Microcystic adnexal carcinoma (MAC) is a rare, insidious, and highly infiltrative cutaneous malignant neoplasm1 that mainly affects the facial region. Eyelid involvement has been described in at least 50 cases, including 8 with orbital extension. We describe 3 patients with MAC invading the orbit or cranium, all referred very late after several years of unexplained progressive eyelid distortion.
An otherwise fit 53-year-old man was referred with slowly progressive left upper eyelid notching for 9 years, ipsilateral supraorbital hypoesthesia for 6 years, and diplopia for 3 years; the left eye was amblyopic from childhood squint. Results from investigations for thyroid disease and myasthenia as well as 2 magnetic resonance imaging scans had been reported as normal and—ignoring the eyelid distortion and cranial hypoesthesia—strabismus surgery was performed. The patient was referred to Moorfields Eye Hospital when his symptoms failed to resolve.
At his initial visit with us, his visual acuity was 20/20 OU and he had no optic nerve dysfunction or intraocular disease; 1-mm left relative proptosis was evident, with ipsilateral hyperphoria, reduced vertical ductions, and supraorbital, supratrochlear, and nasociliary hypoesthesia. The left upper eyelid was peaked and retracted (Figure 1A), with localized skin thickening and distorted tarsus but no madarosis. No orbital mass or lymphadenopathy was detected. Computed tomography revealed an ill-defined superolateral soft-tissue mass involving the superior rectus-levator complex and extending into the cavernous sinus through the superior orbital fissure (Figure 1B). Excision of the eyelid notch and deep orbital biopsies showed an infiltrative malignant neoplasm in a desmoplastic stroma, with nests and strands of epithelial cells showing focal perineural infiltration (Figure 2A and B). Mild cytological atypia and rare mitoses were present. With a diagnosis of MAC, the patient was referred for palliative radiotherapy.
Notched (arrow) and retracted left upper eyelid with no madarosis (A), and axial computed tomography showing a superolateral soft-tissue mass involving the left superior rectus-levator complex and extending into the cavernous sinus through the superior orbital fissure (arrowheads) (B).
Low-power photomicrograph of full-thickness eyelid resection (case 1) showing scattered small islands of tumor set in reasonably well-circumscribed areas of desmoplasia (arrow) (original magnification ×40) (A), and medium-power photomicrographs from case 1 showing solid elements (box) in a desmoplastic background (B) and from case 2 showing ductlike elements (box) in a desmoplastic background (C) (hematoxylin-eosin, original magnification ×100).
A fit 24-year-old woman was referred with progressive right lower eyelid thickening for 7 years, the lesion having been treated as a chalazion following uninformative biopsy 2 years prior to referral. Topical therapy and intralesional steroids were unsuccessful and development of eyelid retraction prompted referral.
Visual functions, globe positions, and ocular ductions were normal on referral. The right lower eyelid margin was thickened medially with pearly changes, telangiectasia, and mild eyelash distortion. There was a subcutaneous mass overlying the lower eyelid retractors (Figure 3A) and MAC was favored on clinical grounds: eyelid and retractor biopsies revealed a dense desmoplastic stroma pervaded by numerous small ducts with occasional tadpole-like morphology and accompanied by bland epithelial cells located within the superficial dermis (Figure 2C). No cytological atypia or mitotic activity was present, but there was an infiltrative growth pattern with early perineural involvement; tumor cells were positive for the epithelial markers BerEP4 and CK7. After Mohs micrographic excision, the area was repaired with a hard palate mucosal graft and a Mustardé cheek rotation flap. Neurogenic ptosis developed 10 months after surgery, with ipsilateral mydriasis and decreased eye movements (Figure 3B). Computed tomography showed patchy opacification from the right cheek to the orbital apex (Figure 3C) and biopsies confirmed extensive tumor infiltration. The patient underwent orbital exenteration and fractionated external beam radiotherapy; tumor was present at the posterior margins of resection.
Right lower eyelid margin showing thickening and pearly changes (A), appearance of onset of right third cranial nerve palsy with a dilated pupil and recurrent ptosis (B), and axial computed tomography showing patchy opacification throughout the right orbit, extending to the orbital apex (C).
A 70-year-old man had slowly progressive right lower eyelid thickening for several years. There were 2 firm intradermal nodules in the medial part of the eyelid but no madarosis, telangiectasia, ulceration, or periocular sensory loss. Right upgaze was reduced and computed tomography revealed an enhancing soft-tissue mass involving the cheek, lower eyelid, and inferior oblique and rectus muscles. Biopsy showed MAC with a slightly hyalinized desmoplastic stroma containing fine sheets and aggregates of epithelial cells with large, atypical nuclei and prominent nucleoli but no mitotic activity; the epithelial cells stained with BerEp4 and CK7. The patient underwent orbital exenteration.
Microcystic adnexal carcinoma is a rare skin tumor of pilar and eccrine differentiation1; the etiology is unknown, although cases have been described after radiotherapy or immunosuppression.2 As in our cases, MAC progresses insidiously and is often missed for years before diagnosis. The tumor may manifest as yellow or flesh-colored nodules, as ill-defined plaques, or with relentless eyelid distortion; skin telangiectasia may be present but ulceration or madarosis is rare.3 Microcystic adnexal carcinoma often shows intraneural and perineural infiltration, and eyelid distortion with pain or periocular numbness should alert the clinician to this diagnosis. Likewise, progressive multiple cranial nerve deficits over years (as in case 1) should always alert a physician to the likelihood of an insidious malignant neoplasm such as MAC.
Histological confirmation of MAC is difficult—the minimal cellular atypia giving it a bland appearance—and such tumors may be thought to be benign or may be missed entirely (as in case 2 before referral). Inadequate tissue sampling may result in less than 10% diagnostic yield.3 Eyelid distortion and retraction are caused by an eosinophilic desmoplastic reaction containing eccrine ducts or keratinized cysts that resemble commas or tadpoles, and perineural invasion is an important diagnostic feature. Although MAC does not have a unique immunophenotype, staining with BerEP4, CK15, and CK7 helps differentiate MAC from desmoplastic trichoepitheliomas, infiltrative basal cell carcinoma, and squamous ductal carcinoma.4
Treatment options for periocular MAC include wide local excision, Mohs micrographic surgery, and radiotherapy. Perhaps reflecting the infiltrative nature of MAC, small series using Mohs surgery have shown a lower recurrence rate (0%-12%) as compared with en bloc excision (30%-47%).5 Toluidine blue staining during Mohs clearance helps highlight tumor strands and perineural invasion. Exenteration is advised for perineural or orbital infiltration, and palliative or adjunctive high-dose radiotherapy may be used. Despite its invasive nature, periocular MAC has a fairly good prognosis, with only 7 cases of metastasis and 1 death reported. Intracranial invasion has been reported, and its presence in 2 of our patients must limit their chance of cure (cases 1 and 2).
Relentless eyelid retraction (in the absence of thyroid dysfunction) or distortion should always be regarded as tumor-induced fibrosis until proven otherwise. Adequate biopsy specimens must be taken and the histopathologist should be alerted to the diagnosis of MAC. In particular, there should be a specific request to search for sparse epithelial cells within deep tissues or dense fibrosis—the presence of which is likely to confirm this diagnosis.
Correspondence: Dr Rose, Adnexal Service, Moorfields Eye Hospital, City Road, London EC1V 2PD, England (firstname.lastname@example.org).
Financial Disclosure: None reported.
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