1. GRANULAR CELL TUMOR OF THE EYELID Anat Stemmer-Rachamimov, MD Associate Professor Division of Neuropathology Massachusetts General Hospital Boston MA
Special Thanks to:
Nora Laver

2. History and clinical findings
15 year old girl
Painless, solitary nodule on eyelid
No other information available.

3. Pathology

9. PAS

10. Sox S100

11. S100

12. S100

13. Discussion First described in 1926 by Abirkosoff
Initially believed to be of muscle origin
Wide variety of cell types have been proposed as cells of origin: myoblasts, fibroblast, smooth muscle cells, histiocytes, neuroendocrine cells, undifferentiated mesenchymal cells
Currently thought to be of neural/Schwann cell origin – based on immunostains (S100 and SOX10 positive), EM features and close relationship of tumor cells to nerve twigs and axons

14. Jaeger MJ et al, Survey of Opthalmology, 31 (6)417-423, 1987

15. Pathology of granular cell tumor
Hallmark of granular cell tumor – granular appearance of the tumor cells
Arranged in sheets, clusters separated by collagen bands
Small, round nucleus
Infiltrating edge
In some cases overlying skin may show pseudo- eptheliomatous hyperplasia

16. S100, SOX10 positive (neural crest) – most widely used marker for GCT
CD68 – lysosomal associated membrane protein
PAS (diastase resistant) positive

17. EM: tumor cells have basement membrane, cytoplasm is distended by numerous cytoplasmic inclusions with heterogenous appearance.
Jaeger MJ et al, Survey of Opthalmology, 31 (6) , 1987

18. Clinical features of granular cell tumor
Benign lesion
Occurs in all ages, but most common in adults ages 30-60
Arises in the skin, mucosa and soft tissues and was described in every part of the body. Most common sites are head and neck, especially the oral cavity
Multiple cutaneous tumors may occur and are more common in blacks (5% -20%) . In some cases multiple granular cell tumors are familial. Rarely, association with tumor syndromes has been reported (Neurofibromatosis 1)

19. Granular cell tumor and the eye
Review of the ophthalmic literature shows granular cell tumors have been reported in the orbit, lacrimal sac, eyelid, conjunctiva and caruncle.
In a review (1987) of 25 cases, half were orbital, the other most common site was the eyelid.

20. Orbital GCT - Eyelid GCT
arise in the orbital soft tissue, often involve the muscles.
often symptomatic, associated with exophthalmos and/or impairment of eye movements
Eyelid GCT
presents as a painless mass, often at the eyelid margin
may cause swelling or mimic a chalazion
when associated with pseudoepitheliomatous hyperplasia, may mimic a carcinoma clinically

22. Although granular cell tumor is almost always benign, malignant granular cell tumor has been described (rare)
Characterized by multiple mitoses, may have foci of necrosis. Clinical course is indolent – local recurrances may occur
Histologically, malignant granular cell tumor has to be differentiated from alveolar soft part sarcoma (S100, SOX10) and melanoma (melanoma markers).

23. Primitive polypoid granular cell tumor
There is a NON neural (S100 negative) tumor composed of granular cells – Primitive polypoid granular cell tumor.
It is histologically similar but considered a different entity – first described in by Le Boit.
Often polypoid and may present with ulcerated epithelial surface
There is often associated inflammation. Mitoses and cytological atypia is common
Tumor cells are S100 and SOX10 negative and are diffusely positive for CD63
60% of these tumors have ALK fusions
Clinical behavior is uncertain, and in rare cases lymph node metastasis has been reported.
Le Boit PE et al. Am J Surg Pathol, 1991
Chaudhry IH et al. Histopathology, 2005

24. Selected references
1. Abrikoffoff A et al. Uber Myome, ausgehend von der quesrgestreif- ten wilkurlichen muskulatur. Virchows Arch (A) 260: , 1926
2. Lace EE et al. Granular cell tumor: a clinicopathologic study of 110 patients. J of Surg Oncol 13: , 1980
3. Jaeger MJ et al. Granular cell tumor of the orbit and ocular adnexae. Survey of Ophthalmol, 31(6):
Ferry AP. Graunular cell tumor (myoblastoma) of the palpebral conjunctiva causing pseudoepitheliomatous hyperplasia of the conjunctival epithelium. Am J of Ophthal, 91: , 1981
Chaudhry IH et al. Dermal non neural granular cell tumor (so called primitive polypoid granular cell tumor): a distinctive entity further delineated in a clinicopathological study of 11 cases. Histopathology 47: , 2005

25. Thank you!