Case 1 -

Endometrial stromal sarcoma Javier Arias-Stella Jr, MD Instituto de Patologia y Biologia Molecular Arias Stella Lima, Peru

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 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Endometrial stromal sarcoma Discussion: 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 [6]. 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 [1, 5, 9, 12, 13]. 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 [7, 3]. The 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 rare [10, 14]. 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 two years. 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 hybridization [8, 3]. 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. IMMUNOPROFILE 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 [11, 4]. 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 [2]. 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. 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