This is a common and benign skin tumor derived from the hair follicle. They usually occur on the head and neck and are more common in women. There is an extremely rare malignant variant of this disease known as a pilomatrical carcinoma.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
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EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Calcifying epithelioma of Malherbe AGE RANGE-MEDIAN Bimodal
>60% occur before the third decade
Second peak takes place between the sixth and seventh decades
SEX (M:F) Females
DISEASE ASSOCIATIONS CHARACTERIZATION GARDNER'S SYNDROME Hautarzt 1990;41:326-8. MYOTONIC DYSTROPHY Arch Dermatol 1978;114:1363-5.
PATHOGENESIS CHARACTERIZATION HARD KERATINS
- Expression of Hard a-Keratins in Pilomatrixoma, Craniopharyngioma, and Calcifying Odontogenic Cyst.
Kusama K, Katayama Y, Oba K, Ishige T, Kebusa Y, Okazawa J, Fukushima T, Yoshino A.
Department of Oral Pathology, Meikai University School of Dentistry, Saitama, Japan.
Am J Clin Pathol. 2005 Mar;123(3):376-81. Abstract quote
To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard a-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard a-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst.
In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components.
Immunoreactivity for phosphothreonine, detected in hard a-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors.
CLINICAL AND GROSS VARIANTS CHARACTERIZATION BULLOUS Pilomatricoma with a bullous appearance.
Yiqun J, Jianfang S.
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, PR China.
J Cutan Pathol. 2004 Sep;31(8):558-60. Abstract quote
Background: Pilomatricoma is a benign, cutaneous neoplasm with differentiation toward hair matrix. The tumor is usually a deep-seated, solitary, firm nodule with overlying normal epidermis. Pilomatricoma with a bullous appearance is very rare.
Methods: A 16-year-old Chinese girl with a soft, purplish, translucent bulla on the left shoulder for 6 months and a nodule underlying the bulla is described.
Results: The histopathologic findings were consistent with pilomatricoma. There was extraordinary dilation of lymphatic vessels in the overlying dermis, which explains the clinical bullous appearance. The surrounding dermis had an edematous appearance. A Verhoeff-van Gieson stain disclosed the marked reduction of the elastic fibers, and an alcian blue stain was negative.
Conclusions: The patient is diagnosed as bullous variant of pilomatricoma.
Multiple familial pilomatricomas: an unusual case
Virginia G. Hubbard and Sean J. Whittaker
Journal of Cutaneous Pathology
Volume 31 Issue 3 Page 281 - March 2004 Abstract quote
Although solitary pilomatricomas are relatively common, multiple pilomatricomas occur rarely, in 2-3.5% of reported cases.
The majority of cases of familial multiple pilomatricomas occur in association with myotonic dystrophy. The occurrence of multiple familial pilomatricomas in patients who are otherwise well is extremely rare.
We describe a 29-year-old man with multiple pilomatricomas whose father and brother also had similar lesions. There is no history of myotonic dystrophy.
HISTOLOGICAL TYPES CHARACTERIZATION General
Epithelial islands of basaloid cells and shadow or ghost cells
Basaloid cells have deeply basophilic oval or round nuclei and are found at the periphery of the islands
Often a transition zone of retained nuclei from the basaloid cells to the eosinophilic shadow cells
Deeply basophilic calcium may also be seen, and ossification occurs occasionally
Mitotic figures may be identified
- Am J Dermatopathol. 2006 Dec;28(6):510-513. Abstract quote
Pilomatricoma is a follicular neoplasm that shows differentiation towards the follicular matrix, as characterized by matrical cells and shadow cells. In addition, this is sometimes accompanied by differentiation toward the follicular infundibulum and outer root sheath. These finding suggest that pilomatricoma can subtly differentiate towards any structure of the follicle. However, morphologically, no distinct germinative cells resembling embryonic follicular germ cells have been found in pilomatricoma to date.
We report on two cases of pilomatricoma in which distinctive follicular germinative cells palisaded at the edges of collections of matrical cells.
We propose two explanations: one is that the metrical cells of pilomatricoma can focally de-differentiate to form follicular germinative cells, and the other is that these follicular germinative cells are the precursor cells of pilomatricoma.
VARIANTS PILOMATRIX CARCINOMA
Cancer 1993; 71:2491-8.
Am J Dermatopathol 1984;6:63-9.
Male-to-female ratio of 2:1
Mean age of affected patients is 48 with a reported range from age 2 to 88
Features of benign pilomatrixoma as well as nuclear atypia and more numerous mitoses, some of which may be atypical
Tumor necrosis is often present
Infiltration into the subcutaneous fat, blood vessels, nerves, and muscle also suggests malignancy
- Expression patterns of hair and epithelial keratins and transcription factors HOXC13, LEF1, and beta-catenin in a malignant pilomatricoma: a histological and immunohistochemical study.
Cribier B, Worret WI, Braun-Falco M, Peltre B, Langbein L, Schweizer J.
Department of Dermatology, University Hospital, Strasbourg, France.
J Cutan Pathol. 2006 Jan;33(1):1-9. Abstract quote
Background: We have previously shown that benign pilomatricomas not only maintain the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1 of normal hair follicles in their transitional cell compartment, but also preserve the association of hHa5 expression with that of its regulatory homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1 expression in the upper transitional cell compartment is uncoupled from the nuclear co-expression of the LEF1/beta-catenin complex seen in normal hair follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078).
Methods: Formalin-fixed paraffin sections of the tumor were examined using a panel of mono- and polyclonal hair and epithelial keratin antibodies as well as antibodies against HOXC13, LEF1, and beta-catenin.
Results: Morphologically, the malignant pilomatricoma investigated here clearly deviated from the described major tumor type by a large number of differently sized parakeratotic squamoid whorls emerging within the mass of basaloid cells and surrounded by cells remembering transitional cells, but only rarely containing shadow cells and signs of calcification. We show that hHa5/HOXC13 co-expression was maintained in transitional cell areas, in which hHa1 expression was much stronger than in benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/beta-catenin expression. Surprisingly, however, and in clear contrast to benign pilomatricomas, these transitional cells co-expressed the epithelial keratins K5, K14, and K17, with the latter being as strongly expressed as hHa1, both also staining the entire inner mass of the parakeratotic whorls.
Conclusions: Although the malignant pilomatricoma investigated here was distinctive in that it contained a multitude of parakeratinizing whorls and no signs of calcification, it shared both hHa5/HOXC13 co-expression and disrupted hHa1/beta-catenin-LEF1 expression in its transitional cell compartment around the whorls with benign pilomatricomas. However, in clear contrast to the latter, transitional cells of the malignant tumor also strongly expressed the epithelial keratins K5, K14, and K17. We speculate that the observed dominance of the epithelial differentiation pathway over the competing conventional shadow cell differentiation pathway may prevent massive calcification of the tumor.
- Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding beta-catenin.
Lazar AJ, Calonje E, Grayson W, Dei Tos AP, Mihm MC Jr, Redston M, McKee PH.
Department of Pathology, Division of Dermatopathology, Brigham and Women's Hospital, Boston, MA, USA.
J Cutan Pathol. 2005 Feb;32(2):148-57. Abstract quote
Mutations in beta-catenin are present in benign pilomatrixomas. beta-catenin is a downstream effector in the WNT-signalling pathway, acting as a signal for differentiation and proliferation. Mutations in CTNNB1, the gene encoding beta-catenin, are present in a wide variety of benign and malignant neoplasms.
We examined beta-catenin in a series of pilomatrix carcinomas (15 cases) by using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1, and compared these to a series of benign pilomatrixomas (13 cases). All 11 pilomatrix carcinomas available for examination showed nuclear localization of beta-catenin and mutations in exon 3 similar to those demonstrated in benign pilomatrixomas. Two of 11 pilomatrix carcinomas showed significant nuclear accumulation of p53, whereas this was absent in all 13 benign pilomatrixomas. Expression of nuclear cyclin D1 was similar in both benign pilomatrixomas and pilomatrix carcinomas.
Clinical follow-up from the 15 malignant cases reported in this study and by others indicates that wide excision offers superior control of local recurrence, compared to simple excision. Immunohistochemical and molecular analysis of beta-catenin reveals that both pilomatrix carcinomas and benign pilomatrixomas harbour mutations in beta-catenin.
This implies a common initial pathogenesis and is compatible with the proposition that pilomatrix carcinomas may at least on occasion arise from their benign counterparts.
- Pilomatrix carcinoma with lymph node metastases.
Bassarova A, Nesland JM, Sedloev T, Danielsen H, Christova S.
Department of Pathology, Alexander University Hospital, Medical University, Sofia, Bulgaria, Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway, and Department of Surgery, Alexander University Hospital, Medical University, Sofia, Bulgaria.
J Cutan Pathol. 2004 Apr;31(4):330-335. Abstract quote
Pilomatrix carcinoma is a rare skin tumor with an origin from hair matrix cells. The tumor is locally aggressive with a great tendency for recurrence, but the metastatic potential is limited.
A pilomatrix carcinoma in 76-year-old female with lymph node metastases is presented. In addition to classical histopathological criteria and DNA ploidy analysis, a broad panel of antibodies was used for evaluation of the metastatic potential. Both primary tumor and lymph node metastasis revealed extremely high proliferation and apoptotic rates. High constant expressions of CD44v6 and P-cadherin were also observed. In the metastasis, significant reduction of E-cadherin and beta-catenin was detected.
The best approach for assessment of metastatic potential of pilomatrix carcinoma seems to be the complex evaluation of routine histological criteria like vessel invasion, mitotic index, apoptotic count, and new molecular markers of cell death and adhesion.
A report of a case arising from a previously excised pilomatrixoma and a review of the literature
J Am Acad Dermatol 2001;44:358-61. Multiple pilomatrix carcinomas of the head and neck Otolaryngol Head Neck Surg 1993;109:543-7. Pilomatrix carcinoma with pulmonary metastasis, report of a case Cancer 1984;54:370-2.
Pilomatrix Carcinoma: A Clinicopathologic Study of Six Cases and Review of the Literature
David Hardisson, M.D.; M. Dolores Linares, M.D.; Jesús Cuevas-Santos, M.D.; Félix Contreras, M.D.
From the Departments of Pathology (D.H., F.C.) and Plastic and Reconstructive Surgery (D.L.), La Paz University Hospital, Autonomous University of Madrid, Madrid, and Department of Pathology (J.C.-S.), University General Hospital of Guadalajara, Alcalá University, Guadalajara, Spain.
Am J Dermatopathol 2001;23:394-401 Abstract quote
Pilomatrix carcinoma, the malignant variant of pilomatrixoma, is a rare entity.
The authors report on six patients with pilomatrix carcinoma and review the pertinent literature.
The lesions showed a predilection for elderly individuals (mean age, 61 years) with a male:female ratio of 5:1, and they presented as dermal or subcutaneous tumors located on the head and neck (5 neoplasms) and chest (1 neoplasm). Tumors varied in size from 0.6 cm to 2.5 cm (mean, 1.78 cm). None of the lesions recurred after wide local excision.
On scanning magnification, all tumors showed the architectural features of a malignant neoplasm (asymmetry and poor circumscription, presence of several markedly sized and variably shaped basaloid aggregations, and ulceration). The tumors were composed of pleomorphic basaloid cells with prominent nucleoli and frequent atypical mitoses accompanied by central areas with keratotic material, shadow cells, and foci of necrosis. The tumor nests were surrounded by a desmoplastic stroma and infiltrated the adjacent tissues. Vascular or perineural infiltration was not observed. In one case, the basaloid cells contained abundant melanin pigment in their cytoplasms.
Pilomatrix carcinoma is a neoplasm of low-grade malignancy that should be distinguished from the conventional pilomatrixoma and its variants (aggressive pilomatrixoma and proliferating pilomatrixoma), matricoma, and basal cell carcinoma with matrical differentiation. Clinicians and pathologists should be aware of the occurrence of pilomatrix carcinoma because of its potential for distant metastases.
Pilomatrix carcinoma with lymph node and pulmonary metastasis: report of a case arising on the knee.
De Galvez-Aranda MV, Herrera-Ceballos E, Sanchez-Sanchez P, Bosch-Garcia RJ, Matilla-Vicente A.
Dermatology Service (M.V.D.G.-A., E.H.-C., P.S.-S., R.J.B.-G.) and Pathology Service (A.M.-V) Faculty of Medicine, Virgen de la Victoria University Hospital, Malaga, Spain.
Am J Dermatopathol 2002 Apr;24(2):139-43 Abstract quote
A 58-year-old woman presented with a pilomatrix carcinoma on the right knee. The tumor developed at the site of a previous lesion that had been present since she was 30 years old.
Histologic study showed the presence of basaloid cells with numerous atypical mitoses, shadow cells, and calcification. After several surgical excisions, the tumor mass infiltrated the subcutaneous tissue, muscle, and bone, resulting in inguinal lymph node and pulmonary metastasis.
We also review the literature and comment on the histopathologic differences from other cutaneous tumors.
- Am J Dermatopathol. 2006 Oct;28(5):426-428 Abstract quote
We describe a pilomatricomal horn on the right arm of a 39-year-old man. Although initially the tumor was clinically thought to be a verruca vulgaris, the microscopic features were similar to those found in classic pilomatricoma, except for the epidermal location and the presence of a cutaneous horn.
Light microscopy showed replacement of the epidermis by basaloid cells, with masses of cornified material containing shadow cells that formed a cutaneous horn.
Whereas classic pilomatricoma is confined to the deep reticular dermis or subcutis, the present case represents a unique heretofore unreported epidermal variant of pilomatricoma that pathologists should be aware of to differentiate it from malignant epidermal tumors.
SPECIAL STAINS/IMMUNO-PEROXIDASE CHARACTERIZATION COLLAGEN, TYPE II
- Bone morphogenetic protein-mediated type II collagen expression in pilomatricoma and cutaneous mixed tumor.
Mieno H, Kuroda K, Tajima S.
Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan.
J Cutan Pathol. 2005 Mar;32(3):206-11. Abstract quote
Background: We have previously reported that type II collagen deposition in overlying dermo-epidermal junction (DEJ) of pilomatricoma is mediated by bone morphogenetic protein 2/4 (BMP 2/4) expressed by shadow cells (SCs) of pilomatricoma.
Objective: This time, we studied the expression of type II collagen and BMP in a large number of cases of pilomatricoma and extended our study to cutaneous mixed tumor (CMT).
Results: We found type II collagen deposition in the overlying DEJ (16 of 50 cases) and in the SCs (19/50) of pilomatricoma. The number of case of type II collagen deposition in DEJ (DEJ(+)) and in SCs (SC(+)) of pilomatricoma correlated to the chronological stage of pilomatricoma. We also found type II collagen deposition in overlying DEJ (two of 11) and in the stromal chondroid tissue (four of 11) of CMT. BMP 2 was expressed in most cases of pilomatricoma (37/50) and CMT (seven of 11).
Conclusions: The expression of type II collagen in pilomatricoma is dependent upon the chronological stage of pilomatricoma. Type II collagen expression in the overlying DEJ and chondroid matrix in CMT may be induced by BMP via the same mechanism as in pilomatricoma.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Metastasis
Cases of Carcinoma
PC is locally aggressive and many cases detail direct invasion into adjacent bone
Local recurrence is common unless the tumor is excised with a wide surgical margin
26 of 72 recurred locally and 8 had metastatic disease
Metastases to the lung, bone,and lymphatics
Widespread metastases may also occur
4 deaths attributed to metastatic disease
Reported systemic associations include angioimmunoblastic lymphadenopathy and hypercalcemia
TREATMENT Simple excision is usually curative for benign tumors
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