REVIEW
Recent advances in the histopathology of stromal tumours of the endometrium

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Summary

Stromal tumours of the endometrium can be difficult to distinguish from smooth muscle tumours of the uterus when evaluating conventional morphology alone. This review focuses on the value of immunohistochemical markers for diagnosing endometrial stromal tumours with emphasis on the recent literature. Low-grade endometrial stromal sarcomas show consistent expression of CD10 but the specificity of staining is low, since approximately 50% of highly cellular leiomyomas and almost all leiomyosarcomas are also positive for CD10. Therefore, a panel of markers must be used for distinguishing an endometrial stromal tumour from a uterine smooth muscle tumour, including antibodies against CD10, desmin, h-caldesmon and oxytocin receptors. On rare occasions, additional markers such as inhibin, CD117 and HMB-45 may be of help in the differential diagnosis.

Introduction

Distinguishing between a low-grade endometrial stromal sarcoma (ESS) and a benign smooth muscle tumour of the uterus is of great clinical relevance, since the former is associated with recurrences and late metastases. Difficulties are most commonly encountered in the distinction of a low-grade ESS from a highly cellular leiomyoma (HCL),1 especially in a biopsy or currettage specimen. Similar problems in differential diagnosis occur with tumours exhibiting mixed endometrial stromal and smooth muscle differentiation,2 ESSs with fibroblastic and smooth muscle differentiation,3 or with the myxoid and fibrous variants.4 In addition, ESSs with intravascular growth can be confused with cellular intravenous leiomyomatosis. Endometrial stromal tumours (ESTs) are divided into benign stromal nodules with pushing margins, and ESSs with infiltrating margins. The cells of stromal nodules and of low-grade ESSs resemble the stromal cells of normal proliferative phase endometrium, and small vessels reminiscent of the spiral arterioles of normal endometrium are usually present. In some cases, cells with foamy cytoplasm may be evident. The recent WHO Classification of Tumours of the Breast and Female Genital Organs5 proposed that high-grade ESSs should be designated as undifferentiated endometrial or uterine sarcomas. Since undifferentiated endometrial sarcomas lack specific differentiation and bear no histological resemblance to endometrial stroma, this review focuses on the value of recently described immunohistochemical markers, which may aid in the differential diagnosis of low-grade ESSs from other uterine mesenchymal tumours.

Section snippets

CD10

Antibodies recognizing the common acute lymphoblastic leukaemia antigen were clustered as CD10 at the First International Workshop on Human Leukocyte Differentiation Antigens.6 CD10 is an integral membrane glycoprotein7 expressed by a wide variety of neoplastic and non-neoplastic haematopoietic, epithelial and mesenchymal cells.8 CD10 was proposed as a marker for ESS and renal cell carcinoma in a large study of 505 non-haematopoietic neoplasms.9 Initially, the consistent expression of CD10 in

H-caldesmon

Caldesmon is a cytoskeleton-associated Ca2+, calmodulin and actin-binding protein involved in the regulation of smooth muscle contraction.14 The high-molecular-weight isoform (h-caldesmon) is thought to be restricted to vascular and visceral smooth muscle and non-neoplastic myoepithelial cells, and is not expressed in myofibroblasts or thereof derived soft tissue tumours.15 Rush et al.16 found all 12 examined ESSs to be negative for h-caldesmon, whereas one out of 12 ESSs displayed diffuse

Oxytocin receptors

Oxytocin receptors (OTRs) are found in a variety of human tissues, including the female and male reproductive systems, the mammary gland and the vascular endothelium. In response to a variety of stimuli such as parturition and suckling, the neurohypophyseal peptide oxytocin is released from the posterior pituitary into the systemic circulation.20 During labour, oxytocin induces the uterine smooth muscle to contract and acts on target cells binding to OTRs, a specific class I G-protein-coupled

Inhibin, CD117, HMB-45 and WT-1

Inhibin is produced by ovarian granulosa cells and is regarded as a sensitive marker for sex-cord stromal tumours of the ovary.26, 27 In the series of Oliva et al.2 all 10 ESTs were negative for inhibin, and its lack of expression in ESSs of the ovary is helpful in distinguishing them from adult granulosa cell tumours.28, 29, 30, 31 A proportion of ESSs with sex-cord-like differentiation has been reported to express inhibin, but only in the sex-cord-like areas. Baker et al.32 found inhibin

Conclusions and future directions

Immunohistochemistry is helpful in differentiating ESTs from other uterine tumours that resemble them. A panel of antibodies including desmin, h-caldesmon, OTRs and CD10 should be used to distinguish low-grade ESSs from smooth muscle tumours of the uterus, especially from HCLs. The results of immunohistochemistry must always be interpreted in the context of conventional morphology, especially in cases of ESSs with smooth muscle differentiation. Their differential diagnosis will remain

Acknowledgements

The authors are indebted to Prof. Dr. G. Dallenbach-Hellweg and Prof. Dr. F.D. Dallenbach for their critical comments and advice regarding this manuscript.

References (48)

  • E. Oliva et al.

    Cellular benign mesenchymal tumors of the uterus. A comparative morphologic and immunohistochemical analysis of 33 highly cellular leiomyomas and six endometrial stromal nodules, two frequently confused tumors

    Am J Surg Pathol

    (1995)
  • E. Oliva et al.

    An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterusa study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies

    Am J Surg Pathol

    (2002)
  • A. Yilmaz et al.

    Endometrial stromal sarcomas with unusual histologic featuresa report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation

    Am J Surg Pathol

    (2002)
  • E. Oliva et al.

    Myxoid and fibrous endometrial stromal tumors of the uterusa report of 10 cases

    Int J Gynecol Pathol

    (1999)
  • F.A. Tavassoli et al.

    World Health Organization Classification of Tumours. Pathology and genetics of the breast and female genital organs

    (2002)
  • A. Bernard et al.

    Joint report of the first international workshop on human Leucocyte differentiation antigens by the investigators of the participating laboratories

  • M.A. Shipp et al.

    Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein

    Proc Natl Acad Sci USA

    (1988)
  • D.A. Arber et al.

    CD10a review

    Appl Immunohistochem

    (1997)
  • P. Chu et al.

    Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma

    Am J Clin Pathol

    (2000)
  • P.G. Chu et al.

    Utility of CD10 in distinguishing between endometrial stromal sarcoma and uterine smooth muscle tumorsan immunohistochemical comparison of 34 cases

    Mod Pathol

    (2001)
  • W.G. McCluggage et al.

    CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms

    Histopathology

    (2001)
  • T. Toki et al.

    CD10 is a marker for normal and neoplastic endometrial stromal cells

    Int J Gynecol Pathol

    (2002)
  • C. Loddenkemper et al.

    Use of oxytocin receptor expression in distinguishing between uterine smooth muscle tumors and endometrial stromal sarcoma

    Am J Surg Pathol

    (2003)
  • K. Sobue et al.

    Purification and characterization of caldesmon77a calmodulin-binding protein that interacts with actin filaments from bovine adrenal medulla

    Proc Natl Acad Sci USA

    (1985)
  • K. Watanabe et al.

    h-Caldesmon in leiomyosarcoma and tumors with smooth muscle cell-like differentiationits specific expression in the smooth muscle cell tumor

    Hum Pathol

    (1999)
  • D.S. Rush et al.

    h-Caldesmon, a novel smooth muscle-specific antibody, distinguishes between cellular leiomyoma and endometrial stromal sarcoma

    Am J Surg Pathol

    (2001)
  • M.R. Nucci et al.

    h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors

    Am J Surg Pathol

    (2001)
  • K. Devaney et al.

    Immunohistochemistry as a diagnostic aid in the interpretation of unusual mesenchymal tumors of the uterus

    Mod Pathol

    (1991)
  • M.M. Miettinen et al.

    Calponin and h-caldesmon in soft tissue tumorsconsistent h-caldesmon immunoreactivity in gastrointestinal stromal tumors indicates traits of smooth muscle differentiation

    Mod Pathol

    (1999)
  • G. Gimpl et al.

    The oxytocin receptor systemstructure, function, and regulation

    Physiol Rev

    (2001)
  • T. Kimura et al.

    Structure and expression of a human oxytocin receptor

    Nature

    (1992)
  • A.R. Fuchs et al.

    Oxytocin receptors in nonpregnant human uterus

    J Clin Endocrinol Metab

    (1985)
  • M. Takemura et al.

    Expression and localization of oxytocin receptor gene in human uterine endometrium in relation to the menstrual cycle

    Endocrinology

    (1993)
  • P. Cassoni et al.

    Oxytocin receptors in human adenocarcinomas of the endometriumpresence and biological significance

    J Pathol

    (2000)
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