Endometrial stromal tumors may pose diagnostic challenges particularly when they exhibit variant histologic appearances, involve extrauterine sites, or present as metastatic disease. In such cases, use of immunohistochemical markers and identification of specific nonrandom chromosomal rearrangements may be helpful. Over the last decade, fluorescence in situ hybridization (FISH) has been progressively incorporated as a diagnostic tool for the evaluation of endometrial stromal tumors. The purpose of this study was to review a series of these tumors and compare the results of FISH analysis with the clinicopathologic characteristics. Three endometrial stromal nodules (ESNs), 13 endometrial stromal sarcomas (ESSs), and 7 undifferentiatedendometrial sarcomas (UESs) were reviewed. Three metastases from 1 of the ESS cases were also analyzed. Nine of these tumors (1 ESN, 8 ESSs, and 1 UES) exhibited unusual histologic features, including smooth muscle (3), sex cord (7), epithelioid (1), fibromyxoid (1), and skeletal muscle (2) differentiation. A tissue microarray was prepared, and FISH analysis was performed using break-apart and fusion probes for JAZF1, SUZ12, EPC1, and PHF1 genes. FISH was successful in 22 cases, and rearrangements involving JAZF1, SUZ12, EPC1, and PHF1 genes were detected in 10 of the 22 (45%) uterine tumors, including 2 of the 3 ESNs and 8 of 12 ESSs. Genetic rearrangements were found neither in the 3 metastases of the ESS nor in any of the UESs. It is noteworthy that a correlation between sex cord differentiation and PHF1 rearrangement was encountered in ESSs (P=0.008). In our series, all ESSs showing sex cords had PHF1 genetic rearrangement, suggesting that such rearrangements may induce sex cord differentiation.

BACKGROUND:

To report the cytologic characteristics of low grade endometrial stromal sarcoma with sex cord-like differentiation.

CASE:

A 49-year-old woman presented with hypermenorrhea, menorrhalgia and anemia. With a diagnosis of degenerated leiomyoma of the uterus, simple total hysterectomy was conducted. Histologic examination revealed cells with ovoid to short, spindle-shaped nuclei resembling endometrial stromal cells proliferating in a space-occupying manner and compressing and partially infiltrating the myometrium. Some tumor cells were arranged in sex cord-like form, and hyalinization was observed in the center of the cord. Low grade endometrial stromal sarcoma with sex cord-like differentiation was diagnosed. Touch imprint cytologic examination of the tumor showed cells containing scanty cytoplasm and ovoid to spindle-shaped nuclei with little atypia; they were scattered individually, aggregated in clusters, or arranged in cord or glandular form. Hyaline-like substance was present in abundance. The histologic characteristics of the endometrial stromal sarcoma withsex cord-like differentiation were confirmed by touch imprint cytology of the tumor.

CONCLUSION:

In this case of low grade endometrial stromal sarcoma with sex cord-like differentiation, cytologic examination revealed hyaline substance and tumor cells aligned in cord or glandular form.

Uterine tumours with sex cord-like differentiation are rare. They are observed, pre- and post-menopausal women between the fourth and the sixth decade and manifest themselves by haemorrhagic anomalies and usually enlarged uteri, misinterpreted as uterus myomatosus. One distinguishes between two groups on account of the share of sex cord-like elements, i.e. tumours with only focal sex cord-like differentiation with a tendency to relapses and metastatic spread, and tumours with predominant differentiation in the sense of ovarian sex cord tumours with a good prognosis because surgical treatment alone often leads to relapse-free survival. Because of the tumours' rarity, there are no randomized studies as to an optimal therapy. Since there have been reports on endometrial stromal sarcoma with low malignant potential in adjuvant therapy of breast cancer with Tamoxifen, one can assume that this entity will occur more frequently in future.

We report a case of monostotic low-grade stromal sarcoma (ESS) with sex cord-like elements metastatic to the thoracic spines, which to the best of our knowledge has not previously been documented. A 48-year-old female who had undergone total abdominal hysterectomy for low-grade endometrial stromal sarcoma 7 years previously presented with insidious onset of severe back pain of 2 months' duration. Magnetic resonance image (MRI) showed involvement of the eleventh and twelfth thoracic vertebral bodies. Decompression at the level of T10-12 was performed. Histologically, the laminae of thoracic vertebrae 11 and 12 were replaced by sheets of ovoid cells with plump nuclei intermixed with anastomosing trabeculae, cords and small nests, reminiscent of a sex-cord stromal tumor pattern. The tumor cells showed diffuse nuclear immunostaining for estrogen receptors (ER) and progesterone receptors (PR), as well as membranous immunostaining for CD10. The immunostaining for smooth muscle actin was focal and sparse. These findings confirmed the diagnosis of metastatic low-grade ESS with sex cord-like differentiation. Low-grade ESS with sex cord-like differentiation is an uncommon tumor which rarely metastasizes to the bone, and use of a panel of ER, PR, CD10, actin, cytokeratin and inhibin immunostains is essential to establish the diagnosis.

A case of low-grade endometrial stromal sarcoma with extensive epithelial-like element (ELE) is reported. This tumor was composed of classical endometrial stromal sarcoma (CESS) showing diffuse proliferation, and ELE occupying approximately 72% of the tumor mass. On immunohistochemistry, ELE was negative for sex-corddifferentiation markers, and was positive for myogenic markers used in our investigation, and had a particularly prominent positivity for alpha-smooth muscle actin within the ELE. Therefore, it was considered that ELE showed no true sex cord feature, but smooth muscle differentiation. Moreover, ELE was also positive for CD10, suggesting that it was derived from CESS. It has been reported that there is a distinct clinical behavior between endometrial stromal tumors with abundant ELE and those with limited ELE. In the present case, the Ki-67 labeling index was markedly higher in CESS than in ELE. Therefore, a difference in cell proliferative activity between ELE and CESS might underlie a different clinical prognosis.

Endometrial stromal sarcomas are rare, low grade, malignant uterine tumours. Sometimes, they manifest an epithelial like or sex-cord like differentiation. This is a report of one such case in a 35 year old female.

OBJECTIVE:

To investigate the clinical and pathomorphological features of multi-differentiated endometrial stromal sarcoma of the uterus and to discuss their behaviour and differential diagnosis.

METHODS:

The histological characteristics of all cases were observed by pathological examination, some of them have been studied by immunohistochemical and/or ultrastructural techniques.

RESULTS:

Multi-differentiation was present in 13 cases of low grade and 4 cases of high grade endometrial stromal sarcoma, of which, 13 cases had sex-cord differentiation, 10 cases had smooth muscle differentiation, osseous differentiation in 2 cases and striated muscle differentiation in 1 case. Two types of multi-differentiation was present in 9 cases.

CONCLUSIONS:

Both low-grade and high-grade endometrial stromal sarcoma of uterus can display multi-differentiation. Sex-cord and smooth muscle differentiation are the most common types. Osseous and striated muscle differentiation are very rare. There is no definite correlation between prognosis and the amount or types of multi-differentiation components.

We describe an interesting case of uterine stromal nodule with sex-cord-like differentiation of retiform type. The tumour occurred in a 51-year-old woman. It contained areas of retiform patterns mimicking an epithelial component of some of mullerian biphasic tumours. Areas of classical sex-cord-like and smooth muscle differentiations were also found. The sex-cord-like cells revealed a smooth muscle phenotype in ultrastructural and immunohistochemical studies.

Low-grade endometrial stromal sarcoma with sex cord-like differentiation occurred in two postmenopausal patients who had received tamoxifen for more than 3 years after surgical resection for breast cancer. Uterine sarcomas have been described in association with the use of tamoxifen. Only two cases of endometrial stromal sarcoma with sex cord-like features associated with tamoxifen use have been reported previously. This report adds an additional two cases of this tumor. Immunohistochemical and ultrastructural examinations of the tumor support the concept of smooth muscle differentiation in the sex cord-like areas. This observation proposes that the low-grade endometrial stromal sarcoma with sex cord-like elements may be a consequence of tamoxifen ingestion, but the exact mechanism of tamoxifen in the development of this tumor remains speculative.

Two cases of endometrial low-grade stromal sarcoma with ovarian sex cord-like differentiation occurring in a 39-year-old woman and a 42-year-old woman are presented. Both tumors, which were intramyometrial and measured 7.5 cm and 7.0 cm in greatest diameter, respectively, showed a multinodular, ill-demarcated, and yellowish white cut-surface. Histologically, most parts of the tumors were composed of trabecular, cord-like, or plexiform arrangements that were reminiscent of the growth pattern seen in ovarian sex cord tumors. Features of conventional endometrial low-grade stromal sarcoma were only focally observed. The tumors showed infiltrative margins and lymphatic invasion. The tumor cells were positive for vimentin, desmin, alpha-smooth muscle actin, and muscle actin (HHF35). The tumors were also positive for both estrogen and progesterone receptors. Both tumors were DNA diploid as determined by flow cytometry. One patient had recurrences, including osteolytic lesions in the pelvic bones, but had no evidence of recurrence or metastasis 11 months after the last surgery. The other patient had no evidence of tumor in a limited follow-up. Familiarity with the neoplasm and other uterine mesenchymal tumors with ovarian sex cord-like differentiation by gynecologists and pathologists is essential in avoiding misdiagnosis because adjuvant hormonal therapy may be effective in treating low-grade stromal sarcomas.