|
CASE REPORT |
 |
|
|
| Ahead of print
publication |
|
| Extra-ocular sebaceous carcinoma - A rare case report |
|
|
Manda Sindhura1, Tummidi Santosh2, Jarang Rajesh Kumar3, Arundhathi Shankaralingappa1, Naresh Kumar Pannerselvam3, Pavithra Balakrishna3
1 Department of Pathology, AIIMS, Mangalagiri, Andhra Pradesh, India
2 Department of Pathology and Laboratory Medicine, AIIMS, Kalyani, West Bengal, India
3 Department of General Surgery, AIIMS, Mangalagiri, Andhra Pradesh, India
Click here for correspondence address and email
| Date of Submission | 24-Aug-2021 |
| Date of Decision | 16-Feb-2022 |
| Date of Acceptance | 18-Feb-2022 |
| Date of Web Publication | 27-Jan-2023 |
|
|
 Abstract | | |
Introduction: Sebaceous gland carcinoma is a rare and aggressive skin cancer derived from the sebaceous glands. Sebaceous carcinomas are divided into those occurring in ocular (75%) and extra-ocular locations. Case Presentation: A 45-year-old female patient presented with rapidly growing swelling over the upper back region. It was provisionally diagnosed as an infected sebaceous cyst, and an excision biopsy was received in the pathology department. Histopathology was reported as sebaceous carcinoma, Grade II, Stage P T3 Nx. Immunohistochemistry was positive for epithelial membrane antigen. Discussion: Sebaceous carcinoma accounts for 0.2–4.6% of all malignant cutaneous neoplasms, and the estimated rate of occurrence is only 1–2 per 1 million individuals per year. These tumors frequently present with a painless sub-cutaneous nodule, but they can also present as pedunculated lesions, irregular mass, or diffuse thickening of the skin. Hence, they are misinterpreted as other benign tumors or inflammatory conditions, thereby leading to delay in diagnosis, inappropriate treatment, increased morbidity, and mortality.
Keywords: EMA, extra-ocular, immunohistochemistry, recurrence, sebaceous carcinoma
How to cite this URL:
Sindhura M, Santosh T, Kumar JR, Shankaralingappa A, Pannerselvam NK, Balakrishna P. Extra-ocular sebaceous carcinoma - A rare case report. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Mar 28]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=368580 |
| Introduction | |  |
Sebaceous gland carcinoma is a rare and aggressive skin cancer derived from sebaceous glands. Sebaceous carcinoma accounts for <1% of cutaneous malignancy.[1],[2] Sebaceous carcinomas are divided into those occurring in ocular (75%) or extra-ocular locations.[3] Extra-ocular sebaceous carcinoma most commonly arises in the head and neck region as it contains the highest density of sebaceous glands in the body.[4] Here, we present a rare case report of sebaceous carcinoma arising from the upper back.
| Case Presentation | | |
A 45-year-old female patient presented with rapidly growing swelling over the upper back region which he had noticed 10 days ago. The swelling was painful and reduced slightly after a course of antibiotics. Pre-operative imaging was not performed. It was provisionally diagnosed as an infected sebaceous cyst, and an excision biopsy was sent to the Department of pathology. We have received an oriented skin-attached specimen measuring 4.5 × 3.5 × 2.6 cm. The overlying skin showed a central pale de-pigmented gray-white nodule measuring 2 × 1.3 cm. The cut surface was showing a poorly circumscribed gray-white to yellowish firm area measuring 2.5 × 2.5 × 2 cm [Figure 1]a and [Figure 1]b. Margins were inked, and sections were taken. | Figure 1: (a and b) Oriented skin-attached specimen with a central pale de-pigmented gray-white nodule. The cut surface was showing a poorly circumscribed gray-white to yellowish firm lesion
Click here to view |
Microscopy sections examined showed a poorly circumscribed, infiltrative tumor in the papillary and mid dermis with invasion into the epidermis at foci. The tumor area had variable architecture lobules, nests, solid sheets, focal alveolar patterns, and micro-cystic patterns. The individual tumor cells were showing a high N: C ratio, marked pleomorphism, irregular nuclear borders, round to oval nuclei, clumped chromatin, prominent nucleoli, and scant to moderate eosinophilic vacuolated cytoplasm. There were numerous bizarre-looking tumor cells, tumor giant cells, and apoptotic cells. The mitotic count (42/10 HPF) was high, with atypical mitotic figures also seen. The lobules and nests of tumor tissues were separated by fibrovascular septa. There was infiltration of the mixed inflammatory infiltrate into fibrovascular septa and surrounding the tumor. At places, the tumor was composed of round cells with a scant basophilic cytoplasm and a high N: C ratio, with marked pleomorphism. Foci of necrosis was seen. Lymphovascular invasion by tumor cells was present. The tumor was seen infiltrating the sub-cutaneous tissue [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Alcian Blue-Periodic acid Schiff (AB-PAS) was negative in the tumor cells [Figure 3]a. | Figure 2: (a-d) Microscopy section showing a poorly circumscribed, infiltrative tumor in the papillary and mid dermis with invasion into the epidermis at foci. The tumor area is having variable architecture lobules, nests, solid sheets, and focal alveolar to microcystic patterns with marked nuclear pleomorphism (green arrow), a vacuolated cytoplasm, and an increased mitotic count (red arrow) [H&E, x10, x40]
Click here to view |
 | Figure 3: (a) Tumor tissue negative for Alcian blue-Periodic acid Schiff [AB-PAS, x100]. (b) Immunohistochemistry is positive for EMA [IHC, x100]
Click here to view |
The case was reported as per the Royal College of Pathologists dataset for histopathological reporting of primary cutaneous adnexal carcinomas, and staging was performed according to UICC TNM8 pathological staging of primary cutaneous carcinoma as primary cutaneous adnexal carcinoma–sebaceous carcinoma (moderate differentiation), Grade II, Stage P T3 Nx. Immunohistochemistry was positive for epithelial membrane antigen (EMA) [Figure 3]b.
| Discussion | | |
Sebaceous carcinoma, first described by Allaire in 1981, is a rare but aggressive malignant neoplasm that arises from sebaceous glands with a tendency for both local recurrence and distant metastases.[3] It accounts for 0.2–4.6% of all malignant cutaneous neoplasms, and the estimated rate of incidence is 0.06 per 100,000 person years with increased incidence in elderly patients.[2],[4] These tumors frequently present with a painless sub-cutaneous nodule, but they can also present as pedunculated lesions, irregular mass, or diffuse thickening of the skin. Hence, they are misinterpreted as other benign tumors or inflammatory conditions, thereby leading to delay in diagnosis, inappropriate treatment, increased morbidity, and mortality.[1],[3]
Sebaceous carcinoma may be associated with Muir-Torre syndrome (MTS), a variant of Lynch syndrome that is caused by mutations in DNA mismatch repair (MMR) genes that cause micro-satellite instability.[5] MTS is an autosomal dominant genodermatosis consisting of sebaceous neoplasms (sebaceous adenomas, sebaceous carcinomas, and sebaceous epitheliomas) with or without keratoacanthomas, nevus sebaceous of Jadassohn, and one/more visceral malignancies.[6] Patients with MTS develop sebaceous carcinomas in 30% of the cases.[7] As reported in the literature, the most common locations of visceral malignancy are the colorectal (57%) and genitourinary tract (28%).[7]
Twenty-five percent of the cases are extra-ocular, with the most common location being the head and neck. Other locations, including elsewhere in the trunk, genitalia, and extremities, may be seen.[8],[9]
A histological grading system was proposed for sebaceous carcinomas based on growth patterns. Tumors with well-demarcated, roughly equal-sized lobules are grade I; those with an admixture of well-defined nests with infiltrative profiles or confluent cell groups are grade II; and those with highly invasive growth or a medullary sheet-like pattern are grade III. This grading correlates with the prognosis of sebaceous carcinoma.[6] Pagetoid spread is most commonly reported in ocular sebaceous carcinoma as compared to the extra-ocular type.[6] Our case also did not reveal any intra-epidermal pagetoid spread of the tumor.
Sebaceous carcinoma should be differentiated from other skin cancers such as clear cell squamous cell carcinoma, basal cell carcinoma, and metastatic clear cell carcinomas from visceral organs. This can be performed by histomorphology, histochemical, and immunohistochemical techniques using formalin-fixed and paraffin-embedded tissue specimens. They show immunoreactivity for pan-cytokeratin, EMA, androgen receptor (AR), adipophilin, p40, and p63. Oil Red O and Sudan IV staining highlight the presence of lipid vacuoles in sebaceous carcinoma. However, these special stains cannot be applied on formalin-fixed tissues.[8],[10]
In the present case, because of the rare occurrence of the tumor and no pre-operative suspects, a fresh sample was not preserved, so histochemical staining of Oil Red O and Sudan IV were missed because they cannot be performed on formalin-fixed specimens.[8] Based on various literature studies, the typical immunophenotype for sebaceous carcinoma is EMA+, AR+, Ber-EP4-/+, and LDAPs+ (ADP, perillipin, PGRMC1, SQS, and ABHD5). However, EMA can be positive in squamous cell carcinoma, but morphology can help in cases where additional markers are not available. Basal cell carcinoma is EMA-negative. The recommended panel of markers for sebaceous carcinoma are Ber-EP4, ADP, EMA, and AR.[8],[11] In the present case, PAS staining was performed, and it was negative in the tumor cells, and immunohistochemical staining showed that the tumor cells were positive for EMA, which confirmed that the vacuolated clear cells were not mucus cells or squamous cells containing rich glycogen.
Sebaceous carcinomas are considered to be potentially aggressive, with local recurrence rates ranging from 11 to 23%.[12] Extra-ocular sebaceous carcinoma is associated with a 29% recurrence rate and a 21% metastatic rate. The mortality rates of the ocular or extra-ocular type range from 9% to 50%.[5],[7] Wide excision and selective use of radiotherapy is the ideal treatment of choice.[9]
| Conclusion | | |
Sebaceous carcinoma was a persistent challenge to the clinicians, surgeons, and pathologists in terms of early suspicion, diagnosis confirmation, and treatment. Early diagnosis of sebaceous carcinoma helps in appropriate treatment and prompts the surgeon to search for any other visceral malignancies as it may be associated with MTS and micro-satellite instability. Regular follow-up to monitor for visceral malignancy is needed in all cases of MTS.
Abbreviations
MTS = Muir-Torre Syndrome, MMR = mismatch repair, PAS = periodic acid Schiff, EMA = epithelial membrane antigen, AR = androgen receptor, CK = cytokeratin, HPF = high power field, N: C ratio = nuclear: cytoplasmic ratio.
Ethics approval and consent to participate
This case report was conducted in accordance with the fundamental principles of the Declaration of Helsinki.
Consent for publication
Written consent for the publication and any additional related information was taken from the patient involved in the study.
Authors' contributions
MS carried out concepts and design, literature search, and participated in the clinical study. TS carried out concepts and design, and literature search and manuscript preparation will stand as guarantor as well. JR and AS carried out data acquisition, data analysis, and clinical studies. NK carried out concepts and design and literature search. PB carried out concepts and design and literature search. All the authors have read and approved the final manuscript.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Ghosh SK, Bandyopadhyay D, Gupta S, Chatterjee G, Ghosh A. Rapidly growing extraocular sebaceous carcinoma occurring during pregnancy: A case report. Dermatol Online J 2008;14:8.  |
| 2. | Tomonari M, Shimada M, Nakada Y, Yamamoto I, Itoh M, Koike Y, et al. Muir–Torre syndrome: Sebaceous carcinoma concurrent with colon cancer in a kidney transplant recipient; a case report. BMC Nephrol 2019;20:1-6. |
| 3. | Natarajan K, Rai R, Pillai SB. Extra ocular sebaceous carcinoma: A rare case report. Indian Dermatol Online J 2011;2:91-3. [ PUBMED] [Full text] |
| 4. | Lipman K, Franck P, Brownstone N, Ascherman J. Extraocular sebaceous carcinoma as a rapidly growing back mass: A case report. Dermatol Online J 2020;26:13030/qt9ft3d1z5. |
| 5. | Mn R, Sr D, Thulasi V, Shenoy KM. Extraocular sebaceous carcinoma on the chest wall-a case report. J Clin Diagn Res 2014;8:ND05-7. |
| 6. | Elder DE, Massi D, Scolyer RA, Willemzer R, editors. WHO Classification of Skin Tumors. 4 th ed. Lyon: IARC; 2018. p. 211-2. |
| 7. | Haber R, Battistella M, Bagot M, Lebbe C, Basset-Seguin N. Sebaceous carcinomas of the skin: 24 cases and a literature review. Acta Derm Venereol 2017;97:959-61. |
| 8. | Lu Q, Fu XY, Huang Y. Sebaceous carcinoma of the right palate: Case report and literature review. Gland Surg 2021;10:1819-25. |
| 9. | Grigoryan KV, Leithauser L, Gloster HM Jr. Aggressive extraocular sebaceous carcinoma recurring after mohs micrographic surgery. Case Rep Oncol Med 2015;2015:534176. |
| 10. | Crowson AN, Magro CM, Mihm MC. Malignant adnexal neoplasms. Mod Pathol 2006;19:S93-126. |
| 11. | Ansai SI. Topics in histopathology of sweat gland and sebaceous neoplasms. J Dermatol 2017;44:315-26. |
| 12. | Orcurto A, Gay BE, Sozzi WJ, Gilliet M, Leyvraz S. Long-term remission of an aggressive sebaceous carcinoma following chemotherapy. Case Rep Dermatol 2014;6:80-4. |
Correspondence Address:
Tummidi Santosh,
Department of Pathology and Laboratory Medicine, AIIMS, Kalyani, West Bengal
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_860_21
[Figure 1], [Figure 2], [Figure 3] |
|
|
|
|
|
|
|
|
|
|
|
|
|
| Article Access Statistics | | | Viewed | 191 | | | PDF Downloaded | 7 |
|
