Hybrid nerve sheath tumor
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Hybrid nerve sheath tumors or hybrid peripheral nerve sheath tumors (HPNST) are benign peripheral nerve sheath tumors displaying combined morphological characteristics of more than one of the conventional tumor types such as schwannoma neurofibroma or perineurioma. Recognized combinations are:
- schwannoma + perineurioma (usually sporadic)
- schwannoma + neurofibroma (usually in the setting of NF1, NF2 or schwannomatosis)
- neurofibroma + perineurioma (rare, usually in the setting of NF1)
Another acceptable term of hybrid nerve sheath tumor is ‘benign nerve sheath tumor NOS’.
Hybrid nerve sheath tumors are generally rare and tumors showing a hybrid morphology of schwannoma/perineurioma or neurofibroma/schwannoma are more common than the neurofibroma/perineurioma hybrid. They have been found in a wide age range but seem to have a peak in young adults. There is apparently no gender predilection 1-3.
The neurofibroma/schwannoma hybrid has been found in association with the following conditions 1,2:
The neurofibroma/perineurioma hybrid has been associated with neurofibromatosis type 1, whereas the schwannoma/perineurioma hybrid seems to occur sporadically 1,2.
The diagnosis of hybrid nerve sheath tumors is established by histological and immunohistochemical criteria 1.
Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 1:
- mixed features of two different types of benign nerve sheath tumors
- appropriate immunohistochemistry of those components
Clinical features are similar to normal benign nerve sheath tumors. Lesions in the subcutaneous tissue and skin often manifest as painless mass, whereas lesions of spinal nerves and larger peripheral nerves can present with pain and neurological deficits 1.
Hybrid nerve sheath tumors are characterized by mixed morphological and immunohistochemical features of at least two types of peripheral nerve sheath tumors 1-3.
Hybrid nerve sheath tumors display a wide anatomic distribution but are most often found in the subcutaneous tissue and the dermis e.g. in the fingers whereas rare cases have been reported for the cranial nerves 1-3.
Macroscopically hybrid nerve sheath tumors are well-demarcated lesions with a similar appearance to other benign nerve sheath tumors 1.
The histological features of hybrid nerve sheath tumors differ with respect to the individual type and are characterized by the following 1,2:
- storiform or fascicular growth with multilobular architecture
- a mixture of Schwann cells and perineural cells
- possible plexiform architecture
- solid nodular Schwann cell proliferation within loose neurofibroma background with myxoid changes
- resemble plexiform neurofibroma with perineurial differentiation
Similar to histological features immunohistochemistry stains differ with respect to the individual type.
Schwann cells generally react to S100, perineurial areas usually demonstrate positivity for epithelial membrane antigen (EMA), claudin 1 or Glut1 but not S100, whereas neurofibromatous components display a mixed picture of CD34, S100, SOX10, and EMA positivity 1-3.
Descriptions of radiographic features of hybrid nerve sheath tumors are very scarce in the literature. One case report on a neurofibroma/schwannoma hybrid described and showed it with the fusiform appearance of a benign nerve sheath tumor and bright signal on STIR sequences as well as peripheral enhancement after gadolinium with relative large non-enhancing components 4.
The radiological report should include a description of the following:
- form, location and size
- tumor margins and transition zone
- affected nerve/plexus and relations to adjacent neurovascular structures
- relations to bones
- relations to the muscular fascia
Treatment and prognosis
Hybrid nerve sheath tumors are benign and rarely recur after local excision 1.
History and etymology
The first major work on hybrid nerve sheath tumors was published by the pathologists by the American pathologist Mel B. Feany and colleagues in 1998 2,5.
Tumors or conditions which can mimic the presentation and/or appearance of a hybrid nerve sheath tumors are obviously their single morphologic counterparts 1:
- 1. Stemmer-Rachamimov AO, Hornick JL. Hybrid nerve sheath tumour. In: WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours. Lyon (France): International Agency for Research on Cancer; 2020. (WHO classification of tumours series, 5th ed.; vol. 3). https://publications.iarc.fr
- 2. Michal M, Kazakov D, Michal M. Hybrid Peripheral Nerve Sheath Tumors: A Review. Cesk Patol. 53(2):81-8. - Pubmed
- 3. Ud Din N, Ahmad Z, Abdul-Ghafar J, Ahmed R. Hybrid Peripheral Nerve Sheath Tumors: Report of Five Cases and Detailed Review of Literature. BMC Cancer. 2017;17(1):349. doi:10.1186/s12885-017-3350-1 - Pubmed
- 4. Lang S, Zager E, Coyne T, Nangunoori R, Kneeland J, Nathanson K. Hybrid Peripheral Nerve Sheath Tumor. J Neurosurg. 2012;117(5):897-901. doi:10.3171/2012.8.JNS111841 - Pubmed
- 5. Feany M, Anthony D, Fletcher C. Nerve Sheath Tumours with Hybrid Features of Neurofibroma and Schwannoma: A Conceptual Challenge. Histopathology. 1998;32(5):405-10. doi:10.1046/j.1365-2559.1998.00419.x - Pubmed