A benign neoplasm with histopathological features of both schwannoma and retiform perineurioma (benign schwannoma-perineurioma): a report of six cases of a distinctive soft tissue tumor with a predilection for the fingers
- First Online:
- Cite this article as:
- Michal, M., Kazakov, D.V., Belousova, I. et al. Virchows Arch (2004) 445: 347. doi:10.1007/s00428-004-1102-5
- 157 Views
We present six cases of a distinctive soft tissue tumor which occurred in five women and one man. None of the patients had signs of neurofibromatosis. All tumors occurred on the fingers (n=5) or the thenar eminence of the hand (n=1). The mean age of the patients was 33 years. The tumors were 1–2.5 cm in diameter (mean size 1.6 cm). Three patients with follow-up were without signs of recurrence or metastasis. Microscopically the lesions were nonencapsulated and featured a multilobular architecture and both myxoid and pseudocystic change. The lobules varied in size and shape and were separated by variably thickened, dense, sclerotic/collagenous septae. The lobules were composed of two components: schwannomatous and perineuriomatous. The schwannomatous component was immunohistochemically S-100 protein positive and CD34 and EMA negative, and the perineuriomatous component had the appearance of retiform perineurioma. The perineurial parts were mostly S-100 protein and CD34 negative and EMA positive. These two components either formed separate nodules or the schwannomatous tissue surrounded the perineurial parts located in the centers of the lobules. We interpreted the lesions as hybrid tumors with features of schwannoma and retiform perineurioma.
KeywordsRetiform perineuriomaReticular perineuriomaBenign schwannoma-perineuriomaNeurothekeoma
Peripheral nerve sheath tumors are traditionally divided into schwannomas, neurofibromas, and perineuriomas. Perineuriomas were described relatively recently , and with the help of immunohistochemical stains for epithelial membrane antigen (EMA) these tumors were defined in recent years [4, 7, 8, 10, 11, 19, 31, 35, 40, 41, 43]. The last distinctive type of perineurioma  was identified in small series in recent years, and it was variously named retiform  or reticular perineurioma . We are aware of only a single case of hybrid tumor containing a component of retiform perineurioma and a schwannian component in the literature . Here we report a small series of six neoplasms with retiform perineurioma/schwannoma features. Our report demonstrates that these hybrid tumors are distinctive lesions.
Materials and methods
Main clinical data (NED no evidence of disease)
Thumb, left hand
4 years NED
2nd finger, left hand
5th finger, left hand
2nd finger, left hand
1 year NED
7 years NED
Antibodies used for immunohistochemical study (EMA epithelial membrane antigen, ASMA α-smooth muscle actin, MSA muscle-specific actin, NFP neurofilament protein)
For electron microscopic investigations wet formol-fixed tissue was available in one case. It was postfixed in 4% paraformaldehyde, contrasted in 1% osmium tetroxide, and embedded in epoxy resin (Durcupan-Epon). Sections were cut 1 µm thick, stained with toluidine blue, and examined by light microscopy. Appropriate areas were selected, and thin sections were cut and stained with uranyl acetate and lead citrate, and examined with a Philips (Eindhoven, Holland) EM 208S electron microscope.
The lesions ranged in size from 1.0 to 2.5 cm (mean 1.6). In five patients the neoplasm was located on a finger. The thenar eminence was involved in one patient. Duration was indicated in one case (no. 6); the lesion was present for 15 years before the patient sought medical advice. All lesions were surgically excised. Three patients had a disease free follow-up 1, 4, and 7 years postoperatively. Two patients underwent the excision recently, and in one patient the follow-up was unknown.
The connective tissue sheath of a peripheral nerve is composed of Schwann cells, perineurial cells, and fibroblasts. Tumors arising from a peripheral nerve sheath can contain these cells in various proportions, as found in many ultrastructural studies [9, 15, 18, 25, 32, 36, 37]. Moreover, some authors [9, 15] have also observed additional cells that had ultrastructural features interpretable as transitional stages among the three main cell types. Erlandson  has described the following cells in neurofibromas: (a) Schwann cells, (b) perineurial cells, (c) cells having features of Schwann cell and fibroblast, (d) fibroblasts, and (e) transitional Schwann-perineurial cells. Although ultrastructural studies of neurofibromas clearly showed that the perineurial cells are part of a cell population in neurofibromas, immunohistochemical studies using EMA as a marker for perineurial cell differentiation failed to demonstrate convincingly this differentiation [1, 18, 33]. EMA+ cells were rarely found only in peripheral areas of some neurofibromas [1, 29, 34], and these were interpreted as remnants of the nerve sheath of the affected nerve.
The presence of perineurial cells was later confirmed by Zamecnik and Michal , who described them as a prominent histological feature in 8% of neurofibromas. The perineurial cells were most often present in pericapsular and perivascular areas. These perineurial cells in pericapsular and perivascular areas are most probably preexisting perineurial cells of the peripheral nerves from which the neurofibromas arose and are not, in contrast to the tumors that we describe, an integral part of the tumors. In addition, the authors presented an interesting tumor which had features of both neurofibroma and retiform perineurioma. This was the first published neoplasm having both perineuriomatous and peripheral nerve sheath differentiation. We again reviewed this case, which is included in our present series, and together with other five similar to identical cases they have now been studied immunohistochemically for the presence of neurofilaments and CD34, which label axons and fibroblasts in neurofibromas respectively [21, 24, 38]. The nonperineuriomatous parts of the tumor were immunohistochemically negative for the antibody to neurofilament proteins and histochemically negative with the Bodian method, findings which confirm that the lesions are devoid of axons. In addition, these parts of the tumors showed an absence of CD34 positive cells. Based upon these findings we think that these nonperineuriomatous parts of the lesions should be interpreted as schwannomatous rather than neurofibromatous component. Interestingly, only the S-100 protein positive schwannomatous parts but not EMA positive perineuriomatous parts of the tumors had sometimes heavy depositions of hemosiderin. The lobular architecture, frequent pseudocystic arrangement of the lobules, myxoid nature of the lesions, the retiform arrangement of the perineuriomatous parts of the lesions, which is identical to the retiform (reticular) perineurioma [28, 30] and predominant occurrence in the fingers highlight the uniqueness of the tumors in this report. We have seen examples of schwannoma-perineurioma hybrid tumors outside the soft tissues of the fingers. These tumors look different from our cases. They can be considerably larger, usually lack the pseudocystic lobular arrangement, the perineuriomatous and schwannomatous components are much more intermingled, and the retiform arrangement of the perineurial component is much less expressed [28, 30].
We reviewed the literature for similar lesions published in the past. Judging purely from a morphological point of view, several reports may have described identical neoplasms under the names of dermal nerve sheath myxoma, cutaneous lobular neuromyxoma, bizarre cutaneous neurofibromas, Pacinian neurofibroma, and neurothekeoma [1, 5, 13, 16, 17, 22, 27]. These lesions had a similar lobular architecture and myxoid areas resembling retiform perineuriomas. In particular, the lesion pictured in Fig. 1 in the report of Argenyi et al.  on nerve sheath myxomas seems to show similarities to our cases. Their detailed Fig. 1B is highly suggestive of a retiform perineurioma arrangement. In addition, at least two of the cases in their report revealed both S-100 protein and EMA positivity. The rest of the reports that we reviewed, however, were published either before the era of immunohistochemistry or presented no information on EMA and/or S-100 protein staining. It is therefore impossible to judge these reports critically and objectively and compare them with our cases.
Owing to distinct histopathological features the differential diagnosis of this neoplasm should pose no problem provided a pathologist is familiar with the appearance of retiform perineurioma, a relatively rare neoplasm and that of schwannoma. However, retiform perineurioma is rare and less known lesion, and therefore we ourselves started to recognize these hybrid tumors only after having seen quite a number of retiform perineuriomas. When a myxoid change is prominent, this hybrid tumor may resemble nerve sheath myxoma (neurothekeoma) . The combination of schwannomatous tissue and perineuriomatous tissue enables a clear distinction from any known neoplasm. In addition, staining for both EMA and S-100 protein assists in revealing the biphasic nature of the neoplasm. We have also recently seen an example of benign schwannoma in which peculiar multifocal myxoid degeneration resulted in an appearance simulating a retiform perineurioma. Microscopically this neoplasm was probably the closest mimic of the reported tumor we ever saw; however, immunohistochemistry facilitated the correct diagnosis.
Retiform perineurioma was first described by Ushigome et al.  and later defined in small series in recent years, and it was named as retiform perineurioma . We use a descriptive name for the reported tumor: a neoplasm with histopathological features of both schwannoma and retiform perineurioma. Because the term “retiform” has been used in some tumors to connote the resemblance of rete testis other term, namely “reticular” was suggested for this tumor . However, we think that there are other well established anatomical terms in which the word “rete” is used, for example, “rete carpi dorsale” , “rete mirabile” , and “rete pedis”  as well as other terms with histological connotations such as “choroid rete”  “rete ridges” in the skin , “rete ridges” in esophagus , and others . We therefore believe that there is no need to compare the term “retiform” to the rete testis. In the case of perineurioma it was devised to describe the typical netlike arrangement of the tumor .
In conclusion, we describe clinicopathological features of distinctive benign hybrid neoplasm composed of schwannoma and retiform perineurioma. In contrast with other nerve sheath tumors, the lesion shows no association with neurofibromatosis or schwannomatosis.