Certain histopathologic features may be suggestive of either a primary or metastatic etiology. Lesions arising in the skin may reveal an in situ component representing ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ. Identification of an in situ component defines a cutaneous primary neoplasm, but its absence does not exclude PMC.5 Additionally, metastatic lesions from the GIT typically have greater pleomorphism and “dirty” necrosis defined as eosinophilic foci containing nuclear debris.5
The expression pattern of cytokeratins (CKs) also can be suggestive. Primary mucinous carcinoma and metastatic breast adenocarcinoma are both CK7+ and CK20−. By contrast, mucinous adenocarcinoma of the GIT stains CK20+ and CK7−.14 Another marker that stains PMC is CK5 and CK6, though infrequently present. Levy et al15 reported positive staining for CK5 and CK6 in only 1 of 5 PMC cases. Positive staining for CK5 and CK6 has not been reported in any metastatic mucinous carcinoma.
The role of p63 immunostaining in the setting of mucinous carcinoma is controversial.16-18 Some practi-tioners have reported using p63 immunostaining to assist in establishing the diagnosis of PMC but only after performing a clinical workup to search for any primary sites of mucinous carcinoma in other organs.11 Other studies, however, have found select metastatic lesions from the breast17,18 and GIT18 to stain positively with p63. It is important to remember that these clinical and pathologic features are only suggestive of the primary etiology and are not replacement for a full clinical investigation.
Primary mucinous carcinoma is considered an indolent tumor with the majority of patient morbidity attributable to local recurrence and regional metastasis. Although uncommon, regional and distant metastasis rates have been reported to be 11% and 3%, respectively.19 Direct lymphatic invasion has been reported and indicates a more aggressive tumor with shorter recurrence-free intervals and predicts nodal metastases. Paradela et al20 recommended the use of D2-40, a monoclonal antibody and specific marker for lymphatic endothelium, to detect lymphatic invasion, particularly in node-negative primary tumors.
In one case of PMC on the jaw of a 39-year-old Japanese man, no recurrence or metastases were discovered until the 11th year of follow-up. At that time, he was found to have lung and bone metastases and died after 3 years.21 Other investigators report death occurring 4 to 24 months following diagnosis of distant metastases.7,22 Direct extension of the tumor into skeletal muscle, periosteum, bone, and dura also has been documented.7
Treatment principally is surgical, with PMC known to be resistant to both chemotherapy and radiation therapy.19,22 The recommended margins for simple excision range from 1 to 2 cm, but this method of treatment yields recurrence rates upward of 30% to 40%, especially for lesions located on the eyelid.12,13 First utilized in PMC of the eyelid to conserve tissue, MMS is rapidly becoming the treatment of choice because of its notably improved recurrence rate. A case series of 4 PMCs of the eyelid treated via MMS or frozen section control found the recurrence rate to be 7%.23 Another report of 2 cases of PMC treated by MMS reported no recurrence after 42 and 26 months.13 Ortiz et al7 reported an additional case of a patient treated by MMS that was recurrence free for 30 months at the time of publication. Further investigation is required to definitively recommend MMS on the basis of improved recurrence rate but should now be considered standard of care in recurrent, sizeable, or eyelid PMC.
Despite its ascension as treatment of choice in many cases of PMC, MMS is not without its risk of metastasis and recurrence. Tam et al24 reported a case of PMC with multiple recurrences and metastases following 3 simple excisions and 2 excisions via MMS. Although the lesion’s previously recurrent nature increased the likelihood of failure of MMS, this case demonstrates that all patients should be followed periodically after the treatment of PMC.
We presented a case of PMC in which standard surgical margins would have been insufficient to clear the lesion. Mohs micrographic surgery was used to remove the majority of the tumor. As is common in PMC, the lesion was indolent and periocular in location. It also was incompletely excised due to notable subclinical extension, which is common for PMC. The distinction of PMC from metastatic mucinous carcinoma is paramount but sometimes difficult. Randomized controlled trials are lacking with regards to preferred method of treatment, but MMS has shown benefit and should be considered for recurrent lesions and lesions in cosmetically sensitive areas.