Mesonephric proliferations of the female genital tract

doi:10.1016/j.pathol.2017.11.084

Pathology

Volume 50, Issue 2, February 2018, Pages 141-150

https://doi.org/10.1016/j.pathol.2017.11.084 Get rights and content

Summary

The mesonephric (Wolffian) duct regresses in females during embryological development. Remnants of this duct may persist typically along the lateral walls of the cervix, vagina, adnexa, and uterine corpus. These mesonephric epithelia may expand into hyperplastic proliferations and rarely form neoplasms. The spectrum of morphology, immunophenotype, clinical presentation, and molecular characteristics of mesonephric lesions is reviewed, with attention to distinction from entities in the differential diagnosis.

Section snippets

Origin of mesonephric proliferations (EMBRYOLOGY)

Mesonephric remnants are vestiges of the Wolffian (or ‘mesonephric’) ducts which regress during normal female development. The term ‘Wolffian’ has its origin from the name of the man who first described the embryology of the kidney (mesonephros) and its excretory ducts, Caspar Friedrich Wolff. Early in embryological development, a pair of Wolffian ducts exist adjacent to the Müllerian (or ‘paramesonephric’) ducts and connect the primitive kidney to the cloaca. During female development, in the

Clinical features

Mesonephric remnants are typically identified in asymptomatic women, most commonly in the lateral wall of the cervix (3 and 9 o'clock) in up to one-third of normal cervices,1, 2 but also may be present within the wall of the uterine corpus and vagina as well as the ovarian hilum (rete ovarii) and mesosalpinx.

The Gartner duct, which is also derived from the mesonephric duct, may become obstructed resulting in a Gartner duct cyst.³ Gartner cysts are uncommon (<1% of women⁴) and are typically

Clinical features

Mesonephric hyperplasia, much like remnants, is usually encountered as an incidental finding and may be associated with abnormal Papanicolaou smear; however, rarely may form a clinically evident mass.7, 17, 18, 19, 20, 21, 22, 23 In such cases, complete excision is required to exclude associated mesonephric carcinoma. If coexisting carcinoma is not identified, the prognosis is excellent with no further treatment necessary.

Gross characteristics

Mesonephric hyperplasia is typically not apparent on gross examination,

Clinical features

Mesonephric carcinomas may occur throughout the female genital tract, but the vast majority arise in the uterine cervix. Even so, this is a rare variant of cervical adenocarcinoma, representing <1% of all carcinomas at this site. Patients most commonly present with abnormal bleeding with or without an apparent mass on physical exam; some are identified by an abnormal Papanicolaou smear. These tumours occur over a wide age range, but rarely are diagnosed in patients under the age of 30 years.

Clinical features

Female adnexal tumour of probable Wolffian origin, or ‘FATWO’, as the name suggests, is a rare tumour of uncertain origin occurring in the adnexa, most commonly paratubal location. It has also been described in the ovary43, 44, 45 and paravaginal soft tissue.⁴⁶ The anatomical location and morphology of this tumour have led many to believe it is of mesonephric origin, which is supported to some degree by immunohistochemistry (discussed later). These tumours occur over a broad age range in women

Mesonephric-like adenocarcinomas of the female genital tract

Mesonephric-like adenocarcinomas have recently been described in the endometrium and ovary. Though not considered to be truly derived from mesonephric epithelia, they exhibit such striking similarity to mesonephric lesions, likely representing mesonephric differentiation, that they are included in this review.

References (84)

J.W. Huffman
Mesonephric remnants in the cervix
Am J Obstet Gynecol
(1948)
M.A. Jones et al.
Mesonephric remnant hyperplasia of the cervix: a clinicopathologic analysis of 14 cases
Gynecol Oncol
(1993)
C. Ersahin et al.
Mesonephric adenocarcinoma of the vagina with a 3-year follow-up
Gynecol Oncol
(2005)
J. Mirkovic et al.
Targeted genomic profiling reveals recurrent KRAS mutations and gain of chromosome 1q in mesonephric carcinomas of the female genital tract
Mod Pathol
(2015)
E.C. Pirog et al.
Prevalence of human papillomavirus DNA in different histological subtypes of cervical adenocarcinoma
Am J Pathol
(2000)
D. Atallah et al.
Malignant female adnexal tumor of probable Wolffian origin relapsing after pregnancy
Gynecol Oncol
(2004)
E. Rorat et al.
Clinical outcome for the female adnexal tumor of probable Wolffian origin
Int J Gynaecol Obstet
(1983)
T. Qiu et al.
Recurrent female adnexal tumor of probably Wolffian origin: a case report
Taiwan J Obstet Gynecol
(2017)
M. Devouassoux-Shisheboran et al.
Wolffian adnexal tumor, so-called female adnexal tumor of probable Wolffian origin (FATWO): immunohistochemical evidence in support of a Wolffian origin
Hum Pathol
(1999)
N. Conlon et al.
A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors
Mod Pathol
(2015)

V.D. Sneeden

Mesonephric lesions of the cervix; a practical means of demonstration and a suggestion of incidence

Cancer

(1958)

W.J. Blackwell et al.

Vaginal cysts of mesonephric duct origin (Gartner's duct cysts); report of 22 cases

Q Bull Northwest Univ Med Sch

(1955)

S.S. Rios et al.

Conservative treatment and follow-up of vaginal Gartner's duct cysts: a case series

J Med Case Rep

(2016)

J.P. Hoogendam et al.

Gartner's duct cyst

N Engl J Med

(2017)

A. Mackles et al.

Benign and malignant mesonephric lesions of the cervix

Cancer

(1958)

J.A. Ferry et al.

Mesonephric remnants, hyperplasia, and neoplasia in the uterine cervix. A study of 49 cases

Am J Surg Pathol

(1990)

K. Koopman et al.

Mesonephric remnant with seminal vesicle-like appearance in the cervix

Pathol Int

(2017)

S. Moritani et al.

Mitotic activity and apoptosis in endocervical glandular lesions

Int J Gynecol Pathol

(2002)

W.G. McCluggage et al.

CD10 and calretinin staining of endocervical glandular lesions, endocervical stroma and endometrioid adenocarcinomas of the uterine corpus: CD10 positivity is characteristic of, but not specific for, mesonephric lesions and is not specific for endometrial stroma

Histopathology

(2003)

J. Ordi et al.

CD10 expression in epithelial tissues and tumors of the gynecologic tract: a useful marker in the diagnosis of mesonephric, trophoblastic, and clear cell tumors

Am J Surg Pathol

(2003)

S.A. Silver et al.

Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings

Am J Surg Pathol

(2001)

B.E. Howitt et al.

GATA3 is a sensitive and specific marker of benign and malignant mesonephric lesions in the lower female genital tract

Am J Surg Pathol

(2015)

S.J. Cina et al.

Immunohistochemical staining for Ki-67 antigen, carcinoembryonic antigen, and p53 in the differential diagnosis of glandular lesions of the cervix

Mod Pathol

(1997)

R. Tambouret et al.

Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix: a manifestation of stage IIb endometrial carcinoma liable to be misinterpreted as an independent carcinoma or a benign lesion

Am J Surg Pathol

(2003)

K. Kalyanasundaram et al.

Diffusely infiltrating endometrial carcinomas with no stromal response: report of a series, including cases with cervical and ovarian involvement and emphasis on the potential for misdiagnosis

Int J Surg Pathol

(2010)

Y. Ayroud et al.

Florid mesonephric hyperplasia of the cervix: a report of a case with review of the literature

Int J Gynecol Pathol

(1985)

G. Lang et al.

The histogenetic origin of cervical mesonephric hyperplasia and mesonephric adenocarcinoma of the uterine cervix studied with immunohistochemical methods

Int J Gynecol Pathol

(1990)

J.D. Seidman et al.

Mesonephric hyperplasia of the uterine cervix: a clinicopathologic study of 51 cases

Int J Gynecol Pathol

(1995)

J. Mirkovic et al.

Cervical mesonephric hyperplasia lacks KRAS/NRAS mutations

Histopathology

(2017)

T. Welsh et al.

Mesonephric remnants or hyperplasia can cause abnormal pap smears: a study of three cases

Int J Gynecol Pathol

(2003)

A. Handoo et al.

Urethral obstruction due to lobular mesonephric hyperplasia of the vagina – a case report

Indian J Pathol Microbiol

(2005)

S. Casey et al.

Adenomyomas of the uterine cervix: report of a cohort including endocervical and novel variants [corrected]

Histopathology

(2015)

H. Ando et al.

Mesonephric adenocarcinoma of the uterine corpus with intracystic growth completely confined to the myometrium: a case report and literature review

Diagn Pathol

(2017)

H. Wu et al.

Mesonephric adenocarcinoma of the uterine corpus

Int J Clin Exp Pathol

(2014)

G. Bifulco et al.

A case of mesonephric adenocarcinoma of the vagina with a 1-year follow-up

Int J Gynecol Cancer

(2008)

Y. Wani et al.

Mesonephric adenocarcinoma of the uterine corpus: a case report and review of the literature

Int J Gynecol Pathol

(2008)

A. Marquette et al.

Second case of uterine mesonephric adenocarcinoma

Int J Gynecol Cancer

(2006)

J. Ordi et al.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation

Am J Surg Pathol

(2001)

P.B. Clement et al.

Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component

Am J Surg Pathol

(1995)

W.R. Hart et al.

Mesonephric adenocarcinomas of the cervix

Cancer

(1972)

M.S. Cavalcanti et al.

Mixed mesonephric adenocarcinoma and high-grade neuroendocrine carcinoma of the uterine cervix: case description of a previously unreported entity with insights into its molecular pathogenesis

Int J Gynecol Pathol

(2016)

C.J. Stewart et al.

Mesonephric adenocarcinoma of the uterine cervix with focal endocrine cell differentiation

Int J Gynecol Pathol

(1993)

Cited by (86)

A rare case of cervical mesonephric adenocarcinoma with right femur metastasis
2023, Asian Journal of Surgery
Mesonephric-like adenocarcinoma arising from endometrioid adenofibroma in a patient with in-utero exposure to diethylstilbestrol: A case report
2023, Case Reports in Women's Health
Mesonephric-like adenocarcinomas are newly classified rare neoplasms of the upper genital tract. They share identical features with mesonephric adenocarcinomas, with the exception of location. There is ongoing discussion on whether mesonephric-like adenocarcinomas arise from mesonephric remnants or are of Müllerian origin.
A 65-year-old woman (G2P1) presented with pelvic pain. Transvaginal ultrasound revealed multiple fibroids, and a robotic total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was planned. Intraoperatively, a complex mass with cystic and solid components was found on the left ovary, which also adhered to the rectosigmoid colon. Pathologic reports documented mesonephric-like adenocarcinoma that appeared to be arising in association with an endometrioid adenofibroma. This case is notable due to the patient's unique background of in-utero exposure to diethylstilbestrol (DES) and multiple gynecological malignancies within her mother, as well as the associated endometrioid adenofibroma. This case contributes evidence to two seemingly opposing theories of mesonephric-like adenocarcinoma histogenesis: the mesonephric remnant theory (supported by the patient's DES exposure), and the Müllerian theory (supported by the associated endometrioid adenofibroma).
Developmental Abnormalities of the Genitourinary System
2023, Avery's Diseases of the Newborn
Congenital anomalies of the kidney and urinary tract (CAKUTs) are found in around 0.5% of pregnancies and account for 20% to 30% of all prenatally diagnosed congenital anomalies. Despite prenatal diagnosis and aggressive treatment, they remain one of the main causes of renal failure in children. CAKUTs are responsible for about 2/3 of all children with chronic kidney disease in developed countries. Prenatal ultrasonography has dramatically changed the management of these conditions. Close to 90% of these conditions are detected prenatally. Many of these are asymptomatic and can be managed conservatively. It is imperative for pediatric providers caring for these patients to identify patients at risk of developing renal impairment.
Developmental genetics of the female reproductive tract
2023, Human Reproductive and Prenatal Genetics
Development of the female reproductive tract is a complex and dynamic process that involves a series of events, all of which are critical for proper tissue and organ differentiation, sex determination, and, ultimately, continuation of the species. Any deviation from this complex orchestration of signaling pathways comes with inevitable risk for errors and abnormalities. Shortly after the fetal to embryonic transition at about 7 weeks in humans, developing urogenital ridges contain bipotential gonads that later differentiate into ovaries and testes in females and males, respectively, Müllerian (paramesonephric) ducts that differentiate into uterus, fallopian tubes and vagina in females, and the Wolffian (mesonephric) ducts that differentiate into the male reproductive tract. This chapter will aim to elaborate the mechanisms of the signaling or transcriptional regulation pathways when known or surmized and how errors in these pathways contribute to congenital anomalies of the female reproductive tract.
Mesonephric Adenocarcinoma and Mesonephric-like Adenocarcinoma of the Urinary Tract
2023, Modern Pathology
Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other anatomical locations that harbor mesonephric remnants. In contrast, mesonephric-like adenocarcinoma (MLA) is thought to arise from Müllerian origin without an association with mesonephric remnants. The current case series characterizes 4 cases of MA arising in the urinary bladder (1 woman and 3 men), 1 case of MA in the perirenal region (woman), and 1 case of MLA in the ureter (woman). All cases displayed morphologic features similar to MA of the uterine cervix and MLA of the ovary and endometrium, characterized by predominant tubular and focal glandular/ductal architecture. Mesonephric remnants in the bladder wall were closely associated with adjacent MA in cases 1 and 4. MLA in case 6 was associated with mesonephric-like proliferations and endometriosis. All cases (6/6) were diffusely positive for Pax8, and all displayed a luminal pattern of CD10 staining, except case 4 for which CD10 immunostain was not available for review. Gata3 was either focally positive (cases 1, 2, and 6), negative (case 3), or diffusely positive (case 5). TTF-1 was diffusely expressed in cases 1 and 3 and negative in cases 2, 5, and 6. Although a KRAS G12C somatic mutation was detected in case 6, hotspot mutations in KRAS, NRAS, and PIK3CA were not present in other tested cases. Our study demonstrates that MAs and MLAs of the urinary tract share similar histopathogenesis, morphology, and immunophenotype to their counterparts in the female genital tract. We propose that, in the urinary tract, MA might be classified as a distinctive tumor that arises from mesonephric remnants or presumed Wolffian origin if they are not related to Müllerian-type precursors. The tumor displaying similar morphology and immunoprofile to MA but associated with Müllerian-type precursors should be classified as MLA.
Somatic mutation analysis of Mesonephric-Like adenocarcinoma and associated putative precursor Lesions: Insight into pathogenesis and potential molecular treatment targets
2022, Gynecologic Oncology Reports
Mesonephric-like adenocarcinoma (MLA) is a recently described histologic tumor subtype of the Müllerian tract. MLA can arise in association with Müllerian lesions that share common mutations. We report three MLAs and hypothesize that concurrent endometriosis and cystadenofibroma with focal borderline changes might also carry common mutations.
We searched “mesonephric” in our database from 2015 to mid-2021 to retrieve MLA cases. Somatic mutation analysis was performed on tumors and on associated benign proliferative lesions. All MLAs (2 ovarian and 1 uterine) harbored KRAS G12D or G12 V mutations. A PIK3CA alteration (H1047Q) was detected in one MLA and in the associated cystadenofibroma with focal borderline changes. The molecular profile of MLA-associated Müllerian lesions (endometriosis and seromucinous cystadenofibroma with focal borderline changes) was similar to concurrent adenocarcinoma. However, tumor contamination could not be excluded in the endometriotic lesion. Patients presented at various stages, with no evidence of post-operative recurrence after 15 months (FIGO IC) and 33 months (FIGO IIA2). One patient (FIGO IIIA1) died of disease 32 months after surgery.
KRAS mutations commonly characterize MLA. At least some MLA-associated Müllerian lesions show MLA-like genetic profiles, suggesting a precursor role. As far as we are aware, we describe for the first time in MLA the potentially actionable H1047Q variant of PIK3CA.

View all citing articles on Scopus

View full text

Gynaecological pathologyMesonephric proliferations of the female genital tract

Summary

Section snippets

Origin of mesonephric proliferations (EMBRYOLOGY)

Clinical features

Clinical features

Gross characteristics

Clinical features

Clinical features

Mesonephric-like adenocarcinomas of the female genital tract

Am J Obstet Gynecol

Gynecol Oncol

Gynecol Oncol

Mod Pathol

Am J Pathol

Gynecol Oncol

Int J Gynaecol Obstet

Taiwan J Obstet Gynecol

Hum Pathol

Mod Pathol

Mesonephric lesions of the cervix; a practical means of demonstration and a suggestion of incidence

Cancer

Vaginal cysts of mesonephric duct origin (Gartner's duct cysts); report of 22 cases

Q Bull Northwest Univ Med Sch

Conservative treatment and follow-up of vaginal Gartner's duct cysts: a case series

J Med Case Rep

Gartner's duct cyst

N Engl J Med

Benign and malignant mesonephric lesions of the cervix

Cancer

Mesonephric remnants, hyperplasia, and neoplasia in the uterine cervix. A study of 49 cases

Am J Surg Pathol

Mesonephric remnant with seminal vesicle-like appearance in the cervix

Pathol Int

Mitotic activity and apoptosis in endocervical glandular lesions

Int J Gynecol Pathol

CD10 and calretinin staining of endocervical glandular lesions, endocervical stroma and endometrioid adenocarcinomas of the uterine corpus: CD10 positivity is characteristic of, but not specific for, mesonephric lesions and is not specific for endometrial stroma

Histopathology

CD10 expression in epithelial tissues and tumors of the gynecologic tract: a useful marker in the diagnosis of mesonephric, trophoblastic, and clear cell tumors

Am J Surg Pathol

Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings

Am J Surg Pathol

GATA3 is a sensitive and specific marker of benign and malignant mesonephric lesions in the lower female genital tract

Am J Surg Pathol

Immunohistochemical staining for Ki-67 antigen, carcinoembryonic antigen, and p53 in the differential diagnosis of glandular lesions of the cervix

Mod Pathol

Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix: a manifestation of stage IIb endometrial carcinoma liable to be misinterpreted as an independent carcinoma or a benign lesion

Am J Surg Pathol

Diffusely infiltrating endometrial carcinomas with no stromal response: report of a series, including cases with cervical and ovarian involvement and emphasis on the potential for misdiagnosis

Int J Surg Pathol

Florid mesonephric hyperplasia of the cervix: a report of a case with review of the literature

Int J Gynecol Pathol

The histogenetic origin of cervical mesonephric hyperplasia and mesonephric adenocarcinoma of the uterine cervix studied with immunohistochemical methods

Int J Gynecol Pathol

Mesonephric hyperplasia of the uterine cervix: a clinicopathologic study of 51 cases

Int J Gynecol Pathol

Cervical mesonephric hyperplasia lacks KRAS/NRAS mutations

Histopathology

Mesonephric remnants or hyperplasia can cause abnormal pap smears: a study of three cases

Int J Gynecol Pathol

Urethral obstruction due to lobular mesonephric hyperplasia of the vagina – a case report

Indian J Pathol Microbiol

Adenomyomas of the uterine cervix: report of a cohort including endocervical and novel variants [corrected]

Histopathology

Mesonephric adenocarcinoma of the uterine corpus with intracystic growth completely confined to the myometrium: a case report and literature review

Diagn Pathol

Mesonephric adenocarcinoma of the uterine corpus

Int J Clin Exp Pathol

A case of mesonephric adenocarcinoma of the vagina with a 1-year follow-up

Int J Gynecol Cancer

Mesonephric adenocarcinoma of the uterine corpus: a case report and review of the literature

Int J Gynecol Pathol

Second case of uterine mesonephric adenocarcinoma

Int J Gynecol Cancer

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation

Am J Surg Pathol

Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component

Am J Surg Pathol

Mesonephric adenocarcinomas of the cervix

Cancer

Gynaecological pathology
Mesonephric proliferations of the female genital tract