Ovary
Sex cord stromal tumors
Signet ring stromal tumor
Authors: Aarti Sharma, M.D., Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 12 September 2019
Last staff update: 2 May 2023 (update in progress)
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed search: Ovarian signet ring stromal tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Sharma A, Bennett J. Signet ring stromal tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorsignetringstromal.html. Accessed June 5th, 2023.
Definition / general
- Rare, benign ovarian stromal tumor with signet ring cells
Essential features
- Primary ovarian stromal neoplasm comprised of various proportions of signet ring and spindle cells
- Cytoplasmic vacuoles in signet ring cells are negative for lipid, mucin and glycogen
- Diffusely positive for vimentin, variably express inhibin A, calretinin and actin - alpha smooth muscle but typically are negative for cytokeratin and EMA
Terminology
- Signet ring stromal cell tumor (SRSCT)
- Signet ring stromal tumor (SRST)
ICD coding
Epidemiology
- < 20 cases reported to date
- No age predilection (range: 21 - 83 years; mean: 54 years; median: 53 years)
Sites
- Ovary
Pathophysiology
- Hypothesized to arise from ovarian stromal cells or multifocal conversion of a fibroma (Adv Anat Pathol 2014;21:443)
Etiology
- Unknown
Clinical features
- Nonspecific including abdominopelvic pain, abnormal uterine bleeding or incidental finding on imaging
Laboratory
- CA125 typically within normal limits
- Mildly elevated (76.1 U/mL; normal < 46 U/mL) in one report (Int J Gynecol Pathol 2020;39:193)
Radiology description
- No defining features to distinguish from other ovarian neoplasms on imaging
- Solid or cystic, may appear complex
Prognostic factors
- No reports of metastasis or recurrence
Case reports
- 44 year old woman with polymenorrhea and 4 cm right adnexal mass (J Turk Ger Gynecol Assoc 2011;12:59)
- 64 year old obese woman with asymptomatic 3.5 cm adnexal mass on imaging (Int J Gynecol Pathol 2017;36:261)
- 69 year old obese woman with bilateral adnexal masses on imaging (Obstet Gynecol 2010;116:556)
- 70 year old woman with abdominal distention, rectal bleeding and bilateral ovarian masses (Int J Gynecol Pathol 2020;39:193)
- 76 year old woman with incidental complex adnexal mass (Med Mol Morphol 2008;41:165)
Treatment
- Surgical excision (oophorectomy)
Gross description
- Most are unilateral
- Bilaterality noted in 2 reports (Obstet Gynecol 2010;116:556, Int J Gynecol Pathol 2020;39:193)
- Typically well circumscribed and unencapsulated
- Yellow to tan and soft to firm cut surface
- May show white fibromatous areas
- Variable hemorrhage, necrosis and cystic spaces
- Range from 1.1 to 13 cm (mean: 6.8 cm; median: 5.5 cm)
Gross images
Case #184
Yellowish with areas of hemorrhage
Images hosted on other servers:
White-gray ovarian mass
Microscopic (histologic) description
- 2 cell populations in variable proportions:
- Diffuse growth of round cells with single to occasionally multiple intracytoplasmic, optically clear vacuoles, which peripherally displace and indent nucleus into crescentic shape (signet ring cells)
- Fusiform cells with eosinophilic cytoplasm and ovoid nucleus
- May have fibroma-like areas that merge with signet ring component
- Absent to minimal cellular atypia, mitotic activity and necrosis
- Elevated mitoses (13/10 and 16/10 high power fields) have been reported (Ultrastruct Pathol 1995;19:401, Int J Gynecol Pathol 2004;23:45)
- PAS+ intracytoplasmic hyaline globules noted in ~50% (Ultrastruct Pathol 1995;19:401, Virchows Arch A Pathol Anat Histopathol 1993;422:333, Int J Gynecol Pathol 2004;23:45, Int J Surg Pathol 2008;16:180, Pathol Oncol Res 2008;14:333, Med Mol Morphol 2008;41:165, J Turk Ger Gynecol Assoc 2011;12:59, Appl Immunohistochem Mol Morphol 2016;24:e28, Int J Gynecol Pathol 2017;36:261, Int J Gynecol Pathol 2020;39:193)
Microscopic (histologic) images
Case #184
Diffuse growth
Signet ring cells
Vimentin
AFIP images
Diffuse growth of cells with eccentric nuclei
Positive stains
- Vimentin diffusely positive
- Variable expression for actin - alpha smooth muscle (~50%), inhibin A (~30%, typically focal) and calretinin (~30%)
- Limited reports evaluating beta catenin (2/3 with nuclear staining), SF1 (2/3 positive), cyclin D1 (1/2 positive), FOXL2 (1 positive) expression
Negative stains
- Hallmark is negativity of intracytoplasmic vacuoles for
- Mucins (mucicarmine, PASD, Alcian blue)
- Glycogen (PAS, Alcian blue)
- Lipid (Sudan III, Oil Red O)
- AE1 / AE3, CAM5.2, EMA, CK7, CK20
Electron microscopy description
- Cytoplasmic vacuoles result from (Ultrastruct Pathol 1995;19:401):
- Generalized edema of cytoplasmic matrix
- Dilatation of mitochondria
- Invagination of cell membranes (pseudoinclusions) by extracellular matrix
- No basement membrane formation and abundant free ribosomes (Cancer 1976;38:166, Gynecol Oncol 2000;77:323)
- Hyaline globules show features of lysosomes or degenerating erythrocytes (Med Mol Morphol 2008;41:165, Ultrastruct Pathol 1995;19:401)
Molecular / cytogenetics description
- CTNNB1 mutation (n=1) (Appl Immunohistochem Mol Morphol 2016;24:e28)
- JAK3 mutation (n=1) (Appl Immunohistochem Mol Morphol 2016;24:e28)
- Negative for FOXL2 mutation (Int J Gynecol Pathol 2020;39:193)
Sample pathology report
- Right ovary, oophorectomy:
- Signet ring stromal tumor (5.0 cm)
Differential diagnosis
- Krukenberg tumor (Am J Surg Pathol 2006;30:277):
- Bilateral in > 50%, often with extraovarian disease at presentation
- Nodular growth
- Admixed with glands, nests or cords of malignant cells (may be very focal)
- Cytokeratin strongly and diffusely positive
- Vacuoles positive for PASD and mucicarmine
- Signet ring cell transformation in sex cord stromal tumors (Adv Anat Pathol 2014;21:443):
- Component of normal sex cord stromal tumor present (i.e. sclerosing stromal tumor, thecoma)
- Typically all cells (including signet ring cells) are strongly and diffusely positive for inhibin A and calretinin
- Signet ring cells contain lipid
- Microcystic stromal tumor (Am J Surg Pathol 2009;33:367, Am J Surg Pathol 2015;39:1420, Am J Surg Pathol 2018;42:137):
- Often separated into lobules by hyalinized bands
- Admixture of microcysts, solid cellular areas and fibrous stroma
- Up to 60% have bizarre nuclei
- Immunohistochemistry overlaps with signet ring stromal tumor
- Characterized by CTNNB1 or APC mutations
- Signet ring cell change (Adv Anat Pathol 2014;21:443):
- Signet ring cells limited to nonneoplastic stroma
- Described in adult granulosa cell tumor (n=1), Brenner tumor (n=1) and serous cystadenofibroma (n=2)
Board review style question #1
Which of the following is true regarding the ovarian lesion pictured below?
- It arises from ovarian stromal cells
- It has a poor prognosis
- It is typically bilateral
- Treatment involves local excision with adjuvant chemotherapy
- Tumor cells are strongly positive for cytokeratin
Board review style answer #1
A. It arises from ovarian stromal cells (this is a signet ring stromal tumor)
Comment Here
Reference: Signet ring stromal tumor
Comment Here
Reference: Signet ring stromal tumor
Board review style question #2
A 32 year old woman without significant past medical history presents with abdominal pain. Workup reveals a 2 cm right adnexal mass on ultrasound and she undergoes salpingo-oophorectomy. Histologic examination of the ovarian tumor reveals sheets of cells with crescent shaped nuclei and intracytoplasmic vacuoles. The vacuoles are negative for mucicarmine and PAS, while the cells are negative for CAM5.2 and inhibin A. What is the likely diagnosis?
- Adult granulosa cell tumor with signet ring cell change
- Krukenberg tumor
- Microcystic stromal tumor
- Signet ring stromal tumor
- Thecoma with signet ring cell transformation
Board review style answer #2
