BRIEF REPORT

Intraepithelial Sebaceous Carcinoma: A Case Report of an Unusual Occurrence Gabriel P. Currie, MD,* Jose A. Plaza, MD,† and Gerald J. Harris, MD‡

Abstract: Sebaceous carcinoma is a malignant neoplasm that occurs most commonly in the periorbital area, usually the eyelid. Its periocular location predisposes to smaller biopsies, thus complicating diagnosis. The neoplasm tends to exhibit aggressive local behavior, metastasizing to regional lymph nodes, and distant organs. Disease limited to the epithelium is rare, with less than 10 cases reported in the literature. We present the case of a 73-year-old woman who presented with left upper eyelid entropion and conjunctival erythema. Multiple punch biopsies showed an intraepithelial proliferation of atypical basaloid cells with enlarged and hyperchromatic nuclei intermingled with vacuolated cells containing bubbly cytoplasms and scalloped nuclei, consistent with a diagnosis of intraepithelial sebaceous carcinoma. After subsequent orbital exenteration and histological examination, a wide intraepithelial sebaceous component was identified; however, there was no invasive growth. This case highlights the rarity and the potential diagnostic pitfalls of intraepithelial sebaceous carcinoma. Key Words: intraepithelial, sebaceous carcinoma, immunohistochemistry (Am J Dermatopathol 2014;36:673–676)

INTRODUCTION Sebaceous carcinoma is a potentially aggressive malignant neoplasm that derives from sebaceous gland cells. It is a rare neoplasm with an overall survival rate at 5 and 10 years of 71.1% and 45.9%, respectively.1 The disease has a predilection for the head and neck, with greater than two-thirds of cases presenting in this location.2 An invasive component is nearly always identified in sebaceous carcinoma, while disease limited to the epithelium is rare, with less than 10 cases reported in the literature.3–10 The main differential diagnostic consideration in sebaceous carcinoma is squamous cell carcinoma in situ, which is often limited to the epithelium.11 The lack of invasive component in a sebaceous carcinoma may cause diagnostic confusion between the 2 entities.12 As the rates of distant metastasis and tumor death are much higher in sebaceous carcinoma, differentiating between the 2 is imperative.1 Fortunately, immunohistochemistry can greatly aid in From the Departments of *Dermatology, †Pathology, and ‡Ophthalmology, Medical College of Wisconsin, Milwaukee, WI. Dr G.J.H. receives ongoing royalties from Wolters Kluwer for previously published texts. The other authors have no conflicts of interest to declare. Reprints: Gabriel P. Currie, MD, Department of Dermatology, Medical College of Wisconsin, 9200 Wisconsin Avenue, Milwaukee, WI 53226 (e-mail: [email protected]). © 2013 Lippincott Williams & Wilkins

Am J Dermatopathol  Volume 36, Number 8, August 2014

distinguishing between the 2 neoplasms.13 We present the case of a patient with intraepithelial sebaceous carcinoma whose subsequent orbital exenteration did not show an invasive component.

CASE REPORT A 73-year-old female was seen in consultation for a 2-year history of a red, swollen, and irritated left upper eyelid and blurry vision. Physical examination was remarkable for left upper eyelid entropion and eyelid and conjunctival erythema. Multiple punch biopsies of the left upper and lower eyelids and the palpebral and bulbar conjunctiva were performed. Light microscopy showed a proliferation of intraepidermal atypical basaloid cells with enlarged and hyperchromatic nuclei intermingled with vacuolated cells containing bubbly cytoplasm and scalloped nuclei and disordered cell growth (Figs. 1, 2). The differential diagnosis included squamous cell carcinoma in situ and sebaceous carcinoma. Given this differential, immunohistochemistry was performed with epithelial membrane antigen (EMA), androgen receptor (AR), and adipophilin (ADP). Although EMA was negative (Fig. 3), both AR and ADP were positive (Figs. 4, 5). The histological and immunohistochemical findings were supportive of a diagnosis of intraepithelial sebaceous carcinoma. The patient underwent orbital exenteration, and serial step sectioning showed a wide intraepithelial proliferation of atypical basaloid cells with enlarged and hyperchromatic nuclei intermingled with vacuolated cells containing bubbly cytoplasm and scalloped nuclei without invasive growth. There were islands of tumor cells completely surrounded by keratinocytes, supporting a diagnosis of an intraepithelial neoplasm (Fig. 6). In the dermis, there was fibrosis and inflammation.

DISCUSSION Sebaceous carcinoma is a potentially aggressive malignant neoplasm that derives from sebaceous gland cells. It is a rare neoplasm, with a recent review citing the incidence at 2.03 per 1,000,000 in whites, 1.07 per 1,000,000 in Asian/ Pacific Islanders, and 0.48 per 1,000,000 in blacks.1 That same review found an overall survival rate at 5 and 10 years of 71.1% and 45.9%, respectively, with 31% due to cancer.1 The disease has a predilection for the head and neck, with estimates around 70%.2 Kass and Hornblass14 found that 63% occurred in the upper eyelid, 27% in the lower eyelid, and 5% diffusely involved both eyelids. Its head and neck location predisposes to smaller biopsies, complicating the diagnosis. Furthermore, it is notorious for its ability to masquerade as other periocular lesions both clinically and histologically, especially squamous cell carcinoma and basal cell carcinoma with clear cell features.3 Several immunohistochemical markers have been used in differentiating sebaceous www.amjdermatopathology.com |

673

Currie et al

FIGURE 1. A low-power view showed a proliferation of atypical basaloid cells with enlarged and hyperchromatic nuclei intermingled with vacuolated cells containing bubbly cytoplasms and scalloped nuclei.

carcinoma from its common mimickers such as squamous cell carcinoma and other basaloid neoplasms. These include anti-EMA, anti-CA15-3, anti-epithelial antigen (Ber-EP4), anti-AR, and ADP.13 EMA, anti-CA15-3, Ber-EP4, and ADP are used in differentiating sebaceous carcinoma from basal cell carcinoma with clear cell features, whereas AR and ADP are used in differentiating sebaceous carcinoma from squamous cell carcinoma. Others have been proposed, including alpha/beta hydrolase domain-containing protein 5, progesterone receptor membrane component-1, and squalene synthase. Alpha/beta hydrolase domain-containing protein 5, progesterone receptor membrane component-1, and squalene synthase are used to differentiate sebaceous carcinoma from basal cell carcinoma with clear cell features but are not widely

FIGURE 2. A high-power view demonstrating disordered cell growth, creating a differential diagnosis that included squamous cell carcinoma in situ and intraepithelial sebaceous carcinoma.

674

| www.amjdermatopathology.com

Am J Dermatopathol  Volume 36, Number 8, August 2014

FIGURE 3. Only background staining noted with EMA.

used.15 It is our experience that EMA and AR can often be negative and that ADP is most useful. In some series, ADP has been shown to stain nearly 100% of sebaceous neoplasms.16 Furthermore, a recent article has shown the sensitivity and specificity of ADP to be 88.5% and 77%, respectively.17 That same article showed ADP positivity in 1 of 10 squamous cell carcinomas, but the pattern of staining was different.16,17 The characteristic staining pattern in sebaceous neoplasms is a membranous vesicular pattern (Fig. 5), whereas nonsebaceous clear cell tumors show more granularity, particularly in histiocytes and basaloid cells (Fig. 7).16 In our patient, the constellation of histological findings demonstrating vacuolated cells containing bubbly cytoplasm and scalloped nuclei and the ADP positivity by immunohistochemistry supported the diagnosis of intraepithelial sebaceous carcinoma. Intraepithelial sebaceous carcinoma refers to a tumor that does not extend beyond the epidermal basement membrane and/or lacks any association with preexisting sebaceous glands. Compounding the difficulty of this diagnosis is the

FIGURE 4. AR positivity. Ó 2013 Lippincott Williams & Wilkins

Am J Dermatopathol  Volume 36, Number 8, August 2014

FIGURE 5. ADP positivity, demonstrating a vesicular pattern.

rarity of intraepithelial disease. To the best of our knowledge, there are less than 10 reported cases of intraepithelial sebaceous carcinoma.3–10 In our patient, no invasive growth was seen on diagnostic multiple punch biopsies or definitive orbital exenteration, creating a diagnostic dilemma. Our case highlights the histological differential diagnosis of intraepithelial sebaceous carcinoma, most importantly squamous cell carcinoma. Sebaceous carcinoma exhibits 2 patterns of growth. In the first, conventionally referred to as pagetoid, large individual neoplastic cells with abundant clear cytoplasm and hyperchromatic nuclei are found throughout all layers of the epithelium. In the second, large, atypical cells are contiguous with one another and partially or fully replace the full thickness of the epithelium.3 It is not known if intraepithelial sebaceous carcinoma occurs by a multicentric process, by intraepithelial spread, or propagation of sebaceous gland carcinoma from the

Intraepithelial Sebaceous Carcinoma

FIGURE 7. ADP positivity in basal cell carcinoma, demonstrating a granular pattern.

conjunctival epithelium. Loeffler and Perlman7 have suggested that it arises from a multicentric growth pattern, whereas Margo and Grossniklaus4 have postulated that the tumor may arise de novo within the conjunctival epithelium because they saw no clear focus of neoplasia in sebaceous glands of the eyelid. Margo and Grossniklaus4 further suggest that there is spontaneous involution of the glandular component, leaving only intraepithelial disease. Furthermore, Jakobiec18 cites the common embryonic origin of the sebaceous glands of the tarsus, caruncle, and conjunctival epithelium. The conjunctival epithelium has the potential to evolve into sebaceous carcinoma.18 Finally, in our patient, the remote possibility exists that a communication with a Meibomian gland in the tarsus was removed before the exenteration when the patient was biopsied. Further studies are needed to discern the method of spread. In summary, sebaceous carcinoma is a rare neoplasm with disease limited to the epithelium even rarer. It must be in the differential diagnosis of squamous cell carcinoma in situ, especially when clear cell change is present. Immunohistochemistry can help to identify this neoplasm. Finally, in considering the mortality of sebaceous carcinoma and the low incidence of intraepithelial disease, this must remain in the differential diagnosis of intraepithelial neoplasm. REFERENCES

FIGURE 6. Tangentially cut section of the exenteration specimen demonstrating islands of tumor cells completely surrounded by keratinocytes, supporting a diagnosis of an intraepithelial neoplasm. Ó 2013 Lippincott Williams & Wilkins

1. Dasgupta T, Wilson LD, Yu JB. A retrospective review of 1349 cases of sebaceous carcinoma. Cancer. 2009;115:158–165. 2. Shields JA, Demirci H, Marr BP, et al. Sebaceous carcinoma of the ocular region: a review. Surv Ophthalmol. 2005;50:103–122. 3. Honavar SG, Shields CL, Maus M. Primary intraepithelial sebaceous gland carcinoma of the palpebral conjunctiva. Arch Ophthalmol. 2001; 119:764–767. 4. Margo CE, Grossniklaus HE. Intraepithelial sebaceous neoplasia without underlying invasive carcinoma. Surv Ophthalmol. 1995;39:293–301. 5. Oka K, Katsumata M. Intraepidermal sebaceous carcinoma: case report. Dermatologica. 1990;180:181–185. 6. Ishida M. Intraepidermal sebaceous carcinoma occurring concurrently with actinic keratosis. J Cutan Pathol. 2012;39:731–732. 7. Loeffler KU, Perlman JI. Diffuse intraepithelial sebaceous carcinoma of the conjunctiva. Br J Dermatol. 1997;81:168–173.

www.amjdermatopathology.com |

675

Currie et al

8. Leibovitch I, Selva D, Huilgol S, et al. Intraepithelial sebaceous carcinoma of the eyelid misdiagnosed as Bowen’s disease. J Cutan Pathol. 2006;33:303–308. 9. Arits A, van Marion AM, Thissen CA, et al. Development and progression of a periorbital sebaceous gland carcinoma in situ. Acta Derm Venereol. 2010;90:529–530. 10. Rosner M, Hadar I, Rosen N. Successful treatment with mitomycin c eye drops for conjunctival diffuse intraepithelial neoplasia with sebaceous features. Ophthal Plast Reconstr Surg. 2003;19:477–479. 11. Chao AN, Shields CL, Krema H, et al. Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion. Ophthalmology. 2001;108:1877–1883. 12. Lai TF, Huilgol SC, Selva D, et al. Eyelid sebaceous carcinoma masquerading as in situ squamous cell carcinoma. Dermatol Surg. 2004;30:222–225. 13. Ansai S, Takeichi H, Arase S, et al. Sebaceous carcinoma: an immunohistochemical reappraisal. Am J Dermatopathol. 2011;33:579–587.

676

| www.amjdermatopathology.com

Am J Dermatopathol  Volume 36, Number 8, August 2014 14. Kass LG, Hornblass A. Sebaceous carcinoma of the ocular adnexa. Surv Ophthalmol. 1989;33:477–490. 15. Chen W, Chen P, Li J, et al. Lipid synthesis and processing proteins ABHD5, PGRMC1 and squalene synthase can serve as novel immunohistochemical markers for sebaceous neoplasms and differentiate sebaceous carcinoma from sebaceoma and basal cell carcinoma with clear cell features. J Cutan Pathol. 2013;40:631–638. 16. Ostler DA, Prieto VG, Reed JA, et al. Adipophilin expression in sebaceous tumors and other cutaneous lesions with clear cell histology: an immunohistochemical study of 117 cases. Mod Pathol. 2010;23: 567–573. 17. Muthusamy K, Halbert G, Roberts F. Immunohistochemical staining for adipophilin, perilipin and TIP47. J Clin Pathol. 2006;59: 1166–1170. 18. Jakobiec FA. Sebaceous tumors of the ocular adnexa. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Vol 3. Philadelphia, PA: WB Saunders; 1994; 1745–1770, 1772.

Ó 2013 Lippincott Williams & Wilkins

Intraepithelial sebaceous carcinoma: a case report of an unusual occurrence.

Sebaceous carcinoma is a malignant neoplasm that occurs most commonly in the periorbital area, usually the eyelid. Its periocular location predisposes...
881KB Sizes 0 Downloads 0 Views