Sebaceous gland carcinoma: analysis based on the 8th edition of American Joint Cancer Committee classification.

PURPOSE: To assess the prognostic value of T category of the 8th edition of American Joint Committee on Cancer (AJCC) classification in periocular sebaceous gland carcinoma (SGC). METHODS: Retrospective interventional case series of 119 cases. RESULTS: Based on the T category of 8th edition of AJCC classification, 119 periocular SGCs were classified into T1 (n = 33, 28%), T2 (n = 37, 31%) T3 (n = 17, 14%) and T4 (n = 32, 27%). There were no statistically significant differences in the rate of tumour recurrence based on T category. The outcome measures that showed significant increase with increase in T category included regional lymph node metastasis (3% for T1, 3% for T2, 12% for T3, and 44% for T4; p < 0.0001), systemic metastasis (0% for T1, 0% for T2, 12% for T3, and 25% for T4; p = 0.002) and death due to metastasis (0% for T1, 0% for T2, 12% for T3, and 22% for T4; p = 0.005). The 5-year Kaplan-Meier estimate rate for regional lymph node metastasis, systemic metastasis and metastasis-related death were all higher for the T4 category tumours (42%, p = 0.005; 34%, p = 0.0002; and 43%, p = 0.0001 respectively) compared to T1 (9%, 0%, and 0%), T2 (5%, 0%, and 0%) and T3 (10%, 17 and 8%) tumours. CONCLUSION: Primary tumour (T) category of the 8th edition AJCC classification predicts the prognosis of patients with periocular SGC. The rates of lymph node metastasis, systemic metastasis, and death is much higher in T4 tumours compared to T1, T2, and T3 tumours. There was no association between T category and tumour recurrence.

Outcome after treatment for sebaceous carcinoma: A multicenter study.

BACKGROUND: Sebaceous carcinoma (SC) is a rare malignant tumour whereby, comprehensive long-term data are scarce. This study aimed to assess the outcome of patients treated with resection for SC. METHODS: Patients treated at four tertiary centres were included. Cumulative incidence curves were calculated for recurrences. RESULTS: A total of 100 patients (57 males, 57%) were included with 103 SCs. The median age was 72 (range, 15-95) years with a median follow-up of 52 (interquartile range [IQR], 24-93) months. Most SCs were located (peri)ocular (49.5%). Of all SCs, 17 locally recurred (16.5%) with a median time to recurrence of 19 (IQR, 8-29) months. The cumulative incidence probability for recurrence was statistically higher for (peri)ocular tumours (p = 0.005), and for positive resection margins (p = 0.001). Two patients presented with lymph node metastases and additional seven patients (8.7%) developed lymph node metastases during follow-up with a median time to metastases of 8 (IQR, 0.5-28) months. Three patients had concurrent in-transit metastases and one patient also developed liver and bone metastases during follow-up. CONCLUSION: SC is a rare, yet locally aggressive tumour. Positive resection margins and (peri)ocular SCs are more frequently associated with local recurrence. SC infrequently presents with locoregional or distant metastases.

Sebaceous Carcinomas: A Clinicopathological Comparison of Ocular and Extraocular Variants.

ABSTRACT: Sebaceous carcinomas (SC) are rare tumors and are currently classified into ocular and extraocular variants. Both variants of SC have very different clinical behavior and different histomorphologic appearance; however, published data are confounding as literature describes prognosis of both variants is similar or even that extraocular variants are more aggressive. In this study we evaluated the clinical and the histopathology of ocular and extraocular SC to confirm the difference between them. We performed a retrospective review of SC in which we studied the clinical and histomorphologic features of 106 cases, including 39 cases of ocular SC and 67 cases of extraocular SC. Only 2/67 cases of extraocular SC had multiple recurrences and none of them metastasized as opposed to our cases of ocular SC wherein 21/39 cases were locally aggressive with multiple recurrences and 5 cases metastasized. Histologically, both neoplasms showed major distinct morphologic features including poor differentiation in cases of ocular SC and well-differentiated tumors in the extraocular anatomic sites. To the best of our knowledge, this is the first case series of SC that compares the clinicopathologic features of ocular and extraocular variants. Awareness of such discrepancy is key to understand this disease and to possibly diagnose and manage these patients accordingly.

Eyelid sebaceous carcinoma: Validation of the 8th edition of the American Joint Committee on cancer T staging system and the prognostic factors for local recurrence, nodal metastasis, and survival.

PURPOSE: To investigate the clinicopathological features and prognostic factors for eyelid sebaceous gland carcinoma (SGC) in an ethnic Chinese population and to validate the performance of the T category of the 8th edition AJCC staging systems, with the aim of providing information for refinements. METHODS: Sixty-three patients with pathological diagnosis of SGC were enroled retrospectively. The clinicopathological features, treatments, and outcomes were collected. Prognostic factors associated with the outcome of local recurrence, regional lymph node metastasis, and tumour-related death were analysed. The performance analysis was performed by comparing the predictive value for survival and the monotonicity of gradients between the 7th and 8th staging systems. RESULTS: The distribution of T1:T2:T3:T4 tumours according to the 7th and 8th edition was 6:40:16:1 and 23:26:5:9, respectively. Positive surgical margin was a poor prognostic factor. Local recurrence was associated with more aggressive histopathological features and surrounding structure invasions. Regional lymph node metastasis was associated with larger tumours. The T category of 8th edition showed better predictability for local recurrence and regional lymph node metastasis, while the T category of 7th edition had better monotonicity of gradients. Tumours classified as T2c or worse had higher risk of regional lymph node metastasis, while tumours T3b or worse in the 8th edition had more tumour-related death. CONCLUSIONS: Patients with higher T category are at risk of regional lymph node metastasis and tumour-related death. Further refinement of the T category of AJCC staging system can focus on the predictability for local recurrence and the monotonicity of gradients.

Mohs micrographic surgery for eyelid sebaceous carcinoma: A multicenter cohort of 360 patients.

BACKGROUND: The decision to perform Mohs micrographic surgery (MMS) or wide local excision (WLE) for eyelid sebaceous carcinoma (SC) is controversial. OBJECTIVE: To compare local recurrence, metastasis, and tumor-related mortality of patients with eyelid SC who were initially treated with MMS versus with WLE. METHODS: A multicenter cohort study. Medical records were reviewed for factors associated with recurrence, metastasis, and tumor-related mortality. All eligible patients were followed up. The impact of initial surgical modality on the prognoses were determined by Cox analyses after control for all confounders. RESULTS: Of the 360 patients included in this cohort, 115 (31.9%) underwent MMS as primary resection, whereas 245 (68.1%) underwent WLE. After a median follow-up period of 60.0 months, local recurrence was observed in 18 patients (15.7%) in the MMS group and 97 patients (39.6%) in the WLE group. Metastasis occurred in 9 patients (7.8%) who underwent MMS and 38 (15.5%) who underwent WLE. In all, 6 patients in the MMS group (5.2%) and 21 in the WLE group (8.6%) died of metastatic SC. Multivariable Cox regression indicated that compared with the WLE group, the MMS group exhibited more favorable local recurrence control (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.24-0.73; P = .002) but a comparable metastasis rate (HR, 1.38; 95% CI, 0.60-3.18; P = .453) and comparable tumor-related mortality (HR, 1.70; 95% CI, 0.59-4.93; P = .329). However, this beneficial effect became nonremarkable for patients with pagetoid intraepithelial neoplasia (HR, 1.73; 95% CI, 0.37-8.21; P = .488). LIMITATIONS: Retrospective nature of the study. CONCLUSION: MMS should be proposed for eyelid SC without orbital involvement to achieve recurrence control; however, this surgical procedure did not change the long-term outcomes in terms of metastasis or tumor-related mortality. Patients with pagetoid intraepithelial neoplasia may require adjuvant measures.

A Case Report of Recurrent Metastatic Sebaceous Carcinoma Which Showed Favorable Response Tt Non-Fluorouracil Based Chemotherapy.

BACKGROUND Sebaceous carcinoma is a rare malignant tumor of the skin adnexa. While surgical resection is a treatment of choice in localized disease, frequent recurrence and distant metastasis make treatment difficult. Moreover, due to its rarity, optimal systemic treatment has not been determined. CASE REPORT A 59-year-old female presented with disseminated subcutaneous nodules. Past history indicated she received repeated surgery, radiation therapy, and fluorouracil-based systemic chemotherapy for recurrent sebaceous carcinoma. Following a subcutaneous nodule biopsy, histopathologic examination confirmed recurrent metastasis of sebaceous carcinoma. Because there was no established regimen as salvage chemotherapy, we decided to administer paclitaxel plus Adriamycin as a combination regimen after a thorough search of previous reports on PubMed. After the patient received 6 cycles of chemotherapy, all masses dramatically regressed. Unfortunately, several new lesions appeared 3 months after cessation of chemotherapy. Therefore, she was treated with anti-HGF antibody through a clinical trial. After that, she received nivolumab. But treatment with all the new agents did not show any response. Furthermore, her disease progressed rapidly. We re-challenged with the paclitaxel and Adriamycin regimen, 2 cycles of chemotherapy, and the follow-up positron emission tomography - computed tomography revealed marked decrement of multiple metastatic nodules. CONCLUSIONS Although several clinical reports have shown the effectiveness of fluorouracil, especially 5-fluorouracil-based chemotherapy, there has been a paucity of reports on other chemotherapeutic agents. We report a case of metastatic sebaceous carcinoma which showed favorable response to non-fluorouracil-based chemotherapy.

Risk Factors for Local Recurrence or Metastasis of Eyelid Sebaceous Gland Carcinoma After Wide Excision With Paraffin Section Control.

PURPOSE: To identify risk factors for local recurrence and metastasis of sebaceous gland carcinoma (SGC) after wide excision with paraffin section control. DESIGN: Retrospective, observational case-control study. METHODS: Setting: Single institution. PATIENT POPULATION: Thirty-four patients with SGC who had undergone excision with 5-mm surgical margins and paraffin section pathologic analysis. Observational Procedures: The following were considered potential risk factors for local recurrence/metastasis of SGC: patient's sex, patient's age, initial diagnosis at other clinics, topical treatments at other clinics, interval between appearance of symptoms and referral to our institution, tumor location, tumor origin, tumor presentation pattern, T category, tumor size, presence/or absence of pagetoid spread, tumor differentiation, mitosis grade, growth pattern. Logistic regression analysis was performed to identify the actual risk factors. MAIN OUTCOME MEASURES: Risk factors for local recurrence or metastasis of SGC after wide excision with paraffin section control. RESULTS: Involvement of both upper and lower eyelids, topical treatments at other clinics, multicentric origin, diffuse pattern, stage T3a, large tumor size, and a nonlobular pattern significantly influenced local recurrence/metastasis (P < .050). Pagetoid spread tended to affect local recurrence/metastasis (P = .052). The other items did not significantly influence local recurrence/metastasis (P > .050). CONCLUSIONS: This study identified risk factors for local recurrence or metastasis of SGC after wide excision with paraffin section pathologic analysis. The results of this study will be helpful to surgeons when planning additional management, such as map biopsy or adjuvant treatment.

Intraoral sebaceous carcinoma metastatic to the lung and subcutis: Case report and discussion of the literature.

BACKGROUND: Intraoral sebaceous carcinoma is a rare form of sebaceous carcinoma with only 9 published cases in the world literature to date. We present a 10th case of intraoral sebaceous carcinoma located in the anterior maxillary gingiva with metastases to the lung and subcutis and discuss 3 possible etiologies for this unique presentation. METHODS: We analyze the clinical presentation, pathology, histology, and genetic testing for a single case study and review relevant literature. RESULTS: The histologic findings of the lung tumor and surgical excisions of the tumors in the gingiva and subcutis suggest the gingiva is the primary site. There is no evidence for the genetic abnormalities consistent with Muir-Torre syndrome. CONCLUSION: The histologic findings suggest the oral cavity is the most likely site of tumor origin. This is the first case of intraoral sebaceous carcinoma reported to arise in the gingiva as well as to spread to cutaneous sites.

Recurrent sebaceous carcinoma of the eyelid: Outcome after postoperative reirradiation.

BACKGROUND: The purpose of this study was for us to describe a case of recurrent sebaceous carcinoma treated with postoperative reirradiation. METHODS: A 38-year-old man was diagnosed with sebaceous carcinoma of the right lower eyelid. The patient developed local recurrence 4 times, with the first one at 30 months after the excision. The first local recurrence was treated with excision and postoperative radiotherapy with 60 Gy/30 fractions/6 weeks. He manifested preauricular nodal metastasis with the third local recurrence, which was confirmed with (18)F-fluorodeoxyglucose positron emission tomography-CT ((18)F-FDG PET-CT). He received 2 courses of adjuvant reirradiation to the right orbit with 45 Gy/25 fractions/5 weeks and 30 Gy/15 fractions/3 weeks, respectively. RESULTS: The patient was successfully treated with no evidence of locoregional recurrence at 2 years after the cancer-directed therapy. The patient's follow-up from the date of diagnosis has been 9 years. CONCLUSION: Adjuvant reirradiation with modest doses may be considered with a view to provide disease control and long-term survival.

Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by differentially expressed microRNAs.

IMPORTANCE: The molecular-genetic alterations contributing to the pathogenesis of sebaceous carcinoma and sebaceous adenoma remain poorly understood. Given that sebaceous carcinoma is associated with substantial morbidity and mortality, there is a critical need to delineate the pathways driving sebaceous carcinoma and candidate molecules for targeted therapy. OBJECTIVE: To describe differentially expressed microRNAs (miRNAs) in a series of periocular sebaceous carcinomas compared with sebaceous adenomas in order to identify pathways driving the pathogenesis of sebaceous carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Thirty sebaceous carcinomas and 23 sebaceous adenomas (including 11 that were confirmed to be related to Muir-Torre syndrome and 6 that were confirmed to be sporadic) were obtained from archives (from 48 patients) of 2 institutions (University of Texas MD Anderson Cancer Center, Houston, and Siriraj Hospital, Mahidol University, Bangkok, Thailand) and profiled. MAIN OUTCOMES AND MEASURES: Expression of miRNAs was determined using total RNA from formalin-fixed, paraffin-embedded tissue and real-time reverse transcription-polymerase chain reaction performed in a microfluidics card containing 378 unique miRNAs. Fold change was determined using the ΔΔCt method (reference probe, RNU48). Median centering was used to normalize the data. Two-sample t tests were used to identify differentially expressed miRNAs. The false discovery rate was assessed by ß-uniform mixture analysis of P values from the t statistics. Significance was defined by this estimated false discovery rate. RESULTS: Serial testing and validation confirmed overexpression of 2 miRNAs previously reported to be oncogenic, miR-486-5p (4.4-fold; P = 2.4 × 10-8) and miR-184 (3.5-fold; P = 1.7 × 10-6), in sebaceous carcinoma compared with sebaceous adenoma and downregulation of 2 miRNAs previously reported to have tumor-suppressive properties, miR-211 (-5.8-fold; P = 2.3 × 10-9) and miR-518d (-4.5-fold; 6.7 × 10-5), in sebaceous carcinoma compared with sebaceous adenoma. CONCLUSIONS AND RELEVANCE: Sebaceous carcinoma exhibits an miRNA expression profile distinct from that of sebaceous adenoma, implicating dysregulation of NF-κB and PTEN (targets of miR-486-5p) and TGF-ß signaling (target of miR-211) in the pathogenesis of sebaceous carcinoma. The identification of miRNAs whose expression is altered in sebaceous carcinoma compared with sebaceous adenoma provides a novel entry point for a more comprehensive understanding of the molecular-genetic alterations pivotal to the development of sebaceous carcinoma.

Prognostic value of clinical and pathologic T stages defined by the American Joint Committee on Cancer for eyelid sebaceous carcinoma in Korea.

PURPOSE: To investigate whether the clinical and pathologic T category classification, as defined by the American Joint Committee on Cancer (AJCC), is associated with lymph nodes (LN) or distant metastasis in patients with eyelid sebaceous carcinoma. METHODS: Forty patients treated for eyelid sebaceous carcinoma at Seoul National University Hospital between March 1999 and December 2011 were retrospectively staged according to the AJCC 7th edition criteria. Three different primary tumor classifications-(1) clinical tumor size at presentation; (2) clinical AJCC T stage (cT) at presentation based not only on size, but also on the extent of involvement and (3) pathologic AJCC T stage (pT) based on histopathological examination-were compared and evaluated with regard to their association with LN or distant metastasis. RESULTS: In univariate analysis, the AJCC cT (p = 0.005) and pT (p = 0.029) categories were significantly associated with metastasis, but clinical tumor size alone did not correlate with metastasis (p = 0.093). Clinical and pathologic AJCC stage T2b or higher tumors were significantly associated with metastasis compared to stage T1 or T2a tumors [odds ratio cT, 8.00 (p = 0.025); pT, 6.91 (p = 0.028)]. CONCLUSIONS: The clinical and pathologic AJCC T category has predictive value for LN or distant metastasis in eyelid sebaceous carcinoma. However, the clinically assessed largest tumor dimension alone is not an effective predictive factor. Clinicians should be aware of the increased risk of metastasis in patients with tumors of stage T2b or higher at initial presentation.

Recrudescent meibomian gland carcinoma treated with Xeloda: case report.

PURPOSE: To observe the curative effect of Xeloda in meibomian gland carcinoma. METHODS: We treated a 53-year-old woman, who had recrudescent meibomian gland carcinoma, with Xeloda. RESULTS: The mass was much smaller with decreased amount of overflow pus after 4 cycles of chemotherapy with Xeloda. CONCLUSIONS: Xeloda played a significant role in treating recrudescent meibomian gland carcinoma in this patient.

Sentinel lymph node biopsy in malignant eyelid tumor: hybrid single photon emission computed tomography/computed tomography and dual dye technique.

PURPOSE: To study the utility of hybrid single photon emission computed tomography / computed tomography (SPECT/CT) scan and dual-dye technique in identification of the sentinel lymph node (SLN) in patients with an advanced malignant eyelid tumor. DESIGN: Nonrandomized prospective interventional study. METHODS: setting: A tertiary eye care center. study population: Patients with an advanced malignant eyelid tumor without clinically involved regional lymph nodes. intervention: SLN biopsy was performed using dual-dye technique (a combination of radiotracer and vital blue dye) following localization by SPECT/CT. main outcome measures: Localization of SLN in the regional node basin by hybrid SPECT/CT scan; SLN identification rate using dual-dye technique; SLN positivity rate; false-negative rate; and complications, if any, of SLN biopsy. RESULTS: Sixteen patients of biopsy-proven eyelid malignancy (7 squamous cell carcinomas [43.75%], 5 sebaceous cell carcinomas [31.25%], and 4 malignant melanomas [25%]) were included in the study. Preoperative localization of SLN was performed using SPECT/CT in 12 patients. SLN biopsy using dual-dye technique was performed in 16 patients. SPECT/CT accurately localized SLN in 11 out of 12 patients. The preauricular region was the most common site of SLN. SLN identification rates for dual-dye, radiotracer, and blue dye techniques were 100% (16/16 patients), 100% (16/16 patients), and 87.5% (14/16 patients), respectively. SLN showed metastasis in 2 patients (12.5%). On follow-up, 1 patient developed cervical lymph node metastasis, thus giving a false-negative rate of 7.14%. There were no complications associated with SLN biopsy. CONCLUSION: Accurate preoperative localization of SLN in relation to adjacent anatomic structures using SPECT/CT aids in intraoperative identification of SLN. SLN biopsy should be considered in patients with eyelid tumors at significant risk for metastasis who have clinically negative nodal basins. Dual-dye technique is safe and feasible in advanced eyelid tumors. Blue dye technique can be used for SLN biopsy in settings where nuclear medicine facilities are not available, albeit with a lower SLN identification rate. Detection of metastasis in SLNs in ∼12% of cases emphasizes the utility of SLN biopsy in accurate staging and treatment of eyelid malignancies.

Expression of Shh and Wnt signaling pathway proteins in eyelid sebaceous gland carcinoma: clinicopathologic study.

PURPOSE: Activation or dysregulation of the Sonic hedgehog (Shh) and Wnt signaling pathways is suggested to lead to the development of many human malignancies. In this study, we investigated Shh and Wnt signaling protein expression in eyelid sebaceous gland carcinoma, and analyzed their correlation with clinical characteristics of the tumor. METHODS: Patients who underwent surgical resection of eyelid sebaceous gland carcinoma from 1999 to 2011 were recruited for the study. Immunohistochemical stainings of Shh signaling proteins (Shh, Gli-1, Gli-2, Gli-3, and ABCG2) and Wnt signaling proteins (Wnt, glycogen synthase kinase 3ß, ß-catenin, lipoprotein receptor-related protein [LRP], and c-Myc) were conducted. RESULTS: Thirty-seven cases of eyelid sebaceous gland carcinoma were included in this study. Twenty-nine patients showed no metastasis, and eight patients showed lymph node or distant metastasis. Shh, ABCG2, and Wnt proteins were more highly expressed in the group with metastasis than in the group without metastasis (P = 0.031, P = 0.015, and P = 0.001, respectively; χ(2) test). Patients showing high ABCG2 expression, Wnt, or LRP expression developed metastasis more commonly than those with low ABCG2, or without Wnt or LRP expression (log rank test, P = 0.019, 0.001, and 0.000, respectively). CONCLUSIONS: The group with metastasis showed higher expression levels of Shh, ABCG2, and Wnt than did the group without metastasis, and patients with strong ABCG2 expression, Wnt, or LRP expression showed higher cumulative incidence of lymph node or distant metastasis, implying that activation of the Shh and Wnt signaling pathway is associated with aggressive behavior of the tumor.

Locally advanced sebaceous cell carcinoma (T3) of eyelid: incidence and pattern of nodal metastases and combined modality management approach.

BACKGROUND: Sebaceous carcinoma (SbCC) is a rare malignancy that often mimics benign conditions. Lymphatic involvement, large T3 tumors herald a dismal survival for patients. We present our series of 13 cases of locally advanced SbCC of the eyelid treated at a surgical oncology unit and describe the clinical profile, patterns of nodal spread and recurrence pattern in this subset of SbCC. METHODS: A retrospective analysis of case records was carried out for patients presenting with orbital tumors between January 1997 and April 2010 in the department of Surgical Oncology, AIIMS, New Delhi, India. All patients underwent orbital exenteration and superficial parotidectomy with neck dissection was added to patients with clinically significant lymphadenopathy. All patients who underwent OE after 2002 were advised radiotherapy as adjuvant therapy. The end point was development of recurrence or end of two year follow up period which ever occurred earlier. RESULTS: Thirteen patients underwent orbital exenteration. Eleven patients had clinically palpable lymphadenopathy. Ten patients (76.9%) had pathologically confirmed metastatic nodes. Parotid lymph node involvement was present in all patients (100%); two of these ten patients also had level II b cervical lymph node involvement. Recurrence was observed in seven patients (53.8%). All recurrences were loco-regional only and no systemic metastases was seen. There were only two recurrences in the group that received PORT. CONCLUSIONS: Eyelid SbCC is a loco-regionally aggressive malignancy and adequate disease control can be achieved with combined modality approach of radical surgery followed by post operative radiotherapy.