Skin Colored Papule on the Left Cheek

Correct answer: B. Sebaceoma

Sebaceoma is a benign but uncommon sebaceous neoplasm that develops primarily as a single flesh-to-yellow–colored papule in the head and neck region, which can grow up to several centimeters in size. The median age of onset is 70 years, and it most often affects women.¹ Dermoscopic findings in sebaceoma include peripheral crown vessels, occasional central ulcerations, loosely arranged yellow comedo-like globules, and/or unfocused arborizing vessels that are blurred in color and distributed at the periphery of the lesion over a homogenous, structureless, white-to-yellow background.^2-4 On histopathology, sebaceoma presents as well-defined lobulated neoplasm within the dermis with varying connections to the epidermis.

More than half of the tumor cells are comprised of immature basaloid germinative cells which distinguishes this entity from sebaceous adenoma. The admixture with mature sebaceous cells with sebaceous ducts and holocrine secretions demonstrates the sebaceous differentiation of this neoplasm. There can be scant mitotic figures, but atypia, pleomorphic nuclei, and tumor necrosis are not observed, which distinguishes sebaceoma from sebaceous carcinoma. Several distinctive growth patterns of sebaceoma have been described, including rippled, sinusoidal or labyrinthine, and carcinoid-like patterns have been previously reported.¹ A previous study also reported rare cases of infundibulocystic structures in the superficial and peripheral parts of the tumors with squamous metaplasia.⁵  

All sebaceous neoplasms stain positively for CK7 immunohistochemistry but negatively for BerEP4. This helps distinguish them from keratinocyte carcinomas. Epithelial membrane antigen (EMA) and adipophilin stains can be used additionally to help identify well-differentiated sebaceous cells, which become less effective at detecting poorly differentiated sebaceous neoplasm.¹ Alternatively, androgen receptors are more reliable at differentiating sebaceous neoplasm, even poorly differentiated ones.⁶ These immunochemistry staining patterns can be helpful to differentiate neoplasms of sebaceous origin from those of other origin intermixed with sebaceous differentiation.

Sebaceous carcinoma (SC) is a rare malignant tumor with a median age of 73 years that affects the head and neck region without gender preference. It is clinically classified by location into two lesions: periocular and extraocular lesions. Periocular lesions often develop on the upper eyelid involving the Meibomian glands. Extraocular lesions can develop in other anatomical regions such as the trunk, extremities, and genitalia.¹ Patients with exposure to immunosuppressive therapy, ultraviolet light, or radiotherapy have higher risk of developing SC. These lesions can grow rapidly and are accompanied by tenderness and ulceration.¹ Sebaceous carcinomas are characterized by polymorphic vascular pattern with focused arborizing vessels on dermoscopy, which is bright red and sharply focused over the central parts of the lesion.^2-4 Histologically, SCs are ill-defined multinodular tumors with diffusely infiltrative growth pattern in the dermal and subcutaneous tissues. These neoplasms are predominantly comprised of basaloid germinative cells with varying proportions of scattered mature sebaceous cells admixed throughout. Atypical mitosis, pleomorphism, and tumor necrosis are commonly observed. Occasionally, malignant sebaceous cells can also present in a pagetoid arrangement within the overlying epidermis.¹ SC is the incorrect diagnosis for this case because of the histopathology characteristics of a well-defined lobulated neoplasm as seen in Figure 1(B) and Figure 2, which lacks significant architectural disorder, invasion, necroses, significant mitoses, or cytologic atypia.

Sebaceous lesions can be difficult to discern from a non-pigmented basal cell carcinoma (BCC). Both have similar features, including yellow-white globules, arborizing vessels, and central ulceration and crusting on dermoscopy.⁷ Additionally, BCCs may demonstrate sebaceous differentiation, making it even more challenging to diagnose. However, BCC demonstrates histologic features of peripheral palisading columnar basaloid cells with elongated nuclei invading into deeper dermal tissue, frequent retraction artifact, and pronounced cytological atypia, which are not observed in sebaceoma.¹ No pagetoid spread of malignant sebaceous cells are seen in BCC with sebaceous differentiation unlike that of sebaceous carcinoma. Immunohistochemical stains of the tumor are androgen receptor and EMA negative except for the focal paucity of mature sebaceous cells admixed within.⁸ Additionally, the BerEP4 marker is usually positive for BCC unlike that of sebaceous neoplasm.¹ CK7 positivity is typically seen in adnexal tumors such as sebaceoma and will be negative in keratinocyte carcinomas, such as BCC and SCC. Negative BerEP4 staining in this case rules out BCC as a diagnosis.

Trichoblastomas is a benign follicular neoplasm with a predilection for the face and scalp. It also presents as a sole skin-colored papule or nodule. It develops most commonly between the fourth to sixth decade of life without gender bias.⁹ Although the dermoscopic distinctions of trichoblastomas involve blue-grey to brown homogenous area and blue-grey ovid nests, they resemble sebaceomas histologically as a well-circumscribed basaloid tumor limited to the dermis.^6,9 Trichoblastoma is composed predominately of basaloid follicular germinative cells with pilar differentiation and variable amounts of associated stroma.⁹ Sebaceous differentiation can aggregate close to the epidermis in a trichoblastoma due to the common embryologic origin of the germinative cells. Several growth patterns of trichoblastoma have been reported, including nodular, cribriform, racemiform, and retiform.¹⁰ Few cases in the literature describe ripple-patterned trichoblastoma, which is also a characteristic pattern of sebaceoma.¹¹ Immunohistochemical marker for stroma fibrocytes, CD34, stains positively, which is negative in BCC. CK20-positive Merkel cells in the basal layer is characteristic for trichoblastoma.^10,11 We include this differential diagnosis due to the similarities and overlaps it shares with sebaceoma on histopathology evaluation. The absence of sebaceous differentiation on histopathology makes trichoblastoma the incorrect diagnosis. Trichoblastoma can be distinguished by focal hair germ differentiation, papillary mesenchymal bodies, peripheral nuclear palisading, and stromal induction, which are absent in sebaceoma.

Treatment and management. The patient was offered Mohs surgery to remove the remainder of the tumor out of an abundance of caution in a cosmetically sensitive area but declined to proceed with surgery for this lesion to prioritize the treatment of other NMSCs found during this appointment.

Outcome and follow-up. The patient underwent Mohs surgery for the other tumors with recommendation for routine annual follow-up. He experienced no recurrence or sequalae from his solitary sebaceoma.

Discussion. Diagnosing sebaceoma can be challenging due to its similar features in clinical presentation, dermoscopy evaluation, and histopathology findings to those of other sebaceous neoplasms, adnexal tumors, and tumors with sebaceous differentiation. Indeed, there is a lack of consensus regarding how to classify sebaceoma.^12,13 The debate stems from the classification of sebaceous adenoma (SA), another benign classification that clinicians widely use. Although the diagnosis of SA can be confused with sebaceoma and SC depending on the partial sample examined, the characteristics of SA are different, which include dermal lobules composed of sebocytes with an architecture vaguely resembling a normal sebaceous lobule and are generally comprised of basaloid cells that are less than half of the tumor cellularity.¹³

Clinicians generally treat sebaceomas with surgical excision due to its low recurrence rate. However, there has been a case of SC arising from a sebaceoma, suggesting that partial and superficial biopsies may not be sufficient for the correct diagnosis of sebaceoma.^1,13 Hence, we initially offered Mohs surgery to the patient. 

Lastly, sebaceous tumors are characteristic of Muir Torre syndrome (MTS), a variant of an autosomal dominant hereditary non-polyposis colorectal carcinoma or Lynch syndrome. The incidence rate of MTS in those with sebaceous tumors are said to be between 14%-50%. This association of MTS is highest when multiple sebaceous neoplasms are present, with SC demonstrating the weakest association.¹ Additionally, these lesions can occur concurrently with the visceral malignancy observed in Lynch syndrome or prior to the diagnosis of MTS. Immunohistochemistry of DNA mismatch repair proteins in sebaceous neoplasms can be used as the first-line screening test for MTS. The loss of expression of one or more DNA mismatch repair proteins such as MLH1, MSH2, MSH6 and PMS2, and a family history of visceral malignancies should prompt additional genetic testing to rule out MTS.¹ Although our patient has no contributory family history nor abnormal immunohistochemistry staining for DNA mismatch repair proteins, routine annual skin examination is still recommended to screen for additional sebaceous neoplasms and to monitor the potential progression of the sebaceoma.

This case highlights the importance of careful consideration of diagnostic features in cases where the clinical characteristics of multiple diagnoses overlap, such as with sebaceomas.

References

1. Ferreira I, Wiedemeyer K, Demetter P, Adams DJ, Arends MJ, Brenn T. Update on the pathology, genetics and somatic landscape of sebaceous tumours. Histopathology. 2020;76(5):640-649. doi:10.1111/his.14044

2. Lallas A, Moscarella E, Argenziano G, et al. Dermoscopy of uncommon skin tumours. Australas J Dermatol. 2014;55(1):53-62. doi:10.1111/ajd.1207

3. Lai M, Muscianese M, Piana S, et al. Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature. J Eur Acad Dermatol Venereol. 2022;36(9):1524-1540. doi:10.1111/jdv.18210

4. Giacomel J, Lallas A, Argenziano G, et al. Dermoscopy of basosquamous carcinoma. Br J Dermatol. 2013;169(2):358-364. doi:10.1111/bjd.12394

5. Flux K, Kutzner H, Rütten A, et al. Infundibulocystic structures and prominent squamous metaplasia in sebaceoma-a rare feature. A clinicopathologic study of 10 cases. Am J Dermatopathol. 2016;38(9):678-682. doi:10.1097/DAD.0000000000000494

6. Bayer-Garner IB, Givens V, Smoller B. Immunohistochemical staining for androgen receptors: A sensitive marker of sebaceous differentiation. Am J Dermatopathol. 1999;21(5):426-431. doi:10.1097/00000372-199910000-00004

7. Ungureanu L, Cosgarea I, Şenilǎ S, Vasilovici A. Role of dermoscopy in the assessment of basal cell carcinoma. Front Med (Lausanne). 2021;8:718855. doi:10.3389/fmed.2021.718855

8. Sushrut Save, Swagata Tambe, Chitra Nayak. Basal cell carcinoma with sebaceous differentiation. Indian Dermatol Online J. 2018;9(4):273-275. doi:10.4103/idoj.IDOJ_219_17

9. Płachta I, Kleibert M, Czarnecka AM, Spałek M, Szumera-Ciećkiewicz A, Rutkowski P. Current diagnosis and treatment options for cutaneous adnexal neoplasms with follicular differentiation. Int J Mol Sci. 2021;22(9):4759. doi:10.3390/ijms22094759

10. Cazzato G, Cimmino A, Colagrande A, et al. The multiple faces of nodular trichoblastoma: review of the literature with case presentation. Dermatopathology (Basel). 2021;8(3):265-270. doi:10.3390/dermatopathology8030032

11. Graham BS, Barr RJ. Rippled-pattern sebaceous trichoblastoma. J Cutan Pathol. 2000;27(9):455-459. doi:10.1034/j.1600-0560.2000.027009455.x

12. Lee DW, Kwak SH, Kim JH, Byeon JY, Lee HJ, Choi HJ. Sebaceous carcinoma arising from sebaceoma. Arch Craniofac Surg. 2021;22(2):126-130. doi:10.7181/acfs.2021.00059

13. Misago N, Mihara I, Ansai Si, Narisawa Y. Sebaceoma and related neoplasms with sebaceous differentiation: A clinicopathologic study of 30 cases. Am J Dermatopathol. 2002;24(4):294-304. doi:10.1097/00000372-200208000-00002.

AFFILIATIONS:
¹SERE West Medical Department, Center for Security Forces North Island Detachment, San Diego, CA
²Department of Dermatology, Naval Medical Center San Diego, San Diego, CA

CITATION:

Zhang SX, Kramer KE. Skin colored papule on the left cheek. Consultant. 2024;64(1):e2. doi:10.25270/con.2023.12.000002

Received June 10, 2023. Accepted October 25, 2023. Published online December 8, 2023.

DISCLOSURE:

Drs Zhang and Kramer are service members of the Department of the Navy; the views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, Defense Health Agency, or the United States Government. 

ACKNOWLEDGEMENTS:

None.

CORRESPONDENCE:

Serena X. Zhang, MD. Center for Security Forces North Island Detachment, PO BOX 357068, San Diego, CA 92135-7068 (s.zhang9876@gmail.com)

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