Intraneural perineurioma: a systematic review with illustrative cases

Share Embed

Descrição do Produto

Review Article

Intraneural Perineurioma A Systematic Review With Illustrative Cases Bobby L. Boyanton, Jr, MD, MT(ASCP); John K. Jones, MD, FRCS, FACS; Saleh M. Shenaq, MD†; M. John Hicks, MD, PhD, DDS; Meenakshi B. Bhattacharjee, MD, MBBS

● Context.—Intraneural perineurioma may be confused with other ‘‘onion bulb’’ Schwann cell entities (localized hypertrophic neuropathy, reactive/demyelinating processes, or inherited polyneuropathies of Charcot-MarieTooth/Dejerine Sottas) due to similar clinical, radiologic, and histologic features. Perineurial and Schwann cells can only be differentiated by ultrastructure and immunohistochemsitry. Objective.—To identify and summarize the clinicopathologic features of true cases of intraneural perineurioma from the English language literature. Data Sources.—A systematic review was performed on definitive intraneural perineuriomas identified through Medline. Baylor College of Medicine–affiliated hospitals’ anatomic pathology databases yielded 2 illustrative intraneural perineurioma cases. Study Selection.—Intraneural perineurioma inclusion criteria consisted of characteristic histology and confirmation of perineurial cell lineage by either immunohistochemistry (epithelial membrane antigen positive, S100 protein negative) and/or ultrastructural analysis (thin cyto-

plasmic processes with an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles). Data Extraction.—Clinicopathologic data were extracted from all identified articles, with subsequent statistical analysis of the following parameters: age, sex, race, tumor location, tumor size, duration of symptoms prior to diagnosis, treatment modalities and outcomes measures, follow-up assessment for tumor recurrence and metastasis, clinical features (history of trauma, motor/sensory abnormalities, clinical/family history), and diagnostic workup (routine histology, immunohistochemistry, ultrastructural analysis, and molecular/cytogenetic characteristics). Conclusions.—Intraneural perineurioma is a neoplastic proliferation of perineurial cells with unique immunohistochemistry and ultrastructural features, and it is distinct from other onion bulb Schwann cell–derived entities. Despite harboring molecular abnormalities of the long arm of chromosome 22, intraneural perineurioma has not been associated with neurofibromatosis. Intraneural perineurioma is a benign peripheral nerve sheath tumor that does not recur or metastasize. (Arch Pathol Lab Med. 2007;131:1382–1392)


acteristically causes progressive loss of motor function.1 A concomitant sensory deficit is uncommon, and a history of preceding trauma is currently debatable. Imaging modalities frequently disclose fusiform, segmental enlargement of the affected nerve, which is histologically expanded predominantly or exclusively by concentric whorls of either spindle-shaped perineurial cells (pseudo–onion bulbs) or Schwann cells (true onion bulbs), with or without the presence of interspersed collagen bundles and/or occasional residual axon–Schwann cell complexes at the whorls’ center. This obscure nomenclature creates difficulty in accurately distinguishing true cases of intraneural perineurioma from histologically similar Schwann cell– derived reactive/demyelinating processes or the inherited polyneuropathies of Charcot-Marie-Tooth and DejerineSottas.2,3 The gold standard to distinguish perineurial cells from Schwann cells is electron microscopy, whereby perineurial cells characteristically show thin, elongated cytoplasmic processes, an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles. These characteristic features were initially observed by Lallemand et al4 and subsequently verified by others.5–8 By immunohistochemistry, perineurial cells are readily distinguished from

n the English language literature, intraneural perineurioma is loosely referred to as localized hypertrophic neuropathy/mononeuropathy, hypertrophic neurofibroma, hypertrophic neuropathy, intraneural neurofibroma, interstitial hypertrophic neuropathy, pseudo–onion bulb neuropathy/mononeuropathy and, occasionally, onion bulb neuropathy/mononeuropathy. These various names describe a unique clinical and radiologic dyad occurring primarily in adolescents or young adults, who present with a slow-growing, painless mononeuropathy that char-

Accepted for publication April 23, 2007. From the Departments of Pathology (Drs Boyanton, Hicks, and Bhattacharjee) and Otolaryngology (Dr Jones), Baylor College of Medicine; Children’s Ear, Nose, and Throat of Houston (Dr Jones); Department of Plastic Surgery, University General Hospital (Dr Shenaq); and Department of Pathology, Texas Children’s Hospital (Drs Hicks and Bhattacharjee), Houston. Dr Boyanton is now with the Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, Mich. † Deceased. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Bobby L. Boyanton, Jr, MD, MT(ASCP), Department of Clinical Pathology, William Beaumont Hospital, 3601 W Thirteen Mile Rd, Royal Oak, MI 48073 (e-mail: [email protected]). 1382 Arch Pathol Lab Med—Vol 131, September 2007

Intraneural Perineurioma—Boyanton et al

Schwann cells by their positive staining for epithelial membrane antigen and negative staining for S100 protein.9–11 Despite the advent of this newer technology, intraneural lesions composed predominantly or exclusively of concentric whorls of perineurial cells are still, albeit less commonly, being classified as localized hypertrophic mononeuropathy, etc—names that should be reserved for those histologically similar intraneural onion bulb lesions composed of Schwann cells. In summary, our primary goal was to objectively and thoroughly review the English language literature and accurately identify and summarize the clinicopathologic characteristics of definitive cases of intraneural perineurioma. In addition to describing two pediatric cases of intraneural perineurioma involving the ulnar nerve and an unnamed nerve of the dorsolateral tongue, we discuss the histologic, immunohistochemical, cytogenetic/molecular, and ultrastructural characteristics and the differential diagnosis of this uncommon and unique neoplasm. MATERIALS AND METHODS Immunohistochemistry Epithelial membrane antigen (EMA; clone E29, dilution 1:150; Dako Inc, Carpinteria Calif), vimentin (VIM; clone 3B4, dilution 1:300; Dako), S100 protein (S100; clone DR96 & BC96, dilution 1: 500, Biocare Medical Inc, Concord, Calif), neurofilament protein (NFP; clone 2F11, dilution 1:25; Dako), and Ki-67 (clone MIB-1, dilution 1:500; Dako) were applied using a BioGenex i6000 automated instrument (BioGenex Inc, San Ramon, Calif). Heat-induced epitope retrieval (HIER), which consisted of steam for 20 minutes in citrate buffer, was performed for each antibody, except NFP, which did not undergo an epitope retrieval procedure.

Ultrastructural Analysis (Electron Microscopy) Fresh tissue was placed in 4% glutaraldehyde and processed for electron microscopic analysis. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a JEM1210 transmission electron microscope (JEOL USA, Peabody, Mass).

Literature Review, Data Acquisition, and Inclusion Criteria Definitive cases of intraneural perineurioma reported in the English language literature were identified through a Medline search (as of November 2006) using ‘‘perineurioma, intraneural perineurioma, perineurial, hypertrophic mononeuropathy, localized hypertrophic mononeuropathy, hypertrophic neurofibroma, hypertrophic neuropathy, intraneural neurofibroma, interstitial hypertrophic neuropathy, pseudo onion-bulb neuropathy, pseudo onion-bulb mononeuropathy, onion-bulb neuropathy, onion-bulb mononeuropathy, pseudo onion-bulb and onion-bulb’’ as key words. The original articles were obtained for all citations, and additional cases were identified from the cited references. In addition, the anatomic pathology databases of Baylor College of Medicine and its affiliated hospitals (Texas Children’s Hospital, Ben Taub General Hospital, and Veterans Affairs Medical Hospital) in Houston, Tex, were queried for additional cases of intraneural perineurioma using the aforementioned key words. The histopathologic features of each reported case were reviewed to identify definitive cases of intraneural perineurioma, despite the original author(s) classifying nomenclature. Inclusion criteria consisted of (1) histologic demonstration of nerve expansion predominantly or exclusively by concentric whorls of spindle-shaped perineurial cells having thin, elongated, eosinophilic, cytoplasmic processes that may or may not envelop residual axons and/or Schwann cells, and with or without interspersed collagen bundles; (2) immunohistochemical confirmation of perineurial cell lineage by demonstrating positive staining with EMA and negative staining with S100; and/or (3) ultrastructural conArch Pathol Lab Med—Vol 131, September 2007

firmation of perineurial cell lineage by demonstrating thin cytoplasmic processes with an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles, all with or without interspersed collagen bundles.

RESULTS Clinical Information Case 1. A 6-year-old Caucasian girl presented with a 1-year history of a right-sided tongue mass that was unassociated with trauma, pain, motor, or sensory abnormalities. Her medical history was significant only for a febrile seizure at 1 year of age. There was no personal or family history of neurofibromatosis (NF) or other inheritable neuropathies. Physical examination disclosed a 1cm, soft, nontender, pink mass on the right lateral border of the tongue. Lingual movement was normal, and there were no abnormalities with swallowing. Six months later the mass was surgically excised. Her postoperative course was unremarkable, and a 4-month follow-up visit showed no evidence of recurrence or motor or sensory deficits. Case 2. A 5-year-old Caucasian boy was noted to have difficulty extending his right fourth and fifth fingers. The duration of the problem was unknown, and there was no associated pain or history of trauma. Physical examination was significant for a flexure deformity of the right fourth and fifth proximal and distal interphalangeal joints, mild dysmorphic facies (cup-shaped prominent ears, a flat nasal bridge, and minor telecanthus), and a total of 4 cafe´ au lait spots on the left flank, right arm, and legs, the largest of which measured 1.5 cm in diameter. Ophthalmologic evaluation was negative for Lisch nodules or other ocular pathology. The patient did not meet criteria for NF. There was no family history of NF or other inheritable neuropathies. Of note, his maternal grandmother had ‘‘a few small cafe´ au lait spots,’’ and his older brother and maternal uncle had similar dysmorphic facies. His medical history was significant for asthma and repeated ear infections, requiring bilateral myringotomy and adenoidectomy by 2 years of age. Electromyography confirmed motor palsy of the right ulnar nerve; however, no sensory deficit was present. Full-body contrast-enhanced magnetic resonance imaging revealed a solitary, homogeneously enhancing 1.5-cm ovoid mass involving the right ulnar nerve and located just proximal to the medial condyle. There was no evidence of metastatic disease. Surgical resection with nerve grafting was performed 6 months later. He underwent physical therapy with some motor improvement (ie, increased strength and attenuation of the claw deformity), and there have been no associated sensory abnormalities. Multiple follow-up visits during the last 3 years have detected no evidence of local tumor recurrence. The patient is currently 8 years of age and is being followed annually until puberty to assess for the possible development of NF. Pathologic Information Gross Findings. The specimen from case 1 was received in 10% neutral-buffered formalin and consisted of a 0.8 ⫻ 0.6 ⫻ 0.5-cm, glistening light tan–to-pink, rubbery nodule with a flattened base. The cut surface was uniformly light tan with peripherally located mucosa. The entire specimen was submitted for routine histologic processing. The specimen from case 2 consisted of an enlarged, fusiform portion of resected light tan nerve (1.5 cm in length ⫻ 0.7 cm maximum diameter), which had a uniformly Intraneural Perineurioma—Boyanton et al 1383

Figure 1. A, Case 1. Representative image of expanded nerve fascicles. B, Case 2. Representative image of resected segment of ulnar nerve (hematoxylin-eosin, original magnification ⫻200 [A and B]). Figure 2. A, Case 1. Same image as shown in Figure 1, A. B, Case 2. Same image as shown in Figure 1, B (epithelial membrane antigen, original magnification ⫻200 [A and B]). Figure 3. A, Case 1. Same image as shown in Figure 1, A. B, Case 2. Same image as shown in Figure 1, B (S100 protein, original magnification ⫻200 [A and B]).

light tan cut surface. A representative cross section was submitted for frozen section, with a preliminary diagnosis of an ‘‘organized Schwann cell proliferation, await permanent sections for further classification.’’ The remaining 1384 Arch Pathol Lab Med—Vol 131, September 2007

specimen was submitted for routine histologic processing as well as cytogenetic and ultrastructural analysis. Histologic, Immunohistochemical, Ultrastructural, and Cytogenetic Findings. Histologic and immunohistoIntraneural Perineurioma—Boyanton et al

Figure 4. A, Case 1. Same image as shown in Figure 1, A. B, Case 2. Same image as shown in Figure 1, B (neurofilament protein, original magnification ⫻200 [A and B]). Figure 5. Case 2. Ultrastructural characteristics of intraneural perineurioma. A, Concentric layers of elongated perineurial cell cytoplasmic processes and interspersed collagen fibers (black asterisk) (original magnification ⫻600). B, Centrally located residual axon (black arrowhead) and Schwann cell (white arrowhead) enveloped by concentric layers of perineurial cell cytoplasmic processes (original magnification ⫻600). C, Perineurial cell cytoplasmic processes showing discontinuous basal lamina, occasional poorly formed tight junctions (black arrowhead), and interspersed collagen fibers (black asterisk) (original magnification ⫻10 000). D, Perineurial cell exhibiting discontinuous basal lamina (white arrows) and pinocytotic vesicles (black arrowheads) (original magnification ⫻12 000).

Arch Pathol Lab Med—Vol 131, September 2007

Intraneural Perineurioma—Boyanton et al 1385

Table 1.


Clinicopathologic Summary of Definitive Cases of Intraneural Perineurioma* Age, y/Sex


Location or Nerve Involved

Maximum History of Size, cm Trauma

Motor Deficit

Sensory Deficit

Duration of Symptoms, mo

Current case 1 Current case 2 Almefty et al70 Dundr et al78 Da Cruz Perez et al75 Cortes et al74 Brock et al72 Chen et al73 Isaac et al83 Beekman et al71

6/F C Tongue (dorsolateral) 0.8 N N N 12 5/M C Ulnar 1.5 N Y N ... 27/F ... Oculomotor 1.5 N Y N ... 16/M ... Buccal mucosa 1.5 N N N ... 12/M ... Tongue (dorsolateral) 0.6 N N N 120 9/F ... Radial 3.5 N Y N 9 11/F ... Ulnar 2 N Y ... 24 7/M ... Wrist (volar) 2.4 ... N N ... 3/F ... Radial 2 N Y N 12 36/F ... Ulnar, left 4 ... Y Y 24 36/F ... Ulnar, right 5 ... Y N ... Hamazaki et al80 7/F ... Ulnar 1 N Y N 24 Rankine et al88 50/F ... Common peroneal 4 ... ... ... ... Huguet et al82 64/M ... Mandible (dental nerve) 2 ... ... ... 6 de La Jarte-Thirouard et al77 21/F ... Neck (jugulocarotid) 3 ... ... ... 3 Damm et al76 26/F ... Tongue (dorsum) 1 ... N N ... Heilbrun et al81 28/F ... Common peroneal 4 ... Y N 24 Alfonso et al69 2/F ... Median 1 ... Y Y 2 Takao et al92 20/F ... Femoral 5 ... Y N 48 Jazayeri et al84 53/M ... Median 5 N Y Y ... Simmons et al89 17/F ... Femoral 18 N Y Y 48 12/F ... Sciatic 12 N Y Y 12 26/F ... Brachial plexus 4 N Y Y 24 19/M ... Brachial plexus ... N Y N 24 Gruen et al67 37/M C Ulnar ... N Y N 36 37/M C Radial ... N Y N 117 16/M C Median ... N Y N 36 38/F C Radial ... N Y N 117 8/F C Peroneal ... N Y N 12 43/F C Peroneal ... N Y N 300 Li et al85 23/F ... Facial (intratemporal) ... N Y N 180 Emory et al79 12/M ... Sciatic 30 N Y Y ... 35/F ... Ulnar 3.5 N Y Y ... 31/M ... Sciatic-tibial 8 N Y Y ... 15/M ... Median 3.5 N Y N ... 38/F ... Posterior interosseous 10 N Y N ... 18/F ... Femoral 7 N Y N ... 11/F ... Nerve root (C8/T1) 6 N Y Y ... 13/F ... Peroneal 5.5 N Y N ... Suarez et al91 31/M ... Proximal tibial 8 N Y Y 96 Chou3 16/M ... Brachial plexus ... ... ... ... ... 20/M ... ... ... ... ... ... ... Mitsumoto H86 42/M ... Median ... N Y N 48 Stanton et al90 13/M ... Ulnar ... N Y N 24 Tranmer et al10 25/M ... Ulnar 4 N Y N ... Bilbao et al68 35/M ... Posterior interosseous 12 ... Y N 36 30/M ... Sciatic 4 ... Y N 60 25/M ... Median 6 ... Y Y 24 Mitsumoto H87 17/M ... Brachial plexus (lateral cord) 14 N Y Y 36 13/F ... Posterior interosseous 0.5 ... Y N 24 40/F ... Tibial 10 N Y N 60 Lallemand et al4 20/F P Posterior interosseous 2 N Y N 60 40/F ... Posterior interosseous 1.2 N Y N 120 * C indicates Caucasian; N, none; E, excision; NER, no evidence of recurrence; FHx, family history; NF, neurofibromatosis; CALS, cafe´ au lait spots (quantity); IHC, immunohistochemistry; EM, electron microscopy; . . ., not available; SRNG, surgical resection with nerve graft; MI, motor improvement; Dx, diagnosis; CC, conventional cytogenetics; STE, subtotal excision; NTG, no tumor growth; SR, surgical resection; NMSFx, no motor or sensory function; BWS, Beckwith-Wiedemann syndrome; TT, tendon transfer; SDP, sensory deficit present; FISH, fluorescence in situ hybridization; EB, excisional biopsy; SI, sensory improvement; NMSI, no motor or sensory improvement; NL, neurolysis; NMI, no motor improvement; PGM, paternal grandmother; SRA, surgical resection with anastomosis; P, Portuguese; and BAS, bilateral acoustic schwannomas.

chemical analysis of both cases disclosed an intraneural perineurioma. Hematoxylin-eosin–stained sections from case 1 showed a plexiform pattern of expanded nerve fascicles embedded within a fibrovascular stroma, whereas case 2 showed an expanded nerve with alteration of normal fascicular compartmentalization. In both cases, the expansion was due to a proliferation of pseudo–onion bulb 1386 Arch Pathol Lab Med—Vol 131, September 2007

structures with interspersed collagen bundles, the former composed of concentric whorls of spindle-shaped cells with thin, elongated, eosinophilic, cytoplasmic processes (Figure 1, A and B). The spindle cells were of perineurial origin due to positive membranous staining with epithelial membrane antigen and negative staining for S100 protein (Figures 2, A and B, and 3, A and B). At the center Intraneural Perineurioma—Boyanton et al

Table 1.


Follow-up Period, mo


4 36 10 24 6 6 ... 72 60 6 6 12 53 ... 6 ... 60 12 ... 11 10 30 2 6 48 6 36 24 6 12 10 48 36 12 12 3 1 ... ... ... ... ... ... ... ... ... ... ... 24 ... 6 ... ...

Clinical Evaluation

NER NER, MI NTG, MI NER NER MI ... NER, NMSFx NER, TT NER, MI, SDP NER, MI, SDP NER NER ... NER ... NER, NMSFx NER, MI, SI ... NER, MI, SDP NER, NMSI NER, NMSI NER, NMSI NER, MI NER, MI ... NER, MI NER, MI NER, NMI NER, MI NER, MI ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... NER, NMSI NMI NER, NMI NMI NMI

Significant Clinical History (Family History)

N (No FHx of NF) CALS ⫻4, No NF Dx (No FHx of NF) N N N N ... BWS N N N N ... ... ... ... ... ... N ... ... ... ... ... N N N N N N ... ... ... ... ... ... ... ... ... ... ... ... ... CALS ⫻3, No NF Dx (PGM with CALS; no FHx of NF) ... ... ... ... N NF with CALS and BAS (FHx of NF) N ... ...

of the concentric whorls, NFP highlighted occasional residual axons in case 1, and NFP and S100 highlighted several axon–Schwann cell complexes in case 2 (Figures 3, A and B, and 4, A and B). Ki-67 (MIB-1) was performed on case 2 and demonstrated less than 2% positive nuclear staining (image not shown). Ultrastructural analysis of case 2 confirmed that the pseudo–onion bulbs were concentric layers of perineurial cells, which enveloped residual axon–Schwann cell complexes. The elongated cytoplasmic processes demonstrated an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles, as well as interspersed collagen bundles (Figure 5, A Arch Pathol Lab Med—Vol 131, September 2007

Extended Diagnostic Modality






through D). Cytogenetic analysis of case 2 was uninformative due to fibroblast overgrowth within cell culture. Literature Review, Data Analysis, and Clinicopathologic Summary Definitive cases of intraneural perineurioma included in our investigation were selected based on appropriate histology and verification of perineurial cell lineage by either immunohistochemical and/or ultrastructural analysis. Cases excluded from our study included the following: (1) those demonstrating classic histologic features of intraneural perineurioma but without verification of perineurial Intraneural Perineurioma—Boyanton et al 1387

Table 2.

Clinicopathologic Summary of Definitive Cases of Intraneural Perineurioma Stratified by Age, Sex, and Site of Involvement Location and/or Nerve Involved

Age Range, y

0–19 20–39 ⱖ40 Summary

Male Cases Female Cases Total Cases Percentage of by Age by Age by Age Cases by Age Range Range* M/F Ratio Range Range

11 9 3 23

Head and Neck Region Buccal Mucosa

Facial Mandible (Intratemporal) (Dental) Neck Tongue Oculomotor

13 0.8 24 4 1 0 13 0.7 22 42 0 1 4 0.8 7 13 0 0 29 0.8 53 100 1 1 Percentage of Cases by Location 2 2 * Beekman et al71: 1 female with bilateral ulnar intraneural perineuriomas; total number of female cases † Chou3: 1 tumor in a 20-year-old man without a site designation.

cell lineage by immunohistochemical or ultrastructural analysis12–17; (2) those demonstrating classic histologic features of intraneural perineurioma but with subsequent demonstration of Schwann cell lineage by immunohistochemistry and/or ultrastructural analysis18–26; (3) cases of extraneural (soft tissue) perineurioma27–63; and (4) cases in which the pathologic process was due or related to a ganglion cyst, trauma, and/or reactive/demyelinating processes.14,64–66 Of note, Gruen et al67 in one of the largest series of localized hypertrophic neuropathy to date, only demonstrated perineurial cell lineage by immunohistochemistry in ‘‘. . . six of the more recent cases . . . ’’ of a total of 14. With this qualifying statement, we only included the 6 most recent cases from that study; the remaining 8 cases were excluded. Also, Ariza et al11 performed immunohistochemical analysis on 2 cases of intraneural perineurioma, which were previously described in detail by Bilbao et al68 in 1984; the clinicopathologic data of the latter is included in our investigation. In summary, 51 definitive cases of intraneural perineurioma were identified from 29 articles within the English language literature, based upon our inclusion criteria.3,4,10,67–92 Additionally, 2 cases of intraneural perineurioma were identified from our computer database search. The clinicopathologic data from the published and 2 current cases, where available, are summarized in Tables 1 and 2. In brief, a total of 53 tumors were identified from 23 males and 29 females, with only one author describing synchronous bilateral intraneural perineuriomas of the ulnar nerves in a 36-year-old woman.71 Taking this case into account, the male-female ratio was 0.8. Tumor size was provided in all but 12 cases, with an average, median, and range of 5.4, 4.0, and 0.5 to 18 cm, respectively. A total of 37 cases reported no history of trauma preceding tumor development; the remaining 16 cases did not provide this information. The duration of symptoms prior to diagnosis was, on average, 53 months, with a median and range of 30 months and 2 to 300 months, respectively. Motor abnormalities were present in 43 cases (81%), absent in 5 cases (9.5%), and not reported in 5 cases (9.5%). Concomitant sensory abnormalities were present in 13 cases (25%), absent in 34 cases (64%), and not reported in 6 cases (11%). Treatment modalities consisted of surgical resection with nerve grafting (15/53), surgical resection (11/53), excisional biopsy (11/53), excision (6/53), neurolysis (2/53), subtotal excision (1/53), surgical resection with primary anastomosis/coaptation (1/53), and none specified (6/53). A total of 35 cases provided information pertaining to the postoperative follow-up period (Table 1), with a mean, 1388 Arch Pathol Lab Med—Vol 131, September 2007

0 0 0 1 1 0 1 1 2 2 reduced by 1.

2 1 0 3 6

0 1 0 1 2

median, and range of 20, 12, and 1 to 72 months, respectively. There was no evidence of tumor recurrence, nor was there mention of metastatic disease in any of the 35 cases. Of the 16 cases treated by surgical resection with nerve grafting or primary anastomosis, 5 (31%) and 11 (69%) reported no improvement and some improvement in motor function, respectively. Personal and family history was available for 22 cases, with pertinent findings identified in only 4. One patient had Beckwith-Wiedemann syndrome,73 2 patients had cafe´ au lait spots but failed to meet diagnostic criteria for NF (current case 2),90 and 1 patient had a personal and family history of NF.87 Patient age was available in each case, with an average, median, and range of 23, 20, and 2 to 64 years, respectively. When stratified by age and sex, there was no significant difference in the percentage of reported cases by sex; however, most cases (46/53; 87%) occurred in individuals 39 years of age or younger (Table 2). Only 1 of the 53 cases failed to disclose a site designation.3 Affected sites in order of decreasing frequency were the ulnar nerve (9/53; 17%), median nerve (6/53; 11%), peroneal nerve (5/53; 9%), posterior interosseous nerve (5/53; 9%), sciatic nerve (4/53; 8%), radial nerve (4/53; 8%), brachial plexus (4/53; 8%), femoral nerve (3/53; 6%), tongue (3/ 53; 6%), and tibial nerve (2/53; 4%). The remaining sites consisted of buccal mucosa, intratemporal facial nerve, mandibular dental nerve, the jugulocarotid region of the neck, oculomotor nerve, C8/T1 nerve root, volar aspect of the wrist, and an undesignated location; each site only contributed 1 reported case (1/53; 2% each). Molecular analyses were performed on only 4 of the 53 reported cases. One case demonstrated the following abnormal karyotype: 45,XX,add(14)(p13),⫺22,add(22)(q11.2) [cp15]/46,XX,add(22)(q11.2)[1].79 Using a combined chromosome 14/22 centromeric probe, fluorescence in situ hybridization of paraffin-embedded tissue from a second case demonstrated 3 fluorescence in situ hybridization signals in 53% of tumor cells, indicating monosomy for the centromeric region of either chromosome 14 or 22.79 Using an LSI BCR/ABL locus-specific probe, a third case was shown to have a deletion of the BCR locus (22q11) in 75% of tumor cells.82 Routine cytogenetic studies were attempted in 1 of our 2 cases (case 2); however, the results were uninformative due to fibroblast overgrowth within cell culture. COMMENT Regarding the peripheral nervous system, the perineurium is composed of concentric layers of perineurial cells, which envelop myelinated and unmyelinated nerve fasciIntraneural Perineurioma—Boyanton et al

Table 2.


Location and/or Nerve Involved Lower Extremity



Posterior Interosseous



Site Not Specified

2 1 2 5 9

1 3 1 5 9

2 2 0 4 8

0 1 1 2 4

0 1 0 1 2

Trunk and Upper Extremity Brachial Plexus

3 1 0 4 8

Nerve Root Median (C8/T1)

3 1 2 6 11

1 0 0 1 2



Wrist (Volar Aspect)

2 2 0 4 8

4 5 0 9 17

1 0 0 1 2

cles and are continuous with the pia-arachnoid membrane at the level of the nerve roots based upon comparative histopathologic analyses.11,59–68,93–96 In contrast to their normal role within the perineurium, perineurial cells are uncommonly implicated in neoplastic processes. Perineurioma, according to the current World Health Organization classification of nervous system tumors, is a benign tumor of neoplastic perineurial cells.1 Histologically, perineurioma is subclassified as ‘‘intraneural’’ or ‘‘extraneural (soft tissue)’’ if the perineurial cell proliferation is confined within or unassociated with a nerve, respectively. The more common extraneural (soft tissue) form, with the exception of the sclerosing variant, usually arises within the limbs or trunk of middle-aged women, less commonly in the retroperitoneum, gastrointestinal tract, and paratesticular region43,46,47,97 and rarely within the ventricular system.42 The sclerosing variant of soft tissue perineurioma arises within the fingers or palm of young adults, with a male predilection.98 The rarely encountered intraneural perineurioma, however, typically presents in adolescents or young adults as a slow-growing, painless mononeuropathy that characteristically causes progressive loss of motor function and, uncommonly, a sensory deficit.1 Imaging studies frequently disclose fusiform, segmental enlargement of the affected nerve, usually less than 10 cm; however, the entire nerve may be affected.1 Although perineurioma was initially deemed a reactive process, mounting evidence supports its true neoplastic nature. Initial molecular findings in two cases of intraneural perineurioma demonstrated abnormalities and/or monosomy of the long arm of chromosome 22,79 a region known to harbor molecular abnormalities in other nervous system tumors—meningioma and schwannoma.99 Subsequent studies of soft tissue perineurioma, focusing on the region 22q11-q13.1, including the NF-2 gene (22q12.2), have not only confirmed monosomy of the long arm of chromosome 22 but cryptic deletions and/or point mutations within this region as well.72,100–103 Lasota et al101 performed DNA sequencing on exons 1 through 15 of the NF2 gene in 8 cases of soft tissue perineurioma and demonstrated 5-point mutations in 4 of the cases—2 in the 5⬘untranslated region and 1 each in exons 3, 6, and 8. More recently, fluorescence in situ hybridization analysis of a single case of intraneural perineurioma that focused on the BCR locus (22q11) showed a deletion of this region in 75% of analyzed nuclei.82 Despite abnormalities within this region, to our knowledge there has been no definitive association between intraneural or soft tissue perineurioma and NF. Based on our review, only 1 patient included in our meta-analysis had NF, and although 2 other patients had multiple cafe´ au lait spots, they did not meet diagnostic criteria for NF. It should be noted, however, that Arch Pathol Lab Med—Vol 131, September 2007


2 1 0 3 6

personal and family history was only available in 22 of the 53 cases. To date, karyotypic findings are available for only 6 cases of perineurioma in the English language literature, with both soft tissue and intraneural perineurioma containing relatively few abnormalities.72,79,102 However, recent data suggest abnormalities of chromosome 10 may be unique to sclerosing perineurioma.72,102 For practical purposes, the differential diagnosis for localized, fusiform enlargement of a peripheral nerve includes schwannoma, neurofibroma, traumatic neuroma, intraneural perineurioma, LHM and its synonyms and, less likely, chronic inflammatory demyelinating polyneuropathy (CIDP) or the inherited polyneuropathies of Charcot-Marie-Tooth (CMT) and Dejerine-Sottas (DS), the latter 3 of which should be distinguishable by clinical history, physical examination, and imaging modalities. By routine histology and immunohistochemistry, CIDP, CMT, DS, and LHM demonstrate similar-appearing S100-positive, EMA-negative onion bulbs in a background of collagen. The presence of macrophages is seen in LHM and CIDP, and the absence of macrophages is seen in DS and CMT.3 For the most part, neurofibroma, schwannoma, and traumatic neuroma lack a significant onion bulb component and should be distinguishable by histology; the latter is also preceded by a history of trauma. The pseudo–onion bulbs of intraneural perineurioma are EMA positive and S100 protein negative compared with other Schwann cell– derived S100 protein positive, EMA-negative onion bulb peripheral nerve sheath lesions. In either situation, if present, NFP and S100 protein will highlight residual axons and Schwann cells, respectively, at the center of the concentric whorls. Because perineurial cells can demonstrate weak EMA staining intensity, alternate antibodies, including CD57 (Leu-7), claudin-1, collagen IV, GLUT-1, laminin, and PGP 9.5 have been recently evaluated for their diagnostic utility in distinguishing perineurioma from neurofibroma and schwannoma. In brief, immunoreactivity (percent positive) for these neoplasms was (1) perineurioma: EMA (99%), S100 (3%), CD57 (0%), claudin-1 (42%), collagen IV (96%), GLUT-1 (90%), laminin (90%), and PGP 9.5 (100%)*; (2) schwannoma: EMA (19%), S100 (98%), CD57 (75%), claudin-1 (60%), collagen IV (100%), GLUT1 (90%), and PGP 9.5 (0%)†; and (3) neurofibroma: EMA (15%), S100 (96%), CD57 (71%), claudin-1 (67%), GLUT-1 (100%), and PGP 9.5 (100%).‡ Of special note, EMA, claudin-1, and GLUT-1 immunoreactivity within neurofibro* References 11, 46, 47, 57, 59, 72, 78–80, 82, 88, 95, 97, 98, 100, 104–107. † References 11, 95, 105, 106, 108–115. ‡ References 11, 57, 72, 95, 98, 100, 104–106, 109, 114, 116. Intraneural Perineurioma—Boyanton et al 1389

ma and schwannoma was confined to elongated spindle cells with delicate cytoplasmic processes predominantly at the periphery or in the capsule of each lesion, suggesting remnants of the perineurial sheath.95,105,106 Additionally, claudin-1–positive, perivascular dendritic cells were noted within neurofibroma and schwannoma, suggesting perineurial cells recapitulating the normal blood-nerve barrier.105 Immunoreactivity for CD57 (Leu-7) was present in neurofibroma and schwannoma and absent in perineurioma. Collagen IV was not evaluated in neurofibroma, and laminin was not evaluated in schwannoma or neurofibroma. Furthermore, to our knowledge, these antibodies (excluding EMA, CD57, and S100 protein) have not been evaluated in cases of S100-positive, EMA-negative Schwann cell–derived onion bulb lesions, due to reactive/ demyelinating processes or the inherited polyneuropathies of CMT or DS. Based on our immunohistochemical review, we feel that EMA and S100 should be initially used and, if necessary, followed by claudin-1 and GLUT-1, with the caveat of recognizing their potential diagnostic pitfall in neurofibroma and schwannoma, whereby claudin-1 and GLUT-1 immunoreactivity has been documented to highlight residual perineurial cells at the periphery or in the capsule of the tumor, and claudin-1 will furthermore highlight perivascular dendritic cells within the lesion. The immunoreactivity of CD57 may also serve a useful function in distinguishing perineurioma from neurofibroma and schwannoma, as CD57 immunoreactivity, to our knowledge, has not been reported in perineurioma. In any event, ultrastructural analysis of either fresh or paraffin-embedded tissue will provide the definitive answer. In review of malignant peripheral nerve sheath tumors with perineurial cell differentiation from the English language literature, confirmed either by immunohistochemistry,117,118 ultrastructural analysis,119 or both immunohistochemistry and ultrastructural analysis,120–124 not a single reported case described a preceding benign perineurioma (soft tissue or intraneural) undergoing malignant transformation. The absence of molecular information on these cases precludes correlation with those associated with perineurioma (soft tissue or intraneural), thereby prohibiting inferences as to whether or not malignant peripheral nerve sheath tumors with perineurial cell differentiation are a continuum of benign perineurioma (soft tissue or intraneural). In conclusion, based upon our systematic review, intraneural perineurioma should be regarded as a benign tumor that does not recur or metastasize and has little if any association with neurofibromatosis. References 1. Scheithauer BW, Giannini C, Woodruff JM. Perineurioma. In: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: IARC Press; 2000: 169–171. World Health Organization Classification of Tumours. 2. Midroni G, Bilbao JM. Genetically determined neuropathies. In: Biopsy Diagnosis of Peripheral Neuropathy. Boston, Mass: Butterworth-Heinemann; 1995: 353–410. 3. Chou SM. Immunohistochemical and ultrastructural classification of peripheral neuropathies with onion-bulbs. Clin Neuropathol. 1992;11:109–114. 4. Lallemand RC, Weller RO. Intraneural neurofibromas involving the posterior interosseous nerve. J Neurol Neurosurg Psychiatry. 1973;36:991–996. 5. Lazarus SS, Trombetta LD. Ultrastructural identification of a benign perineurial cell tumor. Cancer. 1978;41:1823–1829. 6. Ohno T, Park P, Akai M, et al. Ultrastructural study of a perineurioma. Ultrastruct Pathol. 1988;12:495–504. 7. Erlandson RA. The enigmatic perineurial cell and its participation in tumors and in tumorlike entities. Ultrastruct Pathol. 1991;15:335–351. 8. Ide F, Shimoyama T, Horie N, Kusama K. Comparative ultrastructural and immunohistochemical study of perineurioma and neurofibroma of the oral mucosa. Oral Oncol. 2004;40:948–953.

1390 Arch Pathol Lab Med—Vol 131, September 2007

9. Weidenheim KM, Campbell WG Jr. Perineural cell tumor: immunocytochemical and ultrastructural characterization: relationship to other peripheral nerve tumors with a review of the literature. Virchows Arch A Pathol Anat Histopathol. 1986;408:375–383. 10. Tranmer BI, Bilbao JM, Hudson AR. Perineurioma: a benign peripheral nerve tumor. Neurosurgery. 1986;19:134–138. 11. Ariza A, Bilbao JM, Rosai J. Immunohistochemical detection of epithelial membrane antigen in normal perineurial cells and perineurioma. Am J Surg Pathol. 1988;12:678–683. 12. de los Reyes RA, Chason JL, Rogers JS, Ausman JI. Hypertrophic neurofibrosis with onion bulb formation in an isolated element of the brachial plexus. Neurosurgery. 1981;8:397–399. 13. Gullotta F. Localized hypertrophic neuropathy (LHN). Pathol Res Pract. 1992;188:815–816. 14. Peckham NH, O’Boynick PL, Meneses A, Kepes JJ. Hypertrophic mononeuropathy: a report of two cases and review of the literature. Arch Pathol Lab Med. 1982;106:534–537. 15. Simpson DA, Fowler M. Two cases of localized hypertrophic neurofibrosis. J Neurol Neurosurg Psychiatry. 1966;29:80–84. 16. Snyder M, Cancilla PA, Batzdorf U. Hypertrophic neuropathy simulating a neoplasm of the brachial plexus. Surg Neurol. 1977;7:131–134. 17. Johnson PC, Kline DG. Localized hypertrophic neuropathy: possible focal perineurial barrier defect. Acta Neuropathol (Berl). 1989;77:514–518. 18. Boker DK, Schonberg F, Gullotta F. Localized hypertrophic neuropathy— a rare, clinically almost unknown syndrome. Clin Neuropathol. 1984;3:228–230. 19. Chang Y, Horoupian DS, Jordan J, Steinberg G. Localized hypertrophic mononeuropathy of the trigeminal nerve. Arch Pathol Lab Med. 1993;117:170– 176. 20. Hawkes CH, Jefferson JM, Jones EL, Thomas Smith W. Hypertrophic mononeuropathy. J Neurol Neurosurg Psychiatry. 1974;37:76–81. 21. Iyer VG, Garretson HD, Byrd RP, Reiss SJ. Localized hypertrophic mononeuropathy involving the tibial nerve. Neurosurgery. 1988;23:218–221. 22. Kania RE, Cazals-Hatem D, Bouccara D, et al. Hypertrophic neuropathy of the facial nerve. Ann Otol Rhinol Laryngol. 2001;110:257–262. 23. Kretzer RM, Burger PC, Tamargo RJ. Hypertrophic neuropathy of the cauda equina: case report. Neurosurgery. 2004;54:515–518. discussion 518–519. 24. LaPoint SF, Powers JM, Woodruff JM, et al. Schwann cell-onion bulb tumor of the trigeminal nerve: hyperplasia, dysplasia or neoplasia? Acta Neuropathol (Berl). 2000;99:67–72. 25. Neely JG, Armstrong D, Benson J, Neblett C. ‘‘Onion bulb’’ formation associated with a solitary neoplasm of the eighth nerve sheath. Am J Otolaryngol. 1981;2:307–313. 26. Yassini PR, Sauter K, Schochet SS, Kaufman HH, Bloomfield SM. Localized hypertrophic mononeuropathy involving spinal roots and associated with sacral meningocele. Case report. J Neurosurg. 1993;79:774–778. 27. Agaimy A, Wuensch PH. Perineurioma of the stomach. A rare spindle cell neoplasm that should be distinguished from gastrointestinal stromal tumor. Pathol Res Pract. 2005;201:463–467. 28. Aoki T, Hisaoka M, Hashimoto H, et al. Giant degenerative perineurial cell tumor. Skeletal Radiol. 1996;25:757–761. 29. Augusto D, Aubert S, Leroy X. Pathologic quiz case: a deep-seated tumor of the shoulder. Arch Pathol Lab Med. 2003;127:e283–e284. 30. Balarezo FS, Muller RC, Weiss RG, et al. Soft tissue perineuriomas in children: report of three cases and review of the literature [corrected]. Pediatr Dev Pathol. 2003;6:137–141. 31. Baran R, Perrin C. Perineurioma: a tendon sheath fibroma-like variant in a distal subungual location. Acta Derm Venereol. 2003;83:60–61. 32. Barrett AW, Hopper C, Landon G. Intra-osseous soft tissue perineurioma of the inferior alveolar nerve. Oral Oncol. 2002;38:793–796. 33. Beckwith LG, Devaney K, Kragel PJ. Perineurioma. South Med J. 1995;88: 964–968. 34. Begin LR. Perineurioma of the finger: case report of a rare peripheral nerve sheath neoplasm of pure perineurial cell lineage. J Hand Surg [Am]. 1998;23: 342–347. 35. Burgues O, Monteagudo C, Noguera R, et al. Cutaneous sclerosing Pacinian-like perineurioma. Histopathology. 2001;39:498–502. 36. Canales-Ibarra C, Magarinos G, Olsoff-Pagovich P, Ortiz-Hidalgo C. Cutaneous sclerosing perineurioma of the digits: an uncommon soft-tissue neoplasm. Report of two cases with immunohistochemical analysis. J Cutan Pathol. 2003;30:577–581. 37. D’Antonio A, Marra L, Franco R, Ninfo V. A 52-year-old man with a mass in the perineal region. Perineurioma. Arch Pathol Lab Med. 2006;130:e87–e89. 38. Donnellan R. Test and teach. Number eighty five. Extraneural perineurioma. Pathology. 1997;29:277–316. 39. Donnellan R, Rughubar K, Govender D, Chetty R. Perineurioma: an unusual cause of an external auditory canal polyp. ORL J Otorhinolaryngol Relat Spec. 1997;59:336–338. 40. Fagerli JC, Hasegawa SL, Schneck FX. Paratesticular perineurioma: initial description. J Urol. 1999;162:881–882. 41. Gamblin TC, McKinney WB, Stephens RE Jr., Barron T. Perineuroma of the scrotum. Urology. 2002;60:515. 42. Giannini C, Scheithauer BW, Steinberg J, Cosgrove TJ. Intraventricular perineurioma: case report. Neurosurgery. 1998;43:1478–1481; discussion 1481– 1482. 43. Graadt van Roggen JF, McMenamin ME, Belchis DA, et al. Reticular per-

Intraneural Perineurioma—Boyanton et al

ineurioma: a distinctive variant of soft tissue perineurioma. Am J Surg Pathol. 2001;25:485–493. 44. Gullotta F. Localized hypertrophic neuropathy: a perineurialoma? Clin Neuropathol. 1985;4:92. 45. Halkic N, Ksontini R. Case in point. Perineuroma. Hosp Pract (Minneap). 2001;36:48. 46. Hornick JL, Fletcher CD. Intestinal perineuriomas: clinicopathologic definition of a new anatomic subset in a series of 10 cases. Am J Surg Pathol. 2005; 29:859–865. 47. Hornick JL, Fletcher CD. Soft tissue perineurioma: clinicopathologic analysis of 81 cases including those with atypical histologic features. Am J Surg Pathol. 2005;29:845–858. 48. Housini I, Dabbs DJ. Fine needle aspiration cytology of perineurioma: report of a case with histologic, immunohistochemical and ultrastructural studies. Acta Cytol. 1990;34:420–424. 49. Huang HY, Sung MT. Sclerosing perineuriomas affecting bilateral hands. Br J Dermatol. 2002;146:129–133. 50. Meer S, Coleman H, Altini M. Intraoral perineurioma: report of a case with a review of the literature. Oral Dis. 2003;9:99–103. 51. Mirchandani N, Dill SW, Lapidus C, Schappell D, Robinson-Bostom L. A painless palmar nodule. Pediatr Dermatol. 2004;21:606–607. 52. Rank JP, Rostad SW. Perineurioma with ossification: a case report with immunohistochemical and ultrastructural studies. Arch Pathol Lab Med. 1998; 122:366–370. 53. Robson AM, Calonje E. Cutaneous perineurioma: a poorly recognized tumour often misdiagnosed as epithelioid histiocytoma. Histopathology. 2000;37: 332–339. 54. Saft C, Andrich JE, Neuen-Jacob E, et al. Supracubital perineurioma misdiagnosed as carpal tunnel syndrome: case report. BMC Neurol. 2004;4:19. 55. Senghore N, Cunliffe D, Watt-Smith S, Hollowood K. Extraneural perineurioma of the face: an unusual cutaneous presentation of an uncommon tumour. Br J Oral Maxillofac Surg. 2001;39:315–319. 56. Shelekhova K, Kazakov DV, Michal M. Infiltrating retiform perineurioma: a case report. Ann Diagn Pathol. 2005;9:293–294. 57. Skelton HG, Williams J, Smith KJ. The clinical and histologic spectrum of cutaneous fibrous perineuriomas. Am J Dermatopathol. 2001;23:190–196. 58. Thomas C, Yousefi M, Pride H, Maroon M, Tyler W. Soft tissue perineurioma of the finger: expanding the differential diagnosis of a soft tissue tumor presenting on a digit. Cutis. 2005;75:233–237. 59. Tsang WY, Chan JK, Chow LT, Tse CC. Perineurioma: an uncommon soft tissue neoplasm distinct from localized hypertrophic neuropathy and neurofibroma. Am J Surg Pathol. 1992;16:756–763. 60. Yamaguchi U, Hasegawa T, Hirose T, et al. Sclerosing perineurioma: a clinicopathological study of five cases and diagnostic utility of immunohistochemical staining for GLUT1. Virchows Arch. 2003;443:159–163. 61. Zamecnik M. Perineurioma with adipocytes (lipomatous perineurioma). Am J Dermatopathol. 2003;25:171–173; author reply 173–174. 62. Zamecnik M, Gomolcak P. A case of perineurioma. Gen Diagn Pathol. 1997;143:261. 63. Zamecnik M, Koys F, Gomolcak P. Atypical cellular perineurioma. Histopathology. 2002;40:296–299. 64. Hayman M, Roland EH, Hill A. Newborn radial nerve palsy: report of four cases and review of published reports. Pediatr Neurol. 1999;21:648–651. 65. Weig SG, Waite RJ, McAvoy K. MRI in unexplained mononeuropathy. Pediatr Neurol. 2000;22:314–317. 66. Sciacco M, Scarpini E, Baron PL, et al. Sural nerve immunoreactivity for nerve growth factor receptor in a case of localized hypertrophic neuropathy. Acta Neuropathol (Berl). 1992;83:547–553. 67. Gruen JP, Mitchell W, Kline DG. Resection and graft repair for localized hypertrophic neuropathy. Neurosurgery. 1998;43:78–83. 68. Bilbao JM, Khoury NJ, Hudson AR, Briggs SJ. Perineurioma (localized hypertrophic neuropathy). Arch Pathol Lab Med. 1984;108:557–560. 69. Alfonso DT, Sotrel A, Grossman JA. Carpal tunnel syndrome due to an intraneural perineurioma in a 2-year-old child. J Hand Surg [Br]. 2001;26:168– 170. 70. Almefty R, Webber BL, Arnautovic KI. Intraneural perineurioma of the third cranial nerve: occurrence and identification: case report. J Neurosurg. 2006;104: 824–827. 71. Beekman R, Slooff WB, Van Oosterhout MF, Lammens M, Van Den Berg LH. Bilateral intraneural perineurioma presenting as ulnar neuropathy at the elbow. Muscle Nerve. 2004;30:239–243. 72. Brock JE, Perez-Atayde AR, Kozakewich HP, et al. Cytogenetic aberrations in perineurioma: variation with subtype. Am J Surg Pathol. 2005;29:1164–1169. 73. Chen L, Li Y, Lin JH. Intraneural perineurioma in a child with BeckwithWiedemann syndrome. J Pediatr Surg. 2005;40:E12–E14. 74. Cortes W, Cheng J, Matloub HS. Intraneural perineurioma of the radial nerve in a child. J Hand Surg [Am]. 2005;30:820–825. 75. da Cruz Perez DE, Amanajas de Aguiar FC Jr, Leon JE, et al. Intraneural perineurioma of the tongue: a case report. J Oral Maxillofac Surg. 2006;64:1140– 1142. 76. Damm DD, White DK, Merrell JD. Intraneural perineurioma—not restricted to major nerves. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003; 96:192–196. 77. de La Jarte-Thirouard AS, Jacquier I, de Saint-Maur PP. Intraneural reticular perineurioma of the neck. Ann Diagn Pathol. 2003;7:120–123.

Arch Pathol Lab Med—Vol 131, September 2007

78. Dundr P, Povysil C, Tvrdik D, Mazanek J. Intraneural perineurioma of the oral mucosa [published online ahead of print June 3, 2006]. Br J Oral Maxillofac Surg. 79. Emory TS, Scheithauer BW, Hirose T, et al. Intraneural perineurioma: a clonal neoplasm associated with abnormalities of chromosome 22. Am J Clin Pathol. 1995;103:696–704. 80. Hamazaki S, Fujiwara K, Okada S. Intraneural perineurioma involving the ulnar nerve. Pathol Int. 2004;54:371–375. 81. Heilbrun ME, Tsuruda JS, Townsend JJ, Heilbrun MP. Intraneural perineurioma of the common peroneal nerve: case report and review of the literature. J Neurosurg. 2001;94:811–815. 82. Huguet P, de la Torre J, Pallares J, et al. Intraosseous intraneural perineurioma: report of a case with morphological, immunohistochemical and FISH study. Med Oral. 2004;9:64–68. 83. Isaac S, Athanasou NA, Pike M, Burge PD. Radial nerve palsy owing to localized hypertrophic neuropathy (intraneural perineurioma) in early childhood. J Child Neurol. 2004;19:71–75. 84. Jazayeri MA, Robinson JH, Legolvan DP. Intraneural perineurioma involving the median nerve. Plast Reconstr Surg. 2000;105:2089–2091. 85. Li D, Schauble B, Moll C, Fisch U. Intratemporal facial nerve perineurioma. Laryngoscope. 1996;106:328–333. 86. Mitsumoto H, Estes ML, Wilbourn AJ, Culver JE Jr. Perineurial cell hypertrophic mononeuropathy manifesting as carpal tunnel syndrome. Muscle Nerve. 1992;15:1364–1368. 87. Mitsumoto H, Wilbourn AJ, Goren H. Perineurioma as the cause of localized hypertrophic neuropathy. Muscle Nerve. 1980;3:403–412. 88. Rankine AJ, Filion PR, Platten MA, Spagnolo DV. Perineurioma: a clinicopathological study of eight cases. Pathology. 2004;36:309–315. 89. Simmons Z, Mahadeen ZI, Kothari MJ, et al. Localized hypertrophic neuropathy: magnetic resonance imaging findings and long-term follow-up. Muscle Nerve. 1999;22:28–36. 90. Stanton C, Perentes E, Phillips L, VandenBerg SR. The immunohistochemical demonstration of early perineurial change in the development of localized hypertrophic neuropathy. Hum Pathol. 1988;19:1455–1457. 91. Suarez GA, Giannini C, Smith BE, et al. Localized hypertrophic neuropathy. Mayo Clin Proc. 1994;69:747–748. 92. Takao M, Fukuuchi Y, Koto A, et al. Localized hypertrophic mononeuropathy involving the femoral nerve. Neurology. 1999;52:389–392. 93. Shantha TR, Bourne GH. The perineurial epithelium—a new concept. In: Bourne GH, ed. The Structure and Function of the Nervous Tissue. New York, NY: Academic Press; 1968:379–459. 94. Midroni G, Bilbao JM. Normal anatomy of peripheral (sural) nerve. In: Biopsy Diagnosis of Peripheral Neuropathy. Boston, Mass: Butterworth-Heinemann; 1995:13–33. 95. Perentes E, Nakagawa Y, Ross GW, Stanton C, Rubinstein LJ. Expression of epithelial membrane antigen in perineurial cells and their derivatives: an immunohistochemical study with multiple markers. Acta Neuropathol (Berl). 1987; 75:160–165. 96. Theaker JM, Gatter KC, Puddle J. Epithelial membrane antigen expression by the perineurium of peripheral nerve and in peripheral nerve tumours. Histopathology. 1988;13:171–179. 97. Michal M. Extraneural retiform perineuriomas: a report of four cases. Pathol Res Pract. 1999;195:759–763. 98. Fetsch JF, Miettinen M. Sclerosing perineurioma: a clinicopathologic study of 19 cases of a distinctive soft tissue lesion with a predilection for the fingers and palms of young adults. Am J Surg Pathol. 1997;21:1433–1442. 99. Rey JA, Bello MJ, de Campos JM, et al. Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches. Cancer Genet Cytogenet. 1993;66:1–10. 100. Giannini C, Scheithauer BW, Jenkins RB, et al. Soft-tissue perineurioma: evidence for an abnormality of chromosome 22, criteria for diagnosis, and review of the literature. Am J Surg Pathol. 1997;21:164–173. 101. Lasota J, Fetsch JF, Wozniak A, et al. The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases. Am J Pathol. 2001;158:1223–1229. 102. Sciot R, Cin PD, Hagemeijer A, et al. Cutaneous sclerosing perineurioma with cryptic NF2 gene deletion. Am J Surg Pathol. 1999;23:849–853. 103. Kazakov DV, Pitha J, Sima R, et al. Hybrid peripheral nerve sheath tumors: Schwannoma-perineurioma and neurofibroma-perineurioma: a report of three cases in extradigital locations. Ann Diagn Pathol. 2005;9:16–23. 104. Campbell LK, Thomas JR, Lamps LW, Smoller BR, Folpe AL. Protein gene product 9.5 (PGP 9.5) is not a specific marker of neural and nerve sheath tumors: an immunohistochemical study of 95 mesenchymal neoplasms. Mod Pathol. 2003;16:963–969. 105. Folpe AL, Billings SD, McKenney JK, et al. Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. Am J Surg Pathol. 2002;26:1620–1626. 106. Hirose T, Tani T, Shimada T, et al. Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors. Mod Pathol. 2003;16:293–298. 107. Mentzel T, Kutzner H. Reticular and plexiform perineurioma: clinicopathological and immunohistochemical analysis of two cases and review of perineurial neoplasms of skin and soft tissues. Virchows Arch. 2005;447:677–682. 108. Alvarado-Cabrero I, Folpe AL, Srigley JR, et al. Intrarenal schwannoma:

Intraneural Perineurioma—Boyanton et al 1391

a report of four cases including three cellular variants. Mod Pathol. 2000;13:851– 856. 109. Boyle JL, Haupt HM, Stern JB, Multhaupt HA. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors. Arch Pathol Lab Med. 2002;126:816–822. 110. Goldblum JR, Beals TF, Weiss SW. Neuroblastoma-like neurilemoma. Am J Surg Pathol. 1994;18:266–273. 111. Lau SK, Spagnolo DV, Weiss LM. Schwannoma of the adrenal gland: report of two cases. Am J Surg Pathol. 2006;30:630–634. 112. Prevot S, Bienvenu L, Vaillant JC, de Saint-Maur PP. Benign schwannoma of the digestive tract: a clinicopathologic and immunohistochemical study of five cases, including a case of esophageal tumor. Am J Surg Pathol. 1999;23:431– 436. 113. Guarino M. Plexiform schwannoma: immunohistochemistry of Schwann cell markers, intermediate filaments and extracellular matrix components. Pathol Res Pract. 1993;189:913–920. 114. Johnson MD, Glick AD, Davis BW. Immunohistochemical evaluation of Leu-7, myelin basic-protein, S100-protein, glial-fibrillary acidic-protein, and LN3 immunoreactivity in nerve sheath tumors and sarcomas. Arch Pathol Lab Med. 1988;112:155–160. 115. Lopez JI, Ballestin C. Intraoral schwannoma: a clinicopathologic and immunohistochemical study of nine cases. Arch Anat Cytol Pathol. 1993;41:18–23. 116. Michal M, Fanburg-Smith JC, Mentzel T, et al. Dendritic cell neurofibro-

1392 Arch Pathol Lab Med—Vol 131, September 2007

ma with pseudorosettes: a report of 18 cases of a distinct and hitherto unrecognized neurofibroma variant. Am J Surg Pathol. 2001;25:587–594. 117. Ewy MF, Demmy TL, Perry MC, Krishnan MS, Curtis JJ. Massive phrenic perineurioma mimicking an unresectable cardiac tumor. Ann Thorac Surg. 1995; 60:188–189. 118. Karaki S, Mochida J, Lee YH, Nishimura K, Tsutsumi Y. Low-grade malignant perineurioma of the paravertebral column, transforming into a high-grade malignancy. Pathol Int. 1999;49:820–825. 119. Hirose T, Sano T, Hizawa K. Heterogeneity of malignant schwannomas. Ultrastruct Pathol. 1988;12:107–116. 120. Hirose T, Maeda T, Furuya K, Kiyasu Y, Kawasaki H. Malignant peripheral nerve sheath tumor of the pancreas with perineurial cell differentiation. Ultrastruct Pathol. 1998;22:227–231. 121. Hirose T, Scheithauer BW, Sano T. Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases. Am J Surg Pathol. 1998;22:1368–1378. 122. Hirose T, Sumitomo M, Kudo E, et al. Malignant peripheral nerve sheath tumor (MPNST) showing perineurial cell differentiation. Am J Surg Pathol. 1989; 13:613–620. 123. Rosenberg AS, Langee CL, Stevens GL, Morgan MB. Malignant peripheral nerve sheath tumor with perineurial differentiation: ‘‘malignant perineurioma.’’ J Cutan Pathol. 2002;29:362–367. 124. Zamecnik M, Michal M. Malignant peripheral nerve sheath tumor with perineurial cell differentiation (malignant perineurioma). Pathol Int. 1999;49:69– 73.

Intraneural Perineurioma—Boyanton et al

Lihat lebih banyak...


Copyright © 2017 DADOSPDF Inc.