Endometrial stromal tumor

Several endometrial stromal tumor variants have been described (Fig. 18.18). These include the smooth muscle variant (also referred to as mixed endometrial stromal and smooth muscle tumor or stromo-myoma), fibromyxoid variant,sex cord variant, and variants including endometrioid glands or epithelioid cells. The key to understanding the immunophenotype of these tumors is that variant or metaplastic elements often lose the phenotype of endometrial stroma and acquire the phenotype of the corresponding metaplastic element. Therefore, the smooth muscle in a smooth muscle variant of endometrial stromal nodule expresses muscle markers (Fig. 18.18B) and is frequently CD10-negative. T20 endometrioid... 

Endometrial stromal tumors are typically CDIO, ER, and PR positive and lack staining for desmin, h-caldesmon, and CD34. 

If confronted with a possible endometrial stromal tumor variant, concentrate the examination on components that resemble proliferative phase endometrial stroma. 

Endometrial stromal neoplasms, both nodules and sarcomas, almost always express CDIO, ER, PR, and WTl (Fig. 18.17).138>141-143,213,214 Many also express P-catenin.2i 2i They frequently express smooth muscle actin,i°°40i,i38,2i4 cytokeratin, 4i4 qj- androgen receptors patchily. They only unusually express des-j inioo,i35,2i9,220 CD34 (unpublished observation) in varieties where the constituent cells resemble non-neoplastic proliferative endometrial stroma. Diffuse desmin and h-caldesmon expression supports smooth muscle differentiation and disqualifies categorization as an endometrial stromal tumor except in rare cases. 

This is a very rare, possibly benign uterine tumor that is characterized by a cytologically bland and largely mitot-ically inactive proliferation of spindle cells in a myxoid matrix. The main differential diagnostic considerations include myxoid leiomyoma and leiomyosarcoma and endometrial stromal neoplasm with myxoid stroma. All inflammatory myofibroblastic tumors reported in the largest series were ALK-positive, which is similar to what has been described to occur in other sites. " All uterine mesenchymal neoplasms studied were ALK-negative, including smooth muscle and endometrial stromal tumors and carcinosarcomas. 

Oliva E, Young RH, Clement PB, et al. Myxoid and fibrous endometrial stromal tumors of the uterus A report of 10 cases. Int J Gynecol Pathol. 1999 18 310-319. 

Nucci MR, O Connell JT, Huettner PC, et ah h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors. Am J Surg Pathol. 2001 25 455-463. 

Jung CK, Jung JH, Lee A, et al. Diagnostic use of nuclear beta-catenin expression for the assessment of endometrial stromal tumors. Mod Pathol. 2008 21 756-763. 

Koontz JI, Soreng AL, Nucci M, et al. Frequent fusion of the JAZFl and JJAZl genes in endometrial stromal tumors. Proc Natl Acad Sci USA. 2001 98 6348-6353. 

Oliva E, de Leval L, Soslow RA, et al. High frequency of JAZFl-JJAZl gene fusion in endometrial stromal tumors with smooth muscle differentiation by interphase FISH detection. Am J Surg Pathol. 2007 31 1277-1284. 

Burkitt s lymphoma, ALL, angioimmimo-blastic lymphoma, endometrial stromal tumors, renal cell carcinoma... 

As the endometrial stromal tumors does not have a specific immunophenotype and the expression of CD 10 and steroid hormones can also be noted in some other tumors such as hepatocellular carcinoma and few types of renal cell carcinoma, the detection of the JAZFl-JJAZl fusion transcript can be used as a further diagnostic feature to distinguish the endometrial stromal tumors from other tumors, specially if the examined tissue represents a metastatic tumor of unknown primary. 

Bhargava R, Shia J, Hummet AJ, et al. Distinction of endometrial stromal sarcomas from hemangiopericytomatous tumors using a panel of immunohistochemical stains. Mod Pathol. 2005 18 40-47. 

Expression of cytokeratins (AE1/AE3 and CAM5.2) is usually sufficient to confirm epithelial differentiation in tumors of most organ systems. However, in the uterus, cytokeratin expression is not limited to epithelial cells. Both endometrial stromal and smooth muscle cells have been shown to have focal cytokeratin expression. 

The immunophenotype of this tumor closely parallels that of endometrial stromal neoplasms when stromal overgrowth is not present. The mesenchymal component of miillerian adenosarcomas without stromal overgrowth typically expresses ER, PR, androgen receptors, CD 10, and WTl, while significant minorities also express smooth muscle actin and even pan-cytokeratins (Fig. 18.19).2°F227-229 demonstrating stromal... 

As is the case with undifferentiated carcinomas, undifferentiated sarcomas are an extraordinarily heterogeneous collection of different tumors. The undifferentiated endometrial sarcoma (of which many examples were considered high-grade endometrial stromal sarcoma) is the best known member of this group. Despite this, the criteria for diagnosing this tumor and its immunophenotype are not well understood. Some examples might represent de-differentiation from a low-grade endometrial stromal sarcoma.Immunohlstochemistry has been studied in a small series of such cases. CDIO and PR expression were noted to be lost when compared to the differentiated components in most cases. 

FISH for the gene rearrangemenC oo assays used to identify this aberration. t(7 17) is apparently specific for tumors in the endometrial stromal category, as this has not yet been described in other tumor types. 

Oliva E, Clement PB, Young RH, et aL Mixed endometrial stromal and smooth muscle tumors of the uterus—A clinicopatho-logic study of 15 cases. Am J Surg Pathol. 1998 22 997-1005. 

Oliva E, Young RH, Amin MB, et al. An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus—A study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am Surg Pathol. 2002 26 403-412. 

Chu PG, Arber DA, Weiss LM, et al. Utility of CDIO in distinguishing between endometrial stromal sarcoma and uterine smooth muscle tumors An immunohistochemical comparison of 34 cases. Mod Pathol. 2001 14 465-471. 

Loddenkemper C, Mechsner S, Foss HD, et al. Use of oxytocin receptor expression in distinguishing between uterine smooth muscle tumors and endometrial stromal sarcoma. Am J Surg Pathol. 2003 27 1458-1462. 

Yilmaz A, Rush DS, Soslow RA. Endometrial stromal sarcomas with unusual histologic features A report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation. Am J Surg Pathol. 2002 26 1142-1150. 

Oliva E, Clement PB, Young RH. Epithelioid endometrial and endometrioid stromal tumors A report of four cases emphasizing their distinction from epithelioid smooth muscle tumors and other oxyphilic uterine and extrauterine tumors. Int J Gynecol Pathol. 2002 21 48-55. 

Wilms tumor protein-1 (WT-1) Nephroblastoma, mesothelioma, metanephric adenoma, ovarian serous carcinoma AML, desmoplastic small round cell tumor, endometrial stromal sarcoma, uterine leiomyosarcoma, granulosa cell tumor, thecoma, rhabdoid tumor Kidney, mesothelial cells, granulosa cells, Sertoli cells, fallopian tube endometrial stroma, spleen... 

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