• Monoclonal antibody against a protein of perilipin family on the surface of intracellular lipid droplets (Mod Pathol 2010;23:567)

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• Cytoplasmic staining
• Vacuolar / membranous staining pattern (membranous staining around intracytoplasmic lipid vesicles)
• Granular staining (i.e., uptake by keratohyalin granules or in cytoplasm of macrophages) is considered nonspecific / negative
• Staining intensity and pattern may vary from mature sebaceous neoplasms (intense and foamy) to less differentiated sebaceous carcinomas (weak and punctate staining)
• Reference: Mod Pathol 2010;23:567

• Differential diagnosis of skin tumors with foamy or clear cell morphology (e.g., sebaceous carcinoma versus clear cell squamous cell carcinoma) (Mod Pathol 2010;23:567)
  • Caveat: not useful if a differential diagnosis is clear cell renal cell carcinoma (see Positive staining - disease)

• See Interpretation

Contributed by Umberto Maccio, M.D., M.Sc., M.B.A.

• Tumors with sebaceous differentiation (Mod Pathol 2010;23:567)
  • Sebaceoma (100%)
  • Sebaceous adenoma (100%)
  • Sebaceous carcinoma (92%)
• Metastatic clear cell carcinoma of the kidney (62.5%) (J Cutan Pathol 2010;37:1193)
• Hepatocellular carcinoma with fatty changes (Pathol Int 2020;70:199)
• Adrenocortical carcinoma (Lipids Health Dis 2017;16:83)
• Invasive breast carcinoma of no special type (NST) with lipid rich pattern (Am J Surg Pathol 2011;35:861)
• Xanthelasma (100%) (Mod Pathol 2010;23:567)
• Xanthogranuloma (90%) (Mod Pathol 2010;23:567)
• Liposarcoma (88%) (Appl Immunohistochem Mol Morphol 2021;29:152)
• Malignant apocrine and eccrine tumors (58%) (Hum Pathol 2013;44:1811)
• Tumors with ameloblastic differentiation (ameloblastoma and ameloblastic carcinoma) (J Oral Pathol Med 2021;50:708)

An ulcerated tumor in upper eyelid underwent excision. Histology of the lesion (H&E) is shown above. What combination of immunohistochemical markers would be consistent with the diagnosis of sebaceous carcinoma?

1. Adipophilin+, AR-, PAX8+
2. Adipophilin+, AR+, PAX8-
3. Adipophilin-, AR+, PAX8-
4. Adipophilin-, AR-, PAX8-

B. Adipophilin+, AR+, PAX8- would be the typical combination expected in the case of a sebaceous carcinoma. Answer A is incorrect because adipophilin can also be positive in up to 62.5% of clear cell renal cell carcinoma. In combination with positive staining for PAX8, the diagnosis would be more consistent with clear cell renal carcinoma (rather than with sebaceous carcinoma). Answer C is incorrect because positive staining for adipophilin would be expected in sebaceous carcinoma. Additionally, positive staining for AR alone is nonspecific and may occur in many tumors (e.g., prostate cancer, apocrine carcinoma, etc.) and should be further investigated with other markers. Answer D is incorrect because negative results for all of those markers may suggest another diagnosis (e.g., squamous cell carcinoma) that needs to be verified by other markers.

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Reference: Adipophilin

Which of the following statements about adipophilin is correct?

1. In a cutaneous lesion, positivity for adipophilin can distinguish between a sebaceous carcinoma and a metastasis of clear cell renal cell carcinoma
2. Indicates the presence of lipids in the cells and may help in the diagnosis of tumors with clear cell morphology, although it is not specific for sebaceous differentiation
3. It is a sensitive and specific diagnostic marker for sebaceous lesions
4. Tumors with adipophilin expression have a better prognosis in general, so adipophilin can be used a marker for favorable prognosis

B. Indicates the presence of lipids in the cells and may help in the diagnosis of tumors with clear cell morphology, although it is not specific for sebaceous differentiation. Adipophilin indicates the presence of intracellular lipids and can be helpful in identifying tumors with clear cell morphology but it is not specific for sebaceous differentiation and can be seen in a variety of lipid containing tumors. Answer C is incorrect because while adipophilin is a useful marker for identifying lipid droplets in sebaceous lesions, it is not entirely specific or sensitive. It can also be positive in other types of tumors that contain lipid, such as clear cell renal cell carcinoma. Answer A is incorrect because adipophilin positivity is insufficient to distinguish between sebaceous carcinoma and clear cell renal cell carcinoma metastasis. Both tumor types can stain positive for adipophilin. Answer D is incorrect because adipophilin expression has been linked in many studies to a worse prognosis and is not routinely used as a prognostic marker. Its main role is in identifying lipids within cells rather than indicating prognosis.

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Reference: Adipophilin