PCMC is a rare adnexal neoplasm that was first described in 1952 by Lenox et al1. It usually shows an indolent clinical course and is often misdiagnosed clinically as an epidermal cyst, sebaceous carcinoma, cystic basal cell carcinoma, squamous cell carcinoma, neuroma, or pilomatrixoma1. The most common location for PCMC is the head and neck region, especially around the eyelids. PCMC of the axilla is a very rare tumour and only a few cases reported on this site4.
Clinically it usually presents as a solitary, asymptomatic, erythematous skin nodule or papule on the face, scalp, or in the axilla1. This tumor also typically presents as a slow-growing, painless, soft, sometimes indurated, reddish or gray-blue, non-ulcerating nodules that have been present for several years up to 20 years before diagnosis6. Our patient had a similar presentation; he had a painless wart-like skin lesion over his left axilla for many years until it was incidentally detected during the management of unrelated gastrointestinal pathology. PCMC in the form of an ulcer or cyst has also been described6.
Morphologically, it is impossible to differentiate PCMC from metastatic mucinous adenocarcinomas of non-cutaneous organs such as gastrointestinal tract and breast3. The histopathological features are indistinguishable from the corresponding lesions in the breast7. It is characterized as being composed of large pools of basophilic mucin divided by thin fibrous septa, creating a honeycomb pattern. Within the lakes of mucin are small “floating” islands of neoplastic epithelial cells, which may be cribriform. At the periphery of the tumor is a denser epithelial component. The neoplastic cells are described as cuboidal, round, or oval, with abundant cytoplasm, small regular nuclei, and rare mitotic Figs. 1. The presence of dirty necrosis and goblet cells might suggest intestinal origin7.
Challenges arise when the site of the tumour is within the chest and axillary region as these locations are strongly related to mammary origin7. Thus, the differential diagnosis would be PCMC versus metastatic breast carcinoma. Unfortunately, morphology and IHC are identical. In our case, the primary lesion was in the left axilla with a suspicion of nodal metastasis, clinically. Our patient is male and had the mass for many years. It is a known fact that invasive breast carcinoma among male is rare and having on the axillary rest is even rarer. Moreover, most mammary mucinous carcinoma are indolent and very rarely present as a metastatic disease of an occult primary.
To date, no immunohistochemical (IHC) panel has been identified to differentiate primary from metastatic mucinous carcinoma consistently. Yet a variety of stains have been reported to be helpful in this differential differentiation3. For example, metastatic mucinous gastrointestinal carcinoma from the colon can be excluded as cytokeratin 20 (CK 20) is negative in PCMC1. However, immunohistochemistry is not particularly useful in distinguishing PCMC from mucinous adenocarcinoma of the breast like in our patient as both tumors can express CK7, GATA 3, mammaglobin, estrogen receptor (ER), and progesterone receptor (PR)3.
It has recently been suggested in the literature that detection of a myoepithelial component in the tumor (confirmed by positivity for p63, CK5/6, or calponin in isolated peripheral cells) supports or suggests PCMC but unfortunately this is not a common finding3. Qureshi et al.5 suggest that finding an in-situ component of a tumor that stains for myoepithelial cells (positive stains for p63 and CK5/6 among others) can help to exclude metastatic mucinous breast carcinoma5. In our patient we detected the presence of this myoepithelial cells with positive immune stain for p63 but only occasional tumour cells, which can be also occur in breast carcinoma were expressing it and the CK5/6 staining was negative. Thus, the IHC staining cannot specifically diagnose PCMC. Hence the diagnosis was more challenging to confirm whether this lesion is a skin metastasis from occult breast cancer or PCMC1.
Generally, PCMC has a favorable good prognosis. It is a slow-growing tumor and have an indolent behavior3 and often appears well localized. PCMC has direct invasion beyond the reticular dermis and subcutaneous fat or by lymphatic invasion1. The rate of local metastasis to the regional lymph nodes has been reported as 10%8. In our patient he had enlarged matted left axillary nodes which confirmed nodal metastasis.
PCMC is a rare disease and hence there is no established standard of management for it. Wide Local Excision (WLE) with or without regional lymph node dissection is the treatment of choice. As local recurrences are common, excision with 1-cm margin is recommended4. Mohs Micrographic Surgery (MMS) also is an effective surgical treatment for PCMC at head and neck region, recurrent disease and in cases where tissue conservation is necessary1.
Although PCMC has low metastatic potential (3–11%), the local recurrence rate after surgery is high (29–34%). The low frequency of distant metastases is believed to be due to the avascularity of this tumor1. Late recurrence and metastases have been reported probably related to incomplete excision of the tumor9. Such recurrences and metastatic disease have not responded well to treatment with radiotherapy or chemotherapy because they are highly resistant9.
There is limited data in the literature regarding the benefit of adjuvant endocrine therapy in PCMC. Tamoxifen has been successfully used in a few cases of metastasizing eccrine adenocarcinoma12 13 and several case reports10 11 have demonstrated the benefits of the endocrine therapy with an aromatase inhibitor for hormone receptor positive advanced PCMC. Knowing the fact that PCMC frequently expresses ER and PR, it might respond to endocrine therapies. Our patient was started on Tamoxifen as his ER and PR status were positive after the multidisciplinary team discussion. He responded well to the adjuvant endocrine therapy and has not shown any disease recurrent for the past 18 months of follow-up period. He is happy with his overall outcome of this disease.