Ocular and extraocular sebaceous carcinomas: A retrospective study with emphasis on the presence of in situ lesion and discussion and review of the histogenesis of extraocular sebaceous carcinoma

Abstract

Sebaceous carcinoma (SC) is a rare carcinoma classified as ocular or extraocular. Ocular SC is believed to arise from the meibomian glands or the glands of Zeis. However, the origin of extraocular SC is controversial because there is no evidence of carcinoma arising from pre-existing sebaceous glands. Several hypotheses about the origin of extraocular SC have been proposed, including one suggesting an origin from intraepidermal neoplastic cells. Although extraocular SCs have been shown to occasionally comprise intraepidermal neoplastic cells, no study has investigated whether intraepidermal neoplastic cells possess sebaceous differentiation. The present study analyzed the clinicopathological features of ocular and extraocular SC, with an emphasis on the presence of in situ (intraepithelial) lesions. It retrospectively reviewed the clinicopathological features of eight patients with ocular and three patients with extraocular SC (eight women and three men; median age, 72 years), respectively. In situ (intraepithelial) lesions were observed in four of the eight ocular SC cases and one of the three extraocular SC cases and an apocrine component was noted in one patient with ocular SC (seboapocrine carcinoma). In addition, immunohistochemical analyses showed that the androgen receptor (AR) was expressed in all ocular SCs and two of the three extraocular SC cases. Adipophilin expression was observed in all ocular and extraocular SC. In situ lesions of extraocular SC showed positive immunoreactivity for both AR and adipophilin. The present study is the first to demonstrate sebaceous differentiation in in situ lesions of extraocular SC. The possible origin of extraocular SC is speculated to be the progenitor cells present in the sebaceous duct or interfollicular epidermis. The results of the present study and reported cases of SC in situ indicate that extraocular SC also arises from intraepidermal neoplastic cells.

Keywords: extraocular sebaceous carcinoma; histogenesis; in situ lesion; sebaceous carcinoma; seboapocrine carcinoma.

Figure 1.

Histopathological features of sebaceous carcinoma. (A) Proliferation of the neoplastic cells with large round-to-oval nuclei, some of these cells showed scalloped features and multivacuolated cytoplasm (hematoxylin and eosin; magnification, ×400). (B) In situ (intraepithelial) lesion noted in ocular sebaceous carcinoma (arrows) (hematoxylin and eosin; magnification, ×200). (C) In situ (intraepidermal) lesion observed in extraocular sebaceous carcinoma (arrows) (hematoxylin and eosin; magnification, ×100). (D) Seboapocrine carcinoma of the eyelid (Patient 3). Solid proliferation of sebaceous carcinoma component (left side) and infiltrative growth with glandular formation (right side) are present (hematoxylin and eosin; magnification, ×100). (E) Apical snouts are observed in the apocrine carcinoma component (hematoxylin and eosin; magnification, ×400).

Figure 2.

Immunohistochemical features of sebaceous carcinoma. (A) The androgen receptor is expressed in almost all of the neoplastic cells (magnification, ×100). (B) Diffuse-positive immunoreactivity for adipophilin (magnification, ×400). (C) Androgen receptor (left side) and adipophilin (right side) were positive in in situ (intraepidermal) neoplastic cells of extraocular sebaceous carcinoma (arrows; magnification, ×400 for the androgen receptor; magnification, ×200 for adipophilin). (D) Adipophilin was expressed in a diffused manner in both the in situ (intraepithelial) and invasive components of ocular sebaceous carcinoma (magnification, ×200). (E) p53 overexpression is noted in in situ (intraepidermal) neoplastic cells of extraocular sebaceous carcinoma (note: No overexpression was observed in the non-neoplastic epidermal cells; magnification, ×200). (F) Focal keratin 5/6 expression (left) and diffuse p63 expression (right) are observed in in situ (intraepidermal) neoplastic cells of extraocular sebaceous carcinoma. Non-neoplastic epidermal keratinocytes show positive immunoreactivity for keratin 5/6 and p63 [Arrows indicate in situ (intraepidermal) neoplasm; magnification, ×200].

Figure 3.

Possible schematic of the histogenesis of extraocular sebaceous carcinoma. Sebaceous carcinoma may arise from the p63⁺/keratin 5⁺ progenitor cells present in the sebaceous duct or interfollicular epidermis. Intraepidermal neoplastic cells may be the origin of extraocular sebaceous carcinomas, especially those with intraepidermal squamous neoplasia.