Diagnostic Pathology
Cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant
parotid gland tumor--Manuscript Draft-Manuscript Number:

DPAT-D-18-00162R2

Full Title:

Cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant
parotid gland tumor

Article Type:

Case Report

Funding Information:
Abstract:

Background: Pilomatricoma is a relatively common benign cutaneous adnexal
neoplasm with differentiation towards the hair matrix, inner sheath of hair follicle andhair cortex. Proliferating pilomatricoma is a rare variant of pilomatricoma that can
rapidly increase and may be misidentified as a malignant tumor. We herein report thecytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant
parotid tumor. Case Presentation: A 64-year-old man noticed an acne-like nodule in
the left parotid region. It was painless, but it increased to a maximum diameter of 4.5
cm over 2 years. Clinically, left parotid gland carcinoma was suspected, and fineneedle aspiration cytology was performed. Clusters of epithelial cells were observed ina necrotic background, and malignant epithelial cells derived from salivary glands weresuspected. Histologically, the resected tumor was diagnosed as proliferating
pilomatricoma composed of basophilic cells and shadow cells apart from the parotid
gland. However, on a re-evaluation of the cytological specimens, the irregular-shaped
epithelial cells were considered to be from basophilic cells. Shadow cells with nuclear
disappearance were also confirmed. Tumor recurrence and metastasis have not been
observed in the four years since surgery. Conclusion: The present case was firstinterpreted as a malignant parotid gland tumor, but it was actually a benign skinappendage tumor. Pilomatricoma sometimes rapidly increases and may be mistaken
for a malignant tumor. Although it is critical to recognize not only basophilic cells but
also shadow cells, it cannot be diagnosed by cytological findings. The final diagnosis
should be made on excision specimen only.

Corresponding Author:

Nozomu Kurose
Kanazawa Ika Daigaku Byoin
JAPAN

Corresponding Author Secondary
Information:
Corresponding Author's Institution:

Kanazawa Ika Daigaku Byoin

Corresponding Author's Secondary
Institution:
First Author:

Nozomu Kurose

First Author Secondary Information:
Order of Authors:

Nozomu Kurose
Manabu Yamashita
Mariko Nakano
Xin Guo
Akihiro Shioya
Satoko Nakada
Hiroshi Minato
Sohsuke Yamada

Order of Authors Secondary Information:

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Case Report
Cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant
parotid gland tumor

NozomuKurose(k-nozomu@kanazawa-med.ac.jp)1*,

ManabuYamashita(yama-

bu@kanazawa-med.ac.jp)2, Mariko Nakano (mariko-n@kanazawa-med.ac.jp)2, Xin Guo(xinguo@kanazawa-med.ac.jp)1, Akihiro Shioya (a-shioya@kanazawa-med.ac.jp)1, Satoko
Nakada (snakada@kanazawa-med.ac.jp)1, Hiroshi Minato (hminato@ipch.jp)3, Sohsuke
Yamada (sohsuke@kanazawa-med.ac.jp)1
1

Department of Pathology and Laboratory Medicine & 2Department of Pathology, Kanazawa

Medical University, Ishikawa, Japan. 3Department of Diagnostic Pathology, Ishikawa
Prefectural Central Hospital, Ishikawa, Japan.

*Corresponding author: Nozomu Kurose, M.D., Ph.D. Department of Pathology andLaboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 9200293, Japan. Tel: 81-76-218-8264; Fax: 81-76-286-1207; and E-mail: k-nozomu@kanazawamed.ac.jp

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Abstract
Background: Pilomatricoma is a relatively common benign cutaneous adnexal neoplasm withdifferentiation towards the hair matrix, inner sheath of hair follicle and hair cortex. Proliferating
pilomatricoma is a rare variant of pilomatricoma that can rapidly increase and may be
misidentified as a malignant tumor. We herein report the cytopathological findings ofproliferating pilomatricoma misdiagnosed as a malignant parotid tumor. Case Presentation:
A 64-year-old man noticed an acne-like nodule in the left parotid region. It was painless, but it
increased to a maximum diameter of 4.5 cm over 2 years. Clinically, left parotid gland
carcinoma was suspected, and fine-needle aspiration cytology was performed. Clusters ofepithelial cells were observed in a necrotic background, and malignant epithelial cells derived
from salivary glands were suspected. Histologically, the resected tumor was diagnosed as
proliferating pilomatricoma composed of basophilic cells and shadow cells apart from theparotid gland. However, on a re-evaluation of the cytological specimens, the irregular-shaped
epithelial cells were considered to be from basophilic cells. Shadow cells with nuclear
disappearance were also confirmed. Tumor recurrence and metastasis have not been observedin the four years since surgery. Conclusion: The present case was first interpreted as amalignant parotid gland tumor, but it was actually a benign skin appendage tumor.

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Pilomatricoma sometimes rapidly increases and may be mistaken for a malignant tumor.
Although it is critical to recognize not only basophilic cells but also shadow cells, it cannot bediagnosed by cytological findings. The final diagnosis should be made on excision specimen
only.

Key words: proliferating pilomatricoma, basophilic cells, shadow cells, cytology

Short running head: Proliferating pilomatricoma

Word count: 2,046 words (Abstract 249 words); references: 8; figures: 5

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Background
Pilomatricoma, also known as calcifying epithelioma, is a relatively common benign cutaneousadnexal neoplasm with differentiation towards the hair matrix, inner sheath of the hair follicle
and hair cortex. Pilomatricoma is a hard-nodular lesion that occurs in the head and neck region
or upper extremities of children and young adults [1]. It forms an asymptomatic solitary massand shows a slow-growing course. Histologically, pilomatricoma forms a well-circumscribed
nodule and localizes from the dermis to subcutaneous fat tissue. Tumor cells consist of hairmatrix-like cells (matrical or basophilic cells) that are basophilic-stained and shadow cells(ghost cells) that are eosinophilic-stained with nuclear concentration and disappearance [1].
Proliferating pilomatricoma is a rare variant of pilomatricoma. It is relatively large,
rapidly growing and occurs in the elderly [2]. The subtype is primarily composed of basophilic
cells and a small amount of shadow cells, although it can mainly comprise shadow cells insome cases [2].
Parotid region pilomatricoma may be misdiagnosed on fine-needle aspiration (FNA) as
primary malignant cutaneous tumor, salivary gland-type malignant tumor or metastatic tumor[3-7]. We herein report a rare case of proliferating pilomatricoma and discuss its
cytopathological findings.

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Case Presentation
A 64-year-old man noticed an acne-like nodule in the left parotid region 2 years prior to thispresentation. It was painless, but it increased up to a maximum diameter of 4.5 cm. Clinically,left parotid gland carcinoma was suspected, and FNA cytology was performed from the leftparotid region. Clusters of epithelial cells were observed in a necrotic and hemorrhagic
background. These cell clusters had a sheet-like arrangement and high nuclear-cytoplasmic
ratio. The nuclear shape was ovoid with hyperchromasia. Neither nuclear membrane thickening
nor irregular-shaped nuclei were noted. One obvious nucleolus was observed in the central
portion of the cytoplasm (Fig. 1). Small lymphocytes, histiocytes and multinucleated giant cells
were also seen. Malignant epithelial cells derived from salivary glands, including squamouscell carcinoma, myoepithelial carcinoma and carcinoma ex pleomorphic adenoma, weresuspected. Magnetic resonance imaging (MRI) revealed a well-defined multilocular tumor
located close to the outside of the left parotid gland. On T1- and T2-weighted imaging, lowintensity and heterogeneous gadolinium enhancement was seen (Fig. 2). Radiologically,parotid gland cancer was suspected.
One month later, tumor resection of the left parotid region and superficial
parotidectomy were performed. The cut surface showed a well-defined lobulated tumor

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containing yellowish-muddy materials (Fig. 3). Histologically, the resected tumor wasdiagnosed as proliferating pilomatricoma composed of basophilic cells and shadow cells apartfrom the left parotid gland. The tumor was encapsulated by fibrous tissue without stromalinvasion. Approximately 60% of the tumor cells consisted of shadow cells, and basophilic cells
were confirmed at the periphery of the tumor. The basophilic cells were oval-shaped with ahigh nuclear cytoplasm ratio and had an obvious nucleolus. Two mitoses were observed per
high-powered field. Focal squamous metaplasia, coagulative necrosis and apoptotic cells werealso observed. Eosinophilic-stained shadow cells showed nuclear concentration anddisappearance. Transitional histological findings were identified between basophilic cells andshadow cells, and supramatrical cells characterized by incomplete nuclear disappearance werealso seen (Fig. 4).
Immunohistochemically, basophilic cells and shadow cells were negative for anti-pan
cytokeratin antibody (AE1/AE3, diluted 1:800; Leica) and high-molecular-weight keratin(34βE12, diluted 1:200; DAKO), but squamous metaplastic cells were positive. β-catenin (3caten, diluted 1:400; DAKO) was positive for basophilic cells with nuclear and cytoplasmic
staining. Ki-67 (MIB-1, diluted 1:30; Biogenex) labeling index for basophilic cells and shadow
cells were 46.2 % and 0%, respectively, and the p53 (Bp53-12, diluted 1:200; IBL) labeling

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index were 94.8% and 0%, respectively. S-100 protein (2A10, diluted 1:400; IBL), HMB-45(HMB-45, diluted 1:200; DACO) and Ber-EP4 (Ber-EP4, diluted 1:400; DAKO) were negative
for basophilic cells and shadow cells. Fibrosis, calcification, foreign body granulomatous
reaction, foamy macrophage aggregation, and lymphocyte infiltration were observed in thetumor stroma. The tumor was completely resected. There was no metastasis to the lymph nodes
around the parotid gland.
On a re-evaluation of the cytological specimens, the ovoid-shaped epithelial cells wereconsidered to be basophilic cells. Shadow cells with nuclear disappearance were also confirmed.
Keratin fibers were found in the cytoplasm of the shadow cells (Fig. 5). Ultimately, we
concluded that these cytological findings were consistent with pilomatricoma.

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Discussion
This case report describes a rare proliferating pilomatricoma occurring in the parotid region ofan elderly man and rapidly increasing over a period of two years. In addition, the cytologicalfindings of this case were easily misdiagnosed as a malignant tumor, which should berecognized as a diagnostic pitfall.
Proliferating pilomatricoma was a rare variant of pilomatricoma and was first reported
by Kaddu et al. in 1997 [2]. According to their English literature, proliferating pilomatricoma
occurs often in the head and neck region of the elderly. It rapidly forms a large nodule andrarely ulcerates. Although malignancy is often suspected, it grows symmetrically with pushingmargins and lacks vascular or lymphatic permeation and lymph node metastasis [2].
Histologically, this variant is composed mainly of basophilic cells and a small amount of
shadow cells but in some cases comprises mainly shadow cells [2]. Furthermore, in the latephase lesion of pilomatricoma, the growth ability is arrested by the decrease in basophilic cells
and the relative increase in shadow cells [8]. Our case showed similar clinicopathologicalfindings to a previous paper, except for the small amounts of basophilic cell and lack ofulceration. Since the present tumor was considered to be a late-phase lesion of completely
resected proliferating pilomatricoma, a good prognosis is expected.

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On FNA cytology, the presence of basophilic cells causes pilomatricoma to be
misdiagnosed as a malignant tumor. Various diseases, including primary malignant skin tumor[7] (e.g. poorly differentiated carcinoma and Merkel cell carcinoma), primary malignant
salivary gland tumor [3] (e.g. mucoepidermoid carcinoma), metastatic tumor [6, 7] and smallround cell sarcoma [4] (e.g. rhabdomyosarcoma), must be considered, but it is almost
impossible to identify pilomatricoma based on the cytological findings of basophilic cells alone.
Therefore, it is extremely important to make note of the existence of shadow cells to ensure theaccurate cytological diagnosis of pilomatricoma. We did not doubt the clinical diagnosis forparotid gland tumor and failed to properly account for the presence of shadow cells.
Cytopathologists must be aware of the diagnostic pitfalls associated with this tumor.

Conclusions
We herein reported the cytopathological findings of proliferating pilomatricoma. This lesion
sometimes rapidly increases and may be mistaken for a malignant tumor. It is critical torecognize not only basophilic cells but also shadow cells. However, it cannot be diagnosed bycytological findings. The final diagnosis should be made on excision specimen only.

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Declarations
Consent for publication
Written informed consent was obtained from the patient for the publication of this case reportand any accompanying images. A copy of the consent form is available for review by the
Editor of this journal.

Availability of Data and Materials
The dataset supporting the findings and conclusions of this case report is included within thearticle.

Ethics approval and consent to participate.
All of the intended procedures in the present study, including the use of specimens from humansubjects, were approved with the written informed consent of the patient and next of kin,according to the guidelines of the Japan Society of Pathology. Ethical approval was obtainedby Kanazawa Medical University of institutional ethics committee.

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Funding
None.

Competing Interests
The authors declare no conflicts of interest in association with this study.

Authors’ Contributions
NK and SY participated in the conception of the study and writing of the manuscript. MY, MN,
XG,

AS,

SN

and

HM

performed

theclinicalimaging

and/orpathological/cytological/immunohistochemical interpretation of this lesion. All of the authors
have read and approved the final manuscript.

Authors’ Information
NK, XG, AS, SN and SY belong to the Department of Pathology and Laboratory Medicine,
Kanazawa Medical University, Ishikawa, Japan. MY and MN belong to the Department of
Pathology, Kanazawa Medical University, Ishikawa, Japan. HM belongs to the Department of
Diagnostic Pathology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.

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Acknowledgments
We would like to thank Seiya Mizuguchi, Yumi Tsubata, Yoshiiku Ohkanemasa, Michiho
Takenaka, Toshie Terauchi and Motona Kumagai for their expert technical assistance andhelpful comments.

Abbreviations
FNA

Fine-needle aspiration

MRI

Magnetic resonance imaging

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References
1. LeBoit PE, Burg G, Weedon D, Sarasin A. WHO Classification of Tumours. Pathology
and Genetics of Skin Tumours. Lyon: IARC Press, 2006, 153-155.

2. Kaddu S, Soyer HP, Wolf IH, Kerl H. Proliferating pilomatricoma. A histopathologic
simulator of matrical carcinoma. J Cutan Pathol. 1997, 24: 228-234.

3. Lemos LB, Brauchle RW. Pilomatrixoma: a diagnostic pitfall in fine-needle aspiration
biopsies. A review from a small county hospital. Ann Diagn Pathol. 2004, 8: 130-136.

4. Singh S, Gupta R, Mandal AK. Pilomatrixoma: a potential diagnostic pitfall in
aspiration cytology. Cytopathology. 2007, 18: 260-262.

5. Sivakumar S. Pilomatrixoma as a diagnostic pitfall in fine needle aspiration cytology:
a case report. Acta Cytol. 2007, 51: 583-585.

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6. Sharma D, Agarwal S, Jain LS, Kamal V. Pilomatrixoma masquerading as metastatic
adenocarcinoma. A diagnostic pitfall on cytology. J Clin Diagn Res. 2014, 8: FD13-14.

7. Bellafiore S, Tagliavini E, Carlinfante G, Piana S. Pilomatrixoma is a diagnostic trap in
fine-needle aspiration cytology of the parotid region. Diagn Cytopathol. 2016, 44: 516518.

8. Kaddu S, Soyer HP, Hödl S, Kerl H. Morphological stages of pilomatricoma. Am J
Dermatopathol. 1996, 18: 333-338.

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FIGURE LEGENDS
Figure 1. Fine-needle aspiration (FNA) cytology of the left parotid region. A cluster ofepithelial cells was observed (Papanicolaou staining, x400).

Figure 2. T1-weighted magnetic resonance imaging (MRI) of the left parotid region. A
well-defined multilocular tumor with heterogeneous enhancement was seen. The tumor was
located close to the outside of the left parotid gland.

Figure 3. Gross findings of the resected tumor. The cut surface showed a well-defined
lobulated tumor containing yellowish, muddy materials.

Figure 4. Histological findings of the tumor. The resected tumor cells consisted of shadow
cells, and basophilic cells were confirmed at the periphery of the tumor. A normal parotid gland
was located in the lower portion (H&E staining, scanning view). Basophilic cells and shadow
cells (inset) (H&E staining, x400).

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Figure 5. Fine-needle aspiration (FNA) cytology of the left parotid region. Shadow cellswith nuclear disappearance were found. Keratin fibers were seen in the cytoplasm of the shadow
cells (Papanicolaou staining, x1,000).

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Case Report
Cytopathological findings of proliferating pilomatricoma misdiagnosed as amalignant parotid gland tumor

Nozomu Kurose (k-nozomu@kanazawa-med.ac.jp)1*, Manabu Yamashita (yamabu@kanazawa-med.ac.jp)2, Mariko Nakano (mariko-n@kanazawa-med.ac.jp)2, Xin Guo(xinguo@kanazawa-med.ac.jp)1, Akihiro Shioya (a-shioya@kanazawa-med.ac.jp)1,
Satoko Nakada (snakada@kanazawa-med.ac.jp)1, Hiroshi Minato (hminato@ipch.jp)3,
Sohsuke Yamada (sohsuke@kanazawa-med.ac.jp)1
1

Department of Pathology and Laboratory Medicine & 2Department of Pathology,

Kanazawa Medical University, Ishikawa, Japan. 3Department of Diagnostic Pathology,
Ishikawa Prefectural Central Hospital, Ishikawa, Japan.

*Corresponding author: Nozomu Kurose, M.D., Ph.D. Department of Pathology andLaboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa,
920-0293, Japan. Tel: 81-76-218-8264; Fax: 81-76-286-1207; and E-mail: knozomu@kanazawa-med.ac.jp