Pi lomatrica I Ca rci noma:Case Report and Review ofthe LiteratureTony Nakhla, DO; Michael Kassardjian, DO

Pilomatrical carcinoma is a rare malignant tumor that originates from hair matrix cel ls. Pi lomatrical

carcinoma may arise de novo as a sol i tary lesion, or through transformation from its benign

counterpart, pi lomatrixoma. Differentiat ion between pi lomatrixoma and pi lomatrical carcinoma

requires close histologic examination and often is diff icult. Although uncommon, pi lomatrical

carcinoma has the potential to metastasize; therefore, prompt diagnosis and appropriate manage-

ment is essential.

i lomatrical carcinoma is the malignant

counterpart of pilomatrixoma, a benign

cutaneous tumor originating from the hair

ma[rix. It is a rare, aggressive tumor with a

high probability of recurrence after simple

excision, and the potential to metastasrze.

We report a case of a 56-year-old white man

diagnosed with pilomatrical carcinoma. The patient

presented with a 2-month history of ar1 enlarging

asymptomatic growth on the cheek. Physical exami-

nation revealed a 2-cm, well-demarcated, nontender,

moveable, hard subcutaneous nodule on the right

mandible (Figure l). No skin changes or lymphad-

enopathy was noted. The clinical diagnosis strongly

favored a calcified epidermoid cyst or other benign

adnexal tumor. An excisional biopsy was performed at

the request of the patient.

Sections were evaluated histologically and revealed

a multifragmented biopsy of dermal and subcutaneous

tissue containing basaloid proliferation with collections

of ghost cel ls, typical of pi lomatrixoma (Figure 2).

Dr. I'laLthla is from OC Shin Institute, Santa Ana, California.

Dr. Kassardlian is an intern, Pacific Hospital, Long Beach, California.

The authors report no conflict tf interest in relation to

this article.

Correspondence: Michael Kassardjian, DO, PO Box 2152,

Palos Verdes Pen, CA 90275 (miheygh@gmail.com).

3I4 Cosmetic Dermatology@ . JULY 2010 . vol. 23 No. 7

In som e areas, the lesional cells are relatively bland and

noninfiltrative appearirg.

However, this case also shorvs areas with larger more

squamoid appearing cells urth aLyprcal features, includ-

irg Iargenuclei with prominent nucleoli as well as areas of

infiltrative appearing cells, features highly concerning for

malignancy (Figure 3). In the infiltrative appearrngarea,

there is dense stromal sclerosis associated u-ith highly

atyprcal squamoid and spindle cells, with ser-eral mitotic

figures found within these cells (Figure +) In many

areas of the biopsy, there is granulomatolls inflamma-

tion, hemorrhage , and granulation tissue consistent

with a reaction to ruptured material from the tumor

(Figure 5) While the latter findings often are seen in

ruptured pilomatrixoma, the infiltratn\-e areas with

atyprcal spindle cells would not be erpected in a

benign pilomatrixoma, and the findings are most con-

sistent with a diagnosis of malignant pliomarrixoma

(pilom afitcal carcinoma) .

Mult iple laboratory tests using immunohrstochemi-

cal stains, including p63, cytokeratrn i /6, synap-

tophysin, p53, and Ki-67 also \\-ere rer- iewed. The

tumor cells were strongly and diffusely- positive for

p63, highlighting the nuclei of the infiltrative and

spindle cells, which is positirre in mos[ primary cuta-

neous malignancies including adnexal carcinomas. In

addition, results of cytokeratin 5/6 staining aiso were

moderately positive within lesional cells, including the

www.cosderm.com

infi ltrative-appearing spindle cells, which confirmed

that these were epithel ial, and not mesenchymal,

ceiis R.esults of synaptophysin staining were nega-

[ l \-e and not consistent with a neuroendocrine tumor

such as \ ierkel cel l carcinoma. Staining for p53 was

r.,'eakir b'-ri difiusely positive throughout the tumor cell

nuclei. rnc^'-rd.rnE the infiltrative areas, a finding that

also far-ored :rahgnancy. In addit ion, Ki-67 posit ivi ty

was high u ithrn thre basaloid cells and also positive

within man\ c[ rhe spindle cells, highlighting up to

L}o/o of the entrre lesion. Thus, the overal l histologic

and immunohistochemical f indings supported the

diagnosis of pi lomalncal carcinoma.

COMMENTPilomatrixoma first \\-as de scribed in 1BB0 by Malherbe

and Chenantaisr as a calci.it 'tng epithelioma that was

thought to originate from the sebaceous gland. In

L949, Lever and Griesemerr suggested that the actual

origin of the tumor was the harr matrix.3 Thus, the

approprlaLe term pilomatrtxonta was adopted, synony-

mous with calcifying epithehoma of Malherbe, which

also is commonly used.

Clinically, the tumor is described as a solitary, slow

growing, asymptomatic, dermai or subcutaneous mass

that mosl commonly is found in the posterior neck,

upper back, and preauricular area. Duration of tumors

prior to surgery has been reported to range from

4 months to 10 years.3 Pilomatrical carcinomas have

been reported to range in size from 0.5 cm to 20 cff i ,

with a mean of 3.95 cm, which is slightly larger than its

benign counterpart, pilomatrixoma.a The consistency

www.cosderm.com

Figure 1. A 56-year-old whi te man with a2-cm, well-demarcated, nontender, move-able, hard subcutaneous nodule present onthe r ight mandible wi th no skin changes.

of the tumors may vary from soft and friable to firm.They may have red, yellow, white, and tan skinchanges. Lesions cannot reliably be distinguishedbased solely on clinical appe arance, and frequentlyare mistaken for epidermal cysts. The diagnosis ofpilomatrical malign ancy is made exclusively by carefulhistologic evaluation.

Pilomatrical carcinoma has a potential to metast asrzein about 10o/o of cases.5 Cases of metastasis to the lung,bones, and lymphatics, ds well as invasion into thecranial vault, have been reported.3

EPIDEMIOLOGYThe epidemiology of pilomatrical carcinoma differs

from pilomatrixomas. Pilomatrixomas more often are

seen in women (female to male rat io of 3: I ) and

tend to occur in patients younger than 20 years. The

mean age of patients diagnosed with pilomatrixoma is

B .7 years, rangirg from B months to 19 years.5

Pilomatrixomas occur most commonly on the head,

followed by the upper extremities, neck, trunk, and

lower extremities.3 Involvement of the face has been

reported in the frontal, temporal, cheek, periorbital,

and preauricular regions.6 Pilomatrical carcinomas are

more predominant in men and more often middle-

aged or elderly adults. The mean age of patients with

pilomat.rical carcinoma is 48 years, ranging from 2 to

BB years, and in this populat ion are more common

in the posterior neck, upper back, and preauricu-

lar area.3'4 Approximately 60o/o of tumors have been

located on the head, among which half are in the

preauricular region.T

vol. 23 No. 7 . JULv 2010 . Cosmetic Dermatology@ 315

PnouATRIcnr CaRcINoMA

Figure 2. A fragrnented biopsy specimen revealed

basaloid prol i ferat ion and ghost cel ls (H&E, or ig inal

magnif icat ion x 100).

Figure 3. Inf i l t rat ive squamoid and spindle cel ls

with atypical features, including large nuclei

wi th prominent nucleol i (H&E, or ig inal magnif ica-

t ion x400).

HISTOPATHOLOGYThe histologic differential diagnosis of pilomatrical

carcinoma includes pilomatrixoma, squamous cell

carcinoffi?, trichoepithelioma, ly-phoepitheliomalike

316 Cosmetic Dermatology@ . JULY 2010 . vot-. 23 No. 7

carcinoma of the skin, and mixed tumors of the skin.7

Pilomatrical carcinomas have the characteristic features

of epithelial islands of pleomorphic basaloid cells with

vesicular nuclei and prominent nucleoli. Shadow or

www.cosderm.com

l

ghost cells, along with zones of necrosis with surround-ing stromal desmoplasia also are observed. The basaloidcells have deeply basophilic oval or round nuclei and arefound at the periphery of the islands. A transition zorae

www.cosderm.com

PnouATRrcAL CARCTNoMA

Figure 4. Stromal sclerosis, highly atypical squa-moid and spindle cells, and several mitotic figures(H&E, original magnification X400).

Figure 5. Areas of hemorrhage and granulation tis-sue surrounded by infiltrative atypical spindle cells(H&E, original magnification X400).

of retained nuclei from basaloid cells to the anucleate,eosinophilic shadow cells often is seen.8 Tumor necrosisusually is present, as well as frequent atypical mitoticfigures. Basaloid cells may infiltrate the entire dermis and

VOL. 23 NO. 7 . JULY 2010 . Cosmetic Dermatology@ 317

PrlouATRrcAL CnncrNoMA

extend into the subcutaneous fat, deep fascia, and skel-etal. muscle. In pilomatrical carcinoma, the shadow cellstend to form a nested pattern, instead of the flat sheet-like pattern usually observed in benign pilomatrixomas.3Histologic criteria for pilomatrical carcinoma includevessel invasion, mitotic index, apoptotic count, as well asmolecular markers of cell death and adhesion.e

IMMUNOHISTOCHEMISTRYImmunohistochemical studies have not d.finirively

distinguished the markers that differentiate piloma-

trixomas from pilomatrical carcinomas . Lazar et alI0

studied a series of 15 pi lomatrical carcinomas and

13 benign pilomatrixomas to assess expression of

B,-catenin using immunohistochemical staining and

DNA sequencing of exon 3 from the Bl-catenin gene,

CTNNBI, the defect that leads to the expression of

pilomatrixomas. B-Catenin is a downstream effector in

the Wnt signaling pathway that signals for proliferarion

and differentiation. Mutations in the CTNNBI gene

encoding B-catenin are present in both benign and

malignant neoplasms. A11 cases showed nuclear local-

tzatton of B-catenin, mutations on exon 3, as well as

expression of nuclear cyclin D 1 . Howev er, 2 pilomatri-

caI carcinomas exhibited accumulation of p53, which

was absent in aIL 13 benign pilomatrixomas. I0 Past

studies also have reported high constant expression of

CD44v6 and P-cadherin. 11

TREATMENTThe most widely reported treatment for pilomatrical

carcinoma is wide local excision with histologically

confirmed clear margins. Because pilomatrtcal carcinoma

is identifiable by hematoxylin and eosin srain, Mohs

micrographic surgery also is an excellent treatment

option. Currently, there is no consensus on surgical man-

agement, and standard excisional margins have not been

defined.s Adjuvant radiation therapy may be necessary

postexcision. Chemotherapy has been used in cases of

extensive tumor invasion and in cases of metastasis.

Appropriate Iaboratory testing includes liver func-

tion tests, calcium levels, and chest x-ray examination.

If aggressive local invasion is suspected, a computed

tomography scan or magnetic resonance imaging

should be performed to define tumor extension.T Past

studies have found that the radiologic findings of pilo-

matrixoma typically demonstrate a well-circumscribed

lesion with homogeneous or sandlike calcifications on

plain radiograph and computed tomography studies.12

Niwa et aIa reported a case of pilomatrical carcinoma

of the axilla, which demonstrated a diffuse inhomoge-

neous mass with cystic changes on magnetic resonance

rmaging. Areas of low signal intensity corresponded to

318 Cosmetic Dermatology@ . JULv 2010 . vol. 23 No. Z

calcifications, while the inhomogeneous signal intensi-ties related to varying degrees of tumor proliferation.High signal intensity was atrributable ro cysric spacesforming in areas of tumor necrosis

Pilomatrical carcinoma is a rare malignant formof pi lomatrixoma, which arises from hair matr ixcells. Careful histologic evaluation is necess ary todistinguish benign pilomarrixoma from pilomarri-cal carcinoma. Pi lomatrical carcinoma rnay arisede novo or from a preexisting benign pilomatrixoma,

which may be clinically indistinguishable. In caseswhere previously excised or curetted pilomatrixomasrecur, a reexcision with careful histologic evaluationis indi cated.T

Pilomatrical carcinoma occurs more often in middle-aged to older individuals, more commonly in men,and has a predilection for the posterior neck, upperback, and preauricular area. Pilomatrical carcinomasfrequently recur; however, treatment with wide localexcision or Mohs micrographic surgery has beenshown to lower the raLe of recurrence.4,5

Distant metastases have been reported in up to l0o/oof cases.5 Due to the potential for metastasis, promptdiagnosis fol lowed by wide local excision or Mohsmicrographic surgerl- and close clinical and radiologicfol low-up is recommended.

REFERENCES1. Malherbe A, Chenantais J. \ore sur lepirheliome calcifie des

glandes sebaces. Prog JIed LSS0:325-837.2. Lever Wf; Griesemer RD. Calficnng epithelioma of Malherbe;

report of 15 cases, riith ccT-nrnenis on its differentiation from cal-cified epidermal cyst anC on iis histogenesis. Arch Derm Syphilol.L949;59:506-5 18.

3. sau B Lupton GB Graham JH. Pilomatrix carcinoma. cancer.L993:7 L:249L-2498.

4. Niwa T, Yoshida T. Doiuchi T, et al. Pilomatrix carcinoma of theaxtl la CT and MRI features. Br J Radiol.20a5;78:257-260.

5. Scheinfeld N. Pilomatrical carcinoma: a case in a patient with HIVand hepatit is C. Dermatol Online J. 2008;L4:4.

6. Yencha MW Head and neck pilomatricoma in the pediatric agegroup: a retrospective study and literature review. Int J PediatrOtorhinolaryngol. 200 I ;57 '.123-L28.

7. Barbosa A, Guimaraes N, Sadigursky M. Pilomatrix carcinoma(malignant pilomatricoma): a case report and revlew of literature.Anats Br asileiro s de D ermatolo gia. 200 0 ;7 5 : 5 B I - 5 B 5 .

B. Sassmannshausen J, Chaffins M. Pilomatrix carcinoma: a reporiof a case arising from a previously excised pilomatrixoma and areview of the literature. J Am Acad Dermatol. 2001;44(suppl 2).358-36r.

9. omidi AA, Bagheri R, Tavassollan H. Pilomatrix carcinomawith subsequent pulmonary metastases: a case report. Tanaffos.20065:57 -60.

10. Lazar AJ, Calonje E, Grayson W Pilomatrix carcinomas containmutations in CT\lNBl, the gene encodin g beta-catenin. J CutanP athol. 2005;32: I 48- L57 .

I l. Bassarova A,, Nesland JM, Sedloev T, et al. Pilomatrix carcinomawith lymph node metastes . J Cutan Pathol. 2004;3I:330-335.

12. De Beuckeleer LH, De Schepper AM, Neetens I. Magnetic reso-nance imaging of pilomatricoma . Eur Radiol. 1996;6.72-60, I

www.cosderm.com