Mesonephric Hyperplasia and Remnants

Case History:

A some around 35-year-old female patient, hysterectomy specimen received. Sections from cervix tissue show this type of morphology. No gross pathology seen.

Mesonephric Hyperplasia and Remnants

Histopathology:

• Few mesonephric tubules and ducts are lined by cuboidal epithelium with bland nuclei. Some tubules and ducts are also lined by flattened epithelium.
• Occasional tubules contain pink, homogeneous secretions.
• Some areas show striking mesonephric tubules and ducts proliferation in the deeper portion of the cervix (mimic an invasive adenocarcinoma). However, there is absence of complexity of glands, nuclear atypia, mitoses, and desmoplastic stromal response.
• Always note for ABSENCE of cilia, atypia and mucin.
• With efforts, vague lobular architecture is appreciated.
• Few large size ducts are surrounded by a proliferation of small glands.
• In this example, delayed fixation artifacts are also seen!!!!!! Always learn artifacts also along with pathology…

Practical Points of Pathoclinics:

1. In the female, due to absence of testosterone, mesonephric duct is regressed (which normally give rise to kidney in both sexes, while prostate seminal vesicles, epididymis in male) and so distal part of mesonephric remnants are commonly seen in female.  Mesonephric remnants are found in approximately 20-25% of cervical tissue in an adults, while newborn and children have more incidence of mesonephric remnants. Commonly, mesonephric remnant is an incidental asymptomatic finding. Rare cases may present with induration or nodularity.
2. Generous sampling of cervix, especially lateral wall, usually revel mesonephric remnants in good number of cases. Mesonephric remnants and mesonephric hyperplasia can occur in the vagina and present as a cervical erosion and an abnormal Pap smear.
3. Mesonephric hyperplasia and remnants are benign condition. Specific surgical treatment is not needed. However, inexperienced eye may catch these lesion as a well differentiated adenocarcinoma.
4. Histologic features of mesonephric remnants are:

• Mesonephric remnants typically found in the deeper lateral cervical walls but occasionally found in superficial location also.
• Mesonephric remnants appear as small tubules and glands or cyst like structures, in well-circumscribed lobular configuration with orderly distribution in most cases.
• Sometimes glandular and tubular structures are distributed around a central duct and diffuse pattern.
• Tubules and ducts are lined by a single layer of cuboidal cells or sometimes flattened cells, with small nuclei and lack of cilia. The lining epithelium can form small tufts in the lumen. Mild atypia may be seen. However, mucin, significant atypia and mitotic activity are not seen.
• Tubular or glandular lumen contain homogenous dense, colloid-like, eosinophilic PAS-positive secretions.
• PAS and mucicarmine are negative in cytoplasm.
• There is NO stromal response.

4. Mesonephric hyperplasia is explained by presence of multiple larger irregular loosely organized vague lobules of glands and tubules. Histological distinction of mesonephric hyperplasia from mesonephric remnants is vague and has no clinical importance.

5. On immunohistochemistry, EMA, calretinin, PAX2 (strong nuclear positivity), Bcl-2, androgen receptor, GATA3 and CD10 (apical and luminal positivity) are positive in mesonephric remnants and hyperplasia. p16 may be focally positive in cytoplasmic areas only without strong nuclear reactivity.

6. Practically important differential is endocervical adenocarcinoma. Mesonephric hyperplasia and remnants can mimic minimal deviation adenocarcinoma of the endocervix. Mesonephric remnants are lined with non-ciliated, low columnar, or cuboidal epithelium without complex glandular pattern, without surface mucosal involvement, rare occasional mitoses only and absence of stromal response. Also, absence of glycogen or mucin and negative carcinoembryonic antigen (CEA) stain and low Ki-67 index confirm the presence of benign mesonephric glands. p16 reactivity is strong and nuclear in case of endocervical adenocarcinoma, while it is weak patchy and cytoplasmic in mesonephric hyperplasia and remnants.

7. Another close differential is mesonephric adenocarcinoma. Mesonephric remnants may become extensively hyperplastic with florid, tubular and glandular proliferation with further deep extensive involvement of the cervix, can mimic the mesonephric adenocarcinoma. Close evaluation of architectural abnormalities (complexity of glands and solid pattern), more than subtle atypia and frequent mitotic activity should be done. Also patient with mesonephric carcinoma usually present with a cervical mass effect and related symptoms. Also, higher Ki-67 index favors mesonephric adenocarcinoma. GATA-3 is also patchy in mesonephric carcinoma.

8. Prominent tubular morphology mixed with round glands of mesonephric remnants can mimic endometrial carcinoma. However, presence of irregular haphazard and infiltrative pattern of tubular glands with nuclear atypia favors endometrial carcinoma. In addition, presence of papillary and solid growth patterns, clear glycogen-rich cytoplasm and few mitotic figures also pointing towards endometrial carcinoma rather than mesonephric remnants and hyperplasia.