Primary Cutaneous Mucinous Adenocarcinoma of the Left Periorbital Region: A Rare Skin Adnexal Malignancy

Dear Editor, Primary cutaneous mucinous adenocarcinoma (PCMC) is an exceptionally rare neoplasm of sweat gland origin, with an estimated occurrence of approximately one case per 150,000 cutaneous lesions.[1,2] It predominantly affects men, with a male-to-female ratio of 2:1, and is most commonly observed in the fifth and seventh decades of life.[3] While it most frequently manifests on the face, especially the periorbital region (accounting for 40% of cases), it is also observed on the scalp, axilla, trunk, and eyelids.[1,3] These tumors usually manifest as solitary nodules, cysts, or ulcers, often exhibiting a fleshy translucent to blue or red discoloration. Multifocal tumors are also reported.[2,3] The tumor’s histogenesis remains uncertain, with apocrine, eccrine, and neuroendocrine origins being proposed.[4] Although PCMC is considered a low-grade malignancy with limited metastatic potential, it carries a recurrence risk of up to 40%, particularly in the eyelid region, if not excised with adequate margins.[3-5] However, 5.8% of patients diagnosed with PCMC are known to present with distant metastases at the time of diagnosis.[5] A 57-year-old man presented with a progressively enlarging lesion in the left periorbital region for the past two years [Figure 1]. The lesion was asymptomatic and had no associated compressive symptoms.Figure 1: Shows a nodular skin-colored growth around the left periorbital and zygomatic region. Postsurgical wide local excision of the lesion, the sutured wound appears healthy in subsequent imagesOn clinical examination, a single, skin-colored, subcutaneous nodular lesion measuring approximately 4 × 2 cm was noted on the left lateral and infraorbital area. The lesion was soft to hard in consistency, fixed to the underlying tissue, and demonstrated progressive growth without evidence of ulceration, erythema, or altered vision. There were no palpable cervical lymph nodes. An incisional biopsy was performed for histopathological examination with clinical differential diagnoses including microcystic adnexal carcinoma, spiradenoma, cylindroma, and mucinous carcinoma [Table 1]. Hematoxylin and eosin (H and E)-stained sections revealed an unremarkable epidermis. The dermis exhibited a poorly circumscribed tumor characterized by islands of basaloid cells surrounded by pools of mucin, separated by delicate fibrous septa [Figure 2]. The basaloid cells were polygonal with round to oval, mildly atypical, and hyperchromatic nuclei. There was no evidence of increased mitotic activity. The superficial dermis exhibited a mild chronic inflammatory infiltrate. Histochemical staining with periodic acid—Schiff (PAS) and mucicarmine was positive, accentuating the presence of abundant extracellular mucin pools within the tumor matrix [Figure 3]. Immunohistochemical analysis revealed diffuse and strong positivity for GATA Binding Protein 3 (GATA3) [Supplementary Figure 1], Cytokeratin 7 (CK7) [Supplementary Figure 2] in the neoplastic cells, while markers, such as Tumor protein 63 (p63), Cytokeratin 20 (CK20), Caudal-type homeobox 2 (CDX2), and synaptophysin, were uniformly negative [Supplementary Figure 3], aiding in the exclusion of other potential differential diagnoses like metastatic mucinous carcinoma from colorectum and endocrine mucin-producing sweat gland carcinoma (EMPSGC) [Supplementary Table 1], confirming the tumor’s cutaneous origin. A contrast-enhanced computed tomography (CT) of the abdomen and thorax was performed to rule out any metastatic or synchronous lesions. No other lesions were identified, confirming the primary cutaneous nature of the tumor. The findings were consistent with PCMC localized to the left periorbital region. Postsurgical excision, the patient is on regular follow-up and has an uneventful postoperative course.Table 1: Comparison of clinical differentials of primary cutaneous mucinous adenocarcinomaFigure 2: Hematoxylin and eosin-stained section shows unremarkable epidermis. Dermis shows poorly circumscribed tumor islands of basaloid cells, surrounded by pools of mucin (H and E, 40×)Figure 3: Special stain for mucicarmine highlights mucin pools in deep-rose color (mucicarmine, 200×)Supplementary Figure 1: Tumor cells show diffuse nuclear immunopositivity for GATA binding protein 3 (nuclear brown color) (GATA3, 40×)Supplementary Figure 2: Tumor cells positive for low molecular weight cytokeratin (CK7) by immunohistochemistry (cytoplasmic brown color) (CK7, 100×)Supplementary Figure 3: Tumor cells immunonegative for CK20 and CDX2 (100×)Supplementary Table 1: Comparison of histopathological mimickers of primary cutaneous mucinous adenocarcinomaPCMC requires careful exclusion of metastatic mucinous carcinoma, as most mucinous skin tumors are secondary in origin. Common primary tumors include the gastrointestinal tract, breast, and salivary glands.[3] Most lesions are confined to the dermis, extending to the subcutis, but have no connection with the overlying epidermis.[4,5] Despite the diagnostic utility of histology and immunohistochemistry, a full metastatic workup, including CT and Positron Emission Tomography-Computed Tomography (PET-CT), remains essential to exclude secondary lesions.[1] Complete tumor excision is the gold standard treatment for PCMC.[3,4] However, recurrence rates are significantly high, particularly following wide local excision (WLE). Surgical resection with a margin of 1–2 cm is generally recommended to ensure adequate tumor clearance.[3] Mohs micrographic surgery (MMS) is the preferred treatment modality due to its superior outcomes, achieving a recurrence rate of 9.6% compared to over 30% with traditional WLE.[2] These tumors exhibit intrinsic resistance to chemotherapy and radiotherapy. Nevertheless, the presence of unfavorable histopathological features, such as perineural invasion, extracapsular extension, positive surgical margins, marked nuclear atypia, multifocal disease, lymph node involvement, or recurrent disease, necessitates the consideration of adjuvant radiotherapy to reduce the risk of recurrence.[3-5] Factors contributing to recurrence and overall survival include an initial larger tumor size, specific anatomic tumor locations, deep invasion, multifocality, age over 60 years, and incomplete surgical excision.[2,5] To summarize, PCMC is a rare adnexal neoplasm characterized by mucin production and a basaloid cellular pattern. It is typically indolent but requires complete surgical excision due to the potential for local recurrence. Immunohistochemical markers and special stains are critical for accurate diagnosis and differentiation from metastatic mucinous carcinoma of visceral origin. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.