Eyelid Pilomatrixoma: A Description of 16 cases and a Review of the Literature

CLINICAL PATHOLOGIC REVIEWSSTEFAN SEREGARD AND MILTON BONIUK, EDITORS

Eyelid Pilomatrixoma: A Description of 16 cases anda Review of the LiteratureJaime Levy, MD,1 Michael Ilsar, MD,2 Yael Deckel, MD,2 Alexander Maly, MD,3

Irene Anteby, MD,2 and Jacob Pe’er, MD2

1Department of Ophthalmology, Soroka University Medical Center, Beer-Sheva, Israel; 2Department of Ophthalmology,Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and 3Department of Pathology, Hadassah-HebrewUniversity Medical Center, Jerusalem, Israel

Abstract. Pilomatrixoma is an uncommon benign neoplasm that originates from the matrix of thehair root. It occurs more frequently in the head and neck region of children and adolescents, ofteninvolving the eyelid or eyebrow. Pilomatrixoma is often misdiagnosed clinically and the correctdiagnosis can be established only after excision and histological examination. Pathologic diagnosis ofpilomatrixoma is based on the finding of large masses of shadow cells, combined with basophilic cells,inflammation, foreign body giant cells, calcification, and ossification. We report 16 cases of eyelidpilomatrixoma that were treated in our department, and review the relevant literature. (SurvOphthalmol 53:526--535, 2008. � 2008 Elsevier Inc. All rights reserved.)

Key words. benign calcifying epithelioma of Malherbe � eyebrow � eyelid � hair follicletumor � pilomatrixoma

SURVEY OF OPHTHALMOLOGY VOLUME 53 � NUMBER 5 � SEPTEMBER–OCTOBER 2008

Pilomatrixoma, also termed benign calcifying epi-thelioma of Malherbe, is an uncommon benign skinneoplasm of the hair follicle originally described in1880 by Malherbe and Chenantais as a calcifiedepithelioma of sebaceous glands.34 The term piloma-trixoma was suggested by Forbis and Helwig in1961,16 to denote origin from hair matrix cells andto avoid the use of the word epithelioma, whichusually indicates a malignant tumor.1 Since then,the terms pilomatrixoma or pilomatricoma havebeen universally used to name the lesion.

Pilomatrixoma originates from the matrix of thehair root. It can occur almost anywhere in the bodybut has a propensity to occur in the head and neckregion, often involving the eyelid or eyebrow. It is

52

� 2008 by Elsevier Inc.All rights reserved.

more frequent in children and adolescents. Piloma-trixoma is often misdiagnosed clinically and thecorrect diagnosis can only be established afterexcision and histological examination.

The purposes of this article are to present theclinical and histological data of 16 cases of eyelidpilomatrixoma and to review the relevant ophthal-mic and pathologic literature.

Methods

Records from the Ophthalmic Pathology Labora-tory at the Hadassah-Hebrew University MedicalCenter, Jerusalem, Israel, between the years 1990

6

0039-6257/08/$--see front matterdoi:10.1016/j.survophthal.2008.06.007

EYELID PILOMATRIXOMA 527

and 2006, were retrospectively reviewed. Sixteencases of periocular pilomatrixoma were found.

The following data were extracted from patients’files: age at the time of excision, sex, tumor location,symptoms and signs, suspected clinical diagnosis, grossappearance and tumor dimensions, light microscopicfindings, and postoperative complications.

Paraffin sections stained with hematoxylin andeosin were extracted and examined in all cases.

Results

A total of 10,525 records from the OphthalmicPathology Laboratory, Hadassah-Hebrew UniversityMedical Center, Jerusalem, Israel, between the years1990 and 2006 were reviewed. Sixteen cases of eyelidor eyebrow pilomatrixoma were found (frequency of1:658). Demographic data of the patients andclinical and histopathologic features of the lesionsare described in Table 1. Age at the time of excisionranged from 2 to 59 years (mean 16.5 years, median11 years). Twelve of 16 patients (75% of cases) wereyounger than 13 years. There were eight male andeight female patients. The right eye was involved in9 cases (56%), and the upper eyelid or eyebrow wasinvolved in 11 cases (69%).

All patients presented with a slowly growingasymptomatic nodule (Fig. 1). The skin overlyingthe lesion was normal in all but two cases in whicha red blue tinge was noted (Figs. 2 and 3). In threecases, a history of rapid growth was rereported. All

cases presented with solitary lesions. No concurrentdisorders were observed.

Clinical suspected diagnosis included eyelid cyst(eight cases), eyelid tumor (three cases), piloma-trixoma (two cases), trichoepithelioma (two cases),and dermoid cyst (one case).

All the lesions were completely removed. Therewere no intraoperative or postoperative complica-tions. At gross appearance, the tumors were wellcircumscribed, with spherical or ovoid shape. Thelargest dimensions of the lesion varied from 11 � 10� 9 mm to 4 � 3 � 3 mm. The tumor was located inthe dermis or subcutaneous tissue. It was well-encapsulated in six cases (40%).

Histological findings allowed definitive diagnosisin all cases. The typical lesion revealed one or morelobules of tissue that was basically composed of twotypes of cells, basophilic and shadow cells (Fig. 4).The nucleated basophilic cells were characteristi-cally located at the periphery of the tumor lobulesand the shadow cells in the center. Calcificationswere observed in 8 cases (50%) (Fig. 5A and B), andforeign body giant cell reaction was detected in 12cases (75%) (Fig. 6).

Discussion and Review of the Literature

Only a few small case series1,5,29,42,48,49,59,63 andcase reports of eyelid pilomatrixoma have beenpublished in the ophthalmic literature. As notedearlier, pilomatrixoma is a rare eyelid tumor andpreoperative diagnosis is usually inaccurate. We will

TABLE 1

Demographic Data of the Patients Clinical and Histopathologic Characteristics of the Tumor

PatientNo Sex

Age at Diagnosis(years) Location

Size ofTumor (mm)

PreoperativeDiagnosis

ExternalSkin

GiantCells Calcifications

1 F 2 RUL 9.5�9�9 Dermoid cyst Normal þ þ2 M 45 RUL 11�10�9 Trichoepithelioma Normal þ �3 F 4 LUL 7�4�4 Trichoepithelioma Normal þ þ4 M 12 LLL 9.5�6�5 Pilomatrixoma Normal þ �5 M 59 LUL 5�3.5�3.5 Eyelid cyst Red þ �6 M 27 RUL 6.5�3�3 Eyelid tumor Normal � þ7 F 38 Right eyebrow 8.5�6�5 Eyebrow cyst Normal þ þ8 M 12 LUL 10�8�5 Eyelid cyst Normal þ þ9 F 8 RUL 8�5�3 Eyelid cyst Normal þ �10 M 11 LLL 10�6�5 Eyelid cyst Red � �11 F 3 Right eyebrow 4�3�3 Eyebrow cyst Normal þ þ12 F 10 RLL 6�4�3 Pilomatrixoma Normal þ �13 F 9 RUL 7�5�5 Eyelid tumor Normal � þ14 F 13 LLL 5�5�5 Eyelid cyst Normal þ �15 M 7 RLL 11�5.5�4 Eyelid cyst Normal � þ16 M 4 LUL 9�8.5�4 Eyelid cyst Normal þ �

F5female; M5male; RUL5right upper lid; RLL5right lower lid; LUL5left upper lid; LLL5left lower lid; þ5present;�5absent.

528 Surv Ophthalmol 53 (5) September--October 2008 LEVY ET AL

discuss and review our findings and reported data inpathology and ophthalmology journals.

Pathophysiology

The exact etiology of pilomatrixoma is unknown;however, on the basis of light-microscopy, biochem-ical, enzymatic, polaroscopic, immunohistochemi-cal, and ultrastructural similarities, a hair matrixorigin seems most likely.8,10,15,28 Pilomatrixomas arebelieved to result from a disruption of the normalhair anagen progression.15 The basophilic cells ofpilomatrixoma express high levels of bcl-2 protein,which is a proto-oncogene that helps to suppressapoptosis in both benign and malignant tumors.15 Ithas also been demonstrated that bcl-2 expression inapoptotic shadow cells is absent. The mechanism

Fig. 2. Eyelid pilomatrixoma presenting with reddishdiscoloration of the skin.

Fig. 1. Close-up view of a pilomatrixoma with normaloverlying skin; small chalky white nodules can be seenthrough the skin.

that regulates bcl-2 expression may explain thelimited growth potential and benign biologicbehavior of pilomatrixoma.

At least 75% of examined pilomatrixomas werereported to contain b-catenin-stabilizing mutationsin the gene CTNNB1.8 This percentage of CTNNB1mutations is greater than in all other human tumorsexamined. These authors demonstrated that pilo-matrixomas are derived from hair matrix cells andare typified by expression of the b-catenin proteinLEF-1 (a marker of hair matrix cells). Acquisition ofa b-catenin-stabilizing mutation in CTNNB1 resultsin LEF-1 transactivation, leading to the developmentof human tumors of hair matrix differentiation.8

Fig. 3. Close-up view of a pilomatrixoma with reddishdiscoloration of overlying skin; small chalky white nodulescan be seen through the skin.

Fig. 4. Photomicrograph showing a low-power view ofpilomatrixoma with shadow (sh) and basophilic (bs) cells.Externally, foreign body giant cells (**) are detected(hematoxylin and eosin, original magnification �4).


Fig. 5. A: Photomicrograph showing a low-power view of pilomatrixoma with extensive areas of calcifications(hematoxylin and eosin, original magnification �4). B: Photomicrograph showing shadow cells with calcifications andforeign body giant cell reaction (hematoxylin and eosin, original magnification �10).

Up to one-third of pilomatrixomas express hHb1(human hair keratin basic 1), a newly characterizedhair keratin which is expressed specifically bycortical cells of the normal hair shaft, only inband-like areas containing gradual transitionalcells.10 Neither the basophilic matrix cells nor theshadow cells expressed hHb1, thus suggesting thatpilomatrixomas can differentiate toward corticalcells during their maturation process, as this keratinis specifically expressed in the cortex of the normalhair shaft.

Recently, different types of S100 proteins (S100A2, S100 A3, and S100 A6), which specifically labelkeratin cells within the normal hair follicle, havebeen demonstrated to be expressed in the morpho-logical disordered epithelial elements of pilomatrix-oma, suggesting that various types of aberrantlydifferentiated pilomatrixoma cells evolve from the

Fig. 6. High-power view of several foreign body giantcells (hematoxylin and eosin, original magnification�20).

hair cortex, the hair cuticle, and the inner rootsheath.28

Frequency / incidence

The incidence of pilomatrixoma in dermatohis-topathologic material in a large series of 140,000cases was found to be 1:824,41 although other ratiosof tumor incidence found in the literature varybetween 1:10,500 and 1:316.41 When examining allthe ocular pathology specimens and not only eyelidcases reviewed in our laboratory, we found that theincidence of pilomatrixoma was 1:658.

Pilomatrixoma has been reported to be the mostcommon cutaneous adnexal tumor in patients 20years of age or younger, with a reported incidence ofup to 75% of cases.36

Sex

Most studies report a slight preponderance infemale patients. In the largest series reported, theratio of the pilomatrixoma occurrence for female-to-male patients was 3:2.41 In our study we found anequal frequency of the lesion between male andfemale patients.

Age

Up to 40% of pilomatrixomas arise before the ageof 10 years, and more than 60% of cases in the firsttwo decades.41 Eyelid pilomatrixomas are also morefrequent in children, with a frequency rangingbetween 39% and 73% of cases,48 although a slightpreponderance in young adults and not in childrenhas also been reported.40 These figures are similarto our findings of 75% of cases presenting beforethe age of 13 years. In other large series, a higher


frequency of the lesion in younger patients wasreported, with up to 80% of 150 cases of piloma-trixomas occurring in patients younger than 10years.48 More specifically, the peak age of pre-sentation is 5 to 15 years in female patients and upto 5 years in male patients.24 A second peak ofpresentation has been also reported in adultsbetween 50 and 65 years of age.25 Eyelid piloma-trixoma in older patients has been also reported.58

To the best of our knowledge the exact cause of thehigh preponderance of pilomatrixoma in children isnot addressed in the literature.

When comparing pilomatrixoma with all thelesions removed from eyelids in children, piloma-trixoma is a relatively rare eyelid lesion,19 andrepresents about 1.25% of total eyelid lesions.12

The most frequent eyelid lesions in this study werechalazion (20%), dermoid cyst (16.3%), and papil-loma (14.2%).12 In adult patients, pilomatrixomasshow the same anatomical distribution and presentclinical features similar to those in children andadolescents.25

Race

Most reported cases of pilomatrixoma haveoccurred in whites.41 Whether this representspublication bias or a true racial predisposition dueto a significant higher follicle density on theforehead in whites when compared with Asiansand African-Americans35 is unclear.

Location

The head, upper extremities, neck, trunk, andlower extremities are affected with decreasingfrequency, with up to 40% of cases occurring onthe head.24 Although no precise explanation for thisfact is given in the literature, we can stipulate that itis due to the higher hair follicle density in thescalp.50 It has also been suggested that the distribu-tion of pilomatrixoma can correspond to thedistribution of intermediate hairs, such as those inthe hair border.45 An increase in the number of casereports of pilomatrixomas in dental journals hasalso been reported.62,64 No cases of pilomatrixomahave been reported on the palms, soles, or in thegenital region.13

Lesions involve the periorbital region in up to17% of cases.48 The upper lid and brow are involvedmost frequently, as observed in our series in which69% of cases developed in the upper eyelid oreyebrow. Both right and left sides are equallyaffected.29 An unusual pilomatrixoma case involvingthe tarsal conjunctiva has also been reported.2

Systemic associations

Multiple tumors account for 2% to 3.5% of thereported cases,55 but this incidence may be higherbecause additional tumors may have been over-looked or not examined histologically.11 Accordingto the literature, the occurrence of multiple orrecurring lesions justifies testing to rule out associ-ated disorders, such as Steinert disease (myotonicdystrophy), Gardner syndrome, hypercalcemia, orsarcoidosis. Some authors consider pilomatrixomaa cutaneous marker of myotonic dystrophy, whereasothers have stated that it is due to a pleiotrophiceffect of the gene of the disease.13 The generesponsible for the disease is the DMPK (myotonicdystrophy protein kinase) which plays an importantrole in calcium homeostasis and signal transduc-tion.9 Calcium, in the epidermal cells, influencesthe cellular differentiation; when the calciumconcentration is low, there is a higher cell pro-liferation rate but lower terminal differentiation.This concept might explain the higher frequency ofpilomatrixoma in myotonic dystrophy patients.Familial occurrences are usually accepted as anincidental event and in some of these cases thetumor is associated with myotonic dystrophy,although some authors suggest higher incidences.11

In the suspected cases of pilomatrixoma associatedwith myotonic dystrophy, multiple lesions and familyhistory were more frequent.18 Multiple pilomatrix-omas have been also reported in spina bifida,53

Churg-Strauss syndrome,3 and Rubinstein-Taybisyndrome, a multisystem developmental disorderdefined by the presence of peculiar facies, mentalretardation, and broad thumbs and first toes.7

History

Patients usually present with a solitary nodule thathas been slowly growing over several months oryears.42 Some lesions can have a history of rapidgrowth and be accompanied by tenderness or pain,usually only on pressure.16,37 In cases with a large,rapidly growing mass in adults the clinical diagnosisis very difficult.20 A history of trauma can be elicitedin very few cases.42 In these cases, trauma may playa definite role in producing enlargement of anexisting lesion by causing hemorrhage into thetumor.37 There is rarely ulceration or drainage.16

Time between appearance oftumor and biopsy

The average time between appearance of thetumor and biopsy is reported to be of 4.4 years.41


More recent large series report an earlier time forbiopsy (less than 6 months in up to 60% ofcases).24,42

Preoperative diagnosis

A large proportion of cases are preoperativelydiagnosed as eyelid cyst, mainly epidermal anddermoid cyst.5 In our case series, 9 of 16 cases(56%) were diagnosed as eyelid cyst or dermoid cyst.If a patient, mainly young, has a firm, gritty,subcutaneous mass in the upper eyelid or eyebrowarea, a pilomatrixoma should be suspected.60

Accurate preoperative diagnosis is achieved inonly 28.9% to 43% of cases.31,54 The reportedcharacteristics that led to accurate diagnosis priorto excision were found to be as follows:48

� The lesions were not freely movable from theoverlying skin, because the vast majority ofpilomatrixomas are located in the dermis.� The lesions were rock hard, irregularly shaped

and nodular, and chalky white nodules due tothe calcifications could be seen through theskin.� The lesions can have reddish to blue

discoloration.

Clinical findings

The skin overlying the lesion is usually normal orpresents some reddish or bluish discoloration.42,63

In our case series, all but two lesions presented withnormal overlying skin (Fig. 1). Very rarely, reddish-purple lesions have been observed, probably result-ing from hemorrhage. Calcification in the lesioncan cause stretching of the overlying skin, resultingin a multifaceted angulated appearance, known asthe tent sign. In some cases of superficial tumors,calcium can erode the surface and extrude.24 Otherrare variants described are keratotic appearance,resembling a squamous cell carcinoma; basal cellcarcinoma appearance, with telangiectasia androlled edges; vascular variant, with red/blue colorof the lesion (Figs. 2 and 3); and anetodermicvariant, with the overlying skin being stretched andatrophic.24

Gross appearance

In most cases, tumor diameter ranges from 0.5 to3 cm,13 but lesions up to 15 cm have been reportedin the parotid area.30 In the majority of the eyelidreported cases, the tumor is smaller than 1 cm.63

The largest dimensions of our reported cases variedfrom 11 � 10 � 9 mm to 4 � 3 � 3 mm.

The tumors are usually well circumscribed,spherical or ovoid, and sometimes encapsulated.42

The degree of encapsulation varies from case to caseand within an individual tumor.5 On cut section, thelesions are grey, white, or brown with yellowstreaks.16 Their consistency varies from soft tofriable, firm and even stony hard. Most tumors arelocated in the dermis.

Light microscopic findings

Pathologic diagnosis of pilomatrixoma is based onthe finding of large masses of shadow cells, some ofwhich may be calcified, combined with the followingfeatures: basophilic cells, inflammation, foreign bodygiant cells, calcification and ossification, and hemor-rhage (Fig. 4).5 The tumor is composed of sheets andconvolute bands of epithelial cells separated byconnective tissue stroma. The tumor cells are of twotypes: basophilic and shadow.42 The basophilic cellsare characteristically located at the periphery of thetumor and have deeply basophilic, round to ovalnuclei surrounded by scanty pale cytoplasm. Pro-gressing centrally, the basophilic cells show a gradualloss of nuclei resulting in the formation of shadowcells. The shadow cells exhibit a central unstainedarea from which the nucleus has disintegrated,surrounded by faint eosinophilic cytoplasm (Fig. 7).Mitotic figures are frequent in the basophilic cells butabsent in the shadow cells (Fig. 8). Cells in the processof transformation from basophilic to shadow cells,but with pyknotic nuclei, are identified as transitionalcells (Fig. 9A and 9B).42 Shadow cells, although alwayspresent in the lesion, are not pathognomonic ofpilomatrixoma, because they have been reported in

Fig. 7. Photomicrograph showing typical shadow cells(hematoxylin and eosin, original magnification �20).


epidermoid cyst, chronically inflamed hair follicle,and in small numbers in chronic dermatoses withhyperkeratosis.4

The reported incidence of calcification rangesfrom 69% to 85%.16,41 Bone metaplasia is observedin 15% of cases, usually at the site of calcifieddeposits.5,16 Foreign body giant cells are frequentlynoted around the calcified epithelial cell mass.41 Weobserved calcifications in 9 cases (56%) and foreignbody giant cell reaction in 12 cases (75%). Materialreacting to periodic-acid-Schiff staining is observedonly in the shadow cell areas of the tumor.52

The histopathological features of each piloma-trixoma depend on the stage of its development.42

The earlier the stage of the lesion, the morenumerous the basophilic cells; as the lesion prog-resses, an increasing number of shadow cells andamorphous debris are seen. In advanced stages, thetumor contains large masses of shadow cells with

Fig. 8. Photomicrograph showing mitotic figuress in thebasophilic cells (hematoxylin and eosin, original magni-fication �40).

varying degrees of calcification. Finally, the tumorcells can be almost totally replaced by compactbone, leaving only small numbers of calcifiedshadow cells to identify the nature of the lesion.The proposed terms for these four chronologicaland morphological stages of pilomatrixoma areearly stage, fully developed stage, early regressivestage, and late regressive stage, reflecting the life ofa pilomatrixoma, which begins as an infundibularmatrix cyst and ends up as a calcified and ossifiednodule with no visible epithelial component.26

In rare cases, the tumor mass can extrude fromthe skin surface through a perforating epidermalchannel, and this lesion is termed a perforatingpilomatrixoma.44 A case of pilomatrixoma confinedto the epidermis with cutaneous horn induction hasbeen also described.17

Diagnosis

The diagnosis of pilomatrixoma is usually madeafter the histological examination of the excisedlesion. However, some tests can help in selectedcases. Fine-needle aspiration can be used to givea strong presurgical diagnosis.38 However, misinter-pretation of the lesion as carcinoma and basal cellcarcinoma has been reported.32 The presence ofghost cells, basaloid cells, and calcium deposits inthe appropriate clinical setting permits diagnosis. Ifcalcification is shown in imaging, the diagnosis canbe made more precisely.59,64 Ultrasonography ofsuspected pilomatrixoma in children may be a usefuland noninvasive procedure with accurate diagnosisin a high percentage of cases and has been used forselected cases of eyelid lesions.21,22 The lesionappears as an ovoid complex mass at the junctionof the dermis and the subcutaneous fat, with focalthinning of the overlying dermis. It consistentlypresents as a target lesion with a hypoechoic rim,

Fig. 9. A: The transition from basophilic cells to shadow cells extends over an area of several cell layers (hematoxylin andeosin, original magnification �10). B: Photomicrograph showing transitional cells with basophilic granules resemblingkeratohyalin (hematoxylin and eosin, original magnification �40).


corresponding to the connective tissue capsule, andan echogenic center, corresponding to the centralislands of epithelial cells.21

Differential diagnosis

Eyelid pilomatrixomas are usually preoperativelymisdiagnosed. The clinical misdiagnosis appears tobe related to the patient’s age. In children,epidermal and dermoid cysts are the most commonlesions that must be differentiated from eyelidpilomatrixoma.48 Epidermal cysts, unlike piloma-trixomas, are smooth, round, and firm, and do nothave chalky nodules seen in the dermis. They areusually seen in adolescents and adults, whereaspilomatrixomas are most often seen in youngchildren. Both lesions are equally distributed onthe face, but pilomatrixoma is considerably morecommon on the neck and arms, and epidermal cystsare more common on the scalp.16 Dermoid cystshave normal overlying skin and are more firmlyadherent to the underlying tissues. They are smoothand firm, and do not have chalky white nodules seenin the dermis.

Eyelid pilomatrixoma can also be preoperativelymisdiagnosed as pyogenic granuloma or a chala-zion.23,27 If a chalazion involves the overlying skinanterior to the tarsus, it may become inflamed, butit does not show the blue discoloration, the chalkywhite deposits, or the superficial telangiectaticvessels that frequently occur with pilomatrixomas.63

Other dermal lid tumors should be considered inthe differential diagnosis of pilomatrixoma. Thelipid-laden cells of sebaceous adenoma, hyperplasiaor carcinoma can give a similar yellowish color tothese tumors, but there are usually lesions of laterlife rather than childhood.51 Juvenile xanthogranu-loma may occur as an isolated lid tumor, usually inpatients 2 years of age or younger. In light-skinnedpatients these tumors are distinctively orange.Rhabdomyosarcoma may arise as an isolated lidtumor with a blue-purple discoloration of theoverlying skin, but its characteristic fast rate ofgrowth differentiates it from pilomatrixoma.51 Cap-illary hemangiomas that arise in the subcutaneoustissue without involving the skin can have a blue-purple color similar to pilomatrixoma, but thatlesion tends to be soft and compressible bypalpation, and its growth is much faster thanpilomatrixoma.37

In adults, a red-blue lid discoloration should bedifferentiated from a large epidermoid cyst,dermoid cysts, cavernous vascular tumors, andbenign hair follicle-derived eyelid tumors, such astrichoepithelioma, trichilemmoma, trichoblastoma,and inverted follicular keratosis, in approximately

65% of which the diagnosis is histologic, without anyclear previous clinicopathologic correlation.20,61

Other clinical differential diagnoses in adults in-clude basal cell carcinoma, keratoacanthoma, andcutaneous metastasis.25,49 Rare cases of rapidlyulcerating lesions can be mistaken for cutaneouslymphoma, sarcoma, or squamous cell carcinoma.33

Confirmation by incisional biopsy of the nature ofany large lesion suspected of being a basal cellcarcinoma is essential in order to avoid performingan unnecessarily extensive time consuming excisionwhen the accurate diagnosis is pilomatrixoma.61

Treatment

Spontaneous regression of pilomatrixoma hasnever been observed. The treatment of choice isexcision with wide margins,13 although there are alsoreports suggesting the use of Mohs micrographicsurgery.56 As noted previously, incomplete resectionshave been followed by local recurrence;47 wideresection margins are recommended to minimizethe risk of recurrence. No special considerations forthe excision of the tumor are reported in theophthalmic literature. If the patient has undergonea number of minor procedures before diagnosis,definitive surgical excision may be difficult becausethe exact location of the tumor margin may beobscured.6 Because the tumor may be tightly adher-ent to the skin, it may be necessary to remove theoverlying skin. However, the tumor is never adherentto subcutaneous tissue, and separation from theunderlying skin is always easy.13 Recently, goodcosmetic results with endoscopic excision of fore-head/brow pilomatrixomas have been reported.14

Recurrence

Forbis and Helwig reported a 2.6% recurrencerate after surgical excision in 1961,16 althoughsubsequent reports with longer follow-up periodshave shown an almost zero rate of recurrence.Recurrence is less likely with encapsulated lesionsbecause complete resection is easier.13 Incompleteexcision of the lesion can lead to recurrence.5

Secondary pilomatrixomas in new locations aftersuccessful primary surgical excision are rare, withdecreased incidence with age.13 However, closesurveillance after local recurrence has been sug-gested, based on the case of one patient developinga malignant secondary lesion 17 years after the firstoccurrence.39

Pilomatrix carcinoma

The malignant variant of pilomatrixoma (piloma-trix carcinoma) is extremely rare, with only a few


reports in the literature.6,39,43,46,57 It occurs moreoften in middle-aged men, and is usually located inthe head and neck, but very rarely on the eyelid.6,57

The average size of pilomatrix carcinoma is muchlarger than that of benign pilomatrixoma. Micro-scopically, pilomatrix carcinoma is characterized byabundant proliferation of basaloid cell massesarranged haphazardly throughout the tumor anddisplaying an infiltrative growth pattern and extend-ing into deeper soft tissues.57 Varying degrees ofcytologic atypia, frequent mitoses, and areas ofnecrosis are commonly observed.

Pilomatrix carcinomas are locally aggressive tu-mors that have a tendency to recur, especially whenthey are incompletely excised. They have a recur-rence rate as high as 59%. They can metastasize tothe lungs, bone, and viscera, with poor out-come.39,43,46,57 Wide excision is the preferredtreatment, whereas the role of radiotherapy andchemotherapy in the treatment of disseminateddisease is unclear.46

Summary

Pilomatrixoma is an uncommon eyelid tumor thatis more frequent in children and adolescents. It iscommonly misdiagnosed preoperatively, althoughthere are characteristic clinical features of the lesionthat can help clinicians to differentiate it from othertumors seen in children. If a child or young patienthas a firm subcutaneous mass in the upper eyelid oreyebrow area, a pilomatrixoma should be suspected.Complete surgical excision is always curative.

Method of Literature Search

A search of the PubMed database for the years1966--2007 was conducted using various combina-tions of the key words pilomatrixoma, pilomatricoma,calcifying epithelioma of Malherbe, pilar tumor, matrixtumor, hair follicle tumor, malignant pilomatrixoma,pilomatrix carcinoma, eyelid tumor, lid tumor, histopath-ologic examination. Articles in all languages wereconsidered, provided that the non-English articlesincluded English abstracts. Relevant articles thatwere cited in the reference lists of the retrievedarticles were also included. All reports related topilomatrixoma located on the eyelid or eyebrowwere included. Selected reports on pilomatrixomasat other locations and reports of other types oftumors with similar features were included forpurposes of comparison.

References

1. Ashton N: Benign calcified epithelioma of eyelid. TransOphthalmol Soc UK 71:301--7, 1951

2. de Azevedo ML, Milani JA, de Souza EC, Nemer RS:Pilomatrixoma. An unusual case with secondary cornealulcer. Arch Ophthalmol 103:553--4, 1985

3. Bayle P, Bazex J, Lamant L, et al: Multiple perforating andnon perforating pilomatricomas in Churg-Strauss syndromeand Rubinstein-Taybi syndrome. J Eur Acad DermatolVenereol 18:607--10, 2004

4. Bingul O, Graham JH, Helwig EB: Pilomatrixoma (calcifyingepithelioma) in children. Pediatrics 30:233--40, 1962

5. Boniuk M, Zimmerman LE: Pilomatrixoma (benign calcify-ing epithelioma) of the eyelids and eyebrow. Arch Oph-thalmol 70:399--406, 1963

6. Cahill MT, Moriarty PM, Mooney DJ, Kennedy SM: Pilomatrixcarcinoma of the eyelid. Am J Ophthalmol 127:463--4, 1999

7. Cambiaghi S, Ermacora E, Brusasco A, et al: Multiplepilomatricomas in Rubinstein-Taybi syndrome: a case report.Pediatr Dermatol 11:21--5, 1994

8. Chan EF, Gat U, McNiff JM, Fuchs E: A common human skintumour is caused by activating mutations in beta-catenin.Nat Genet 21:410--3, 1999

9. Cigliano B, Baltogiannis N, De Marco M, et al: Pilomatrico-ma in childhood: a retrospective study from three Europeanpaediatric centres. Eur J Pediatr 164:673--7, 2005

10. Cribier B, Asch PH, Regnier C, et al: Expression of humanhair keratin basic 1 in pilomatrixoma. A study of 128 cases.Br J Dermatol 140:600--4, 1999

11. Demircan M, Balik E: Pilomatricoma in children: a pro-spective study. Pediatr Dermatol 14:430--2, 1997

12. Doxanas MT, Green WT, Arentsen JJ, Elsas FJ: Lid lesions ofchildhood: a histopathologic survey at the Wilmer Institute.J Pediatr Ophthalmol 13:7--39, 1976, 1923--1974

13. Duflo S, Nicollas R, Roman S, et al: Pilomatrixoma of thehead and neck in children: a study of 38 cases and a reviewof the literature. Arch Otolaryngol Head Neck Surg 124:1239--42, 1998

14. Dutta S, Lorenz HP, Albanese CT: Endoscopic excision ofbenign forehead masses: a novel approach for pediatricgeneral surgeons. J Pediatr Surg 41:1874--8, 2006

15. Farrier S, Morgan M: bcl-2 expression in pilomatricoma. AmJ Dermatopathol 19:254--7, 1997

16. Forbis R Jr, Helwig EB: Pilomatrixoma (calcifying epitheli-oma). Arch Dermatol 83:606--18, 1961

17. Garcıa de la Torre JP, Saiz A, Garcıa-Arpa M, Rodrıguez-Peralto JL: Pilomatricomal horn: a new superficial variant ofpilomatricoma. Am J Dermatopathol 28:426--8, 2006

18. Graells J, Servitje O, Badell A, et al: Multiple familialpilomatricomas associated with myotonic dystrophy. Int JDermatol 35:732--3, 1996

19. Hsu HC, Lin HF: Eyelid tumors in children: a clinicopath-ological study of a 10-year review in southern Taiwan.Ophthalmologica 218:274--7, 2004

20. Huerva V, Sanchez MC, Asenjo J: Large, rapidly growingpilomatrixoma of the upper eyelid. Ophthal Plast ReconstrSurg 22:401--3, 2006

21. Hughes J, Lam A, Rogers M: Use of ultrasonography in thediagnosis of childhood pilomatrixoma. Pediatr Dermatol 16:341--4, 1999

22. Hwang JY, Lee SW, Lee SM: The common ultrasonographicfeatures of pilomatricoma. J Ultrasound Med 24:1397--402,2005

23. Izquierdo-Rodrıguez C, Mencıa-Gutierrez E, Gutierrez-Dıaz E, Suarez-Gauthier A: An unusual presentation ofa pilomatrixoma in the eyelid. Arch Soc Esp Oftalmol 81:483--6, 2006

24. Julian CG, Bowers PW: A clinical review of 209 pilomatrico-mas. J Am Acad Dermatol 39:191--5, 1998

25. Kaddu S, Soyer HP, Cerroni L, et al: Clinical andhistopathologic spectrum of pilomatricomas in adults. Int JDermatol 33:705--8, 1994

26. Kaddu S, Soyer HP, Hodl S, Kerl H: Morphological stages ofpilomatricoma. Am J Dermatopathol 18:333--8, 1996

27. Katowitz WR, Shields CL, Shields JA, et al: Pilomatrixoma ofthe eyelid simulating a chalazion. J Pediatr OphthalmolStrabismus 40:247--8, 2003


28. Kizawa K, Toyoda M, Ito M, Morohashi M: Aberrantlydifferentiated cells in benign pilomatrixoma reflect thenormal hair follicle: immunohistochemical analysis of Ca-binding S100A2, S100A3 and S100A6 proteins. Br JDermatol 152:314--20, 2005

29. Kleener J: Pilomatrixoma (epithelioma calcificans Mal-herbe). A clinical and histopathological survey of Danishmaterial from 1954 to 1971. Acta Ophthalmol (Copenh) 51:692--9, 1973

30. Krausen AS, Ansel DG, Mays BR Jr: Pilomatrixoma masquerad-ing as a parotid mass. Laryngoscope 84:528--35, 1974

31. Kumaran N, Azmy A, Carachi R, et al: Pilomatrixoma—accuracy of clinical diagnosis. J Pediatr Surg 41:1755--8,2006

32. Lemos LB, Brauchle RW: Pilomatrixoma: a diagnostic pitfallin fine-needle aspiration biopsies. A review from a smallcounty hospital. Ann Diagn Pathol 8:130--6, 2004

33. Lozzi GP, Soyer HP, Fruehauf J, et al: Giant pilomatricoma.Am J Dermatopathol 29:286--9, 2007

34. Malherbe A, Chenantais J: Note sur l’epithelioma calcifiedes glandes sebacees. Prog Med 8:826--37, 1880

35. Mangelsdorf S, Otberg N, Maibach HI, et al: Ethnicvariation in vellus hair follicle size and distribution. SkinPharmacol Physiol 19:159--67, 2006

36. Marrogi AJ, Wick MR, Dehner LP: Pilomatrical neoplasms inchildren and young adults. Am J Dermatopathol 14:87--94,1992

37. Mathen LC, Olver JM, Cree IA: A large rapidly growingpilomatrixoma on a lower eyelid. Br J Ophthalmol 84:1203--4, 2000

38. McBrien M, Victor T, Wolff AP: Pathologic quiz case 2.Pilomatrixoma. Arch Otolaryngol Head Neck Surg 114:1042--3, 1045, 1988

39. McCulloch TA, Singh S, Cotton DW: Pilomatrix carcinoma andmultiple pilomatrixomas. Br J Dermatol 134:368--71, 1996

40. Mencıa-Gutierrez E, Gutierrez-Dıaz E, Garcıa-Suarez E,Ricoy JR: Eyelid pilomatricomas in young adults: a reportof 8 cases. Cutis 69:23--6, 2002

41. Moehlenbeck FW: Pilomatrixoma (calcifying epithelioma).A statistical study. Arch Dermatol 108:532--4, 1973

42. Ni C, Kimball GP, Craft JL, et al: Calcifying epithelioma:a clinicopathological analysis of 67 cases with ultrastructuralstudy of 2 cases. Int Ophthalmol Clin 22:63--86, 1982

43. Niedermeyer HP, Peris K, Hofler H: Pilomatrix carcinomawith multiple visceral metastases. Report of a case. Cancer77:1311--4, 1996

44. Niitsuma K, Kuwahara M, Yurugi S, Iioka H: Perforatingpilomatricoma on the upper eyelid. J Craniofac Surg 17:372--3, 2006

45. Noguchi H, Hayashibara T, Ono T: A statistical study ofcalcifying epithelioma, focusing on the sites of origin. JDermatol 22:24--7, 1995

46. O’Donovan DG, Freemont AJ, Adams JE, Markham DE:Malignant pilomatrixoma with bone metastasis. Histopa-thology 23:385--6, 1993

47. O’Grady RB, Spoerl G: Pilomatrixoma (benign calcifyingepithelioma of Malherbe). Ophthalmology 88:1196--7, 1981

48. Orlando RG, Rogers GL, Bremer DL: Pilomatricoma ina pediatric hospital. Arch Ophthalmol 101:1209--10, 1983

49. Ozdal PC, Callejo SA, Codere F, Burnier MN: Benign ocularadnexal tumours of apocrine, eccrine or hair follicle origin.Can J Ophthalmol 38:357--63, 2003

50. Otberg N, Richter H, Schaefer H, et al: Variations of hairfollicle size and distribution in different body sites. J InvestDermatol 122:14--9, 2004

51. Perez RC, Nicholson DH: Malherbe’s calcifying epithelioma(pilomatrixoma) of the eyelid. Clinical features. ArchOphthalmol 97:314--5, 1979

52. Peterson WC Jr, Hult AM: Calcifying epithelioma ofMalherbe. Arch Dermatol 90:404--10, 1964

53. Pielop JA, Metry D: Multiple pilomatricomas in associationwith spina bifida. Pediatr Dermatol 22:178--9, 2005

54. Pirouzmanesh A, Reinisch JF, Gonzalez-Gomez I, et al:Pilomatrixoma: a review of 346 cases. Plast Reconstr Surg112:1784--9, 2003

55. Rotenberg M, Laccourreye O, Cauchois R, et al: Head andneck pilomatrixoma. Am J Otolaryngol 17:133--5, 1996

56. Sable D, Snow SN: Pilomatrix carcinoma of the back treatedby Mohs micrographic surgery. Dermatol Surg 20:1174--6,2004

57. Sau P, Lupton GP, Graham JH: Pilomatrix carcinoma.Cancer 71:2491--8, 1993

58. Seitz B, Holbach LM: Medial canthus pilomatrixoma in an80-year-old patient. Klin Monatsbl Augenheilkd 203:444--5,1993

59. Seitz B, Holbach LM, Naumann GO: Pilomatrixoma of theeyelids—clinical differential diagnosis and follow-up. Reportof 17 patients. Ophthalmologe 90:746--9, 1993

60. Shields JA, Shields CL, Eagle RC Jr, Mulvey L: Pilomatrix-oma of the eyelid. J Pediatr Ophthalmol Strabismus 32:260--1, 1995

61. Simpson W, Garner A, Collin JR: Benign hair-follicle derivedtumours in the differential diagnosis of basal-cell carcinomaof the eyelids: a clinicopathological comparison. Br JOphthalmol 73:347--53, 1989

62. Strobl H, Emshoff R: Pilomatrixoma of the cheek: report ofcase. J Oral Maxillofac Surg 53:1355--7, 1995

63. Yap EY, Hohberger GG, Bartley GB: Pilomatrixoma of theeyelids and eyebrows in children and adolescents. OphthalPlast Reconstr Surg 15:185--9, 1999

64. Yoshimura Y, Obara S, Mikami T, Matsuda S: Calcifyingepithelioma (pilomatrixoma) of the head and neck: analysisof 37 cases. Br J Oral Maxillofac Surg 35:429--32, 1997

The authors reported no proprietary or commercial interest inany product mentioned or concept discussed in this article.

Reprint address: Jacob Pe’er, MD, Department of Ophthalmol-ogy, Hadassah-Hebrew University Medical Center, P.O. Box 12000,Jerusalem 91120, Israel.

Eyelid Pilomatrixoma: A Description of 16 cases and a Review of the Literature

Documents

Transcript of Eyelid Pilomatrixoma: A Description of 16 cases and a Review of the Literature