Clinicopathological features of patients with wide local excision of eyelid malignant neoplasms: a more than five years retrospective study from China

According to our findings, BCC was found to be the most common type of eyelid malignancies. The prognosis of tumor is related to its pathological classification, and BCC has the best prognosis. BCC may be associated with a primary secondary tumor—lung squamous cell carcinoma. The disease composition of our study is similar to that of previous Asian populations [6,7,8,9,10].

The overall mean follow-up time after treatment was 102.52 months (36–144), the follow-up time is longer than most of the previous reports (between 2 months and 4 years) [11]. Because of the long follow-up time, our results are more likely to reflect the long-term outcomes of eyelid malignancies treated with wide local excision. Through our long-term follow-up of at least 5 years, the survival time of the tumors that received wide local excision was primarily related to the pathology of the eyelid tumors. The tumor-related mortality of BCC after wide local excision was significantly lower than that of MMS and other surgical procedures [12]. An unexpected finding in our study was that two patients with BCC were associated with a second tumor, original lung squamous cell carcinoma, which had not been reported in the previous literature. There were few reports on metastasis of basal cell carcinoma, The published incidence of metastasis is from 0.0028 to 0.55%. Thomas et al. reported a lung metastases in a case of basal cell carcinoma of the eyelid, Whether this tumor arises de novo or develops from an existing BCC is debated, Thomas supports the former scenario [13]. The two patients with lung squamous cell carcinoma were both 75 years old with no tumor history or family history. The tumor size was T2a and T2b, respectively. The anatomical location of one patient was on the upper eyelid and the other on the lower eyelid, but both were located on the temporal side. No local recurrence occurred in the both patients. The mechanism of original second lung squamous cell carcinoma in the two patients is unclear. Attention should be paid to the lung condition of patients with BCC, although the incidence is very low. Song et al. reported that the 3–5 years mortality rate of SGC is 25.6%, and they adopted the method of paraffin section to control the incision margin. If the incision margin is positive, it needs to be enlarged again, and then eyelid reconstruction is performed after the incision margin is clean [14]. This method increases the times of biopsies and the length of surgery. The use of wide local excision in SGC was verified to reliable through our study, and its mortality was greatly reduced compared with previous reports [15]. Mortality in SCC was 20%, significantly higher than previously reported (1.9–14.7%) [16]. We speculate that the higher recurrence rate of SCC in our study is associated with the high TNM staging. The tumor size of 81.7% in all SCC in our study was greater than or equal to T2b. The mortality of MM in our case was 66.6%, but their 5-year mortality was 0 because both patients died in the sixth year after surgery. Breslow et al. found that lesions measuring 0.76 mm or less were associated with a 5-year survival rate of 100%, whereas patients with tumors that had invaded more than 1.5 mm had a 5-year survival rate being 50% to 60% [17]. In our study, the maximum transverse diameters of both patients with MM were greater than 20 mm at the time of initial treatment. At the time of initial treatment, MM in this group was both greater than T2b, which may be the reason for the high mortality of this group of cases.

TNM stage was also a factor influencing overall survival rate. The overall survival rate of T4b stage was the lowest, followed by T2c stage. Joshua Ford et al. investigated the prognostic value of the 7th Edition of AJCC in eyelid malignant tumor and concluded nodal metastasis was significantly correlated with T2b or more extensive tumor at presentation [18]. Yun Hsia [6] et al. validate the performance of the T category of the 8th edition AJCC staging systems, they concluded tumors classified as T2c or worse had higher risk of regional lymph node metastasis, while tumors T3b or worse in the 8th edition had more tumor-related death [6]. In general, we should pay more attention to T2c or worse.

The recurrence of BCC is very low, and Poignet el al. concluded that after complete resection of BCC with negative margins, the rate of local recurrence is less than 1% at 5 years of follow-up; with incomplete excision, the local recurrence rate can be as high as 38% at 5 years [12]. Our cohort showed no recurred case in the cases followed up. One patient developed BCC in the contralateral eye 7 years after surgery. The time of last follow-up, 4 SGC patients (10.53%) recurred and 1 of the 4 “recurrences” developed pagetoid recurrence at new sites that were previously not involved by tumor, this result is similar to previous reports [19]. our study had a longer follow-up period. The advantage of our study was that the mean follow-up time of SGC was 94.97 \(\pm 3.71\)(36–132) months, compared with 20 to 44 months in previous studies. In this group of cases, two malignant melanomas recurred 3 years after surgery, the recurrence rate was 100%. Such a high recurrence rate was also associated with the TNM stage greater than or equal to T3a at the time of MM visit. Two more rare neoplasms were non-Hodgkin's lymphoma and mucinous adenocarcinoma. Non-Hodgkin’s lymphoma recurred locally 3 years after surgery, and mucinous adenocarcinoma was free of recurrence at the end of the follow-up period. Previous reports have suggested that the mean time to recurrence was 20 months and most carcinomas recurred within 2 years of surgery [15, 20]. Our study believed that the recurrence time of eyelid malignant tumor was 3 years after surgery, so the follow-up frequency within 4 years after surgery should be once every six months and switch to once every year after 4 years postoperative. We performed multivariate Cox regression on pathological classification, surgical history of the eyelid tumor and TNM stage. The results showed that the pathological classification and surgical history of the eyelid tumor was an independent risk factor for relapses. Patients who had a surgical history of eyelid tumor had a higher recurrence rate even after extensive resection with negative margin. The reason for eyelid tumor resection without margin control is that malignant eyelid tumor was misdiagnosed as benign eyelid tumor and underwent surgery without margin control at that time. Many ophthalmologists, however, are not intimately familiar with the clinical manifestations of malignant neoplasms of the eyelids, which are reasons for misdiagnosis. It is necessary for eye tumor specialists to carry out continuous education on eyelid malignant tumor to general ophthalmologists, so as to reduce the misdiagnosis rate of eyelid malignant tumor.

At the end of follow-up, 17 patients had metastases. Cox regression model showed that pathological classification was an independent risk factor for metastasis. Three cases of SGC died from liver metastasis, lung metastasis and parotid gland metastasis, respectively, without recurrence at the primary site of tumor. The time of discovery of metastasis was 5 years after surgery. Tumors larger than stage T2b at initial diagnosis were present in all deaths. Three SCC patients died at the end of follow-up, two died of pulmonary metastasis and one died of intestinal metastasis. The time of metastasis was 2 to 8 years postoperatively. All SCC deaths were larger than T2b and had local recurrence. Both MM patients died 6 years after surgery, one died of brain metastasis and the other died of lung metastasis. Previous reports have suggested that MM is more prevalent in liver metastases [21]. Paola et al. suggested that Patients affected by advanced malignant eyelid carcinoma need to be strictly controlled because metastasis can develop at least 5 years after surgical treatment [22].

Orbital exenteration surgery, a procedure that is catastrophic in terms of ocular function and appearance, was administered sparingly but only when eyelid neoplasms are potentially fatal or relentlessly progressive cannot be treated more effectively in other ways [23]. In our study, 7 patients underwent orbital exenteration, of these patients, 29% were BCC, 57% were SGC and 14% were malignant melanoma. The 5-year survival after surgery was 100%, one patient with MM died of brain metastatic neoplasm in 6 years after surgery. Although orbital exenteration is a severely disfiguring procedure, it is still an effective and economical treatment for eyelid malignancies that cannot be controlled by simple excision or radiotherapy [24].

In general, our study found that 4–5 mm incision edge for BCC, and 5–6 mm incision edge for SGC, SCC and MM were practicable, because both intraoperative frozen section and postoperative paraffin section confirmed that the resection edge of the tumor was controlled by the tumor resection edge. Wide local excision can reduce the times of eyelid tumor biopsy and shorten the operation time. There is no need for special pathologists to cooperate with ophthalmologist. It is more suitable for ophthalmic hospitals with a large number of patients and no professional pathologists to cooperate.

However, there were some limitations in our study. First, all patients were recruited from a single-center and hospital based design. Secondly, as a retrospective study, it’s also limited in terms of recall of patients and makes our findings skewed. Last but not least, the explanation for variations of eyelid malignant neoplasms is merely based on speculation, needs further mechanism investigation.

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