SGC is a rare and potentially aggressive malignancy. Most SGC tumors are located in the extraocular head and neck skin (face/ear/scalp/neck/lip, 42.8%), followed by the eyelid (34.5%), trunk (14.8%), and extremities (6.5%). Ocular SGC arises from the sebaceous glands, whereas the origin of extraocular sebaceous carcinoma has not been determined [2]. SGC of the eyelid is a malignant eyelid tumor that is derived from sebaceous glands, such as the meibomian gland and Zeis gland. The proportion of histologic types of eyelid tumors differs among ethnicities. In the USA and Europe, basal cell carcinoma (BCC) accounts for 80% of all eyelid tumors, followed by squamous cell carcinoma (SCC), and SGC accounts for < 5% of all eyelid tumors [3,4,5]. In contrast, it is reported that SGC of the eyelid is as prevalent as or even more common than BCC in Asian countries, including Japan [3, 6]. The clinical appearance of ocular SGC is highly heterogeneous and often mimics other ocular benign conditions, such as chalazion, posterior blepharitis, superior limbic keratoconjunctivitis, and keratitis [5]. Thus, the diagnosis might be delayed, resulting in a poor outcome.
The overall mortality rate of eyelid SGC is 5–10%. It is reported that metastatic sites of SGC include the regional lymph nodes, liver, brain, bone, and lung. Regional lymph node metastasis was noted in 20% of all cases and systemic metastasis in 14% [6]. The duration from the diagnosis of primary SGC to metastasis may range from 0 to 62 months [7]. In the present case, pulmonary metastasis was discovered 4 years after the operation of primary SGC. Based on our experience, we propose that long-term follow-up for at least 5 years be performed after surgery for primary SGC.
The diagnosis of SGC of the eyelid is made based on the pathologic diagnosis of specimens from surgical resection or a biopsy. Pathologic findings of SGC vary widely, ranging from well-differentiated tumors to undifferentiated tumors. The diagnosis of SGC is generally based on HE staining and Oil Red O staining for lipids [4, 5]. Recently, it was reported that an immunohistochemical analysis can replace Oil Red O staining, helping to differentiate primary SGC from BCC and SCC [5]. In the present case, both the primary SGC and pulmonary metastases were positive for EMA, AR, and p53 and negative for BerEP-4 according to an immunohistochemical analysis. Based on these findings, the pulmonary disease was diagnosed as pulmonary metastasis from SGC.
The standard treatment strategy for recurrent pulmonary metastasis of SGC has not been established. Evidence to support systemic therapy for the treatment of sebaceous carcinoma with curative or palliative intent is confined to case reports. The majority of regimens include 5-fuorouracil or cisplatin-based chemotherapy [8]. Recently, the administration of cetuximab or pembrolizumab for the treatment of metastatic SGC has been reported [9, 10]. However, level of evidence in these reports was not high; thus, it is said that there are no promising systemic treatments. Because pulmonary metastasectomy is an established treatment for resectable pulmonary metastasis [11], pulmonary metastasectomy was considered as the most appropriate mode of treatment in the present case. On the other hand, stereotactic body radiotherapy (SBRT) for pulmonary metastasis could be an alternative to pulmonary resection. Although it is reported that SBRT provides a favorable 3-year local control rate for pulmonary metastasis from epithelial tumors [12], there have been no reports on the use of SBRT in the treatment of pulmonary metastasis from SGC. Based on these findings and the fact that the treatment was considered tolerable based on the patient’s good pulmonary function, we performed repeat pulmonary resection.
Thus far, only two cases in which surgical resection was performed for pulmonary metastasis from SGC have been reported [7, 13]. One case was pulmonary metastasis of the right upper lobe that was found 6 years after the operation of left primary SGC. The patient underwent wide wedge resection of the right upper lobe, and 7 months after pulmonary operation, she is doing well without disease. Another case was pulmonary metastasis of the left upper and lower lobes found 5 years after the operation of right primary SGC. Following neoadjuvant chemotherapy, the patient underwent wide wedge resection of the left upper and lower lobes. Three months after pulmonary resection, she is doing well without disease. Both cases are similar to our own in that pulmonary metastasis was detected during long-term follow-up after an operation for primary SGC.
Repeat pulmonary metastasectomy is reportedly beneficial in many types of cancer [11]. Our case underwent four pulmonary metastasectomies for recurrent pulmonary metastasis from SGC. To our knowledge, the present case is the first to undergo repeat pulmonary metastasectomy for recurrent pulmonary metastasis of SGC. Given that a long-term survival was ultimately achieved in the present case, repeat pulmonary metastasectomy may be beneficial for recurrent pulmonary metastasis from SGC.
