pilomatrixoma osificane

8/20/2019 Pilomatrixoma osificane

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CASE REPORT

Ossifying pilomatrixoma with marrow formation of

the left cheek region – Case report with review of

literature

Ashwin Ashok Jaiswal a,*, Amrish Kumar Garg a, Ravindranath Membally b,

Tanuja Anand c, Manoj Kumar Mohanty d

a Department of ENT & Head Neck Surgery, J.L.N. Hospital & Research Centre, Bhilai (CG), Indiab Department of Pathology, J.L.N. Hospital & Research Centre, Bhilai (CG), Indiac Department of Anaesthesia, J.L.N. Hospital & Research Centre, Bhilai (CG), Indiad Department of Paediatric Surgery, J.L.N. Hospital & Research Centre, Bhilai (CG), India

Received 4 January 2015; accepted 5 February 2015

Available online 24 February 2015

KEYWORDS

Pilomatrixoma;

Ossification;

Marrow;

Neoplasm;

Otorhinolaryngologist;

Benign

Abstract Pilomatrixoma is a rare, benign, circumscribed, calcifying epithelial neoplasm that arises

from thehair follicle on anypart of thebody.It maypresent to theotorhinolaryngologist as a palpable

mass in the head and neck region. They are usually found in girls during the first two decades of life.

These tumors may contain calcification, which, when present, is helpful in suggesting the diagnosis.

We present a rare case of ossifying pilomatrixoma in a 15 year old female who presented with a pain-

less hard slow growing swelling over the left cheek region. FNAC could not provide any clue whereas

USG and CT scan showed the swelling to be in subcutaneous plane, superficial to the parotid gland.

Complete excision of the mass along with the overlying adherent skin in toto with preservation of

facial nerve wasdone.The diagnosiswas confirmed after histopathological examination of theexcised

specimen which revealed pilomatrixoma with extensive ossification and marrow formation.

ª 2015 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier

B.V. All rights reserved.

1. Introduction

Pilomatrixoma, also known as pilomatricoma, is a rare, benign

tumor that originates in the cells of the hair follicle matrix.1 The

tumor was first described in 1880 by Malherbe and Chenantais,

who believed that it arose from the sebaceous gland and called

it as calcifying epithelioma of Malherbe.2 In 1922, Dubreuilh

and Cazenave described its unique histopathology consisting

of basaloid cells and shadow/ghost cells. In 1942, Turhan and

Krainer determined that the origin of this neoplasm is from hair

* Corresponding author at: Department of ENT & Head Neck

Surgery, J.L.N. Hospital & Research Centre, Sector 9, Bhilai, Dist.

Durg, Chhattisgarh 490009, India. Tel.: +91 9407983605; fax: +91

0788 2227814.

E-mail addresses: [email protected], ash1978jaiswal@

gmail.com (A.A. Jaiswal), [email protected] (A.K. Garg),

[email protected] (R. Membally), [email protected]

(T. Anand), [email protected] (M.K. Mohanty).

Peer review under responsibility of Egyptian Society of Ear, Nose,

Throat and Allied Sciences.

Egyptian Journal of Ear, Nose, Throat and Allied Sciences (2015) 16, 193–199

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cortex cells.3 Later, the term pilomatrixoma was coined by

Forbis and Helwig in 1961 thus avoiding the term epithelioma

which carries the connotation of malignancy and it was sug-

gested that the cells of origin are the outer root sheath cells

of the hair follicle.1

Clinically, pilomatrixoma presents as a single, slowly grow-

ing, well-circumscribed, 5–30 mm in size, deep dermal and sub-

cutaneous, firm to hard, superficial, mobile nodule. Usually

they are solitary nodules but multiple and familial cases arealso reported. The majority of these tumors arise during the

first two decades of life; however, a second peak of occurrence

is seen in older patients.4 Overall, there is a female pre-

dominance. Even though the pilomatrixoma is more common

in the head and neck, it tends to skip from the clinical diagno-

sis and diagnosis is usually made by histopathological

examination of the excisional biopsy.5,6 Hence, we report a

unusual case of ossifying pilomatrixoma with marrow forma-

tion along with extensive review of literature.

2. Case report

A 15 year old female patient presented to OPD of J.L.N.Hospital & Research Centre, Bhilai, with a slowly progressive

swelling over the left cheek region since 3 years. On examina-

tion, well circumscribed swelling of size approx 3 cm · 3 cm

was seen over the left cheek region located 2 cm above the

mandibular margin, 3 cm above and anterior to the angle of

mandible and 3 cm below the zygomatic arch, the skin over

the swelling was tethered with no visible pulsations. On palpa-

tion it was non tender, stony hard in consistency, the skin over

the swelling was adherent to the swelling (Fig. 1). On intraoral

examination, no bulge was seen on the buccal mucosa. There

were no lymph nodes enlarged in the neck. The patient also

had alopecia areata of left eyebrow. USG on left cheek region

showed a large linear hyperechoic lesion of size 2 cm with a

strong posterior acoustic shadowing obscuring the left parotidparenchyma. FNAC was tried but could not be done as needle

could not be introduced into the stony hard swelling. Taking

into consideration its consistency contrast enhanced CT scan

on the head & neck was done which showed a large non

enhancing lesion (of attenuation 1138–1140 HU) of size

11 mm · 23 mm · 24 mm in the subcutaneous tissue plane

above the angle of mandible occupying the left cheek region

with extensive calcification within soft tissue and maintained

fat planes (Fig. 2(a–d)). A differential diagnosis was consid-

ered and the patient was planned for excisional biopsy under

GA. The main concern was preservation of the facial nerve

branches. Complete excision of the mass along with the over-lying adherent skin in toto with preservation of the facial nerve

was done. The wound was sutured meticulously with 6.0 pro-

lene. Excised tumor of approx size 3 cm · 3 cm with stony

hard consistency was sent for HPE (Fig. 3(a–d)). Grossly it

was a hard tissue mass with the skin adhered on it which on

cut section showed extensive bone formation. Histopatho-

logical examination showed irregular islands of epithelial cells

which consist of basophilic cells as well as shadow cells. The

stroma surrounding the epithelial island showed extensive ossi-

fication, at places in the ossified stroma hemopoietic cells were

seen enclosed by bony trabeculae suggesting marrow forma-

tion (Fig. 4(a–d)). The postoperative course was uneventful

and facial nerve functions were normal. Immunohistochem-

istry revealed pancytokeratin positive in ghost cells and Ki67 negative for basaloid cells (Fig. 5(a and b)) favoring ossify-

ing pilomatrixoma.

3. Discussion

Pilomatrixoma, or calcifying epithelioma of Malherbe, is a

rare benign tumor of hair-follicle origin that usually arises in

the head and neck region, most commonly in the first two dec-

ades of life.7 However, the onset age varies from 4 months to

86 years.2,8 Approximately 60% of pilomatrixoma occurs in

patients younger than 20 years, of which in 40% of cases it

occurs before the age of 10 years and in 60% of cases before

the age of 20 years, whereas the distribution is somewhat inthe bimodal age group.2 It is more common in women (1.5–

2.5:1) than men and even most authors have reported a female

preponderance.9 Our case was a 15 year old female patient.

In the 1970s, Moehlenbeck reviewed 140,000 skin tumors

and f ound that pilomatrixoma accounted for only 0.12% of

them.10 The head and neck region is involved in about 40–

77% of the patients with this tumor, followed by the cheek,

scalp and periorbital areas; but it is not known to occur on

the palms, soles, or genitalia.2 In the head it occurs pre-

dominantly in the cheek followed by around the eyes, scalp

and least of all in the preauricular region. Usually solitary,

2–3.5% are found in multiple.2 In our case, a solitary swelling

was situated over the left cheek region.

The etiology of pilomatrixoma is subject to controversy.Based on these anatomical features, several authors have sug-

gested that the most likely mechanism for development of pilo-

matrixoma is inclusion of epidermic elements in abnormal

locations during embryonic life and subsequent growth after

birth.11 Lever and Griesemer classified pilomatrixoma as a

hamartoma, but Dubreuilh and Cazenave proposed two alter-

native hypotheses. The first is that, these tumors arise from

branchial clefts. This theory seems unlikely because piloma-

trixomas can develop at any age and it does not account for

the lesions on the extremities.11 The second hypothesis states

that pilomatricoma is of ectodermal origin and that evidence

exists to show that they originate from the hair germinal

Figure 1 Clinical photograph showing, well circumscribed

swelling of size approx 3 cm · 3 cm was seen over the left cheek

region located 2 cm above the mandibular margin, 3 cm above and

anterior to the angle of mandible and 3 cm below the zygomatic

arch. On palpation the skin over the swelling was adherent to the

swelling {White arrow}.

194 A.A. Jaiswal et al.


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matrix.2,11 Pilomatricoma formation represents a disturbance

of the hair follicle cycle in which limited cytologic differen-

tiation of pilar keratinocytes occurs but further development

into mature hair fails to take place. There is a study suggesting

that apoptosis is the main mechanism leading to the develop-ment of the dead shadow cells and is most probably responsi-

ble for the biological behavior of pilomatricoma.2 Guinot-

Moya et al., did study on 211 lesions and they recorded that

antecedents of trauma, insect bites or surgery, intradermal

reaction of vaccine, history of alopecia areata as the etiology.12

In the reported case there was a history of alopecia areata of

the eyebrow. Moehlenbeck observed and stated that there were

no familial presentations in their retrospective study.10 There

are suggestions that an activating mutation in the b-catenin

gene mapped chromosome 3 p22-21.3 plays a major role in

the tumor genesis.13

Clinically, it is rare for otorhinolaryngologists or head and

neck surgeons or pediatric surgeons to encounter pilomatrixo-

ma and mainly receives referrals to treat pilomatrixoma in the

intraparotid or periparotid region because of the possibility of

postoperative facial palsy. Clinical presentation is usually

asymptomatic,14 may present with superficial, solitary firm

mass associated with reddish-blue discoloration overlying the

skin.15 Usually these are slow growing,15 It presents as a soli-

tary cystic swelling that is typically painless and therefore often

ignored. It eventually progresses to become a calcified lesion.

The diagnosis should be suspected when the mass is nodular,

subcutaneous or intradermal and adherent to the skin but

not fixed to the underlying tissue.16 The tumor usually varies

in diameter from 0.5 to 3.0 cm17 but there are also variance

in sizes up to as large as 13.5 cm which have been reported.18

In the present case the swelling was approximately 3 cm in size,

solitary, painless, hard in consistency, adherent to the skin and

freely mobile over the underlying tissue.

Multiple pilomatrixoma are uncommon, as most authorsreport an incidence in the range of 2–10%. Multiple lesions

have occurred in association with myotonic muscular dystro-

phy, Gardner syndrome, Turner syndrome, Steinert disease,

Rubinstein–Taybi syndrome, sarcoidosis1–3 and skull dysosto-

sis. A rare familial occurrence has also been reported.19 In our

case, the patient did not have any family history of piloma-

trixoma and also did not demonstrate any of the features of

these associated syndromes. In view of the rarity of piloma-

trixoma, high chances of missing the diagnosis of pilomatrixo-

ma on clinical examination.

The differential diagnosis includes dermal and subcuta-

neous masses (sebaceous cyst, epidermoid cyst, basal cell

epithelioma, giant cell tumor and neurofibroma), calcified

lesions (calcified epidermoid cyst, foreign body reactions or

calcified hematomas),12 chondroma, degenerating fibroxan-

thoma, metastatic bone formation, and osteoma cutis.19 In

the head and neck regions, they often present as intraparotid

or periparotid tumors and may be confused with benign mixed

tumors of the parotid.20 The other differential diagnosis

should include vascular malformation, branchial cyst, heman-

gioma, inflammatory lesion, calcinosis cutis and ossifying

hematoma.21,22

Although diagnosis of pilomatrixoma can usually be made

solely on the basis of clinical features because of its superficial

occurrence in the skin, the accuracy is reportedly low, and a

Figure 2 Computed Tomography scan (a and b) – Axial view, (c and d) – 3D Reconstructed view showing a large non enhancing lesion

(of attenuation 1138–1140 HU) of size 11 mm · 23 mm · 24 mm in the subcutaneous tissue plane above the angle of mandible occupying

the left cheek region with extensive calcification within soft tissue and maintained fat planes { White arrows}.

Ossifying pilomatrixoma with marrow formation – Case report 195


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correct preoperative diagnosis was made from 28.9% to 49%

of the time.20,23,24 The diagnostic rate is highly dependent on

a clinician’s knowledge and experience of this tumor. As pre-

operative examinations, ultrasonography, CT scan, MRI and

FNAC are useful. Ultrasound is non-invasive, fast and inex-

pensive and can be performed even in children or babies with-

out sedation or general anesthesia.15 The ultrasound (US)

findings demonstrated a well-defined nature of the lesions,

internal calcification, and a peripheral hypoechoic rim or a

complete echogenic mass with strong posterior acoustic shad-

owing.25 On USG our case showed a large linear hyperechoic

lesion of size 2 cm with a strong posterior acoustic shadowing

obscuring the left parotid parenchyma. Although CT and MRI

are often used in the diagnosis of large, deep-seated pilomatri-

comas, those modalities are expensive and technically limitedin most cases of small pilomatricomas versus ultrasonography.

In computed tomographic (CT) scan, pilomatrixoma is

demonstrated as a noninfiltrating mass containing calcifica-

tions located within the subcutaneous tissues.26 Our case on

CT scan revealed a large non enhancing lesion (of attenuation

1138–1140 HU) of size 11 mm · 23 mm · 24 mm in the subcu-

taneous tissue plane above the angle of mandible occupying

the left cheek region with extensive calcification within soft tis-

sue and maintained fat planes. MRI findings of pilomatrixoma

are homogenous intermediate T1-weighted signal intensity,

heterogenous high T2-weighted signal intensity and no

enhancement.27,28 Some authors, however, insisted that

radiologic imaging is of little diagnostic value for pilomatrixo-

ma to differentiate it from other subcutaneous tumors with

any certainty.11,20 FNAC has been described as a preoperative

diagnostic investigation. However, the results can be mislead-

ing if there are no ghost cells present in the aspirate. 20,29

Standard treatment recommends the surgical tumor resec-

tion with safety margins in order to minimize the risk of recur-

rence of the malignant variants.9,30 Generally, adhesion to the

surrounding tissue is not very dense and resection is technically

easy. In the intraparotid and periparotid regions, the protec-

tion of facial nerve function is important. In most cases of pilo-

matrixoma, the tumor exists just under the skin and the risk of

facial palsy is relatively low, however meticulous dissection

and closure has to be carried out for excellent cosmetic results.

Yoshimura et al. recommended that the lesion should beexcised completely, together with the adherent skin.16 Especial-

ly in the cheek, the protection of facial nerve function is impor-

tant. Complete excision of the mass along with the overlying

adherent skin in toto with preservation of the facial nerve

was done in this reported case.

Relapses are rare but if it occurs it may b e due to incom-

plete removal of the lesion, occurring in 2–6%.9,12 If the tumor

recurs then the possibility of malignancy should be

considered.31

Though these tumors are commonly benign, rarely

malignant changes are described due to mutation changes in

betacatenin genes (CTNNB1) which were detected in 75% of

Figure 3 Intraoperative photograph (a) showing marking for skin incision overlying the mass including the adherent skin {White arrow};

(b) showing mass with part of the adherent skin dissected out from the underlying tissue { White arrow}; (c) showing meticulously sutured

wound with 6.0 prolene {White arrow} and (d) showing excised specimen of tumor of approx size 3 cm · 3 cm with the adhered skin

{White arrow} and stony hard consistency.



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cases.32 The exact role of mutation remains to be elucidated. In

the literature some 60 cases of malignant transformation have

been documented till date. The rare, malignant counterpart of

pilomatrixoma is pilomatrix carcinoma, and the differential

diagnosis of this malignant lesion includes basal cell carcinoma

with matrix differentiation and metastasis.33 The principal

indicators of malignancy are cellular pleomorphism, frequent

mitotic figures and atypias, central necrosis and infiltration

of the skin, soft tissues and lymphatic and vascular elements.

The malignant version of pilomatrixoma is more frequent in

males (with a 3:1 predominance over females) and in elderly

individuals (60% are over 40 years of age). Once the diagnosis

has been confirmed, management consists of radical excision

with adequate resection margins, due to the high associated

Figure 4 Photograph of histopathological examination. (a) Panoramic view showing irregular islands of epithelial cells consisting of

basophilic cells as well as shadow cells {Black arrows} and the surrounding stroma with extensive ossification{Blue arrow}[H&E, 10X], (b)

Epithelial islands consisting of basophilic cells{ Black arrow} as well as shadow cells { Blue arrow} [H&E, 10X], (c, d) Showing ossified

stroma highlighting haemopoetic cells {Blue arrows }enclosed by bony trabeculae {Black arrows} suggesting marrow formation [H&E,

40X].

Figure 5 Photograph of immunohistochemistry showing (a) Pancytokeratin positive in ghost cells {Black arrows} [2CK_10X] and (b) Ki

67 negative for basaloid cells {Black arrow} [KI67_10X] favoring ossifying pilomatrixoma.



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relapse rate (49% of controlled cases).12 In our case no malig-

nant variants were diagnosed and there has been no recurrence

in the follow up of 1 year of the patient. Black et al. reported

that the clinical behavior of pilomatrix carcinoma in adults

resembles that of basal cell carcinoma in its potential to metas-

tasize.20,33 Distant metastases are rare, with only 6 cases

described to date in the literature. Patient survival in such cases

has been 3–18 months from the time of diagnosis of metastatic

disease.12

Histopathologic examination will reveal a sharply demar-

cated dermal nodule. At the periphery are the nucleated basa-

loid cells and at the center are non-nucleated ghost cells. The

basaloid cells generally have small, uniform nuclei, scant cyto-

plasm, and indistinct cell borders surrounded by fibrillary

material. Sheets of ghost cells, which evolve from basaloid

cells, represent dead cells that have retained their shape. A

transitional area is noted between the basaloid area and the

ghost cells. Calcification is predominantly seen in the area of

the ghost cells. Giant cells, which represent a foreign-body

reaction to the ghost cells, are also seen in the area where ker-

atin is abundant.2 Four distinct morphological stages of pilo-

matricomas have been proposed.

(1) Early: small and cystic lesions. (2) Fully developed: largeand cystic neoplasms. (3) Early regressive: foci of basaloid

cells, shadow cells and lymphocytic infiltrate with multinucle-

ated giant cells. (4) Late regressive: numerous shadow cells,

absence of basaloid or inflammatory cells, calcification and

ossification may be present.34

It is known that approximately 75% of pilomatricomas

show calcification and 15–20% show ossification. Ossification

takes place in the stroma next to shadow cells, probably via

fibroblast–osteoblast differentiation.17 Hirota et al. suggested

that osteopontin produced by macrophages surrounding shad-

ow cell nests might play a role in the deposition of calcium

phosphate in pilomatricoma.35 Calcification is mostly seen in

the ghost cell regions, with the incidence ranging from 69%to 85% while areas of dystrophic ossification are seen in 15–

20% of cases.17,36,37 Foreign body giant cell reaction, which

represents a granulomatous response to the shadow cells, can

also be identified in regions where keratinized debris is abun-

dant.11,17,38 The histopathological examination of our excised

specimen showed irregular islands of epithelial cells which con-

sist of basophilic cells as well as shadow cells. The stroma sur-

rounding the epithelial island showed extensive ossification, at

places in the ossified stroma haemopoietic cells were seen

enclosed by bony trabeculae suggesting marrow formation.

Such extensive ossification and marrow formation have not

been reported in literature.

On histopathological examination, findings of a basaloid

cell which has high mitotic activity, does not ascertain thediagnosis of malignancy, as the presence of other features such

as cellular atypia, local aggressive behavior, vascular invasion

and infiltrative basaloid nodules leads to diagnosis of rare pilo-

matrixoma carcinoma.39 Pilomatrixoma carcinoma is typically

a highly locally aggressive neoplasm with high rate of local

recurrence, it metastasizes through lymphatics and blood ves-

sels with the most affected organ being the lung.40

On immunohistochemistry, Park et al. demonstrated that,

the basophilic epithelial cells were intensely positive for Bcl-2

and HSP-70, and the shadow epithelial cells were positive for

BMP-2 but BMP-4, directly inducing the bony deposition in

the vicinity of the epithelium. On the other hand, the transition-

al epithelial cells of the primitive hair follicle were strongly posi-

tive for b-catenin, APC, and TGase C. Especially, b-catenin

and APC were clearly localized at the nuclei of the transitional

epithelial cells, while E-cadherin and Wnt-1 were mainly posi-

tive in the mesenchymal cells of underlying connective tissue.

On the other hand, the whole tumor epithelial cells were entire-

ly negative for the antibodies of PCNA, p21, p53, Bax, TGase

E, and TGase K, and even more the shadow epithelial cells were

also negative for the TUNEL stain. They suggested that thetumor cells of the ossifying pilomatrixoma are abnormally

regulated for their cytodifferentiation and cellular apoptosis,

resulted in the accumulation of the shadow epithelial cells,

which produce the downstream effector molecules of Wnt/

b-catenin pathway, that is the osteogenic molecules of BMP-2

enable to induce the bony tissue directly in the vicinity of the

epithelium.41 Immunohistochemistry in our case revealed

pancytokeratin positive in ghost cells and Ki 67 negative in

basaloid cells favoring ossifying pilomatrixoma.

4. Conclusion

Pilomatrixoma, or calcifying epithelioma of Malherbe, is arare benign tumor of hair-follicle origin that usually arises in

the head and neck region.

Calcification is seen but extensive ossification and marrow

formation is extremely rare.

As preoperative examinations, ultrasonography, CT scan,

MRI and FNAC are useful in diagnosis, knowing the extent

of tumor and calcification status.

Standard treatment recommends the surgical tumor resec-

tion with safety margins together with the adherent skin.

In the intraparotid and periparotid region, the protection of

facial nerve function is important.

Histopathological examination and Immunohistochemistry

are helpful in confirmation of diagnosis.

Conflict of interest

None declared.

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