PilomatricaI Carcinoma: of CaseReportandReview the Literature Tony Nakhla, DO; Michael Kassardjian, DO
from hairmatrixcells.Pilomatrical carcinoma is a raremalignanttumorthat originates Pilomatrical from its benign carcinomamay arisede novo as a solitarylesion,or through transformation Differentiation betweenpilomatrixomaand pilomatricalcarcinoma counterpart,pilomatrixoma. requiresclose histologicexaminationand often is difficult.Although uncommon,pilomatrical promptdiagnosisand appropriatemanagetherefore, carcinomahasthe potentialto metastasize; ment is essential.
ilomatrical counterpart
carcinoma
is the malignant
of pilomatrixoma,
a benign
noninfiltrative
appearirg.
cutaneous tumor originating from the hair
However, this case also shorvs areas with larger more
ma[rix. It is a rare, aggressive tumor with a
squamoid appearing cells urth aLyprcalfeatures, includ-
high probability of recurrence after simple
irg Iargenuclei with prominent nucleoli as well as areasof
man
infiltrative appearing cells, features highly concerning for malignancy (Figure 3). In the infiltrative appearrngarea,
carcinoma. The patient
there is dense stromal sclerosis associated u-ith highly
excision, and the potential to metastasrze. We report a case of a 56-year-old white diagnosed with presented with
pilomatrical a 2-month
history
of ar1 enlarging
asymptomatic growth on the cheek. Physical examination revealed a 2-cm, well-demarcated, nontender, moveable, hard subcutaneous nodule on the right mandible (Figure l). No skin changes or lymphadenopathy 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 cells, typical of pilomatrixoma (Figure 2). Dr. I'laLthla is from OC Shin Institute, Santa Ana, California. Dr. Kassardlianis an intern, PacificHospital,LongBeach,California. The authors report no conflict tf interest in relation to thisarticle. Michael Kassardjian,DO, PO Box 2152, Correspondence: PalosVerdesPen,CA 90275 (miheygh@gmail.com). 3I4
In som e areas, the lesional cells are relatively bland and
. JULY 2010. vol. 23 No. 7 CosmeticDermatology@
atyprcal squamoid and spindle cells, with ser-eralmitotic figures found within these cells (Figure +) In many areas of the biopsy, there is granulomatolls inflammahemorrhage , and granulation tissue consistent with a reaction to ruptured material from the tumor (Figure 5) While the latter findings often are seen in tion,
ruptured
pilomatrixoma,
atyprcal spindle
the infiltratn\-e areas with
cells would
not
be erpected
in a
benign pilomatrixoma, and the findings are most consistent with a diagnosis of malignant pliomarrixoma (pilom afitcal carcinoma) . Multiple laboratory tests using immunohrstochemip63, cytokeratrn i/6, synaptophysin, p53, and Ki-67 also \\-ere rer-iewed. The tumor cells were strongly and diffusely- positive for cal stains, including
p63, highlighting
the nuclei of the infiltrative
and
spindle cells, which is positirre in mos[ primary cutaneous malignancies including adnexal carcinomas. In addition, results of cytokeratin 5/6 staining aiso were moderately positive within lesional cells, including the www.cosderm.com
Fi gure 1. A 56-year-ol dw hi te man w i th a 2-cm, well-demarcated, nontender, moveabl e, hard subcutaneousnodul e presenton the ri ght mandi bl ew i th no ski n changes.
infiltrative-appearing
spindle cells, which
confirmed
that these were epithelial, and not mesenchymal, ceiis R.esults of synaptophysin staining were nega[l\-e and not consistent with a neuroendocrine tumor such as \ierkel cell carcinoma. Staining for p53 was r.,'eakir b'-ri difiusely positive throughout the tumor cell nuclei. rnc^'-rd.rnEthe infiltrative areas, a finding that also far-ored :rahgnancy. In addition, Ki-67 positivity 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 overall histologic findings supported the and immunohistochemical diagnosis of pilomalncal carcinoma.
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 for epidermal cysts. The diagnosis of pilomatrical malign ancy is made exclusively by careful histologic evaluation. Pilomatricalcarcinomahas a potential to metastasrze in about 10o/o of cases.5 Casesof metastasisto the lung, bones, and lymphatics, ds well as invasion into the cranialvault, have been reported.3
EPIDEMIOLOGY The epidemiology
COMMENT Pilomatrixoma 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
of pilomatrical
carcinoma differs
from pilomatrixomas. Pilomatrixomas more often are 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
L949, Lever and Griesemerr suggested that the actual origin of the tumor was the harr matrix.3 Thus, the
Pilomatrixomas occur most commonly on the head,
approprlaLe term pilomatrtxonta was adopted, synonymous with calcifying epithehoma of Malherbe, which
lower extremities.3 Involvement of the face has been
also is commonly used.
reported in the frontal, temporal, cheek, periorbital,
Clinically, the tumor is described as a solitary, slow growing, asymptomatic, dermai or subcutaneous mass
more predominant
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
from
to
19 years.5
followed by the upper extremities, neck, trunk, and
and preauricular regions.6 Pilomatrical carcinomas are 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 population are more common in the posterior neck, upper back, and preauricu-
been reported to range in size from 0.5 cm to 20 cffi, with a mean of 3.95 cm, which is slightly larger than its
lar area.3'4Approximately
benign counterpart, pilomatrixoma.a The consistency
preauricular region.T
www.cosderm.com
B months
60o/o of tumors have been
located on the head, among which
half are in the
vol. 23 No. 7 . JULv2010. Cosmetic Dermatology@ 315
PnouATRIcnr CaRcINoMA
Figure 2. A fragrnented biopsy specimen revealed b as aloidpro l i f e r a t i o na n d g h o st ce lls ( H&E,o r ig in a l magnif ic at i o nx 1 0 0 ) .
Fi gure 3. I n f i l t r a t i v e s q u a m o id a n d sp in d le ce lls w it h at y pi c a l f e a t u r e s , i n c lu d in g la r g e n u cle i w it h promin e n t n u c l e o l i ( H & E,o r ig in a l m a g n ifica ti o n x 400).
HISTOPATHOLOGY The histologic carcinoma
carcinoma of the skin, and mixed tumors of the skin.7
differential diagnosis of pilomatrical
includes
pilomatrixoma,
carcinoffi?, trichoepithelioma,
squamous
cell
ly-phoepitheliomalike
. JULY 2010. vot-.23 No. 7 316 CosmeticDermatology@
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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PnouATRrcAL CARCTNoMA
Figure4. Stromalsclerosis, highly atypicalsquamoid and spindlecells,and severalmitoticfigures (H&E, X400). originalmagnification
Figure5. Areasof hemorrhage andgranulation tissuesurrounded by infiltrative atypicalspindlecells (H&E, X400). originalmagnification
ghost cells, along with zones of necrosiswith surrounding stromaldesmoplasiaalso are observed.The basaloid cellshave deeplybasophilicoval or round nuclei and are found at the periphery of the islands.A transition zorae www.cosderm.com
of retained nuclei from basaloid cells to the anucleate, eosinophilicshadow cells often is seen.8Tumor necrosis usually is present, as well as frequent atypical mitotic figures.Basaloidcells may infiltrate the entire dermis and VOL.23 NO. 7 . JULY2010 . Cosmetic Dermatology@ 317
l
PrlouATRrcAL
CnncrNoMA
extend into the subcutaneousfat, deep fascia,and skeletal.muscle. In pilomatrical carcinoma,the shadow cells tend to form a nested pattern, instead of the flat sheetlike pattern usually observedin benign pilomatrixomas.3 Histologic criteria for pilomatrical carcinoma include vesselinvasion,mitotic index, apoptoticcount, aswell as molecular markersof cell death and adhesion.e
calcifications, while the inhomogeneous signal intensities related to varying degrees of tumor proliferation. High signal intensity was atrributable ro cysric spaces forming in areas of tumor necrosis Pilomatrical carcinoma is a rare malignant form of pilomatrixoma, which arises from hair matrix cells. Careful histologic distinguish
IMMUNOHISTOCHEMISTRY Immunohistochemical
studies have not
benign
evaluation is necessary to from pilomarri-
pilomarrixoma
cal carcinoma.
d.finirively
distinguished the markers that differentiate pilomatrixomas from pilomatrical
Pilomatrical carcinoma rnay arise de novo or from a preexisting benign pilomatrixoma, which may be clinically indistinguishable. In cases
carcinomas . Lazar et alI0 studied a series of 15 pilomatrical carcinomas and 13 benign pilomatrixomas to assess expression of
where previously excised or curetted pilomatrixomas recur, a reexcision with careful histologic evaluation
B,-catenin using immunohistochemical staining and DNA sequencing of exon 3 from the Bl-catenin gene,
Pilomatrical carcinoma occurs more often in middleaged to older individuals, more commonly in men, and has a predilection for the posterior neck, upper
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 localtzatton of B-catenin, mutations on exon 3, as well as expression of nuclear cyclin D 1 . Howev er, 2 pilomatricaI 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
TREATMENT The most widely carcinoma is wide
reported
treatment for pilomatrical
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 function 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 pilomatrixoma 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 inhomogeneous mass with cystic changes on magnetic resonance rmaging. Areas of low signal intensity corresponded to . JULv2010. vol. 23 No. Z 318 CosmeticDermatology@
is indi cated.T
back, and preauricular
area. Pilomatrical carcinomas frequently recur; however, treatment with wide local excision or Mohs micrographic surgery has been shown to lower the raLe of recurrence.4,5 Distant metastases have been reported in up to l0o/o of cases.5Due 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.
REFERENCES 1. Malherbe A, ChenantaisJ. \ore sur lepirheliome calcifie des glandessebaces. ProgJIed LSS0:325-837. 2. Lever Wf; Griesemer RD. Calficnng epithelioma of Malherbe; report of 15 cases,riith ccT-nrnenis on its differentiation from calcified epidermal cyst anC on iis histogenesis.Arch Derm Syphilol. L949;59:506-5 18. 3. sau B Lupton GB Graham JH. Pilomatrix carcinoma. cancer. L993:7L:249L-2498. 4. Niwa T, Yoshida T. Doiuchi T, et al. Pilomatrix carcinoma of the axtlla CT and MRI features.Br J Radiol.20a5;78:257-260. 5. ScheinfeldN. Pilomatrical carcinoma:a casein a patient with HIV and hepatitisC. DermatolOnlineJ. 2008;L4:4. 6. Yencha MW Head and neck pilomatricoma in the pediatric age group: a retrospective study and literature review. Int J Pediatr Otorhinolaryngol. 200 I ;57'.123-L28. 7. Barbosa A, Guimaraes N, Sadigursky M. Pilomatrix carcinoma (malignant pilomatricoma): a casereport and revlew of literature. AnatsBrasileiros de D ermatolo gia. 2000 ;75 :5BI - 5B5 . B. Sassmannshausen J, 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 subsequent pulmonary metastases:a case report. Tanaffos. 20065:57-60. 10. Lazar AJ, Calonje E, Grayson W Pilomatrix carcinomas contain mutations in CT\lNBl, the gene encoding beta-catenin.J Cutan Pathol.2005;32:I 48- L57. I l. BassarovaA,, Nesland JM, SedloevT, et al. Pilomatrix carcinoma with lymph node metastes . J CutanPathol.2004;3I:330-335. 12. De BeuckeleerLH, De Schepper AM, Neetens I. Magnetic resonance imaging of pilomatricoma. Eur Radiol. 1996;6.72-60, I
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