Major Review
Apocrine Adenocarcinoma of the Eyelid: Case Series and Review Edwin C. Figueira, M.B.B.S., M.S.*, Jenny Danks, F.R.A.N.Z.C.O.†, Akihide Watanabe, M.D.‡, Jwu Jin Khong, F.R.A.N.Z.C.O.§, Lorraine Ong, F.R.A.N.Z.C.O.§, and Dinesh Selva, F.R.A.C.S., F.R.A.N.Z.C.O.* *South Australian Institute of Ophthalmology and Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia; †Department of Ophthalmology, Sydney Hospital and Sydney Eye Hospital, Sydney, New South Wales, Australia; ‡Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; and §The Royal Victorian Eye and Ear Hospital, Orbital Plastics and Lacrimal Unit, Melbourne, Australia
Purpose: To report 2 patients with apocrine adenocarcinoma of the eyelid and review the literature. Design: Noncomparative, retrospective case series and review. Participants: Clinical data of 2 patients with histopathologic diagnoses of apocrine adenocarcinoma of the eyelid were obtained from medical records. The histopathology and immunohistochemistry data for the 2 cases were studied. A retrospective review was performed on all reported cases of eyelid apocrine carcinoma. Main Outcome Measures: Clinical features, histopathology, immunohistochemistry, and clinical course following treatment are reported. The results of a retrospective review of clinical presentations, local and systemic spread, treatment method, and prognosis from published case reports on eyelid apocrine adenocarcinoma are discussed. Results: One patient had orbital invasion at presentation. This patient had radiotherapy alone and had no systemic or local recurrence at 2 years. One patient underwent a 4-mm margin wide surgical excision. This patient had no local or systemic recurrences at 1 year. A review of the literature suggests that the prognosis of adnexal apocrine tumors is indeterminate and variable. Most patients have successful outcomes following local surgical excision. Radiotherapy has been used as an adjunctive treatment for local metastatic disease. Conclusions: Apocrine adenocarcinoma is a rare adnexal tumor of the eyelid, which may present with orbital invasion. (Ophthal Plast Reconstr Surg 2013;29:417–423)
A
pocrine adenocarcinomas are rare ocular adnexal tumors that arise mainly from the glands of Moll. Stout and Cooley1 were the first to report on apocrine carcinoma in 1951. There are 19 reported cases of apocrine gland carcinoma of the eyelids.1–15
Accepted for publication July 2, 2013. The authors disclose no financial or conflicts of interest. Address correspondence and reprint requests to Edwin C. Figueira, M.B.B.S., M.S., South Australian Institute of Ophthalmology, Level 8, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia. E-mail: [email protected] DOI: 10.1097/IOP.0b013e3182a64fe5
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This study describes 2 new cases and reviews the literature on apocrine adenocarcinoma of the eyelids.
CASE 1 An 87-year-old man had progressive right ptosis of 1-year duration associated with decreased vision (Fig. 1A). He was treated for glaucoma. Snellen decimal visual acuities were 20/40 in the affected OD and 20/20 in the OS. Extraocular movements of the right globe were reduced in all directions. A firm mass was palpable in the upper and lower eyelids. CT revealed an enhancing mass infiltrating the soft tissues of the orbit with no bone erosion. MRI demonstrated an enhancing mass involving both intraconal and extraconal spaces, which was isointense to muscle on T1-weighted images and hyperintense on T2 (Fig. 1B,C). A right subbrow incisional biopsy revealed a grey mass. Histopathology showed invasive apocrine adenocarcinoma and gland-like structures with irregularly shaped lumina. The columnar cells had eosinophilic cytoplasm with basal nuclei. The luminal cells demonstrated decapitation secretion. Immunohistochemical testing for GCDFP-15 (gross cystic disease fluid protein 15; Fig. 1E) and CK7 (cytokeratin 7) was positive. Further immunostaining was negative for CK20, S100, estrogen receptor, and progesterone receptor. Staging including a positron emission tomography (PET)-CT scan was negative for regional or distant spread. Clinically, the eyelid tumor was staged as IIIA based on the 7th Edition Eyelid Carcinoma Classification System from the American Joint Committee on Cancer-International Union Against Cancer.16 The patient refused exenteration and underwent a course of 45-Gy radiation therapy over 3 weeks. At 10 months of follow up, visual acuity had improved to 20/30. Extraocular movements were much improved, and there was a significant reduction in the orbital and eyelid mass (Fig. 1F) on imaging (Fig. 1G,H). The intraocular pressure remained medically controlled.
CASE 2 A 56-year-old woman presented with an 18-month history of a left lower eyelid lesion that had occasionally bled over the last 2 weeks. She had a 5 mm ×4 mm hemorrhagic cystic lesion, just below the eyelash line. Ocular and orbital examination was normal. Due to the unusual appearance of the swelling, an incisional biopsy was performed. An incisional biopsy revealed histologic features of apocrine cystadenocarcinoma (Fig. 2A–D). The diagnosis was based on the histopathologic criteria of
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FIG. 1. A, Upper, lower eyelid and orbital involvement by tumor (TNM stage IIIA). B and C, Coronal and axial MRI showing contrastenhancing orbital mass. D, Glandular epithelium showing decapitation secretion (hematoxylin-eosin, ×60). E, Immunostaining: positive for GCFDP-15 (×60). F, Clinical reduced proptosis. G and H, Reduced orbital mass after radiotherapy.
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FIG. 2. A, Cribriform glandular epithelium with decapitation secretion (hematoxylin-eosin, ×100); (B) papillary and cribriform structure (hematoxylin-eosin, ×40); (C) micropapillary structure (hematoxylin-eosin, ×40); (D) iron-positive intracellular pigment (hematoxylin-eosin ×40).
Kipkie and Haust.17 The patient underwent a 4-mm wide margin resection. The residual eyelid defect was primarily closed. The histopathology revealed dermal scarring, with no residual malignancy. Clinically, this patient was staged as IB (T2a, N0, M0).16 At last follow up at 12 months, there was no recurrence.
DISCUSSION Apocrine adenocarcinomas are rare ocular adnexal tumors that arise mainly from the glands of Moll. The glands of Moll are modified apocrine glands that lie at the base of the follicles of the eyelashes.18 To the best of knowledge, there are 19 cases of ocular adnexal apocrine adenocarcinoma reported.10–15,19,20 A recent review of cutaneous apocrine adenocarcinoma using the Surveillance, Epidemiology and End Results (SEER) Program registry data in the United States revealed that the primary site for these tumors is the axilla.21 Extra-axillary disease is reported in around 50% of cases. Thirty-five percent of the cases were noted to be in the head and neck. Cutaneous apocrine adenocarcinomas were reported in older patients (median age, 67 years), with no racial or gender predilection.21 Histopathology of this tumor is characterized by an invasive adenocarcinoma with gland-like structures. The malignant cells are eosinophilic or opaque glass like and form irregularly shaped lumina of varying size. The pathologic diagnosis
of these tumors can be challenging as distinguishing malignant from benign subtypes can be difficult. Kipkie and Haust17 described the following criteria for histologic diagnosis of apocrine adenocarcinoma: 1) periodic acid-Schiff (PAS) positive, (2) strongly eosinophilic cytoplasm, (3) decapitation secretion, (4) iron-positive intracellular pigment, and (5) occurrence in areas where apocrine glands are normally located. The principal diagnostic histopathologic feature of apocrine glandular differentiation used in this case series is the decapitation secretion from eosinophilic cuboidal cells (case 2).22 In well-differentiated tumors, apocrine tumors show pathognomonic decapitation secretion, while in poorly differentiated tumors, the cells can infiltrate as single cells or small cords of cells. The PAS-positive malignant apocrine epithelial cells often have diastase-resistant granules containing iron.22 Immunohistochemical demonstration of GCDFP-15 has become a useful adjunctive diagnostic tool in cases where decapitation secretion is not readily apparent. GCDFP-15 has been shown to stain apocrine-related neoplasms in 84% of the specimens (21/25) by Ansai et al.23 This immunostaining method for diagnosis was used in patient 1 in this series. GCDFP-15 immunostaining was performed in the second case because histology revealed characteristic decapitation secretion. Apocrine adenocarcinoma has to be differentiated from apocrine hidrocystomas and apocrine cystadenoma. Apocrine hidrocystomas are either unilocular or multilocular
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dermal cysts lined by columnar epithelial cells, with abundant granular eosinophilic cytoplasm and lack of cellular atypia. The cells have round basal nuclei. They possess PAS-positive and diastase-resistant granules. Papillary infolding into the cystic cavity present as “decapitation” secretion, with an underlying layer of flattened myoepithelial cells. The abundant secretory granules and other features characteristic of mature apocrine secretory epithelium help establish the diagnosis.24 Apocrine cystadenomas stain distinctly with immunoreactive stains for cytokeratins and human milk fat globulin 1.24 Primary cutaneous apocrine adenocarcinoma has been reported in older patients (mean age 67 years), with no racial or gender predilection.21 Extra-axillary disease is reported in around 50% of cases, with 35% of the cases involving the head and neck region. The most commonly documented surgical procedure for cutaneous apocrine adenocarcinoma was local excision (50%), followed by wide excision (30%) or mastectomy (4%), and amputation (0.6%), depending on the extent and location of the tumor.21 Most of the reports have not reported on the extent of excised margins. Data were reported from the SEER registry. The median overall survival is 51.5 months for cutaneous apocrine adenocarcinoma based on the SEER registry.21 The absence of lymph node metastases was associated with a significant survival advantage of 55 versus 33 months.21 The data from the SEER registry suggest that lymph node staging would better define prognosis. Patients with metastatic disease in the study by Hollowell et al.21 did poorly with a median survival of 14.5 months and a 5-year survival of 10%.21 This study reviewed 19 published cases of eyelid apocrine adenocarcinoma (Table).1–15 The mean age was 61.4 years (range, 36–85 years), 26% were women. Fifty-three percent of the cases had tumor limited to the eyelids. Most patients (18/19) presented with a painless blue-brown, eyelid lump. Local orbital and periorbital invasion was described in 47% of the patie nts.4,5,7,11–13 Thirty-five percent of patients had local lymph nodes involved.4,5,7,11–13 The mean follow up of the published cases reviewed was 40.4 months (range, 4–108 months).1,4,5,7,8,10–14,19 Seven cases were managed with wide local resections without local recurrence. Six cases required orbital exenteration for eyelid aporine adenocarcinoma with orbital invasion. Radiotherapy was used as an adjuvant treatment in 4 of 19 cases for local orbital or nodal disease. Radiotherapy was used as a primary treatment for local orbital invasion in 1 patient who refused exenteration. That patient underwent a course of 45-Gy radiation therapy over 3 weeks. At 24 months of follow up, visual acuity had improved to 20/30. The patient had no local or systemic recurrences at 2 years of follow up. The use of adjuvant radiotherapy to prevent local recurrence is not well established. Chemotherapy was described in 1 of the published cases, with no follow-up reports documented on the survival or control of the disease. Combined exenteration surgery and radiotherapy were used in eyelid apocrine carcinomas with aggressive metastatic spread.1,3,12 Local lymph node dissections have been reported to have variable success.7,11,12 Chemotherapy was described in 1 of the published cases, with no follow-up reports documented on the survival or control of the disease. Death was reported in 2 of the 19 cases with metastases.1,12 Distant metastasis was described in the bone (pelvic bones), lung, and brain.1,12 Various chemotherapy regimens have been used for cutaneous adenocarcinomas (combination of doxorubicin, cyclophosphamide, vincristine and bleomycin, fluorouracil, combination of methotrexate, and bleomycin) with variable success.25–27 The mean follow up of the published cases reviewed was 40.4 months (range, 4–108 months).1,4,5,7,8,10–14,19 Death was reported in 2 of the 19 cases (Table).1,12
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The published case reports lack data regarding staging, management, and survival. This study recommends that the reporting of eyelid tumors should include TNM staging to help clinicians better apply these results to individual patients. The American Joint Committee’s 7th Edition Eyelid Carcinoma Classification System on Cancer can be used for staging individual cases of apocrine carcinoma of the eyelids.16 This review indicates that the primary determinants of survival in patients with eyelid apocrine adenocarcinomas were the presence of lymph node metastasis, local (orbital, periorbital) invasion, and systemic metastasis. There is significant variation in the reported application of lymph node evaluation in patients with apocrine adenocarcinomas.21 Sentinel lymph node biopsy can identify clinically occult disease and define prognosis in patients with clinical lymphadenopathy. Staging may also include MRI, CT, and [(18)F]fluoro-2-deoxy-D-glucose PET/CT imaging.28 The published case reports lack data regarding staging, management, and survival. This review recommends that the reporting of eyelid tumors should include TNM staging to help clinicians better apply these results to individual patients. The American Joint Committee’s 7th Edition Eyelid Carcinoma Classification System on Cancer can be used for staging individual cases of apocrine carcinoma of the eyelids.16 Current surgical therapy based on these small case series remains unclear. Wide local excision of 1- to 2-cm margins for apocrine axillary adenocarcinoma has been recommended, as for other dermatologic neoplasms.29 Based on 9 cases of apocrine adenocarcinoma reported in the eyelid and the current case series, this review recommends complete excision under frozen section control or with a 4-mm clinical resection margin for discrete localized eyelid apocrine adenocarcinoma. Nine cases of localized eyelid apocrine adenocarcinoma treated with wide local excision in the current case series and reviewed cases had no local or regional recurrence. This review suggests that lymph node dissection should be performed for all patients with clinically positive nodes after appropriate TNM staging of the disease. Further case studies are required to confirm if a sentinel node biopsy followed by therapeutic lymphadenectomy will improve survival. The current series and review of previously reported cases suggest that these tumors may respond to adjuvant radiotherapy in locally advanced or recurrent local disease. Isolated case reports suggest some radiosensitivity of these tumors, and adjuvant radiation is recommended in high-risk cases (i.e., large >5 cm tumors, positive surgical margins within 1 cm, moderate-topoorly differentiated tumors, lymphovascular invasion).29,30 Adjuvant radiation to the involved lymph nodes basin can also be recommended in the setting of extranodal extension or extensive involvement (>4 lymph nodes).29,31 This review suggests that lymph node dissection should be performed for all patients with clinically positive nodes after appropriate TNM staging of the disease. Further case studies are required to confirm, if a sentinel node biopsy followed by therapeutic lymphadenectomy will improve survival. In apocrine adenocarcinoma lesions that are poorly circumscribed or that have extended into neighboring structures, a more radical dissection should be considered. The radical procedures may include orbital exenteration ± en bloc excision of the lacrimal drainage system, nasal cavity with sinuses, ± radical neck dissection, depending on the structures that are involved. In conclusion, adnexal apocrine adenocarcinoma appears to be aggressive, a third of cases had orbital invasion, and 10% had metastases and related mortality. Eyelid apocrine adenocarcinoma presented early could be treated with wide local excision alone with successful outcome.
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Summarized review of case reports on eyelid apocrine carcinomas Age/ Sex
Study
Location: presentation (duration)
Hunold et al.
63/M LLL: small painless brown nodule (6 m)
Valenzuela et al.3
78/M RLL: chalazion-like mass (12 m)
Akcay et al.4
57/M RLL: nontender, soft, 50 × 35 mm nodule (1 Y)
Akhtar et al.5
65/M Right eyelid: mass (6 m)
2
LN −
Extension None
+, NA Anterior orbit
NA
Intraconal, maxillary sinus mass Parotid metastasis
Barker-Griffith 66/M LLL: 5 × 6 mm bluish, NA et al.6 infraciliary thickening, madarosis (10.3 Y)
NA
Barker-Griffith 53/M RLL: firm, domeshaped, infraciliary et al.6 mass, telangiectatic vessels (5 Y)
NA
NA
Barker-Griffith 71/M LLL: lash line, grey nontender, cystic, et al.6 2 × 2 mm nodule, telangiectasia (6 m)
NA
NA
Shintaku et al.7 57/M LUL: chalazion-like subcaruncular tumor in medial canthus (14 m)
+
Local: caruncle, systemic: sclerotic pelvis lesions
−
NA
Paridaens and Mooy8
80/M RUL: 6 × 4 mm, soft blue-brown, elastic, painless, lump, lash loss (2 m)
Paties et al.9
36/F Right eyelid: painless ulcerated, 5-mm nodule, (NA)
Seregard10
85/F LUL: marginal bluish nodule (NA)
+3 m NA
−
Histopathology/ immunostaining
NA
Management: initial (adjuvant)
Inner columnar, outer Wedge resection myoepithelium, Prussian (none) blue+, CD68+, CK18+, Ki67+ Poorly differentiated cells, Orbitotomy lymphatic permeation, (exenteration+ infiltrative mass in ethmoidectomy, eyelid/ RT: orbit neck) bulbar conjunctiva, GCDFP-15+ NA Excisional biopsy (exenteration: refused, RT for residual tumor) Well-differentiated Wide excision papillary (parotidectomy+ adenocarcinoma, cystic neck dissection + component chemo + RT) Irregular tubular and focal Wedge resection papillary proliferations, (none) apical snouts, prominent nucleoli, pleomorphic nuclei, double-layered duct, GCDFP-15+, S100-, CEACystic nodules: papillary Wedge resection apocrine(none) type epithelium, fibrovascular core, mitoses. Solid areas: irregular adenoid, vesicular nuclei, nucleoli, iron+, GCDFP-15+, S100Papillary islets of Wedge resection moderately pleomorphic (none) epithelial cells GCDFP-15+, S100-, iron + Clusters/trabeculae of Excisional biopsy large, eosinophilic (left exenteration, polygonal, left radical neck hyperchromatic cells, dissection) PAS +, Prussian blue-, CD68-, GCDFP-15+, B72.3+, Vimentin, S100Strongly eosinophilic cells, Full-thickness, wide pleomorphic nuclei, block excision nucleoli, decapitation secretion, iron +, PAS + diastaseresistant granules, lymphangio invasion, EMA + Infiltrating Wide excision nonencapsulated, (none) papillary trabeculae and solid structures, PAS +ve, S100 +ve, GCDFP-15+, colloidal iron + Cytokeratin Wide excision antibodies(AE1/AE3) (none) stain +
Follow up NA
2.5 Y (alive, no recurrence)
16 m (alive, MRI: slight change) NA
>9 Y (alive, no recurrence)
>9 Y (alive, no recurrence)
>9 Y (alive, no recurrence) 9 m (alive, no recurrence)
2 Y (alive, no recurrence)
3 Y (alive, no recurrence)
1 Y (alive, no recurrence) (Continues)
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(Continued)
Study
Age/ Sex
Location: presentation (duration)
LN
Histopathology/ immunostaining
Extension
Infiltrating discrete acini lined by cuboidal epithelium (flattened, large nuclei, granular chromatin, variably eosinophilic), PAS +, Turnbull’s stain + RLL: cystic, mottled − − Various sized tubules, purple, translucent outer irregularly telangiectatic lesion columnar and inner (3 Y) eosinophilic layer with basal nuclei, proliferating epithelium, papillary projections LLL: chalazion-like − 1 Y: orbit, 2 Y: Various sized doublegrowth (6 m) intracranial layered ducts (tall columnar, eosinophilic, basal nuclei, outer illdefined smaller cells), perineural + LLL: firm rubbery mass +, NA Proptosis, impaired Invasive adenocarcinoma, (1 Y) EOM, reduced orbital irregular lumina resiliency, lacrimal with lining columnar gland eosinophilic cells, decapitation secretion, iron +, muscle, nerve, lymph, lacrimal gland invasion RUL: 1 × 1 cm +, 9 m Parotid gland Large pale, round nonulcerated, cells, finely granular nontender nodule eosinophilic cytoplasm, (7 m) irregular nuclei, small nucleoli, numerous mitoses, finely granular PAS +, granular iron + LUL: 7 × 6 × 6 mm, − − Cuboidal, acidophilic cells, red, slow, irregular, active decapitation, enlarging lesion, variable hyperchromatic serosanguinous (6 Y) nuclei, prominent nucleoli, PAS +, iron +
Management: initial (adjuvant)
Follow up
Thomson and Tanner11
66/M RLL: round, painless +, NA Periorbital fat, floor + tarsal cyst like lesion medial orbital wall (9 m)
Excision: frozen section control (radical exenteration, split skin grafts)
15 m (alive, no recurrence: CT orbit, neck, chest)
Ni et al.12
58/F
Wedge excision: frozen section control (none)
5 m (alive, no recurrence)
Ni et al.12
66/M
Full-thickness eyelid resection (none)
2 Y (died: intracranial metastasis)
Ni et al.12
50/M
Left exenteration+ maxillectomy+ ethmoidectomy, 3 Y later: RT+ radical neck dissection and chemo
5 Y (alive, no recurrence)
Futrell et al.13
59/F
Wide excision (right superficial parotidectomy + radical neck dissection)
7 Y (alive, no recurrence)
Aurora and Luxenberg14
58/M
4 m (alive, no recurrence)
Whorton and Patterson15
55/M RUL: 15 × 5 mm, red, granular, eroded, crusted mass, madarosis (4 Y)
−
Superior and medial margins involved
Eyelid split + lamellar resection: incomplete (6 M later: fullthickness excision 3-mm margin) Full-thickness excision (frozen section) (1 m later: 4 excisions, exenteration)
Stout and Cooley1
44/F RLL: inner canthal smooth bluish fluctuant mass (2 m)
−
Orbit, ethmoids, nasal cavity
Wide excision (2 re-excisions + RT + 11 m: exenteration + excision of ethmoidal and nasal tumor
2 Y (died:lung metastasis)
Circular and tubular masses of cells, eosinophilic cuboidal layer with high nuclear: cytoplasmic ratio, surrounded by amphophilic cells Cystic and nodular pattern, double-layered epithelium
7 m (alive, no recurrence)
EOM, extraocular movements; chemo, chemotherapy; F, female; GCDFP-15, gross cystic disease fluid protein 15; LLL, left lower eyelid; LN, lymph nodes; LUL, left upper eyelid; m, months; M, male; PAS, Periodic acid-Schiff base; RLL, right lower eyelid; RT, radiotherapy; RUL, right upper eyelid; Y, year(s); NA, data not available; +,NA, case series with data available only for some patients; EMA, epithelial membrane antigen.
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3. Valenzuela AA, Cupp DG, Heathcote JG. Primary apocrine adenocarcinoma of the eyelid. Orbit 2012;31:316–8. 4. Akcay EK, Simsek S, Cagil N, et al. Apocrine adenocarcinoma of the right eyelid and apocrine adenoma of the left maxillary sinus. Can J Ophthalmol 2008;43:609–10. 5. Akhtar I, Ispas CL, Flowers R, et al. Ductopapillary apocrine carcinoma of the eyelid metastatic to the parotid gland: report of a
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case diagnosed by fine-needle aspiration biopsy. Diagn Cytopathol 2009;37:91–5. 6. Barker-Griffith AE, Streeten BW, Charles NC. Moll gland neoplasms of the eyelid: a clinical and pathological spectrum in 5 cases. Arch Ophthalmol 2006;124:1645–9. 7. Shintaku M, Tsuta K, Yoshida H, et al. Apocrine adenocarcinoma of the eyelid with aggressive biological behavior: report of a case. Pathol Int 2002;52:169–73. 8. Paridaens D, Mooy CM. Apocrine sweat gland carcinoma. Eye (Lond) 2001;15(pt 2):253–4. 9. Paties C, Taccagni GL, Papotti M, et al. Apocrine carcinoma of the skin: a clinicopathologic, immunocytochemical, and ultrastructural study. Cancer 1993;71:375–81. 10. Seregard S. Apocrine adenocarcinoma arising in Moll gland cystadenoma. Ophthalmology 1993;100:1716–9. 11. Thomson SJ, Tanner NS. Carcinoma of the apocrine glands at the base of eyelashes; a case report and discussion of histological diagnostic criteria. Br J Plast Surg 1989;42:598–602. 12. Ni C, Wagoner M, Kieval S, et al. Tumours of the Moll’s glands. Br J Ophthalmol 1984;68:502–6. 13. Futrell JW, Krueger GR, Chretien PB, et al. Multiple primary sweat gland carcinomas. Cancer 1971;28:686–91. 14. Aurora AL, Luxenberg MN. Case report of adenocarcinoma of glands of Moll. Am J Ophthalmol 1970;70:984–90. 15. Whorton CM, Patterson JB. Carcinoma of Moll’s glands with extramammary Paget’s disease of the eyelid. Cancer 1955;8: 1009–15. 16. Ainbinder DJ, Esmaeli B, Groo SC, et al. Introduction of the 7th Edition Eyelid Carcinoma Classification System from the American Joint Committee on Cancer-International Union Against Cancer staging manual. Arch Pathol Lab Med 2009;133:1256–61. 17. Kipkie GF, Haust MD. Carcinoma of apocrine glands; report of case. AMA Arch Derm 1958;78:440–5. 18. Warkel RL. Selected apocrine neoplasms. J Cutan Pathol 1984;11:437–49. 19. Kage M, Nakamura Y, Ozumi K. A case report of equivocal neoplasm originating from an apocrine gland on the eyelid. Acta Pathol Jpn 1990;40:431–4.
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20. Nishikawa M, Takahashi K, Kanai K, et al. A case of apocrine adenocarcinoma originating from Moll’s gland. Folia Ophthalmol 1990;41:1087–92. 21. Hollowell KL, Agle SC, Zervos EE, et al. Cutaneous apocrine adenocarcinoma: defining epidemiology, outcomes, and optimal therapy for a rare neoplasm. J Surg Oncol 2012;105:415–9. 22. Requenal L, Kiryu H, Ackerman AB. Neoplasms With Apocrine Differentiation. Philadelphia, PA: Lippincott-Raven, 1998:116. 23. Ansai S, Koseki S, Hozumi Y, et al. An immunohistochemical study of lysozyme, CD-15 (Leu M1), and gross cystic disease fluid protein-15 in various skin tumors. Assessment of the specificity and sensitivity of markers of apocrine differentiation. Am J Dermatopathol 1995;17:249–55. 24. de Viragh PA, Szeimies RM, Eckert F. Apocrine cystadenoma, apocrine hidrocystoma, and eccrine hidrocystoma: three distinct tumors defined by expression of keratins and human milk fat globulin 1. J Cutan Pathol 1997;24:249–55. 25. Mezger J, Remberger K, Schalhorn A, et al. Treatment of metastatic sweat gland carcinoma by a four drug combination chemotherapy: response in two cases. Med Oncol Tumor Pharmacother 1986;3:29–34. 26. Bellman B, Gregory NA, Silvers D, et al. Sweat gland carcinoma with metastases to the skin: response to 5-fluorouracil chemotherapy. Cutis 1995;55:221–4. 27. Morabito A, Bevilacqua P, Vitale S, et al. Clinical management of a case of recurrent apocrine gland carcinoma of the scalp: efficacy of a chemotherapy schedule with methotrexate and bleomycin. Tumori 2000;86:472–4. 28. Singh H, Sharma P, Suman Kc S, et al. Apocrine sweat gland carcinoma: initial evaluation, staging, and response monitoring using 18F-FDG PET/CT. Clin Nucl Med 2013;38:e223–5. 29. Chamberlain R, Huber K, White J, et al. Apocrine carcinoma of the axilla: review of the literature and recommendations for treatment. Am J Clin Oncol 1999;22:131–5. 30. Tlemcani K, Levine D, Smith RV, et al. Metastatic apocrine carcinoma of the scalp: prolonged response to systemic chemotherapy. J Clin Oncol 2010;28:e412–4. 31. Sharma CRD, Badran R, Singhal V, et al. Metastatic sweat gland adenocarcinoma: a clinico-pathological dilemma. World J Surg Oncol 2003;1:13.
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Apocrine Adenocarcinoma of the Eyelid: Case Series and Review Edwin C. Figueira, M.B.B.S., M.S.*, Jenny Danks, F.R.A.N.Z.C.O.†, Akihide Watanabe, M.D.‡, Jwu Jin Khong, F.R.A.N.Z.C.O.§, Lorraine Ong, F.R.A.N.Z.C.O.§, and Dinesh Selva, F.R.A.C.S., F.R.A.N.Z.C.O.* *South Australian Institute of Ophthalmology and Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia; †Department of Ophthalmology, Sydney Hospital and Sydney Eye Hospital, Sydney, New South Wales, Australia; ‡Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; and §The Royal Victorian Eye and Ear Hospital, Orbital Plastics and Lacrimal Unit, Melbourne, Australia
Purpose: To report 2 patients with apocrine adenocarcinoma of the eyelid and review the literature. Design: Noncomparative, retrospective case series and review. Participants: Clinical data of 2 patients with histopathologic diagnoses of apocrine adenocarcinoma of the eyelid were obtained from medical records. The histopathology and immunohistochemistry data for the 2 cases were studied. A retrospective review was performed on all reported cases of eyelid apocrine carcinoma. Main Outcome Measures: Clinical features, histopathology, immunohistochemistry, and clinical course following treatment are reported. The results of a retrospective review of clinical presentations, local and systemic spread, treatment method, and prognosis from published case reports on eyelid apocrine adenocarcinoma are discussed. Results: One patient had orbital invasion at presentation. This patient had radiotherapy alone and had no systemic or local recurrence at 2 years. One patient underwent a 4-mm margin wide surgical excision. This patient had no local or systemic recurrences at 1 year. A review of the literature suggests that the prognosis of adnexal apocrine tumors is indeterminate and variable. Most patients have successful outcomes following local surgical excision. Radiotherapy has been used as an adjunctive treatment for local metastatic disease. Conclusions: Apocrine adenocarcinoma is a rare adnexal tumor of the eyelid, which may present with orbital invasion. (Ophthal Plast Reconstr Surg 2013;29:417–423)
A
pocrine adenocarcinomas are rare ocular adnexal tumors that arise mainly from the glands of Moll. Stout and Cooley1 were the first to report on apocrine carcinoma in 1951. There are 19 reported cases of apocrine gland carcinoma of the eyelids.1–15
Accepted for publication July 2, 2013. The authors disclose no financial or conflicts of interest. Address correspondence and reprint requests to Edwin C. Figueira, M.B.B.S., M.S., South Australian Institute of Ophthalmology, Level 8, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia. E-mail: [email protected] DOI: 10.1097/IOP.0b013e3182a64fe5
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This study describes 2 new cases and reviews the literature on apocrine adenocarcinoma of the eyelids.
CASE 1 An 87-year-old man had progressive right ptosis of 1-year duration associated with decreased vision (Fig. 1A). He was treated for glaucoma. Snellen decimal visual acuities were 20/40 in the affected OD and 20/20 in the OS. Extraocular movements of the right globe were reduced in all directions. A firm mass was palpable in the upper and lower eyelids. CT revealed an enhancing mass infiltrating the soft tissues of the orbit with no bone erosion. MRI demonstrated an enhancing mass involving both intraconal and extraconal spaces, which was isointense to muscle on T1-weighted images and hyperintense on T2 (Fig. 1B,C). A right subbrow incisional biopsy revealed a grey mass. Histopathology showed invasive apocrine adenocarcinoma and gland-like structures with irregularly shaped lumina. The columnar cells had eosinophilic cytoplasm with basal nuclei. The luminal cells demonstrated decapitation secretion. Immunohistochemical testing for GCDFP-15 (gross cystic disease fluid protein 15; Fig. 1E) and CK7 (cytokeratin 7) was positive. Further immunostaining was negative for CK20, S100, estrogen receptor, and progesterone receptor. Staging including a positron emission tomography (PET)-CT scan was negative for regional or distant spread. Clinically, the eyelid tumor was staged as IIIA based on the 7th Edition Eyelid Carcinoma Classification System from the American Joint Committee on Cancer-International Union Against Cancer.16 The patient refused exenteration and underwent a course of 45-Gy radiation therapy over 3 weeks. At 10 months of follow up, visual acuity had improved to 20/30. Extraocular movements were much improved, and there was a significant reduction in the orbital and eyelid mass (Fig. 1F) on imaging (Fig. 1G,H). The intraocular pressure remained medically controlled.
CASE 2 A 56-year-old woman presented with an 18-month history of a left lower eyelid lesion that had occasionally bled over the last 2 weeks. She had a 5 mm ×4 mm hemorrhagic cystic lesion, just below the eyelash line. Ocular and orbital examination was normal. Due to the unusual appearance of the swelling, an incisional biopsy was performed. An incisional biopsy revealed histologic features of apocrine cystadenocarcinoma (Fig. 2A–D). The diagnosis was based on the histopathologic criteria of
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FIG. 1. A, Upper, lower eyelid and orbital involvement by tumor (TNM stage IIIA). B and C, Coronal and axial MRI showing contrastenhancing orbital mass. D, Glandular epithelium showing decapitation secretion (hematoxylin-eosin, ×60). E, Immunostaining: positive for GCFDP-15 (×60). F, Clinical reduced proptosis. G and H, Reduced orbital mass after radiotherapy.
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FIG. 2. A, Cribriform glandular epithelium with decapitation secretion (hematoxylin-eosin, ×100); (B) papillary and cribriform structure (hematoxylin-eosin, ×40); (C) micropapillary structure (hematoxylin-eosin, ×40); (D) iron-positive intracellular pigment (hematoxylin-eosin ×40).
Kipkie and Haust.17 The patient underwent a 4-mm wide margin resection. The residual eyelid defect was primarily closed. The histopathology revealed dermal scarring, with no residual malignancy. Clinically, this patient was staged as IB (T2a, N0, M0).16 At last follow up at 12 months, there was no recurrence.
DISCUSSION Apocrine adenocarcinomas are rare ocular adnexal tumors that arise mainly from the glands of Moll. The glands of Moll are modified apocrine glands that lie at the base of the follicles of the eyelashes.18 To the best of knowledge, there are 19 cases of ocular adnexal apocrine adenocarcinoma reported.10–15,19,20 A recent review of cutaneous apocrine adenocarcinoma using the Surveillance, Epidemiology and End Results (SEER) Program registry data in the United States revealed that the primary site for these tumors is the axilla.21 Extra-axillary disease is reported in around 50% of cases. Thirty-five percent of the cases were noted to be in the head and neck. Cutaneous apocrine adenocarcinomas were reported in older patients (median age, 67 years), with no racial or gender predilection.21 Histopathology of this tumor is characterized by an invasive adenocarcinoma with gland-like structures. The malignant cells are eosinophilic or opaque glass like and form irregularly shaped lumina of varying size. The pathologic diagnosis
of these tumors can be challenging as distinguishing malignant from benign subtypes can be difficult. Kipkie and Haust17 described the following criteria for histologic diagnosis of apocrine adenocarcinoma: 1) periodic acid-Schiff (PAS) positive, (2) strongly eosinophilic cytoplasm, (3) decapitation secretion, (4) iron-positive intracellular pigment, and (5) occurrence in areas where apocrine glands are normally located. The principal diagnostic histopathologic feature of apocrine glandular differentiation used in this case series is the decapitation secretion from eosinophilic cuboidal cells (case 2).22 In well-differentiated tumors, apocrine tumors show pathognomonic decapitation secretion, while in poorly differentiated tumors, the cells can infiltrate as single cells or small cords of cells. The PAS-positive malignant apocrine epithelial cells often have diastase-resistant granules containing iron.22 Immunohistochemical demonstration of GCDFP-15 has become a useful adjunctive diagnostic tool in cases where decapitation secretion is not readily apparent. GCDFP-15 has been shown to stain apocrine-related neoplasms in 84% of the specimens (21/25) by Ansai et al.23 This immunostaining method for diagnosis was used in patient 1 in this series. GCDFP-15 immunostaining was performed in the second case because histology revealed characteristic decapitation secretion. Apocrine adenocarcinoma has to be differentiated from apocrine hidrocystomas and apocrine cystadenoma. Apocrine hidrocystomas are either unilocular or multilocular
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dermal cysts lined by columnar epithelial cells, with abundant granular eosinophilic cytoplasm and lack of cellular atypia. The cells have round basal nuclei. They possess PAS-positive and diastase-resistant granules. Papillary infolding into the cystic cavity present as “decapitation” secretion, with an underlying layer of flattened myoepithelial cells. The abundant secretory granules and other features characteristic of mature apocrine secretory epithelium help establish the diagnosis.24 Apocrine cystadenomas stain distinctly with immunoreactive stains for cytokeratins and human milk fat globulin 1.24 Primary cutaneous apocrine adenocarcinoma has been reported in older patients (mean age 67 years), with no racial or gender predilection.21 Extra-axillary disease is reported in around 50% of cases, with 35% of the cases involving the head and neck region. The most commonly documented surgical procedure for cutaneous apocrine adenocarcinoma was local excision (50%), followed by wide excision (30%) or mastectomy (4%), and amputation (0.6%), depending on the extent and location of the tumor.21 Most of the reports have not reported on the extent of excised margins. Data were reported from the SEER registry. The median overall survival is 51.5 months for cutaneous apocrine adenocarcinoma based on the SEER registry.21 The absence of lymph node metastases was associated with a significant survival advantage of 55 versus 33 months.21 The data from the SEER registry suggest that lymph node staging would better define prognosis. Patients with metastatic disease in the study by Hollowell et al.21 did poorly with a median survival of 14.5 months and a 5-year survival of 10%.21 This study reviewed 19 published cases of eyelid apocrine adenocarcinoma (Table).1–15 The mean age was 61.4 years (range, 36–85 years), 26% were women. Fifty-three percent of the cases had tumor limited to the eyelids. Most patients (18/19) presented with a painless blue-brown, eyelid lump. Local orbital and periorbital invasion was described in 47% of the patie nts.4,5,7,11–13 Thirty-five percent of patients had local lymph nodes involved.4,5,7,11–13 The mean follow up of the published cases reviewed was 40.4 months (range, 4–108 months).1,4,5,7,8,10–14,19 Seven cases were managed with wide local resections without local recurrence. Six cases required orbital exenteration for eyelid aporine adenocarcinoma with orbital invasion. Radiotherapy was used as an adjuvant treatment in 4 of 19 cases for local orbital or nodal disease. Radiotherapy was used as a primary treatment for local orbital invasion in 1 patient who refused exenteration. That patient underwent a course of 45-Gy radiation therapy over 3 weeks. At 24 months of follow up, visual acuity had improved to 20/30. The patient had no local or systemic recurrences at 2 years of follow up. The use of adjuvant radiotherapy to prevent local recurrence is not well established. Chemotherapy was described in 1 of the published cases, with no follow-up reports documented on the survival or control of the disease. Combined exenteration surgery and radiotherapy were used in eyelid apocrine carcinomas with aggressive metastatic spread.1,3,12 Local lymph node dissections have been reported to have variable success.7,11,12 Chemotherapy was described in 1 of the published cases, with no follow-up reports documented on the survival or control of the disease. Death was reported in 2 of the 19 cases with metastases.1,12 Distant metastasis was described in the bone (pelvic bones), lung, and brain.1,12 Various chemotherapy regimens have been used for cutaneous adenocarcinomas (combination of doxorubicin, cyclophosphamide, vincristine and bleomycin, fluorouracil, combination of methotrexate, and bleomycin) with variable success.25–27 The mean follow up of the published cases reviewed was 40.4 months (range, 4–108 months).1,4,5,7,8,10–14,19 Death was reported in 2 of the 19 cases (Table).1,12
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The published case reports lack data regarding staging, management, and survival. This study recommends that the reporting of eyelid tumors should include TNM staging to help clinicians better apply these results to individual patients. The American Joint Committee’s 7th Edition Eyelid Carcinoma Classification System on Cancer can be used for staging individual cases of apocrine carcinoma of the eyelids.16 This review indicates that the primary determinants of survival in patients with eyelid apocrine adenocarcinomas were the presence of lymph node metastasis, local (orbital, periorbital) invasion, and systemic metastasis. There is significant variation in the reported application of lymph node evaluation in patients with apocrine adenocarcinomas.21 Sentinel lymph node biopsy can identify clinically occult disease and define prognosis in patients with clinical lymphadenopathy. Staging may also include MRI, CT, and [(18)F]fluoro-2-deoxy-D-glucose PET/CT imaging.28 The published case reports lack data regarding staging, management, and survival. This review recommends that the reporting of eyelid tumors should include TNM staging to help clinicians better apply these results to individual patients. The American Joint Committee’s 7th Edition Eyelid Carcinoma Classification System on Cancer can be used for staging individual cases of apocrine carcinoma of the eyelids.16 Current surgical therapy based on these small case series remains unclear. Wide local excision of 1- to 2-cm margins for apocrine axillary adenocarcinoma has been recommended, as for other dermatologic neoplasms.29 Based on 9 cases of apocrine adenocarcinoma reported in the eyelid and the current case series, this review recommends complete excision under frozen section control or with a 4-mm clinical resection margin for discrete localized eyelid apocrine adenocarcinoma. Nine cases of localized eyelid apocrine adenocarcinoma treated with wide local excision in the current case series and reviewed cases had no local or regional recurrence. This review suggests that lymph node dissection should be performed for all patients with clinically positive nodes after appropriate TNM staging of the disease. Further case studies are required to confirm if a sentinel node biopsy followed by therapeutic lymphadenectomy will improve survival. The current series and review of previously reported cases suggest that these tumors may respond to adjuvant radiotherapy in locally advanced or recurrent local disease. Isolated case reports suggest some radiosensitivity of these tumors, and adjuvant radiation is recommended in high-risk cases (i.e., large >5 cm tumors, positive surgical margins within 1 cm, moderate-topoorly differentiated tumors, lymphovascular invasion).29,30 Adjuvant radiation to the involved lymph nodes basin can also be recommended in the setting of extranodal extension or extensive involvement (>4 lymph nodes).29,31 This review suggests that lymph node dissection should be performed for all patients with clinically positive nodes after appropriate TNM staging of the disease. Further case studies are required to confirm, if a sentinel node biopsy followed by therapeutic lymphadenectomy will improve survival. In apocrine adenocarcinoma lesions that are poorly circumscribed or that have extended into neighboring structures, a more radical dissection should be considered. The radical procedures may include orbital exenteration ± en bloc excision of the lacrimal drainage system, nasal cavity with sinuses, ± radical neck dissection, depending on the structures that are involved. In conclusion, adnexal apocrine adenocarcinoma appears to be aggressive, a third of cases had orbital invasion, and 10% had metastases and related mortality. Eyelid apocrine adenocarcinoma presented early could be treated with wide local excision alone with successful outcome.
© 2013 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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Summarized review of case reports on eyelid apocrine carcinomas Age/ Sex
Study
Location: presentation (duration)
Hunold et al.
63/M LLL: small painless brown nodule (6 m)
Valenzuela et al.3
78/M RLL: chalazion-like mass (12 m)
Akcay et al.4
57/M RLL: nontender, soft, 50 × 35 mm nodule (1 Y)
Akhtar et al.5
65/M Right eyelid: mass (6 m)
2
LN −
Extension None
+, NA Anterior orbit
NA
Intraconal, maxillary sinus mass Parotid metastasis
Barker-Griffith 66/M LLL: 5 × 6 mm bluish, NA et al.6 infraciliary thickening, madarosis (10.3 Y)
NA
Barker-Griffith 53/M RLL: firm, domeshaped, infraciliary et al.6 mass, telangiectatic vessels (5 Y)
NA
NA
Barker-Griffith 71/M LLL: lash line, grey nontender, cystic, et al.6 2 × 2 mm nodule, telangiectasia (6 m)
NA
NA
Shintaku et al.7 57/M LUL: chalazion-like subcaruncular tumor in medial canthus (14 m)
+
Local: caruncle, systemic: sclerotic pelvis lesions
−
NA
Paridaens and Mooy8
80/M RUL: 6 × 4 mm, soft blue-brown, elastic, painless, lump, lash loss (2 m)
Paties et al.9
36/F Right eyelid: painless ulcerated, 5-mm nodule, (NA)
Seregard10
85/F LUL: marginal bluish nodule (NA)
+3 m NA
−
Histopathology/ immunostaining
NA
Management: initial (adjuvant)
Inner columnar, outer Wedge resection myoepithelium, Prussian (none) blue+, CD68+, CK18+, Ki67+ Poorly differentiated cells, Orbitotomy lymphatic permeation, (exenteration+ infiltrative mass in ethmoidectomy, eyelid/ RT: orbit neck) bulbar conjunctiva, GCDFP-15+ NA Excisional biopsy (exenteration: refused, RT for residual tumor) Well-differentiated Wide excision papillary (parotidectomy+ adenocarcinoma, cystic neck dissection + component chemo + RT) Irregular tubular and focal Wedge resection papillary proliferations, (none) apical snouts, prominent nucleoli, pleomorphic nuclei, double-layered duct, GCDFP-15+, S100-, CEACystic nodules: papillary Wedge resection apocrine(none) type epithelium, fibrovascular core, mitoses. Solid areas: irregular adenoid, vesicular nuclei, nucleoli, iron+, GCDFP-15+, S100Papillary islets of Wedge resection moderately pleomorphic (none) epithelial cells GCDFP-15+, S100-, iron + Clusters/trabeculae of Excisional biopsy large, eosinophilic (left exenteration, polygonal, left radical neck hyperchromatic cells, dissection) PAS +, Prussian blue-, CD68-, GCDFP-15+, B72.3+, Vimentin, S100Strongly eosinophilic cells, Full-thickness, wide pleomorphic nuclei, block excision nucleoli, decapitation secretion, iron +, PAS + diastaseresistant granules, lymphangio invasion, EMA + Infiltrating Wide excision nonencapsulated, (none) papillary trabeculae and solid structures, PAS +ve, S100 +ve, GCDFP-15+, colloidal iron + Cytokeratin Wide excision antibodies(AE1/AE3) (none) stain +
Follow up NA
2.5 Y (alive, no recurrence)
16 m (alive, MRI: slight change) NA
>9 Y (alive, no recurrence)
>9 Y (alive, no recurrence)
>9 Y (alive, no recurrence) 9 m (alive, no recurrence)
2 Y (alive, no recurrence)
3 Y (alive, no recurrence)
1 Y (alive, no recurrence) (Continues)
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(Continued)
Study
Age/ Sex
Location: presentation (duration)
LN
Histopathology/ immunostaining
Extension
Infiltrating discrete acini lined by cuboidal epithelium (flattened, large nuclei, granular chromatin, variably eosinophilic), PAS +, Turnbull’s stain + RLL: cystic, mottled − − Various sized tubules, purple, translucent outer irregularly telangiectatic lesion columnar and inner (3 Y) eosinophilic layer with basal nuclei, proliferating epithelium, papillary projections LLL: chalazion-like − 1 Y: orbit, 2 Y: Various sized doublegrowth (6 m) intracranial layered ducts (tall columnar, eosinophilic, basal nuclei, outer illdefined smaller cells), perineural + LLL: firm rubbery mass +, NA Proptosis, impaired Invasive adenocarcinoma, (1 Y) EOM, reduced orbital irregular lumina resiliency, lacrimal with lining columnar gland eosinophilic cells, decapitation secretion, iron +, muscle, nerve, lymph, lacrimal gland invasion RUL: 1 × 1 cm +, 9 m Parotid gland Large pale, round nonulcerated, cells, finely granular nontender nodule eosinophilic cytoplasm, (7 m) irregular nuclei, small nucleoli, numerous mitoses, finely granular PAS +, granular iron + LUL: 7 × 6 × 6 mm, − − Cuboidal, acidophilic cells, red, slow, irregular, active decapitation, enlarging lesion, variable hyperchromatic serosanguinous (6 Y) nuclei, prominent nucleoli, PAS +, iron +
Management: initial (adjuvant)
Follow up
Thomson and Tanner11
66/M RLL: round, painless +, NA Periorbital fat, floor + tarsal cyst like lesion medial orbital wall (9 m)
Excision: frozen section control (radical exenteration, split skin grafts)
15 m (alive, no recurrence: CT orbit, neck, chest)
Ni et al.12
58/F
Wedge excision: frozen section control (none)
5 m (alive, no recurrence)
Ni et al.12
66/M
Full-thickness eyelid resection (none)
2 Y (died: intracranial metastasis)
Ni et al.12
50/M
Left exenteration+ maxillectomy+ ethmoidectomy, 3 Y later: RT+ radical neck dissection and chemo
5 Y (alive, no recurrence)
Futrell et al.13
59/F
Wide excision (right superficial parotidectomy + radical neck dissection)
7 Y (alive, no recurrence)
Aurora and Luxenberg14
58/M
4 m (alive, no recurrence)
Whorton and Patterson15
55/M RUL: 15 × 5 mm, red, granular, eroded, crusted mass, madarosis (4 Y)
−
Superior and medial margins involved
Eyelid split + lamellar resection: incomplete (6 M later: fullthickness excision 3-mm margin) Full-thickness excision (frozen section) (1 m later: 4 excisions, exenteration)
Stout and Cooley1
44/F RLL: inner canthal smooth bluish fluctuant mass (2 m)
−
Orbit, ethmoids, nasal cavity
Wide excision (2 re-excisions + RT + 11 m: exenteration + excision of ethmoidal and nasal tumor
2 Y (died:lung metastasis)
Circular and tubular masses of cells, eosinophilic cuboidal layer with high nuclear: cytoplasmic ratio, surrounded by amphophilic cells Cystic and nodular pattern, double-layered epithelium
7 m (alive, no recurrence)
EOM, extraocular movements; chemo, chemotherapy; F, female; GCDFP-15, gross cystic disease fluid protein 15; LLL, left lower eyelid; LN, lymph nodes; LUL, left upper eyelid; m, months; M, male; PAS, Periodic acid-Schiff base; RLL, right lower eyelid; RT, radiotherapy; RUL, right upper eyelid; Y, year(s); NA, data not available; +,NA, case series with data available only for some patients; EMA, epithelial membrane antigen.
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