Primary cutaneous mucinous carcinoma was originally believed to be of eccrine gland origin.⁸ However, more recent evidence suggests apocrine differentiation, although this remains somewhat controversial.¹⁴,¹⁵,¹⁶,¹⁷,¹⁸ The role of ultraviolet radiation exposure in the pathogenesis of sweat gland carcinomas remains unclear, but the primary distribution on the head and neck and the greater occurrence in light-skinned individuals suggest that this may be a risk factor.¹⁹

PCMC has a predilection for the head and neck with about 65% to 70% occurring in this region.²⁰ The most common sites are the scalp, face, eyelids, and neck. The eyelid is one of the more common sites of presentation, but still, only about 60 cases have been described.¹¹,¹⁴,²¹,²²,²³,²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰ On the eyelids, these tumors may present with a variety of clinical presentations but generally are slow-growing, nontender, soft to firm, nodular, papular, or cystic lesions measuring 5 mm to 2 cm (Figures 142.1 and 142.2), but some lesions may be 4 cm or more in size. They are usually single and unilateral but rarely may be multiple or even bilateral.³¹,³² Lesions may be skin colored, blue, pink, or red with or without telangiectasias, and rarely may be ulcerated.²⁷,³³ Although growth is usually slow, there have been several reports of rapid enlargement and more aggressive behavior.⁸,³⁴

The upper and lower eyelids are involved equally at about 45% each, and in 10% of cases, the tumor involves the medial canthus. On other parts of the body, PCMC has a high male predominance of about 70% to 80%, but on the eyelids, the sexes seem to be more equivalent with a male predominance of about 56%. They occur primarily in patients from middle to old age with a mean age at presentation of 62 years, but rare cases have been described in children.²²

The clinical differential diagnosis includes basal cell carcinoma, squamous cell carcinoma, melanoma, sebaceous carcinoma, cutaneous metastasis, papilloma, chalazion, keratoacanthoma, nevus, apocrine hidrocystoma, and epidermal inclusion cyst.

Following surgical excision, primary cutaneous mucinous carcinomas are associated with a high local recurrence rate of 30% or more.¹¹,²⁷,³⁴,⁵²,⁵³ However, lymphatic spread to regional
lymph nodes is uncommon with a rate of about 10%, and distant metastasis is rare at about 2%.¹¹ Tumor recurrence and metastasis are associated with poor outcomes.³⁸

Histopathologic examination reveals an unencapsulated, dermis-based tumor that may show extension into the subcutis and deeper tissues when located outside the eyelid.⁸,¹⁷ In the eyelid, the tumor often invades the orbicularis oculi muscle.¹⁴ The tumor contains islands of neoplastic basaloid cells having solid to cribriform arrangements within slightly basophilic, PAS-positive mucinous pools, sometimes partitioned by thin fibrous septa (Figure 142.3A-C).⁸,¹⁸ The mucin is alcian blue positive (pH 2.4-2.5)⁸,²⁷,⁵⁴ and stains with mucicarmine⁵⁴,⁵⁵,⁵⁶,⁵⁷ and colloidal iron.⁸,⁵⁴ As a sialomucin, it is hyaluronidase resistant and sialidase labile.⁸,⁵⁴ Cytologically, the tumor cells are characteristically round to cuboidal with moderate amounts of cytoplasm and typically with a low mitotic count and little nuclear atypia.⁸,¹⁴

The tumor cells of PCMC may stain positively using antibodies to AE1/AE3 cytokeratins,¹⁵ α-lactalbumin,²⁵,⁵⁸ beta-2-microglobulin,⁵⁸ carcinoembryonic antigen (CEA),¹⁵,²⁵,⁵⁸,⁵⁹ CD56,⁵⁷ chromogranin,¹⁵,⁵⁷,⁶⁰ CK5/6,⁵⁹ CK7/8 (CAM5.2),⁵⁷ E-cadherin,¹⁵ epithelial cell adhesion molecule (BerEP4),⁵⁹ epithelial membrane antigen (EMA),¹⁵,⁵⁸,⁶⁰ gross cystic disease fluid protein-15 (GCDFP-15),¹⁴,¹⁵,²⁵,⁵⁷,⁵⁹ high-molecular-weight cytokeratin (34βE12),⁵⁹ low-molecular-weight cytokeratin,⁶⁰ lysozyme,¹⁵ MUC1,¹⁵ MUC2,¹⁵ MUC6,¹⁵ neuron specific enolase,⁶⁰ S100 protein,²⁵,⁵⁸,⁵⁹ salivary-type amylase,⁵⁸ synaptophysin,⁵⁷,⁶¹,⁶² trefoil factor-1 (TFF-1),⁶³ WT1,⁵⁷ and estrogen (ER)¹⁵,⁵⁷,⁶⁰,⁶¹,⁶²,⁶³ and progesterone (PR)¹⁵,⁵⁷,⁶⁰,⁶¹,⁶²,⁶³ receptors. PCMC tumor cells are CK7+ and CK20-,¹⁴,¹⁵,⁵⁷,⁵⁹,⁶¹,⁶²,⁶⁴ similar to breast cancer but different from gastrointestinal adenocarcinoma, which is CK7- and CK20+.¹⁵ Thus, approximately half of cases of mucinous carcinomas (ie, those from the gastrointestinal tract) can be effectively eliminated from consideration using CK7 and CK20 immunostains.¹⁵ The tumor cells are negative for expression of CD10,¹⁵ CDX2,⁵⁷ p53 protein,¹⁵,⁶⁰ prostate-specific antigen (PSA),¹⁵,⁵⁹ prostate-specific alkaline phosphatase,¹⁵ smooth muscle actin,¹⁵ and thyroid transcription factor 1 (TTF1).⁵⁹ Most primary mucinous carcinomas are CK7+, E-cadherin+, EMA+, GCDFP-15+, ER+, PR+, and CK20-.¹⁵