Uterus
Other mesenchymal tumors
Uterine tumors resembling ovarian sex cord tumors
Last author update: 1 March 2017
Last staff update: 27 April 2023 (update in progress)
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PubMed search: uterine tumors resembling ovarian sex cord tumors
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Ardighieri L, Ayhan A. Uterine tumors resembling ovarian sex cord tumors. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusUTROSCT.html. Accessed June 2nd, 2023.
Definition / general
- Rare neoplasms that resemble ovarian sex cord tumors, without a component of recognizable endometrial stroma (IARC: WHO Classification of Tumors of the Female Reproductive Organs, 4th Edition, 2014)
- Accounts for less than 0.5% of all uterine malignancies and 10% - 15% of mesenchymal uterine malignancies (Crum: High Yield Pathology - Gynecologic and Obstetric Pathology, 2016)
- Etiology uncertain and most have benign behavior without infiltrative properties
- 1945: Morehead and Bowman first described a case of a uterine neoplasm resembling a granulosa cell tumor
- 1976: Clement and Scully clarified the concept of sex cord differentiation of uterine tumors and categorized into two groups:
- Group I is endometrial stromal tumors with foci of sex cord differentiation (ETSCLE) < 50% (associated with recurrences and metastases)
- Group II composed predominantly or exclusively by sex cord-like elements; this latest group continues to be classified as UTROSCTs
- Miscellaneous category in WHO classification
Essential features
- Rare uterine tumor of uncertain histogenesis; morphologically shows overlap with ovarian sex cord tumors, affecting perimenopausal or menopausal women (mean age 51)
- Differential diagnosis crucial; different behavior
- Present mostly as intramural, less frequently submucosal or subserosal or polypoid / intracavitary masses
- Organized in sex cord structures (sheets, cord, nests, trabeculae, tubules) composed of epithelioid-looking cells with scant / abundant eosinophilic / clear cytoplasm and bland nuclei with minimal atypia and rare mitoses
- Coexpression of epithelial (KL1, CK AE1 / AE3, CAM5.2, EMA), smooth muscle (smooth muscle actin, desmin, h-caldesmon, smooth muscle myosin heavy chain, histone deacetylase-8), sex cord markers (WT1, calretinin, inhibin, CD99, MelanA, CD56, FOXL2, SF1) and hormone receptors (ER, PR, AR)
- Absence of JAZF1 / SUZ12 fusion (JAZF1-JJAZ1) and PFH1 gene rearrangements distinguish these neoplasms from endometrial stromal tumors
- Treated by surgical removal, based on age / parity of the patients (total hysterectomy with bilateral adnexectomy or conservative surgery with hysterectomy / mass resection)
- Benign behavior; however, low rates of recurrence (5%) have been reported and rarely development of metastases can occur
ICD coding
- 8590/1
Epidemiology
- Perimenopausal or menopausal women (22 - 84 years); mean age is 51
- < 1% of uterine mesenchymal tumors
Sites
- Corpus, mostly intramural, less frequently submucosal or subserosal or polypoid / intracavitary
- Rarely endocervix (Int J Gynecol Pathol 2003;22:297)
Etiology
- Tumors of uncertain histogenesis (miscellaneous category in latest WHO classification)
- Postulated theories include (Int J Gynecol Pathol 2016;35:301):
- Derivation from ovarian sex cord cells which have been displaced during embryogenesis
- Derivation from uncommitted mesenchymal stem cells
- Overgrowth of sex cord elements within endometrial stromal neoplasm or adenosarcoma (however please notice that these tumors do not have the cytogenetic abnormalities found in stromal neoplasms)
Clinical features
- Abnormal bleeding, pelvic pain, enlarged uterus, mass sensation
- A subset found incidentally
- Endometrial sampling may not reveal the diagnosis (Crum: High Yield Pathology - Gynecologic and Obstetric Pathology, 2016)
Diagnosis
- Based on histomorphologic features including a predominant pattern of the cords, nests and trabeculae resembling sex cord tumors of the ovary and immunophenotype, characterized by coexpression of epithelial, smooth muscle, sex cord markers and steroid receptors
- Imaging studies are not diagnostic; histopathology is the gold standard (Arch Pathol Lab Med 2013;137:1832)
Radiology description
- They can be diagnosed with US, CT and MRI
- No specific image findings: at transvaginal pelvic ultrasound they may be seen in an normal or enlarged uterus and may appear as myometrial masses, with myomatous features or as masses protruding in the endometrial cavity suggesting a polypoid lesion
Prognostic factors
- Most tumors exhibit benign behavior
- However, considered to have uncertain malignant potential because of a low rate of recurrence (Int J Clin Exp Pathol 2015;8:4158) and rare metastases (lymph nodes, epiploic appendix, omentum, small bowel, subcutaneous) (Int J Clin Exp Pathol 2014;7:1051, Cesk Patol 2014;50:46, Int J Gynecol Pathol 2008;27:58)
Case reports
- 22 year old woman (nulligravida) with uterine tumor resembling ovarian sex cord tumor (UTROSCT) (Gynecol Endocrinol 2015;31:856)
- 36 year old and 68 year old women with UTROSCT (Obstet Gynecol cases Rev 2015;2:4)
- 38 year old and 57 year old women with UTROSCT with metastasis (Int J Clin Exp Pathol 2014;7:1051)
- 43 year old woman with recurrent vaginal bleeding and multiple endometrial and cervical polyps (Pathologica 2014;106:73)
- 52 year old woman (Oncol Lett 2016;11:1496)
- 53 year old woman with a tumor sized 1.5 cm in diameter localized in the subendometrial region of the uterine wall (Cesk Patol 2014;50:46)
- 3 cases manifesting classical histomorphological features of UTROSCT alongside diverse immunohistochemical findings (Ann Diagn Pathol 2010;14:432)
Treatment
- No established treatment protocol
- Surgical removal differs based on consideration of age and parity of the patients:
- Total hysterectomy with bilateral adnexectomy is the most common treatment (Eur J Obstet Gynecol Reprod Biol 2014;181:163)
- Conservative surgery: hysterectomy or organ preserving surgery, especially for young patients (cases reported with postoperative conceptions during followup, Oncol Lett 2016;11:1496, Case Rep Obstet Gynecol 2016;2016:5736865, Gynecol Endocrinol 2015;31:856) should have long term followup
- Some patients receive chemotherapy or pelvic radiation because of extrauterine extension (to parametrium and ovarian hilum) and positive surgical margins or in the setting of locoregional / distant recurrent disease (Gynecol Oncol Rep 2015;15:22)
Gross description
- Intramural / submucosal / subserosal nodules or polypoid tumors growing in the endometrial cavity
- Solid, round, well circumscribed masses
- Average 6 cm; ranging from 2 to 24 cm
- Yellow, tan, grayish white surface; firm to soft to rubbery consistency
- Cut surface grayish yellow to white
- Rarely predominantly cystic
- Hemorrhage can be seen; necrosis unusual
Gross images
Contributed by Ayse Ayhan, M.D., Ph.D.
44 year old patient, fundus posterior 6 cm intramural neoplasm
Seirei Mikatahara Hospital, Hamamatsu, Japan
Microscopic (histologic) description
- Usually well circumscribed but unencapsulated; may have a pseudoinfiltrative appearance due to incorporated smooth muscle bundles; true myometrial invasion rare
- Organized in sheets, cords, nests, trabeculae, hollow or solid tubules with repetitive pattern of cordlike / tubular growth; more rarely has retiform or glomeruloid appearance or papillae and solid pattern predominance
- Neoplastic cells are small, round to ovoid with monotonous nuclei, inconspicuous nucleoli, mild nuclear hyperchromasia, rare nuclear grooves
- Call-Exner-like bodies may be rarely present
- Scant intervening stroma (hyalinised, fibroblastic or edematous)
- In some tumors endometrial stromal-type cells or benign appearing smooth muscle may be present; rare findings are a sparse lymphocytic infiltrate accompanied by foamy histiocytes, a few multinucleated giant cells, hemosiderin deposition or cholesterol crystals
- Occasionally vascular invasion, heterologous elements and necrosis
Microscopic (histologic) images
Contributed by Ayse Ayhan, M.D., Ph.D.
Images demonstrate well circumscribed but unencapsulated neoplasm organized in sheets, cords, nests, trabeculae or tubules; neoplastic cells have round to ovoid monotonous nuclei, inconspicuous nucleoli, mild nuclear hyperchromasia, rare nuclear grooves and almost no mitoses; notice that sex cord and epithelial markers are positively stained
Images hosted on other servers:
Various images
Tumor cells resemble granulosa cells
Various images
Cytology description
- Cells resembling epithelial cells, with scant cytoplasm or abundant eosinophilic / clear (including vacuolated) / foamy cytoplasm, reminiscent of Sertoli cell or granulosa cell tumors
- Can show rhabdoid features (J Clin Pathol 2007;60:1148) with abundant eosinophilic cytoplasm and eccentric nuclei
- Minimal atypia; rare mitoses (ranging from < 1 to 5 / 10 high power fields)
- Ovoid and small nuclei with irregular contours (sometimes grooved)
- Finely distributed chromatin with small to indistinct nucleoli
- Leydig-like cells may be present
Positive stains
- Ovarian sex cord markers: calretinin (positive in 95.8%), WT1 (83.3%), inhibin (48%), CD99, MelanA (85%), CD56, FOXL2, SF1 (Ultrastruct Pathol 2010;34:16, Mod Pathol 2006;19:17)
- Epithelial markers: KL1, CK AE1 / AE3 (50%), CAM5.2, EMA (34.4% focal) (Am J Surg Pathol 2010;34:1749)
- Smooth muscle markers: smooth muscle actin (40.8%), desmin (25.3%), h-caldesmon, smooth muscle myosin heavy chain and histone deacetylase-8 (66.6%) (Am J Surg Pathol 2010;34:1749)
- CD10 (60%), ER and PR and less commonly AR may be positive (J Clin Pathol 2007;60:1148)
- CD117 (weakly, 33.3%), S100 (18.2%) in occasional tumors (Am J Surg Pathol 2010;34:1749)
- Vimentin, bcl2 (Int J Clin Exp Pathol 2014;7:1051)
Negative stains
Electron microscopy description
- Cell junctions, desmosome-like junctions, tonofilaments, lumina formation, microvilli (indicative of epithelial differentiation)
- Sex cord like features (nuclear indentation, abundant intracellular filaments, endoplasmic reticulum [granulosa cells], intracytoplasmic lipid droplets
- No dense bodies, subplasmalemmal densities or pinocytotic vesicles (indicating no smooth muscle differentiation)
- Reference: Ultrastruct Pathol 2010;34:16
Molecular / cytogenetics description
- No JAZF1 / SUZ12 fusion seen in endometrial stromal tumors or PFH1 gene rearrangements (Am J Surg Pathol 2009;33:1206)
- No DICER1 and FOXL2 mutations (Int J Gynecol Pathol 2016;35:301)
- Presence of t (X;6) (p22.3;q23.1) and t(4;18)(q21.1;q21.3) in a single case (Diagn Mol Pathol 2003;12:174)
- Focal amplification on chromosome 17q11.2 including the SUZ12 gene in a single UTROSCT (Am J Surg Pathol 2009;33:1206)
Differential diagnosis
- Endometrial stromal tumor with sex cord-like elements have irregularly distributed sex cord elements and endometrial stromal component is prominent; 60% contain JAZF1-JJAZZ1 gene fusion - not present in UTROSCT and sex cord-like areas should be negative for sex cord markers (Am J Surg Pathol 2009;33:1206, Nucci, Oliva: Diagnostic Pathology: Gynecological, 1st Edition, 2014)
- Leiomyomas, including epithelioid and plexiform, vascular leiomyoma with plexiform pattern (Ann Diagn Pathol 2010;14:355) and leiomyoma with tubules (Int Semin Surg Oncol 2008;5:15): prominent thick walled blood vessels, frequent and diffuse smooth muscle markers
- Metastatic ovarian sex cord stromal tumor (presence of ovarian sex cord tumor and EMA negativity in ovarian SCT)
- Adenosarcoma: no sex cord elements
- Endometrioid carcinoma (spindled and chorded pattern): has conventional endometrial carcinoma areas and high degree of cytologic atypia (Nucci, Oliva: Diagnostic Pathology: Gynecological, 1st Edition, 2014), nuclear beta-cathenin positivity (Histol Histopathol 2009;24:149)
- PEComa: HMB45+
