Soft tissue

• Benign nerve sheath tumor arising from differentiated Schwann cells

• Most cases have an indolent course
• Malignant transformation is exceedingly rare:
  • Most commonly reported after receiving stereotactic radiation (typically in acoustic schwannoma) (Front Oncol 2021;11:655260, Otol Neurotol 2015;36:1301)
  • Sporadic malignant transformation may occur in very rare cases (Asian J Neurosurg 2018;13:810, Otol Neurotol 2015;36:1301)
  • To malignant peripheral nerve sheath tumor (BMJ Case Rep 2021;14:e246445, Front Oncol 2021;11:655260)

Contributed by Mark R. Wick, M.D.

Contributed by Jose G. Mantilla, M.D., Mark R. Wick, M.D. and Case #334

Contributed by Dia Eldin Kamel, M.D., Ph.D. and Case #50



Plexiform schwannoma:


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Microcystic / reticular schwannoma:

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Case #59


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• Keratin (cytokeratin) immunoreactivity may be seen in some cellular schwannomas, which may represent cross reactivity with GFAP (Acta Neuropathol 2012;123:295)
• Neurofilament (rare staining)
• Desmin, SMA
• EMA (expressed in the capsule / perineural fibroblasts)

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• May occur spontaneously
• Can occur in familial tumor syndromes such as neurofibromatosis type 2 (NF2), schwannomatosis or Carney complex
• Can be caused by loss of function of the tumor suppressor gene, merlin (schwannomin)
• Merlin acts as a tumor suppressor gene
  • Overexpression can hinder cell proliferation and the changes induced by oncogenes
  • Its downregulation leads to neoplastic transformation
• Mutations affecting SMARCB1 have a role in the pathogenesis of a small subset of spinal schwannomas and biallelic inactivation of SMARCB1 may cooperate with deficiency of NF2 function (J Neurooncol 2018;137:33)

• Leiomyoma and leiomyosarcoma:
  • May show palisading and extensive degenerative changes in the form of hyalinization, calcification, myxoid changes and ancient nuclear atypia
  • Cells are elongated with eosinophilic or occasional fibrillar cytoplasm with distinct cell membranes
  • S100-
  • SMA+ and desmin+
  • Ultrastructurally evidence of leiomyogenic differentiation
• Malignant melanoma:
  • May be a challenge in small biopsies
  • Spindle cell and desmoplastic melanoma often lose expression of HMB45 and MelanA
• Malignant melanotic nerve sheath tumor:
  • Formerly known as melanotic schwannoma (misnomer)
  • Often arises in the paraspinal region
  • Tumors are usually heavily pigmented
• Malignant peripheral nerve sheath tumor (MPNST):
  • Infiltrative growth
  • Hypercellular, pleomorphic nuclei and high mitotic activity
  • Areas of geographic necrosis can show divergent differentiation
  • Patchy S100 or negative
• Neurofibroma:
  • Usually lacks capsule, formed of spindle cells, shredded carrot collagen and mast cells
  • Hypocellular, myxoid areas without hypercellular areas
  • Weaker S100, focal calretinin, stronger CD34, factor XIIIa+
• Pleomorphic hyalinizing angiectatic tumor (PHAT) (J Clin Diagn Res 2017;11:ED15):
  • Nonencapsulated with infiltrative border
  • Large ectatic vascular spaces with perivascular hyalinization
  • Fibrin in and around vessels
  • Negative for S100 and CD31, positive for CD34
• Solitary circumscribed neuroma (palisaded encapsulated neuroma):
  • Encapsulated dermal or subcutaneous tumor, which may be seen with club-like extension in the subcutaneous tissue
  • May show nuclear palisading
  • Silver stains show the axons traversing the Schwann cells; however, they are near the capsule in schwannomas
  • Peripheral delicate EMA positivity

Which of the following immunohistochemical stains best differentiates schwannoma from neurofibroma?

1. Calretinin
2. CK5/6
3. MNF116
4. p63
5. S100

E. S100 shows strong and almost diffuse positivity with schwannoma in contrast to neurofibroma, which variably expresses the antigen due to the presence of other cell populations.

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Reference: Schwannoma

Which of the following is true regarding the tumor represented in the picture?

1. Its cytologic atypia is degenerative in nature
2. The degree of cytologic atypia suggest malignant transformation
3. Melanin pigment may be seen in some of these lesions
4. These tumors are usually poorly circumscribed and difficult to excise
5. Local recurrence and malignant transformation are common

A. The picture represents schwannoma with degenerative changes (ancient schwannoma). Tumors with extensive degenerative changes may have extensive hyalinization with loss of their characteristic architectural features, as well as conspicuous degenerative cytologic atypia. Malignant transformation of schwannoma is exceedingly rare and most commonly reported in the setting of stereotactic radiation. Malignant melanotic nerve sheath tumor (formerly called melanotic schwannoma) is a rare tumor with metastatic potential, which often arises in the paraspinal region. Given its different biological behavior, it should not be labeled as schwannoma. Most schwannomas are encapsulated and easily separated from their nerve of origin. Local recurrence is rare after excision.

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Reference: Schwannoma