Abstract: Trichomegaly is a benign tumor that occurs in the skin and is more common on the head, face and neck. It is known from the accumulation of cases, and the pathogenesis is not well understood. It occurs in adolescents and is more common in females. It is often diagnosed as a hard nodule on examination, and microscopic shadow cells are the main basis for diagnosis. This tumor has the potential to recur and become cancerous. Patients with multiple hairy stromal tumors may also have a familial genetic predisposition. Surgical removal of the tumor and its adherent tissues is an effective means of treatment. Maxillofacial surgeons should be more aware of this disease to improve the correct diagnosis.
Pilomatricoma (PM) is a benign tumor that occurs at the junction between the deep dermis and the subcutaneous fat of the skin. However, due to its diverse clinical manifestations, it can be easily confused with various cysts of the maxillofacial region and even parotid gland tumors and misdiagnosed (the misdiagnosis rate is quite high, sometimes up to 100%) [4], which may lead to recurrence (excisional coverage is too small) [9] or cause unnecessary damage to the patient (excisional coverage is too small) [9]. The result can be recurrence (under-resection) [9] or unnecessary damage to the patient (over-resection) [1] [4]. Therefore, it is necessary to improve the understanding of this disease.
1. Nomenclature and etiology of PM
Malherbe (1880) first called this hard skin mass a calcified epithelioma, thinking it to be a sebaceous gland tumor, but in 1905 he himself rejected it. 1961 Forbis and Helwig suggested the name pilomatrixoma, which was later changed to pilomatricoma (PM) [1].
PM originates from hair stromal cells, and electron microscopy and biochemistry confirmed its differentiation to the hair cortex and the presence of guanine within the cell nest keratin, suggesting the formation of hair keratin; and mutations in the N-terminal region of the cytoplasmic β-chain protein (encoded by CTNNB1) were found by genetic studies (at least 75% of PM undergo misfolding of the β-chain protein) to be the main cause of hair stromal tumor transformation [5].
Most patients with PM develop spontaneously without causative and uncomfortable symptoms, with the exception of a few. 5 (1.4%) of 355 patients reviewed by Hiromitsu et al [3] had experienced injury (bruises, scratches or animal scratches) at this site before developing PM, so some authors have proposed mechanical irritation as a causative factor for PM [6]. It has also been reported that at the injection entry point (0.56% of cases)
as well as in chemotherapy areas, surgical incision sites, foreign body invasion sites, etc. PM can occur [3].
However, the underlying cause of PM may be the stimulation of these sites, which causes changes in the local internal environment and induces genetic mutations, leading to hair stromal cell neoplasia.
2, Pathogenesis
The case of Moehlenbeck et al [2] showed that PM accounted for 1/824 of the skin tissue examinations in the same period, and the ratio of men to women was close to 2:3, while domestic data showed that it accounted for 1/20 to 1/1000 of the same period [4], and the ratio of men to women was close to 1:2 [7]. The disease can occur at all ages, Moehlenbeck et al [2] reported that 40.7% of the total number of cases occurred within 10 years of age and 61% within 20 years of age; domestic data [4] [7] showed that about 20% of cases occurred within 10 years of age and 50% within 20 years of age, i.e., it is more likely to occur in adolescents, but Celia [1] believed that the disease has a high incidence between 50-60 years of age. A high incidence period.
Hiromitsu et al [3] showed that 41.7% of cases occurred on the face, 30.4% on the upper extremities, 11.6% on the head, and 9.7% on the neck, and domestic data [4] and [7] also showed that the head, face and upper extremities accounted for about 80% of the total incidence, but it has not been reported to occur in the palm and abdomen, and some studies suggested that the growth site of PM is related to the density of hair follicles on the body surface. Some studies suggest that the growth site of PM is related to the density of hair follicles on the body surface. For example, the average density of hair follicles on the face is 705/cm2 and 459/cm2 on the scalp, but this does not explain the difference between the upper and lower extremities (similar density of hair follicles, but the incidence in the upper extremities is 30 times more than that in the lower extremities). This tumor occurs mainly at the junction between the deep dermis and subcutaneous fat (pathology shows only 7% of PM with clear fat encapsulation) [2]. The size of PM is generally 0.5-6.0 cm, [1], and up to 15 cm has been reported [9]. Most of them are single, with multiple occurrence accounting for 1.37% to 9.3% of the total [3] [4]. In China, Zhang Zicheng [7] observed 73 cases of solitary nodules, but 16.9% of them had scattered tumor nodules outside the microscopic envelope, which may be the histological basis for multiple PM, and 41 multiple PM nodules were also reported to be detected at one time abroad [10].
The nodules are mostly nodular, covered with translucent epidermis, and can be normal skin color (80%), red, blue, purple, light brown, etc. [11], and 25% can be faintly seen inside the white or yellow calcified spots. 20% of PM do not protrude from the skin, and a hard node can be palpated by palpation, and if the skin is tensed, it can show “tent-like” multiple nodules. There are two special types of PM, namely blistering type and penetrating type PM. The latter often shows red, red-blue, and black-brown nodules with marked skin keratinization and secretion of “lime-like” particles. ［The size of PM is generally proportional to the duration of the disease, but is not absolute [5].
3. Pathological features
Some scholars believe that most PM have intact envelope [4], but others believe that only 16.7% have clear envelope [7]. [7] Most of the sections are solid, grayish white, grayish red interspersed with grayish yellow granular material or with necrosis in the center in the form of bean pulp; when cystic, there may be reddish brown cystic fluid.
Microscopically, irregular clusters of epithelial cells were seen in the tumor interstitium, mainly composed of two types of cells: one kind of basophilic (present in 58% of PM), shaped like epidermal basal cells and located in the periphery; the other kind of cytoplasmic eosinophilic, with uncolored nuclei and only residual shadow, also called shadow cells (present in 100% of PM). The latter is necessary for the diagnosis of PM [7]. Statistically, eosinophils decrease or even disappear with the course of the disease, and shadow cells gradually increase, but shadow cells are not unique to this disease and are also seen in certain skin diseases, such as hair epithelial disease [13].
Eosinophils are immature megamastigmatocytes-primary germ cells that have a tendency to form irregular clusters of shadow cells, but are composed entirely of hair cortex and may have small, round eosinophilic keratinized centers in the center (in 23% of PM). Shadow cells as endogenous foreign bodies often cause foreign body giant cell reaction (in 83% of PM); calcification (in 69% – 85% of PM), ossification (in 15% of PM), and iron-containing heme (in 25% of PM), melanin (in 17% of PM) are seen in the interstitium. [2] Ossification is presumed to be due to the transformation of fibroblasts into osteoblasts [14], and ossification is proportional to the disease course [7]. The tumor parenchyma and interstitium may also form cyst-like due to degeneration.
4.Diagnosis, differential diagnosis and treatment of PM
The diagnosis of PM can be made according to the physical signs and clinical manifestations, but the gold standard of diagnosis needs to be combined with pathology. Ultrasound has advantages in determining whether it is a superficial soft tissue mass, cystic solidity, and boundary, and is more suitable for children with parotid masses to clarify the relationship with fascia (children often need general anesthesia for CT or MRI) [15]. Radiographs are of little diagnostic value for PM, and only large and calcified PM are shown [9]. The diagnosis of PM by needle aspiration cytology can be misdiagnosed as malignant in up to 50% of cases, so it is not advocated. [11].
Clinical misdiagnosis of PM is often due to the diverse presentation of the disease, the uncommonness of the cases, and the fragmentation of the consulting departments and the lack of physician awareness. The differential diagnosis of PM is to pay attention to some diseases similar to PM in terms of tissue origin, site of origin and appearance. When PM is light blue or light red, it should be distinguished from hemangioma (5% of misdiagnosis), and when it is located in the parotid area in front of the ear, it should be distinguished from mixed tumor, etc. Blister type PM should also be distinguished from lichen planus, blister type fixed drug rash, epidermolysis bullosa, etc. The main points of differentiation are: etiology, relationship with parotid occlusal fascia, presence of shadow cells, infiltrative growth, and presence of cellular heterogeneity. [1] [6] [13] [16]
The conventional and effective method of treating PM is surgical excision of the tumor and its adherent tissues (skin or subcutaneous tissues), and pathological examination to achieve both diagnostic and therapeutic purposes. Regarding the scope of surgery, many scholars only perform complete removal of the subcutaneous tumor (for the case of PM under the skin) and almost no recurrence is seen, so it is believed that preoperative surgery guided by correct diagnosis can reduce unnecessary damage to the patient [1] [4]. If PM adheres to the skin or surrounding tissues, invades the parotid occlusal fascia, ruptures, or is of the blister type, more tissue removal is also necessary.
PM has also been treated with CO2 laser and no recurrence has been seen after surgery. The disadvantage is that 4.1% of postoperative scars are formed and 7.5% have pigmentary changes. Hypothermic freezing, systemic or topical antimicrobial therapy is ineffective. [9].
5. Recurrence and carcinoma
Due to the limitation of the number of cases and follow-up time, there are differences in the statistics of recurrence rate, but most of them are less than 3% in Forbishe and Helwig [9]. PM carcinoma is clinically rare, and there were only 60 cases in foreign literature until 1999 [17]. McCulloch et al [18] observed a case of PM with multiple benign recurrences and carcinoma after 17 years. The hairy stromal carcinoma showed a typical PM image, but with active basophilic cell growth in some areas, marked heterogeneity, and increased nuclear division. Hairy stromal carcinoma is also called infiltrative PM, malignant PM, etc. The biological behavior is invasive, and the recurrence rate after surgery is as high as 46%-58% [19], and distant metastases such as lung and liver can also occur [17].
6, concomitant diseases of multiple PM
Multiple PM often suggests that the patient has other concomitant diseases. It has been reported that multiple PM can be associated with familial ankylosing muscular dystrophy [10], chromosome 9 trisomy [20], Steinert’s disease, sarcoidosis, Gardner syndrome, Turner syndrome, etc. [9]. The concomitant causes are not known.
REFERENCES
1, Julian CG, Bowers PW. et al. A clinical review of 209 pilomatricomas. J Am Acad Dermatol. 1998;39:191
2, Moehlenbeck FW. Pilomatrixoma (calcifying epithelioma). A statistical study.Arch Dermatol. 1973;108:532
3, Noguchi H, Hayashibara T, Ono T. A statistical study of calcifying epithelioma, focusing on the sites of origin.J Dermatol. 1995; 22:24
4, He H, Gao T, Li Q, et al. A clinical review of 146 cases of trichomegaly. Journal of Clinical Dermatology.2002;31;79
5, Chan EF, Gat U, Mcniff JM, et al. A common human skin tumour is caused by activating mutations in beta-catenin.Nat Genet. 1999;21;410
6, Inui S, Kanda R, Hata S. Pilomatricoma with a bullous appearance .J Dermatol. 1997; 24: 57
7, Zhang ZC, Li QH. Pathological histological observation of 73 cases of calcified epithelioma. Chinese Journal of Oncology.1991;13;313
8. Yang JJ, Tian JM, Qian ZM, et al. A case of subdeltoid calcified epithelial tumor of the shoulder. Journal of Clinical Radiology.1999;18;477
9, Duflo S, Nicollas R, Roman S, et al. Pilomatrixoma of the head and neck in children: a study of 38 cases and a review of the literature.Arch Otolaryngol Head Nech Surg. 1998;124:1239
10, Geh JL, Moss AL. Multiple pilomatrixomata and myotonic dystrophy: a familial association. Br J Plast Surg. 1999;52;143
11, MM, Kindblom LG, Meis-Kindblom JM, et al. Fine-needle aspiration features of pilomatrixoma. Cancer.2001;93;252
12, Fetil E, Ozkan S, Ilknur T, et al. Multiple pilomatricoma with perforation. Int J Dermatol. 2002;41:892
13, Qiu B S. Hair follicle tumors. Journal of Clinical Dermatology. 1990;19;36
14, Boyd AS, Martin RW 3rd.Pathologic quiz case Pilomatricoma (calcified epithelioma of Malherbe) with secondary ossification.Arch Otolaryngol . Head Neck Surg. 1992; 118:212
15, Fink, Melbourne, Robert, et al. Imaging case study of the month sonography in preauricular pilomatrixoma of childhood. ann otol rhinol laryngol. 1997;106: 167
16, Marrogi AJ, Wick MR, Dehner LP.Pilomatrical neoplasms in children and young adults.Am J Dermatopathol. 1992; 14:87
17, Bremnes RM, Kvamme JM, Stalsberg H, et al. Pilomatrix carcinoma with multiple metastases: report of a case and review of the literature.Eur J Cancer.1999;35:433
18, McCulloch TA, Singh S, Cotton DW.Pilomatrix carcinoma and multiple pilomatrixomas.Br J Dermatol, 1996;134:368-371.
19, Sau P, Lupton GP, Graham JH.Pilomatrix Ccarcinoma.Cancer.1993;71;2491
20, Atsuura H, Hatamochi A, Nakamura Y, et al. Multiple pilomatricoma in trisomy9.Dermatology. 2002;204;82