Vulvar Lactating Adenoma: A Rare Representation of Mammary-Like Anogenital Glands

Introduction

Mammary-like anogenital glands are considered a normal constituent of the anogenital area rather than ectopic breast tissue as previously thought. ¹ The concept of “milk lines” is not supported by observations in human embryos, where the primordia of the mammary glands do not extend beyond the axillary-pectoral area. ² In addition, these mammary-like anogenital glands have epithelial components with eccrine or apocrine features. ² They often undergo transformation into mammary-like lesions, such as lactating glands, lactating adenoma, fibroadenoma, hidrocystoma, hidradenoma papilliferum, extramammary Paget's disease, and invasive adenocarcinoma. ² Similar to pectoral breast tissue, these mammary-like anogenital glands can be hormonally responsive. ³ Evidence of this hormonal responsiveness can be observed during the lactational changes of pregnancy and the breastfeeding period. ⁴ When they form mass lesions they are referred to as lactating adenomas. Although rare, vulvar lactating adenomas have been reported in the literature. ⁵

Patient Presentation

A 26-year-old woman presented to her OB-GYN 6 weeks after delivery by cesarean section with complaints of an enlarging lesion in her right vulva. This was described as a mildly tender 3 cm cystic mass in the right mid-labia minora. It was presumed to be a Bartholin's gland cyst and an incision with drainage was performed. The wound culture was unremarkable. A biopsy of the site showed small fragments of fibrous tissue with Bartholin's glands, suggestive of a Bartholin's cyst. Three weeks later, the patient returned with complaints of a painful, enlarging lesion at the same site. Since the initial biopsy, the raw pink area enlarged to a 3 × 1.5 cm exophytic, indurated lesion with an overlying 1 × 1 cm area of ulceration and a milky white discharge was expressed. A repeat biopsy showed an atypical proliferation of Bartholin gland duct-like structures in the stroma, with complete excision recommended to exclude malignancy. The patient subsequently underwent a simple partial right vulvectomy which revealed a lactating adenoma arising in mammary-like anogenital glands.

On microscopic examination, we noted irritated skin with underlying loosely packed glandular structures morphologically identical to terminal duct lobular units of the breast (Figure 1A). The glands demonstrated an inner ductal layer and an outer myoepithelial layer. A focus of fibroadenomatoid changes was present, with ductal lumens partially compressed by an expansion of the stroma (Figure 1B). On higher power, closely packed hyperplastic glands were separated by thin strands of connective tissue (Figure 1C). These glands appeared dilated, with ductal cells displaying a hobnail appearance. Secretory changes were also noted, including eosinophilic luminal material as well as intracytoplasmic vacuolization (Figure 1D). These changes were consistent with a diagnosis of a benign lactating adenoma. The ductal epithelial cells were positive for the breast markers GATA3 and estrogen receptor (ER) while negative for the gynecologic marker PAX8, supporting mammary-like differentiation. The myoepithelial markers p63 and calponin were positive at the periphery of the ducts.

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Figure 1.

Histology of vulvar lactating adenoma. (A) H&E—mammary-like anogenital glands in vulvar tissue, analogous to terminal duct lobular units of the breast. (B) H&E—benign ducts surrounded by proliferating stroma, resembling fibroadenomatoid changes. (C) H&E—hyperplastic glands separated by thin strands of connective tissue. (D) H&E—glands with hobnail appearance and intracytoplasmic vacuolization, reminiscent of lactational changes in the breast. Magnifications: A, 10 ×; B, 20 ×; C, 50 ×; and D, 200 ×.

Discussion

Vulvar lactating adenomas have been rarely reported in the literature. Ectopic lactating adenomas are known to vary in size (measuring from 3.0 cm up to 17 cm), appearance (cystic, solid, or multilobulated), and can even present with milk leakage.^4,5 They typically present as painful masses which grow larger during the pregnancy and breastfeeding period and subsequently shrink . ³ The mass may have both cystic and solid components, which can clinically be mistaken for a Bartholin's or other vulvovaginal cyst. A rapidly enlarging or predominantly solid mass can even be worrisome for malignancy.

Lactating adenomas of the vulva are microscopically identical to lactating adenomas of the breast and are composed of mammary-like glands with a bilayer of epithelium and myoepithelium. The glands are arranged in closely packed lobules which are separated by a delicate fibrovascular connective tissue meshwork. ⁵ These glands show classic lactational changes, including cuboidal luminal cells with small round nuclei and a hobnail appearance. Luminal eosinophilic material and intracytoplasmic vacuolization are also present.

In a small biopsy, lactational changes in mammary-like anogenital glands can be misdiagnosed as mammary carcinomas, Bartholin gland carcinoma, clear cell carcinoma of the GYN tract or kidney, or an adnexal tumor of the skin. A panel of immunostains including PAX8 (which is expressed in the GYN tract and kidney) and breast markers, such as GATA3, mammaglobin, and BRST-2 (PIP), can help identify the lesion as arising from mammary-like glands and exclude origin from other sites. ⁶ Mammary-like carcinomas of the vulva which may enter into the differential diagnosis include secretory carcinoma, cystic hypersecretory carcinoma, and acinic cell carcinoma. Stains for keratin 7 paired with myoepithelial markers, such as p63 and calponin, will highlight the bilayered epithelium and myoepithelium in lactational changes, excluding most mammary-like carcinomas. Secretory carcinoma can resemble lactational changes at low power, but its malignant nature can be recognized by its complex architecture with solid, cribriform, or microcystic growth patterns. ⁷ If any doubt remains, molecular testing for the characteristic balanced translocation t(12;15)(p13;q25) resulting in ETV6::NTRK3 gene fusion product can help to rule in a secretory carcinoma. ⁸ Acinic cell carcinomas closely resemble secretory carcinoma but contain coarse cytoplasmic granules which are positive for Periodic Acid-Schiff with diastase (PAS-D), ⁹ which are not seen in benign lactational changes. Cystic hypersecretory carcinomas are characterized by grossly visible cystic spaces filled with eosinophilic secretory material which can mimic lactational changes; however, carcinomas contain a greater degree of nuclear pleomorphism and hyperchromasia, beyond that which would be expected in a benign lesion. ¹⁰ The luminal eosinophilic secretions seen in secretory and cystic hypersecretory carcinomas are not present in lactational changes. A Bartholin gland carcinoma, which has multiple histological subtypes including squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC), can be distinguished from a lactating adenoma by its lack of a bilayered epithelium and myoepithelium as well as its distinctive morphology resembling SCCs and ACCs of other sites. ¹¹ A metastatic clear cell carcinoma of the GYN tract or kidney can be excluded using a panel of immunostains including PAX8 and HNF1 β (which is positive in GYN clear cell carcinomas). ⁶ The category of cutaneous adnexal tumors arising in the vulva includes varied entities such as hidradenocarcinoma, sebaceous carcinoma, and microcystic adnexal carcinoma. Significant immunohistochemical overlap between mammary-type glands and cutaneous adnexal glands exists, ¹ which adds additional complexity. The correct diagnosis can be made by recognizing the secretory changes which characterize mammary-like glands undergoing lactational changes, in addition to a lack of malignant features such as infiltration into deep tissues and adjacent structures, perineural or lymphovascular invasion, and nuclear atypia. Finally, it is prudent to rule out metastasis from the breast using a combination of a thorough clinical history and histomorphological features.

If lactational changes and potentially the presence of mammary-like anogenital glands are recognized in a vulvar biopsy specimen, the diagnosis of a benign lactating adenoma can be made. As a result, the patient can possibly avoid wide excision with any related complications such as infection, pain, or cosmetic defects.

Conclusion

To summarize, we present a rare lesion of a vulvar lactating adenoma arising in mammary-like anogenital glands. On skin biopsy, the morphologic features were worrisome for malignancy and the possibility of a Bartholin's gland carcinoma was considered. The mass was excised for definitive diagnosis and found to be a benign lactating adenoma, arising in mammary-like anogenital glands and associated with fibroadenomatoid changes. Although rare, this entity should be considered in pregnant and breastfeeding patients presenting with an enlarging lesion along their vulva. This entity can be a clinically and morphologically challenging diagnosis, as it can resemble a variety of benign and malignant conditions. Immunohistochemical stains can assist in the diagnosis of limited biopsy material.