Sarcomas of the Female Genital Tract
Moderator: Dr. Marisa Nucci
Case 1 -
Endometrial stromal sarcoma
Javier Arias-Stella Jr, MD
Instituto de Patologia y Biologia Molecular Arias Stella
Clinical History :
A 59 year old woman presented to her physician with complaints of
menometrorrhagia of 2 months duration. After clinical workup, she underwent a total abdominal
hysterectomy and bilateral salpingo-oophorectomy
Case 1 - Slide 1
Endometrial stromal sarcoma
Within the uterine neoplasias, endometrial stromal tumors represent a group of
mesenchymal tumors that are defined primarily by the morphologic similarity of their cells to normal
endometrial stromal cells in the proliferative phase . Endometrial stromal tumors may show various
morphologic and immunophenotypic features that may become diagnostically challenging or be a possible
cause of confusion. Within the morphologic features recorded in the literature there are: smooth muscle
differentiation and rarely skeletal muscle differentiation; fibrous and myxoid changes; cells with clear
or granular eosinophilic cytoplasm; epithelial differentiation with a sex-cord like pattern or the
presence of endometrial glands; and cells with a rhabdoid phenotype, bizarre nuclei and fatty metaplasia.
Multicystic changes and osteoclast –like giant cells, have also been described
These neoplasms are divided into three major categories. A better differentiated form composed of
cells resembling those of proliferative phase endometrial stroma with numerous thin-walled small
arteriolar type vessels (mimicking spiral arterioles) that is histologically well circumscribed- the
endometrial stromal nodule. The endometrial stromal sarcoma, was traditionally divided
into low and high grade types, based on mitotic counts. However, since high-grade endometrial stromal
sarcomas lack specific differentiation and show no close histologic resemblance to endometrial stroma, it
has been proposed that they be designated undifferentiated endometrial sarcoma
current WHO classification scheme therefore has two categories of endometrial stromal sarcoma: low grade
and undifferentiated, which is based on differences in tumor morphology rather than mitotic activity.
Low grade endometrial stromal sarcoma is a tumor composed of cells that morphologically
resemble non neoplastic proliferative phase endometrial stroma that infiltrates the surrounding
myometrium in a "fingerlike" fashion. The endometrial stromal sarcoma low grade accounts for only 0.2%
of all genital tract malignancies in general and they affect more young woman; studies has demonstrated
that the mean age ranges from 42-58 years, and 10-25% of patients are pre-menopausal. They are indolent
tumors with a propensity for local recurrence, usually many years after surgery. Distant metastasis is
On the other hand, undifferentiated endometrial sarcomas are aggressive tumors
with the patients showing extrauterine disease at the time of diagnosis and dying of the disease within
Cytogenetics abnormalities have been reported in endometrial stromal tumors, most often as chromosomal
rearrangements involving chromosomes 6,7 and 17. Recently two genes have been identified, JAZF1 and JJAZ1 with chromosomal sites of breakage in
7p15 and 17q21 respectively. Endometrial stromal nodules and low grade endometrial stromal sarcomas may
show evidence of the t(7;17) translocation by fluorescence in situ
The immunoprofile of the neoplastic cells of both the stromal nodule and low-grade endometrial stromal
sarcoma have been reviewed in several articles over the last decade. Here is a list of the markers
studied in several articles over the last few years.
|Immunostain Class ||% Pos ||Total Cases|
|BCL-2 ||100 ||17|
|CD10 ||95 ||84|
|PRP ||94 ||31|
|ERP ||92 ||46|
|AROMATASE ||85 ||46|
|GNRH-R ||76 ||29|
|VIMENTIN ||75 ||24|
|EGFR PHRMDX ||74 ||23|
|CALPONIN ||64 ||19|
|B-CATEN-NUC ||60 ||10|
|ACTIN-SM ||52 ||68|
|CEA-P ||50 ||2|
|DESMIN ||44 ||95|
|AE1_AE3 ||35 ||32|
|ACTIN-HHF35 ||25 ||24|
|APO D ||23 ||9|
|CALRETININ ||15 ||7|
|CAM 5.2 ||12 ||17|
|KERATIN-PAN ||12 ||18|
|CHROMOGRANA ||8 ||14|
|H-CALDESMON ||7 ||64|
|HMB-45 ||4 ||25|
|CD34 ||3 ||41|
|INHIBIN ||2 ||68|
Immuno query developed by Dennis M Frisman, MD.
There are several other markers that have been used, but the list showed here are the more relevant,
especially for those cases emphasized in recent years with confusing patterns including prominent fibrous
foci and the formation of structures resembling sex cord as well as other described patterns mentioned
above. The first line of antibodies to be used in the differential diagnosis of endometrial stromal
sarcoma with other mesenchymal tumors could be: vimentin, keratin, CD10, ER, PR, muscle actin, desmin,
S-100 and CD34
It is important to be aware of the heterogeneous pattern of intermediate filament expression these
tumors may demonstrate. For those cases with sex cord elements calretinin, CD99, melan-A and inhibin may
be helpful in the differential diagnosis .
The expression of epidermal growth factor receptors may provide the basis for a new therapeutic
strategy using monoclonal antibodies against EGFR (such as cetuximab) as demonstrated by Monfair where
70% of the 20 cases of ESS where positive fro EPGFR.
In summary, the diagnosis of endometrial stromal sarcoma and their variants should be familiar to the
pathologist. The use of immunohistochemistry can be supportive and confirmatory, but careful light
microscopic examination is usually sufficient for the diagnosis.
- Baker PM, Moch H, Oliva E. Unusual morphologic features of endometrial stromal tumors. A report of 2 cases. Am J Surg Pathol, 2005 Oct; 29(10):1394-8.
- Binder SW, Nieberg RK, Cheng L, Al-Jitawi S. Histologic and immunohistochemical analysis of nine endometrial stromal tumors: an unexpected high frequency of keratin protein positivity. Int J Gynecol Pathol, 1991; 10:191-197.
- Crum CP, Lee KR. Diagnostic gynecologic and obstetric pathology. Elsevir Inc, 2006.
- de Leval L, Waltregny D, Boniver J, Young RH, Castronovo V, Oliva E. Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus. Am J Surg Pathol, 2006 Mar; 30(3) 319-27.
- Fadare O, McCalip B, Mariappan MR, Hileeto D, Parkash V. An endometrial stromal tumor with osteoclast-like giant cells. Ann Diagn Pathol, 2005 Jun; 9(3):160-5.
- Fadare O, Zheng W. A 44-year-old woman with menometrorrhagia. Arch Pathol Lab Med, 2005 Oct; 129(10) Residents' Pages:e195-8.
- Fattaneh A. Tavassoli & Meter Devilee. World Health Organization Classification of Tumors. Pathology & Genetics. Tumors of the Breast and Female Genital Organs. WHO OMS, Lyon, 2003.
- Hrzenjak A, Moinfar F, Tavassoli FA, Strohmeier B, Kremser ML, Zatloukal K, Denk H. JAZF1/JJAZ1 gene fusion in endometrial stromal sarcomas: molecular analysis by reverse transcriptase-polymerase chain reaction optimized for paraffin-embedded tissue. J Mol Diagn 2005; 7:388-95.
- Irving JA, Carinelli S, Prat J. Uterine tumors resembling ovarian sex cord tumors are polyphenotypic neoplasms with true sex cord differentiation. Modern Pathology, 2006 Jan; 19(1):17-24.
- Kim KR, Jun SY, Park IA, Ro JY, Nam JH. Endometrial stromal tumor with limited infiltration and probable extrauterine matastasis: report of a case. Ann Diagn Pathol, 2005 Feb; 9(1):57-60.
- McCluggage WG, Sumathi VP, Maxwell P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology, 2001; 39:273-8.
- Oliva E, Young RH, Clement PB, Scully RE. Myxoid and fibrous endometrial stromal tumors of the uterus: a report of 10 cases. . Int J Gynecol Pathol, 1999; 18:310-9.
- Oliva E, Clement PB, Young RH. Endometrial stromal tumors: an update on a group of tumors with a protean phenotype. Adv Anat Pathol, 2000 Sep; 7(5):257-81.
- Young RH, Scully RE. Sarcomas metastatic to the ovary: a report of 21 cases. Int J Gynecol Pathol, 1990; 9:231-252.