Periocular Sebaceous Carcinoma Research Articles

S1‐Leitlinie Talgdrüsenkarzinom

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable or metastatic sebaceous gland carcinomas. Local procedures and system therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually in an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

S1-Guideline Sebaceous Carcinoma.

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

Periocular sebaceous carcinoma: updates in the diagnosis, treatment, staging, and management.

Periocular sebaceous carcinoma (PSC) is a rare, aggressive, and potentially metastatic adnexal malignancy. Due to the ability of PSC to resemble several benign and malignant conditions, diagnosis is often delayed or mistaken. In addition, even with a known diagnosis, choosing the right treatment is still an open debate. For this reason, we decided to review the most up-to-date literature on PSC and propose a dedicated procedural protocol to help clinicians when dealing with PSC. A PubMed search was carried out using the terms "Sebaceous Carcinoma", "Adnexal Periocular Cancer", "Sebaceous Carcinoma AND eyelid", "Periocular Sebaceous Carcinoma", and "Ocular Adnexa". Pertinent studies published in English from 1997 up to December 2022 were compared to the selection criteria and if suitable, included in this review. Through the initial search, 84 articles were selected. Of these, 36 were included in the final study. Several papers explored different diagnostic and therapeutic strategies regarding PSC diagnosis and management. In light of the current literature review and the multidisciplinary experience of three clinical centers, a dedicated procedural protocol is proposed. PSC diagnosis may be achieved through accurate clinical evaluation, but it requires histopathologic confirmation, which can be challenging. Dermoscopy, in vivo reflectance confocal microscopy, and optical coherence tomography may facilitate PSC clinical examination, while immunohistochemistry stains may support histological diagnosis. Appropriate disease staging is necessary before choosing the treatment, as local disease requires radically different treatment compared to advanced disease. In addition, recent innovations in nonsurgical treatments, including radio-chemotherapy, immunotherapy, and targeted therapy, may be a viable option in the most challenging cases.

Periocular Sebaceous Carcinoma: A Case Audit from the National Specialist Ophthalmic Pathology Service in Liverpool from 2009 to 2022 to Assess the Diagnostic Utility of PRAME Expression

Introduction: Periocular sebaceous carcinoma (PSC) remains a common diagnostic pitfall both clinically and histomorphologically. PRAME (preferentially expressed antigen in melanoma) has been studied in the various neoplasms as proposed as diagnostic and therapeutic markers. PRAME is expressed in normal sebaceous units and in some sebaceous lesions; however, its utility in sebaceous carcinoma diagnosis has not yet been extensively investigated. We conducted a 13-year retrospective review of the patients diagnosed with PSC at the National Specialist Ophthalmic Pathology Service in Liverpool. Herein, we report the histomorphological and immunohistochemical (IHC) features of these tumors, particularly PRAME expression in this cohort. Methods: Thirty-one PSC cases diagnosed between 2009 and 2022 were retrieved from the histopathology archives. Twenty cases diagnosed as invasive PSC and 11 cases with in situ PSC were included. The hematoxylin and eosin (H&E) slides and previously performed IHC slides were reviewed; clinical information data were obtained. Cases with an adequate tissue were also stained for PRAME (preferentially expressed antigen in melanoma) and adipophilin (if not already performed). Results: In total, there were 24 females and 7 males diagnosed with PSC, ranging from 55 to 90 years (median, 78 years). The types of specimens received were 11 conjunctival mapping biopsies, 19 excisions/wedge resections, and 1 orbital exenteration. The eyelid was the commonest site involved (n = 24), followed by eyelid with conjunctiva (3), and conjunctiva alone (4). All patients presented with the clinical suspicion of malignancy. Histologically, 11 invasive PSC (55%) exhibited poorly differentiated morphology, composed of predominantly atypical basaloid cells with minimal sebocytic differentiation; 9 cases (45%) were moderately differentiated with noticeable finely multivacuolated cytoplasm; and 3 (15%) showed associated comedo necrosis. Most invasive PSC showed moderate-to-brisk mitotic activities. Of those cases with available immunostains (n = 31), 25 (80.6%) expressed adipophilin; 18 (58.1%) Ber-EP4; 14 (45.2%) epithelial membrane antigen (EMA); and 5 (16.1%) both androgen receptor and perforin positivity. PRAME expression was seen in normal sebaceous glands; however, only (5/19; 26%) of invasive PSC showed focal weak-to-moderate PRAME positivity, and mostly in moderately differentiated tumors. None of the in situ PSCs were PRAME-positive. Conclusions: Most PSCs are moderate-to-poorly differentiated. Although PRAME is expressed in normal sebaceous units, it appears less useful as diagnostic marker for PSC, especially in poorly differentiated tumors. In difficult cases, panels of IHC studies (adipophilin, Ber-EP4, and EMA) achieve a definitive diagnosis.

Consultations in Eye Pathology: Experience at the Ophthalmology Specialty Hospital.

Ophthalmic pathology is a discipline that relies heavily on a knowledge of clinical ophthalmology. The diagnosis of ocular and periocular lesions can be challenging because some lesions and diseases are unique to this region, whereas others may demonstrate site-specific differences from nonocular counterparts. Because of these challenges, ocular and periocular biopsies are frequently referred to specialized ophthalmic pathology centers for second opinion diagnoses. To analyze the referral patterns, diagnostic challenges, and diagnostic discrepancies for second opinion referrals at a dedicated ophthalmic pathology laboratory with an emphasis on lesions of special interest in ophthalmic pathology. Data sources included the pathology records of all slides and blocks received in consultation at the referral eye pathology center between December 1, 2015, and December 1, 2022, the personal experience of senior authors, and published peer-reviewed literature. Corneal, intraocular, and conjunctival biopsies are the most common types of cases received in consultation without the referring pathologist's diagnosis, likely reflecting diagnostic challenges. Degenerative intraocular processes occasionally raise concern for a neoplasm. Conjunctival melanocytic lesions are the most common conjunctival biopsies referred for second opinion diagnosis and require careful tissue sampling and clinical-pathologic correlation. Careful clinical-pathologic correlation, a high level of suspicion, and adequate sampling also are required for the accurate diagnosis of periocular sebaceous carcinoma. The diagnostic discrepancies involving uveal, retinal, conjunctival, eyelid, and temporal artery biopsies are most likely to adversely influence patient management and possible outcome. Such specimens may benefit from referral to specialized ophthalmic pathology laboratories.

Combination treatment of bilateral periocular sebaceous carcinomas with microsatellite instability with neoadjuvant pembrolizumab and Mohs surgery.

This case highlights the successful use of pembrolizumab for neoadjuvant treatment of MMR-deficient sebaceous carcinoma of bilateral eyelids to reduce tumour burden allowing smaller defect post-Mohs surgery and better reconstructive outcome. Microsatellite stability, tumour mutational burden and PD-L1 expression are important prognostic factors to be considered for the use of neoadjuvant pembrolizumab. Further studies are needed to determine if neoadjuvant pembrolizumab consistently improves surgical and cosmetic outcomes and reduces local recurrence and metastasis.

Yield of sentinel lymph node biopsy in sebaceous carcinoma and predictors of advanced disease: A retrospective analysis of the National Cancer Database

To the Editor: Sebaceous carcinoma (SC) is a rare cutaneous malignancy with potential for lymph node or distant metastasis. Most SC presents as localized disease, but periocular SC manifests distinct tumor behavior from extraocular SC with a greater propensity for metastasis. Present guidelines suggest that American Joint Committee on Cancer, Eighth Edition stage T2c periocular or greater tumors can be considered for sentinel lymph node biopsy (SLNB), although SLNB is not recommended for extraocular SC because subclinical nodal metastasis is thought to be uncommon in this setting.

Abstract 2987: Comparison of the anticancer effects of Mitomycin-C and 5-Fluorouracil on novel periocular sebaceous carcinoma cell lines

Abstract Background: Sebaceous carcinoma (SC) is a highly malignant and potentially lethal neoplasm that most commonly arises from the ocular adnexa. Surgical management is the current mainstay of treatment; however, globe sparing tumor control is often complicated by pagetoid (or intraepithelial) invasion. Topical mitomycin-c (MMC) or 5-fluorouracil (5-FU) have been used as adjunctive medical therapy on the basis of their success in treating other ocular neoplasms. Yet, little is known of their effects on SC tumorgenicity. Here, we characterized effects of MMC and 5-FU in SC in vitro. Methods: Periocular SC tissue samples were collected from two patients with histologically confirmed disease. This study was approved by the University of Miami Institutional Review Board and was conducted in a Health Insurance Portability and Accountability Act of 1996—compliant manner. Molecular characterization of the SC cells was done by immunocytochemistry and whole exome sequencing. SC cells were treated with MMC and 5-FU. The cytotoxic effects were evaluated using a viability assay and the kinetics of these effects were investigated by measuring cell proliferation over time. Migration capability of SC cells after drug treatment was examined by wound healing assays. Results: Two SC cell lines, called Bascom Palmer 50 and 52 (BP50 and BP52), were established. Both cell lines retain the immunophenotypic and molecular features of SC. MMC reduced cell viability in both cell lines in a dose-dependent manner. MMC decreased SC cell proliferation and reduced overall cell number significantly compared to the untreated controls in a dose-dependent manner. MMC also inhibited SC migration capacity significantly. Conversely, 5-FU treatment did not affect cell viability or migration capacity in a dose-dependent fashion. While treatment with high-dose 5-FU inhibited SC proliferation, it did not reduce cell number below baseline. Conclusions: We successfully generated SC cell lines and characterized the effects of MMC and 5-FU on these lines. Clinical medical management of periocular SC has been based of empirical data. Our findings suggest that MMC possess superior cytotoxic and cytostatic activity against SC compared to 5-FU in vitro. Taken together, these preliminary findings indicate that MMC may be more efficacious than 5-FU in the treatment of periocular SC. Currently, investigations are underway to identify novel therapeutic targets and test their efficacy in our cell lines. Citation Format: Steven H. Lang, Ryan A. Gallo, Michelle G. Zhang, David T. Tse, Daniel Pelaez, Andrew J. Rong. Comparison of the anticancer effects of Mitomycin-C and 5-Fluorouracil on novel periocular sebaceous carcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2987.

Could Extension Into the Lacrimal Gland and Sac Thwart Topical Chemotherapy for Intraepithelial Sebaceous Carcinoma?

To identify the frequency of intraepithelial (Pagetoid) spread beyond the ocular surface-namely beyond conjunctiva and cornea-in patients undergoing orbital exenteration for advanced periocular Sebaceous carcinoma (SC). A retrospective, noncomparative observational case series. Patients undergoing orbital exenteration for biopsy-proven SC, at Moorfields Eye Hospital between 1997 and 2013. Review of clinical records and histological specimens, with particularly reference to involvement of conjunctiva and the extent of Pagetoid infiltration beyond the examinable ocular surface-here termed "hidden" disease. Histological evidence of intraepithelial SC within the lacrimal sac or lacrimal gland. Twenty-nine patients had clinical data and histological specimens adequate for review. Seventeen (59%) did not have a discrete mass (clinically or histologically) and, on clinical examination, were thought to only have extensive intraepithelial carcinoma; foci of microscopic invasion were, however, detected histologically in 11/17 (65%) of these specimens. Moreover, the in situ carcinoma was found to have invaded far in lacrimal gland ductules in 1/17 patients, in the lacrimal sac (in 2 patients; 12%) or in both the gland and sac (in 2 patients); these 5/17 (29%) cases all showed extensive poorly differentiated intraepithelial SC. Of the 12 other patients who had both Pagetoid spread and a clinically evident nodule, 3 had histological evidence of "hidden" disease. Although-due to their being operated in the era prior to the accepted usage of topical therapy for this condition-some of these exenterations might have had particularly advanced in situ SC, over a quarter of patients with periocular SC warranting orbital exenteration show "hidden" intraepithelial tumor within the lacrimal gland and sac. This important finding might significantly reduce the efficacy (particularly in the lacrimal gland) of the various topical therapies used for in situ SC of the ocular surface, and it also emphasizes the importance of excising both the lacrimal gland and sac in all orbital exenterations for this particular tumor.

Differences in 7th and 8th edition American Joint Committee on Cancer staging for periocular sebaceous carcinoma

ObjectiveTo examine the clinicopathological features of periocular sebaceous carcinoma and describe the differences in T category between the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging system for eyelid carcinoma in a Canadian population. MethodsThis study is a single-centre retrospective review of consecutive patients diagnosed with periocular sebaceous carcinoma at Vancouver General Hospital over a 24-year period. Medical records and pathological slides were reviewed. Clinicopathological features, management, and outcomes were recorded. Each carcinoma was staged as per both the seventh and eighth editions AJCC staging system for eyelid carcinoma. ResultsForty-five patients (25 women, 20 men) were identified with a median age of 74 years (range 42–91 years). Tumour size was with a median of 4 mm (range 1–30 mm) and a mean of 6.7 mm. Using the seventh edition, patients were assigned the following T categories: Tis = 10, T1 = 9, T2 = 11, T3 = 8, T4 = 0. Under the eighth edition, 18 of 45 patients (40%) were restaged, with the majority of these (15 patients, 33%) being downstaged. The eighth edition categories were as follows: Tis = 10, T1 = 22, T2 = 3, T3 = 0, T4 = 3. Three patients developed disease recurrence, 2 of whom (staged T2c and T4b) died of disease. ConclusionsThere were substantial differences in the seventh and eighth editions of AJCC for the staging of periocular sebaceous carcinoma. Our series had small tumours at presentation with infrequent recurrences or metastases. We found a high number of patients with in-situ-only disease.

Periocular Sebaceous Carcinoma Masquerading as an Intratarsal Cyst.

A 60-year-old woman with no significant medical history presented to an outside eye care provider for a persistent right lower eyelid lesion. This lesion was diagnosed as a chalazion, and she underwent incision and drainage. Postoperatively, the lesion did not resolve and maintained the same size and appearance. She was referred 6 months later for tarsal cyst excision. Examination was remarkable for an intratarsal cystic lesion involving the margin of the right lower eyelid (Fig. A, B). There was no associated madarosis, ulceration, bleeding, keratinization, or telangiectasia. A wedge excision and reconstruction were performed. Pathologic examination revealed a poorly differentiated sebaceous carcinoma (Fig. C, D). The patient underwent a second resection and conjunctival map biopsies, which showed negative surgical margins and no conjunctival involvement. She subsequently underwent reconstruction, and there was no evidence of recurrence at 6-month follow-up.External photograph demonstrating a right lower eyelid sebaceous cell carcinoma and corresponding histological findings. A,B, The cystic lesion involves the posterior aspect of the tarsus and extends to the margin. C, Lower power photomicrograph demonstrating the cystic growth pattern of the lesion (hematoxylin and eosin; original magnification = ×10). D, High magnification photomicrograph demonstrating that the cyst wall is composed of atypical cells with marked nuclear pleomorphism and vacuolated or foamy cytoplasm in many cells (hematoxylin and eosin; original magnification = ×300).Sebaceous carcinoma is a relatively rare, aggressive malignancy most commonly arising from the periocular tissues including the meibomian glands of the tarsus, and the glands of Zeis of the eyelashes, caruncle, and skin of the eyebrow. Although sebaceous carcinoma accounts for only 0.5% of all eyelid lesions, it is the most concerning because it is associated with increased morbidity and mortality. This periocular malignancy is notoriously difficult to diagnose, masquerading as an assortment of conditions which frequently leads to delays in diagnosis and proper treatment in greater than two thirds of cases. Despite a seemingly benign appearance, any lesion with yellow coloration and thickening of the eyelid or adjacent conjunctiva should cause the clinician to consider sebaceous carcinoma as a possibility with a low threshold for biopsy.

Sebaceous carcinoma: controversies and their evidence for clinical practice.

Sebaceous carcinoma (SC) is a potentially aggressive malignancy of periocular or extraocular skin. It arises sporadically or is associated with Muir-Torre syndrome (MTS). Here, we review three controversial clinical conundra related to the diagnosis and treatment of SC and offer evidence-based recommendations. First, following a diagnosis of SC, deciding which patients to screen for MTS can be challenging. The Mayo MTS Risk Score is a clinical score that incorporates the key cutaneous findings in MTS but relies heavily on personal and family history that may not be available at the time of SC diagnosis, especially in young patients. Young patients, who have extraocular SC and are suspected to have MTS though do not meet criteria by Mayo MTS Risk Score, should have their tumors tested usingimmunohistochemistry for mismatch repair proteins. Second, sentinel lymph node biopsy (SLNB) is used in periocular SC to evaluate nodal disease. Patient selection is critical for SLNB. Periocular SC stage ≥ T2c (by American Joint Commission on Cancer, 8th edition) may be considered for SLNB given positivity rates over fifteen percent in expert hands. Lastly, treatment of metastatic SC is an area of active investigation. When possible, tumor profiling may be used to select targeted agents. Future research into these three key questions is needed.

Muir-Torre syndrome appropriate use criteria: Effect of patient age on appropriate use scores.

Muir-Torre syndrome (MTS) is a rare inherited syndrome, with an increased risk of sebaceous and visceral malignancy. Prior reports suggest screening for mismatch repair (MMR) deficiency may be warranted in patients <50 years and when sebaceous neoplasms are located on a non-head and neck location. Previously, appropriate use criteria (AUC) were developed for clinical scenarios in patients >60 years concerning the use of MMR protein immunohistochemistry (MMRP-IHC). This analysis explores the appropriateness of testing in patients ≤60 years. Panel raters from the AUC Task Force rated the use of MMRP-IHC testing for MTS for previously rated scenarios with the only difference being age. Results verify the previously developed AUC for the use of MMRP-IHC in neoplasms associated with MTS in patients >60 years. Results also show that in patients ≤60 years with a single sebaceous tumor on a non-head and neck site, MMRP-IHC testing should be considered. Testing can also be considered with a 2-antibody panel on periocular sebaceous carcinoma in younger patients. Our findings align with known evidence supporting the need to incorporate clinical parameters in identifying patients at risk for MTS, with age being a factor when considering MMRP-IHC testing.

Current review of sebaceous cell carcinoma.

Periocular sebaceous cell carcinoma is a rare malignancy that is often misdiagnosed leading to increased morbidity and mortality. This review aims to describe current knowledge on the disease to aid clinicians in timely diagnosis and treatment. New research has shown that the diagnosis of sebaceous cell carcinoma can be aided with immunohistochemical stains. A revision in the American Joint Committee on Cancer staging system incorporates new tumor size classifications in the staging of eyelid carcinomas. Wide local excision and Mohs micrographic surgery continue to represent the standard of care for initial treatment of localized disease. The current review highlights diagnostic and treatment modalities to allow clinicians to make timely diagnosis and tailor treatment plans for individual patient presentations.

Analysis of hedgehog signaling in periocular sebaceous carcinoma

PurposeSebaceous carcinoma (SC) is a clinical masquerader of benign conditions resulting in significant eye morbidity, sometimes leading to extensive surgical treatment including exenteration, and even mortality. Little is known about the genetic or molecular basis of SC. This study identifies the involvement of Hedgehog (Hh) signaling in periocular SC.MethodsFifteen patients with periocular SC patients were compared to 15 patients with eyelid nodular basal cell carcinoma (nBCC; a known Hh tumor), alongside four normal individuals as a control for physiological Hh expression. Expression of Patched 1 (PTCH1), Smoothened (SMO), and glioma-associated zinc transcription factors (Gli1 and Gli2) were assessed in histological sections using immunohistochemistry and immunofluorescence (IF) techniques. Antibody specificity was verified using Western-blot analysis of a Gli1 over-expressed cancer cell line, LNCaP-Gli1. Semi-quantification compared tumors and control tissue using IF analysis by ImageJ software.ResultsExpression of the Hh pathway was observed in SC for all four major components of the pathway. PTCH1, SMO, and Gli2 were more significantly upregulated in SC (P < 0.01) compared to nBCC. Stromal expression of PTCH1 and Gli2 was observed in SC (P < 0.01). In contrast, stromal expression of these proteins in nBCC was similar or down-regulated compared to physiological Hh controls.ConclusionsThe Hh signaling pathway is significantly more upregulated in periocular SC compared to nBCC, a known aberrant Hh pathway tumor. Furthermore, the stroma of the SC demonstrated Hh upregulation, in particular Gli2, compared to nBCC. Targeting of this pathway may be a potential treatment strategy for SC.

Squared-Off Nuclei and "Appliqué" Pattern as a Histopathological Clue to Periocular Sebaceous Carcinoma: A Clinicopathological Study of 50 Neoplasms From 46 Patients.

The histopathological diagnosis of periocular sebaceous carcinoma can be difficult in poorly differentiated cases showing few mature sebocytes. The authors examined 50 periocular sebaceous carcinomas from 46 patients to determine the frequency of 2 features seen in this neoplasm, namely cells with squared-off nuclei and so-called "appliqué" pattern (peritumoral subnecrosis of peripherally located neoplastic cells). Neoplastic cells with squared-off nuclei were found in varying numbers in both the intraepithelial and dermal (invasive) components in all neoplasms, whereas the appliqué pattern was observed in a third of the cases. It is concluded that these features, taken together, may serve as a clue for the diagnosis of periocular sebaceous carcinoma.

An Analysis of Conjunctival Map Biopsies in Sebaceous Carcinoma.

To evaluate the need for standardized conjunctival map biopsies in periocular sebaceous carcinoma and to formulate recommendations regarding map biopsy number, location, size, and utility based on analysis of biopsy locations, results, and outcomes. Retrospective consecutive series of patients with sebaceous carcinoma treated at a tertiary care hospital from 1988 to 2013. Main outcome measures included conjunctival biopsy locations, number, size, and pathology. A diffuse eyelid pattern was evident on presentation in 28/51 patients (54.9%) versus a solitary eyelid nodule in 23/51 (45.1%). Forty-five patients underwent a total of 429 conjunctival biopsies. The conjunctiva was negative in 277 specimens (64.6%), positive in 121 (28.2%), suspicious in 26 (6.1%), and nondiagnostic in 5 (1.2%). Intraepithelial conjunctival involvement was present in 36 patients (70.6%) of whom 23 (63.9%) presented with a diffuse eyelid appearance. There was no statistically significant correlation between primary tumor location and sites of positive biopsies or biopsy size. The pattern at presentation and location of primary tumor did not correlate with biopsy results. Clinical assessment regarding conjunctival involvement was incorrect in 10 of 23 patients (43.5%) with a solitary nodule. Despite primary tumor resection with clear margins confirmed on pathology, 5 of 45 (11%) patients had locally recurrent sebaceous carcinoma. Conjunctival biopsy size does not correlate with the presence of tumor in the biopsy. Primary tumor location and pattern of tumor at presentation do not correlate with conjunctival biopsy results. Irrespective of the clinical tumor features, standardized conjunctival map biopsies are essential in staging periocular sebaceous carcinoma.

P16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma

To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. Retrospective observational case series with laboratory investigations. Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA insitu hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of >70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC.

Sebaceous Carcinoma of the Eyelid.

Periocular sebaceous carcinoma (PSC) is a rare but aggressive neoplasm that tends to clinically and histopathologically mimic other conditions. PSC can be challenging to diagnose using histomorphology alone given its overlap with 2 more common tumors that occur in this area (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]). Use of immunohistochemistry can help resolve this differential diagnosis. A review of the literature was performed, focusing on the epidemiology, morphology, and immunohistochemical features of PSC. The most useful immunostains in the differential diagnosis of PSC are epithelial membrane antigen, Ber-Ep4, androgen receptor (AR), and adipophilin. To discern PSC from BCC, one should use EMA, Ber-Ep4, AR, and adipophilin, whereas discerning PSC from SCC can be achieved by evaluating AR and adipophilin. In addition, p53 and ERBB2 (formally known as HER2/neu) are other potentially useful immunohistochemical markers for the differential diagnosis of PSC. Use of new immunohistochemical techniques, as well as the elucidation of molecular alterations, such as the presence of ERBB2 amplification, will advance our understanding of PSC.

TERT promoter mutations in periocular carcinomas: implications of ultraviolet light in pathogenesis

Background/aimsUltraviolet light-signature mutations in the telomerase reverse transcriptase (TERT) gene promoter have been identified in cutaneous melanomas, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs). Whether these mutations also...