TOPICS

Primary Eccrine Adenocarcinoma: A Rare but Dangerous Lesion of the Eyelid

J Clin Aesthet Dermatol. 2021;14(4):24–26.

by John Awad, MB ChB, FRCOphth and David Cheung, BSc (Hons), MB ChB, FRCOphth, FRCSEd (Ophth)

Mr. Awad is with New Cross Hospital in Wolverhampton, England. Mr. Cheung is with Russell Hall Hospital in Dudley, England.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.


ABSTRACT: Sweat gland carcinomas can be of eccrine or apocrine origin, with the former being more common in the eyelid. They can also be of three different types, the most common of which is mucin-producing sweat gland carcinoma, which is most often a low-grade malignancy. Here, we report a case of a primary estrogen receptor-positive eccrine adenocarcinoma of the eyelid that clinically presented like a cyst of Moll. Importantly, in our experience with this lesion, this rare malignancy was repeatedly misdiagnosed as less sinister lesions, surgical resection margins of the lesion could be easily underestimated, and close liaison with our general surgical colleagues was vital to exclude more common breast carcinoma. This case highlights the dangers of referral recommendation policies (e.g., procedures of limited clinical value as used by primary care) and the importance of incisional biopsy in the management of periocular lesions.

Key words: Cyst of Moll, eyelid lesion, sweat gland carcinoma


Sweat gland carcinomas can be of eccrine or apocrine origin, with the former more common in the eyelid. There are three types which are described in the periocular region: signet ring cell carcinoma, malignant syringoma, and mucinous sweat gland carcinoma.1 The most common subtype is the mucin-producing sweat gland carcinoma; which is most commonly a low grade malignancy.2 These most frequently occur in the head and 47 percent of patients present with this carcinoma in the eyelids.2 Histologically, these are characterized by the presence of large pools of intradermal mucin, which contain small areas of epithelial cells with malignant features.2 

Case Presentation

A 79-year-old Caucasian female patient presented to her general practitioner and optician with a lesion on her right lower eyelid, which she reported had been present for seven years (Figure 1). She was referred to the general ophthalmology service for “a cyst” and was seen by the general ophthalmology team consultant, who confirmed the diagnosis as a likely benign cyst. Medical history included type 2 insulin-dependent diabetes mellitis and hypothyroidism.

She was subsequently referred to the oculoplastic team and seen by the registrar of the oculoplastic team. Due to the lesion’s progressive enlargement that would likely cause future interference with the patient’s vision in the right eye, the registrar decided that excisional surgery should be offered under the eligibility criteria of the local Clinical Commissioning Group’s “procedures of limited clinical value.”3

However, on the day of the planned surgery, the patient was seen by the oculoplastic consultant on the preoperative ward round, who observed that the lesion did not transilluminate nor was it fluctuant like a simple cyst of Moll or hydrocystoma. The patient was informed that clinically, this was more likely to be a solid lesion of unknown origin, and that an incisional biopsy might prove helpful in management. 

Histology showed the tumor was a well-defined but infiltrative, solid lesion, which had infiltrated into the underlying palpebral muscle fibers with a cohesive front. The tumor was composed of multiple, expansile nodules with a solid and cribriform architecture and focal mucin production. The tumor cells were of a small-to-intermediate size, polygonal-to-round ductal cells with amphophilic-to-bluish cytoplasm and round-to-oval nuclei and inconspicuous nucleoli (Figure 2). The mitotic rate was very low, with no necrosis. The focal presence of the in-situ component was confirmed with basal layer markers of CK14, smooth muscle myosin, and p63. Immunohistochemistry showed that the tumor cells were positive for carcinoembryonic antigen, epithelial membrane antigen, estrogen receptor, progesterone receptor, and synaptophysin (Figure 3) and negative for S100 and chromogranin. These features were deemed consistent with an endocrine mucin-producing sweat gland carcinoma with areas, suggestive of progression to mucinous carcinoma.

Following discussion with the histopathology team, a differential diagnosis was made of either a rare primary lesion of the eyelid or a more common metastatic secondary lesion from elsewhere (most commonly from a primary breast carcinoma). It was recommended that our patient be seen by a breast surgeon, who clinically excluded any presence of a primary breast lesion by clinical examination and a mammogram. 

The patient underwent margin-controlled excisional biopsy with fast paraffin histological analysis of the eyelid lesion. Of note during excision was how deeply and diffusely spread the lesion was within the orbicularis layer and that this deeper component only became apparent during excision, not being visible during a previous examination. Following histological confirmation of clearance of the lesion, reconstruction of the lateral eyelid and lateral canthal defect was performed with a lateral orbital rim periosteal hinge flap and sliding subcilary skin flap. The patient’s recovery was uneventful. 

Discussion

The diagnosis of primary mucinous sweat gland carcinomas is usually challenging, not only because this is a rare entity not often seen in practice, but also because the presentation can be highly variable; the eyelid tumor can appear as a nodule, cyst, papule, or as diffuse swelling.4 

Primary mucinous sweat gland carcinomas are intradermal tumors that are slow-growing lesions with no specific predisposing factors.4 The treatment modality of choice is surgical excision with wide margins and, in some cases, adjunct radiotherapy. However, due to the rarity of this tumor, there are no definitive established treatment guidelines. In a literature review from Segal et al,4 which included 25 articles published between 1971 and 2010 and a total of 55 patients, the recurrence rate of primary mucinous sweat gland carcinomas was found to be 30 percent. We hypothesize that recurrence rates are high, as these lesions might have been misdiagnosed as cysts of Moll and therefore excised without margin control. 

The differential diagnoses of such lesions mainly include metastatic disease commonly from a primary breast, gastric, or bladder carcinoma, histiocytoma, apocrine sweat gland carcinoma, and sebaceous gland carcinoma.1,5,6 It is therefore of the utmost importance to manage such cases in conjunction with other specialties as part of a multidisciplinary team approach to rule out extracutaneous metastases in all such patients. Therefore, primary mucinous sweat gland carcinoma should be considered a diagnosis of exclusion. 

The review article by Segal et al4 noted that earlier studies demonstrated approximately one in five patients were found to have a primary mucinous sweat gland carcinoma that was initially diagnosed as recurrence of a “benign” lesion that had previously been surgically excised from the same location several months or years prior. This highlights the importance of an accurate detailed history specifically regarding previous periocular surgeries as well as the importance of performing margin-controlled excision. In cases where there is suspected recurrence of a slow-growing tumor, mucinous sweat gland carcinoma should be high on a clinician’s list of differential diagnoses. 

In the majority of cases, this eyelid tumor might seem superficial; however, they can extend into the orbit and spread to regional lymph nodes. The main specific surgical method of choice is Mohs’ micrographic surgery, which was found to be the most common procedure adopted following a literature review.7 Complete excision with wide margins (4–5mm) is the mainstay of treatment, as incomplete excision has a high risk and incidence of recurrence.8 There are some case reports in the literature of such tumors invading the orbit and requiring exenteration.9 

Theoretically, there might be a benefit to treatment with an antiestrogen medication, such as tamoxifen, in estrogen receptor-positive cases in the same way that this has been a treatment approach in patients with breast cancer for more than 30 years.10

Conclusion

The nomenclature for this tumor is varied and this adds to the difficulty in accumulating demographic information concerning this rare disease. Primary mucinous sweat gland carcinoma is a diagnosis of exclusion and meticulous workup to exclude metastatic disease is imperative. The mainstay of treatment is complete surgical excision and, given the high recurrence rate, close and regular long-term follow up is advocated. 

In today’s tough climate and increasing medico-legal claims, we advocate that if a clinician is in doubt regarding the diagnosis, there should be a low threshold for referral. In addition, the treating surgeon may monitor with photographic documentation and, should any change occur, proceed to an excisional biopsy with wide clearance margins.

References

  1. Wollensak G, Witschel H, Bohm N. Signet ring cell carcinoma of the eccrine sweat glands in the eyelid. Ophthalmology. 1996;103(11):1788–1793. 
  2. Tanboon J, Uiprasertkul M, Luemsamran P. Signet-ring cell/histiocytoid carcinoma of the eyelid: a case report and review of the literature. Am J Dermatopathol. 2013;35(1):e1–e5.
  3. Dudley Clinical Commissioning Group. FREEDOM OF INFORMATION ACT 2000—Dudley CCG: NHSE consultation on evidence based interventions—Ref: RFI1050. https://www.dudleyccg.nhs.uk/wp-content/uploads/2018/09/RFI1050-Combined-Response.pdf. Accessed March 16, 2021. 
  4. Segal A, Segal N, Gal A, Tumuluri K. Mucinous sweat gland adenocarcinoma of the eyelid—current knowledge of a rare tumor. Orbit. 2010;29(6):334–340. 
  5. Tan J, McKelvie P, Hardy T. Primary signet ring cell carcinoma of the eyelid. Orbit. 2013;32(6):399–401. 
  6. Arnold A, Bullock J, Foos R. Metastatic eyelid carcinoma. Ophthalmology. 1985;92(1): 114–119.
  7. Clark S, Young A, Piatigorsky E, et al. Mohs micrographic surgery in the setting of squamoid eccrine ductal carcinoma. Addressing a diagnostic and therapeutic challenge. J Clin Aesthet Dermatol. 2013;6(4):33–36.
  8. Khoramnia R, Mayer C, Glaser E, et al. Primary signet ring cell carcinoma of the eyelid in a young woman. Eye. 2011;25(1):1380–1382.
  9. Mortensen A, Heegaard S, Clemmensen O, et al. Signet ring cell carcinoma of the eyelid—the monocle tumour. APMIS. 2008;116(4):326–332.
  10. Lazzeroni M, Serrano D, Dunn B, et al. Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug. Breast Cancer Res. 2012;14(5):214. 
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