Indian Journal of Dermatology
: 2016  |  Volume : 61  |  Issue : 3  |  Page : 348-

Twelve years' observation of multiple familial trichoepithelioma with squamous carcinoma

Huifu Ma1, Song Feng1, Wenjun Pei2, Feng Jin1,  
1 Department of Neurosurgery, Affiliated Hospital of Jining Medical College, Jining, Shandong, PR China
2 Department of Pathology, Tuha Petroleum Hospital, Hami, Sinkiang, PR China

Correspondence Address:
Dr. Song Feng
Department of Neurosurgery, Affiliated Hospital of Jining Medical College, Jining, Shandong 272029
PR China


Long-standing trichoepithelioma lesion on scalp with 12 years follow-up. The patient was observed for 12 years, and the carcinoma recurred 3 times during 8 years after surgical excision and radiation therapy. Malignant transformation may occur in multiple familial trichoepitheliomas; Moderate radiation therapy should be given for malignant transformation patients with lower radiation dose and shorter time. Removing the trichoepithelioma as soon as possible if the tumor suddenly or continuously increased is recommended.

How to cite this article:
Ma H, Feng S, Pei W, Jin F. Twelve years' observation of multiple familial trichoepithelioma with squamous carcinoma.Indian J Dermatol 2016;61:348-348

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Ma H, Feng S, Pei W, Jin F. Twelve years' observation of multiple familial trichoepithelioma with squamous carcinoma. Indian J Dermatol [serial online] 2016 [cited 2021 Oct 19 ];61:348-348
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Multiple familial trichoepithelioma (MFT) is a congenital dermatosis characterized by the presence of many small tumors located predominantly on the face and is inherited as an autosomal dominant trait. Basal cell carcinoma, pilomatrix, and trichoblastic carcinoma are the only malignant hair follicle tumors that have been well established as entities up to now.[1],[2] The hypothesis that trichoblastic carcinoma develops from trichoblastoma has been debated.[3],[4] Herein, we report a case of trichoepithelioma co-existing with squamous carcinoma on scalp for 12 years.

 Report of a Case

A 63-year-old Chinese woman (Nationality: Uyghur) presented with numerous, dome-shaped, skin colored, painless, pea-sized papules, and nodules on her scalp and back. All the papules had developed since childhood and enlarged slowly. Our recommendation was that she should be treated surgically, but she refused as she was asymptomatic. Four years later, the lumps on the frontal, occipital and posterior scalp enlarged suddenly and the size of tumors were 15 cm × 8 cm, 9 cm × 6 cm, 8 cm × 8 cm corresponding [Figure 1]. The diameter of the other nodules ranged from 1 cm - 5 cm. The frontal mass enlarged rapidly and had been ulcerated for 1 year, with a cauliflower-like hairless surface that bled easily with a fishy smell and the center of the tumors had pus-filled ulcers. The base was indurated, and pale granulation tissue was observed at the bottom of the ulcer.{Figure 1}

After admission to the hospital all the tumors were removed radically, and the frontal scalp was repaired gradually. During the operation, we found the masses grew homogeneously in the subcutis with a flexible, grayish, and complete capsule except the frontal one. The pathological diagnosis showed trichoepithelioma, composed of epithelial cell nests, horn cysts, and there was keratotic materials and calcium salt deposition in the cell nests [Figure 2]. The frontal tumor was hard, cauliflower-like, rich in blood supply, and without a complete capsule. The skull bone under the center of mass was eroded, and the erosion area was a 2 cm circle, deep into the inner table of the skull. The rongeur was used to bite 2 cm more skull around the erosion area. Postoperative pathological examination revealed a trichoepithelioma with squamous cell carcinoma [Figure 3] and [Figure 4]. The histopathology revealed cancerous areas with wide-ranging nest sizes cancer cells (squamous cell) with large nuclei, cellular atypia, cornified pearls and intercellular bridges, and interstitial fibrous and tissue hyperplasia. Further inquiry about the patients' history provided history of similar swellings in other family members. Therefore, a diagnosis of MFT in association with squamous cell carcinoma of scalp was made. Radiotherapy was recommended, but the patient refused due to economical reasons.{Figure 2}{Figure 3}{Figure 4}

One year and a half after the surgery, the swelling on the frontal scalp became swollen gradually with ulceration and progressed to the area where the tumor had been removed. Approximately, 2 years after resection, the frontal tumor was larger than its preoperative size, cauliflower-like, and the skin was ulcerated [Figure 5]. However, other parts of the scalp where the nonmalignant trichoblastoma had been excised were flat. Head computed tomography (CT) showed the recurrence of the frontal scalp tumor and an osteolytic lesion could be seen on the frontal bone, but the tumor did not penetrate into dura mater [Figure 6]. Now the patient accepted radiation therapy (DT = 40 Gy/20f/4w), 5 months later the lump became small gradually and disappeared, but the surface of the lump was still eroded.{Figure 5}{Figure 6}

Around the 4th to 5th year after resection which was about 2 or 3 years after radiation therapy, the frontal tumor relapsed again, and this time, the shape of the tumor was similar with previous one, but the size was smaller [Figure 7]. To avoid the further increase, the patient accepted the second course of radiotherapy (DT = 60 Gy/30F/6W), with similar efficacy as the primary treatment.{Figure 7}

In the 6th year after resection which was about 1 year after the second radiotherapy, she felt discomfort in the right upper abdomen and had decreased appetite. In addition to the gastrointestinal symptom, her right limbs developed tremors and lost strength; sometimes she presented with seizures, but she was conscious after twitching. Abdominal CT showed a low signal lesion in liver [Figure 8]. On the basis of the past medical history, we deduced that the scalp squamous cell carcinoma had progressed to liver metastasis. Magnetic resonance imaging examination of the brain showed that she suffered from radiation encephalopathy of left cerebrum, and the skull damage continued to expand, but cancer had not infiltrated the brain [Figure 9]. At that time, she opted for palliative care and refused further treatment.{Figure 8}{Figure 9}

Around the a 7th year after excision, the squamous carcinoma on frontal scalp relapsed for the 3rd time, and the condition was same as the previous two relapse with surface infection and ulceration. The other tumors that had been removed and diagnosed as trichoepithelioma were free from relapse. The general condition of the patient became worse, with low intelligence poor appetite, weight loss, decreased strength, right limb tremor, and intermittent convulsions. She refused any form of examination and treatment, and the general condition of the patient continued to deteriorate. She ate less or even skipped meals, which caused her significant weight loss and malnutrition. Soon she appeared cachexia, completely bedridden, but she was conscious until she died. In January 2013, the 8th year after the surgical excision, the patient died at home at the age of 75.

It should be mentioned that, there were 17 patients had similar symptoms in her family out of 122 people, but with less severe lesions and the tumors grew slowly or not at all. The other family members were in good health.


Trichoepithelioma is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face, neck and upper trunk beginning in childhood. When more than one family member is affected, the disease is known as MFT. There can be small trichoepitheliomas on the scalp; large ones may develop malignant degeneration. The previous report is similar with our report in the following aspects: Older patient; numerous, painless papules and nodules since young; some tumors which enlarged suddenly in recent years; the tumors had ulcerated surfaces; easy bleeding and a fishy smell with similar cases in the family.[5]

Malignant follicular neoplasms include basal cell carcinoma trichoblastic carcinoma, and pilomatrix carcinoma.[3],[6],[7] Small basaloid cells are the typical feature of basal cell carcinoma. The trichoblastic carcinoma cells were made up of large cells with abundant cytoplasm. There is no peripheral palisading of neoplastic cells and no cleft between the tumor lobule and the surrounding stroma.[3] and lack the typical shadow cells, which is mandatory for a diagnosis of pilomatrix carcinoma.[6]

Squamous cell carcinoma must be taken into consideration when amphophilic cytoplasms of neoplastic cells are observed.[1] Our case shared the features of MFT coexisting

with squamous carcinoma, the tumors were large in size, solitary, asymmetric, infiltrative growth with high mitotic activity, at the base of a long-standing trichoepithelioma with sudden enlargement with inflammation and osteolytic lesions. The key histopathology features of squamous cell carcinoma are intercellular bridges, squamous eddies, and areas with a glassy cytoplasmic appearance, which is consistent with our observation.

Lung and liver are the most common organs of metastasis. In this case, opinions diverge that whether the mass in the liver was caused by metastasis. Although it had not been pathologically proven, we predicted that the tumor was more likely caused by tumor metastasis according to the pain of upper abdominal, anorexia, history of malignancy tumor, and radiographic characteristics.

There is controversy whether a malignant transformation of trichoblastoma actually occurs. Regauer suggested that the tumor may have arisen de novo in a patient predisposed to the formation of follicular tumors.[8] On the other hand, it may have been a malignant degeneration of a preexisting benign neoplasm. Schulz reported a case of trichoblastic carcinoma at the base of a trichoepithelioma; they also documented a clearly visible transitional zone between this malignant follicular tumor and the adjacent trichoepithelioma.[3]

MFT has been associated with mutations in the CYLD gene on a chromosome.[9] Mutations in this gene have also been linked to familial cylindromatosis and Brooke–Spiegler syndrome, in which the patients develop trichoepitheliomas and cylindromas.[10] CYLD gene has tumor suppressor properties and influences cell survival and proliferation. CYLD has also been shown to negatively regulate tumor necrosis factor alpha-induced activation of nuclear factor kappa beta.[9]

As the tumor occurred in the skin when it relapsed, subsequent surgery was improper for iatrogenic risk of metastasis, so for maintenance of quality of life, radiation therapy was selected, as it is effective for controlling a wide range of tumors. Although the efficacy of radiation therapy for malignant trichoepithelioma is limited due to a limited number of studies and its rare occurrence, this treatment has been widely accepted and in common use. The modality of this treatment can be used alone or in combination with other therapies, including surgery and chemotherapy. Radiation therapy is expected to down-regulate regional inflammation, and decrease the progression of metastatic lesions. In our case, partial response was observed, the size of all the skin tumors decreased obviously after radiation therapy. Although acute and chronic adverse effects of radiation have been reported, serious adverse effects were observed in our case, unfortunately. After receiving the second dose of radiotherapy, the patient suffered from radiation encephalopathy of the left cerebrum. Hence, we recommend moderate radiation therapy should be used for osteolytic lesion patients with lower dose and shorter time.


In summary, this rare case shared the features of MFT coexisting with squamous cell carcinoma. The patient was observed for 12 years, and the carcinoma recurred 3 times during 8 years after surgical excision. Histopathology revealed trichoepithelioma and squamous cell carcinoma in the same tumor on the frontal area and the presence of the trichoepithelioma cells and the squamous carcinoma cells adjacent to each other. So the possible mechanism is that the trichoepithelioma deteriorated to squamous carcinoma or the normal skin cells transformed into carcinomatous cells due to inflammation, ultraviolet radiation and other factors. In addition, squamous cell carcinoma can directly develop from the skin follicle cells by mutation must be taken into account.

To be on the safe side, removing the trichoepithelioma as soon as possible if the tumor suddenly or continuously increase is recommended. Surgical excision appears to be appropriate and prudent treatment, as these lesions may have a slow but persistent growth and attain a considerable size. The previously unrecognized plaque variant is also slow growing and may become quite large with ill-defined tumor margins. This variant may demonstrate locally aggressive behavior with an infiltrative growth pattern. If the patient refuses excision, he/she should be kept under long-term observation because there is a possibility of malignant transformation.

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