,microscope.JPG 
Indiana Association 
of Pathologists, Inc.
Histology Laboratory, Indiana Medical History Museum 

Final Diagnosis:

Metastatic breast carcinoma of the eyelid

Discussion:

Because this was a female patient and the lesion showed peculiar “Indian file” pattern, additional immunohistochemical stains were performed to rule out metastatic carcinoma from the breast. The tumor cells were immunoreactive for CKAE1/AE3, EMA, GATA3 and ER (Fig. 4), which was compatible with metastatic breast carcinoma. The other breast cancer prognostic biomarkers analysis performed demonstrated non-immunoreactivity for PR, and HER-2 was negative (Score 0).

After the eyelid biopsy, further investigation by the digital mammogram demonstrated a spiculated mass in the right breast with adjacent skin retraction and multiple malignant appearing calcifications on the left breast consistent with bilateral breast cancer. So far the biopsy of the breast lesion has not been performed. However, the histological features of the eyelid lesion and immunostaining profile are characteristic of metastatic breast cancer.

Metastatic tumor to the eyelid is uncommon, representing less than 1% of the eyelid lesions. [1] Clinically, eyelid metastasis presents more frequently as a solitary subcutaneous nodule that might simulate a chalazion with fewer inflammatory signs, more progressive enlargement and eventual ulceration.[2-4]

Breast cancer accounts for the majority of the ocular and orbital metastases. [2, 4, 5] A 15 -year retrospective study of metastatic disease to the eyelid conducted by the Armed Forces Institute of Pathology identified 31 patients. Among these cases, the majority were women (female/male = 4:1) with mean age of 69 years (range, 3-92). The most common primary sites were breast (35%), skin (16%), and gastrointestinal and urogenital tracts (each 10%). Metastasis to the eyelid was initially suspected in only 32% of the cases; the most common misdiagnoses were chalazion, cyst, granuloma, and xanthoma. The eyelid lesions were detected before the primary sites in 45% of the cases.[6] Another publication demonstrated similar findings. [3]

The metastatic breast carcinoma to the eyelid has unusual histologic features. Hood et al. were the first to describe this entity, and they called those tumors metastatic mammary carcinoma with histiocytoid appearance. [7] Those authors described 13 metastatic cases to the eyelid. They demonstrated a tumor composed of cells having bland eccentric nuclei, uniform chromatin, and an inconspicuous nucleolus; the cytoplasm was generally abundant, amphophilic, with a “ground glass” appearance and small or large vacuoles; the cell membrane was distinct and delicate; and the tumor cells either dispersed in a loose ground substance or compacted together in a dense stroma. Importantly, the cells of this tumor were usually arranged singly, in small groups, or larger masses, but commonly found in columns of single cells, having a well-developed file arrangement. Mitotic figures were absent or very sparse.

Many other publications followed Hood et al., and although the term histiocytoid breast carcinoma has being now accepted as a variant of breast cancer by many pathologists, this term is not included in the WHO classification of breast cancer due to its controversial histogenesis, most authors believe that this tumor is an apocrine variant of lobular carcinoma. [6, 8-15] Similar to other breast carcinomas, tumor cells usually stain for mucicarmine, and are positive for epithelial markers such as EMA, CK34βE12, CK7, AE1/AE3 and CAM 5.2. Tumor cells are also commonly strongly positive for carcinoembryonic antigen (CEA) and gross cystic disease fluid protein-15 (GCDFP-15). The later is an apocrine differentiation marker. [10, 14, 16] The prognosis of this tumor is usually poor. [16]

Metastatic lesion rarely occurs in the eyelid. However, if histology reveals some atypical cells with the peculiar linear arrangement, metastatic breast cancer should be ruled out.

References:

1. Wang, J.K., et al., Malignant eyelid tumours in Taiwan. Eye (Lond), 2003. 17(2): p. 216-20.

2. Shields, J.A. and C.L. Shields, Eyelid, conjunctival, and orbital tumors : an atlas and textbook. Third edition. ed. 2016, Philadelphia: Wolters Kluwer. xvii, 806 pages.

3. Bianciotto, C., et al., Metastatic tumors to the eyelid: report of 20 cases and review of the literature. Arch Ophthalmol, 2009. 127(8): p. 999-1005.

4. Homer, N., et al., Periocular breast carcinoma metastases: correlation of clinical, radiologic and histopathologic features. Clin Exp Ophthalmol, 2017. 45(6): p. 606-612.

5. Ahmada, S.M. and B. Esmaeli, Metastatic tumors of the orbit and ocular adnexa. Current Opinion in Ophthalmology, 2007. 18: p. 405–413.

6. Mansour, A.M. and A.A. Hidayat, Metastatic Eyelid Disease. Ophthalmology, 1987. 94(6): p. 667-670.

7. Hood, C.I., R.L. Font, and L.E. Zimmerman, Metastatic mammary carcinoma in the eyelid with histiocytoid appearance. Cancer, 1973. 31(4): p. 793–800.

8. Tomasini, C., E. Soro, and M. Pippione, Eyelid Swelling: Think of Metastasis of Histiocytoid Breast Carcinoma. Dermatology, 2002. 205(1): p. 63-6.

9. Hutchinson, C.B. and J. Geradts, Histiocytoid carcinoma of the male breast. Ann Diagn Pathol, 2011. 15(3): p. 190-3.

10. Murali, R., E. Salisbury, and N. Pathmanathan, Histiocytoid change in breast carcinoma: a report of 3 cases with an unusual cytomorphologic pattern of apocrine change. Acta Cytol, 2006. 50(5): p. 548-52.

11. Eroglu, A. and A. Sari, Histiocytoid breast cancer: an uncommon histologic variant of lobular carcinoma. J BUON, 2006. 11(3): p. 359-62.

12. Augros, M., et al., [Infiltrating lobular carcinoma of the breast with histiocytoid features: three cases]. Ann Pathol, 2004. 24(3): p. 259-63; quiz 227.

13. Walford, N. and J. ten Velden, Histiocytoid breast carcinoma: an apocrine variant of lobular carcinoma. Histopathology, 1989. 14(5): p. 515-22.

14. Li, P., et al., Histiocytoid breast carcinoma: a case report showing immunohistochemical profiles. Int J Clin Exp Pathol, 2013. 6(11): p. 2609-14.

15. Kitamura, H., et al., Histiocytoid Breast Carcinoma: A Case Report with Immunohistochemical and Ultrastructural Studies. Breast Cancer, 1996. 3(1): p. 57-63.

16. Tan, P.H., et al., Histiocytoid breast carcinoma: an enigmatic lobular entity. J Clin Pathol, 2011. 64(8): p. 654-9.


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