Encapsulated papillary carcinoma originating from the vulva anogenital mammary-like glands: a rare case report

Introduction

Vulvar malignancies predominantly consist of squamous cell carcinomas, with adenocarcinomas being significantly rarer, particularly primary vulvar adenocarcinomas. The estimated incidence of primary vulvar adenocarcinoma is 0.9–2.5 cases per one million women per year, according to a population-based analysis in the Netherlands (1), which also indicates that 45% of adenocarcinomas involving the vulva are secondary, either directly extending or metastasizing from other sites. True primary vulvar adenocarcinoma is very rare. In the 5^th edition of World Health Organization (WHO) Classification of Female Reproductive System tumors (2), primary gonadal epithelial malignant lesions of vulva include a unique subtype, originating from anogenital mammary-like glands, shares numerous features with breast cancer. Literature often describes these as aggressive malignancies akin to their breast cancer counterparts, necessitating comprehensive treatment. This report highlights an indolent variant—encapsulated papillary carcinoma—originating from anogenital mammary-like glands, offering a comparative analysis with existing clinical and pathological reports.

The anogenital area encompasses the anus, external genitalia, and their intervening soft tissues. This area contains mammary-like glands, now seen as a normal part of its anatomy, rather than ectopic breast tissue. These glands, present in 1–6% of women, are typically found in the labial grooves and resemble breast tissue histologically (3). They form glandular structures to complex lobular units, transitioning to squamous epithelium near the surface. These glands, sharing features with breast tissue, can give rise to diseases akin to breast pathologies, including epithelial malignancies, termed adenocarcinomas originating from anogenital mammary-like glands. Adenocarcinomas from anogenital mammary-like glands are extremely rare, with fewer than 40 reported cases (4). These tumors, primarily located in the labia majora, appear as solitary masses measuring 3–4 cm. Patients range in age from 46 to 82 years, averaging 60 years. Predominantly, these cases include ductal, lobular, and various other types, with ductal carcinomas being most frequent, most exhibit an invasive growth pattern (5). Despite the invasive growth pattern, distinguishing these tumors from other glandular malignancies can be challenging. However, we can accurately identify mammary adenocarcinoma in the anogenital area by observing the presence of mammary-like glands between the surrounding tissue and the tumor area. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-35/rc).

Case presentation

A 73-year-old woman, American Society of Anesthesiologists (ASA) class 1, non-smoker, reported she found a mass of the vulva 8 years ago, about soybean volume and is painless. She had no previous vulvar disease, but thyroid papillary carcinoma 4 years ago. Because the mass skin surface color of the tumor was normal, there was no ulceration, redness, heat and pain, no skin itching and abnormal secretions, and walking was not affected, so regular outpatient follow-up, biopsy and any treatment were not performed. In the 8 years, the mass is slowly enlarging and now the patient has the feeling of foreign body when walking. On this visit, the gynecological examination revealed a 3 cm cyst-like nodule on the left vulva, located in the subcutaneous site of the intergroove between labium majus and labium minus. In view of the slow growth, clear palpation boundaries, and reasonable motion, benign cysts were considered and the site was special, so ultrasound or magnetic resonance imaging (MRI) was not performed. Bilateral inguinal lymph nodes were not enlarged. Surgical enucleation was performed, designed to remove the vulvar mass completely. Pathology showed a 2.5 cm nodular mass with a soft, mucinous texture, typically present within a cystic space and surrounded by a fibrous capsule. Microscopic analysis revealed a uniform cell distribution with papillary and solid patterns, accompanied by fine fibrovascular stalks. Immunohistochemical staining showed estrogen receptor (ER), progesterone receptor (PR), epithelial membrane antigen (EMA), pan-cytokeratin [CK(pan)], CK8/18, GATA-binding protein 3 (GATA3), E-cadherin (a calcium-dependent cell-cell adhesion molecule) expression, with a Ki67 (a nuclear protein associated with cellular proliferation, with the index indicating growth fraction) index around 10%, suggesting a specific tumor profile-encapsulated papillary carcinoma (Figure 1). The patient did not receive any postoperative treatment i.e., radiation, chemotherapy, or hormone therapy, and was no recurrence evidence. After the surgery, the breast ultrasound showed no mass.

Figure 1 Encapsulated papillary carcinoma originating from the vulva anogenital mammary-like glands. (A) The gross appearance of the nodular mass with a clear boundary and a solid, partly gelatinous cut surface. (B) The tumor displays a fibrous capsule under low magnification (HE staining, 4×). (C) At medium magnification, the fibrous capsule appears thicker in some areas (HE staining, 10×). (D) It shows uniform tumor cells with papillary and solid nest patterns amidst a fibrovascular core and mucinous background (HE staining, 10×). (E) High magnification reveals mildly to moderately atypical tumor cells with prominent nucleoli and mitotic figures (HE staining, 20×). (F) Positive expressions of ER (IHC, 10×). (G) Positive expressions of PR (IHC, 10×). (H) Positive expressions of CK8/18 (IHC, 10×). (I) GATA3 positive (IHC, 10×). HE, hematoxylin and eosin; ER, estrogen receptor; IHC, immunohistochemical; PR, progesterone receptor; CK8/18, cytokeratin 8/18, high molecular weight keratin, is a protein marker for adenodifferentiation; GATA3, GATA-binding protein 3, is a transcription factor related to normal mammary gland development.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

In this unique case, a woman in her seventies presented with a rare, indolent adenocarcinoma originating from anogenital mammary-like glands, a type not previously documented. The tumor, encapsulated within a cystic space, displayed low-to-intermediate grade epithelial cells organized over slender fibrovascular cores. The immunohistochemical profile, marked by the expression of epithelial and glandular markers such as ER, PR, GATA3, E-cadherin, and gross cystic disease fluid protein 15 (GCDFP-15), underlines its malignancy. This tumor’s striking resemblance to breast encapsulated papillary carcinoma led to its distinctive diagnosis, enriching our understanding of this rare pathology.

In the realm of medical diagnosis, distinguishing encapsulated papillary carcinoma originating in the perianal genital area’s mammary-like glands is crucial due to its distinct treatment and prognosis. This differentiation is necessary from other mammary-like adenocarcinomas, common primary adenocarcinomas in the vulva, and adenocarcinomas that are metastatic or directly spreading. The key differential diagnoses include:

• Mucinous carcinoma: initially diagnosed as mucinous carcinoma from the perianal genital mammary-like glands, this case’s diagnosis was influenced by mucinous material accumulation. However, mucinous carcinoma is characterized by tumor cells, low to intermediate in grade, floating in extracellular mucin lakes, making up more than 90% of the tumor. This contrasts with the solid papillary carcinoma, which often shows neuroendocrine characteristics, not seen in this case.
• Ductal or lobular carcinoma: both these carcinomas grow invasively, with ductal carcinoma now known as invasive breast carcinoma (no special type) and lobular carcinoma retaining its name.
• Bartholin’s gland adenocarcinoma: this diagnosis is specific to tumors in the Bartholin’s gland area, characterized by deep infiltrative growth and carcinoembryonic antigen (CEA) expression.
• Sweat gland adenocarcinoma: these are distinguished morphologically and by their nearly universal expression of CEA.
• Adenoid cystic carcinoma: this type features structures formed by epithelial and myoepithelial cells, expressing CK7, CK8/18 in epithelial cells, and p63 and calponin in myoepithelial cells.
• Metastatic carcinoma: exclusion of metastasis is done through additional tests and medical history, with primary diagnosis supported by identifying residual mammary-like glands.
• Vulvar myoepithelial-like tumors: these slow-growing, painless masses are found in the superficial subcutaneous area of the female vulva. Characterized by a mix of epithelioid or spindle-shaped cells and a varying proportion of mucinous regions, they express markers like vimentin, smooth muscle actin (SMA), EMA, ER, PR, and show loss of integrase interactor-1 (INI-1) expression.

The recognition of adenocarcinoma originating from primary vulvar mammary-like glands, though rare, is critical. Its treatment protocol cannot refer from primary vulvar cancer (6). For primary vulvar cancer, extensive episiotomy and concurrent chemoradiotherapy are generally performed, most of which require inguinal lymph node dissection. Pathologists must undertake comprehensive immunohistochemical analysis to accurately differentiate it from the more commonly occurring malignant glandular epithelial tumors of the vulva, including metastatic and adnexal skin tumors. Currently, no specific treatment guidelines or prognostic data are established for this rare cancer. Previous studies highlight the tumor’s breast cancer-like traits (7). Therefore, treatment strategies are aligned with those for primary breast cancer, primarily involving surgical resection and lymph node dissection, followed by adjunctive radiotherapy, chemotherapy, and hormone therapy (3). For encapsulated papillary carcinoma, those origin from anogenital mammary-like glands can refer from the counterpart primary from breast, therapeutic options range from local to more extensive surgical excision (2).

Conclusions

This paper presents a novel case of primary vulvar encapsulated papillary carcinoma, originating from the mammary-like glands in the perianal genital area. This tumor type exhibits morphological, immunohistochemical, and biological characteristics akin to those of breast encapsulated papillary carcinoma. Its clinical approach, distinct from other primary vulvar glandular carcinomas, aligns more with the treatment strategies for breast encapsulated papillary carcinoma, treated as carcinoma in situ. The current consensus suggests that complete surgical removal or marginally extended excision is adequate, often leading to a favorable prognosis without the necessity for additional radiotherapy or chemotherapy. The rarity of such cases, however, limits our understanding and research, highlighting the need for more clinical data accumulation. For accurate diagnosis and to avoid inappropriate treatment, pathologists must meticulously review the patient’s medical history and rigorously examine the tumor’s morphological features, using effective immunohistochemical markers as an adjunct.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-35/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-35/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-35/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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