Abstract
Mesonephric adenocarcinoma is a rare tumor type that is usually found in areas where the Wolffian duct was present during the fetal period. We report a case of mesonephric adenocarcinoma of the uterine corpus in a 66-year-old woman who presented with vaginal bleeding. Pelvic magnetic resonance imaging revealed a 2.7-cm-sized irregular thickening and enhancement of the uterine body. The diagnosis following endometrial curettage biopsy was endometrioid adenocarcinoma, and the patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. The tumor was composed of small tubular and ductal components, and a retiform appearance was also observed in the deeper areas. The tumor cells were immunopositive for cytokeratin, vimentin, CD10 with a luminal staining pattern, PAX2, and PAX8, and immunonegative for estrogen receptor and progesterone receptor, which was consistent with tumor of mesonephric origin. Mesonephric neoplasms reveal relatively low-grade nuclear feature, characteristic immunoprofiles (immunonegative for ER and PR, and immunopositive for CD10, PAX2, PAX8, and GATA3), and unique tumor location (myometrium), whereas Müllerian neoplasms such as endometrial adenocarcinoma show various morphology, immunopositivity for ER and PR, and primarily endometrial location. As described above, an integration of the clinical features, morphologic characteristics, and immunohistochemical profiles is needed to make a diagnosis.
Introduction
Mesonephric remnants are commonly found in the epoophoron, paraoophoron, and uterine cervix. Lesions arising in mesonephric duct remnants could be classified as mesonephric remnants, mesonephric hyperplasia, and mesonephric adenocarcinoma. 1 Mesonephric adenocarcinoma is a rare tumor type of the female genital tract, especially the uterine corpus. Histomorphologically, it is characterized by cuboidal epithelial-lined ducts and tubules, which frequently contain eosinophilic colloid-like material. Mesonephric adenocarcinoma also shows diverse growth patterns, such as tubular, ductal, papillary, and retiform patterns. Depending on the growth pattern, it can be confused with endometrial adenocarcinoma and uterine tumors resembling ovarian sex cord tumors (UTROSCT). Since Wolffian and Müllerian neoplasms can reveal a variety of histomorphology and immunophenotype depending on the differentiation, a combination of clinical data, such as tumor location, characteristic histomorphologic features, and immunohistochemical profiles, is needed to make a diagnosis.
Case Presentation
A 66-year-old woman presented with a 1-month history of vaginal bleeding and was referred for further evaluation and treatment. She had no medical history of hormonal substitution. Laboratory test results, including blood cell counts and tumor marker such as CA-125, were within the normal ranges. Pelvic magnetic resonance imaging revealed a 2.7-cm-sized irregular thickening and enhancement of the uterine body with diffusion restriction in the left anterolateral aspect. This lesion invaded more than half of the myometrium but not the cervix. Endometrial curettage biopsy showed exclusively small tubular and ductal (glandular) cells with a back-to-back arrangement. A diagnosis of endometrioid adenocarcinoma was made, and the patient underwent a total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection.
Macroscopically, the mass was located on the myometrium and extended into the endometrium. It was a relatively well-marginated nodular mass measuring 2.7 × 2.2 cm at its greatest dimension. It was tan in color and rubbery in consistency. There was no evidence of hemorrhage or necrosis.
Microscopically, the tumor was mainly composed of small tubular and ductal components, which gave it an endometrioid adenocarcinoma-like appearance in a low-power view, as evident in the biopsy. In addition to tubular or ductal patterns, papillary, retiform, and glomeruloid features were also noted in the deeper areas (Figure 1A-D). Intensely hyaline eosinophilic material was rarely observed in the tubular lumen. Because the small tubular components revealed uniform and cuboidal lining cells without intervening stroma, the overall appearance of the lesion was a low-grade morphology and slightly different to well-differentiated endometrioid adenocarcinoma, which usually showed nuclear stratification. Overlying endometrial tissue was invaded by adenocarcinoma and adjacent nonneoplastic endometrium revealed atrophic change. Although adenomyosis was observed, mesonephric hyperplasia or remnant was not noted in the resected uterine corpus and cervix. Furthermore, neither squamous differentiation nor mucin was noted in the lesion. Mitotic figures were found at more than 10 per 10 high-power fields in the glandular areas.
Morphologic features. The tumor revealed predominantly tubular, papillary, retiform, and glomeruloid patterns (A-D). Cytologically, the tumor cells showed relatively low-grade nuclear morphology.
Immunohistochemically, the tumor cells were positive for cytokeratin (1:200; AE1/AE3, Dako), vimentin (1:100; V9, Dako), epithelial membrane antigen (EMA, 1:100; E29, Dako), CK7 (1:100; OV-TL 12/30, Dako), PAX2 (1:100; polyclonal, Invitrogen), PAX8 (1:100; MRQ50, Cell Marque), and TTF-1 (1:50; 8G7G3/1, Dako); and were focally positive for CD10 (1:80; 56C6, Dako) with a luminal staining pattern but not for estrogen receptor-α (ER-α, 1:50; 1D5, Dako), Progesterone receptor (PR, 1:50; PgR 636, Dako), androgen receptor (1:50; AR441, Dako), calretinin (1:50; DAK-Calret1, Dako), CEA (1:100; polyclonal, Dako), inhibin-α (1:50; R1, Dako), and p53 (1:50; DO-7, Dako) (Figure 2A-F). The endometrial glands in the adenomyosis were immunoreactive for ER, PR, PAX2, and PAX8 but not for CD10 and TTF-1.
The tumor cells were immunopositive for CK (A), vimentin (B), CD10 (C) with a luminal staining, PAX2 (D), and PAX8 (E). The tumor cells were immunonegative for estrogen receptor whereas stromal cells were immunoreactive (F).
Discussion
Mesonephric remnants are a vestige of the Wolffian ducts, which are commonly found in the broad ligament, mesosalpinx, ovarian hilum, uterine cervix, and lateral wall of the vagina. 2 The Wolffian system can be divided into an upper cephalic zone and a lower caudal zone. 3 The upper part includes the rete ovarii, epoophoron, and paraoophoron, which are derived from mesonephric tubules. The lower caudal area of the Wolffian system includes the lateral wall of the uterus, cervix, and vagina. Mesonephric lesions are characterized by cuboidal epithelial-lined ducts and tubules, which frequently contain eosinophilic colloid-like material in the areas where Wolffian duct vestiges are found. Lesions arising in the mesonephric duct remnants can be classified into mesonephric remnants, lobular mesonephric hyperplasia, mesonephric ductal hyperplasia, diffuse mesonephric hyperplasia, and mesonephric adenocarcinoma. 1 Sometimes it is difficult to differentiate between diffuse mesonephric hyperplasia and mesonephric adenocarcinoma as they both reveal a diffuse proliferation of small glands or tubules. Mesonephric adenocarcinoma reveals increasing degrees of cytologic and architectural atypia rather than diffuse florid hyperplasia, which comprise a back-to-back arrangement of glands, malignant cytologic features, perineural invasion, and vascular invasion.3,4
Mesonephric duct remnants are common and may be found in up to 22% of adult cervices and in up to 40% of those in newborns and children. 2 Nevertheless, malignant changes of a mesonephric origin are rare events and are usually observed in the cervix. Mesonephric adenocarcinoma is much rarer in the uterine corpus, and there are only 8 reports in the English literature (Table 1).4 -10 The age at diagnosis in these cases ranged from 33 to 81 years. Most of the patients presented with abnormal uterine bleeding. CA-125 levels were variable preoperatively, and most of the tumors were confined to the uterine wall (FIGO stage IB). The tumor sizes ranged from 2.5 to 14 cm at the greatest dimension. Microscopically, the tumor cells revealed various patterns, such as small tubular, retiform, ductal, and papillary patterns. Mesonephric remnants or lesions were observed in the cervix of 2 tumors, and sarcomatous components were noted in 4 tumors. Immunoreactivity for CD10 was seen in 5 of 6 tumors, with luminal positivity. The tumor cells were immunopositive for CK (4/4) and vimentin (7/8) but not for ER (0/6), PR (0/6), and CEA (0/4).
Clinicopathologic Features of Malignant Mesonephric Tumors in the Uterine Corpus.
Abbreviations: NA, not available; WNL, within normal limit; TH, total hysterectomy; BSO, bilateral salpingo-oophorectomy; PLND, pelvic lymph node dissection; DOD, dead of disease; NED, no evidence of disease; AWD, alive with disease.
Present case.
Tumor marker.
Luminal positivity.
When a mesonephric adenocarcinoma shows a prominent ductal or glandular pattern, endometrial adenocarcinoma, including endometrioid, serous, and clear cell types, must be excluded. Since mesonephric adenocarcinoma lacks prominent nuclear stratification, squamous differentiation, mucin, and immunoreactivity for ER and PR, endometrioid adenocarcinoma could be excluded. 8 Mesonephric adenocarcinoma could also reveal other microscopic patterns, such as retiform or tubular patterns. When clear cell carcinoma shows papillary and solid patterns and immunonegativity for ER and PR, histomorphologic findings such as prominent clear cell change, hobnail cells, and hyaline bodies or a hyalinized core are helpful, which are usually found in clear cell carcinoma. Serous adenocarcinomas with ductal, papillary, and adenoid cystic patterns could be excluded as they show high-grade nuclear atypia, a lack of eosinophilic intraluminal material, and a higher positive rate for p53, ER, and PR. 4 Immunopositivity for CD10 is infrequent in clear cell carcinomas and serous adenocarcinomas. Most Müllerian neoplasms originate from the endometrium and invading myometrium, whereas the epicenter of mesonephric adenocarcinoma is the myometrium where Wolffian vestiges are usually found. Mesonephric adenocarcinoma and UTROSCT share some histomorphologic and immunohistochemical features, such as relatively small monotonous round-to-oval nuclei, tubular and retiform growth patterns, and immunopositivity for CK, vimentin, calretinin, and CD10; however, UTROSCT are well-circumscribed masses and often admixed with a stromal component, which could reveal endometrial stromal or smooth muscle differentiation. They also often express ER, PR, smooth muscle actin, and desmin, which are not found in mesonephric adenocarcinoma.4,11
There have been several studies to investigate possible immunohistochemical markers of Wolffian tumors to differentiate from those of Müllerian system. Silver et al suggested that a combination of several antibodies with specific immunoprofiles could be useful for the differential diagnosis of mesonephric adenocarcinoma and Müllerian endometrioid adenocarcinoma. 12 They reported that mesonephric adenocarcinomas are immunopositive for epithelial markers, calretinin, and vimentin but not for ER and PR. Ordi et al demonstrated that CD10 expression is observed in Wolffian-derived structures and tumors in males and females, and it is a useful diagnostic marker for tumors with mesonephric differentiation. 6 Notwithstanding, some researchers showed that immunoreactivity for calretinin, CD10, and vimentin is lower than that found in previous studies. 4 Goyal et al proposed that a panel of PAX8, p16, and ER could be used to differentiate between mesonephric adenocarcinoma and Müllerian adenocarcinoma. 13 Recently, a few reports demonstrated that GATA3 can be a sensitive and specific marker of mesonephric lesions in the lower female genital tract.14 -16
In conclusion, we reported a rare case of mesonephric adenocarcinoma in the uterine corpus with distinct immunohistochemical profiles. Since there are many sharing morphologic or immunohistochemical features between Wolffian duct and Müllerian duct, the following data need to be integrated for diagnosis: (a) clinical information, such as tumor location; (b) histomorphologic features (the presence of mesonephric remnants or hyperplasia in the adjacent tissue, bland-looking nuclear morphology, and various growth patterns); and (c) immunopositivity to CD10, PAX2, PAX8, and GATA3, and immunonegativity to ER and PR.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.