Soft tissue
Peripheral nerve
Other benign
Perineurioma

Editorial Board Member: Borislav A. Alexiev, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Andrea Saggini, M.D.

Topic Completed: 12 April 2021

Minor changes: 12 April 2021

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PubMed Search: Perineurioma[title] pathology soft tissue

Andrea Saggini, M.D.
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Cite this page: Saggini A. Perineurioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissueperineurioma.html. Accessed April 18th, 2021.
Definition / general
  • Perineuriomas are soft tissue neoplasms almost exclusively composed of cells resembling normal perineurium
  • 2 main types of perineurioma are recognized: intraneural perineuriomas and soft tissue perineuriomas, including cutaneous and sclerosing perineuriomas
Essential features
  • Perineurioma are soft tissue neoplasms almost exclusively composed of cells resembling normal perineurium
  • 2 main types of perineurioma are recognized: intraneural perineuriomas and soft tissue perineuriomas, including cutaneous and sclerosing perineuriomas
  • Perineurial cells have typical slender, fibroblast-like appearance with long, delicate cytoplasmic processes
  • Perineuriomas express antigens that are identical to normal perineurium (EMA, GLUT1, claudin1)
Terminology
  • Localized hypertrophic neuropathy: old designation of intraneural perineuriomas (not recommended)
  • Hybrid benign peripheral nerve sheath tumors: rare tumors consisting of 2 intermingled neoplastic cell populations with neural differentiation, including hybrid perineurioma schwannoma and hybrid perineurioma neurofibroma
ICD coding
  • ICD-O: 9571/0 - perineurioma
  • ICD-O: 9571/3 - malignant perineurioma
Epidemiology
Sites
  • Intraneural perineurioma
    • Predilection for upper limbs (radial, ulnar, median nerves) and lower limbs (sciatic nerve)
  • Soft tissue perineurioma
    • Predilection for superficial soft tissues of the extremities and trunk
    • 30% of cases: deep soft tissues / visceral organs
    • Sclerosing perineurioma: predilection for hands (fingers, palms) (Am J Surg Pathol 1997;21:1433)
Pathophysiology
  • Intraneural perineurioma
    • Intraneural clonal (neoplastic) proliferation of perineurial cells
    • TRAF7 mutations (60% of cases) (Ann Neurol 2017;81:316)
  • Soft tissue perineurioma
Clinical features
  • Intraneural perineurioma
    • Muscle weakness, progressive loss of sensory function, muscle atrophy if untreated
  • Soft tissue perineurioma
    • Solitary, slowly growing nodule / tumor
    • Painful in a minority of cases
  • Reference: Arch Pathol Lab Med 2007;131:625
Diagnosis
  • Intraneural perineurioma
  • Soft tissue perineurioma
Radiology images

Images hosted on other servers:

Intraneural perineurioma
MRI showing enlarged brachial plexus MRI showing enlarged brachial plexus

MRI showing enlarged brachial plexus

MRI showing enlarged median nerve

MRI showing enlarged median nerve


Soft tissue perineurioma
MRI of the retriperitoneum

MRI of the retriperitoneum

Prognostic factors
  • Intraneural perineurioma
  • Soft tissue perineurioma
    • Typically benign behavior
    • Atypical perineuriomas: overall benign behavior
    • Malignant perineurioma: exceptionally rare, regarded as variant of malignant peripheral nerve sheath tumor
Case reports
Treatment
  • Intraneural perineurioma
    • No standard treatment guidelines
    • Complete resection with nerve grafting (but variable loss of neural function may be inevitable)
  • Soft tissue perineurioma
    • Complete excision (recurrences are uncommon)
Clinical images

Images hosted on other servers

Intraneural perineurioma
Preoperative photos of enlarged sciatic nerve

Preoperative photos of enlarged sciatic nerve

Preoperative photo of enlarged brachial plexus

Preoperative photo of enlarged brachial plexus


Soft tissue perineurioma
Swelling of the scalp

Swelling of the scalp

Endobronchial nodule

Endobronchial nodule

Gross description
  • Intraneural perineurioma
    • Fusiform expansion of affected nerve, extending several centimeters in length
  • Soft tissue perineurioma
    • Circumscribed white masses (1 - 20 cm in diameter)
  • Reference: Am J Surg Pathol 2005;29:845
Gross images

Images hosted on other servers

Intraneural perineurioma
Resected specimen from brachial plexus

Resected specimen from brachial plexus


Soft tissue perineurioma
Well circumscribed, whitish, solid mass

Well circumscribed, whitish, solid mass

Solid, whitish, homogeneous mass

Solid, whitish, homogeneous mass

Microscopic (histologic) description
  • Intraneural perineurioma
    • Multiple small "onion bulbs" expanding the affected nerve, consisting of concentric layers of perineurial cells ensheathing a central axon and Schwann cell
  • Soft tissue perineurioma
    • Nonencapsulated, well demarcated spindle cell tumor (Am J Surg Pathol 2005;29:845)
    • Perineurial cells have typical slender, fibroblast-like appearance with long, delicate cytoplasmic processes
    • Variable degree of cellularity, from paucicellular to densely cellular
    • Fibrotic / sclerotic stroma but frequent foci of myxoid degeneration
    • Metaplastic ossification (rare)
    • Storiform, whorled, lamellar or short fascicular patterns may be observed
    • Sclerosing perineurioma: spindled to rounded cells with pale cytoplasm with indistinct cell borders, arranged in cords / trabeculae / chains within a densely sclerotic stroma (Am J Surg Pathol 1997;21:1433)
    • Reticular perineurioma: lace-like arrangement of cells, resulting in formation of microscopic cysts (Virchows Arch 2005;447:677)
    • Rare histologic variants:
    • Atypical perineurioma: variable combination of scattered cytological atypia, mildly increased mitotic activity, increased cellularity or infiltration of muscle (Am J Surg Pathol 2005;29:845)
    • Malignant perineurioma (malignant peripheral nerve sheath tumor variant): diffuse cytological atypia, increased mitotic activity (> 13 figures/30 high power fields), necrotic foci (Clin Neuropathol 2012;31:424)
Microscopic (histologic) images

Contributed by Andrea Saggini, M.D.
Spindle cell tumor

Spindle cell tumor

Hemangiopericytoma-like pattern

Hemangiopericytoma-
like pattern

Storiform pattern

Storiform pattern

Pseudovascular pattern

Pseudovascular pattern

Fibrous histiocytoma-like pattern

Fibrous histiocytoma-like pattern

Perineurial cells

Perineurial cells


Spindled morphology

Spindled morphology

Sclerosing variant

Sclerosing variant

Reticular variant

Reticular variant

Cytology

Cytology

Vascularization

Vascularization

Myxoid changes

Myxoid changes


EMA

EMA

GLUT1

GLUT1

Claudin1

Claudin1



Contributed by Mark R. Wick, M.D.

Cutaneous

EMA

Positive stains
Negative stains
Electron microscopy description
  • Soft tissue perineurioma
    • Slender, nontapered processes containing large numbers of pinocytotic vesicles and partial encasement by basal lamina
Electron microscopy images

Contributed by Mark R. Wick, M.D.

Perineurioma

Molecular / cytogenetics description
Sample pathology report
  • Soft tissue of arm, incisional biopsy:
    • Benign spindle cell tumor with morphological and immunophenotypical features (EMA+, claudin1+, S100-, pancytokeratin-, alpha smooth muscle actin-) consistent with soft tissue perineurioma, extending to all the specimen margins. Despite the apparent lack of cytological atypia, complete excision of the neoplasm is advisable.
Differential diagnosis
Board review style question #1

A 34 year old man presented with a fibroma-like nodule on the left thigh. The tumor was completely excised. Histologic details are shown in the image above. Regarding this entity, which of the following statements is true?

  1. EMA positivity is sufficiently sensitive and specific for the diagnosis
  2. Positivity for claudin1 is often observed and may be helpful for diagnostic purposes
  3. S100 may be diffusely positive due to the neural differentiation of the neoplasm
  4. SOX10 is always positive
Board review style answer #1
B. Positivity for claudin1 is often observed and may be helpful for diagnostic purposes

The picture shows a nonencapsulated, well demarcated tumor consisting of a population of benign spindle cells with slender, fibroblast-like appearance and long, delicate cytoplasmic processes; the degree of cellularity is intermediate and the vascularity is increased at the periphery of the tumor.

EMA positivity is typically observed in the normal perineurium as well as in neoplastic cells with perineurial differentiation but EMA positivity alone is not specific for perineurial differentiation and requires concomitant positivity for at least another perineurial marker among GLUT1 and claudin1. S100 and SOX10 are typically negative in perineuriomas, due to the lack of cells with Schwannian differentiation; an exception is represented by hybrid neural tumors with concomitant perineurial and schwannomatous / neurofibromatous differentiation.

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Reference: Perineurioma
Board review style question #2
A 36 year old woman presented with a subcutaneous nodule on the left buttock. The nodule was completely excised and the final histopathologic report rendered a diagnosis of soft tissue perineurioma. Regarding this entity, which of the following statements is true?

  1. Atypical soft tissue perineuriomas exhibit clinically indolent behavior
  2. EMA is a useful immunohistochemical marker in the differential diagnosis with meningioma
  3. FISH plays no role in the diagnostic process of soft tissue perineurioma
  4. Immunohistochemical expression of alpha smooth muscle actin virtually rules out a diagnosis of soft tissue perineurioma
Board review style answer #2
A. Atypical soft tissue perineuriomas exhibit clinically indolent behavior

Atypical soft tissue perineuriomas are defined by presence (in variable combination) of scattered cytological atypia, mildly increased mitotic activity (> 13 figures/30 high power fields), increased cellularity or infiltration of muscle. Despite such partially worrisome histopathologic features, they normally exhibit clinically indolent behavior.

Immunohistochemical expression of alpha smooth muscle actin (patchy or rarely, diffuse) may be observed in up to 20% of soft tissue perineuriomas, while expression of desmin should be never observed. FISH may be employed to rule out the presence of PDGFB rearrangements in cases characterized by strong positivity for CD34 coupled with a storiform pattern suspicious for dermatofibrosarcoma protuberans. EMA is also positive in meningiomas; the differential diagnosis with the latter may be aided by immunohistochemical staining for SSTR2A and PR (which are negative in perneurioma but positive in most meningiomas).

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Reference: Perineurioma
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