils or eosinophils
• lymphoid follicles often
• histiocytes
• touton type giant cells
• fibrosis and calcification in stroma maybe
• invasion rarely
• blood vessels
• pleura

Immunophenotype:

Marker:	Sensitivity:	Specificity:
SMA & MSA (focal to diffuse)
CK (focal)	1/3
Anaplastic lymphoma kinase (ALK1) and p80	40-60%, correlates well with presence of ALK rearrangements, mainly in children, uncommon > 40 y	Not specific for IMT
Vimentin (strong, diffuse)	Virtually all
Myogenin (neg)
Myoglobin (neg)
CD117 (neg)
S100 (neg)
p53	Rare, associated with recurrence and malignant transformation
Desmin	many

Molecular features:

• gene fusions involving ALK at 2p23
• fusion fo ALK C-terminal kinase domain with tropomyosin N-terminal coiled-coil domain (subset)
• fusion of ALK with the clathrin heavy chain (subset)
• euploid
• occasionally aneuploidy (malignant behaviour
• TP53 mutation (some)
• HMGIC (HMGA2) (chromosome 12) rearrangements in a subset lacking ALK

Other features:

• EM – fibroblastic and myofibroblastic
• Invade adjacent viscera
• May metastasize (< 5%)
• ~25% mortality
• Complete excision in lung has excellent survival (most)
• Extrapulmonary invasion (5%)
• Poor prognostic factors:
• Focal invasion
• Vascular invasion
• Increased cellularity
• Nuclear pleomorphism with bizarre giant cells
• High mitotic rate (> 3/50 HPF)
• necrosis
• constitutional symptoms frequently:
• fever
• weight loss
• pain frequently
• syndrome (1/3):
• fever
• growth failure
• malaise
• weight loss
• anemia
• thrombocytosis
• polyclonal hyperglobulinemia
• elevated ESR
• Presentation in lung:
• Endobronchial:
• Bronchial irritation:
1. Cough
2. Wheeze
3. Haemoptysis
4. Chest pain
• Constitutional symptoms rarely
• Response to corticosteroids and NSAIDs rarely

References:

• Gastrointestinal and Liver Pathology 2005
• Silverberg SG, DeLellis RA, Frable WJ, LiVolsi VA, Wick MR. Silverberg's Principles and Practice of Surgical Pathology and Cytopathology: 2-Volume Set. 4th ed. Churchill Livingstone; 2005.
• WHO lung 2004
• WHO soft tissues 2002