Mesonephric adenocarcinoma

Cervix

Adenocarcinoma

Authors: Jennifer Pors, M.D., Lynn Hoang, M.D.

Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 3 September 2019

Minor changes: 10 March 2020

Copyright: 2007-2020, PathologyOutlines.com, Inc.

PubMed Search: Mesonephric adenocarcinoma[TIAB] cervix

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Table of Contents

Cite this page: Pors J, Hoang L. Mesonephric adenocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixmesonephricadeno.html. Accessed August 8th, 2020.

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

Radiology images

Images hosted on other servers:

MRI cervical tumor

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.

Mix of morphologic patterns

Tubular pattern

Tubular pattern with adjacent mesonephric remnants

Tubular pattern with desmoplasia

Ductal
(pseudoendometrioid)
pattern

Ductal pattern

Papillary pattern

Sieve-like pattern

Solid pattern

Mesonephric carcinosarcoma

GATA3+

ER-

TTF1+

CD10+

Wild type p53

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)
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)
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)
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)
NapsinA: 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+, napsinA+ (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

Which immunohistochemical staining profile would you expect in the cervical neoplasm depicted in this image?

PAX8-, ER-, GATA3+, AMACR+
PAX8+, ER-, GATA3+, napsinA-
PAX8+, ER+, GATA3-, napsinA-
PAX8+, ER-, napsinA+, AMACR+

Board review answer #1

B. PAX8+, ER-, GATA3+, napsinA-. Mesonephric carcinomas of the cervix are typically PAX8+, ER-, GATA3+ and napsinA-.

Reference: Mesonephric adenocarcinoma

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Board review style question #2

Which mutation is frequently harbored by mesonephric adenocarcinomas of the cervix?

BRAF
BRCA
KRAS
RET

Board review answer #2

C. KRAS. Mesonephric adenocarcinomas of the cervix frequently harbor KRAS mutations.

Reference: Mesonephric adenocarcinoma

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