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CASE REPORT
Trichoepithelioma and Basal Cell Carcinoma with Squamous Differentiation: Is it Causal or Coincidental? Palak Agarwal, Charu Agarwal, Minakshi Bhardwaj, Arvind Ahuja, Seema Rani1
Abstract Trichoepitheliomas (TEs) are benign cutaneous tumors that occur either as solitary non‑familial or multiple familial. We report a case of multiple familial trichoepithelioma (MFT) in a 55‑year‑old female patient and her son who came with complaints of single ulcerated mass involving the left nasolabial fold and cheek. She had multiple papules and nodules all over the face and neck since 25 years. Histopathological examination of an ulcerated lesion revealed features of basal cell carcinoma (BCC) with squamous differentiation, which was confirmed by immunohistochemistry. A skin biopsy obtained from the papule on neck showed features of TE. However, whether BCC developed independently or by transformation from TE was uncertain. Her 36‑year‑old son presented with similar lesions on the face and a skin biopsy showed features of TE. Though malignant transformation of TE is quite rare, awareness of the potential for evolution of carcinoma in patients with MFT is important for management of these patients.
From the Department of Pathology and 1Dermatology, PGIMER, Dr. RML Hospital, New Delhi, India Address for correspondence: Dr. Arvind Ahuja, Department of Pathology, PGIMER, Dr. RML Hospital New Delhi - 110 001, India. E‑mail:
[email protected]
Key Words: Basal cell carcinoma, immunohistochemistry, multiple familial trichoepithelioma, squamous differentiation, trichoepithelioma What was known? • TE rarely undergoes malignant transformation commonly into BCC. • BCC and TE are diagnostic challenges in terms of their differential diagnosis.
Introduction
Case Report
Trichoepitheliomas (TEs) are regarded as poorly differentiated hamartomas of hair germ[1], located mainly on face, nasolabial folds, forehead, upper lip and scalp.[2] There are three variants of TE: Solitary, multiple and desmoplastic. Multiple familial trichoepithelioma (MFT), also known as epithelioma adenoides cysticum, present as small papules with strong predilection for central part of the face. The onset of lesions is usually in childhood or at the time of puberty.[1]
A 55‑year‑old female came to dermatology outpatient department with a single ulcerated mass measuring 5 × 4 cm, involving left nasolabial fold and cheek. The lesion had developed 3 years back. Base of the ulcer was covered with granulation tissue. She also had multiple asymptomatic, small, firm, skin‑colored papules and nodules all over the face and neck since 25 years [Figure 1a]. General physical and systemic examination revealed no abnormality. Routine laboratory investigations were within normal limits. There was no history of consanguinity in the family. A skin biopsy was performed from both the ulcerated mass and one of the papules present on the neck.
TE is a benign neoplasm that shares both clinical and histologic features with basal cell carcinoma (BCC). Malignant transformation of such lesions is quite rare.[2,3,4] It is important to distinguish these neoplasms.[5] BCC and TE are diagnostic challenges in terms of their differential diagnosis.[6] Limited immunohistochemical stains are available to separate them.[5]
Histopathological examination of the ulcerated mass showed focal ulceration of epidermis with underlying tumor composed of basaloid cells in nests, cords and solid sheets in a myxoid background [Figure 2a]. Focal peripheral palisading and retraction artifact was also seen [Figure 2b]. The cells were small, monomorphic with round to oval hyperchromatic nuclei and scant cytoplasm. Squamous differentiation was seen within some of the cell nests [Figure 2c]. Frequent mitosis was present with focal areas of necrosis [Figure 2d]. Intervening stroma showed acute and chronic inflammatory cells. On immunohistochemistry (IHC), basaloid cells were positive for Bcl2 (diffuse, Figure 3a) and CD10 [Figure 3b]. CD34 was negative in the stromal as well as the epithelial
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DOI: 10.4103/0019-5154.160494
Indian Journal of Dermatology 2015; 60(4)
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cells [Figure 3c] while an epithelial membrane antigen (EMA) was positive in the squamous cells [Figure 3d]. Based on these findings, a diagnosis of basal cell carcinoma with squamous differentiation was rendered.
The lesions of TE are characterized by firm skin‑colored papules or nodules 2 to 8 mm in size, mainly concentrated around the nasolabial folds and forehead. The lesions first appear in childhood and may grow larger and increase in number over time. In the present case the patient and her son had similar lesions all over the face since childhood, thereby suggesting familial disease.
A skin biopsy from a papule on the neck showed a circumscribed tumor in dermis composed of multiple keratin‑filled horn cysts surrounded by basaloid cells and solid aggregates with peripheral palisading surrounded by proliferating fibroblasts. No mitosis was seen. Overlying epidermis showed mild thinning. A diagnosis of TE was made [Figure 1b].
TEs are superficial dermal lesions with focal continuity with the epidermis.[1] Small keratinous cysts lined by basaloid cells are the most characteristic histologic feature. Also, present are islands of uniform basaloid cells, showing peripheral palisading. The fibroblasts encircle these islands, which lack retraction artifact typical of BCC. These solid aggregates show invaginations which contain numerous fibroblasts and resemble follicular papillae also known as papillary mesenchymal bodies.
Her son who is 36 year old presented with similar multiple papulonodular lesions all over the face since childhood [Figure 4a]. A skin biopsy from the lesion showed features of TE [Figure 4b].
TE causes only cosmetic disfigurement to the patients but occasionally BCC can develop in association with it.[2,3,4] Histologically, the presence of horn cysts, papillary‑mesenchymal bodies, lack of atypia and mitoses along with a cribriform pattern and stromal fibrosis favor a diagnosis of TE, whereas the presence of mucin, stromal edema and retraction artifact around the basaloid islands and mitoses suggest a diagnosis of BCC.
Discussion TE is a benign neoplasm of follicular germinative cells. Clinically, this tumor occurs either as a solitary lesion without familial association or as multiple lesions in MFT.[2] MFT have an autosomal dominant mode of inheritance, with lessened expressivity and penetrance in a male.[1] The putative gene for MFT has been localized to chromosome 9p21.[6]
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a
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c
d
b
Figure 1: (a) Clinical presentation of mother having multiple papulonodular lesions on the face with ulcerated mass involving the left nasolabial fold and cheek. (a) Histopathology of the papule present on the neck of the mother showing trichoepithelioma (H and E, ×40)
Figure 2: Histopathology of the ulcerated lesion present on the left nasolabial fold. (a) Basal cell carcinoma with focal ulceration (H and E, ×40). (b) Basaloid cells with peripheral palisading and retraction artifacts (H and E, ×100). (c) Squamous differentiation (H and E, ×400). (d) Mitosis (H and E, ×400)
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b
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d
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Figure 4: (a) Clinical presentation of the son having multiple papulonodular lesions on the face. (b) Histopathology of the lesion on the face of the son showing trichoepithelioma (H and E, ×40)
Figure 3: Immunohistochemistry using antibodies directed against (a) Bcl2 (IHC, ×100), (b) CD10 (IHC, ×200), (c) CD34 (IHC, ×100) and (d) EMA (IHC, ×200)
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However, the distinction between BCC and TE on histopathological basis is quite difficult. IHC has been considered for the differential diagnosis.[7] TE shows CD10 stromal immunoreactivity, while in BCC staining involves basaloid cells. Focal positive CD34 staining of fibroblastic stroma has been shown in TE, whereas in BCC, this staining pattern is not seen but it may be seen in BCC with squamous differentiation (metatypical). Staining of the outermost epithelial layer for Bcl2 has been seen in TE. In contrast, BCC frequently stains diffusely for Bcl2 [Table 1].[7] Follicular stem cell marker, PHLDA1 (pleckstrin homology‑like domain, family A, member 1), also known as TDAG51 (T‑cell death‑associated gene 51), and CK20 are positive in TE and negative in BCC.[8] Malignant transformation of TE to BCC is very rare. Nevertheless, there have been few cases of BCC arising in the setting of multiple TEs.[7] In the present case, patient had features of multiple TEs along with an ulcerated lesion showing features of BCC with squamous differentiation, a subtype not reported in the previous published literature.[2,3,4] Whether BCC developed independently or by transformation from TE was uncertain.
by mutations of the CYLD gene resulting in multiple cylindromas and TEs.[9] Any suspicion of malignant change which is indicated by rapid growth and ulceration in the pre‑existing lesion calls for excision and histological examination.[10] TE is a benign lesion that may be excised with a small margin of healthy tissue, thereby facilitating surgical repair; however, BCC is the locally malignant tumor treated by excision with 3‑4 mm margins. Hence, the differentiation between both the lesions is mandatory. To conclude, awareness of the potential for the evolution of carcinoma in patients with MFT is important for further management. What is new? • In a patient with multiple TE, any new lesion with progressive growth or ulceration should undergo biopsy to rule out malignancy. • Malignant transformation of TE to BCC with squamous differentiation is not reported yet in the literature.
References 1. Weedon D. Weedon’s skin pathology. Section 7 Tumors. London: Elsevier Publications, Churchill livingstone; 2010. p. 760‑2. 2. Samaka RM, Bakry OA, Seleit I, Abdelwahed MM, Hassan RA. Multiple familial trichoepithelioma with malignant transformation. Indian J Dermatol 2013;58:409. 3. Pincus LB, McCalmont TH, Neuhaus IM, Kasper R, Oh DH. Basal cell carcinomas arising within multiple trichoepitheliomas. J Cutan Pathol 2008;35:59‑64. 4. Lee KH, Kim JE, Cho BK, Kim YC, Park CJ. Malignant transformation of multiple familial trichoepithelioma: Case report and literature review. Acta Derm Venereol 2008;88:43‑6. 5. Pham TT, Selim MA Jr. Burchette JL, Madden J, Turner J, Herman C. CD10 expression in trichoepithelioma and basal cell carcinoma. J Cutan Pathol 2006;33:123‑8. 6. Fernandez‑Flores A. Advanced differentiation in trichoepithelioma and basal cell carcinoma investigated by immunohistochemistry against neurofilaments. Folia Histochem Cytobiol 2009;47:61‑4. 7. Elder DE, Elenitsas R, Johnson BL, Murphy GF, Xu X. Lever’s Histopathology of the skin. 10th ed. Tumors of the epidermal appendages. Philadalphia: Lippincott Williams and Wilkins; 2009. p. 857‑9. 8. Sellheyer K, Nelson P, Follicular stem cell marker PHLDA1 (TDAG51) is superior to cytokeratin‑20 in differentiating between trichoepithelioma and basal cell carcinoma in small biopsy specimens. J Cutan Pathol 2011;38:542‑50. 9. Doherty SD, Barrett TL, Joseph AK, Brooke‑Spiegler syndrome: Report of a case of multiple cylindromas and trichoepitheliomas. Dermatol Online J 2008;14:8. 10. Kaur T, Puri KJ, Chahal KS, Budhwar J. Multiple Familial Trichoepitheliomas: A case report and review. Egypt Dermatol Online J 2012;8:11.
The close relationship between TE and BCC has been explained on the basis of assumption that they have a common genesis from pluripotential cells, which, like primary epithelial germ cells, may develop toward hair structures. This hypothesis is supported by the fact that PATCH gene mutations are seen in both tumors.[7] Recently, cylindromatosis tumor suppressor gene (CYLD) mutation is also seen in MFT.[3] Brooke‑Spiegler syndrome is a rare autosomal dominant disorder caused Table 1: Immunohistochemical markers to differentiate TE and BCC Parameters Bcl2 expression
TE
BCC
Epithelial
Positive in the outermost layer
Diffusely positive
Stromal
Negative
Negative
Negative
Positive
Positive
Negative
CD10 expression Epithelial Stromal CD34 expression Epithelial
Negative
Negative
Stromal EMA expression
Positive Negative
PHLDA1 CK20
Positive Positive
Negative Positive in areas of squamous differentiation in the case of BCC with squamous differentiation Negative Negative
How to cite this article: Agarwal P, Agarwal C, Bhardwaj M, Ahuja A, Rani S. Trichoepithelioma and basal cell carcinoma with squamous differentiation: Is it causal or coincidental?. Indian J Dermatol 2015;60:394-6.
BCC: Basal cell carcinoma, TE: Trichoepithelioma, EMA: Epithelial membrane antigen, PHLDA1: Pleckstrin homology-like domain, family A, member 1, CK20: Cytokeratin 20 Indian Journal of Dermatology 2015; 60(4)
Received: November, 2014. Accepted: December, 2014. Source of support: Nil, Conflict of Interest: Nil.
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