title: Unusual pleomorphic adenoma of the lacrimal Gland: Immunohistochemical demonstration of PLAG1 and HMGA2 oncoproteins.
abstract: Painless low-grade right proptosis with 20/25 visual acuity developed slowly in a 49-year-old woman with a past history of breast cancer. Imaging studies disclosed an oval-to-round superotemporal mass in the right lacrimal fossa without bone erosion. Excisional biopsy revealed a pseudoencapsulated, bosselated tumor with a spindled, hypocellular, and heavily periodic acid Schiff-positive stroma constituted of abundant basement membrane material and collagen. Scattered lumens and focal cribriform cellular clusters were present in the peripheries of several of the lobules. Immunohistochemistry showed epithelial membrane antigen+ and cytokeratin (CK) 7+ in many small luminal structures. The spindled cells were calponin+, CK5/6+, CK14+, and p63+, confirming their myoepithelial nature. The Ki67 proliferation index was 2-3%, and upregulation of nuclear p53, a tumor suppressor gene product which may be aberrantly overexpressed in malignancy, was observed in rare cells. Immunohistochemical probes for HMGA2 and PLAG1 oncoproteins, characteristic of pleomorphic adenoma, were stained intensely and less intensely, respectively. MYB and c-KIT (CD117) were negative, thereby strongly arguing against the diagnosis of adenoid cystic carcinoma. In atypical epithelial tumors of the lacrimal gland, genetic probes identifying distinctive gene translocations or their oncoprotein products complement traditional immunohistochemical biomarkers such as cytokeratins and other structural or secretory molecules. Characteristic genetic abnormalities demonstrated by immunohistochemistry for their upregulated protein products, or by in situ hybridization for translocations, are increasingly being relied on for diagnostic precision.
authors: David G. Cogan Laboratory of Ophthalmic Pathology, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: Fred_Jakobiec@meei.harvard.edu.
authors: Frederick A
authors: FA
authors: Jakobiec
authors: David G. Cogan Laboratory of Ophthalmic Pathology, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors: Anna M
authors: AM
authors: Stagner
authors: The Wills Eye Hospital, Department of Ophthalmology, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors: Ralph C
authors: RC
authors: Eagle
authors: Oncology Service and Ophthalmic Pathology Laboratory, Department of Ophthalmology, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors: Sara E
authors: SE
authors: Lally
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Jeffrey F
authors: JF
authors: Krane
mesh_terms: D008949:Adenoma, Pleomorphic / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D025743:HMGA2 Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000473:pathology; D007766:Lacrimal Apparatus Diseases / Q000175:diagnosis / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; C104382:PLAG1 protein, human
keywords: HMGA2; MYB-NFIB; PLAG1; adenoid cystic carcinoma; calponin; gene translocation; immunohistochemistry; lacrimal gland; myoepithelial cell; pleomorphic adenoma