cal Carcinoma a Case Report by Dr. Tony Nakhla of OC Skin Institute

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Piomatrica Cacinoma:Case eport ndReviewftheLiteratureTony Nakhla, DO; Michael Kassardjian, DO

Pilomatricalarcinomasa raremalignantumor hatoriginatesrom hairmatrix el ls. i lomatrical

carcinomamay arisede novo as a soli tary esion, r through ransformationrom its benign

counterpart, i lomatrixoma. if ferentiat ionetweenpilomatrixoma nd pilomatrical arcinoma

requires losehistologic xamination nd often is dif f icult .Althoughuncommon, i lomatrical

carcinoma as he potentialo metastasize;herefore,romptdiagnosis ndappropriate anage-

ment sessential.

i lomatrical carcinoma is the malignant

counterpart of pilomatrixoma, a benign

cutaneous tumor originating from th e hair

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

high probability of recurrence after simple

excision, an d th e 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 ar 1 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 th e patient.

Sections were evaluated histologically and revealed

a multifragmented biopsy of dermal and subcutaneous

tissue containing basaloid proliferation with collections

of ghost cells, typical of pilomatrixoma (Figure 2) .

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

Dr. Kassardlians an ntern,PacificHospital,LongBeach,California.

The authors report no conflict tf interest in relation to

thisarticle.

Correspondence: ichael Kassardjian,DO, PO Box 2152,

Palos erdes en,CA 90275([email protected]).

3I4 Cosmetic ermatology@JULY010 vol. 23No.7

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

noninfiltrative appearirg.

However, this case also shorvs areaswith larger more

squamoid appearing cells urth aLyprcal eatures, includ-

irg Iargenuclei with prominent nucleoli aswell as areasof

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-eralmitotic

figures found within these cells (Figure +) In many

areas of the biopsy, there is granulomatoll s i nflamma-

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 th e findings ar e most con-

sistent with a diagnosis of malignant pliomarrixoma

(pilom afitcal carcinoma) .

Multiple laboratory tests using immunohrstochemi-

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

tophysin, p53, an d Ki-67 also \\-ere rer- iewed. Th e

tumor cells were strongly and diffusely- positive fo r

p63, highlighting th e nuclei of th e 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 th e

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spindle cells, which confirmed

these were epithelial, an d not mesenchymal,

R.esults of synaptophysin staining were nega-

an d not consistent with a neuroendocrine tumor

as \ierkel cell carcinoma. Staining for p5 3 wa s

difiusely positive throughout the tumor cell

rnc^'-rd.rnEhe infiltrative areas, a finding that

far-ored :rahgnancy. In addition, Ki-67 positivity

s high u ithrn thre basaloid cells and also positive

man\ c[ rh e spindle cells, highlighting up to

of the entrre lesion. Thus, the overall histologic

immunohistochemical findings supported the

of pilomalncal carcinoma.

first \\-asdescribed in 1BB0 by Malherbe

as a calci.it'tng epithelioma that was

to originate from the sebaceous gland. In

Lever and Griesemerr suggested that the actual

of th e tumor wa s the harr matrix.3 Thus, the

term pilomatrtxonta was adopted, synony-

with calcifying epithehoma of Malherbe, which

is commonly used.

th e tumor is described as a solitary, slow

asymptomatic, dermai or subcutaneous mass

mosl commonly is found in th e posterior neck,

back, an d preauricular area. Duration of tumors

to surgery has been reported to range from

to 10 years.3 Pilomatrical carcinomas have

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

a mean of 3.95 cm, which is slightly larger than it s

counterpart, pilomatrixoma.a Th e consistency

Figure 1. A 56-year-oldwhi te man wi th a

2-cm, well-demarcated, nontender, move-

able,hard subcutaneous odule presenton

the right mandiblewi th no skinchanges.

of the tumors may vary from soft and friable to firm.

They may have red, yellow, white, and tan skin

changes. Lesions cannot reliably be distinguished

based solely on clinical appearance,and frequently

are mistaken fo r epidermal cysts. The diagnosis of

pilomatrical malignancy s made exclusivelyby careful

histologicevaluation.

Pilomatricalcarcinomahasa potential o metast srze

in about 10o/o f cases.5 ases f metastasiso the ung,

bones, and lymphatics, ds well as invasion into the

cranialvault, havebeen eported.3

EPIDEMIOLOGYTh e epidemiology of pilomatrical carcinoma differs

from pilomatrixomas. Pilomatrixomas more often ar e

seen in women (female to male ratio 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, an d

lower extremities.3 Involvement of the face has been

reported in the frontal, temporal, cheek, periorbital,

and preauricular regions.6Pilomatrical carcinomas ar e

more predominant in men an d 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 population ar e more common

in the posterior neck, upper back, an d preauricu-

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

located on the head, among which half are in th e

preauricular region.T

vol. 23 No. 7 . JULv2010 Cosmetic Dermatology@ 315



PnouATRIcnr CaRcINoMA

Figure 2. A fragrnentedbiopsy specimen evealed

basaloidprol i feration nd ghost cel ls H&E, rig inal

magni f ication 100).

Figure3. Infi l trat ivesquamoid and spindle cel lswi th atypical features, including large nuclei

wi th prominent nucleol i (H&E, rig inal magni f ica-

t ion x400).

HISTOPATHOLOGYTh e histologic differential diagnosis of pilomatrical

carcinoma includes pilomatrixoma, squamous cell

carcinoffi?, trichoepithelioma, ly-phoepitheliomalike

316 Cosmetic ermatology@JULY010 vot-.23No.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

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alongwith zonesof necrosiswith surround-

desmoplasia lsoareobserved. he basaloid

have deeplybasophilicoval or round nuclei and are

at the periphery of the islands.A transition zorae

PnouATRrcAL CARCTNoMA

Figure4. Stromalsclerosis, ighly atypicalsqua-moidan d spindle ells, nd severalmitotic igures(H&E,riginalmagnification400).

Figure . Areas f hemorrhagendgranulationis -suesurroundedy infiltrative typical pindle ells(H&E,riginalmagnification400).

of retained nuclei from basaloidcells to the anucleate,

eosinophilicshadowcellsoften s seen.8 umor necrosis

usually is present, as well as frequent atypical mitotic

figures.Basaloid ells may nfiltrate the entire dermisand

VOL.23 NO. 7 . JULY 010 Cosmetic Dermatology@ 317



PrlouATRrcAL CnncrNoMA

extend nto the subcutaneousat, deep fascia,and skel-

etal.muscle. n pilomatrical carcinoma, he shadowcells

tend to form a nestedpattern, nsteadof the flat sheet-

like pattern usually observed n benign pilomatrixomas.3

Histologic criteria for pilomatrical carcinoma include

vesselnvasion,mitotic index, apoptoticcount, aswell as

molecularmarkersof cell deathand adhesion.e

IMMUNOHISTOCHEMISTRYImmunohistochemical studies have no t d.finirively

distinguished th e markers that differentiate piloma-

trixomas from pilomatrical carcinomas Lazar et alI0

studied a series of 15 pilomatrical carcinomas and

13 benign pilomatrixomas to assess expression of

B,-catenin using immunohistochemical staining and

DNA sequencing of exon 3 from th e Bl-catenin gene,

CTNNBI, the defect that leads to th e expression of

pilomatrixomas. B-Catenin is a downstream effector in

the Wnt signaling pathway that signals for proliferarion

an d differentiation.Mutations

in th e CTNNBI geneencoding B-catenin ar e present in both benign and

malignant neoplasms. A11cases 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 aI L 13 benign pilomatrixomas. I0 Past

studies also have reported high constant expression of

CD44v6 an d P-cadherin. 11

TREATMENT

The most widely reported treatment for pilomatrical

carcinoma is wide local excision with histologically

confirmed clear margins. Becausepilomatrtcal 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 casesof metastasis.

Appropriate Iaboratory testing includes liver func-

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

If aggressive ocal invasion is suspected, a computed

tomography scan or magnetic resonance imaging

should be performed to define tumor extension.T Past

studies have found that th e 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 lo w signal intensity corresponded to

318 CosmeticDermatology@JULv 010 vol. 23No.Z

calcifications, while th e inhomogeneous signal intensi-

ties related to varying degrees of tumor proliferation.

High signal intensity was atrributable ro cysric spaces

forming in areasof tumor necrosis

Pilomatrical carcinoma is a rare malignant form

of pilomatrixoma, which arises from hair matrix

cells. Careful histologic evaluation is necessar y to

distinguish benign pilomarrixoma from pilomarri-ca l carcinoma. Pilomatrical carcinoma rnay arise

de novo or from a preexisting benign pilomatrixoma,

which may be clinically indistinguishable. In cases

where previously excised or curetted pilomatrixomas

recur, a reexcision with careful histologic evaluation

is indi cated.T

Pilomatrical carcinoma occurs more often in middle-

aged to older individuals, more commonly in men,

and has a predilection fo r the posterior neck, upper

back, and preauricular area. Pilomatrical carcinomas

frequently recur; however, treatment with wide local

excision or Mohs micrographic surgery ha s beenshown to lower the raLeof recurrence.4,5

Distant metastaseshave been reported in up to l0o/o

of cases.5Du e to the potential for metastasis, prompt

diagnosis followed by wide local excision or Mohs

micrographic surgerl- and close clinical and radiologic

follow-up is recommended.

REFERENCES1. Malherbe A, ChenantaisJ. \ore sur lepirheliome calcifie des

glandes ebaces. ro g Ie d LSS0:325-837.

2. Lever Wf; Griesemer RD. Calficnng epithelioma of Malherbe;

report of 15 cases, iith ccT-nrnenisn its differentiation rom cal-

cified epidermalcyst anC on iis histogenesis. rch Derm Syphilol.

L949;59:506-58.

3. sau B Lupton GB Graham JH. Pilomatrix carcinoma. cancer.

L993:7 :249L-2498.

4. Niwa T, YoshidaT. Doiuchi T, et al. Pilomatrix carcinoma of the

axtl la CT and MR I features. rJ Radiol.20a5;78:257-260.

5. ScheinfeldN. Pilomatrical carcinoma:a casen a patient with HIV

and hepatitisC. DermatolOnline . 2008;L4:4.

6. Yencha MW Head and neck pilomatricoma in the pediatric age

group: a retrospectivestudy and literature review. In t J Pediatr

Otorhinolaryngol.00 ;57 .123-L28.

7. BarbosaA, Guimaraes N, Sadigursky M. Pilomatrix carcinoma(malignant pilomatricoma):a case eport and revlew of literature.

AnatsBrasileiro deDermatolo ia. 2000 75 5B -5B5

B. Sassmannshausen, Chaffins M. Pilomatrix carcinoma: a repori

of a case arising from a previously excised pilomatrixoma and a

review of the literature.J Am Acad Dermatol.2001;44(suppl 2) .358-36r.

9. omidi AA, Bagheri R, Tavassollan H. Pilomatrix carcinoma

with subsequentpulmonary metastases: case report. Tanaffos.

20065:57 60.

10. Lazar AJ, Calonje E, GraysonW Pilomatrix carcinomascontain

mutations in CT\lNBl, the gene encoding beta-catenin. Cutan

Pathol.2005;32: 48- L57

I l. Bassarova ,, NeslandJM, SedloevT, et al. Pilomatrix carcinoma

with lymph node metastesJ CutanPathol.2004;3I:330-335.

12. De BeuckeleerLH, De SchepperAM, Neetens . Magnetic reso-

nance maging of pilomatricoma Eur Radiol. 1996;6.72-60 , I

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cal Carcinoma a Case Report by Dr. Tony Nakhla of OC Skin Institute