Inflammatory Myofibroblastic Tumor



Inflammatory Myofibroblastic Tumor


Karen S. Thompson, MD





Key Facts


Terminology



  • Tumor of myofibroblastic spindle cells with inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils


  • Intermediate biological potential: Propensity to recur, but metastases are rare


Clinical Issues



  • Most common sites include lung, mesentery, and omentum


  • 1/3 of patients present with clinical syndrome including



    • Fever, malaise, growth failure, weight loss, anemia, thrombocytosis, polyclonal hyperglobulinemia, elevated ESR


  • Prognosis is difficult to predict based on histopathology alone


  • Increased aggressive potential: Aneuploidy, p53 positivity, cytologic atypia


Microscopic Pathology



  • 3 histologic patterns



    • Loosely arranged plump myofibroblasts


    • Compact spindle cells in fascicles


    • Low cellularity scar-like pattern


  • Immunohistochemical positivity for ALK not specific for IMT but positive in 50% of cases


Ancillary Tests



  • 50-70% of IMTs are positive for ALK gene rearrangements involving 2p23







Bisected inflammatory myofibroblastic tumor of the lung is seen as a well-circumscribed mass with a tan, fleshy to gelatinous cut surface. A central tan-yellow hyalinized area with a histiocytic infiltrate is seen.






Inflammatory myofibroblastic tumors are composed of spindle-shaped myofibroblasts within a variably collagenous background interspersed with an inflammatory infiltrate of varying density.


TERMINOLOGY


Abbreviations



  • Inflammatory myofibroblastic tumor (IMT)


Synonyms



  • Inflammatory pseudotumor, plasma cell granuloma, plasma cell pseudotumor, pseudosarcomatous myofibroblastic lesion


Definitions



  • Lesion of myofibroblastic spindle cells with inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils



    • Intermediate biological potential


    • Unknown etiology


  • Term inflammatory pseudotumor has been used to describe multiple different entities, thus its use is discouraged


ETIOLOGY/PATHOGENESIS


Anaplastic Lymphoma Kinase (ALK) Mutations



  • Many IMTs have clonal rearrangement of ALK gene thought to be a key event in its pathogenesis, which supports current view of this tumor as true neoplasm


  • Mutation results in expression and activation of ALK gene


  • Various fusion partners have been described, which explains the different patterns of ALK protein immunoreactivity


CLINICAL ISSUES


Epidemiology



  • Age



    • Occurs most commonly in children and young adults; average age: 10 years


  • Gender



    • Slight female predominance


Presentation



  • Visceral and soft tissue tumor



    • Most common sites



      • Lung, mesentery, omentum, and gastrointestinal tract


    • Other sites



      • Soft tissue and bladder


  • Presenting symptoms related to anatomic location of tumor



    • Pulmonary IMT can present with chest pain and dyspnea


    • Abdominal IMT can present with gastrointestinal obstruction


    • May also be asymptomatic with discovery as incidental finding during work-up for unrelated disease or symptom


  • Clinical syndrome in 1/3 of patients



    • B symptoms



      • Fever, growth failure, malaise, weight loss


    • Anemia


    • Thrombocytosis


    • Polyclonal hyperglobulinemia


    • Elevated erythrocyte sedimentation rate (ESR)


  • Syndrome resolves with excision of mass


Treatment



  • Complete surgical resection is preferred treatment modality


  • Chemotherapy, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been tried as adjunctive therapies with variable success



    • May be tried in aggressive or metastatic disease


Prognosis



  • Difficult to predict based on histopathology alone


  • Vast majority behave in benign fashion



  • Increased aggressive potential associated with the following



    • Aneuploidy


    • Expression of p53


    • Cytologic atypia


  • Recurrence rates



    • ALK gene rearrangements associated with younger age and higher recurrence rates


    • Pulmonary tumors confined to lung (1.5%)


    • Extrapulmonary tumors confined to a single organ (8%)


    • IMTs found outside a single organ at presentation (35%)


    • Abdominal IMTs (33%)


  • Metastases are rare


IMAGE FINDINGS


Radiographic Findings



  • Lobulated solid mass with or without calcifications


MACROSCOPIC FEATURES


General Features



  • Circumscribed, solitary or multinodular mass


  • Firm, rubbery, tan-yellow, white or gray fleshy cut surface


  • Focal hemorrhage, necrosis, and calcifications in some cases


  • 6 cm in average diameter, reported range 1-22 cm



    • Most tumors are 5-10 cm in diameter


MICROSCOPIC PATHOLOGY


Histologic Features



  • 3 histologic patterns, all of which may intermingle within a single tumor



    • Loosely arranged plump myofibroblasts, “nodular fasciitis-like”



      • Edematous myxoid background


      • Mixed infiltrate of plasma cells, lymphocytes, and eosinophils


      • Ganglion-like myofibroblasts


      • Numerous blood vessels


      • Extravasated red blood cells infrequently seen


    • Compact spindle cells with storiform or fascicular growth pattern



      • Variable myxoid and collagenized regions


      • Mixed infiltrate of plasma cells, lymphocytes, and eosinophils


      • Small aggregates of plasma cells or lymphoid nodules


      • Ganglion-like myofibroblasts


    • Low cellularity scar-like pattern



      • Plate-like collagen


      • Sparse inflammation with plasma cells and eosinophils


      • Osseous metaplasia or calcifications may be present


  • Collections of foam cells are seen in some cases


  • Mitoses may be present but are not atypical


  • Many tumors have large amounts of plasma cells (thus old name of plasma cell granuloma) and lymphocytes


  • Histologic evolution to a higher grade



    • Does not necessarily predict aggressive behavior or metastases



      • Highly atypical polygonal cells


      • Oval vesicular nuclei with prominent nucleoli


      • Variable mitoses, some of which may be atypical


      • Large ganglion-like cells


      • Reed-Sternberg-like cells


      • Associated with p53 immunoreactivity


ANCILLARY TESTS


Molecular Genetics

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Inflammatory Myofibroblastic Tumor

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