SC show positive for epithelial membrane antigen(EMA), BerEp4, Androgen receptor(AR). BCC is negative for EMA and SCC is negative for BerEp4, as well as AR. 3 Using these stains looking for focal sebocytic morphologic features will most likely lead to diagnosis of SC, however there is overlap. If diagnosis is still unclear, additional staining with adipophilin renders both high sensitivity and specificity for SC 10 . This stain requires careful scrutiny at high power since only the characteristic cytoplasmic microvesicular membranous rimming pattern in atypical sebocytes is considered a positive staining pattern, whereas granular cytoplasmic staining is nonspecific and can be seen in BCC, SCC, and other tumors 12 (Figure 2D). The recommended treatment for sebaceous carcinoma of the eyelid is either surgical with complete circumferential peripheral and deep margin assessment or Mohs micrographic surgery, with or without radiotherapy 1,2 . The recognition, rapid biopsy and start of treatment is critical in achieving better outcomes for SC patients. A primary care physician or specialist should always maintain a high index of clinical suspicion for SC in regards to presenting lesions on the eyelid or periorbital region. Likewise, the pathologist must maintain a high index of suspicion for possibility of SC when confronted with this anatomic region, with a low threshold for ancillary staining studies when any ambiguity exists. Along with recognition, treatment is difficult and cosmetic results are often not fully successful due to the cancer’s location. CONCLUSION This case showcases how this rare masquerading malignancy can be so difficult to diagnose. In order to effectively and efficiently diagnose and treat SC patients, all clinicians involved must expand their differential and pay close attention to detail in effort to not prevent delay of therapy. Treatment of SC on the eyelid is further complicated by how it can affect the patient functionally and cosmetically, therefore, collaboration with the patient and other specialists should be included in the care plan. Achieving a rapid, reliable diagnosis with optimized patient prognosis and clinical outcome is difficult but can be achieved with utilization of the most up-to-date pathologic diagnostic modalities, a high index of clinical and pathologic suspicion, and a multidisciplinary team approach. SOURCES 1. Ling M, Silkiss R. Diagnosis and Management of Sebaceous Carcinoma of the Eyelid. Fekrat S, Scott I, eds. EyeNet. Published online August 2013:33-35.
Epub 2020 Sep 9. PMID: 32907843; PMCID: PMC7854832
5. Sargen MR, Cahoon EK, Lynch CF, Tucker MA, Goldstein AM, Engels EA. Sebaceous carcinoma incidence and survival among solid organ transplant recipients in the United States, 1987–2017: a registry-based cohort. JAMA Dermatol 2020;In Press 6. Desiato VM, Byun YJ, Nguyen SA, Thiers BH, Day TA. Sebaceous Carcinoma of the Eyelid: A Systematic Review and Meta-Analysis. Dermatol Surg. 2021 Jan 1;47(1):104-110. doi: 10.1097/DSS.0000000000002660. PMID: 33347004. 7. Lanoy E, Dores GM, Madeleine MM, Toro JR, Fraumeni JF Jr., Engels EA. Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States. AIDS 2009;23:385–93
8. Gall R, Ortiz-Perez S. Sebaceous Gland Carcinoma. [Updated 2023 Aug 14]
Figure 1
Figure 2
(A)Presenting nodule. (B)Postoperative Hughs Tarsoconjunctival flap Stage 1. (C)Postoperative Hughs Tarsoconjunctival flap Stage 2. (D)Fully healed
(A)Basaloid invasive nodular SC at low power(40x) (B)SC at medium power(100x). Red arrows- intraepidermal spread of atypical sebocytes in SC (C)High power(400x) atypical sebocytes (D)Adophilin stain(400x). Red arrows-perivesicular staining
9. Johnson S, Nerad JA, Syed NA. Sebaceous Cell Carcinoma: A Masquerade Syndrome. EyeRounds.org. January 23, 2007
10. Plaza JA, Mackinnon A, Carrillo L, Prieto VG, Sangueza M, Suster S. Role of immunohistochemistry in the diagnosis of sebaceous carcinoma: a clinicopathologic and immunohistochemical study. Am J Dermatopathol. 2015 Nov;37(11):809-21. doi: 10.1097/DAD.0000000000000255. PMID: 26485238.\ 11. Esmaeli B, Nasser QJ, Cruz H, Fellman M, Warneke CL, Ivan D. American Joint Committee on Cancer T category for eyelid sebaceous carcinoma correlates with nodal metastasis and survival. Ophthalmology. 2012 May;119(5):1078-82. doi: 10.1016/j.ophtha.2011.11.006. Epub 2012 Feb 11. PMID: 22330966; PMCID: PMC3869195. 12. Shalin SC, Lyle S, Calonje E, Lazar AJ. Sebaceous neoplasia and the Muir-Torre syndrome: important connections with clinical implications. Histopathology. 2010 Jan;56(1):133- 47. doi: 10.1111/j.1365-2559.2009.03454.x. PMID: 20055911; PMCID: PMC2805836. 13. Dourmishev LA, Rusinova D, Botev I. Clinical variants, stages, and management of basal cell carcinoma. Indian Dermatol Online J. 2013 Jan;4(1):12-7. doi: 10.4103/2229-5178.105456. PMID: 23439912; PMCID: PMC3573444. 14. Yanofsky VR, Mercer SE, Phelps RG. Histopathological variants of cutaneous squamous cell carcinoma: a review. J Skin Cancer. 2011;2011:210813. doi: 10.1155/2011/210813. Epub 2010 Dec 29. PMID: 21234325; PMCID: PMC3018652.
DISCUSSION SC is a rare malignant disease only affecting one to two per 1,000,000 per year 1,2 . It is the third most common malignancy of the eyelid after basal cell(BCC) and squamous cell carcinoma(SCC) 1,3 . SC develops from the sebaceous cells of sebaceous glands which are most concentrated on the face and scalp. Development of SC is thought to be multifactorial with several risk factors. Genetic risk factors have been seen in the loss of expression in the mismatch repair genes MSH2, MSH6, PMS2, and MLH13. This is why SC is found more often in the autosomal dominant Muir-Torre syndrome, a varient of Lynch syndrome. Ultraviolet exposure has been seen to increase risk for SC shown by its geographic predication and increased incidence in races with less melanin 3 . Immunosuppressed patients have been shown to be at increased risk of SC. People with AIDs show an eightfold increase 3 and solid transplant recipients showing as high as a 25 fold increased incidence 5 . Clinically patients will most commonly present as older and white with an enlarging nodule most often in the upper eyelid, where basal cell and squamous cell carcinoma typically present in the lower eyelid 1,3,6 . The five year survival rate for SC has been recorded as low as 70% with a metastasis rate as high as 18%. SC accounts for only 1% of all eyelid tumors but 4.7% of eyelid malignancy. It also shows high rates of local aggression and recurrence and can metastasize to regional lymph nodes or other organs 11 . Historically, much like the case presented, these cancers have been difficult to diagnose. Earning the name the “Great Masquerader, ‘’ SC cases clinically appear similar to many pathologies of the eye such as a chalazion, blepharoconjunctivitis or other eyelid
malignancies 1,2,9 . Not only is SC a clinical masquerader, but even when the lesions are biopsied, they can resemble other skin cancers like BCC and SCC. Incorrect original pathological diagnoses have been reported in 45-75% of SC cases 1 . SC tumor cells’ morphologic characteristics show atypical sebocytes, with scalloped nuclei and multivacuolated clear cytoplasm with hematoxylin and eosin stained sections. Although these atypical cells can be focal in a given tumor, which can contribute to difficulty in diagnosis 12 (Figure 2C). At low power — where sebocytes are often inconspicuous — SC tumors share a similar appearance to BCC by showing invasive nodules of basaloid cells(Figure 2A). Rarely, BCC can contain sebocytes, but BCC will additionally show diagnostic areas of classic BCC morphology, such as peritumoral cleft formation, peritumoral stromal mucin, lack of intraepidermal pagetoid spread, and peripheral palisading of basaloid cells at periphery of tumor nests 13 . A lack of this typical diagnostic constellation of features of BCC in H&E stained histologic sections should alert the pathologist to the possibility of SC and careful study of the tumor for sebocyte differentiation, which can be focal. A single focus in a basaloid tumor, particularly poorly differentiated examples, can serve to distinguish SC from BCC. An important and reliable feature distinguishing SC from BCC is the presence of pagetoid intraepidermal spread of tumor cells with basaloid and sebocyte tumor cells, a feature universally absent in BCC but not present in all SC 12 (Figure 2B). SCC, specifically the clear cell variant, can mimic the clear cell appearance of SC but will show keratinization, lack of true adipocytic vacuolization, and different immunohistochemical staining pattern 14 . Sebocytes in
2. Gall R, Ortiz-Perez S. Sebaceous Gland Carcinoma. [Updated 2023 Aug 14]
3. Patterson JW, Hosler GA, Prenshaw KL, Weedon D. Weedon’s Skin Pathology. Elsevier; 2021.
4. Sargen MR, Starrett GJ, Engels EA, Cahoon EK, Tucker MA, Goldstein AM. Sebaceous Carcinoma Epidemiology and Genetics: Emerging Concepts and Clinical Implications for Screening, Prevention, and Treatment. Clin Cancer Res. 2021 Jan 15;27(2):389-393. doi: 10.1158/1078-0432.CCR-20-2473.
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J LA MED SOC | VOL 176 | FALL 2024
J LA MED SOC | VOL 176 | FALL 2024
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