Conjunctival mapping biopsies from an elderly patient
This conjunctival specimen is folded, which is why we have epithelium on the top and bottom of the image. The epithelium is disorganised and has lost its normal maturation pattern. That is, for much of the specimen we don’t have a neat basal row of small cells with scanty cytoplasm, maturing to cells with more generous eosinophilic cytoplasm as they approach the surface.
In the annotated image, I’ve marked the base of the epithelium with a green line. The discontinuity in the lower half is because of folding. It’s difficult to see on this image, but the epithelial basement membrane is intact.
Higher power shows some preservation of the basal layer, and residual areas of normal maturation. But within the suprabasal epithelium are atypical cells (singly and in small nests: a pagetoid pattern). The atypical cells have larger irregular nuclei and less cytoplasm than we’d expect. The cytoplasm of some abnormal cells is pale and bubbly/foamy. There are scattered acute inflammatory cells within the epithelium, and the stroma has an infiltrate of chronic inflammatory cells (mainly lymphocytes with smaller numbers of plasma cells).
In the annotated image, I’ve outlined a few nests of atypical cells in green. Blue asterisks indicate single cells with foamy cytoplasm.
In another field, we see keratinisation of the surface (abnormal in conjunctiva). There are scattered mitoses and apoptotic bodies. Most of the epithelial cells in this field have rather pale cytoplasm with a hint of a foamy texture. I think that all of this epithelium is abnormal.
In the annotated image, I’ve marked the surface keratinisation with green lines. Blue asterisks highlight mitoses, and green asterisks highlight apoptotic bodies.
This is immunohistochemistry for androgen receptor. In this context, androgen receptor is expressed in nuclei of sebaceous cells. We can see that positive cells are scattered through the epithelium, both singly and in clusters.
This is immunohistochemistry for epithelial membrane antigen (EMA). It can outline cytoplasmic (lipid) vacuoles in cells of sebaceous differentiation. Here, I think it highlights the “background” epithelium, with the pagetoid neoplastic cells outlined in negative profile. (That is, we see the abnormal cells because they are immunonegative rather than immunopositive.)
This is sebaceous carcinoma in situ. Sebaceous carcinoma (in situ and invasive) is relatively rare, but it’s more common in the periocular region than at other body sites. At a rough guess, we get a case every 1-2 months. Clinically, it can mimic unilateral blepharitis or a non-resolving chalazion, so sometimes it presents at an advanced stage.
Histologically, it’s sometimes difficult to tell whether intraepithelial neoplasia is sebaceous or squamous. I find useful features for favouring sebaceous differentiation to be: pagetoid pattern (but beware melanocytic neoplasia), vacuolated or foamy cytoplasm, and a purplish hue to the nuclei. Additionally, sebaceous neoplasia often looks more wild than squamous, and invasive disease more often shows comedo necrosis. These aren’t absolute features, however! I have a low threshold for suggesting mapping biopsies.
Here are some relevant articles.
Periocular intraepithelial sebaceous neoplasia: critical appraisal of nomenclature and prognostic importance by Curtis Margo (2020). This one’s not open access, but worth a look if you have access to the Journal of Clinical Pathology.As the title suggests, it addresses hazards of overlapping and ambiguous terminology. Since periocular sebaceous carcinoma may need to be treated by disfiguring exenteration surgery (removal of the eye, orbital contents +/- eyelids), the more accurate we can be with predicting likely outcomes, the better.
Updates on the clinical diagnosis and management of ocular sebaceous carcinoma: a brief review of the literature by Xu et al (2018) gives an overview of ocular sebaceous carcinoma.
For non-ocular specialists, A retrospective review of 1349 cases of sebaceous carcinoma by Dasgupta et al is a survey of cases over a 3 decade period.
Periocular sebaceous gland carcinoma: A comprehensive review by Mulay et al (2013) is another open access review article.