Uterus

Other mesenchymal tumors

Inflammatory myofibroblastic tumor



Last author update: 8 July 2022
Last staff update: 8 July 2022

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PubMed search: Uterus inflammatory myofibroblastic tumor

Jennifer A. Bennett, M.D.
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Cite this page: Bennett JA. Inflammatory myofibroblastic tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusinflammpseudo.html. Accessed December 9th, 2022.
Definition / general
  • Uncommon mesenchymal neoplasm of myofibroblastic / fibroblastic origin with variable amounts of myxoid stroma and lymphoplasmacytic inflammation; often characterized by ALK fusions
Essential features
  • Best classified as a neoplasm of uncertain malignant potential, as histologically bland uterine confined tumors may recur
  • Comprised predominantly of spindle cells with hypercellular (fascicular / storiform) and hypocellular (myxoid rich) areas, admixed with a variably prominent lymphoplasmacytic infiltrate
  • Often positive for ALK and smooth muscle / stromal markers but staining is of variable intensity and distribution
  • Most harbor ALK fusions but rearrangements involving ROS1, RET and ETV6::NTRK3 have also been reported
Terminology
  • Inflammatory pseudotumor
  • Plasma cell granuloma
ICD coding
  • ICD-10:
    • D39.0 - neoplasm of uncertain behavior of uterus
    • C54.9 - malignant neoplasm of corpus uteri, unspecified
  • ICD-11:
    • 2F76 - neoplasms of uncertain behaviour of female genital organs
    • 2C76.Z - malignant neoplasms of corpus uteri, unspecified
Epidemiology
Sites
  • Uterine corpus is the most common site in the gynecologic tract
    • Rarely arises in the cervix, placenta, ovary, fallopian tube, cul de sac, broad ligament
Pathophysiology
  • Fusion occurs between the promoter of the 5' partner gene and the 3' ALK kinase domain, resulting in ligand independent dimerization and constitutive activation of ALK (Nat Rev Cancer 2013;13:685)
    • Other tyrosine kinase receptors (ROS, RET, ETV6::NTRK3) are less frequently involved
  • TIMP3 and THBS1 are genes involved in endometrial remodeling during implantation and pregnancy (Am J Surg Pathol 2020;44:970)
    • Common 5' partner genes in pregnancy associated tumors
Etiology
  • Unknown
Clinical features
  • Generally present with nonspecific gynecologic symptoms (abnormal uterine bleeding, abdominopelvic pain) or presumed fibroids
  • May be incidentally discovered at cesarean section
Diagnosis
  • Hysterectomy or myomectomy
  • Rarely endometrial sampling
Radiology description
  • No defining features to distinguish from other uterine mesenchymal neoplasms on imaging
Radiology images

Images hosted on other servers:

CT shows intrauterine mass

Axial MRI shows local lesion

Prognostic factors
Case reports
Treatment
  • Surgery (hysterectomy, myomectomy) is first line therapy, as many are presumed leiomyomas
  • Tyrosine kinase inhibitors (i.e., crizotinib) have shown durable responses of at least 12 months in one study (Gynecol Oncol Rep 2021;37:100852)
Gross description
Gross images

Images hosted on other servers:

Polypoid lesion within endometrial cavity

Microscopic (histologic) description
  • Borders range from well circumscribed, to focally irregular, to infiltrative
  • 3 main growth patterns: myxoid, fascicular / compact, hyalinized (Mod Pathol 2017;30:1489)
    • Myxoid: loosely arranged spindle cells (nodular fasciitis-like) in a myxoid background, hypocellular
    • Fascicular / compact: densely arranged spindle cells with fascicular or storiform architecture; may have a smooth muscle appearance or myxoid stroma, hypercellular
    • Hyalinized (infrequent): sparsely cellular collagen resembling a scar
  • Variable degree of lymphoplasmacytic inflammation, occasionally lymphocyte predominant
  • Lymphoid aggregates, foamy histiocytes, neutrophils, eosinophils and Touton giant cells may be seen
  • Thin walled and elongated vessels, occasional thick walled (leiomyoma-like) or staghorn vessels (Mod Pathol 2017;30:1489, Am J Surg Pathol 2019;43:64)
  • Spindle cells have open vesicular nuclei with variable cytologic atypia (rarely severe)
  • Ganglion-like cells (abundant eosinophilic cytoplasm, eccentric nuclei, prominent nucleoli) may be seen and typically comprise a minority of the tumor
  • Spindle cells may show a decidualized appearance during pregnancy (Mod Pathol 2017;30:1489, Am J Surg Pathol 2020;44:970, Hum Pathol 2020;106:62)
  • Mitotic index is usually low and tumor cell necrosis is uncommon
Microscopic (histologic) images

Contributed by Jennifer Bennett, M.D.

Hyper and hypocellular areas

Myxoid pattern

Acellular myxoid areas

Myxoid areas resemble nodular fasciitis

Plasma cell aggregates

Compact pattern


Severe nuclear atypia

Ganglion-like cells

Pregnancy associated IMT

ALK

Positive stains
Negative stains
Electron microscopy description
  • Spindle cells show features of myofibroblasts and are focally surrounded by basal lamina-like material (Int J Gynecol Pathol 1987;6:275)
    • Nondilated rough endoplasmic reticulum
    • Thin filaments with peripheral dense bodies
    • Pinocytic vesicles, occasional Golgi bodies, lipid droplets
Molecular / cytogenetics description
Molecular / cytogenetics images

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FISH: classic ALK rearrangement

Sample pathology report
  • Uterus, hysterectomy:
    • Inflammatory myofibroblastic tumor (see comment)
    • Comment: The tumor consists of spindled cells in a myxoid stroma admixed with lymphoplasmacytic inflammation. The cells show minimal cytologic atypia, without appreciable mitoses or tumor cell necrosis. The tumor is positive for ALK (granular cytoplasmic staining), desmin (patchy) and CD10 (patchy) but negative for BCOR and caldesmon. The morphology and immunohistochemical profile is consistent with an inflammatory myofibroblastic tumor. If clinically indicated, FISH or RNA fusion analysis can be performed.
Differential diagnosis
Board review style question #1

A 44 year old woman presents with an infiltrative spindle cell neoplasm in the myometrium that has prominent myxoid stroma and a dense lymphoplasmacytic infiltrate. It is positive for desmin, smooth muscle actin and ALK by immunohistochemistry and shows ALK rearrangement by FISH. What is the most likely diagnosis?

  1. BCOR rearranged endometrial stromal sarcoma
  2. Inflammatory myofibroblastic tumor
  3. Myxoid endometrial stromal sarcoma
  4. Myxoid leiomyosarcoma
  5. Postoperative spindle cell nodule
Board review style answer #1
B. Inflammatory myofibroblastic tumor

Comment Here

Reference: Inflammatory myofibroblastic tumor
Board review style question #2
Which gene is rearranged in the majority of uterine inflammatory myofibroblastic tumors?

  1. ALK
  2. BCOR
  3. RANBP2
  4. RRBP1
  5. STAT6
Board review style answer #2
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