Nasal Sebaceous Carcinoma: A Case Report and Review of the Literature
Omar Kholaki, DDS, MD,*Dongkun Chang, MD,yand Roderick Y. Kim, DDS, MDz
Sebaceous carcinoma arising from the nasal vestibule is exceedingly rare, with 3 cases previously reported.
We have described the case of a 69-year-old man with an indolent exophytic growth on the medial aspect of his right nasal vestibule. Incisional biopsy demonstrated sebaceous carcinoma. The clinical and patho- logic features, in addition to the surgical course and the postoperative outcome, are discussed. We also report our findings from a review of the reported data, focusing on the diagnosis and treatment of this rare skin malignancy.
Ó 2019 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 78:82-86, 2020
An estimated 1 in 5 Americans will have developed skin cancer by the age of 70 years.1,2 Skin cancers can be classified as nonmelanoma skin cancer (NMSC) and melanoma, with NMSC cases accounting for one third of all US cancer cases and more than 95% of all skin cancer cases.2-4 Of the NMSC cases, 75% will be basal cell carcinoma,3 20% squamous cell carcinoma,5,6 and 5% will include rare entities such as adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans, and sebaceous carcinoma. Although rare, this subset of NMSC should be considered in every differential diagnosis, given the significant differences in the prognosis, treatment, and follow-up protocols.
In the present case report and review of the re- ported data, an exceedingly rare NMSC arising from the cutaneous sebaceous glands, a sebaceous carci- noma (SC), is discussed. Oral and maxillofacial sur- geons (OMSs), with frequent examination of the head and neck region in their daily practice, are likely to encounter NMSC. Despite the familiar clinical appearance, this rare subset of NMSC can have a more aggressive potential, and OMSs should famil- iarize themselves with these less common lesions.
A 69-year-old man with a medical history significant for diabetes mellitus, hypertension, and gastroesopha- geal reflux disease had been referred by his primary physician to the maxillofacial oncology and recon- structive surgery clinic. He presented with a 4-year his- tory of a slowly enlarging mass of the right nasal vestibule. His chief complaint was the presence of the mass and intermittent symptoms of pain when the lesion was irritated by nose blowing. No previous biopsy or treatment had been rendered. He denied any significant increase in size in the previous few months, unintentional weight loss, fevers, chills, or night sweats. His social history was unremarkable, because he was a nonsmoker and nondrinker. On physical examination, a fleshy 4 6-mm exophytic mass with associated telangiectasia was appreciated on the medial aspect of the right nasal vestibule along the membranous columella (Fig 1). The anterior nasal speculum examination showed that the lesion was limited to this area, with no other lesions within the nasal cavity. No palpable lymphadenopathy was present.
*Resident Surgeon, Department of Oral and Maxillofacial Surgery, Parkland/University of Texas Southwestern Medical Center, Dallas, TX.
yPathologist, John Peter Smith Health Network, Fort Worth, TX.
zAssistant Fellowship Director and Director of Research, Division of Maxillofacial Oncology and Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, John Peter Smith Health Network, Fort Worth, TX.
Conflict of Interest Disclosures: None of the authors have any relevant financial relationship(s) with a commercial interest.
Address correspondence and reprint requests to Dr Kholaki:
Department of Oral and Maxillofacial Surgery, Parkland/University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dal- las, TX 75390-9109; e-mail:Omar.Kholaki@phhs.org
Received July 2 2019 Accepted August 13 2019
Ó 2019 American Association of Oral and Maxillofacial Surgeons 0278-2391/19/31034-1
To confirm the diagnosis, an incisional biopsy of the specimen was performed with the patient under local anesthesia. Hematoxylin and eosin-stained sections showed nests of mildly atypical cells with foamy, finely vacuolated cytoplasm and distinct cell borders.
Minimal mitotic activity was present, with no evidence of necrosis. The initial pathology analysis revealed a well-differentiated sebaceous carcinoma (Fig 2). Given the rarity of this diagnosis, a dermatologic–pathologic review was conducted, which confirmed the orig- inal diagnosis.
The patient was then taken to the operating room for wide local excision (WLE) and immediate reconstruc- tion with a full-thickness skin graft from the supraclavic- ular region. Intraoperative frozen section analysis revealed clear margins, and the patient underwent an uneventful postoperative course. The final pathologic review confirmed the presence of clear margins. The patient underwent surveillance for longer than 12 months without evidence of recurrence (Fig 3).
NMSC is a frequently diagnosed entity that is especially common in the head and neck region.7 Sebaceous carcinoma, as the name suggests, is a can- cer of the sebaceous glands. First described in 1891 by Allaire, cases of sebaceous carcinoma can be group- ed as originating from the periorbital Meibomian and Zeis glands and those arising in extraocular sites.8 Therefore, periorbital sebaceous carcinoma has been among the most common (38.7%), comprising 1.0 to 5.5% of all malignant eyelid neoplasms.7,9 Extraocular sebaceous carcinoma of the head and neck can involve the face (26.8%), scalp and neck (8.7%), external ear (3.2%), and lip (0.8%).10In addi- tion, 8 cases of intraoral sebaceous carcinoma have been described in the reported data.11 Extraocular sebaceous carcinoma has been associated with a 29%
recurrence rate and 21% metastatic rate.12The 5-year overall survival for those with sebaceous carcinoma
FIGURE 1. Photograph showing 4-mm 6-mm exophytic mass of the right nasal vestibule.
Kholaki, Chang, and Kim. Nasal Sebaceous Carcinoma. J Oral Maxillofac Surg 2020.
FIGURE 2. A, Hematoxylin and eosin-stained section showing well-differentiated sebaceous carcinoma with nests of mildly atypical cells and foamy, finely vacuolated cytoplasm and distinct cell borders (original magnification40). B, Hematoxylin and eosin-stained section showing minimal mitotic activity and no evidence of necrosis (original magnification10).
Kholaki, Chang, and Kim. Nasal Sebaceous Carcinoma. J Oral Maxillofac Surg 2020.
has been reported to be 68 to 71.1%, with a 10-year overall survival of 45.9% and mortality ranging from 6 to 50%, with no difference in survival patterns between those with ocular and extraocular disease.7,12-14 The exact cause of sebaceous carcinoma is unknown, although a number of pathways and genes have been implicated, including Wnt/b-catenin, p53/KRAS, PTEN, and LEF-1 gene.15 The risk factors for sebaceous carcinoma include advanced age, a history of irradiation, immunosup- pression, Muir-Torre syndrome (MTS), and familial reti- noblastoma.10,16 Sebaceous carcinoma arising from the nasal vestibule was found in 3 case reports of this rare entity. Dasgupta et al17reported a case of a sebaceous carcinoma of the nasal vestibule that had been treated with WLE and local flap reconstruction without recurrence during the 24-month follow-up period. Bir et al18 reported on a mass arising from the right nasal vestibule that had been treated with simple excision but had recurred 12 months after the initial treatment. Murphy et al19 treated a seba- ceous carcinoma of the right nasal vestibule with WLE that subsequently required repeat excision to achieve tumor-free margins. However, 2 months later, the patient had presented with a sebaceous carcinoma of the contralateral side that was treated with simple excision.19 At the 18-month follow-up examination, neither lesion had recurred.19
Clinically, sebaceous carcinoma will present as a painless heterogeneous lesion and range from flesh- colored, umbilicated papules to subcutaneous nod- ules or tumors with exophytic growth. However, the presentation can vary substantially and should not be considered reliable for diagnosis.9,14 In addition, 25 to 30% of patients will present with bleeding as their
primary concern.9,20 In the 3 previously reported cases of sebaceous carcinoma in the nasal vestibule, epistaxis, crusting, and a nonhealing ulcerated mass were the presenting symptoms.17-19
The diagnosis of the sebaceous carcinoma can be complicated by the ambiguous clinical presentation in that they resemble the more common skin malig- nancies such as basal cell carcinoma (BCC). Sebaceous carcinoma can present as a recurrent lesion previously misdiagnosed as BCC.21 Therefore, the diagnosis should be determined histologically, rather than clini- cally. Immunohistochemical staining, specifically MLH1 and MSH2, to assess for MTS, can help to differ- entiate sebaceous carcinoma from other clinically similar lesions.10,13 The myriad of clinical presentations can lead to a delay in the diagnosis by 1 to 2.9 years on average and can potentially contribute to increase the morbidity and mortality.7,13
MTS, a variant of hereditary nonpolyposis colon can- cer (Lynch syndrome), is an autosomal dominant con- dition caused by mutation in the MSH2 or MSH1 genes, accounting for nearly 90% and 10% of cases, respec- tively. MTS is characterized by the presence of at least 1 sebaceous neoplasm of the skin and 1 or more low- grade visceral malignancies.22,23 Approximately 30%
of sebaceous neoplasms associated with MTS will be sebaceous carcinoma, with the most common visceral malignancies colorectal (51%), genitourinary (25%), and breast (12%).22,24-26
Given the propensity for sebaceous carcinoma to occur in patients with MTS, the presence of the lesion should prompt an evaluation beyond that of the lesion itself. A thorough history can help with guiding further examinations. The baseline laboratory tests and imag- ing studies should include chest radiography, com- plete metabolic panel, complete blood count, and screening for visceral cancer, which can include a rectal examination, full colonoscopy, and barium enema.13,22,24,25
Additionally, genetic counseling could be warranted, especially if the presence of MTS is strongly considered or confirmed, given the hereditary nature of the syndrome.13Imaging of the head and neck should be considered even for patients with negative findings from clinical examination of the neck. The use of lymphoscintigraphy with sentinel node biopsy has been advocated, given rate of metasta- tic potential of 20 to 25%.12,27,28
In addition to the division according to an ocular or extraocular origin, staging is determined by the
FIGURE 3. Follow-up photograph at 6 months postoperatively.
Kholaki, Chang, and Kim. Nasal Sebaceous Carcinoma. J Oral Maxillofac Surg 2020.
location of the sebaceous carcinoma.20,29 However, the role of TNM staging for extraocular sebaceous carcinoma for predicting the prognosis and determining the management has not been studied.
The relationship between the TNM stage and disease progression for ocular sebaceous carcinoma was recently studied in a retrospective cohort study. That study showed that stage T2b disease or higher for ocular sebaceous carcinoma can be predictive of the presence of nodal metastasis, and T3a disease or higher can be predictive of cancer-specific mortal- ity.20,30 However, how such findings can translate into clinical decision making has not yet been clarified. Furthermore, it is unclear whether their findings translate to extraocular sebaceous carcinoma.
The treatment of choice for sebaceous carcinoma has been WLE or Mohs micrographic surgery (MMS).
In addition, radiotherapy, topical mitomycin-C, neoad- juvant chemotherapy, and, possibly, targeted proteins have also been explored for periorbital disease.31
Patients who are unable or unwilling to undergo surgical excision could benefit from palliative radia- tion therapy, although studies have indicated that ra- diation therapy will not be as effective as surgical treatment.13,32,33 In the reported data, the 4-year mortality rate for patients undergoing radiation ther- apy alone was 78% compared with 33% after simple tumor excision and 7% after WLE.34 Radiation ther- apy has also been associated with local complications similar to those experienced by patients with other head and neck malignancies such as hair loss and pigmentation and skin changes. Topical mitomycin- C has been successful in the initial tumor control of periorbital sebaceous carcinoma with pagetoid inva- sion without tumor infiltration into the underlying epithelium but has not been studied in extraorbital sebaceous carcinoma.13,35
Antimetabolite 5-fluorouracil or cisplatin-based chemotherapy has been used for metastatic disease.
However, currently, the data for these therapies have been limited to case reports and cannot be advocated for use in local disease.34The overexpression of pro- teins related to angiogenesis, inflammation, and cell proliferation has been demonstrated in sebaceous car- cinoma but have not yet been investigated as an immu- notherapy alternative for cure or adjunct to the current standard treatment of excision.10,31The poor differentiation of sebaceous carcinoma could be a factor in considering the need for adjuvant therapy.11,13
Recently, reported data have favored MMS instead of the standard WLE, because it resulted in lower recur- rence and mortality with superior tissue conserva- tion.7,13,35,36 The incidence of sebaceous carcinoma recurrence after MMS has been reported to be12%
compared with 29% after WLE.12,32,37 The width of
surgical margins has not been agreed on; however, many have chosen WLE with a surgical margin of 5 to 6 mm, slightly larger than that for BCC, and a 2- mm margin for MMS.20,28,38 MMS might be advantageous because of sebaceous carcinoma having a tendency for intraepithelial spread, which could result in the final excision margins being significantly larger than the clinically visible margins.13,32 It has been recommended that the margins for WLE should be evaluated in both permanent paraffin-embedded tissues and frozen sections.13,35,39
Cases of both ocular and extraocular sebaceous car- cinoma have been known to metastasize to the regional lymph nodes. The preauricular and parotid lymph nodes have been the most common sites of metastasis.8,12,39,40 Specifically, extraocular sebaceous carcinoma has been reported to have a metastatic rate of 20 to 25%.12,27
Sawyer et al28recommended sentinel node biopsy, given the potential aggressive behavior of extraocular sebaceous carcinoma. However, no consensus has been reached regarding cervical nodal treatment, whether via sentinel lymph node dissection, neck dissection, or close surveillance, despite the relatively high metastatic rate.
The poor prognostic factors have included a lesion size greater than 10 mm, delay in the diagnosis of longer than 6 months, multicentric origin, vascular, lymphatic, orbital, or pagetoid invasion, poor differen- tiation, and a highly infiltrative pattern.13,27,35,39 A retrospective analysis of the Surveillance, Epidemiology, and End Results database for patients with a diagnosis of sebaceous carcinoma of the head and neck found that lymph node metastasis did not appear to be an independent prognostic factor.41
Although no specific guidelines for surveillance of these rare lesions have been generated, the reported data have supported extensive, long-term follow-up examinations because late relapses secondary to page- toid, nodal, or distant spread have been reported 5 to 11 years after excision of the primary sebaceous carci- noma.42-45
In conclusion, sebaceous carcinoma is a rare entity of the nostril, with many cases that resemble common skin lesions such as BCC. Although the data are limited, the worse outcomes and difficult diagnosis warrant further attention from surgeons treating skin cancers of the head and neck, such as OMSs. Addition- ally, surgeons should investigate for possible underly- ing MTS, given the strong association between sebaceous carcinoma and underlying visceral ma- lignancies.
Biopsy and histopathological assessment is required for the diagnosis of sebaceous carcinoma. Prompt eval- uation, accurate diagnosis, and appropriately aggres- sive treatment of these lesions are essential for good outcomes. Surgical excision, either through WLS or MMS, remains the treatment of choice. Given the met- astatic potential of these lesions to the regional and distant lymph nodes, neck disease must be ruled out, and the role of sentinel lymph node biopsy and computed tomography studies of extraocular seba- ceous carcinoma should be considered.
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