Case report
Year : 2023 Month : October Volume : 12 Issue : 4 Page : PC07 - PC09 Full Version

Orbital Adnexal Malignant Tumours: A Report of Two Cases
Deepali Singh, Doyel Halder, Ankita Pranab Mandal, Mamata Guha Mallick Sinha
1. Postgraduate Trainee, Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India. 2. Demonstrator, Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India. 3. Senior Resident, Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India. 4. Professor and Head, Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India.
 
Correspondence Address :
Deepali Singh, Doyel Halder, Ankita Pranab Mandal, Mamata Guha Mallick Sinha,
Dr. Ankita Pranab Mandal
Flat No. B501, GulmoharII CHS Ltd., Plot No. 13, Sector-42, Nerul, Navi Mumbai-400706, Maharashtra, India.
E-mail: ankitapmandal@gmail.com
 
ABSTRACT
: Sebaceous carcinoma of the eyelid is a very rare malignant tumour, accounting for 1-1.5% of total eyelid malignancies. It typically arises from the meibomian glands, making it more common in the upper eyelids. It predominantly affects individuals in their sixth to eighth decade, with a higher incidence in females. Histologically, the tumour cells are arranged in well-defined lobules with circumscribed borders. These cells exhibit pleomorphism, eccentric hyperchromatic nuclei, inconspicuous nucleoli, and multivacuolated cytoplasm. The clinical course of sebaceous carcinoma is aggressive, often characterised by recurrences and metastasis to regional lymph nodes. Unfortunately, it is not commonly considered in the differential diagnosis of eyelid tumours, leading to delayed treatment. Thus, it is crucial to raise awareness about this uncommon neoplasm occurring at unusual sites in order to improve patient survival. In the present case report, the authors present two cases: a 54-year-old male patient with intraocular sebaceous carcinoma, which recurred, and an 83-year-old male patient with extraocular sebaceous carcinoma. In both the cases, imaging and other investigations were performed, followed by excision of the mass and confirmation of the diagnosis through histopathological reporting. Subsequent follow-up was conducted for both cases and the postoperative recovery was uneventful.
Keywords : Eyelid, Extraocular, Immunohistochemistry, Intraocular, Sebaceous gland carcinoma
DOI and Others : DOI: 10.7860/NJLM/2023/65247.2773 Date of Submission: May 05, 2023 Date of Peer Review: Jun 16, 2023 Date of Acceptance: Jul 24, 2023 Date of Publishing: Oct 01, 2023 AUTHOR DECLARATION: • Financial or Other Competing Interests: None • Was informed consent obtained from the subjects involved in the study? Yes • For any images presented appropriate consent has been obtained from the subjects. Yes PLAGIARISM CHECKING METHODS: • Plagiarism X-checker: May 11, 2023 • Manual Googling: Jun 30, 2023 • iThenticate Software: Jul 22, 2023 (6%) ETYMOLOGY: Author Origin EMENDATIONS: 6
 
Case Report
Case 1

A 54-year-old male patient presented to the eye Outpatient Department (OPD) three years ago with a complaint of a lump over the medial canthus of the right upper eyelid. The lump was operated on as a sebaceous cyst in 2019. Cutler Beard stage I and stage II surgery was performed. The postoperative period was uneventful. However, the histopathological report revealed sebaceous carcinoma.

Again in 2022, the patient returned to the eye OPD with a recurrence in the previously operated area due to positive surgical margins. An MRI (T1 weighted) showed a heterogeneous lesion involving the medial portion of the right orbit, the right peri-orbital region, the right eyelid, and affecting the extraocular muscles and right lacrimal gland (Table/Fig 1)a. The features were suggestive of a neoplastic mass, with squamous cell carcinoma with hydropic changes and basal cell carcinoma with sebaceous differentiation considered as differential diagnoses. There was also pressure effect observed on the right ocular bulb with involvement of the extraocular muscles. Patient was also examined for any enlargement of sentinel lymph nodes.

He underwent reoperation and the specimen was sent to the Pathology department for histopathology. Grossly, the size of the specimen was 7.5×4.5×3 cm, with the optic nerve measuring 0.8 cm. On grossing, a greyish-white growth measuring 4.5×3.5×3 cm was noted (Table/Fig 1)b. Microscopically, the tumour mass was arranged in a lobular pattern, composed of pleomorphic cells with eccentric hyperchromatic nucleus, inconspicuous nucleolus (Table/Fig 1)c, (Table/Fig 1)d. Extensive areas of comedo necrosis were observed, along with lymphovascular invasion. The adjacent inferior orbital bone margin showed invasion by the growth. The histomorphological features were suggestive of sebaceous carcinoma with stage pT3bNxMx. Immunohistochemical expression of HER2/neu was negative. The patient had an uneventful postoperative recovery and is doing well after six months of follow-up.

Case 2

An 83-year-old male patient presented to the eye OPD with pain, swelling, and a foreign body sensation in the left lower eyelid for the last six months. On examination, his visual acuity was 6/18 in both eyes, with senile immature cataracts in both eyes and a normal fundus. During the local examination of the left lower lid, a vascular mass measuring 5×10 mm and located near the lateral lid margin was discovered. Due to suspicion of a pre-malignant lesion, he was examined for any enlargement of sentinel lymph nodes. An ultrasound revealed a heterogeneous lesion on the left lower eyelid, which raised concerns of a malignant lesion. No bone involvement was observed. Fine needle aspiration cytology was performed using a standard technique, followed by staining with Papanicolaou and May Grunwald Giemsa (MGG). The smear showed irregular clusters of tumour cells with pleomorphic centrally located nuclei and coarse chromatin. The patient underwent surgery, and the specimen was sent for histopathology.

Macroscopically, the specimen was a globular skin-covered tissue piece measuring 2×1×1 cm (Table/Fig 2)a. Microscopically, the section revealed the histology of a neoplastic lesion composed of pleomorphic, hyperchromatic cells with centrally placed vesicular nuclei, prominent nucleoli, and granular eosinophilic cytoplasm. These cells were arranged in lobules, sheets, and glands separated by fibrocollagenous tissue (Table/Fig 2)b,c. Mitosis, necrosis, and haemorrhage were present. The histomorphological features were suggestive of sebaceous carcinoma with pT3bNxMx. Immunohistochemical expression of HER2/neu was negative. The patient’s postoperative recovery was uneventful, but he was lost to follow-up after two months.
 
 
Discussion
Sebaceous carcinoma of the eyelid is a very rare malignant tumour, accounting for 1-1.5% of all eyelid malignancies (1). It is more commonly observed in the sixth to eighth decade of life, with a higher incidence in females. Typically, it originates from the meibomian glands, making it more prevalent in the upper eyelids. This aggressive tumour has a tendency to metastasise to regional lymph nodes and distant organs, resulting in a poor prognosis (2). Extraocular sebaceous carcinoma constitutes approximately 25% of sebaceous neoplasms and primarily affects the head and neck regions, followed by the trunk, salivary glands, genitalia, breast, ear canal, and intra-oral cavity (3).

Clinically, sebaceous carcinoma on the eyelid can be mistaken for persistent conjunctivitis, chronic blepharophlebitis, or chalazion. If conjunctivitis or chalazion does not improve after three months of observation, a biopsy should be performed. It predominantly occurs in elderly Caucasian individuals. Ocular sebaceous carcinoma often exhibits regional metastasis and affects both sexes equally, whereas extraocular sebaceous carcinoma is more common in men. In this case, both patients were elderly males, consistent with previous studies (4),(5),(6),(7).

The clinical presentation of sebaceous carcinoma varies, presenting as a small, erythematous, or yellow slowly enlarging firm papule or nodule on the skin. Diagnosis is often delayed, requiring pathological confirmation of neoplastic cells with sebaceous differentiation. Histologically, the tumour cells are arranged in well-defined lobules with circumscribed borders. The cells display pleomorphism with eccentric hyperchromatic nuclei, inconspicuous nucleoli, and multivacuolated cytoplasm. Lymphovascular invasion is observed, and common findings include mitosis, marked nuclear atypia, hemorrhage, and necrosis. Microscopically, sebaceous carcinoma often resembles molluscum contagiosum, pyogenic granuloma, keratoacanthoma, and squamous cell carcinoma with hydropic changes, as well as basal cell carcinoma with sebaceous differentiation. Squamous cell carcinoma is ruled out due to the absence of evidence of keratinization in the form of dyskeratotic cells and keratin pearls. Additionally, the absence of basaloid differentiation and peripheral palisading excludes basal cell carcinoma as a diagnosis. Sebaceous carcinoma has poorly differentiated and anaplastic types. The poorly differentiated variant exhibits marked 8pleomorphism, prominent nucleoli, and a high mitotic count, while the anaplastic variant displays scanty basophilic cytoplasm and extensive necrosis. Poorly differentiated squamous cell carcinoma and anaplastic basal cell carcinoma can be differentiated from these variants using oil red O stain and Sudan black stain, which show positive results (8).

The clinical course of sebaceous carcinoma is aggressive, with frequent recurrences and metastasis to regional lymph nodes. The recurrence rates for ocular sebaceous carcinoma range from 11% to 30%, and distant metastases occur in 3% to 25% of cases (9). Poor prognostic indicators include large size, multicentricity, poor differentiation, infiltrative pattern, vascular invasion, and orbital infiltration. Immunohistochemical markers such as cytokeratin, Epithelial Membrane Antigen (EMA), Cam 5.2, and anti-breast carcinoma-associated antigen-225 antibody are expressed by sebaceous carcinoma cells. HER2/neu, the human epidermal growth factor receptor 2, is often evaluated through Immunohistochemistry (IHC) to identify molecular alterations that could be potential therapeutic targets. In both cases mentioned, the expression of HER2/neu was negative. Adipophilin, an IHC test, is useful in differentiating sebaceous carcinoma from other dermatological malignancies, like squamous cell carcinoma and basal cell carcinoma, with a sensitivity and specificity of 100% (2),(10),(11). Unfortunately, adipophilin was not available in the department, so the authors were unable to perform the test. Recent studies are investigating the molecular mechanisms underlying tumour development and progression, suggesting that the loss of p53 and disruption of genomic integrity may play a critical role in sebaceous carcinoma progression (12).

When considering a diagnosis of sebaceous carcinoma, a detailed history and physical examination should be conducted. Colonoscopy and barium enema are essential for ruling out internal malignancies associated with Muir-Torre syndrome, an autosomal dominant genetic condition caused by germline mutations in DNA mismatch repair genes. Muir-Torre syndrome is a variant of Lynch syndrome and is characterised by a predisposition to skin malignancies and visceral malignancy, particularly colorectal cancer (13). In cases of extraocular sebaceous carcinoma, IHC for microsatellite instability (MLH1, MSH2, MSH6, PMS2) should be performed to exclude Muir-Torre syndrome.

Although extraocular sebaceous carcinoma is generally less aggressive than ocular carcinomas, there have been reports of regional and distant metastasis (14). In one of the cases, the tumour recurred at the local site after treatment, which was also observed in another study (4). Mohs Micrographic Surgery (MMS) is an ideal treatment option, while subtotal or complete exenteration may be required if the tumour is large, recurrent, or has spread to the bulbar conjunctiva, other eyelids, or orbital tissue. Radical neck dissection, along with partial parotidectomy, is performed if there is spread to regional lymph nodes. Due to its fastgrowing nature, postoperative patients should be followed-up at three-month intervals during the first year, six-month intervals during the second year, and then annually for life (15). Metastatic disease, if present, may be treated with a combination of excision, radiation, and chemotherapy. The mortality rates for both ocular and extraocular sebaceous carcinoma range from 9% to 50% (16).
 
 
Conclusion
Sebaceous cell carcinoma is a rare condition with an unfavorable prognosis and a tendency to metastasise. It is generally not considered as a differential diagnosis for tumours arising from the eyelids, resulting in delayed treatment. Hence, we emphasise the need to raise awareness about this uncommon neoplasm occurring in unusual sites to expedite patients’ survival.
 
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TABLES AND FIGURES