Benign nerve sheath myxoma: Light and electron microscopic features of two cases Thomas C. Sist, Jr., B.S., D.D.S.,* B~lffLllo, N. Y. STATE
UNIVERSITY
OF NEW
YORK
und George W. Greene, Jr., B.S., D.D.S.,**
AT BUFFALO
Two new cases of the rare benign nerve sheath myxoma (NSM) are presented. The light microscopic findings are compared with previously reported cases. In addition, the ultrastructural features of three constituent cell types are described. The lesion is confirmed as a neural sheath neoplasm, and its similarities to other myxomas are discussed.
T
he nerve
sheath
myxoma
scribed
by Harkin
arising
in the endoneurium
characterized matrix. first
tongue
by stellate
Subsequently,
intraoral two
Mincer
mucinosis.
The present
cases and includes trastructural
what
description
nerves
in an abundant and Spears’
in his
article
man. report
concerns
we believe
and
mucoid
reported
on the dorsum
Caucasian
cases
de-
neoplasm
of peripheral
case of the lesion more
was initially
as a cutaneous
cells
of a 23-year-old
scribed
(NSM)
and Reed’
the
of the
Tomich3 of two
oral
defocal
additional
to be the first
ul-
of NSM.
CASE REPORTS CASE 1 A 30-year-old Caucasian woman presented with a 0.5 cm. (diameter) mucosal elevation in the left retromolar area. According to the patient, the lesion had been present for about I year and had not increased in size during that time. Pain had been present initially, but the area had become asymptomatic. The lesion was excised in toto and submitted for microscopic examination with a clinical diagnosis of fibroma. Postoperative recovery was uneventful. and there has been no recurrence after 2 years. CASE2 A 41 -year-old Caucasian woman presented with a raised, pale lesion in the left buccal mucosa. She reported first noticing the abnormality 6 months previously and said it had been slowly enlarging but had caused no pain. Excisional biopsy was performed and the specimen was submitted for histologic *This paper was prepared while Dr. Sist was a Postdoctoral Fellow, Department of Pathology. **Professor and Chairman, Department of Oral Pathology. 0030.4220/79/050441+04$00.40/0
0
1979
The C. V. Mosby Co.
evaluation with a clinical healing was satisfactory, after 7 months.
diagnosis of fibroma. Postoperative and there has been no recurrence
MATERIALS AND METHODS Each specimen was received in IO percent neutral buffered formalin. The tissues were embedded in paraffin, sectioned, and stained with hematoxylin and eosin, alcian blue at pH 2.5, Wilder’s method for reticulum, toluidine blue, and methyl green pyronine for mast cells. Tissue for electron microscopy was retrieved from paraffin, rehydrated through a series of graded alcohols, and placed in 3 percent glutaraldehyde over night. The specimens were postfixed in I percent osmium tetroxide, dehydrated through graded ethanol, and left overnight in a I : I mixture of propylene oxide and epon-araldite. The sections were then embedded in eponaraldite. Sections of 500 “A thickness were cut with glass knives on a Porter-Blum MT-I ultramicrotome, collected on carbon-coated grids, and stained with uranyl acetate and lead citrate. The sections were then examined on a Hitachi HS-8 electron microscope at an accelerating voltage of 50 kv.
LIGHT MICROSCOPY FINDINGS The central portion of each specimen was composed of a lobulated mass which compressed the overlying epithelium and displaced the rete ridges. The lobules were of varying size and separated by connective tissue septa. A condensed fibrous connective tissue sheath resembling perineurium completely surrounded the lesion (Fig. I). Each lobule was composed of elongated and frequently stellate cells in a pale, basophilic, mutinous ground substance. The cells terminated in long fibrillar processes which intermingled with each other (Fig. 2). The reticulum stain revealed a network of fine fibers within the lobules. Occasional giant cells were noted in the lobules. Alcianophilia at pH 2.5 was marked in both lesions,
441
442
Sist und Greene
Ora1 Surp. May. IY-TY
Fig. 1. Photomicrograph ot‘ NSM shouing lobules 01 myxomatoua tissue outlined by tihroua septa. (Hematoxylin and cosin stain. Original magnification. X IO. 1
Fig. 2. Hlghcr-power \ KM ot NSM lobule. The clongatcd and often stcllate-shaped cells arc immcrscd 111 a basophilic ground substance. (Hematoxylin and cosin stain. Original magnitication. ‘* 160. i
Fig. 3. Electron photomicrograph of Type I cell t’rom central area 01’ NSM lobule. The cytoplasnl contams much rough endoplasmic reticulum IER). Collagen CC) is sparse. The insert demonstrates that the cell is surrounded bq basement membrane (EM). (Original magnification. *:3.5(K).) and metachromasia was noted within the lobules t’ollowm~ toluidinc blue staining. Mast ceils were prominent as well. These findings were consistent Mith a diasnoaia of ncr\c sheath myxoma. ELECTRON
MICROSCOPY
FINDINGS
Three cell types were discernible within the \~;II-w collagenous stroma. Type 1 was characterized by a i’usif’orm shape and cytoplasm densely populated by dilated rough CIV doplasmic reticulum. Free rihosomes and numerous tine tilamerits were also dispersed throughout the cytoplasm. The nucleus was frequently lohulated. Pvknotic vesicles wet-e oc casionally observed at or near the plasma memhranc. Buemerit membrane material was present but incomplete (Fig. 3)
The second ceil type closely resembled Type I but had no basement membrane. The Type 3 cell was found at the pcrlphet? of the lesions. Its cytoplasm contained numerous iinc lilaments. s~mc mitochondria. and onI> ;I moderate amount 01 granular cndoplasmic reticulum. The nuclelts was lobulatcd and contained much cuchromatin. Basement membrane completely surrounded thih cell type and was frequently arranged in multiple layers. .Axons were associated with some id the Type 7 ccl15 t Fis. 4),
DiSCUSSiON ‘Three
cases
01’ NSM
of the oral
reported in the English literature.“. riLcs the clinical data on these as well
cavity
have
been
‘j Table I summaas our two cases.
Benign
Volume 47 Number 5
nrrve
sheath
mpoma
443
Fig. 4. Electron photomicrograph of Type 3 cells from edge of NSM lobule. Basement membrane (BM) is seen arranged in multiple layers surrounding these cells. Axons (Ax) with their distinctive vesicles (I/) are associated with the Type 3 cells. (Original magnification, x6.000.)
Table I. Summary of reported oral NSM cases Patient age (years)
Patient sex
23
Case No.
Author(s)
1 2 3 4
Mincer and Spears’ Tomich3 Tomich3 Present authors
45 30
5
Presentauthors
41
Locafion of lesion
Duration
M
Dorsum of tongue
Several months
F
Buccal mucosa
M F F
Tip of tongue Retromolar area
1 Ye= 2 months 1 year
Buccal mucosa
6 months
Few conclusions are possible from such a small series. However, the innocuous clinical appearance and apparent surgical cure of the few reported cases certainly support the benign nature of the lesion suggested by its microscopic features. Furthermore, the reported locations within the oral cavity raise the possibility that trauma may play a role in the etiology of NSM. The neuroectodermal nature of this lesion was confirmed in our study by electron microscopy. The Type 1 cell matches the ultrastructural description given by other investigators for the perineural cell of the epineurium, and the Type 3 cell corresponds to that given for the Schwann cell.“-x These two cells are characterized by the presence of basement membrane and may, in fact, be functional variants of the same sheath cell.” The Type 2 cell resembled the perineurial cell, but the conspicuous lack of basement membrane qualified it as an endoneurial fibroblast.” The question remains whether the NSM is a true myxoma or a degenerative process within a pre-existing nerve sheath neoplasm.‘* 3 Stout’s” criteria for myxoma are the presence of stellate cells in a loose mucoid stroma with fine reticulin fibers and a ground substance containing hyaluronic acid. The morphologic criteria of
Clinical diagnosis
Papilloma Mucocele
Fibroma Fibroma
Stout are met by all of the reported cases, and the presence of hyaluronic acid has been established by Tomich.:’ Our histochemical findings support the presence of hyaluronic acid, although hyaluronidase digestion was not performed. Ultrastructural descriptions of “true” myxoma are uncommon in the literature, although the evidence suggests that the principal cell of the myxoma is similar to the cells observed in NSM. 11P13The presence of abundant rough endoplasmic reticulum and Golgi complexes indicates that the cells of myxomas, including the nerve sheath variety, are in an active. synthetic phase rather than a degenerative one. Consequently, we believe that the NSM is a true myxoma of neuroectodermal sheath cell derivation. The presence of Schwann cells, perineural cells, and endoneural fibroblasts may reflect the interchangeability of the components of the nerve sheath.” REFERENCES I. Harkin. J. C., and Reed, J. J.: Tumors of the Peripheral Nervous System, 2nd series, Fast. 3, Washington, 1969. Armed Forces Institute of Pathology, pp. 60-64. 2. Mincer, H. H., and Spears, K. D.: Nerve Sheath Myxoma in the Tongue, OKAL SURG. 37: 428-430, 1974.
444
Sist and Greene
Oral Surg. May, 1979
Tomich, C. E.: Oral Focal Mucinosis. A Clinicopathologic and Histochemical Study of Eight Cases, ORAL SURG. 38: 714-724, 1974. Thomas. P. K. : The Connective Tissue of Peripheral Nerve. An Electron Microscopy Study, J. Anat. 97: 35-44, 1963. Shanthaveerappa, T. R., and Bourne, G. H.: Perineural Epithehum: A New Concept of Its Role in the Integrity of the Peripheral Nervous System, Science 154: 1464- 1467, 1966. Waggener, J. D., Bunn, S. M., and Beggs, J.: The Diffusion ot Ferritin Within the Peripheral Nerve Sheath: An Electron Micro(topic Study. J. Neuropathol. Exp. Neurol. 24: 430-443, 1965. Craviotto. H.: The Perineurium as a Diffusion BarrierUltrastructural Correlates, Bull. Los Angeles Neurol. Sot. 31: 196-208. 1966. Gamble. H. J.: Comparative Electron-Microscopic Observatwn\ on the Connective Tissues of a Peripheral Nerve and a Spinal Nerve Root in the Rat, J. Anat. 98: 17-25, 1964. ConleT. F. K., Rubinstein, L. J., and Spence, A. M.: Studie\ on ExperImental Malignant Nerve Sheath Tumors Maintained in Tissue and Organ Culture SystemsII. Electron Microscopic Obgervations, Acta Neuropathol. 34: 293-3 IO, 1976.
COPYRIGHT
IO.
Stout, A P.: Myxoma. the Tumor ot Primm\c Mesenchymc. Ann. Surg. 127: 706-713, 1948. I I. Merkou. L. F., Kooros. M. A., Magwet-n, G., Hayeslip. I). Weikers. N. J.. Pardo, M.. and Fisher, D : Ultrastructure of a Cardiac Myxoma. ,4rch. Pathol. 88: 390.399. 1969. II. Leak, L. V.. Caufield. J. B.. Burke, J. F.. and McKhann. C. IElectron Microscopic Studies on a Human Fibromyxoharcome. Cancer Rer. 27: X-28.5. 1967. 13. Simea. R, J.. Barro. R. E.. Klein-SIanto. A. J I’.. dnd Cabrim. R. L.: Ultra\tructure of an Odontogenic Mqxoma, ORAI SL RG 39: 640-616. I')75
Rqmr
rcyrr\r.\
IO
Reprint request\ Department
to: Dr Thomas of Oral Pathology
C. SI\I. JI
State Univerait) of Neu York at Buffalo School of Dentrtrb Buffalo. N Y I4jl-l
INFORMATION
The appearance of a code at the bottom of the first page of an original article in this journal indicatea the copyright owner’s consent that copies of the article may be made for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition. however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc., P.O. Box 765, Schenectady. N. Y. 1230 I, 5 i&3744430, for copying beyond that permitted by Sections 107 or I08 of the U. S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution. for advertising or promotional purposes, for creating new collective works, or for resale.
UNIVERSITY
OF NEW
YORK
und George W. Greene, Jr., B.S., D.D.S.,**
AT BUFFALO
Two new cases of the rare benign nerve sheath myxoma (NSM) are presented. The light microscopic findings are compared with previously reported cases. In addition, the ultrastructural features of three constituent cell types are described. The lesion is confirmed as a neural sheath neoplasm, and its similarities to other myxomas are discussed.
T
he nerve
sheath
myxoma
scribed
by Harkin
arising
in the endoneurium
characterized matrix. first
tongue
by stellate
Subsequently,
intraoral two
Mincer
mucinosis.
The present
cases and includes trastructural
what
description
nerves
in an abundant and Spears’
in his
article
man. report
concerns
we believe
and
mucoid
reported
on the dorsum
Caucasian
cases
de-
neoplasm
of peripheral
case of the lesion more
was initially
as a cutaneous
cells
of a 23-year-old
scribed
(NSM)
and Reed’
the
of the
Tomich3 of two
oral
defocal
additional
to be the first
ul-
of NSM.
CASE REPORTS CASE 1 A 30-year-old Caucasian woman presented with a 0.5 cm. (diameter) mucosal elevation in the left retromolar area. According to the patient, the lesion had been present for about I year and had not increased in size during that time. Pain had been present initially, but the area had become asymptomatic. The lesion was excised in toto and submitted for microscopic examination with a clinical diagnosis of fibroma. Postoperative recovery was uneventful. and there has been no recurrence after 2 years. CASE2 A 41 -year-old Caucasian woman presented with a raised, pale lesion in the left buccal mucosa. She reported first noticing the abnormality 6 months previously and said it had been slowly enlarging but had caused no pain. Excisional biopsy was performed and the specimen was submitted for histologic *This paper was prepared while Dr. Sist was a Postdoctoral Fellow, Department of Pathology. **Professor and Chairman, Department of Oral Pathology. 0030.4220/79/050441+04$00.40/0
0
1979
The C. V. Mosby Co.
evaluation with a clinical healing was satisfactory, after 7 months.
diagnosis of fibroma. Postoperative and there has been no recurrence
MATERIALS AND METHODS Each specimen was received in IO percent neutral buffered formalin. The tissues were embedded in paraffin, sectioned, and stained with hematoxylin and eosin, alcian blue at pH 2.5, Wilder’s method for reticulum, toluidine blue, and methyl green pyronine for mast cells. Tissue for electron microscopy was retrieved from paraffin, rehydrated through a series of graded alcohols, and placed in 3 percent glutaraldehyde over night. The specimens were postfixed in I percent osmium tetroxide, dehydrated through graded ethanol, and left overnight in a I : I mixture of propylene oxide and epon-araldite. The sections were then embedded in eponaraldite. Sections of 500 “A thickness were cut with glass knives on a Porter-Blum MT-I ultramicrotome, collected on carbon-coated grids, and stained with uranyl acetate and lead citrate. The sections were then examined on a Hitachi HS-8 electron microscope at an accelerating voltage of 50 kv.
LIGHT MICROSCOPY FINDINGS The central portion of each specimen was composed of a lobulated mass which compressed the overlying epithelium and displaced the rete ridges. The lobules were of varying size and separated by connective tissue septa. A condensed fibrous connective tissue sheath resembling perineurium completely surrounded the lesion (Fig. I). Each lobule was composed of elongated and frequently stellate cells in a pale, basophilic, mutinous ground substance. The cells terminated in long fibrillar processes which intermingled with each other (Fig. 2). The reticulum stain revealed a network of fine fibers within the lobules. Occasional giant cells were noted in the lobules. Alcianophilia at pH 2.5 was marked in both lesions,
441
442
Sist und Greene
Ora1 Surp. May. IY-TY
Fig. 1. Photomicrograph ot‘ NSM shouing lobules 01 myxomatoua tissue outlined by tihroua septa. (Hematoxylin and cosin stain. Original magnification. X IO. 1
Fig. 2. Hlghcr-power \ KM ot NSM lobule. The clongatcd and often stcllate-shaped cells arc immcrscd 111 a basophilic ground substance. (Hematoxylin and cosin stain. Original magnitication. ‘* 160. i
Fig. 3. Electron photomicrograph of Type I cell t’rom central area 01’ NSM lobule. The cytoplasnl contams much rough endoplasmic reticulum IER). Collagen CC) is sparse. The insert demonstrates that the cell is surrounded bq basement membrane (EM). (Original magnification. *:3.5(K).) and metachromasia was noted within the lobules t’ollowm~ toluidinc blue staining. Mast ceils were prominent as well. These findings were consistent Mith a diasnoaia of ncr\c sheath myxoma. ELECTRON
MICROSCOPY
FINDINGS
Three cell types were discernible within the \~;II-w collagenous stroma. Type 1 was characterized by a i’usif’orm shape and cytoplasm densely populated by dilated rough CIV doplasmic reticulum. Free rihosomes and numerous tine tilamerits were also dispersed throughout the cytoplasm. The nucleus was frequently lohulated. Pvknotic vesicles wet-e oc casionally observed at or near the plasma memhranc. Buemerit membrane material was present but incomplete (Fig. 3)
The second ceil type closely resembled Type I but had no basement membrane. The Type 3 cell was found at the pcrlphet? of the lesions. Its cytoplasm contained numerous iinc lilaments. s~mc mitochondria. and onI> ;I moderate amount 01 granular cndoplasmic reticulum. The nuclelts was lobulatcd and contained much cuchromatin. Basement membrane completely surrounded thih cell type and was frequently arranged in multiple layers. .Axons were associated with some id the Type 7 ccl15 t Fis. 4),
DiSCUSSiON ‘Three
cases
01’ NSM
of the oral
reported in the English literature.“. riLcs the clinical data on these as well
cavity
have
been
‘j Table I summaas our two cases.
Benign
Volume 47 Number 5
nrrve
sheath
mpoma
443
Fig. 4. Electron photomicrograph of Type 3 cells from edge of NSM lobule. Basement membrane (BM) is seen arranged in multiple layers surrounding these cells. Axons (Ax) with their distinctive vesicles (I/) are associated with the Type 3 cells. (Original magnification, x6.000.)
Table I. Summary of reported oral NSM cases Patient age (years)
Patient sex
23
Case No.
Author(s)
1 2 3 4
Mincer and Spears’ Tomich3 Tomich3 Present authors
45 30
5
Presentauthors
41
Locafion of lesion
Duration
M
Dorsum of tongue
Several months
F
Buccal mucosa
M F F
Tip of tongue Retromolar area
1 Ye= 2 months 1 year
Buccal mucosa
6 months
Few conclusions are possible from such a small series. However, the innocuous clinical appearance and apparent surgical cure of the few reported cases certainly support the benign nature of the lesion suggested by its microscopic features. Furthermore, the reported locations within the oral cavity raise the possibility that trauma may play a role in the etiology of NSM. The neuroectodermal nature of this lesion was confirmed in our study by electron microscopy. The Type 1 cell matches the ultrastructural description given by other investigators for the perineural cell of the epineurium, and the Type 3 cell corresponds to that given for the Schwann cell.“-x These two cells are characterized by the presence of basement membrane and may, in fact, be functional variants of the same sheath cell.” The Type 2 cell resembled the perineurial cell, but the conspicuous lack of basement membrane qualified it as an endoneurial fibroblast.” The question remains whether the NSM is a true myxoma or a degenerative process within a pre-existing nerve sheath neoplasm.‘* 3 Stout’s” criteria for myxoma are the presence of stellate cells in a loose mucoid stroma with fine reticulin fibers and a ground substance containing hyaluronic acid. The morphologic criteria of
Clinical diagnosis
Papilloma Mucocele
Fibroma Fibroma
Stout are met by all of the reported cases, and the presence of hyaluronic acid has been established by Tomich.:’ Our histochemical findings support the presence of hyaluronic acid, although hyaluronidase digestion was not performed. Ultrastructural descriptions of “true” myxoma are uncommon in the literature, although the evidence suggests that the principal cell of the myxoma is similar to the cells observed in NSM. 11P13The presence of abundant rough endoplasmic reticulum and Golgi complexes indicates that the cells of myxomas, including the nerve sheath variety, are in an active. synthetic phase rather than a degenerative one. Consequently, we believe that the NSM is a true myxoma of neuroectodermal sheath cell derivation. The presence of Schwann cells, perineural cells, and endoneural fibroblasts may reflect the interchangeability of the components of the nerve sheath.” REFERENCES I. Harkin. J. C., and Reed, J. J.: Tumors of the Peripheral Nervous System, 2nd series, Fast. 3, Washington, 1969. Armed Forces Institute of Pathology, pp. 60-64. 2. Mincer, H. H., and Spears, K. D.: Nerve Sheath Myxoma in the Tongue, OKAL SURG. 37: 428-430, 1974.
444
Sist and Greene
Oral Surg. May, 1979
Tomich, C. E.: Oral Focal Mucinosis. A Clinicopathologic and Histochemical Study of Eight Cases, ORAL SURG. 38: 714-724, 1974. Thomas. P. K. : The Connective Tissue of Peripheral Nerve. An Electron Microscopy Study, J. Anat. 97: 35-44, 1963. Shanthaveerappa, T. R., and Bourne, G. H.: Perineural Epithehum: A New Concept of Its Role in the Integrity of the Peripheral Nervous System, Science 154: 1464- 1467, 1966. Waggener, J. D., Bunn, S. M., and Beggs, J.: The Diffusion ot Ferritin Within the Peripheral Nerve Sheath: An Electron Micro(topic Study. J. Neuropathol. Exp. Neurol. 24: 430-443, 1965. Craviotto. H.: The Perineurium as a Diffusion BarrierUltrastructural Correlates, Bull. Los Angeles Neurol. Sot. 31: 196-208. 1966. Gamble. H. J.: Comparative Electron-Microscopic Observatwn\ on the Connective Tissues of a Peripheral Nerve and a Spinal Nerve Root in the Rat, J. Anat. 98: 17-25, 1964. ConleT. F. K., Rubinstein, L. J., and Spence, A. M.: Studie\ on ExperImental Malignant Nerve Sheath Tumors Maintained in Tissue and Organ Culture SystemsII. Electron Microscopic Obgervations, Acta Neuropathol. 34: 293-3 IO, 1976.
COPYRIGHT
IO.
Stout, A P.: Myxoma. the Tumor ot Primm\c Mesenchymc. Ann. Surg. 127: 706-713, 1948. I I. Merkou. L. F., Kooros. M. A., Magwet-n, G., Hayeslip. I). Weikers. N. J.. Pardo, M.. and Fisher, D : Ultrastructure of a Cardiac Myxoma. ,4rch. Pathol. 88: 390.399. 1969. II. Leak, L. V.. Caufield. J. B.. Burke, J. F.. and McKhann. C. IElectron Microscopic Studies on a Human Fibromyxoharcome. Cancer Rer. 27: X-28.5. 1967. 13. Simea. R, J.. Barro. R. E.. Klein-SIanto. A. J I’.. dnd Cabrim. R. L.: Ultra\tructure of an Odontogenic Mqxoma, ORAI SL RG 39: 640-616. I')75
Rqmr
rcyrr\r.\
IO
Reprint request\ Department
to: Dr Thomas of Oral Pathology
C. SI\I. JI
State Univerait) of Neu York at Buffalo School of Dentrtrb Buffalo. N Y I4jl-l
INFORMATION
The appearance of a code at the bottom of the first page of an original article in this journal indicatea the copyright owner’s consent that copies of the article may be made for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition. however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc., P.O. Box 765, Schenectady. N. Y. 1230 I, 5 i&3744430, for copying beyond that permitted by Sections 107 or I08 of the U. S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution. for advertising or promotional purposes, for creating new collective works, or for resale.
