Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology images | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | 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: Pors J, Hoang L. Mesonephric adenocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixmesonephricadeno.html. Accessed February 8th, 2023.
Definition / general
- Rare, nonhuman papillomavirus (HPV) associated cervical neoplasm that is thought to derive from mesonephric / Wolffian remnants
Essential features
- Shows a variety of morphologic patterns, presenting a risk of misdiagnosis
- GATA3+, p16-, ER- immunoprofile
- Frequently harbors KRAS mutations
Terminology
- Mesonephric carcinoma of the cervix
- Mesonephric carcinosarcoma of the cervix
- Mesonephric adenocarcinoma of the cervix
ICD coding
- ICD-10: C53.9 - malignant neoplasm of cervix uteri, unspecified
Epidemiology
- Rare, accounts for < 1% of all cervical adenocarcinomas (Am J Surg Pathol 2018;42:214)
- Mean age at diagnosis of 52 in one literature review (Gynecol Oncol Rep 2016;17:7)
- Unassociated with human papillomavirus (HPV) (Am J Pathol 2000;157:1055, Histopathology 2010;57:342)
Sites
- Cervix, more common in lateral walls
- Rarely uterine corpus, ovary, vagina
Pathophysiology
- Unknown at this time
Etiology
- Thought to derive from mesonephric duct remnants / hyperplasia (Mod Pathol 2015;28:1504)
- Mesonephric remnants are found in the lateral cervical wall in up to 22% of adult uterine cervices (Int J Gynecol Pathol 2002;21:327)
Clinical features
- Most common clinical presentation is abnormal vaginal bleeding
- Can be detected by abnormal cervical cytology but less frequently than cervical squamous cell carcinoma (BMJ Case Rep 2012 Dec 10;2012)
- Can also present as cervical mass or incidentally
Diagnosis
- Cervical biopsy, endometrial curettage or hysterectomy specimen
Prognostic factors
- 70% diagnosed at stage IB (Gynecol Oncol Rep 2016;17:7)
- Stage I: recurrence rate 32%, mean recurrence interval 24 months, mean overall survival 50 months (Gynecol Oncol Rep 2016;17:7)
- Spindle component may portend a worse outcome (Gynecol Oncol Rep 2016;17:7)
Case reports
- 48 year old woman with lung metastasis; tumor showed mutations in KRAS and CTNNB1 and gain of 1q (Diagn Pathol 2019;14:71)
- 51 year old woman with neoadjuvant chemotherapy and radical surgery (Tumori 2016;102:S82)
- 59 year old woman with mesonephric carcinosarcoma of the cervix who presented with tumor rupture (Int J Clin Exp Pathol 2014;7:1212)
- 64 year old woman with mesonephric adenocarcinoma of the cervix (BMJ Case Rep 2012 Dec 10;2012)
- 64 year old women with cytologic findings (Cytopathology 2013;24:129)
- 2 patients with mesonephric carcinosarcomas of the cervix and vagina (Int J Gynecol Pathol 2014;33:624)
Treatment
- Mainstay of treatment is hysterectomy with or without bilateral salpingo-oopherectomy and pelvic lymph node dissection
- Roles of neoadjuvant or adjuvant chemotherapy and radiation therapy remain unclear
Microscopic (histologic) description
- Many histologic patterns, often varying between tumors and between different microscopic fields of the same tumor (Am J Surg Pathol 1995;19:1158, Int J Gynecol Pathol 2002;21:327)
- Tubular pattern: most common; consists of small back to back tubules lined by cuboidal cells, containing intraluminal colloid-like secretions that stain positive for PASD and mucicarmine
- Ductal pattern: glands lined by columnar cells, reminiscent of endometrioid adenocarcinoma
- Sarcomatoid: stromal component of mesonephric carcinosarcomas usually consists of sheets of spindled cells but heterologous elements can also be seen (Am J Surg Pathol 1995;19:1158)
- Other reported histologic patterns: retiform, sex cord-like, papillary, hobnail, glomeruloid, solid, sieve-like
- Mild to moderately pleomorphic nuclei with inconspicuous to prominent nucleoli (Am J Surg Pathol 1995;19:1158)
- Mitotic figures can be rare or readily apparent (Am J Surg Pathol 1990;14:1100, Am J Surg Pathol 1995;19:1158)
- Often deeply infiltrative but may show little desmoplasia (Am J Surg Pathol 1990;14:1100)
- Often associated with peripheral mesonephric remnants or mesonephric hyperplasia
Microscopic (histologic) images
Contributed by Lynn Hoang, M.D.
Cytology description
- Clusters of epithelial cells in tubular, cribriform and sheet-like proliferations (Cytopathology 2013;24:129)
- Round to oval, occasionally angulated, small to medium sized nuclei with mild to moderate atypia and increased nuclear to cytoplasmic ratio (Cytopathology 2013;24:129)
- Intraluminal eosinophilic material (Cytopathology 2013;24:129)
- Infrequently detected by cervical cytology compared to cervical squamous cell carcinoma (BMJ Case Rep 2012 Dec 10;2012)
Positive stains
- GATA3: nuclear staining, > 85% (Am J Surg Pathol 2015;39:1411, Am J Surg Pathol 2018;42:1596)
- Caveat: solid / spindled lesions show loss of GATA3 staining (Am J Surg Pathol 2018;42:1596)
- PAX8: nuclear staining, > 88% (Am J Surg Pathol 2012;36:799, Am J Surg Pathol 2018;42:1596)
- TTF1: nuclear staining (Am J Surg Pathol 2012;36:799, Am J Surg Pathol 2018;42:1596)
- Positive in mesonephric-like carcinoma of the ovary and uterus; can have inverse staining pattern with GATA3 (Am J Surg Pathol 2018;42:1596)
- CD10: luminal staining, > 70% (Am J Surg Pathol 2012;36:799, Am J Surg Pathol 2018;42:1596)
- Calretinin: nuclear and cytoplasmic staining, 57 - 88% (Am J Surg Pathol 2001;25:379, Am J Surg Pathol 2004;28:601, Am J Surg Pathol 2012;36:799, Am J Surg Pathol 2018;42:1596)
- HNF1β: nuclear staining, 38 - 64% (Am J Surg Pathol 2012;36:799, Appl Immunohistochem Mol Morphol 2019 Jul 29 [Epub ahead of print])
- Androgen receptor: nuclear staining, 33% (Am J Surg Pathol 2001;25:379)
Negative stains
- Estrogen receptor / ER: nuclear staining (Am J Surg Pathol 2018;42:1596, Am J Surg Pathol 2001;25:379)
- Caveat: positive in a subset of cases (Am J Surg Pathol 2012;36:799, Appl Immunohistochem Mol Morphol 2019 Jul 29 [Epub ahead of print])
- Progesterone receptor / PR: nuclear staining (Am J Surg Pathol 2001;25:379)
- p16: usually negative; positive (nuclear and cytoplasmic block staining) in subset of cases but does not correlate with HPV status (Am J Surg Pathol 2012;36:799, Histopathology 2010;57:342)
- Napsin A: usually negative; focally positive (cytoplasmic granular staining) in a subset of cases (Appl Immunohistochem Mol Morphol 2019 Jul 29 [Epub ahead of print])
- AMACR: usually negative; focally positive (cytoplasmic staining) in a subset of cases (Appl Immunohistochem Mol Morphol 2019 Jul 29 [Epub ahead of print])
Electron microscopy description
- One case report demonstrated the presence of cytotelolysomes (Pathol Res Pract 2008;204:671)
- A distinctive feature of mesonephric epithelium (Int J Gynecol Pathol 1985;4:245)
Molecular / cytogenetics description
- Majority associated with mutations in KRAS and gain in 1q, in contrast to their HPV associated cervical adenocarcinoma counterparts (Mod Pathol 2015;28:1504)
- Mutations in NRAS, chromatin remodeling gene mutations (ARID1A, ARID1B, SMARCA4), BCOR, TP53 have also been described (Mod Pathol 2015;28:1504)
- Mesonephric hyperplasia does not harbor KRAS or NRAS mutations (Histopathology 2017;71:1003)
Sample pathology report
- Uterus (with cervix), fallopian tubes and ovaries, total hysterectomy and bilateral salpingo-oophorectomy:
- Mesonephric adenocarcinoma (see comment and synoptic report)
- Comment: This tumor demonstrates several distinct histologic patterns (tubules, glandular and papillary regions) with associated peripheral mesonephric remnants. By immunohistochemistry, this tumor shows diffuse and strong expression of GATA3 and PAX8 and no expression of ER. Taken together, these features are diagnostic of mesonephric adenocarcinoma of the cervix.
Differential diagnosis
- Endometrioid endometrial adenocarcinoma:
- Also shows a variety of histologic patterns
- ER+, GATA3-, CD10- (Am J Surg Pathol 2018;42:1596)
- Clear cell carcinoma:
- Can also show solid, papillary and tubulocystic morphologic patterns
- Both are ER- and variably HNF1β+
- AMACR+, napsin A+ (Appl Immunohistochem Mol Morphol 2019 Jul 29 [Epub ahead of print])
- High grade serous carcinoma:
- Mutant p53 pattern, GATA3-, CD10- (Mod Pathol 2015;28:1504, Int J Gynecol Pathol 2014;33:624, Am J Surg Pathol 2018;42:1596)
- Mesonephric hyperplasia:
- Rarely shows atypia or mitoses and does not have back to back glandular crowding
- Does not harbor KRAS mutations (Histopathology 2017;71:1003)
- Malignant mixed Müllerian carcinoma:
- Both have variable GATA3 expression
- Mutant p53 pattern (Am J Surg Pathol 2018;42:1596)
Board review style question #1
Board review style answer #1
B. PAX8+, ER-, GATA3+, napsin A-.
Mesonephric carcinomas of the cervix are typically PAX8+, ER-, GATA3+ and napsin A-.
Comment Here
Reference: Mesonephric adenocarcinoma
Comment Here
Reference: Mesonephric adenocarcinoma
Board review style question #2
Which mutation is frequently harbored by mesonephric adenocarcinomas of the cervix?
- BRAF
- BRCA
- KRAS
- RET
Board review style answer #2
C. KRAS. Mesonephric adenocarcinomas of the cervix frequently harbor KRAS mutations.
Comment Here
Reference: Mesonephric adenocarcinoma
Comment Here
Reference: Mesonephric adenocarcinoma