Case 6 -
Granulomatous Response to Tissue Filler
MD Anderson Cancer Center
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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.
Case 6 - Slide 1 - DiffQuik
Case 6 - Slide 2 - Pap Stain
Case 6 - Slide 3 - Pap Stain
Case 6 - Slide 4 - Pap Stain
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
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
- Pathologists must be aware of iatrogenic tissue changes
that may produce pitfalls in diagnosis
Differential Diagnosis of Granulomas:
- Infections, fungi, TB
- Rheumatoid arthritis
- Foreign body
Differential Diagnosis of Extracellular Matrix:
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.
- Chondroid matrix
- Myxoid matrix
- Mucoid matrix
- Basement membrane material
- Implantable biomaterials
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.
Note: This chapter is an excellent reference for iatrogenic changes in tissues and gives references
to the cytology literature.
- 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.
- 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.