Granulomatous Response to Tissue Filler Tina Fanning MD Anderson Cancer Center Houston, TX

Clinical History A 47 year old female complained of a right cheek mass which was present for several months. She noted decreased sensation in the area of the mass. There was no previous history of skin lesions or excisions. Slide 1 - DiffQuik Click to view with ImageScope Click to view with a Web-Based Viewer Slide 2 - Pap Stain Click to view with ImageScope Click to view with a Web-Based Viewer Slide 3 - Pap Stain Click to view with ImageScope Click to view with a Web-Based Viewer Slide 4 - Pap Stain Click to view with ImageScope Click to view with a Web-Based Viewer Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Diagnosis: Granulomatous Response to Tissue Filler The basic approach to this unique lesion is to make the simple observation that we have cellular constituents and an extracellular material. We can ask, "What are the cells?" The cellular elements are adherent to or grouped around and between the extracellular material. Some cells appear spindled. Some multinucleated giant cells are noted. On close observation the spindle-like cells have very pale nuclei that are elongate and often curved or indented. They look exactly like epithelioid histiocytes. Association with multinucleated giant cells supports a granulomatous lesion. The matrix material is rather thick and well defined with almost a buttressed appearance. It does not resemble the more fluid appearance of myxoid matrix seen in myxoid sarcomas and other myxoid soft tissue lesions. It does not have the fibrillar appearance no the bright magenta color on Diff- Quik that chondroid matrix often has. What is the matrix? Perhaps it is a foreign material. At this point, a good history is useful. The patient was still in our FNA clinic while I was asked to review the smears. My colleagues returned to clinic and proceeded to elicit the history that our 45 year old female patient had undergone several procedures involving injection of dermal filling agents for cosmetic effect. We called the referring head and neck surgeon who then cancelled her excisional surgery. We obtained samples of well-know tissue fillers, prepared smears and stained them with Diff-Quick and Papanicolaou stains and compared them with our smears from the patient. We found and match. This case provides an example of the use of a minimally invasive procedure to establish a diagnosis. This particular patient with a facial lesion had undergone procedures for improving her appearance and would have been less than pleased to have had a surgical scar in this area had diagnosis depended on open biopsy or excisional biopsy. The needles used to obtain our samples were 25g and 1" in length. Lessons Learned from this Case: Epithelioid histiocytes are still epithelioid histiocytes where ever they occur Have a differential diagnosis for extracellular matrix A good history is important Pathologists must be familiar with the appearance of injectable biomaterials Pathologists must be aware of iatrogenic tissue changes that may produce pitfalls in diagnosis Differential Diagnosis of Granulomas: Infections, fungi, TB Sarcoidosis Rheumatoid arthritis Foreign body Differential Diagnosis of Extracellular Matrix: Chondroid matrix Myxoid matrix Mucoid matrix Basement membrane material Implantable biomaterials Extracellular chondroid matix can be seen in chondrosarcomas, enchondromas, chondroblastomas, chondromyxoid fibromas, chordomas, chondroblastic osteosarcomas and perhaps most familiar to cytotechnologists and cytopathologists, in pleomorphic adenomas (benign mixed tumor) of salivary gland. Myxoid matrix is seen in a wide variety of reactive mesenchymal lesions including nodular fasciitis as well as in benign and malignant soft tissue tumors. Mucoid material is seen in mucinous/colloid adenocarcinomas such as those seen in the breast, pancreas, stomach and colon. Mucin stains are useful in indentifying epithelial mucins. In recent years, dermal filler substances consisting of highly viscous fluids or polymer particle suspensions have been used in facial reconstructive surgery and aesthetic procedures. They have also been used in unilateral vocal cord paralysis, in augmentation of the lip and soft palate in cleft lip patients and in reconstructing orbits. They are also being used as bulking agents in the lower esophageal sphincter, bladder neck or anal sphincter in patient suffering from gastroesophageal reflux, urinary incontinence or fecal incontinence, respectively. Increasing demands for injectable dermal fillers makes pathologists face new and sometimes puzzling granuloma types. It is important to be aware of these substances and their appearance. Most of the cosmetic injections are done in the perioral, periorbital and cheek areas of middle-aged women to smooth out wrinkles or augment cheek or lip volume to rejuvenate appearance. In their paper on injectable filler substances, Lemperle et al have stated: "All injectable filler materials cause normal foreign-body-type reactions that may develop into a foreign body granuloma in selected patients." These granulomas occur at a rare of 0.01% to 1.0% according to the nature of the injectable material. The cause of granulomas formation in some patients is yet unknown and unpredictable. General Reference: Fechner RE, Nicholis GE, Yeh I-T. Iatrogenic Lesions in Silverberg's Principles and Practice of Surgical Pathology and Cytopathology. Churchill Livingstone Elsevier 2006, 4th ed., volume 1, ch. 5:135-166. Note: This chapter is an excellent reference for iatrogenic changes in tissues and gives references to the cytology literature. Dermal Fillers: Lombard T, Samson J, Plantier F, et.al. Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. J Oral Pathol Med 2004;33:115. Lemperle G. Morhenn V, Charrier U. Human histology and persistence of various injectable filler substances for soft tissue augmentation. Aesth Plast Surg 2003;27:354.