Clinical History
A 63 year-old female with a history of a previous total abdominal hysterectomy and bilateral
salpingo-oophorectomy for uterine leiomyomas presented to the emergency room with diffuse abdominal pain.
Imaging studies, including CT scan of the abdomen and pelvis, were normal. The patient underwent a
colonoscopic examination that was unremarkable and was given treatment for her symptoms. The abdominal
pain persisted, and a second CT scan of the abdomen and pelvis performed three months later showed a 9 cm
mass in the right lower quadrant. The patient underwent exploratory laparotomy, resection of the mass,
and omentectomy.
Case 1 - Figure 1 - One of the areas of the tumor with dense cellularity (low power).
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Case 1 - Figure 2 - An area of hyalinization adjacent to an area of dense cellularity (low power).
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Case 1 - Figure 3 - A variably fascicular to storiform pattern. Note the absence of a discrete vascular pattern and the nuclear pleormorphism (intermediate power).
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Case 1 - Figure 4 - A variably fascicular to storiform pattern. Note the absence of a discrete vascular pattern and the nuclear pleormorphism (intermediate power).
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Case 1 - Figure 5 - An area of necrosis (intermediate power).
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Case 1 - Figure 6 - Nuclear pleomorphism (high power).
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Case 1 - Figure 7 - Conspicuous mitotic activity in the pleomorphic area of the tumor.
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Case 1 - Figure 8 - Conspicuous mitotic activity in the pleomorphic area of the tumor.
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Case 1 - Figure 9 - Tumor infiltrating the adipose tissue as discrete islands (low power).
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Case 1 - Figure 10 - Small and uniform cells surrounding arteriole-like vessels (same area as figure 9, intermediate power).
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Case 1 - Figure 11 - Collagen deposition (intermediate power).
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Case 1 - Figure 12 - Absence of mitotic activity, uniform cells, and arteriole-like vessels (high power).
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Gross and Microscopic Examination
A 13.5 x 9.5 x 8.5 cm tan-white, trabeculated, focally hemorrhagic intraabdominal mass was resected.
In addition, a 24.5 cm omentectomy specimen with fibrotic and hemorrhagic areas was obtained.
Microscopic examination of sections from both specimens shows two distinct patterns. In one area (slide
1A), the tumor shows dense cellularity adjacent to areas of hyalinization and necrosis. The cells are
pleomorphic and arranged in a fascicular or storiform pattern. Up to 55 mitoses per 10 high power fields
are seen. This area represented approximately 17% of the tumor sampled. In another area (slide 1B), the
tumor shows small, uniform cells arranged in islands that infiltrate the adipose tissue. The neoplastic
cells surround arteriole-like vessels, and there is collagen deposition. The mitotic activity is
inconspicuous (1 mitosis per 10 high power fields). Immunoperoxidase studies show that the neoplastic
cells in the pleomorphic portion of the tumor are very focally positive for CD10 (less than 10% of the
cells stained) and positive for progesterone receptors (PR) (up to 50% of the cells stained). The tumor
cells were also positive for estrogen receptors (ER) and negative for desmin, CD34, and c-kit. In
contrast, the more uniform portion of the tumor showed more CD10 expression (patchy staining) and was
diffusely and strongly positive for PR. This portion of the tumor was also positive for ER and negative
for desmin, CD34, and c-kit.
Extended Clinical History
There was no residual tumor, and the patient was not given further therapy. One year after diagnosis,
the patient is alive with no evidence of disease.
Discussion
In 1982, Evans proposed a change to the traditional approach for classifying endometrial stromal
sarcomas. Previously, these tumors had been divided into two categories, low and high grade, based on
the mitotic index as established by Norris and Taylor. The lowgrade category encompassed neoplasms with
a mitotic index of fewer than 10 mitoses per 10 high power fields, and the high grade category was used
to designate tumors with a mitotic count of 10 or more mitoses per 10 high power fields. According to
Evans' work, there were clinical and pathologic differences that allowed the separation of endometrial
stromal sarcoma from poorly differentiated endometrial sarcoma. The former is usually seen in women
younger than 50 years of age, has an indolent course, and is characterized histologically by the presence
of small- to medium-sized uniform cells and small, arteriole-like vessels. The cells can be arranged in
sheets or interlacing fascicles. A plexiform pattern, myxoid changes, smooth muscle differentiation,
fibrotic background, "sex cord-like areas" or collagen deposition can be seen. In contrast, poorly
differentiated endometrial sarcoma is typically found is patients older than 50 years of age and is
highly aggressive. This type of neoplasm is recognized as an endometrial sarcoma only because of its
topographic relationship to the endometrium. Histologically, the neoplastic cells tend to be larger than
those seen in endometrial stromal sarcoma, they vary from round to spindle to bizarre, and they are
arranged in a diffuse or vaguely fascicular pattern. Some degree of nuclear hyperchromasia and
pleomorphism is always present, and in a rare case, the cells are smaller than the ones usually seen in
these tumors. Arteriole-like vessels are not present. In this study, it was found that the mitotic rate
was unrelated to prognosis. The validity of this approach was confirmed by a subsequent study by Chang,
et al in 1990.
The synchronous or metachronous association of a high grade sarcoma with an endometrial stromal
sarcoma (dedifferentiation) is a rare event. So far, five cases of this type have been reported in the
English literature. In three of these cases, the dedifferentiation was evident in the original uterine
tumor, while in two cases, it became apparent in tumor recurrences detected after radiotherapy. In all
the cases, typical areas of endometrial stromal sarcoma could be seen in addition to the high grade
sarcoma. Of interest, in one of these cases, immunohistochemical stains for ER and PR were performed;
the neoplastic cells in the typical endometrial stromal sarcoma component expressed ER and PR, while
those in the high grade sarcoma component were negative. Additionally, chromogenic in situ hybridization
performed in this case showed that the endometrial stromal sarcoma component was diploid for chromosomes
X, 11, 12, and 17, while the high grade sarcoma was aneuploid. Of these five patients, two patients had
progressive disease after a follow-up of 15 and 18 months, respectively; two died of disease within four
months and two years in spite of treatment with Depo-Provera, and Depo-Provera and chemotherapy,
respectively; and one was alive with no evidence of disease, 18 months after receiving postoperative
radiotherapy.
In our experience, dedifferentiation in endometrial stromal sarcoma is uncommon. The preliminary
results of an ongoing study at The University of Texas M. D. Anderson Cancer Center encompassing13 cases
collected over a period of 8 years (1996-2004) are the following: patients' ages ranged from 35 to 63
years (median, 50 years). The combination of endometrial stromal sarcoma and high grade sarcoma
(dedifferentiation) was detected in the primary uterine tumors in eight cases, and in the recurrent
tumors in four cases (three in the pelvis and one in the lung). In a single case, the tumor arose in
extragenital endometrial stromal sarcoma. In accordance with the FIGO system, the uterine cases were
staged as follows: stage I (two cases), stage II (two cases), stage III (three cases), and stage IV (one
case). In one case with dedifferentiation in the uterine tumor, the patient had received radiotherapy
for a cervical cancer; in another case in which dedifferentiation was detected in a lung metastasis, the
patient had received radiotherapy for the treatment of the original uterine endometrial stromal sarcoma.
In all cases but one, endometrial stromal sarcoma and high grade sarcoma were present together; the
latter component comprised anywhere from 10% to 95% of the tumor sampled. In a single case, the high
grade sarcoma represented the entirety of the tumor, which had recurred in the lung 19 years after
hysterectomy, radiotherapy, and chemotherapy for the original uterine endometrial stromal sarcoma.
In three cases, immunohistochemical stains were performed on both the endometrial stromal sarcoma
component and the high grade sarcoma component. In one case, positivity for CD10 and PR was seen in both
components, while in the other two cases, staining for CD10 and PR was decreased or absent in the high
grade component. After follow-up ranging from 12 months to 132 months, six patients had died of disease
(median interval, 48 months); two patients were alive with disease at 33 months and 72 months,
respectively; and three patients were alive with no evidence of disease at 33 months, 36 months, and 72
months, respectively. No follow-up information was available regarding two of the patients.
In summary, dedifferentiation in endometrial stromal sarcoma is an uncommon event that must be
recognized due to its importance from the diagnostic standpoint and its potential therapeutic
implications.
References
- Evans HL. Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma. Cancer 50: 2170 –2182, 1982.
- Norris HJ, Taylor HB. Mesenchymal tumors of the uterus. I: A clinical and pathological study of 53 endometrial stromal tumors. Cancer 19:755-766, 1966.
- Chang KL, Crabtree GS, Lim-Tan SO, Kempson RL, Hendrickson MR. Primary uterine endometrial stromal neoplasms: A clinicopathologic study of 117 cases. Am J Surg Pathol 14:415-438,1990.
- Yoonessi M, Hart WR. Endometrial stroma sarcomas. Cancer 40:898-906, 1977.
- Smith ML, Faaborg LL, Newland JR. Dedifferentiation of endolymphatic stromal myosis to poorly differentiated uterine stromal sarcoma. Gynecol Oncol 9:108-113, 1980.
- Thatcher SS, Woodruff JD. Uterine stromatosis: A report of 33 cases. Obstet Gynecol 59:428-434,1982.
- Chumas JC, Patsner B, Mann WJ. High–Grade pelvic sarcoma after radiation theraphy for low-grade endometrial stromal sarcoma. Gynecol Oncol 36:428-431, 1990.
- Cheung AN, Ng WF, Chung LP, Khoo US. Mixed low-grade and high-grade endometrial stromal sarcoma of uterus: differences on immunohistochemistry and chromosome in situ hybridization. J Clin Pathol 49:604-607, 1996
