Case 1 -
Inflammatory Myofibroblastic Tumor of the Uterus
Marisa R. Nucci
Brigham and Women's Hospital
Click on each slide thumbnail image for an enlarged view
Myomectomy specimen from a 37 year old woman with menorrhagia and fibroids.
Case 1 - Slide 1
Case 1 - Figure 1
Intramyometrial mass with predominantly rounded, pushing borders.
Case 1 - Figure 2
In one area there is a slightly irregular interface with the myometrium. Note the prominent chronic inflammatory infiltrate.
Case 1 - Figure 3
The tumor is composed of fascicular spindle cells set within a myxoid matrix.
Case 1 - Figure 4
The spindle cells have palely eosinophilic cytoplasm and elongated nuclei with dispersed chromatin and occasional nucleoli.
Case 1 - Figure 5
Chronic inflammatory cells, particularly plasma cells, are scattered throughout the tumor.
Case 1 - Figure 6
Mitotic activity was scarce, but focally numbered up to 2 per 10 high power fields (arrows indicate mitotic figures).
Inflammatory Myofibroblastic Tumor of the Uterus
Inflammatory myofibroblastic tumor (IMT) is a cellular, fascicular myofibroblastic/fibroblastic
neoplasm with a variably myxoid to collagenous stroma and associated prominent lymphoplasmacytic
Although first described in the lung, it is now well known that IMT can
occur at a variety of anatomic sites with lung, mesentery, omentum and retroperitoneum representing the
most common locations. IMT was recently recognized to also occur in the uterus, with a series of 6 cases
reported.  Since this tumor has a wide anatomic distribution, a number of terms have been
used historically to describe this entity; however, based on clinical and morphologic overlap, the
majority of lesions formerly known as inflammatory pseudotumor, plasma cell granuloma, inflammatory
fibrosarcoma, and omental-mesenteric myxoid hamartoma are now recognized to be IMTs.
IMT may occur at any age although they have a predilection for children and adolescents. Of the six
cases that have been described in the uterus, the patients' ages ranged from 6 to 46 years. At
extrauterine sites, patients typically present with non-specific symptoms related to its location such as
cough and chest pain for pulmonary IMT or vague abdominal pain and discomfort for intraabdominal IMT. A
constitutional syndrome consisting of fever, weight loss and malaise may be seen in 15-30% of patients.
The most common symptoms of the patients with uterine IMT were menorrhagia and abdominal pain; one
patient presented with weight loss and fever.
Uterine IMTs typically occur as a polyp extending from the lower uterine wall or as a
circumscribed myometrial mass. On gross examination, IMTs may appear fibrous, fleshy or gelatinous.
Uterine IMTs range in size from 1 to 12 cm (median 5 cm, mean 6 cm); this mean size at presentation is
similar to extrauterine IMTs.
Histologically, IMT is characteristically a cellular, fascicular
myofibroblastic/fibroblastic proliferation in a variably myxoid to collagenous stroma with an associated
prominent lymphoplasmacytic infiltrate. Three patterns of IMT have been described: 
1) myxoid/vascular pattern
2) compact spindle cell pattern
3) fibromatosis-like pattern
The myxoid/vascular pattern is composed of plump spindle cells in an edematous to myxoid matrix,
having an appearance akin to fasciitis. The compact spindle cell pattern typically has spindle cells
arranged in a fascicular or storiform pattern set in a more collagenous appearing stroma. The
fibromatosis-like pattern is hypocellular with a densely collagenous to sclerotic, hyalinized matrix
containing elongate (and less plump appearing) spindle cells.
Uterine IMTs typically have rounded pushing borders with the myometrium but they may also
have focally irregular borders; two of the six cases from the series of Rabban et al 
infiltrated the endometrium and entrapped benign glands.
Useful Diagnostic Criteria for recognition in the uterus
- Fasciitis-like, storiform, and/or fascicular appearance
- Typically pushing borders
- Myxoid to collagenous stroma
- Lymphoplasmacytic infiltrate
Molecular Genetics 
Cytogenetic and molecular genetic analyses have shown that approximately 50% of IMTs have
rearrangements involving the ALK gene on chromosome 2p23. These
abnormalities are more common in pediatric patients and have been described in tumors at both pulmonary
and extrapulmonary sites. The case presented herein is the first description of ALK gene rearrangement (by FISH) in a uterine IMT.
ALK gene rearrangement typically results in overexpression of ALK protein, which can be
diagnostically useful. Approximately 50% of extrauterine IMTs will be positive for ALK by
immunohistochemistry; however, ALK positivity is not entirely specific for IMT as it can be positive in
other mesenchymal neoplasms, particularly MPNST and rhabdomyosarcoma. All uterine IMTs described to date
(including the case presented herein) were positive for ALK (cytoplasmic) by immunohistochemistry.
According to the most recent WHO, IMTs are defined as a tumor of intermediate biologic
potential because of their risk for local recurrence and metastasis. The risk of recurrence depends on
site and ability for a complete resection. Tumors within the lung for example have a low risk of
recurrence (of about 2%) as compared to tumors arising in the retroperitoneum (that tend to be
multinodular), which have a recurrence risk of up to 25%. Histologic features however do not reliably
predict which IMTs will behave in an aggressive fashion. In the four patients with uterine IMT with
followup, all are alive with no evidence of disease at 1.5 - 5 years; two patients were treated with
hysterectomy (NED at 2.5 and 5 years) and two patients were treated with hysteroscopic resection (NED at
1.5 and 3 years). Distant metastasis of IMT is rare but may occur years (up to a decade) after initial
Leiomyosarcoma, myxoid variant
Similar to the conventional spindle cell type of uterine leiomyosarcoma, this variant also typically
affects women in their sixth decade who may present with abnormal vaginal bleeding, pelvic pain and/or a
pelvic mass. However, in contrast, myxoid leiomyosarcoma usually will have a more gelatinous gross
appearance with a glistening cut surface, although this may vary in extent depending on the amount of
extracellular myxoid matrix deposition. The tumor cells may be spindled or stellate and the degree of
(Alcian blue positive) extracellular matrix deposition may obscure the tumors fascicular architecture.
Although the majority of the tumor may have a bland cytomorphologic appearance, tumor cells typically
exhibit at least focal moderate atypia. Diagnostic criteria separating myxoid leiomyosarcoma from myxoid
leiomyoma is not well established since this type of tumor is rare. Atkins et
al. have suggested that a mitotic rate in excess of 2 per 10 high power fields, regardless of the
presence or absence of either atypia or necrosis, will separate benign and malignant myxoid tumors. For
practical purposes, the diagnosis of myxoid leiomyosarcoma should be considered if any of the following
1) There is moderate to marked cytologic atypia.
2) There is coagulative tumor cell necrosis.
3) Mitotic activity exceeds 2 per 10 high power fields.
4) There is destructive infiltration of the surrounding myometrium.
Inflammatory myofibroblastic tumor  can be distinguished from myxoid leiomyosarcoma by
its 1) typically pushing border without vascular invasion, 2) its prominent lymphoplasmacytic infiltrate
and 3) its immunohistochemical expression of ALK.
Leiomyoma, myxoid variant
Because uterine IMTs typically have a rounded, pushing border and may have a fascicular growth pattern
and myxoid appearance, myxoid leiomyoma may be considered in the differential diagnosis. On gross
examination this extremely uncommon variant of leiomyoma typically appears gray and gelatinous although
this feature depends on the extent of myxoid change within the tumor. Histologically, an abundant pale
blue myxoid matrix separates the bland appearing smooth muscle bundle fibers. Features helpful in the
recognition of IMT vs a myxoid leiomyoma is the presence in the former of 1) a fasciitis-like growth
pattern, 2) a storiform growth pattern (if present), 3)a lymphoplasmacytic infiltrate and 4) positive
staining for ALK by immunohistochemistry.
Endometrial Stromal Sarcoma, Myxoid Variant
Similar to IMT, the myxoid variant of endometrial stromal sarcoma 
also may present as a polypoid endometrial mass however, it, 1) has a characteristic multinodular or
tongue-like pattern of myometrial infiltration, 2) at least focally exhibits the presence of typical
endometrial stromal neoplasia with its characteristic growth pattern and prominent (arteriolar) vascular
component, and 3) is negative for ALK-1 by immunohistochemistry.
Take Home Message
1) The myxoid variant of leiomyosarcoma should be considered if any one of the
following histologic features are present in a myxoid smooth muscle tumor:
moderate to severe nuclear atypia (i.e. discernible at 4X), tumor cell necrosis,
mitotic activity > 2 per 10 high power fields, and destructive infiltration of
2) Myxoid leiomyoma is uncommon and should only be considered if a myxoid smooth
muscle tumor is well circumscribed, lacks significant cytologic atypia, lacks
tumor cell necrosis, and has a mitotic count of < 2 per 10 high power fields.
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