Uterus
Other mesenchymal tumors
Inflammatory myofibroblastic tumor
Author: Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 23 May 2019
Minor changes: 12 August 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed search: Uterus inflammatory myofibroblastic tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Bennett J. Inflammatory myofibroblastic tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusinflammpseudo.html. Accessed January 23rd, 2021.
Definition / general
- Rare mesenchymal neoplasm of myofibroblastic / fibroblastic origin with variable amounts of myxoid stroma and lymphoplasmacytic inflammation
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
- Most express ALK, CD10, smooth muscle actin and desmin but with variable staining intensity and distribution
- Multiple fusion partners have been identified, some with complex genetic rearrangements, which might result in false negative FISH testing
Terminology
- Inflammatory myofibroblastic tumor (IMT)
- Inflammatory pseudotumor
- Plasma cell granuloma
ICD coding
Epidemiology
- ~80 cases reported to date (corpus and cervix)
- Most commonly present at age 30 - 60 (range: 6 - 78)
Sites
- Uterine corpus most common site in gynecologic tract
- Rarely cervix (6 cases), ovary, fallopian tube, cul de sac, broad ligament, placenta
Pathophysiology
- Unknown
Etiology
- Unknown
Clinical features
- Generally present with nonspecific gynecologic symptoms (abnormal uterine bleeding, abdominal / pelvic pain) or presumed fibroids (Mod Pathol 2017;30:1489)
- May be incidentally discovered at cesarean section
- Occasionally present with constitutional symptoms (may be related to IL6 production by tumor) (Am J Obstet Gynecol 2003;189:890)
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
- Not well defined since only a small subset (~20%) have recurred or metastasized
- Large size (> 7 cm), moderate to severe atypia, high mitotic activity (> 10 per 10 high power fields), tumor cell necrosis and infiltrative border have been associated with more aggressive behavior (Adv Anat Pathol 2017;24:354)
- Often fascicular / compact predominant, although one study showed myxoid dominant tumors had worse outcome (Am J Surg Pathol 2015;39:157)
- Can recur years after original diagnosis
Case reports
- 10 year old girl with menorrhagia and abdominal pain (J Clin Oncol 2015;33:e7)
- 30 year old woman with irregular menstruation (Gynecol Oncol Case Rep 2013;6:39)
- 36 year old woman with severe vaginal bleeding (Medicine (Baltimore) 2017;96:e8974)
- 44 year old woman with left uterine sidewall mass (J Int Med Res 2018;46:3498)
- 50 year old woman with increasing pelvic pain (J Hematol Oncol 2015;8:66)
Treatment
- Surgery (hysterectomy, myomectomy) is first line therapy, as many are presumed leiomyomas
- Experience with ALK inhibitors is limited and has resulted in mixed responses (J Hematol Oncol 2015;8:66, Am J Surg Pathol 2017;41:1433, Am J Surg Pathol 2019;43:64)
Gross description
- Variable and resemble other mesenchymal lesions (Am J Surg Pathol 2015;39:157, Mod Pathol 2017;30:1489)
- Typically submucosal or intramural but may be polypoid
- Tan, white, pink, solid and cystic mass, often soft and gelatinous / myxoid
- May have whorling, hemorrhage, necrosis
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 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)
- Mitotic index is usually low and tumor cell necrosis 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
Spindle cells with decidualized appearance
ALK
Virtual slides
Images hosted on other servers:
Myomectomy specimen
Positive stains
- ALK (~95%) (Am J Surg Pathol 2005;29:1348, Am J Surg Pathol 2015;39:157, Am J Surg Pathol 2017;41:773, Mod Pathol 2017;30:1489, Am J Surg Pathol 2017;41:1433, Am J Surg Pathol 2019;43:64, Am J Surg Pathol 2018;42:1353)
- Variable staining intensity and extent but often stronger in myxoid areas
- 2 main patterns have been described: granular cytoplasmic and granular cytoplasmic with paranuclear accentuation
- Smooth muscle actin (~85%), CD10 (~80%), desmin (~80%), PR (~80%), ER (~65%), caldesmon (~40%) (Am J Surg Pathol 2015;39:157, Am J Surg Pathol 2017;41:773, Mod Pathol 2017;30:1489, Am J Surg Pathol 2017;41:1433, Am J Surg Pathol 2019;43:64)
- Variable staining intensity and extent
- Smooth muscle markers are more frequently positive in the fascicular / compact areas
Negative stains
- Keratin
- Wildtype p53 and normal p16 (defined as patchy or heterogeneous) (Histopathology 2017;70:1138)
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
- ALK fusions
- Classic rearrangement with split 3' and 5' signals (~75%)
- Abnormal patterns:
- Isolated 5' signal (2 cases) (Am J Surg Pathol 2016;40:285, Mod Pathol 2017;30:1489)
- Isolated 3' signal (2 cases) (Am J Surg Pathol 2019;43:64, Int J Gynecol Pathol 2019 Feb 7 [Epub ahead of print])
- Numerous isolated 3' signals (1 case) (Am J Surg Pathol 2019;43:64)
- False negative FISH can result from complex genetic rearrangements (intrachromosomal inversion) (Am J Surg Pathol 2017;41:773)
- Fusion partners identified include IGFBP5 (9 cases), THBS1 (7 cases), FN1 (2 cases), DES (3 cases), TIMP3 (2 cases), DCTN1 (1 case), SEC31 (1 case), TPM3 (1 case) (Mod Pathol 2017;30:1489, Am J Surg Pathol 2018;42:1353)
- Many fuse to ALK exon 17, 18 or 19
- ETV6-NTRK3 fusion (1 case) (J Int Med Res 2018;46:3498)
- ROS1, PDGFRB and RET fusions have not yet been identified
Molecular / cytogenetics images
Images hosted on other servers:
FISH: classic ALK rearrangement
Sample pathology report
- Uterus, hysterectomy:
- Inflammatory myofibroblastic tumor with (list any atypical features here, including tumor cell necrosis, > 7 cm, moderate to severe atypia, > 10 mitoses per 10 high power fields, infiltrative borders)
- Surgical margins, negative for tumor
Differential diagnosis
- Myxoid smooth muscle tumors (leiomyoma, smooth muscle tumor of uncertain malignant potential / STUMP, leiomyosarcoma) (Am J Surg Pathol 2016;40:285, Histopathology 2017;70:1138):
- Myxoid low grade endometrial stromal sarcoma (Int J Gynecol Pathol 1999;18:310):
- Tongue-like invasion
- Prominent small arterioles
- Typically find areas of conventional endometrial stromal sarcoma
- No lymphoplasmacytic infiltrate
- ALK-
- BCOR rearranged endometrial stromal sarcoma (Mod Pathol 2017;30:1251, Mod Pathol 2018;31:674):
- Tongue-like growth
- Variable vasculature but small arterioles most frequent
- Brisk mitotic activity
- Cyclin D1 and BCOR strong and diffuse
- ZC2H7B-BCOR fusion or BCOR internal tandem duplication
- Epithelioid inflammatory myofibroblastic sarcoma (Int J Gynecol Pathol 2018;37:468):
- Epithelioid dominant with only minor spindle cell component
- Typically neutrophil rich but can also see lymphocytes, plasma cells and eosinophils
- CD30+
- RANBP2-ALK or RRBP1-ALK fusion
- Only one has been reported in the gynecologic tract (ovary) (Int J Gynecol Pathol 2018;37:468)
- Solitary fibrous tumor (Histopathology 2018;72:749):
- Postoperative spindle cell nodule:
- Prior history of surgery or instrumentation
- Most common in the vagina
- Prominent vasculature, often see hemorrhage and edema
- Brisk mitotic activity
- Cytokeratin+
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?
- BCOR rearranged endometrial stromal sarcoma
- Inflammatory myofibroblastic tumor
- Myxoid endometrial stromal sarcoma
- Myxoid leiomyosarcoma
- Postoperative spindle cell nodule
Board review style answer #1
Board review style question #2
Which gene is rearranged in the majority of uterine inflammatory myofibroblastic tumors?
- ALK
- BCOR
- RANB2
- RRBP1
- STAT6
Board review style answer #2
