Understanding Penile Fibroadenoma and Anogenital Mammary-Like Glands

Anogenital mammary-like glands, abbreviated as AGMLG, represent normal anatomical structures distributed along the anogenital sulcus. Although clinicians historically classified these tissues as ectopic mammary remnants along the embryologic milk line, researchers now recognize them as specialized cutaneous adnexal glands. Consequently, these structures possess the remarkable capacity to develop the entire spectrum of benign and malignant pathologies normally encountered in the breast. A recently documented clinical case describes a penile fibroadenoma arising from AGMLG in a twenty-nine-year-old transgender woman. The patient presented with a progressively enlarging genital nodule while receiving cross-sex feminizing hormone therapy. Therefore, this extraordinary finding underscores how exogenous estrogens can stimulate hormone-sensitive genital structures. Primary care physicians, urologists, dermatologists, and surgical pathologists must maintain awareness of these rare fibroepithelial neoplasms. Because male genital anatomy rarely exhibits overt mammary differentiation, such lesions can easily lead to diagnostic confusion. Furthermore, understanding the cellular biology and presentation of these neoplasms facilitates prompt surgical care and avoids excessive tissue excision.

Embryology and Distribution of Anogenital Mammary-Like Glands

The embryological origin of anogenital mammary-like glands has sparked considerable scientific debate over several decades. Early anatomists proposed that AGMLG represented caudal persistence of the embryonic mammary ridge, also known as the milk line. However, modern histological and immunohistochemical investigations confirm that these specialized structures represent normal constituents of the anogenital region in both sexes. In genetic females, AGMLG are frequently situated along the interlabial sulcus, labia majora, and perineum. Conversely, in individuals with male genital anatomy, these glands occur infrequently along the penile shaft, scrotum, and perianal region. Histologically, normal AGMLG exhibit tubuloalveolar units lined by an inner luminal epithelial layer and an outer myoepithelial layer. In addition, these specialized glands express estrogen receptors, progesterone receptors, and androgen receptors. Because they contain functional hormone receptors, they respond dynamically to physiological endocrine changes. Consequently, puberty, pregnancy, exogenous hormone exposure, or gender-affirming hormone therapy can trigger prominent hyperplastic or neoplastic changes within these dormant tissues.

Role of Feminizing Hormone Therapy in Neoplasm Growth

Feminizing hormone therapy remains a fundamental cornerstone of medical gender transition for many transgender women. This pharmacological regimen typically incorporates exogenous estrogens combined with potent anti-androgens to promote female secondary sexual characteristics. Specifically, systemic estrogens stimulate ductal elongation, lobuloalveolar proliferation, and stromal expansion in native breast tissue. Similarly, exogenous estrogens exert strong biological effects on peripheral anogenital mammary-like glands. In the documented clinical case, long-term exposure to cross-sex hormones directly stimulated the proliferation of hormone-responsive glandular and stromal cells within the penis. As a result, the patient experienced the gradual growth of a well-demarcated subcutaneous mass. Furthermore, the withdrawal of androgen signaling eliminates the inhibitory tone that normally keeps male adnexal structures quiescent. Therefore, medical professionals must recognize that hormone therapy can induce benign breast-like tumors in anatomically unusual locations. Clinicians should reassure patients that such enlargements represent benign proliferative processes rather than malignant transformations, provided proper diagnostic confirmation occurs.

Histopathological and Immunohistochemical Hallmarks

Microscopic evaluation serves as the definitive diagnostic standard for identifying a penile fibroadenoma. On gross examination, the excised nodule appears as a well-circumscribed, lobulated, grayish-white mass with a firm consistency. Histological sections reveal a classic biphasic fibroepithelial architecture characterized by proliferating ductal structures surrounded by fibrous stroma. Moreover, the epithelial elements demonstrate an intracanalicular or pericanalicular growth pattern, where stromal expansion compresses glandular lumens into linear clefts. The glandular structures maintain a normal bilayered arrangement consisting of inner luminal epithelial cells and outer basal myoepithelial cells. Importantly, neither the epithelial nor the stromal components show cellular atypia, pleomorphism, or abnormal mitotic figures. Immunohistochemical staining provides indispensable confirmation of mammary lineage. Specifically, the luminal epithelium demonstrates strong nuclear positivity for estrogen receptors, progesterone receptors, and gross cystic disease fluid protein fifteen. Meanwhile, p63, calponin, and smooth muscle actin highlight the intact myoepithelial layer, decisively confirming the benign nature of the lesion.

Differential Diagnosis and Diagnostic Challenges

Evaluating solitary penile and perineal masses presents significant clinical and histopathological challenges for practitioners. Because genital fibroadenomas remain exceptionally uncommon in male anatomy, clinicians often suspect more frequent conditions first. For instance, the differential diagnosis includes epidermal inclusion cysts, steatocystomas, hidradenoma papilliferum, syringomas, and leiomyomas. Additionally, surgical oncologists must carefully rule out malignant entities such as primary cutaneous adenocarcinoma, squamous cell carcinoma, and extramammary Paget disease. From a pathological standpoint, distinguishing a fibroadenoma from a benign phyllodes tumor is particularly essential. Although both are biphasic fibroepithelial tumors, phyllodes tumors exhibit exaggerated leaf-like architecture, increased stromal cellularity, and focal stromal hypercellularity. Furthermore, pathologists must exclude pseudoangiomatous stromal hyperplasia, which can present as an isolated perineal nodule. Therefore, adequate tissue sampling and comprehensive immunohistochemical evaluation are crucial for establishing an accurate diagnosis. Misidentifying these lesions as invasive malignancies could lead to unnecessarily radical surgery, whereas precise histological assessment ensures conservative management.

Clinical Management and Therapeutic Implications

The standard therapeutic approach for symptomatic or enlarging lesions of anogenital mammary-like glands consists of complete surgical excision. Because penile fibroadenomas represent entirely benign neoplasms, conservative local resection with clear surgical margins provides definitive cure. Consequently, local recurrence remains exceedingly rare following complete removal. Surgeons should prioritize tissue preservation to maintain optimal cosmetic and functional outcomes in delicate genital tissues. Moreover, routine adjustment or discontinuation of feminizing hormone therapy is usually unnecessary once the lesion is excised. Multidisciplinary coordination between endocrinologists, dermatologists, urologists, and pathologists ensures holistic patient care. Additionally, clinicians should provide reassuring counseling to transgender patients, explaining that benign breast pathologies can occasionally manifest outside typical anatomical boundaries. Periodic routine clinical follow-up is recommended to monitor wound healing and inspect for any rare secondary lesions. Ultimately, growing clinical awareness of AGMLG-derived pathology enables healthcare teams to deliver compassionate, accurate, and evidence-based clinical management.

Frequently Asked Questions

What causes a penile fibroadenoma to develop in transgender women?

A penile fibroadenoma develops from pre-existing anogenital mammary-like glands situated in genital subcutaneous tissues. When a transgender woman receives feminizing hormone therapy, exogenous estrogens and anti-androgens directly stimulate these hormone-receptor-positive structures. Consequently, this persistent hormonal exposure triggers localized stromal and epithelial proliferation analogous to classic breast fibroadenoma growth. Thus, the quiescent glands enlarge over time into a distinct, benign palpable nodule.

How do pathologists distinguish penile fibroadenoma from other genital neoplasms?

Pathologists distinguish a penile fibroadenoma by identifying its characteristic biphasic architecture composed of compressed glandular ducts and paucicellular stroma without atypia. Furthermore, immunohistochemical staining confirms mammary differentiation through strong estrogen and progesterone receptor positivity in luminal cells. Meanwhile, markers like p63 and calponin highlight a preserved, continuous myoepithelial layer, effectively ruling out invasive carcinomas, hidradenomas, and cellular phyllodes tumors.

What is the standard treatment approach for lesions arising from anogenital mammary-like glands?

The standard therapeutic approach involves conservative complete surgical excision with clear margins. Because these fibroepithelial lesions are entirely benign, local resection offers definitive cure without requiring radical surgery. Moreover, patients typically do not need to discontinue or modify their gender-affirming feminizing hormone therapy. Postoperative recovery is generally uneventful, and recurrence rates remain exceptionally low following adequate surgical removal.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. Consult qualified healthcare professionals for diagnosis and treatment. Refer to the latest local and national guidelines for clinical practice.

References

1. Gomolin T et al. Penile Fibroadenoma Arising From Anogenital Mammary-Like Glands in a Transgender Woman. J Cutan Pathol. 2026 Aug 26. doi: 10.1111/cup.70189. PMID: 42643118.


2. Kazakov DV, Spagnolo DV, Kacerovska D, Michal M. Lesions of anogenital mammary-like glands: an update. Adv Anat Pathol. 2011;18(1):1-11.


3. Carter JE, Mizell KN, Tucker JA. Mammary-type fibroepithelial neoplasms of the vulva: a case report and review of the literature. J Cutan Pathol. 2008;35(2):246-249.