Mohs micrographic surgery for the treatment of trichoblastic carcinoma: Case presentation and discussion of clinical outcomes and considerations

Introduction

Trichoblastic carcinoma (TC) is a rare malignancy of follicular origin with only 105 previously published cases.¹ It commonly affects the scalp or face of middle-aged men and typically presents as a single, smooth, or ulcerated nodule.1, 2, 3 The pathogenesis of TC is considered multifactorial, involving UV radiation, chronic skin irritation, and mutations in TP53, Wnt, and B-catenin that induce malignant transformation of germinative cells of a preexisting trichoblastoma. A comprehensive review reports de novo synthesis in a majority of cases (87.1%; 81/93).^2,4 Practice guidelines for diagnosis and treatment are not yet published by the National Comprehensive Cancer Network. Current literature recommends surgical resection to obtain clear margins and adjuvant radiation or chemotherapy for metastatic or unresectable tumors.² Given that wide local excision (WLE) of TC frequently results in positive margins, we propose Mohs micrographic surgery (MMS) be considered for treatment. Our case outlines a 68-year-old man with TC of the face successfully treated with MMS.

Case report

A 68-year-old White male with no significant past medical history presented to dermatology for a skin-colored nodule on the right jawline. It had gradually increased in size over 4 decades, but more recently he noted intermittent bleeding and inflammation with shaving. The nodule measured 2.2 × 1.5 cm with a firm, rubbery texture (Fig 1). No clinical lymphadenopathy was appreciated, and the differential included a neurofibroma, epidermal inclusion cyst, or lipoma.

Fig 1.

Right jawline demonstrating a light pink, firm but mobile, 2.2 × 1.5 cm nodule. A, Clinical presentation at initial clinical visit for biopsy. B, Clinical presentation 3 months later at MMS appointment. C, Final defect after 2 stages of MMS. D, Final reconstruction with primary closure. MMS, Mohs micrographic surgery.

A deep punch biopsy identified multiple lobules of basaloid cells arranged in poorly defined clusters within the dermis with infiltration of cells into a mildly fibroblastic stroma (Fig 2, A). Cells showed a high nuclear-to-cytoplasmic ratio, back-to-back crowding, and heterogeneity in nuclear size and shape (Fig 2, B). Some areas of the lesion showed sheets of basaloid cells with central necrosis forming pseudoglandular spaces. Immunohistochemical staining was positive for cytokeratin 7, GATA3, and BerEP4 but negative for cytokeratin 20, TRPS1, CD56, CDX2, synaptophysin, and chromogranin (Fig 2, C-E).

Fig 2.

A, The 2× magnification hematoxylin and eosin (H&E) pathology slide showing multiple lobules of malignant basaloid cells arranged in balls within the dermis with stranding of cells into a mildly fibroblastic stroma. B, The 10× magnification of H&E with tumor cells showing a high nuclear to cytoplasmic (N/C) ratio with small ducts noted within the groups of cells. C, The 20× magnification of H&E demonstrates closely packed basaloid cells with a high N/C ratio and heterogeneity in nuclear size and shape. Despite the atypia, the organoid morphology of the lesion, mimicking primitive hair germ structures, can be appreciated. D, The 20× and (E) 100× magnification of H&E of positive first Mohs layer. The 10× magnification of immunohistochemistry staining showing positivity for (F) CK7, (G) GATA3, and (H) BerEP4. Additional staining was negative for CK20, CDX2, TRPS1, CD56, synaptophysin, and chromogranin (not pictured).

The patient subsequently underwent positron emission tomography/computed tomography (PET/CT) that identified no hypermetabolic adenopathy or fluorodeoxyglucose-avid distant metastases. A left cervical lymph node (LN) of 3 mm with mild uptake was thought to be reactive; fine needle aspiration was nondiagnostic. The case was reviewed at multidisciplinary tumor board with referral to otolaryngology for discussion of sentinel LN biopsy, which the patient declined. MMS with frozen sections was recommended over slow MMS, given the tumor’s clear visibility on hematoxylin and eosin and contiguous nature. During MMS, the tumor cleared after 2 stages with a final defect size of 3.7 × 3.1 cm and was repaired with a primary closure. At a skin examination 5 months later, he had no signs of recurrence or palpable lymphadenopathy.

Case discussion

TC is a rare adnexal neoplasm that often resembles basal cell carcinoma clinically and histologically. It is classified morphologically as either low-grade or high-grade and most commonly occurs de novo on the face. TC can be distinguished from basal cell carcinoma with follicular differentiation by its lack of retraction artifact and epidermal connection and presence of a nonmyxoid, hypercellular, fibrous stroma.^2,3 Low-grade TC shows peripheral palisading basophilic cells that may be adjacent to a benign trichoblastoma.^3,5 High-grade TC demonstrates brisk mitotic activity, geographical necrosis, invasion of subcutaneous adipose tissue, and may show focal perineural and lymphovascular invasion.^4,6 Immunohistochemistry is helpful but not specific, with positive markers including BerEP4 and CK7 and negative markers including synaptophysin, chromogranin, CK20, EMA, CEA, HMB45, and CD10 (Table I).^2,5

Table I.

Comparison of clinical and dermoscopic features and H&E and IHC stains for basal cell carcinoma, trichoblastoma, and trichoblastic carcinoma

	Basal cell carcinoma	Trichoblastoma	Trichoblastic carcinoma
Clinical features	Pearly pink or pigmented (brown, blue, or black) papule or plaque, often ulcerated	Well-circumscribed, skin-colored to brown or blue-black papule or nodule	Large, growing, sometimes ulcerated, skin-colored to blue-gray, pink, or yellow plaque or nodule
Dermoscopic features∗7	Arborizing vessels, pink structureless areas, microulcerations, spoke-wheel and leaf-like structures, blue ovoid nests, microulcerations	Blue-gray homogenous areas, white-yellow structureless areas, and a pinkish to orange background can have thin, arborizing vessels, but background color is paler and the vessels are thinner than expected in BCC	Heterogenous pigmentation with blue and black pigmented areas with whitish veil can have thin arborizing vessels and blue-gray ovoid globules and nests
H&E features1	Blue islands of basaloid cells with peripheral palisading, epidermal connection often present, variable mitotic activity, variable pleomorphism, variable necrosis, tumor-stroma clefting (retraction artifact), fibromyxoid stroma; subtypes include superficial, nodular, infiltrative, micronodular, morpheaform, basosquamous, adenoid, fibroepitheliomatous type	Cribriform to solid nodules of basaloid cells with peripheral palisading, no epidermal connection, variable mitotic activity, minimal pleomorphism, absent necrosis, fibrocellular nonmyxoid stroma with papillary mesenchymal bodies, and stroma-stroma clefting (no true retraction artifact)	Infiltrative growth pattern of cribriform to solid nodules of basaloid cells with variable peripheral palisading, no epidermal connection, conspicuous mitotic activity, nuclear pleomorphism, focal necrosis, fibrocellular nonmyxoid stroma, occasional papillary mesenchymal bodies, and background benign trichoblastoma may be seen
Positive IHC stains2,5	Androgen receptor, BerEP4, CD10 (stains epithelial cells), BCL2 (diffuse), Variable: GATA3	CD10 (stains stroma), CD34 (stains stroma), BCL2 (foal, peripheral epithelial cells), BerEP4, Variable: CK20	BerEP4, p63, PHLDA1, Variable: GATA3, CK7
Negative IHC stains2,5	CK20, SOX10, CD34, CD44, MART1, S-100, EMA, CK7 (variable)	Androgen receptor, CK7, GATA3, synaptophysin, chromogranin, CK20, EMA, CEA, HMB45	CD34, CK7, CK15, CEA, CAM5.2, synaptophysin, chromogranin, CK20, EMA, CEA, HMB45

BCC, Basal cell carcinoma; H&E, hematoxylin and eosin; IHC, immunohistochemistry.

^∗Dermoscopic features can be nonspecific, and in some cases of subcutaneous trichoblastoma or trichoblastic carcinoma, dermoscopy can show normal skin.

Because the risk of metastases ranges from 5% to 11%, WLE with a lateral margin of 1-3 cm to deep fascia is recommended.^2,8,9 In a recent systematic review of 127 patients with TC and trichoblastic carcinosarcoma, 75 patients (50.1%) were treated with surgical excision and 22 patients (17.3%) with MMS.¹ In a case series by Thomas et al, 65% (14/21) of TCs presented on the face with an average size of 2.3 cm (range 0.7-15 cm). Standard excision attained clear margins in only 38% (8/21) of cases, with an average of 1.6 revisions. Only 5 cases underwent primary closure, 8 required skin grafts, 6 involved local flaps, and 2 combined a flap and graft technique. Despite WLE, 3 of 18 cases recurred over a mean follow-up of 36 months, and 1 developed LN metastases.⁸ In 93 cases reviewed by Boettler et al, 62.4% presented on the face or scalp with an average size of 4.3 cm (0.7-20.0 cm, SD: 4.4). WLE was performed in 84 cases with an average margin of 0.97 cm (0.5-3.0 cm, SD: 0.42). Among 40 patients with reported follow-up, 4 developed local recurrence, 5 had nodal metastases, 3 had distant metastases, and 1 patient died from metastatic disease.² Treatment of locally advanced and metastatic TC includes lymphadenectomy, radiation therapy, and systemic therapy. Reported systemic agents include carboplatin, cisplatin with 5-fluorouracil, sunitinib, and vismodegib.1, 2, 3

To date, only 7 studies report MMS for TC in 23 patients (Table II). The largest case series by Gonzalez-Lara et al reports 17 cases of TC treated with slow MMS and with clearance attained in 1 stage for 13 cases, 2 stages for 1 case, 3 in 2 cases, and unattainable in 1 case, despite 9 stages. Seven cases underwent primary closure, 4 required a skin graft, 2 involved local flaps, 2 healed by secondary intention, 1 had a composite graft, and 1 utilized a nasal prosthetic.⁹ The other 6 studies present single case reports of TC treated with MMS with frozen section involving a maximum of 2 reported MMS stages and closures including linear, skin grafting, and a retroauricular flap (Table II).^3,5,10,11

Table II.

Previously reported cases utilizing Mohs surgery for treatment of trichoblastic carcinoma

Article	Patient	Preoperative size	Length present	Location	Number of stages	Closure
Park et al, 20243	65-y-old man	1 × 1 cm	1 y	Glabella	1	Complex linear closure
Gonzalez-Lara et al, 20229 (n = 17)	66-y-old (average) male (n = 12), female (n = 5)	1.5 × 1.5 cm	Not specified	Head and neck (n = 13)	1 (n = 13), 2 (n = 1), 3 (n = 2), unresectable (n = 1)	Skin graft (n = 4), direct closure (n = 7), local flap (n = 2), secondary intention (n = 2), composite graft (n = 1), nasal epithesis (n = 1)
Leeman et al, 20215	50-y-old woman	1.5 × 1.5 cm	10 y	Chin	Not specified	Not specified
Garcia et al, 202010	94-y-old woman	0.3 × 0.2 cm	6 mo	Nasal tip	2	Full-thickness skin graft
Toberer et al 201712	35-y-old man	Not specified	Not specified	Upper back	Not specified	Not specified
Cogrel, 201411	77-y-old man	Not specified	Not specified	Concha	2	Retroauricular revolving door island flap
Müller et al, 201313	83-y-old woman	1 cm	Not specified	Back of nose	Not specified	Not specified

We report a case of facial TC with no evidence of metastasis on PET/CT and clearance of tumor after two MMS stages. Given the rarity of TC, no National Comprehensive Cancer Network guidelines, and a LN metastases rate exceeding 5%, we recommend PET/CT imaging, referral to surgical oncology, and discussion at a multidisciplinary tumor board. Given its contiguous nature, distinct appearance on hematoxylin and eosin staining, high recurrence rates, frequent occurrence in cosmetically sensitive areas, and difficulty attaining margin control with WLE, we propose that MMS be strongly considered as a treatment option for TC.

Conflicts of interest

None disclosed.