A Rare Case Of Trichilemmal Carcinoma In A Sun-unexposed Area

Trichilemmal carcinoma (TC) is a rare adnexal malignant tumor that rises from the outer root sheath of the hair follicular epithelium [1]. Headington was the first person to describe it in 1976 as an invasive, atypical clear cell neoplasm made up of adnexal keratinocytes that are connected to the epidermis and/or follicular epithelium [2,3]. It is most commonly found in elderly populations between the ages of 40 and 90, and the male-to-female ratio of occurrence is relatively equal [4,5]. It is considered to be the malignant counterpart of trichilemmoma [2,3].It has a preference for sun-exposed areas like the face, neck, back, and extremities, taking different clinical lesions in the form of plaques, papules, or solitary nodules with evidence of ulceration [1, 2, 4-6].

The specific pathophysiology of TC is not well stated, but the majority of patients have had extensive sun exposure throughout their lives [7]. TC should be distinguished from other skin tumors with similar histomorphology because of the difference in management plans [1]. Surgical excision is considered to be the first choice for curative treatment [6]. In general, TC accounts for only 1% of all adnexal carcinomas, and a diagnosis in a sun-exposed area like ours makes it even more rare [7]. There are very few reports of TC worldwide, and up to now, we have not found a single published case report of a similar case in our country.

Our case is a 60-year-old female patient from the Sidama region, Bensa Woreda, who has presented with swelling over the left proximal leg of 5 years duration. Initially, the lesion was small in size and did not have any associated symptoms. However, over the previous year, the swelling increased rapidly to attain its current size. Associated with this, the swelling started to bleed and became itchy, with a skin color change in the past 3 months. Otherwise, the patient had no history of trauma, burns to the site, or similar lesions elsewhere. She has no family history of diabetes mellitus, hypertension, or immunocompromization. There is no history of similar illness in the family.

Physical findings

On general appearance, the patient looked chronically sick and emaciated. Her vital signs were all within the normal limits. The musculoskeletal system examination showed an 8×5 cm, non-tender, firm fungating mass over the left proximal anteromedial leg (Fig. 1).

The integumentary system examination showed multiple small hypopigmentations all over both lower extremities. A bilateral inguinal area evaluation revealed no significant lymphadenopathy.

Investigation findings

Her full blood count (WBC-6.6 x 10 9/L, Hgb-10.1 g/dl, platelet- 215 x 10 9/L), and liver and renal function tests were within the normal range. A left leg x-ray revealed a left proximal anteromedial leg area soft tissue mass with normal-appearing adjacent bone having a smooth cortical outline (Fig. 2).

The lesion’s fine needle aspiration cytology (FNAC) results showed a hemorrhagic background with tight clusters and single cells of pleomorphic round to oval cells showing hyperchromasia, coarse chromatin, prominent nucleoli, and a moderate amount of cytoplasm with pinkish stromal fragments. This led to the conclusion of a poorly differentiated malignancy and therefore an excisional biopsy was recommended.

Following the above provisional diagnosis, the patient and her family were counseled for a wide surgical excision and possible revision and reconstruction. Under spinal anesthesia, an excisional biopsy with a possible gross tumor-free margin was performed (Figs. 3), and the specimen was sent for histopathologic confirmation.

A gross evaluation of the biopsy specimen revealed an ulcerated and fungating soft tissue mass measuring 6x5x4 cm. On the cut surface, it was a 6x5x4 cm gray-white, firm lesion throughout with multiple microcystic and hemorrhagic spaces, with the largest microcystic space measuring 1×0.5×0.5. (Fig. 4)

The lesion’s microscopic examination revealed a tissue with hyperkeratotic bland stratified squamous epithelium with focal ulceration and sub-epithelial lobules, solid sheets, and trabecular architectures of basaloid round to oval and polygonal cells exhibiting marked pleomorphism and a moderate amount of clear to eosinophilic cytoplasm with peripheral palisade. The lesion in certain areas had a hair-follicle-like architecture set in the desmoplastic and myxoid stroma. There were invasive squamous morules and trichilemmal keratinization, as well as a lot of abnormal mitosis and comedo- and geographic-type necrosis. Deep margins were involved. The biopsy report said that the growth was a malignant skin adnexal tumor that is TC and had a deep margin that was involved (Figs. 5–8).

The patient was advised for revision surgery during the first follow-up visit but deferred the operation. Subsequently, she has been on follow-up and came to the follow-up clinic twice during the subsequent six months, and there was no significant lesion at the site except a granulating clean surgical wound. Despite her refusal to have another surgery, she was advised to have a strict follow-up.

Headington was the first to classify hair-follicle tumors, followed by Mehregan and Rosen. Currently, no system is universally acceptable owing to considerable overlapping histological features [1]. Trichilemmal tumors are a group of neoplasms characterized by cells differentiating toward the outer root sheath of hair follicles. This is witnessed as the accumulation of glycogen causes a variable degree of clear change in the cytoplasm [1]. This entity comprises several benign and malignant tumours and has an association with Cowden’s syndrome [13].

Headington first described trichilemmal carcinoma (TC) in 1976. He said that it was a clear cell neoplasm made up of adnexal keratinocytes that were invasive and cytologically atypical. It was seen to be continuous with the epidermis and/or follicular epithelium [1]. He stated that the tumor cells were high in glycogen and had a palisading pattern around the edges. The basement membrane was PAS-reactive and diastase-sensitive, and the cells had a trichilemmal type of keratinization [2].

In a cross-sectional study by the year 2014, 103 cases of trichilemmal carcinoma (TC) were published, with 82 cases providing anatomic distribution data, half of which occurred on the face [8].

Typically, TC occurs on sun-exposed and hair-bearing areas in elderly individuals with fair skin [3, 4, 5, 6]. Although multiple local recurrences are commonly found, it is uncommon to find metastasized trichilemmal carcinoma [5]. Unlike most reports, our patient has TC over an area not exposed to the sun since women in Ethiopia, especially in rural areas like ours, usually wear dresses up to the feet.

Even though the exact pathogenesis of TC is still not well established, some risk factors have been linked to it, such as UV rays, weakened immune systems, previous skin injuries including burns and scars, and genetic conditions like xeroderma pigmentosum and Cowden syndrome [10]. It most commonly arises de-novo but may arise from an underlying proliferating trichilemmal cyst with a loss of p53, a seborrheic keratosis, a nevus sebaceous, or a scar [9]. The histomorphologic differential diagnosis of TC includes other skin tumors like squamous cell carcinoma, basal cell carcinoma, keratoacanthoma, and malignant nodular melanoma [3, 7].

There are different forms of lesions in TC, but typical lesions are nodular, ulcerated, or exophytic with a keratotic or crusted appearance. They are usually present for less than a year and exhibit a characteristic accelerated growth phase, which prompts medical consultation [3]. In contrast, our case presented with a lesion that lasted for five years and had accelerated growth in the past year, and in our case, the lesion was ulcerated and fungated.

Since TC can resemble a wide range of clinical entities, histological examination and, if required, IHC are the primary methods used for diagnosis. [17] Furthermore, it is crucial to differentiate TC from a number of skin tumors that may display clear cell alterations, including basal cell carcinoma, clear cell hidradenocarcinoma, balloon cell melanoma, clear cell squamous cell carcinoma, sebaceous carcinoma, clear cell porocarcinoma, and metastatic renal cell carcinoma. [1, 9, 10, 11].

For a histologic diagnosis of TC, Headington suggested six criteria: [12]

1. Continuity with a coexisting benign epithelial tumor, usually a trichilemmoma
2. Continuity with the outer sheath epithelium of a coexisting hair follicle
3. Light microscopy showing glycogen-rich epithelium, peripheral palisading, and prominent basement membrane zone
4. Trichilemmal keratinization (absent or minimal granular layer, abrupt single-cell keratinization, and formation of dense nonlamellar keratin)
5. Electron microscopic details similar to normal outer sheath epithelium or trichilemmoma
6. Immunocytochemical details are similar to those of a those of a normal outer sheath epithelium or trichilemmoma.

Microscopically, trichilemmal carcinoma features a solid, lobular, or trabecular growth pattern, often centered around a pilosebaceous unit [17, 20]. The neoplasm’s extent may either stay within the intraepithelial space or extend to the reticular dermis [17, 21, 25]. The tumor cells are clear, polygonal, and glycogen-rich (periodic acid-Schiff positive [PAS], diastase-sensitive [26, 27]), reminiscent of the clear cells of the normal ORS [17, 28]. TC exhibits peripheral palisading [26] of basaloid cells abutting a sometimes thickened hyalinized basement membrane [17]. Upon closer inspection, cytologic atypia, nuclear pleomorphism, prominent nucleoli, and a high mitotic index can be seen [17]. Trichilemmal keratinization, when it occurs, is an important characteristic that helps with the histologic diagnosis [17]. CD34 stains can be used to indicate outer sheath differentiation since they label the outer layer of the ORS without labeling the remainder of the follicle [22, 25]. IHC was not done for our patient because the histomorphologic features were consistent with trichilemmal carcinoma.

Wide local excision with histological demonstration of clear margins has traditionally been the treatment of choice [27]. Anecdotal reports equate the risk of recurrence and lymph node metastasis to that of squamous cell carcinoma (SCC) [1, 25], and, therefore, trichilemmal carcinoma (TC) is treated accordingly [17]. Surgical margins typically follow the 4 to 6 SCC standard margins; however, some surgeons recommend using safety margins greater than 1 cm [29, 30]. Histologically clear margins must be documented because of the potential recurrences, as encountered in a study by Zhuang et al [30]. The other treatment modalities are Mohs micrographic surgery and immunomodulation with imiquimod cream. The main prognostic factors are surgical margins and lymph node status [31]. Local recurrences and metastases mandate chemotherapy and adjuvant radiotherapy [12]. Our case needed revision surgery because of the positive margin; however, the patient declined the procedure.

Even though the typical location of TC is in photo-exposed areas of the body, it can arise in sun-unexposed areas like the proximal leg. In elderly patients who present with skin nodules and ulcerations, TC should be considered a differential diagnosis, even in sun-unexposed areas. In the case of malignant skin adnexal tumors like TC, to rule out a common alternative diagnosis like SCC, FNAC seems to be important. However, a histopathological examination is needed for a final histopathologic diagnosis. The mainstay of treatment is surgery with wide local excision of the tumor and active follow-up.