DERMATOLOGIC
SURGERY
Desmoplastic trichoepithelioma Adam J. Mamelak, MD,a,b Leonard H. Goldberg, MD, FRCP,a,b Tracy M. Katz, MD,b Jeffery J. Graves, MD,a Ofer Arnon, MD,c and Arash Kimyai-Asadi, MDb Houston, Texas, and Beer-Sheva, Israel Background: Desmoplastic trichoepithelioma (DTE) is an uncommon adnexal tumor usually found on the face of young women. Objective: We sought to describe the clinical and histologic characteristics of DTE and discuss management strategies for these tumors. Methods: We conducted a retrospective case series and review of the literature. Results: A series of 17 cases of DTE is reported. Of our patients, 82% were female and half of all these cases occurred on the cheek. Unlike previous reports, the patients in our study were slightly older, with 53% older than 51 years and 71% between the ages of 31 and 60 years at the time of surgery (mean age 49 years, median age 52 years, range 14-81 years). Approximately 38% of the tumors had been present for 1 to 2 years before presentation. The average size of the tumors at the time of surgery was 0.8 3 0.6 cm. All cases were treated with Mohs micrographic surgery. To date, none of the tumors have recurred. Limitations: This is a small case series. The referral patterns of our predominantly Mohs micrographic surgery clinic might further bias this study. Conclusion: DTE is a benign tumor that has a predilection for the face. With its rapid growth, aggressive histologic features that may be confused with basal cell carcinoma, and tendency to arise in cosmetically and functionally sensitive areas, these tumors should be removed in a manner that assures clear surgical margins, such as Mohs micrographic surgery. ( J Am Acad Dermatol 2010;62:102-6.) Key words: adnexal neoplasm; basal cell carcinoma; cutaneous tumors; Mohs micrographic surgery; skin cancer.
D
esmoplastic trichoepithelioma (DTE) was first described by Zeligman1 in 1960 as a ‘‘solitary trichoepithelioma.’’ This asymptomatic lesion, typically less than 2 cm in diameter, was noted to be annular and papular in morphology with a ‘‘thread-like elevated border,’’ and most frequently found on the face. In 1977, MacDonald et al2 described the same entity as a ‘‘sclerosing epithelial hamartoma,’’ and in that same year,
From the Department of Dermatology, the Methodist Hospital, Houstona; DermSurgery Associates, Houstonb; and Department of Plastic and Reconstructive Surgery, Soroka University Medical Center, Beer-Sheva.c Funding sources: None. Conflicts of interest: None declared. Reprints not available from the authors. Correspondence to: Leonard H. Goldberg, MD, FRCP, 7515 Main, Suite 240, Houston, TX 77030. E-mail:
[email protected]. 0190-9622/$36.00 ª 2009 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2009.06.066
102
Abbreviations used: BCC: basal cell carcinoma DTE: desmoplastic trichoepithelioma TE: trichoepithelioma
Brownstein and Shapiro3 reported 49 patients with this tumor that they called ‘‘desmoplastic trichoepithelioma,’’ a name that has persisted. Brownstein and Shapiro3 specifically distinguished this tumor from a morpheaform basal cell carcinoma (BCC) and other cutaneous neoplasms. They characterized the clinical features of the lesion as an annular, firm papule that was asymptomatic and white to yellowish in color, ranging from 3 to 8 mm in diameter. The center was frequently depressed, not ulcerated, with a raised border. The investigators noted that the clinical differential diagnoses most commonly included BCC, sebaceous hyperplasia, trichoepithelioma (TE), granuloma annulare, scar, and scleroderma.
Mamelak et al 103
J AM ACAD DERMATOL VOLUME 62, NUMBER 1
Original studies and other reports have suggested that DTE is a solitary benign tumor that appears most frequently on the face of young women.1,3,4 In our current study, we sought to further define the clinical characteristics and histologic behavior of DTE. We discuss the presentation and course of these lesions, and suggest modes for definitive management of these tumors.
November 2007. Two patients were omitted because their histology was not consistent with DTE (one had pathology consistent with a trichoadenoma, the other had a BCC). Of the remaining 17 patients with a confirmed diagnosis of DTE, 3 of the patients treated were men and 14 were women. The mean age at the time of surgery was 49 years (median 52 years; range 1481 years). The most comCAPSULE SUMMARY INDEX CASE mon locations were the A 32-year-old Caucasian cheek (10), followed by the Desmoplastic trichoepithelioma is an woman with Fitzpatrick skin nose (4) and forehead (3) uncommon adnexal tumor that appears type III presented to our including the glabella. Nine to have a predilection for the face of clinic with an asymptomatic, of the lesions occurred on young women. slow-growing plaque on her the right side of the face, 4 The rapid growth and aggressive right cheek (patient No. 16). on the left side, and 4 in the histologic features often observed in The patient claimed the lemid line. The lesions had these tumors can cause diagnostic sion had been present for 12 been present from 2 months uncertainty and they are often confused to 15 years. The patient’s up to 15 years before surwith basal cell carcinoma. medical history was unregery (Table I) and ranged in markable and her medicasize from 2 to 18 mm in The tendency of desmoplastic tions included multivitamins diameter (Table II). Clinical trichoepithelioma to arise in cosmetically and an oral contraceptive. presentations varied from and functionally sensitive areas and She was allergic to penicillin. an erythematous papule to resemblance to BCC suggests that these She denied any personal or a hypopigmented plaque tumors should be removed in a manner family history of skin cancer with elevated borders that assures clear surgical margins, such and could not recall ever (Fig 1, A). The size of the as Mohs micrographic surgery. having blistering sunburns. tumors ranged from 0.3 3 On examination, a poorly 0.2 cm to 1.8 3 1.2 cm. defined hypopigmented plaque measuring 0.7 3 Histologically, all tumors revealed small strands of 0.6 cm in diameter was noted on her right cheek basaloid cells in a desmoplastic stroma. (Fig 1, A). A biopsy specimen from the cheek Keratinaceous cysts adjacent and attached to the revealed a circumscribed dermal lesion composed basaloid cells could also be observed. The cellular of small stands and nests of epithelial cells in proliferations were seen primarily in the papillary association with a keratinous cyst embedded in a and mid-reticular dermis, but often extended deeper fibrous stroma. Significant atypia was not identi(Fig 1, B). Morpheaform or sclerosing BCC was listed fied. The pathologist diagnosed the lesion as a DTE in the differential diagnosis in 7 of the 17 pathology (Fig 1, B). The tumor was excised with Mohs reports reviewed. Microcyctic adnexal carcinoma micrographic surgery and was cleared in two was noted as the differential diagnosis on two of stages. the 17 reports. All of our cases were treated with Mohs microMETHODS graphic surgery because of the tumors’ aggressive A retrospective analysis of 24,970 patients with histologic pattern, propensity for subclinical skin malignancies treated in a Mohs micrographic growth, and occurrence in a cosmetically and surgery practice in Houston, TX, between July 1997 functionally important area. Seven of the cases and November 2007 was performed and the cases of required greater than one Mohs stage to clear the DTE were selected. Diagnosis was confirmed by tumor, including a tumor that required 5 stages reviewing patients’ pathology reports and histology (data not shown). As of November 2007, none slides. The following variables were examined: age of the tumors had recurred (mean follow-up and sex of the patients, location of the malignancy, 3.61 years; median follow-up 3.25 years). Seven duration before surgery, and size. patients developed other cutaneous neoplasms in addition to the DTE. Five of these patients had BCCs (one patient had 3 tumors), one had a RESULTS squamous cell carcinoma, and one developed an Nineteen patients with the diagnosis of DTE eccrine hidrocystoma. were treated at our clinic between July 1997 and d
d
d
104 Mamelak et al
J AM ACAD DERMATOL JANUARY 2010
Table I. Patient demographics No.
Age category, y (n = 17) 11-20 21-30 31-40 41-50 51-60 61-70 71-80 $ 81 Sex (n = 17) Male Female Lesion location (n = 17) Cheek Nose Forehead (including glabella) Duration before surgery (n = 13) 0-12 mo 1-2 y 2-5 y [5 y Unknown Fig 1. A, White sclerotic plaque with slightly elevated borders is noted on right cheek. B, Biopsy specimen reveals small strands of basaloid cells in desmoplastic stroma and keratinaceous cysts adjacent and attached to basaloid cells filling papillary dermis. (Hematoxylin-eosin stain; original magnification: 340.)
DISCUSSION The majority of our patients presented with a slowly expanding, white-gray to skin-colored solitary sclerotic plaque on the face. It is not surprising that morpheaform BCC is the major differential diagnosis, listed in 41% of our patients’ pathology reports. Some have suggested that the lack of surface telangiectasias and thinned epidermis can be helpful in identifying DTE3; however, differentiation from BCC can still be challenging. In fact, Takei et al4 noted that a large proportion of the clinically diagnosed DTEs in their study were actually BCC. Other lesions were melanocytic nevi, sebaceous hyperplasias, TE, hamartoma, and keratosis.4 Microcystic adnexal carcinoma can also resemble DTE both clinically and microscopically,5 and was listed in the differential diagnosis in two of 17 of our patients’ pathology reports. Studies in the literature report DTE appears anytime from birth to the fourth decade of life, with a slow growth pattern and no discernible inheritance pattern.1 The patients range between 8 and 79 years of age. One third of the patients in one study were 30 years of age, and 71% to 85% of the patients were
Percent
1 1 4 2 6 1 1 1
5.9 5.9 23.5 11.7 35.3 5.9 5.9 5.9
3 14
17.6 82.4
10 4 3
58.8 23.5 17.7
4 5 2 2 4
30.8 38.4 15.4 15.4
female. The tumors had been present for 1 to 5 years and the majority of these lesions appear on the face, including the chin, forehead, nose, periorbital region, lip, and temple.3,4 Fourteen (82%) of our patients were female and all lesions occurred on the face, most commonly the cheek (59%). However, we did note that our patients tended to be older, with more than half (53%) older than 50 years and approximately three-quarters (71%) between 31 and 60 years of age. A greater proportion of the tumors occurred on the right side (53%) compared with the left side (23.5%) and mid line (23.5%). Our clinic specializes in dermatologic and Mohs micrographic surgery and we recognized that our referral patterns might introduce bias into this study. As specialists in surgery in anatomically and cosmetically sensitive areas and tissue conservation, we commonly treat tumors on the head and neck. This could account for our patient population’s more advanced age and the tumor location. Histologically, DTE is characterized by a triad of microscopic findings: narrow strands of tumor cells, keratinous cysts, and a desmoplastic stroma. The strands of tumor range from 1 to 3 cells thick. These cells are small and basaloid with prominent oval nuclei and minimal cytoplasm, and the stroma typically contains multiple horn cysts.3 DTE can be differentiated from other tumors by its lack of loose
Mamelak et al 105
J AM ACAD DERMATOL VOLUME 62, NUMBER 1
Table II. Tumor characteristics Sex
Age, y
Duration before surgery
1
F
65
N/A
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
M F M F F F F F F F F F F M F
56 56 38 78 52 14 57 35 47 42 56 56 37 81 33
N/A 1y 2y 1.5-2 y N/A 5y 1y ;1 y 6 mo Several months 2 mo Several years 2y N/A 12-15 y
17
F
26
$7 y
Patient
Location
Preoperative diagnosis
Right cheek Right forehead Right nasal ala Right medial cheek Left nose Right cheek Right cheek Left cheek Right cheek Forehead Upper nasal bridge Tip of nose Glabella Left lower cheek Left cheek Right cheek Right cheek
Sclerosing epithelial neoplasm DTE DTE DTE DTE DTE DTE DTE DTE TE DTE DTE DTE TE DTE Microcystic adnexal carcinoma Sclerosing BCC
Preoperative length (cm)
Preoperative width (cm)
1.2
0.7
1.1 0.5 0.3 1 0.5 0.3 0.8 0.9 1.2 0.7 0.5 0.7 0.3 1.1 0.7
0.5 0.4 0.2 0.7 0.5 0.3 0.6 0.6 0.8 0.5 0.4 0.6 0.2 1 0.6
1.8
1.2
BCC, Basal cell carcinoma; DTE, desmoplastic trichoepithelioma; F, female; M, male; N/A, not applicable; TE, trichoepithelioma.
stroma and absence of large masses of tumor cells, as seen in conventional TE. DTEs also tend to be solitary and lack the ductal differentiation observed in syringomas. Interestingly, the most significant histologic differential diagnosis is morpheaform BCC. The clinical and histologic features of DTE are not straightforward. Both DTE and morphea-like BCC can exhibit aggregates of basaloid cells, cells in cords, sclerotic stroma, connections to the epidermis, cystlike structures, deposits of calcium, and, rarely, ossification, solar elastosis, fibroplasia, inflammatory-cell infiltration, and extension into subcutaneous fat.3 Compared with these tumors, no frank cellular atypia, large tumor masses, or peripheral palisading are present in DTE. Mitotic figures are rare and neither nuclear pleomorphism nor an ‘‘Indian-filing’’ configuration is observed.3 Takei et al4 emphasized the finding of slightly refractile ‘‘shadow’’ cells with keratolysis in the epithelium lining the cysts of DTE. Although not specific for DTE, these cells are not seen in BCC. Furthermore, clefting between tumor and the surrounding stoma is well described in BCC. Although the stroma is typically opposed to the tumor strands in DTE, we often observe stroma-stroma clefting, adjacent to the tumor. Finally, DTEs tend to be confined to the upper two thirds of the reticular dermis.6 Biopsy specimens are too superficial and small for full pathologic evaluation making differentiation impossible.
Re-excision or resampling is therefore often necessary for definitive diagnosis.7 Attempts have been made to differentiate DTE from morpheaform BCC with immunohistochemistry. Izikson et al8 analyzed androgen receptor expression in 32 BCCs and 10 benign trichoblastic tumors (6 TE and 4 trichoblastomas). The investigators noted focal expression of androgen receptors in 78% of BCC and none in the trichoblastic tumors. More recent studies have examined the expression of bcl-2 and CD34 in BCC and TE. In cases of TE, spindle-shaped cells surrounding the islands of tumor cells were found to be focally positive for CD34, whereas these cells did not stain in BCC.9 This sheath of CD341 dendrocytes around tumor nests, and the presence of significant numbers of Merkel cells within the tumor nests, supports the notion that these tumors arise from the undifferentiated germinative cells of the follicular-sebaceous-apocrine unit, such as those found in the hair bulge.10 Bcl-2 has been noted to stain morpheaform BCC more diffusely compared with DTE. However, Swanson et al11 cautioned against the use of bcl-2 and CD34 immunostains in distinguishing BCC from TE with only few corroborative studies supporting this approach. As such, there is currently no method other than conventional microscopy that can definitely differentiate DTE from morpheaform BCC. Reported cases of DTE generally exhibit slow growth. The majority of our patients claimed that
106 Mamelak et al
J AM ACAD DERMATOL JANUARY 2010
their lesions had been present for less than 5 years, with 38% noting that their tumors were present for 1 to 2 years’ duration. The tumors in our series were asymptomatic, with cosmetic appearance and the fear of facial disfigurement being our patients’ major concerns. Rare cases of DTE and TE have been reported with aggressive behavior, including ulceration and recurrence; however, investigators suggested that these were probably follicular tumors and not TE.3,4,12 The treatment of choice for DTE is local surgical excision with frozen section margin control.7 Despite a benign diagnosis, these tumors can penetrate widely and have aggressive histologic features. The average preoperative size of the tumors in our patients was 0.8 3 0.6 cm. The average postoperative defect size after excision of the tumors by Mohs micrographic surgery was 1.2 3 1.6 cm (data not shown). The majority of tumors were cleared in one stage, however, 6 required two stages (patient Nos. 2, 3, 4, 11, 16, and 17) and one tumor on the tip of the nose (patient No. 12) required 5 stages. There was no predilection for any anatomic site for these more aggressive tumors. There is often diagnostic uncertainty with DTE and confusion with morpheaform BCC. Furthermore, these tumors have a predilection for cosmetically sensitive areas where sparing of normal tissue is of utmost importance. It is for these reasons that Mohs micrographic surgery has been recommended for this ‘‘benign’’ tumor to prevent recurrence and subclinical local invasion.7
REFERENCES 1. Zeligman I. Solitary trichoepithelioma. Arch Dermatol 1960;82: 89-94. 2. MacDonald DM, Jones EW, Marks R. Sclerosing epithelial hamartoma. Clin Exp Dermatol 1977;2:153-60. 3. Brownstein M, Shapiro L. Desmoplastic trichoepithelioma. Cancer 1977;40:2979-86. 4. Takei Y, Fukushiro S, Ackerman AB. Criteria for histologic differentiation of desmoplastic trichoepithelioma (sclerosing epithelial hamartoma) from morphea-like basal-cell carcinoma. Am J Dermatopathol 1985;7:207-21. 5. Harada H, Hashimoto K, Ko MS. The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J Invest Dermatol 1996;107:41-3. 6. McCalmont TH. Adnexal neoplasms. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. New York (NY): Mosby; 2003. pp. 1733-55. 7. Behroozan DS, Goldberg LH, Glaich AS, Kaplan B, Kaye VN. Mohs micrographic surgery for deeply penetrating, expanding benign cutaneous neoplasms. Dermatol Surg 2006;32: 958-65. 8. Izikson L, Bhan A, Zembowicz A. Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors. Am J Dermatopathol 2005;27:91-5. 9. Kirchmann TT, Prieto VG, Smoller BR. CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma. Arch Dermatol 1994;130:589-92. 10. Hartschuh W, Schulz T. Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study. J Cutan Pathol 1995;22: 413-21. 11. Swanson PE, Fitzpatrick MM, Ritter JH, Glusac EJ, Wick MR. Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens. J Cutan Pathol 1998;25:153-9. 12. Kechijian P, Connors RC, Ackerman AB. Trichoepithelioma vs basal-cell carcinoma: criteria for histologic differentiation. J Dermatol Surg 1975;1:22-3.
