Trichilemmal carcinoma in China: A case report and systematic literature review

Abstract

Purpose: This study aimed to delineate the clinicopathological characteristics of trichilemmal carcinoma (TLC) in China, analyze its evolving epidemiological trends, and provide insights to improve clinical diagnosis and management through a comprehensive literature review and case-based analysis. Methods: A retrospective analysis of 40 years (1984–2023) was conducted by reviewing Chinese and English databases for TLC cases in Chinese populations. Data on epidemiology, clinical presentation, histopathology, treatment modalities, and prognosis were systematically collated, supplemented by a detailed case report to illustrate diagnostic and therapeutic challenges. Results: Among 230 documented cases, TLC exhibited a near-equal gender distribution (113 males, 117 females) and a rising incidence, with 50.43% (116/230) reported in the last decade (2014–2023). The patients showed a broad age distribution (20–97 years), with lesions predominantly concentrated in the head/neck region (87.83%, 202/230). Non-specific clinical features (papules, nodules, ulceration) contributed to frequent misdiagnosis. Metastasis (13 cases) and recurrence (14 cases), primarily in head/neck tumors, correlated with high mortality. Immunohistochemistry identified CK-H and EMA as key positive markers and S-100/CK-L as negative discriminators, with 23.91% (55/230) showing periodic acid-Schiff (PAS) positivity. Surgical excision was the primary treatment (87.39%), while adjuvant therapies (radiotherapy/chemotherapy) demonstrated limited efficacy. Conclusion: The increasing incidence of TLC in China, its anatomical predisposition to aggressive behavior, and poor prognosis in metastatic/recurrent cases necessitate improving early detection and optimizing treatment strategies for this rare malignancy.

Introduction

Trichilemmal carcinoma (TLC), also known as tricholemmal carcinoma, was first reported by the American pathologist Headington in 1976. ¹ TLC is a type of low-grade malignant tumor of the skin that grows slowly, with infrequent recurrence and metastasis. Recurrence typically occurs locally, and metastases commonly involve lymph nodes near the tumor. The occurrence of metastasis occurs indicates a poor prognosis. ²

The clinical presentation of TLC lacks specificity, manifesting as slowly growing papules, plaques, or nodules with a smooth surface, crusting, or keratosis. TLC may also present with ulceration, bleeding, and ulcer formation, increasing its likeliness of being misdiagnosed as a common skin tumor, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma, and keratoacanthoma. In recent years, the incidence of TLC has shown an increasing trend, especially in Asia and China, ³ albeit mostly reported as sporadic cases. In this study, a systematic analysis of Chinese TLC patient reports retrieved from both Chinese and English databases was performed, providing comprehensive insights into the epidemiological status, clinical manifestations, treatment methods, and prognosis of TLC patients. Additionally, by presenting a patient with TLC treated at our institution, we aimed to provide a more comprehensive analysis of the clinical and pathological characteristics, treatment, and prognosis of Chinese individuals with TLC. The goal of this study was to serve as a reference for the clinical diagnosis and treatment of TLC.

Materials and methods

We searched for relevant literature on “TLC” and all its variant terms in the Chinese databases CNKI, Wanfang Data, and VIP (Figure 1). After excluding duplicates and non-TLC cases, a total of 67 Chinese articles including 204 patients were obtained. The same method was employed to search relevant studies on Chinese patients in PubMed, Embase, and Web of Science. After excluding duplicate articles and non-Chinese TLC patients, 12 articles reporting 53 patients were obtained. The literature inclusion period ranged from December 26, 1984, to March 1, 2023. The exclusion criteria were as follows: (1) Duplicate articles exclusion: Duplicate articles were identified through cross-referencing of key clinical variables, including patient age, gender, lesion location, onset time, and institutional affiliation. Cases with ≥3 overlapping variables across different publications were considered duplicates and excluded after manual verification by two independent reviewers (L.L and Y.C.H). Discrepancies were resolved through discussion with a third reviewer (Z.D.Y). (2) Articles with unclear pathological diagnoses: Cases lacking sufficient pathological evidence (e.g., incomplete histology reports) were excluded, and cases with controversial pathological diagnoses were evaluated by senior pathologist H.P in accordance with the established diagnostic criteria for TLC. (3) Articles with incomplete information. (4) Articles with non-Chinese TLC patients. A further search and full-text analysis of both the Chinese and English studies yielded a total of 79 articles, with 27 duplicate cases removed. Finally, a total of 77 Chinese and English articles reporting 230 patients were included for analysis.

Figure 1.

Flowchart of the selection process for Chinese and English articles on trichilemmal carcinoma in a Chinese population.

Representative case

A 60-year-old male presented with a gradually enlarging mass on the skin of the left axilla for more than 30 years, which ruptured and discharged fluid 50 days before admission. Thirty years ago, a painless lump, approximately the size of a peanut, was discovered in the patient’s left anterior axilla; the lump gradually increased in size and was not treated with any intervention. Fifty days ago, the patient noticed a red and swollen lump of unknown origin in the same area, which subsequently ruptured and discharged fluid. A biopsy performed outside the hospital revealed TLC. The patient had no significant past medical or family history. On physical examination, a protruding skin mass approximately 6.0 cm × 8.0 cm in size was observed near the chest wall in the left anterior axillary region. The mass appeared deep brown in color, with a volcanic-like ulceration at its base, accompanied by a foul odor and adhesion to surrounding tissues. Multiple enlarged lymph nodes were palpable in the left axilla, which were firm and not tender. Ultrasonography revealed multiple abnormal lymph nodes in the left axilla. Positron Emission Tomography-Computed Tomography (PET-CT) imaging indicated metabolic activity in the subcutaneous mass of the left axilla, with accompanying lymph node metastasis. Chest MR imaging revealed multiple nodules and masses in the left axilla with surrounding infiltration and unclear demarcation from the left pectoralis major muscle. Preoperative examinations, including blood routine, blood biochemistry, coagulation function, and infectious disease screening, showed no significant abnormalities.

After admission, under general anesthesia, the patient underwent left axillary and chest wall TLC wide excision with a 2-cm margin, intraoperative frozen section, left axillary lymph node dissection, and reconstruction with a thoracodorsal artery perforator flap. Histological examination revealed infiltration of the TLC into the dermis and subcutaneous fibrofatty tissue, with thrombi observed in blood vessels but no evidence of neural invasion. Tumor involvement was not identified at the margins or the base. Lymph node examination revealed metastasis (8/11 in the surrounding left axilla, 0/9 at the apex of the left axilla). Immunohistochemistry showed positive staining results for CK-pan, CK5/6, CK7, EMA, P40, P53, and P63 and approximately 50% positive staining for Ki67. Special staining with PAS was also positive. The skin flap showed good survival at 2 weeks postoperatively. The discharge diagnosis was left axillary and chest wall TLC with left axillary lymph node metastasis.

One month postoperatively, the patient returned to our department due to a skin mass on the left shoulder. On examination, masses of varying sizes were observed at the edge of the previous surgical incision on the left shoulder, and the skin mass was approximately 4 cm × 5 cm in size on the shoulder. The patient underwent enlarged resection of the left shoulder and chest wall mass, with Split-thickness skin grafting. Postoperative pathology revealed TLC, with no tumors identified at the margins, but the closest distance from the tumor to the basal margin was less than 1 mm. Ki67 staining was approximately 60% positive. The skin graft survived well 2 weeks postoperatively, as shown in Figure 2(f). After discharge, the patient was transferred to a nearby provincial cancer hospital for radiotherapy and chemotherapy, though the specific treatment regimen remained unclear. Regrettably, the patient died of disease progression 3 months after the second surgery. Details of the two surgeries and the pathology results are shown in Figure 2. Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

Figure 2.

Surgical and pathological characteristics of the representative case. (a) Left anterior axilla and chest wall trichilemmal carcinoma (TLC). (b) Enlarged resection of the TLC lesion, axillary lymph node dissection, and design of the thoracodorsal artery perforator flap during surgery. (c) Well-preserved skin flap 5 days postoperatively. (d) Recurrence of TLC in the left shoulder and chest region. (e) After enlarged resection of the TLC tumor. (f) Skin graft survival 2 weeks after surgery. (g) Hematoxylin and eosin (HE) staining (magnification 100x). (h) HE is staining (magnification 200x). (i) Positive staining for P63 (magnification 200x). (j) Positive staining for CK5/6 (magnification 200x).

Results

China’s increasing TLC case trend

Over the past 40 years, there has been a constant increase in TLC patients in China since the first reports were made in 1984. There have been 230 documented cases of TLC in Chinese people. There were only two cases reported between 1984 and 1993; however, practically every year thereafter, there has been a notable increase in the number of reported cases. As Figure 3 illustrates, there has been a discernible upward trend over the last 10 years, with 116 cases (50.43% of all cases) reported between 2014 and 2023.

Figure 3.

Reports of trichilemmal carcinoma (TLC) cases in Chinese individuals from 1984 to the present, a span of 40 years.

Clinical characteristics

Among the 230 TLC patients, there were 113 males (49.13%) and 117 females (50.87%), with ages ranging from 20 to 97 years. The duration of the disease varied, with the shortest duration being approximately 1 month and the longest exceeding 70 years. The most common site of onset was the head and neck region in 202 patients (87.83%), while other cases were distributed across the trunk (chest, abdomen, shoulder, and back), perineal region, upper extremities (arms and hands), and lower extremities (buttocks and legs), as shown in Table 1.

Table 1.

Distribution of lesion sites in 230 patients with TLC.

Location		Number of people	Percentage (%)
Head and neck		202	87.83
Trunk	Chest	3	1.30
	Abdomen	3	1.30
	Shoulder	3	1.30
	Back	2	0.87
Upper extremities	Arms	2	0.87
	Hands	1	0.43
Lower extremities	Buttocks	7	3.04
	Legs	4	1.74
Perineum		3	1.30

The most common clinical manifestations of TLC were skin papules and exogenous nodules. Some patients experienced pruritus, local ulceration, or atypical manifestations such as erythema or skin horns.^4,5 Additionally, TLC was associated with other diseases, including 2 cases each of seborrheic keratosis, sebaceous hyperplasia, and psoriasis^6–9 and 1 case each of SCC, ⁶ breast cancer, ³ lung cancer, ¹⁰ and liver cancer. ¹¹ Five patients had a history of burns, with TLC tumors occurring at the site of burn wounds or scars without any other obvious triggers. Cases of TLC occurring in rare locations, such as the axilla and chest wall, with recurrence within 1 month after wide excision were rarely documented.

Detection of TLC-Specific tumor markers

All patients were subjected to immunohistochemical analysis, including a total of 36 antigen markers (Figure 4), with an average frequency of 8.33. Using a filtering criterion of frequency ≥8, 15 markers were identified. The top 7 markers based on positive and negative likelihood ratios are listed in Figure 5. Among the positive markers, high-molecular-weight cytokeratin (CK-H) was the most common marker, with a frequency of 24, followed by EMA, Pan-CK, c-erbB-2, P53, Ki-67, and P63. The most common negative marker was S-100, followed by CK-L, CEA, HMB45, CK, CK7, and CK8. Of the 230 patients, 55 showed positive PAS staining, consistent with the glycogen-rich characteristics of trichilemmal differentiation.

Figure 4.

Immunohistochemical markers in 231 patients with TLC.

Figure 5.

Rankings of positive and negative antigens with frequencies greater than 8.

Treatment and prognosis

Among the 230 TLC patients, 201 (87.39%) underwent surgical treatment, nine of whom received a combination of surgery and radiotherapy or chemotherapy. Additionally, 5 patients received only radiotherapy or chemotherapy, 1 patient underwent radiotherapy combined with electrochemical therapy, 2 patients underwent radiotherapy combined with microwave hyperthermia, and 1 patient received PD-1 inhibitor therapy(Pembrolizumab Injection).^8,12 Five patients refused treatment and the remainder did not report treatment results.

Thirteen patients were reported to have metastases, and 14 patients experienced recurrence, all who were diagnosed with head and neck TLC. Thirteen patients died, the majority of whom succumbed to the recurrence and metastasis of TLC. The follow-up period ranged from 1 month to more than 12 years, with some studies not reporting follow-up information or loss to follow-up, making it challenging to accurately assess recurrence and mortality rates.

Discussion

Literature analysis shows that the number of reported TLC cases in the Chinese population ranks first globally. Over the past 40 years, a total of 230 TLC cases have been reported among Chinese patients. Recent literature reports indicate an upward trend in the diagnostic rate of this disease, especially in the most recent decade (116 cases out of the total 230 cases reported between 2014 and 2023). This increase may be attributed to improvements in diagnostic techniques, perfection of reporting systems, or the influence of environmental factors.^13,14

Studies have shown that TLC lesions predominantly involve the head and neck region, with a broad age distribution and no significant gender predilection. However, previous Chinese studies often reported a higher incidence in females, while foreign studies tend to indicate a male predominance.^15,16 TLC lesions primarily occur in sun-exposed areas of the head and neck, which may be associated with ultraviolet radiation. ³ Some studies also suggest a correlation with the rich distribution of skin appendages in the head, face, and neck regions. ¹⁷ Common symptoms of TLC include skin papules and nodules, often accompanied by pruritus or ulceration. TLC is associated with multiple risk factors, including actinic keratosis, burn scars, seborrheic keratosis, psoriasis, immunosuppressive therapy after organ transplantation, ¹⁸ ionizing radiation exposure, ¹⁹ frequent physical irritation, hormonal changes,^15,20,21 and low socioeconomic status. A minority of cases occur in the trunk, extremities, and perineal region, with axillary cases being particularly rare in foreign reports. ²²

Tumors differentiating toward the hair follicles are predominantly benign but may also include malignant tumors such as pilomatricoma, malignant proliferating trichilemmal tumor (MPTT), and TLC, which are often difficult to distinguish. ²³ In addition, clinically, it is necessary to differentiate TLC from other tumors such as SCC, sebaceous carcinoma, keratoacanthoma, and malignant melanoma. TLC lacks specific clinical manifestations, and definitive diagnosis relies primarily on histopathological features. The tumor is composed of glycogen-rich clear cells and associated keratinocytes, often connected to the epidermis and/or follicular epithelium, and exhibits tissue invasiveness and cytological atypia. ¹ MPTT is mostly located in the dermis and even extends to the subcutaneous tissue; its main cellular component is spinous cell-like squamous cells, and it is often associated with trichilemmal cysts. ²⁴ Pilomatric carcinoma is composed of basophilic basaloid cells with characteristic shadow cells, which can be used for differentiation. SCC lacks the multilobular structure and outer root sheath differentiation of TLC; instead, it exhibits intercellular bridges, and the cells at the periphery of the cancer nests do not show palisading arrangement. It has ill-defined boundaries with the surrounding tissues, and keratin pearl formation can be observed. Keratoacanthoma forms a crater-like ulcer in the tissue, which contains keratinous material. Malignant melanoma shows diverse pathological morphologies without fixed tissue structure or growth pattern; its tumor cells are positive for both S-100 and HMB45, which can facilitate differentiation. The main component of sebaceous carcinoma is multivacuolated foam cells; the cancer nests have clear boundaries with the surrounding stroma, showing positive results for fat staining and negative results for PAS staining. ²⁵

Cases with atypical histological presentations may require immunohistochemistry, special staining, and other auxiliary diagnostics. Studies have shown that positivity for CK-H, EMA, PanCK, Ki-67, p63, and p53 and negativity for S-100, CK-L, CEA, HMB-45, CK7, and CK8 can serve as diagnostic indicators for TLC. TLC usually originates from the outer root sheath of the hair follicle, and positivity for CK-H in TLC can help to differentiate the tumor’s keratinization source. ²⁶ The presence of PanCK, a broad-spectrum keratin antibody, indicates cellular keratinization, but its value in differential diagnosis is limited. The expression of c-erbB-2 is increased in various malignant tumors and is correlated with a poor prognosis.^27,28 The expression of C-erbB-2 in TLC has only been reported by Ge Xia et al., with a positive rate of 50% (11/22). ²⁶ Studies have shown that C-erbB-2 is involved in the activation of TLC and associated with its differentiation, with both gene expression and protein levels increasing as the degree of cell differentiation decreases. Whether c-erbB-2 can serve as a specific diagnostic marker for TLC requires further validation through more studies. In addition to the aforementioned immunomarkers, studies have shown that positivity for CK15 and CK1 and negativity for Vimentin, MelanA, and SMA are also valuable in the diagnosis of TLC. ³

The main treatment for both primary and recurrent TLC tumors is surgical excision, with resection margins typically ranging from 1 mm to 20 mm. Patients with lymph node metastasis may require lymph node dissection. Mohs micrographic surgery (MMS), known to preserve as much healthy tissue as possible while ensuring negative margins, is also employed in TLC excision. For larger TLC surgeries leading to substantial skin defects, repair is achieved through techniques such as flap transfer and skin grafting. There is no consensus on the use of postoperative radiotherapy or chemotherapy, but a combination of both is clinically considered for patients with recurrent or metastatic TLC. ¹⁵ In cases where the TLC diameter exceeds 5 cm, radiation therapy or chemotherapy may be considered. ³ In recent years, there have been reports of favorable outcomes in the treatment of TLC with PD-1 inhibitors, combined radiotherapy and microwave hyperthermia, chemotherapy combined with radiotherapy, and radical radiotherapy.

Despite the invasive growth characteristics observed in the histology of TLC, it tends to be a relatively indolent tumor in terms of clinical course, with lymph node metastasis and recurrence being relatively uncommon. The occurrence of metastasis in TLC indicates a poor prognosis; Xie ² reported that 11 out of 136 TLC patients with regional and distant metastasis died. Notably, all cases of recurrence and metastasis in this study involved head and neck TLC patients, a phenomenon that highlights the aggressive characteristics of TLC in specific anatomical sites.

This report describes a rare case of TLC in the axillary chest wall with lymph node metastasis. Despite an extended resection of 20 mm from the tumor margin, lymph node dissection, and concurrent flap transfer for reconstruction, the patient experienced recurrence within 1 month after surgery. The rapid progression of the disease led to the patient’s death. This may be associated with residual tumor micrometastasis after surgery and delayed adjuvant therapy. This case serves as a warning, highlighting the need for further exploration and research in TLC patients with a prolonged medical history, extensive tumor involvement, lymph node metastasis, and occurrence at uncommon sites. Questions regarding the sufficiency of the extent of surgical excision, the choice of reconstruction methods, and the timely development of effective postoperative radiotherapy and chemotherapy regimens still require further investigation and study.

Some cases lacked complete follow-up data, potentially underestimating the recurrence rate (14 reported cases) and mortality rate (13 reported cases)—patients lost to follow-up may have had unrecorded events. This could overestimate favorable outcomes, especially for aggressive head and neck lesions. Currently, there are no specific guidelines for the follow-up of TLC, with recommendations ranging from every 6 to 12 months. ³ However, there have been reports of TLC recurrence 2 years after surgery, ²⁶ indicating the necessity of extending the follow-up duration for TLC patients. For future studies, standardized follow-up protocols are recommended: (1) 6-months, 1-year, and annual follow-ups with clinical exams and imaging (e.g., lymph node ultrasound); (2) multi-center collaboration to lower loss-to-follow-up rates; (3) electronic medical records for long-term outcome tracking; and (4) integrating follow-up requirements into study design.

Research on TLC in the Chinese population is currently focused on clinical case reports, which illustrate the clinical characteristics and diagnostic and treatment methods of TLC in China to some extent. However, there is a lack of research on the pathogenesis of TLC. Due to incomplete data provided in some of the studies, it was challenging to reflect the characteristics of TLC in China comprehensively and accurately. It is imperative to accumulate more clinical cases, further exploring effective treatment modalities, investigating the pathogenesis of TLC, and enhancing the diagnostic and treatment standards for TLC in China.

Conclusion

In conclusion, this comprehensive analysis of TLC in Chinese populations reveals a rising incidence trend, with 50.43% of cases reported in the recent decade (2014–2023). The disease exhibits a broad age distribution, near-equal gender involvement, and marked predilection for sun-exposed head/neck regions, contributing to its aggressive behavior in these anatomical sites. Non-specific clinical manifestations and absence of unique biomarkers pose significant diagnostic challenges, often leading to misidentification as benign skin lesions or other malignancies. Immunohistochemical profiling highlights CK-H, EMA, and PAS positivity as diagnostic indicators, while S-100 and CK-L negativity aids differentiation. Surgical excision remains the cornerstone of treatment, but adjuvant therapies show limited benefit in preventing recurrence or metastasis, which are strongly associated with mortality, particularly in head/neck cases. The rapid recurrence and poor prognosis in the presented axillary TLC case emphasize the need for standardized diagnostic algorithms, optimized surgical margins, and evidence-based adjuvant strategies. We recommend that a surgical margin of at least 1-2 cm should be maintained for primary TLC. For cosmetically sensitive areas (e.g., the face), MMS is suggested to ensure negative surgical margins. Longitudinal studies with extended follow-up are imperative to refine early detection and management protocols for this rare malignancy. In addition to following the conventional follow-up protocol for common cutaneous malignant tumors, for high-risk cases (including head and neck lesions and lymph node metastasis), intensive follow-up is recommended every 3-6 months in the first 2 years (a period of high recurrence risk). After that, annual follow-up should be conducted for at least 5 years, with the integration of imaging examinations during the follow-up process.