J Cutan Pathol 2002: 29: 421–425 Copyright C Blackwell Munksgaard 2002Blackwell Munksgaard . Printed in Denmark

Journal ofCutaneous Pathology

ISSN 0303-6987

CD34-positive glomus tumor:clinicopathologic andimmunohistochemical analysis of six caseswith myxoid stromal changes

Background: Glomus tumors are benign, mainly superficially located Thomas Mentzel, Heino Hügelperivascular neoplasms, composed of cytologically characteristic and Heinz Kutznerneoplastic cells staining immunohistochemically positive for vimentin Dermatohistopathologischesand muscle actin, closely associated with often branching blood vessels. Gemeinschaftslabor, Friedrichshafen, GermanyMethods: Six cases of glomus tumor were analysed histologicallyand immunohistochemically.Results: We report six cases of glomus tumor (three solid glomustumors, two glomangiomas, one glomangiomyoma) arising on thefingers of adult patients (five female and one male patient; age range35–65years) that showed prominent myxoid stromal changes andimmunohistochemically a coexpression of alpha-smooth muscle actinand CD34 by neoplastic cells.Conclusions: Neoplastic cells in glomus tumor may show acoexpression of alpha-smooth muscle actin and CD34, an importantfinding regarding the differential diagnosis of these lesions and the Dr Thomas Mentzel, Dermatohistopathologischesrelationship of perivascular neoplasms. Gemeinschaftslabor, Siemensstrasse 6/1, D-88048

Friedrichshafen, GermanyTel. 49-7541-56071Mentzel T, Hügel H, Kutzner H. CD34-positive glomus tumor:Fax: 49-7541-604410clinicopathologic and immunohistochemical analysis of six cases with e-mail: tmentzel/w-4.de

myxoid stromal changes.J Cutan Pathol 2002; 29: 421–425. C Blackwell Munksgaard 2002. Accepted 9 February, 2002

Perivascular neoplasms comprise traditionally glomustumors including solid glomus tumor, glomangiomaand glomangiomyoma as well as hemangiopericytom-as. Nowadays, hemangiopericytoma represents a di-agnosis of exclusion, since reproducible diagnostic cri-teria are debatable and mesenchymal entities of dif-ferent lines of differentiation have been summarizedunder this heading in the past.1,2 Most recently, athird group of perivascular lesions has been reportedas myopericytomas (glomangiopericytoma). Theseneoplasms show a myoid differentiation and overlap-ping morphologic features to hemangiopericytomaand glomus tumor.3 Neoplastic cells in glomus tumorsare regarded as modified smooth cells and stain im-munohistochemically positive for vimentin andmuscle specific actin;4–7 more rarely an expression ofdesmin has been reported.5,7

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We describe six cases of glomus tumor arising onthe fingers of adult patients that showed prominentmyxoid stromal changes and strong coexpression ofCD34.

Materials and methodsAll six cases were identified in the routine diagnosticfiles of the Department of Dermatohistopathology inFriedrichshafen, Germany. Clinical information wasobtained from the laboratory request forms and con-tributing clinicians (see ‘Acknowledgements’). In eachcase, tissue was fixed in 4% buffered formalin, rou-tinely processed and embedded in paraffin; 4-mmthick sections were stained with hematoxylin andeosin. In addition, sections in all cases were alsostained immunohistochemically by the labelled

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Streptavidin Biotin (LSAB) technique using commer-cially available antibodies; antigen retrieval was usedfor all antibodies. The antibodies used, their sourcesand dilutions are given in Table1. Appropriate nega-tive and positive controls were used in each case.

ResultsThe clinical findings are summarized in Table2.Briefly, the six neoplasms arose in five females andone male patient (age range 35–65years), and werelocated on the fingers (two in subungual location).Cases 2, 3, and 4 were completely excised (marginalexcision), and in cases 5 and 6 a piecemeal excisionwas performed; in case 1, only biopsy material wasavailable. All lesions were smaller than 2cm in diam-eter. There was no sign of recurrence; however, allcases were excised within the last 2 years, and follow-up time is therefore quite limited.

Histologically, all cases arose in dermal tissue.Cases 4, 5, and 6 showed features of solid glomustumor composed of solid sheets and clusters of roundto oval tumor cells containing an eosinophilic cyto-plasm with distinct cell borders, and round, sharplydemarcated nuclei. Tumor cells were closely associ-ated with numerous thin-walled, sometimesbranching capillaries (Fig. 1). In case 3, features ofglomangioma with numerous dilated vascular spaceswere noted, and in case 2 a partly solid, partly angi-omatous glomus tumor was seen. The lesion in case1 was composed of dilated vascular spaces with sur-rounding glomus cells and more myoid, spindle-shaped, eosinophilic cells arranged perivascularly orin a lace-like pattern; this lesion was classified as glo-mangiomyoma. Enlarged and often vesicular tumorcell nuclei were found in cases 2, 3, 4, and 5; in ad-

Table1. Immunohistochemical reagents used

Antibody Clone Dilution Source

Pancytokeratin MNF116 1:100 Dako, Glostrup, DenmarkEMA, Mc-5 1:200 BioGenex, San Ramon, CADesmin D33 1:200 Dako, Glostrup, DenmarkS-100 protein polyclonal 1:4000 Dako, Glostrup, DenmarkCD34 Qbend10 1:50 Dako, Glostrup, DenmarkASMA 1A4 1:300 Dako, Glostrup, Denmark

ASMA, alpha-smooth muscle actin.

Table2. Clinical findings in six cases of CD34-positive glomus tumors

Case Age (year) Sex Location

1 59 M Finger (subungual)2 42 F Thumb3 65 F Middle finger4 35 F Digital finger5 35 F Finger (subungual)6 37 F Finger

M, male; F, female.

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Fig. 1. A case of glomus tumor composed of dilated vascular struc-tures and perivascular arranged glomus cells (H&E).

Fig. 2. In case 3, scattered enlarged vesicular nuclei were noted(H&E).

dition scattered mono- and multinucleated giant cellswith features similar to what is seen in so-calledsymplastic glomus tumor8 were noted in case 3 (Fig.2). Despite enlargement of tumor cell nuclei in anumber of cases, neither prominent nucleoli nor anincreased mitotic activity were evident. Tumor cellsin all cases were set in an intercellular matrix withprominent myxoid changes (Fig. 3).

Immunohistochemically, endothelial cells stainedpositively for CD31 and CD34, and perivascular glo-mus cells were positive for alpha-smooth muscle actin(Fig. 4). In addition, a homogeneous positivity of neo-plastic cells and endothelial cells for CD34 was seenin all cases (Fig. 5). Spindled-shaped myoid cells incase 1 stained at least focally positive for desmin; thetumor cells of the remaining cases were negative forthis marker. None of the cases tested stained positivelyfor S-100 protein, cytokeratin, and EMA.

DiscussionThe majority of glomus tumors are small, often pain-ful dermal neoplasms typically located in the subung-

CD34-positive glomus tumor

Fig. 3. In all cases, myxoid stromal changes were present (H&E).

Fig. 4. Tumor cells stained positively for alpha-smooth muscle ac-tin. Note bundles of spindle-shaped tumor cells in this case of glom-angiomyoma (case 1) (LSAB).

Fig. 5. In all neoplasms, tumor cells showed coexpression of CD34(LSAB).

ual region of the fingers, and other parts of the distalextremities. However, the anatomic distribution iswide, and rare examples of this entity have been re-ported in almost every part of the body. Histolog-ically, four main types were recognized in the past,

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including solid glomus tumor, glomangioma, gloman-giomyoma, and rare glomangiosarcoma.1 Most re-cently, a reclassification of atypical and malignant glo-mus tumors has been proposed, which includes malig-nant glomus tumor, glomus tumor of uncertainmalignant potential, symplastic glomus tumor andglomangiomatosis.8

All types of glomus tumor are composed of neo-plastic cells that resemble normal glomus cells ar-ranged around a varying number of thin-walled,sometimes branching capillaries. Immunohistochem-ically and ultrastructurally, neoplastic cells in glomustumors clearly exhibit smooth muscle characteristicswith expression of muscle-specific actin and alpha-smooth muscle actin, whereas desmin is coexpressedmore rarely. Given the fact that pericytes associatedwith larger vessels may transform into vascularsmooth muscle cells or, in other words, that pericyteshave the potential to differentiate into smooth musclecells,9,10 it seems reasonable to interpret neoplasticglomus cells or glomus tumors in general as perivas-cular neoplasms with a myoid phenotype. In contrastand despite a shared perivascular arrangement ofneoplastic cells, rare hemangiopericytomas, the sec-ond group of perivascular neoplasms, are composedof undifferentiated spindle-shaped cells with ultra-structural expression of beta- and gamma-actins butlack positivity for alpha-smooth muscle actin.5,7 Inabout 50% of hemangiopericytomas, a CD34 positiv-ity of tumor cells has been reported.11 The thirdgroup of perivascular lesions, designated as myope-ricytoma (glomangiopericytoma), emphasizes theclose relationship between glomus tumor and heman-giopericytoma.3

The six cases reported showed clear histologicaland immunohistochemical features of benign glomustumor, including its variants of glomangioma, glom-angiomyoma and symplastic glomangioma. All neo-plasms arose in a distal location and showed promi-nent myxoid stromal changes, and, most importantly,a coexpression of alpha-smooth muscle actin andCD34 by neoplastic cells was found. In all six cases,a strong and homogeneous CD34 positivity of tumorcells was noted. CD34, first regarded as an endo-thelial marker in soft tissue neoplasms, has been re-ported in many spindled and more rarely also in epi-thelioid mesenchymal neoplasms, including dermato-fibrosarcoma protuberans, giant cell fibroblastoma,solitary fibrous tumor, giant cell angiofibroma, epi-thelioid sarcoma, neural and perineural neoplasms,some myogenic neoplasms, spindle cell and pleomor-phic lipoma, gastrointestinal stromal tumors, super-ficial angiomyxoma, superficial acral fibromyxomaand others.12–14 The diagnostic use of CD34 alone istherefore limited, and additional immunohistochem-ical markers should be applied in questionable cases.

There are only a few reports in the literature con-

Mentzel et al.

cerning the expression of CD34 in glomus tumors.In a comprehensive review of atypical and malignantglomus tumors, it is said that five out of 27 casestested stained positively for CD34 but neither a speci-fic comment nor illustrations are given.8 In addition,two rare cases of nasal glomus tumors showed a coex-presion of smooth muscle actin and CD34 and therelationship to sinonasal hemangiopericytoma wasdiscussed by the authors.15 In the Japanese literature,a CD34 expression in five out of six cases is docu-mented,16 and an irregular positive staining of tumorcells for CD34 in analysed glomus tumors has beenmentioned in a clinical report.17

The reported CD34 coexpression in our six casesraises additional questions regarding the differentialdiagnosis and the relationship of perivascular neo-plasms. We observed this peculiar immunophenotypeonly in glomus tumors with a prominent myxoid ma-trix, an unexplained phenomenon, whereas cases ofsolid glomus tumor, glomangioma or glomangiomy-oma in our files without these stromal changes, whichwere stained for comparison, were characterized byan actin-positive/CD34-negative immunophenotype.Tumor cells in epithelioid sarcoma, also occurring fre-quently in distal locations, may coexpress CD34;18

however, these neoplasms lack the characteristic vas-cular pattern of glomus tumor and are composed ofepithelioid tumor cells that stain positively for cyto-keratin and EMA. Although rare cases of superficiallylocated solitary fibrous tumor, which may show anepithelioid cytomorphology,19 contain branching andhemangiopericytoma-like blood vessels as well, a dis-tinction to glomus tumor is easily made. Neoplasticcells in solitary fibrous tumor do not express homoge-neously muscle actin and lack a close perivascular ar-rangement. Given the fact of overlapping morpholog-ical features of glomangioma, glomangiomyoma, andmyopericytoma (glomangiomyopericytoma), respec-tively,3 as well as the known CD34 expression inabout half of the cases of hemangiopericytoma, thereported coexpression of actin and CD34 in a smallsubset of glomus tumor adds support to the interpre-tation of these lesions as a family of perivascular neo-plasms.

In summary, we have described and illustrated thecoexpression of actin and CD34 in a subset of glomustumors with a prominent myxoid matrix occurring onthe fingers of adult patients. This finding is importantin the differential diagnosis of these neoplasms andemphasizes the relationship of different entities in thefamily of perivascular neoplasms.

AcknowledgementsThe authors are very grateful to the following colleagues whokindly provided material and clinical follow-up information: Dr G.Schmid, Erlangen (cases 1 and 5), PD Dr C. Sander, München

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(case 2), PD Dr A. Kuhn, Köln (case 3), Dr W. Bischof, Bad Soden(case 4), and Prof Dr D. Kistler, Ravensburg (case 6), all fromGermany.

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