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Slide 1: I rci Pilomatrica Ca noma: Report Review and of Case the Literature Tony Nakhla, DO; Michael Kassardjian, DO from hairmatrixcells. Pilomatrical carcinoma a raremalignant is tumorthat originates Pilomatrical from its benign may arisede novo as a solitarylesion, through transformation or carcinoma pilomatrixoma. Differentiation betweenpilomatrixoma and pilomatrical carcinoma counterpart, pilomatrical Although uncommon, examination and often is difficult. close histologic requires promptdiagnosis appropriate therefore, managehas to and carcinoma the potential metastasize; ment is essential. ilomatrical counterpart carcinoma is the malignant a benign 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 aLyprcalfeatures, includirg Iargenuclei with prominent nucleoli as well 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 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, the infiltratn\-e areas with not be erpected in a atyprcal spindle cells would of pilomatrixoma, 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 diagnosed with presented with pilomatrical a 2-month history man carcinoma. The patient 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. California. is Dr. Kassardlian an intern, PacificHospital,LongBeach, relation to The authors report no conflict tf interest in thisarticle. Michael Kassardjian,DO, PO Box 2152, Correspondence: Pen,CA 90275 (miheygh@gmail.com). Verdes Palos 3I4 . . JULY 2010 vol. 23 No. 7 Dermatology@ Cosmetic 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
Slide 2: Fi gure 1. A 56-year-ol dw hi te man w i th a 2-cm, well-demarcated, nontender, moveabl e, hard subcutaneous nodul 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 the infiltrative areas, a finding that nuclei. rnc^'-rd.rnE 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 cases.5 of Cases metastasis the lung, of to bones, and lymphatics, ds well as invasion into the cranialvault, have been reported.3 EPIDEMIOLOGY The epidemiology 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 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 middleaged 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 preauricular area.3'4Approximately preauricular region.T vol. 23 No. 7 . JULv2010. Cosmetic Dermatology@ 315 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 L949, Lever and Griesemerr suggested that the actual origin of the tumor was the harr matrix.3 Thus, the approprlaLe term pilomatrtxonta was adopted, synonymous 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 cffi, with a mean of 3.95 cm, which is slightly larger than its benign counterpart, pilomatrixoma.a The consistency www.cosderm.com 60o/o of tumors have been half are in the located on the head, among which
Slide 3: PnouATRIcnr CaRcINoMA Figure 2. A fragrnented biopsy specimen revealed o a b as aloidpro l i f e r a t i o n n d g h o st ce lls ( H&E, 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 differential diagnosis of pilomatrical pilomatrixoma, squamous cell ly-phoepitheliomalike includes 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 carcinoffi?, trichoepithelioma, . JULY . 2010 vot-.23 No. 7 Dermatology@ 316 Cosmetic www.cosderm.com
Slide 4: PnouATRrcAL CARCTNoMA l Figure4. Stromalsclerosis, highly atypicalsquamoid and spindlecells, and several mitoticfigures (H&E, X400). original magnification Figure5. Areas hemorrhage granulation of and tissuesurrounded infiltrative by atypical spindle cells (H&E, X400). original magnification ghost cells, along with zones of necrosiswith surroundalso are observed. The basaloid ing stromaldesmoplasia 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.8 Tumor 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
Slide 5: PrlouATRrcAL CnncrNoMA 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 benign cal carcinoma. pilomarrixoma evaluation is necessary to from pilomarri- extend into the subcutaneous fat, deep fascia,and skelmuscle. In pilomatrical carcinoma,the shadow cells etal. tend to form a nested pattern, instead of the flat sheetlike pattern usually observedin benign pilomatrixomas.3 Histologic criteria for pilomatrical carcinoma include invasion,mitotic index, apoptoticcount, aswell as vessel molecular markersof cell death and adhesion.e IMMUNOHISTOCHEMISTRY Immunohistochemical studies have not d.finirively distinguished the markers that differentiate pilomacarcinomas . 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 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 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 and differentiation. Mutations trixomas from pilomatrical 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 middleaged to older individuals, more commonly in men, and has a predilection for the posterior neck, upper 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 glandes sebaces. ProgJIed LSS0:325-837. 2. Lever Wf; Griesemer RD. Calficnng epithelioma of Malherbe; report of 15 cases,riith ccT-nrnenis its differentiation from calon 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 the axtlla CT and MRI features. J Radiol.20a5;78:257-260. Br 5. ScheinfeldN. Pilomatrical carcinoma:a case a patient with HIV in and hepatitisC. Dermatol Online 2008;L4:4. J. 6. Yencha MW Head and neck pilomatricoma in the pediatric age group: a retrospective study and literature review. Int J Pediatr Otorhinolaryngol. I ;57'.123-L28. 200 7. Barbosa A, Guimaraes N, Sadigursky M. Pilomatrix carcinoma (malignant pilomatricoma): a casereport and revlew of literature. AnatsBrasileiro de D ermatolo s gia. 2000 ;75 :5BI - 5B5 . B. Sassmannshausen Chaffins M. Pilomatrix carcinoma: a repori J, 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: case report. Tanaffos. a 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. Bassarova Nesland JM, SedloevT, et al. Pilomatrix carcinoma A,, with lymph node metastesJ 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 TREATMENT The most widely carcinoma is wide reported treatment for pilomatrical histologically local excision with 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 . JULv . Dermatology@ 2010 vol. 23 No. Z 318 Cosmetic www.cosderm.com