Glomus tumor: a comprehensive review of the clinical and histopathologic features with report of two intraoral cases
D1X XMolly Housley Smith,D2X XDMD,aD3X XIndraneel Bhattacharyya,D4X XDDS, MSD,bD5X XDonald M. Cohen,D6X XDMD, MBA, MS,b D7X XSteven R. Hinze,D8X XDDS,candD9X XMohammed N. Islam,D10X XDDS, BDSb
Background. Glomus tumors are benign neoplasms that most commonly present in the subungual region. Their occurrence in the oral cavity is exceedingly rare. Here, we present 2 cases from the oral cavity, detail their clinical and histopathologic features, and review the literature for solitary cases involving the oral regions.
Study Design. The English language literature was queried for cases of benign glomus tumors in/around the oral cavity. Additional citations were cross-referenced from the identified sources.
Results. Thirty-one cases of solitary glomus tumor in the oral and paraoral regions have been described, including the present cases. Patient age ranged from 10 to 85 years, with an average age of 47 years. In 12 of the 31 cases, the tumors occurred in the lips, 5 in the palate, 4 in the tongue, 4 in the buccal mucosa, 3 in the gingiva, and 1 each in the parotid, pterygoid fossa, and oro- pharynx. Only 18 of these cases had accompanying immunohistochemical stains, with 14 expressing positivity for muscle cell markers.
Conclusions. Although glomus tumors have distinct histopathologic features, diagnostic confusion may exist with regard to extra- digital locations. Detailed documentation and discussion of the clinical and histopathologic features of rare tumors like these are vital to understanding them. (Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:62 70)
Glomus tumors are uncommon, benign, mesenchy- mal neoplasms, initially described in the literature, in 1812 by Wood, as a painful tubercle about “the size and form of a flattened garden pea” and none “larger than a coffee-bean.”1Although Wood has been cred- ited with the earliest well-documented description, earlier literature suggests that these painful growths may have been known in the time of Hippocrates and Galen.2In 1924, more than 100 years after Wood’s clinical description, Masson described the histopath- ologic characteristics and origin of the glomus tumor.3
The classic presentation of a glomus tumor is a pain- ful nodule that usually occurs in the distal phalanges around the nailbed. They are thought to arise from the glomus apparatus, a specialized arteriovenous (AV) shunt first described by Grosser in 1902.4,5 This AV anastomosis is a normal structure that permits blood to pass directly from the veins to the arteries, and vice versa, and is involved in temperature regulation.6-8The glomus apparatus is typically found in the stratum reticularis of the skin, most notably in the subungual or digital pad location, but also in lesser known locations,
such as the ear pinna, the tip of the nose, sacrococcy- geal region (arising from the glomus coccygeum), nasal cavity, and trachea.6,7,9-11Glomera are made up of complex vascular channels called Sucquet-Hoyer canals and are surrounded by modified smooth muscle cells termed glomus cells.6Although structures analo- gous to the glomus apparatus have been described in the periodontal and temporomandibular regions (the so-called genu vasculosis menisci),12,13 for the most part, their occurrence in the oral cavity largely remains undocumented. The etiology of glomus tumors is diffi- cult to explain because these tumors can arise in loca- tions not known to have such a structure. Three theories of origin have been proposed: (1) Glomus tumors are hyperplasias or hamartomas of glomus cells associated with glomera present throughout the body but are scattered so thin that routine biopsy in those areas does not allow discovery14,15; (2) they are hetero- topic proliferations of glomus cells from the glomus apparatus known to be in other sites14; or (3) they arise from perivascular cells in the area of the tumor and have undergone glomocytic differentiation.10,16 Cur- rently, the third theory seems to be the most accepted
Statement of Clinical Relevance
Oral glomus tumors are extremely rare and demon- strate overlapping features with other neoplasms.
Scarcity, inconsistent nomenclature, and perplexing etiology of these tumors contribute to confusion.
Documentation with review of the literature is valu- able to head and neck pathologists.
aDivision of Oral and Maxillofacial Pathology, University of Kentucky College of Dentistry, Lexington, KY, USA.
bDivision of Oral and Maxillofacial Pathology, University of Florida College of Dentistry, Gainesville, FL, USA.
cPrivate Practice, Great Plains Oral Surgery and Implant Center, North Platte, NE, USA.
Received for publication May 7, 2018; returned for revision Jun 26, 2018; accepted for publication Jul 23, 2018.
Ó 2018 Elsevier Inc. All rights reserved.
2212-4403/$-see front matter
http://doi.org/10.1016/j.oooo.2018.07.056
62
one because many investigators believe that myoperi- cytomas, myofibromas, angioleiomyomas, and glomus tumors form a morphologic continuum.16-19Sato et al.
demonstrated viral structures on electron microscopy in one intraoral case; however, a viral etiology has not been documented in other reports.20
Additionally, controversy exists as to whether or not glomus tumors are true neoplasms or, rather, hyperpla- sias/malformations of the normal glomus body.21,22It is generally accepted, however, that the solid glomus tumors are neoplasms, whereas the other types (glo- mangioma, glomangiomyoma) may be reactive or malformations.10
In this article, we present 2 new cases of oral glomus tumors, one from the tongue in a 58-year-old female and the other from the lower lip of a 26-year-old male.
Additionally, we review the literature for cases of benign glomus tumor in the oral regions and offer data on the clinical and histopathologic features of this rare tumor.
CASE REPORT 1
A 58-year-old white female with no significant medical history presented to her oral surgeon with an asymp- tomatic nodule on her anterior ventral tongue (Figure 1A). The nodule was approximately 2£ 1 cm and first noted by the patient 2 months prior to excision. The clinical impression was a minor salivary gland tumor.
The tumor was excised with no complications (Figure 1B). The patient exhibited normal healing at the 1- month follow-up appointment.
Upon gross sectioning, the tumor appeared as a well- circumscribed, rounded nodule approximately 1 cm in greatest dimension, located subjacent to the overlying epithelium. The cut surface was tan to focally brown in color, homogeneous, and glistened slightly (Figure 1C). Microscopic examination revealed a well-circum- scribed, encapsulated tumor (Figure 2A) comprising dense sheets of round to polygonal cells in a mucinous and myxoid stroma (Figure 2B). The cells demon- strated large, uniform, round-to-ovoid nuclei with prominent nucleoli and a fine, open chromatin pattern (Figure 2C). Moderate amounts of pale pink to clear cytoplasm were present around many of the nuclei.
Although most areas consisted of densely packed cells, focal areas demonstrated a loose and myxoid back- ground with clumping of the cells around blood vessels (see Figure 2B). Small blood vessels were scattered throughout the tumor. No nuclear pleomorphism or mitotic figures were identified. Focal areas of signet ring like cells were noted (Figure 2D). Immunohisto- chemical studies revealed positive reactivity to a-smooth muscle actin (SMA) (Figures 2E and2F) and muscle-specific actin (MSA, HHF-35) with lack of reactivity to S-100 protein (S100), p63, glial fibrillary acidic protein (GFAP), chromogranin, Sox10, AE 1/
3and p63. Vascular markers CD31 and CD34 highlighted the blood vessels.
CASE REPORT 2
A 26-year-old white male presented to an oral surgeon with a painful mass that had been present for months on his lower lip. The clinical impression was a muco- cele. Grossly, the tumor was described as a dark tan nodule measuring1.5£ 0.5 £ 0.5 cm. Histopathologic examination demonstrated a well-defined tumor sur- rounded by a fibrous capsule (Figure 3A). The encap- sulated nodule contained large pools of erythrocytes and fibrinous material admixed with islands and clus- ters of round to ovoid glomus cells. The glomus cells tended to form collars around blood vessels (Figure 3B) and demonstrated distinct cell borders with a fine nuclear chromatin pattern (Figure 3C). They were occasionally arranged in a nodular fashion surrounded by hyalinized and myxoid fibrous connective tissue (Figure 3D). Immunohistochemical staining revealed positive reactivity in the tumor cells for HHF-35 (Figure 3E) and SMA (Figure 3F), although no reac- tion to AE1/3, STAT-6, CD31, or CD34 was noted. No clinical follow-up data are available for this case.
LITERATURE REVIEW
The English language literature was searched for cases of benign glomus tumor in the oral and paraoral regions via PubMed and Web of Science. The follow- ing key terms were searched: “glomus tumor,”
“glomangioma,” “oral cavity,” and “oral.” Additional citations were cross-referenced from the identified
Fig. 1. Clinical presentation of case #1 prior to (A) and after (B) excisional biopsy. Gross examination revealed an encapsulated nodule with a tan, homogenous cut surface (C).
OOOO REVIEW ARTICLE
Volume 127, Number 1 Smith et al. 63
Fig. 2. A, Microscopic examination of case #1 revealed a well-circumscribed nodule with a thin fibrous capsule (magnifica- tion£ 1.5). B, The tumor cells are arranged in clusters and collars around blood vessels and set in a loose, myxomatous back- ground (magnification£ 10). C, A high-power image demonstrates sheets of monotonous round-ovoid cells with abundant pale eosinophilic-to-clear cytoplasm and distinct cell borders. The nuclei have a fine chromatin pattern with a prominent nucleolus (magnification£ 100). D, Occasional foci of signet ring like cells are seen (magnification £ 40). E, Diffuse reactivity to a-smooth muscle actin (a-SMA) is apparent throughout the entire tumor (magnification £ 2). F, a-SMA reactivity is intensively positive in the cytoplasm of tumor cells (magnification£ 40). A high resolution version of this slide is available as eSlide:
VM05172.
sources. We excluded any cases known to have multi- ple glomus tumors.9,23-25Data from 4 reports in lan- guages other than English (German and Italian) were included in our review because other authors had included them in their reviews.26-29
Thirty-two cases of solitary, oral or paraoral glo- mus tumors were found in the English language litera- ture, including the cases presented here.8,10,15,18-22,26- 46We excluded 1 case that did not provide a thorough histopathologic description or photomicrographs.40 Of the 31 total cases (Table I), patient age ranged from 10 to 85 years (average age 47 years; median age 54 years). There was an almost equal ratio of male-to-female patients (16 males, 15 females). The most common site was the lips (8 in the upper lip, 4 in the lower lip). Less common sites included the tongue, palate, buccal mucosa, gingiva, parotid, pter- ygoid fossa, and oropharynx. Twelve case reports described pain or tenderness as a clinical symptom.
Of the 18 reported cases with accompanying immuno- histochemical stains, only 14 expressed positivity for muscle markers. Two of the remaining cases did not run actins,39, 42 and the other 2 cases were negative for muscle markers,21,36 bringing into question the accuracy of the diagnosis.
DISCUSSION
Representing less than 2% of all soft tissue tumors,16,47,48glomus tumors are exceptionally rare, and even rarer in the oral regions. We identified 29 cases of benign oral or paraoral glomus tumors from the English language literature and added 2 more cases. Of these, only 14 were confirmed with immunohistochemistry.
Contributing to confusion about the entity, the termi- nology for glomus tumor is inconsistent throughout the literature. The word glomus is defined as an anastomosis of arterioles and venuoles; thus, the term glomus tumor came about because it is a proliferation of those cells that surround the AV anastomosis of the glomus apparatus.
Glomus tumor, however, has also been used to describe paragangliomas, which were originally believed to derive from a blood vessel origin. Despite the discovery that par- agangliomas actually derive from the nonchromaffin cells of the neural crest, the incorrect terminology has, unfortu- nately, persisted (e.g., glomus tympanicum, glomus jugu- lare).49Furthermore, various other names have been used to identify the perivascular glomus tumor, including glomangioma, glomuvenous malformation, glomangio- myoma, neuromyoarterial glomus, angioneuroma, angio- neuromyoma, painful subcutaneous tubercle, Popoff tumor, and subcutaneous glomal tumor.16,50
Fig. 3. A, Low power examination (magnification£ 1) shows a well-circumscribed nodule of tumor cells arranged in islands interspersed with abundant blood-filled cavities. A thin fibrous capsule surrounds the tumor. B, Glomus cells characteristically cuff a bordering blood vessel. C, The tumor cells are regular with distinct cell borders. The nuclei demonstrate an open chromatin pattern. Infrequent cells with cleared-out cytoplasm are seen (magnification£ 50). D, Occasional balls of glomus cells are noted, surrounded by spindled and myxoid tumor cells (magnification£ 20). E, Immunohistochemistry for muscle-specific antigen (MSA) reveals diffuse positivity for tumor cells (magnification£ 2). F, a-smooth muscle actin (a-SMA) is intensely positive within the cytoplasm of the glomus cells (magnification£ 40). A high resolution version of this slide is available as eSlide:
VM05173.
OOOO REVIEW ARTICLE
Volume 127, Number 1 Smith et al. 65
Case Author Age Gender Race Duration Site Clinical description Immunohistochemical profile
1 Boros et al., 2010 34 M H 1 year Lower lip Asymptomatic SMA+, MSA+, S-100+, keratin , EMA , CD34 ,
CD31 , chromogranin-
2 Derand et al., 2010 11 F Lower lip Well defined, painless
discoloration
SMA+, vimentin+, factor XIII
3 Ficarra et al., 1986 51 F C 6 years Upper Lip Painless, bluish swelling NA
4 *Frenkel, 1965 13 M Buccal mucosa NA
5 Geraghty et al., 1992 71 M C Several years Palate Painless, slowly enlarging,
cream colored mass
Actin , desmin-, chromogranin , NSE , PGP9.5
6 Gonzalez-Campora et al., 1995 72 F 7 years Oropharynx Dyspnea, dysphagia, dyslalia,
bleeding, tenderness
Vimentin+, SMA and desmin focally +,
7 *Grande, D’Angelo, 1962 42 M Hard palate NA
8 Harris and Griffin, 1965 35 F 3 weeks Periodontium/gingiva Pain caused by an “antral
abscess” of 3 weeks’
duration
NA
9 Harvey, Walker 1987 15 F C 2 years Pterygoid fossa Painful Myosin+, vimentin+
10 Ide et al., 2008 57 M Upper lip SMA+, MSA+
11 Ide et al., 2008 54 M Upper lip SMA+, MSA+
12 Kessaris et al., 2001 46 F 10 years Palate Painless, bluish swelling
increasing in size for 10 years
Vimentin +, S100+, actin , desmin , chromogranin , NSE , cytokeratin , EMA , factor VIII
13 King, 1954 32 M 5 years Maxillary gingiva Tender NA
14 *Kirschner, Strassburg, 1962 56 M Gingiva/alveolar mucosa NA
15 Kusama et al., 1995 57 M A Several years Upper lip Tender swelling Actin+, desmin+, S100+, vimentin+
16 Lanza et al., 2005 65 M 4 months Lower lip Blue mass, painful on
palpation
NA
17 Moody et al., 1986 65 F Several years Upper lip Asymptomatic swelling Vimentin+, factor VIII , CD45 , AbgA ,
cytokeratin
18 Rallis et al., 2004 85 F 10 years Upper lip Mildly painful (especially at
night), brown swelling
SMA+, MSA+, vimentin+, desmin , S100 , EMA , NSE , AE1/3 , leu7 , CD31 , CD34 , CD45 , CD3 , CD20 , Cytokeratins-
19 Sakashita et al., 1995 63 F At least 4 years Parotid Pain upon opening Vimentin +, S100 , keratin , desmin , EMA ,
chromagranin , factor VIII related antigen for tumor
20 Sakashita et al., 1997 54 M 5 years Upper lip Painless swelling SMA+, vimentin+, factor VIII related antigen
21 Saku et al., 1985 45 M 6 months Left buccal mucosa UNK Actin+, smooth muscle myosin+
22 Sato et al., 1979 29 M Japanese 1 year Tongue Painless, firm, smooth,
slightly reddish, movable nodule
NA; (author mentions the possibility of malignant behavior caused by presence of atypia and sporadic mitoses)
23 Savaci, 1996 55 F >1 year Left buccal mucosa Mass; burning pain NA
24 Sidhu, Subherwal, 1967 10 F A 6 months Hard palate Asymptomatic pink mass,
soft
NA
(continued on next page)
ANDMAXILLOFACIALPATHOLOGYOOOO
etal.January2019
The most common clinical presentation of glomus tumors is a subcutaneous nodule, often blue, purple, or red in color and that occurs in the third to fifth deca- des.10,32,51 The majority arises in the subungual loca- tion; however, they have been found in all parts of the body, including the stomach, heart, uterus, vagina, penis, mediastinum, lung, bone, trachea, gastrointesti- nal tract, and kidney.16,32,51-53Although a female pre- dilection has been noted for subungual tumors, no gender predilection (or slight male) exists for glomus tumors in other locations.10,22,39,51 In the 31 cases of oral/paraoral tumors in this review, no gender predilec- tion was seen.
A striking clinical symptom associated with glomus tumors is the presence of pain that is disproportionate to the size of the tumor. The pain may vary from slight tenderness upon palpation to excruciating burning, shooting, or stabbing pain that radiates up the limbs and involve the trunk or even half of the body.1,5,22 The pain frequently has been described as paroxysmal or associated with changes in temperature or pres- sure.5,10,32Pain or tenderness was noted in 12 of 31 of the cases evaluated in this review. Investigators have hypothesized that the pain may be associated with the tumor being tightly bound down (e.g., in the nail bed)
19; however, the presence of painful tumors in loosely bound tissue argues against that point.10,43,45,present case
The high concentration of nerve fibers noted through- out some tumors may explain the pain.21,54Occasional cases have been reported to contain substance P, a pain-related vasoactive peptide, and cyclooxygenase-2, which may contribute to the pain mechanism.55,56 Notably, a history of trauma has also been associated with glomus tumors.5,22,48,50
The current World Health Organization classifica- tion system lists several types of glomus tumors, including solid glomus tumors, which represent about 75% of cases.16 Other variants of the tumor include glomuvenous malformations (also known as gloman- giomas), glomangiomyomas, glomangiomatosis, symplastic glomus tumors, malignant glomus tumors, and glomus tumors of uncertain malignant potential.
The major distinction between solid glomus tumor, glomangioma, and glomangiomyoma lies in the dis- tribution of glomus cells and the amount of vascular and smooth muscle within the lesion; however, no exact percentage for each of these features exists within the classification system.16 Histopathologi- cally, solid glomus tumors typically present as encap- sulated or well-circumscribed masses of glomus cells arranged in sheets, aggregates, or collars around blood vessels (seeFigure 3B). Our first case is most appropriately classified as a solid glomus tumor. The glomus cells are monomorphous and round-to-ovoid in shape with a sharply delineated, round nucleus and Table?I.Continued CaseAuthorAgeGenderRaceDurationSiteClinicaldescriptionImmunohistochemicalprofile 25Stajcic,Bojic,198755M6monthsTonguePainless,pinkmass,softNA 26Tajimaetal.,198163FVentraltongueAsymptomaticnoduleNA 27Vasconcelosetal.,201867F5yearsUpperlipSlightlypainfulswelling; Painnotaggravatedbycold ortouch.
SMA+,CD34+,vimentin+,S100,cytokeratin 28*VonLanger,194952MHardpalateNA 29Yoruketal.,201030F4yearsBuccalmucosaMassandtendernessSMA+,vimentin+,p53focallypositive,CD31, CD34,chromogranin,desmin,S100, cytokeratin,CD117,LCA,BCL2 30Presentcase158FC2monthsVentraltongueAsymptomaticnoduleSMA+,MSA+,P63,S100,GFAP, chromogranin,Sox10,AE1/3,p63,CD31, CD34 31Presentcase226MCmonthsLowerlipPainfulmassSMA+,MSA+,AE1/3,STAT6,CD31,CD34 *Originalpublicationinanon-Englishlanguage,butincludedinEnglishlanguageliteraturereviews. ASMA,a-smoothmuscleactin;C,Caucasian;EMA,epithelialmembraneantigen;F,female;GFAP,glialfibrillaryacidicprotein;H,Hispanic;M,male;MSA,muscle-specificactin;NA,notapplicable;NSE, neuron-specificenolase;PGP9.5,proteingeneproduct9.5;SMA,smoothmuscleactin.
OOOO REVIEW ARTICLE
Volume 127, Number 1 Smith et al. 67
pale eosinophilic cytoplasm. The stroma may appear myxoid or hyalinized (as seen inFigure 2B). Occa- sionally, the glomus cells may demonstrate either an oncocytic or a signet-ring-like appearance (see Figure 2D).7,47 Glomangiomas (glomuvenous mal- formations) tend to exhibit large, dilated vascular spaces with small collections of glomus cells. This subtype is most commonly associated with multiple lesions.16 Glomangiomyomas contain more elon- gated spindle-to-ovoid shaped cells that are more typical of mature smooth muscle cells. Our second case is difficult to classify because it is a combination of subtypes, containing not only large vascular spaces but also large clusters of glomus cells and spindled cells demonstrating smooth muscle differentiation (shown inFigure 3D at the periphery of the ball-like cluster of glomus cells). Glomangiomatosis is most similar to diffuse angiomatosis; however, clusters of glomus cells are noted around the vessels.
Some glomus tumors demonstrate marked nuclear atypia or nuclear hyperchromatism but do not exhibit other features of malignancy, such as increased mitotic activity, necrosis, large size, or deep location. These tumors are referred to as symplastic glomus tumors.16 The symplastic nature may best be compared to
“ancient” or degenerative features seen in other soft tis- sue tumors (e.g., Schwannomas).47,57To make a diag- nosis of symplastic glomus tumor, it is helpful to find at least focal areas of normal-appearing glomus cells, most commonly found along the periphery of the lesion. Malignant glomus tumors (also referred to as glomangiosarcomas) demonstrate nuclear atypia along with increased and atypical mitotic figures. The World Health Organization classification system breaks malignant tumors down into 2 categories: (1) spindle- cell (resembling fibrosarcoma and leiomyosarcoma) and (2) round-cell. Tumors that lack obvious qualifica- tion for malignancy but do demonstrate other worri- some features, such as deep location, infiltrative growth, vascular space involvement, or large size, are classified as “glomus tumors of uncertain malignant potential.”16
Immunohistochemically, glomus tumors should demonstrate positivity to vimentin, SMA, MSA, and h- caldesmon.16,54 Distinct cell borders may be highlighted by a periodic acid Schiff (PAS) stain or toluidine blue. Cytokeratins, S100 protein, and factor VIII related antigen are reportedly negative.54 Des- min is usually negative, although occasional cases have been reported to demonstrate weak positiv- ity.51,54,58Although most authors agree that S100 pro- tein should be negative, occasional cases have reported positive reactivity.30,36,37The case reported by Kessaris et al.36demonstrated uniformly round cells but was nega- tive for actin and positive for S100, questioning a
diagnosis of glomus tumor being appropriate. Addition- ally, a case published by Geraghty et al.21demonstrated no reactivity toa-actin, desmin, chromogranin, neuron- specific enolase or protein gene product, but electron microscopy disclosed filamentous material within the glomus cells, compatible with smooth muscle myofi- brils. Furthermore, the case presented by Geraghty et al.21showed a classic hematoxylin and eosin presentation of uniformly round glomoid cells cuffing blood vessels.
In certain locations (e.g., the digits), the diagnosis of glomus tumor often is easily made; however, in extradigital sites, diagnostic difficulty may exist.
When the nodules occur under the skin, adnexal tumors (e.g., eccrine spiradenoma, nodular hidrade- noma) may be considered but are usually excluded with cytokeratin markers. Salivary gland tumors (e.
g., myoepitheliomas) may also be excluded by dis- covery of negative cytokeratin markers. Neuroendo- crine markers frequently are performed,21,30,36,41,46
likely because of the fine chromatin pattern of the glomus nuclei. Because of occasional signet ring like cells, cells with abundant pale cytoplasm, and the mucin- ous background in case 1 presented here, we considered a myoepithelioma or a signet-ring cell (mucin-produc- ing) adenoma of minor salivary glands (the benign counterpart to the adenocarcinoma first described by Ghannoum and Freedman in 2004).59,60-62 Negative reactivity to cytokeratins and myoepithelial markers (Sox10, S100, p63), as well as lack of mucicarmine staining within the cytoplasm of the cells, ruled out those diagnostic considerations. For the most part, glomus tumors are diagnostic on hematoxylin and eosin staining and confirmatory immunohistochemical reactivity with SMA. Categorizing the type of glomus tumor often is the more difficult challenge.
Like other tumors in the perivascular/myoid cate- gory (e.g., myofibroma), glomus tumors have a ten- dency to be multiple and/or familial. Generally, glomus tumors are multiple in less than 10% of cases.23,48,57 At least 3 cases of multiple glomus tumors (glomuvenous malformations) affecting the oral regions have been described.9,23,25Notably, mul- tiple glomus tumors have been associated with neuro- fibromatosis type I.16,63,64Multiple occurrences have been linked to chromosome 1p21Y22 (the glomulin gene) and demonstrate an autosomal dominant inheri- tance pattern with variable expressivity and incom- plete (approximately 90%) penetrance.23,48,57,65,66
The treatment for glomus tumors is excision. The recurrence rate varies from 2% to 50%, depending on the tumor site (e.g., the nailbed may pose a more difficult challenge in excising the entire tumor) or atypical fea- tures.47,51,67Of the 16 cases in this review that had the follow-up period specified, no recurrences were reported.
The average follow-up time was 2.6 years (of 1 month
to 7 years). In a review of glomus tumors (not specifi- cally oral) by Mravic et al., only 3 of 137 tumors recurred (median follow-up period of 2 years).68Malig- nant cases demonstrate a higher rate of recurrence and metastasis compared with benign tumors.10,51,68,69When pain is associated with the tumor, removal often provides immediate relief, although hypersensitivity may persist for weeks after the surgery.5
CONCLUSIONS
Glomus tumors are rare and even rarer in the oral cavity.
We presented here 2 cases with benign intraoral tumors and a comprehensive review of the clinical and histo- pathologic features common to this entity. Although the histopathologic diagnosis often is not difficult to make, unfamiliarity with this tumor may lead to diagnostic challenges. Therefore, oral and maxillofacial patholo- gists and head and neck pathologists should be knowl- edgeable about and cognizant of this entity when dealing with perplexing soft tissue lesions in the oral regions.
REFERENCES
1. Wood W. On painful subcutaneous tubercle. Edinburgh Med J.
1812;8:283-291.
2. Greig DM. Subcutaneous glomal tumours: painful subcutaneous nodule. Edinburgh Med J. 1928;35:565-582.
3. Masson P. Le glomus neuromyo-arteriel des regions tactiles et ses tumeurs. Lyon Chir. 1924;21:256-280.
4. Grosser O. Ueber arterio-venoese anastomosen an den extremi- taetenenden beim Menschen und den krallentragenden Saeuge- thieren. Arch Mikr Anat. 1902;60:191.
5. Shugart RR, Soule EH, Johnson Jr., EW. Glomus tumor. Surg Gynecol Obstet. 1963;117:334-340.
6. Albrecht S, Zbieranowski I. Incidental glomus coccygeum.
When a normal structure looks like a tumor. Am J Surg Pathol.
1990;1:922-924.
7. Goldblum JR, Folpe AL, Weiss SW. Perivascular tumors. In:
Soft Tissue Tumors.6th ed. Philadelphia, PA: Saunders Elsevier;
2014. p. 749-765.
8. Stajcic Z, Bojic P. Intraoral glomus tumour. A case report. J Cra- niomaxillofac Surg. 1987;15:376-378.
9. Charles NC. Multiple glomus tumors of the face and eyelid. Arch Ophthalmol. 1976;94:1283-1285.
10. Rallis G, Komis C, Mahera H. Glomus tumor: a rare location in the upper lip. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98:327-336.
11. Santos LD, Chow C, Kennerson AR. Glomus coccygeum may mimic glomus tumour. Pathology. 2002;34:339-343.
12. Griffin CJ. A neuro-myo-arterial glomus in the temporomandibu- lar meniscus. Med J Aust. 1961;48:113-116.
13. Provenza DV, Biddix JC, Cheng TC. Studies on the etiology of periodontosis. II. Glomera as vascular components in the peri- odontal membrane. Oral Surg Oral Med Oral Pathol.
1960;13:157-164.
14. Murray MR, Stout AP. The glomus tumor: investigation of its distribution and behavior, and the identity of its “epithelioid”
cell. Am J Pathol. 1942;18:183-203.
15. Sidhu SS. Glomus tumour of palate. J Indian Dent Assoc.
1967;39:167-168.
16. Fletcher CDM, Bridge JA, Lee JC. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon, France: IARC Press; 2013.
17. Granter SR, Badizadegan K, Fletcher CD. Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. Am J Surg Pathol. 1998;22:513-525.
18. Ide F, Mishima K, Yamada H, et al. Perivascular myoid tumors of the oral region: a clinicopathologic re-evaluation of 35 cases.
J Oral Pathol Med. 2008;37:43-49.
19. Saku T, Okabe H, Matsutani K, Sasaki M. Glomus tumor of the cheek: an immunohistochemical demonstration of actin and myosin. Oral Surg Oral Med Oral Pathol. 1985;60:65-71.
20. Sato M, Shirasuna K, Sakuda M, et al. Fine structure of a glomus tumor of the tongue and expression of C type virus in its tumor cells. Int J Oral Surg. 1979;8:199-204.
21. Geraghty JM, Thomas RW, Robertson JM, Blundell JW. Glomus tumour of the palate: case report and review of the literature. Br J Oral Maxillofac Surg. 1992;30:398-400.
22. King ES. Glomus tumour. Aust N Z J Surg. 1954;23:280-295.
23. Boon LM, Mulliken JB, Enjolras O, Vikkula M. Glomuvenous malformation (glomangioma) and venous malformation: distinct clinicopathologic and genetic entities. Arch Dermatol. 2004;140:
971-976.
24. Mounayer C, Wassef M, Enjolras O, Boukobza M, Mulliken JB.
Facial “glomangiomas”: large facial venous malformations with glomus cells. J Am Acad Dermatol. 2001;45:239-245.
25. Yu HJ, Kwon SJ, Bahn JY, Park JM, Park YW. Localized multi- ple glomus tumors of the face and oral mucosa. J Dermatol.
2000;27:211-213.
26. Frenkel G. Occurrence of leiomyofibroangioma (glomangioma) in the cheek and zygomatous arch region. Dtsch Zahnarztl Z.
1965;20:168-172. [in German].
27. Grande R, D’Angelo E. Un tumore glomico del palato duro. Arch Ital Laringol. 1962;70:89.
28. Kirschner H, Strassburg M. Ein am zhanlosen Alveolarfortsatz des Unterkiefers lokalisierter Glomustumor. Dtsch Zahnarzl Z.
1962;17:912.
29. Von Langer R. Glomustumor am harten Gaumen. Wein Med Wochenschr. 1949;99:67.
30. Boros AL, Davis JP, Sedghizadeh PP, Yamashita DD. Glo- mus tumor: report of a rare case affecting the oral cavity and review of the literature. J Oral Maxillofac Surg.
2010;68:2329-2334.
31. Derand 3rd, P, Warfvinge G, Thor A. Glomangioma: a case pre- sentation. J Oral Maxillofac Surg. 2010;68:204-207.
32. Ficarra G, Merrell PW, Johnston WH, Hansen LS. Intraoral solitary glomus tumor (glomangioma): case report and litera- ture review. Oral Surg Oral Med Oral Pathol. 1986;62:
306-311.
33. Gonzalez-Campora R, Villar Rodrıguez JL, Vazquez Ramırez F, Dıaz Cano S, Galera Ruiz H. Glomus tumour of the oropharynx.
J Laryngol Otol. 1995;109:63-65.
34. Harris R, Griffin CJ. Glomus tumour of the periodontal tissues.
Aust Dent J. 1965;10:33-37.
35. Harvey JA, Walker F. Solid glomus tumor of the pterygoid fossa:
a lesion mimicking an epithelial neoplasm of low-grade malig- nancy. Hum Pathol. 1987;18:965-966.
36. Kessaris P, Klimis T, Zanakis S. Glomus tumour of the hard pal- ate: case report and review. Br J Oral Maxillofac Surg.
2001;39:478-479.
37. Kusama K, Chu L, Kidokoro Y, et al. Glomus tumor of the upper lip. J Nihon Univ Sch Dent. 1995;37:97-101.
38. Lanza A, Moscariello A, Villani R, Colella G. Glomus tumor of the lower lip. A case report. Minerva Stomatol. 2005;54:687-690.
OOOO REVIEW ARTICLE
Volume 127, Number 1 Smith et al. 69
39.Moody GH, Myskow M, Musgrove C. Glomus tumor of the lip.
A case report and immunohistochemical study. Oral Surg Oral Med Oral Pathol. 1986;62:312-318.
40.Quesada R, Gonzalez-Lagunas J, Raspall G. Aggressive glomus tumor of the tongue: report of a case. Med Oral. 2004;9:
350-354.
41.Sakashita H, Miyata M, Miyamoto H, Kurumaya H. Glomus tumor originating in the parotid region. J Oral Maxillofac Surg.
1995;53:830-834.
42.Sakashita H, Miyata M, Nagao K. Glomus tumor in the upper lip.
A case report. Int J Oral Maxillofac Surg. 1997;26:301-302.
43.Savaci N, Emiroglu M, Gumren M, Gungor S. A rare case of glo- mus tumour; buccal localization. Br J Oral Maxillofac Surg.
1996;34:199-200.
44.Tajima Y, Weather DR, Neville BW, Benoit PW, Pedley DM.
Glomus tumor (golomangioma) of the tongue. A light and elec- tron microscopic study. Oral Surg Oral Med Oral Pathol.
1981;52:288-293.
45.Vasconcelos ACU, Loyola AM, Gomes APN, et al. A symptom- atic swelling of the upper lip. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125:107-111.
46.Yoruk O, Ucuncu H, Aktan B, Calik M, Kilic K. Glomuvenous malformations in the buccal area. J Craniofac Surg. 2010;21:
2001-2003.
47.Falleti J, Vita G, De Cecio R, et al. Symplastic glomus tumor:
report of a challenging lesion with literature review. Pathol Res Pract. 2012;208:372-375.
48.Kale SS, Rao VK, Bentz ML. Glomus tumor of the index finger.
J Craniofac Surg. 2006;17:801-804.
49.Wolter NE, Adil E, Irace AL, et al. Malignant glomus tumors of the head and neck in children and adults: evaluation and manage- ment. Laryngoscope. 2017;127:2873-2882.
50.Stout A. Tumors of the neuromyoarterial glomus. Am J Cancer.
1935;24:255.
51.Gombos Z, Zhang PJ. Glomus tumor. Arch Pathol Lab Med.
2008;132:1448-1452.
52.Gaertner EM, Steinberg DM, Huber M, et al. Pulmonary and mediastinal glomus tumors—report of five cases including a pul- monary glomangiosarcoma: a clinicopathologic study with liter- ature review. Am J Surg Pathol. 2000;24:1105-1114.
53.Miettinen M, Paal E, Lasota J, Sobin LH. Gastrointestinal glo- mus tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 32 cases. Am J Surg Pathol.
2002;26:301-311.
54.Dervan PA, Tobbia IN, Casey M, O’Loughlin J, O’Brien M. Glo- mus tumours: an immunohistochemical profile of 11 cases. His- topathology. 1989;14:483-491.
55.Kishimoto S, Nagatani H, Miyashita A, Kobayashi K. Immuno- histochemical demonstration of substance P-containing nerve fibres in glomus tumours. Br J Dermatol. 1985;113:213-218.
56. Yanai T, Tanaka T, Ogawa T. Immunohistochemical demonstra- tion of cyclooxygenase-2 in glomus tumors. J Bone Joint Surg Am. 2013;95:725-728.
57. Kamarashev J, French LE, Dummer R, Kerl K. Symplastic glo- mus tumor—a rare but distinct benign histological variant with analogy to other “ancient” benign skin neoplasms. J Cutan Pathol. 2009;36:1099-1102.
58. Bertalot G, Falchetti M, Parafioriti A. Glomus tumour: the immunohistochemical characteristics of twenty-three cases.
Pathologica. 1994;86:509-512.
59. Ghannoum JE, Freedman PD. Signet-ring cell (mucin-produc- ing) adenocarcinomas of minor salivary glands. Am J Surg Pathol. 2004;28:89-93.
60. Foschini MP, Baldovini C, Pennesi MG, Cocchi R, Simpson RH.
Signet ring cell tumor of the minor salivary gland exhibiting benign behavior. Hum Pathol. 2012;43:303-306.
61. Gnepp DR. Mucinous myoepithelioma, a recently described new myoepithelioma variant. Head Neck Pathol. 2013;7:S85-S89.
62. Skalova A, Gnepp DR, Lewis Jr., JS, et al. Newly described entities in salivary gland pathology. Am J Surg Pathol. 2017;41:e33-e47.
63. Okada O, Demitsu T, Manabe M, Yoneda K. A case of multiple subungual glomus tumors associated with neurofibromatosis type 1. J Dermatol. 1999;26:535-537.
64. Sawada S, Honda M, Kamide R, Niimura M. Three cases of sub- ungual glomus tumors with von Recklinghausen neurofibromato- sis. J Am Acad Dermatol. 1995;32:277-278.
65. Brouillard P, Boon LM, Mulliken JB, et al. Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations (“glomangiomas”). Am J Hum Genet. 2002;70:866-874.
66. Brouillard P, Boon LM, Revencu N, et al. GVM Study Group.
Genotypes and phenotypes of 162 families with a glomulin mutation. Mol Syndromol. 2013;4:157-164.
67. Song M, Ko HC, Kwon KS, Kim MB. Surgical treatment of sub- ungual glomus tumor: a unique and simple method. Dermatol Surg. 2009;35:786-791.
68. Mravic M, LaChaud G, Nguyen A, Scott MA, Dry SM, James AW.
Clinical and histopathological diagnosis of glomus tumor: an institu- tional experience of 138 cases. Int J Surg Pathol. 2015;23:181-188.
69. Folpe AL, Fanburg-Smith JC, Miettinen M, Weiss SW. Atypical and malignant glomus tumors: analysis of 52 cases, with a pro- posal for the reclassification of glomus tumors. Am J Surg Pathol. 2001;25:1-12.
Reprint requests:
Molly Housley Smith, Division of Oral and Maxillofacial Pathology, University of Kentucky College of Dentistry, 800 Rose Street, Rm.
530, Lexington, KY 40536, USA.
molly.housley.smith@gmail.com
