Virchows Archiv

, Volume 456, Issue 1, pp 71–76

Multinucleated floret-like giant cells in sporadic and NF1-associated neurofibromas: a clinicopathologic study of 94 cases

  • Gaetano Magro
  • Paolo Amico
  • Giada Maria Vecchio
  • Rosario Caltabiano
  • Marine Castaing
  • Denisa Kacerovska
  • Dmitry V. Kazakov
  • Michal Michal
Original Article


Multinucleated floret-like giant cells (MNFGCs), similar to those commonly observed in pleomorphic lipoma and giant cell fibroblastoma, have been occasionally reported in gynecomastia and neurofibromas from patients affected by neurofibromatosis type 1 (NF1). Accordingly, it has been suggested that their detection, especially in an otherwise typical neurofibroma, could be a morphological clue to diagnosis of NF1. The aim of the present study was the identification of MNFGCs in a large series (94 cases) of sporadic and NF1-associated neurofibromas, to assess if their presence may indeed be a morphological marker of NF1. Numerous MNFGCs, namely, those that were easily apparent at low magnification (×50 and ×100), were identified only in 5.3% of cases. In 18.1% of cases, a low number of these cells could be observed but only after a careful search, especially at higher magnification (×200 and ×400). Immunohistochemically, all MNFGCs were stained with vimentin and CD34, but not with S-100 protein. Interestingly, there was no statistically significant correlation between MNFGCs (presence or absence) and NF1 (p = 0.73), gender (p = 0.59), age (p = 0.43), and site of tumor (cutaneous vs deep-seated soft tissue; p = 0.27). Our clinicopathologic findings suggest that MNFGCs in an otherwise typical neurofibroma are not a reliable marker of NF1, likely representing a morphological reactive change of the indigenous dermal or endoneurial fibroblasts or dendritic cells in response to unknown microenvironmental stimuli.


Neurofibroma Neurofibromatosis type I Multinucleated floret-like cells CD34 


  1. 1.
    Weiss SW, Goldblum JR (2008) Enzinger and Weiss’s soft tissue tumors. Mosby, St LouisGoogle Scholar
  2. 2.
    Scheithauer BW, Louis DN, Hunter S et al (2000) Malignant peripheral nerve sheath tumour (MPNST). In: Louis DN, Ohgaki H, Webster OD, Cavenee WK (eds) Pathology and genetics. Tumours of the central nervous system. IARC, Lyon, pp 155–162Google Scholar
  3. 3.
    Megahed M (1994) Histopathologic variants of neurofibroma: a study of 114 lesions. Am J Dermatopathol 16:486PubMedCrossRefGoogle Scholar
  4. 4.
    Gonzalez-Vela MC, Val-Bernal JF, Gonzalez-Lopez MA et al (2006) Pure sclerotic neurofibroma: a neurofibroma mimicking sclerotic fibroma. J Cutan Pathol 33:47CrossRefPubMedGoogle Scholar
  5. 5.
    MacLennan SE, Melin-Aldana H, Yakuboff KP (1999) Pacinian neurofibroma of the hand: a case report and literature review. J Hand Surg [Am] 24:413–416CrossRefGoogle Scholar
  6. 6.
    Val-Bernal JF, Gonzales-Vela MC (2005) Cutaneous lipomatus neurofibroma: characterization and frequency. J Cutan Pathol 32:274–279CrossRefPubMedGoogle Scholar
  7. 7.
    Plaza JA, Wakely PE, Suster S (2006) Lipoblastic nerve sheath tumors. Report of a distinctive variant of neural soft tissue neoplasm with adipocytic differentiation. Am J Surg Pathol 30:337–344PubMedGoogle Scholar
  8. 8.
    Kazakov DV, Vanecek T, Sima R et al (2005) Dendritic cell neurofibroma with pseudorosettes lacks mutations in exons 1–15 of the neurofibromatosis type 2 gene. Am J Dermatopathol 27:286CrossRefPubMedGoogle Scholar
  9. 9.
    Ferner RE (2007) Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol 6:340CrossRefPubMedGoogle Scholar
  10. 10.
    Magro G, Scavo S, Ruggieri M (2002) Floretlike multinucleated giant cell in a neurofibroma from a patient with NF1: an unusual finding for such a tumor. Virchows Arch 441:525–526CrossRefPubMedGoogle Scholar
  11. 11.
    Shaktawat SS, Golka D (2007) Floret-like multinucleated giant cells in neurofibroma. Diagn Pathol 8:2–47Google Scholar
  12. 12.
    Swick BL (2008) Floret-like multinucleated giant cells in a neurofibromatosis type 1-associated neurofibroma. Am J Dermatopathol 30:632–634CrossRefPubMedGoogle Scholar
  13. 13.
    Taungjaruwinai WM, Golbert LJ (2009) Multinucleate giant cells in neurofibromas: a clue to the diagnosis of neurofibromatosis. J Cutan PatholGoogle Scholar
  14. 14.
    Groisman GM, Amar M, Polak-Charcon S (2000) Multinucleated stromal cells of the anal mucosa: a common finding. Histopathology 36:224–228CrossRefPubMedGoogle Scholar
  15. 15.
    Groisman GM, Polak-Charcon S (1998) Fibroepithelial polyps of the anus: a histologic, immunohistochemical, and ultrastructural study, including comparison with the normal anal subepithelial layer. Am J Surg Pathol 22:70–76CrossRefPubMedGoogle Scholar
  16. 16.
    Ohtsuki Y, Furihata M, Iwata J et al (2000) Multinucleated giant cells in submucosal layer of human urinary bladder: an immunohistochemical and electron microscopic study. Pathol Res Pract 196:293–298PubMedGoogle Scholar
  17. 17.
    Pitt MA, Roberts IS, Agbamu DA et al (1993) The nature of atypical multinucleated stromal cells: a study of 37 cases from different sites. Histopathology 23:137–145CrossRefPubMedGoogle Scholar
  18. 18.
    Damiani S, Eusebi V (2001) Gynecomastia in type-1 neurofibromatosis with features of pseudoangiomatous stromal hyperplasia with giant cells. Report of two cases. Virchows Arch 438:513–516CrossRefPubMedGoogle Scholar
  19. 19.
    Zamecnik M, Michal M, Gogora M et al (2002) Gynecomastia with pseudoangiomatous stromal hyperplasia and multinucleated giant cells. Association with neurofibromatosis type 1. Virchows Arch 441:85–87CrossRefPubMedGoogle Scholar
  20. 20.
    Powell CM, Cranor ML, Rosen PP (1994) Multinucleated stromal giant cell in mammary fibroepithelial neoplasm. A study of 11 patients. Arch Pathol Lab Med 118:912–916PubMedGoogle Scholar
  21. 21.
    Ryska A, Reynolds C, Keeney GL (2001) Benign tumors of the breast with multinucleated stromal giant cell. Immunohistochemical analysis of six cases and review of the literature. Virchows Arch 439:768–775PubMedGoogle Scholar
  22. 22.
    Lin BT, Weiss LM, Medeiros LJ (1997) Neurofibroma and cellular neurofibroma with atypia: a report of 14 tumors. Am J Surg Pathol 21:1443–1449CrossRefPubMedGoogle Scholar
  23. 23.
    Jokinen CJ, Argenyi ZB (2009) Atypical neurofibroma of the skin and subcutaneous tissue: clinicopathologic analysis of 11 cases. J Cutan Pathol. doi:10.1111/j.1600-0560.2009.01293.x Google Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Gaetano Magro
    • 1
  • Paolo Amico
    • 1
  • Giada Maria Vecchio
    • 1
  • Rosario Caltabiano
    • 1
  • Marine Castaing
    • 2
  • Denisa Kacerovska
    • 3
  • Dmitry V. Kazakov
    • 3
  • Michal Michal
    • 3
  1. 1.Dipartimento G.F. IngrassiaPoliclinico Universitario G. Rodolico, Anatomia Patologica, Università di CataniaCataniaItaly
  2. 2.G.F Ingrassia DepartmentIntegrated Tumor Registry of Messina-Catania-Siracusa, Hygiene and Public Health InstituteCataniaItaly
  3. 3.Sikl’s Department of PathologyCharles University Medical Faculty HospitalPilsenCzech Republic

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