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Table 1. 
Malignant Tumors of the Eyelid, Florida Cancer Data System, 1981-1994
Malignant Tumors of the Eyelid, Florida Cancer Data System, 1981-1994
Table 2. 
Primary Malignant Tumors of the Eyelid, Patient Characteristics
Primary Malignant Tumors of the Eyelid, Patient Characteristics
Table 3. 
Histologic Diagnoses of Primary Lymphomas of the Eyelid
Histologic Diagnoses of Primary Lymphomas of the Eyelid
1.
Lee  JAH Epidemiology of cancers of the skin. Friedman  RJRigel  DSKopf  AWHarris  MNBaker  Deds.Cancer of the Skin. Philadelphia, Pa WB Saunders Co1991;
2.
Scotto  JFears  TFraumeni  JJ The Incidence of Non-Melanoma Skin Cancer in the United States.  Bethesda, Md Public Health Service, National Institutes of Health1981;NIH publication 82-2433
3.
Wright  JDFont  RL Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations. Cancer. 1979;441757- 1769Article
4.
Rao  NAHidayat  AAMcLean  IWZimmerman  LE Sebaceous carcinoma of the ocular adnexa: a clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol. 1982;13113- 122Article
5.
Doxanas  MTGreen  WR Sebaceous gland carcinoma: a review of 40 cases. Arch Ophthalmol. 1984;102245- 249Article
6.
Garner  AKoornneeff  LLevene  ACollin  JRO Malignant melanoma of the eyelid skin: histopathology and behaviour. Br J Ophthalmol. 1985;69180- 186Article
7.
Kivela  TTarkkanen  A The Merkel cell and associated neoplasms in the eyelids and periocular region. Surv Ophthalmol. 1990;35171- 187Article
8.
Percy  CedVan Holten  VedMuire  Ced The International Classification of Diseases for Oncology, Second Edition.  Geneva, Switzerland World Health Organization1990;
9.
Percy  CLedVan Houlten  VedMuir  Ced International Histologic Classification of Tumours.  Geneva, Switzerland World Health Organization1967;
10.
Percy  CLO'Conor  GRies  LGJaffe  ES Non-Hodgkin's lymphoma: application of the International Classification of Disease for Oncology (ICD-O) to the Working Formulation. Cancer. 1984;541435- 1438Article
11.
Office of Budget and Planning, Population Report.  Tallahassee, Fla Office of the Governor1994;
12.
Office of Vital Statistics, Population Report.  Jacksonville, Fla Dept of Health and Human Resources1995;
13.
Not Available, SAS Language and Procedures. Version 6. Cary, NC SAS Institute1989;
14.
Hirsch  RPRiegelman  RK Statistical First Aid: Interpretation of Health Research Data.  Boston, Mass Blackwell Scientific Publishers1992;
15.
Register, Florida Cancer Data System Newsletter. Spring 1996;
16.
Howe  HedLehnherr  Med Cancer Incidence in North America, 1989-1993.  Sacramento, Calif North American Association of Central Cancer Registries1997;
17.
Egan  KMSeddon  JMGlynn  RJGragoudas  ESAlbert  DM Epidemiologic aspects of uveal melanoma. Surv Ophthalmol. 1988;32239- 251Article
18.
Reintgen  DSMcCarty  KM  JrCox  ESeigler  HF Malignant melanoma in black American and white American populations: a comparative review. JAMA. 1982;2481856- 1859Article
19.
Rao  NAMcLean  IWZimmerman  LE Sebaceous carcinoma of the eyelid. Jakobiec  FAed.Ocular and Adnexal Tumors. Birmingham, Ala Aesculapius1978;
20.
Wolfe  JT  IIIYeats  RPWick  MRCampbell  RJWaller  RR Sebaceous carcinoma of the eyelid. Am J Surg Pathol. 1984;8597- 606Article
21.
Ni  CSearl  SSKuo  PK  et al.  Sebaceous cell carcinomas of the ocular adnexa, tumors of the eyelid and orbit: a Chinese-American collaborative study. Int Ophthalmol Clin. 1982;2223- 61Article
22.
Burg  G Cutaneous B-cell lymphomas. J Dermatol Surg Oncol. 1984;10229- 328
23.
Garia  CFWeiss  LMWarnke  RAWood  GS Cutaneous follicular lymphoma. Am J Surg Pathol. 1986;10454- 463Article
24.
Devesa  SSFears  T Non-Hodgkin's lymphoma time trends: United States and international data. Cancer Res. 1992;52(suppl)5432s- 5440s
25.
Gilchest  BAMarjan  GMina  Y Aging and photoaging affect gene expression in cultured human keratinocytes. Arch Dermatol. 1994;13082- 86Article
Clinical Sciences
February 1998

Malignant Tumors of the EyelidA Population-Based Study of Non–Basal Cell and Non–Squamous Cell Malignant Neoplasms

Author Affiliations

From the Departments of Ophthalmology and Pathology, College of Medicine (Dr Margo), and the Cancer Control Program, H. Lee Moffitt Cancer Center and Research Institute (Mr Mulla), University of South Florida, Tampa.

Arch Ophthalmol. 1998;116(2):195-198. doi:10.1001/archopht.116.2.195
Abstract

Objective  To determine the relative frequencies, average annual incidences, and patient characteristics of non–basal cell and non–squamous cell malignant neoplasms of the eyelid in a defined geographic population.

Design and Setting  A retrospective study using the Florida Cancer Data System to identify malignant tumors of the eyelid, except for basal cell and squamous cell carcinomas, from 1981 through 1994. Cases were limited to persons who resided within Florida.

Main Outcome Measure  Incidence of histologically confirmed malignant eyelid tumors.

Results  Two hundred six primary malignant eyelid tumors were identified. The 3 most common, in order of frequency, were melanoma, sebaceous carcinoma, and lymphoma. The median age at diagnosis for all patients was 73 years. Only 3 of the 206 malignant neoplasms occurred in blacks. The annual incidence of eyelid melanoma and sebaceous carcinoma in whites older than 20 years was 0.6 and 0.5 per million, respectively. Kaposi sarcoma was the most common type of mesenchymal tumor. Eleven different histologic types of lymphoma were found in the eyelid. Only 2 of 27 lymphomas had T-cell lineage.

Conclusions  Malignant tumors of the eyelid other than basal cell and squamous cell carcinoma are uncommon and usually occur in elderly white persons. Primary eyelid tumors of any type are rare in blacks. The risk of a non–basal cell and non–squamous cell malignant neoplasm of the eyelid in Florida is 6.4 times greater for whites than for blacks (95% confidence interval [CI], 2.1-20.2). A variety of B-cell lymphomas can be manifested as primary eyelid tumors.

THERE ARE few population-based studies on malignant tumors of the skin other than those for melanoma, basal cell, and squamous cell carcinoma.1,2 Even less epidemiologic information exists for malignant tumors from defined anatomic regions such as the eyelids. Knowledge about uncommon malignant tumors of the eyelid is based principally on case series from tertiary care facilities, where referral bias may affect results and incidence rates cannot be determined because denominator populations are unknown.37 We used the Florida Cancer Data System (FCDS) registry to study the types and distribution of malignant tumors of the eyelid other than basal cell and squamous cell carcinoma.

SUBJECTS, MATERIALS, AND METHODS

Florida has required all acute care medical facilities to report cancer cases, except basal cell and squamous cell carcinoma of the skin, to the cancer registry within 6 months of diagnosis. The FCDS was set up in 1981 to accomplish this legislated mandate. Data from the statewide cancer registry are available on a commercial file (CD-ROM) and include the 1981 through 1994 calendar years. Files were compiled at the Sylvester Comprehensive Cancer Center at the University of Miami, Fla. Data were subjected to extensive logic analysis and inter-item and intra-item edit checks. Duplicate entries were removed at our institution. The commercial file does not contain information on follow-up and contains limited information on treatment.

The cancer coding system used by the FCDS is based on the International Classification of Diseases for Oncology (ICD-O).8 Tumor nomenclature is designed to be interchangeable with terms used in the International Histological Classification of Tumours.9 Morphology codes for non-Hodgkin lymphoma are compatible with the terminology adopted by the Working Formulation.10 The diagnosis of extranodal lymphoma is based on the timing of the diagnosis. The eyelid would be designated as the primary site if it were the initial site of histologically confirmed lymphoma. Vital statistics were abstracted by trained registrars. Patient race classification was based on information in the patient's medical record.

The anatomic code for the eyelid was cross-referenced with the behavior code for malignant tumor to identify all primary invasive malignant neoplasms of the eyelids. The search was limited to persons who resided within the state. Incidence rates were calculated using data from the 1980 and 1990 Florida census.11,12 Incidence in this study was defined as the number of new cases of eyelid cancer in 14 years divided by the total number of person-years at risk. This ratio is expressed in cases per million population per year. Statistical inference for relative risk of developing cancer of the eyelid in whites vs blacks was performed by calculating 95% confidence intervals (CIs) with the logit method.13 Poisson CIs were used for incidence rates.14 The incidence of eyelid tumors in blacks was age-adjusted to the 1987 white population in Florida to control for any differences in age distribution between the races.

RESULTS

Two hundred six primary malignant neoplasms of the eyelids were recorded in the FCDS registry from 1981 through 1994 (Table 1). Diagnoses of skin cancer had to be histologically established for inclusion in the FCDS. The 3 most common eyelid tumors were malignant melanoma (72 cases), sebaceous carcinoma (59 cases), and lymphoma (27 cases). The median age at diagnosis was 68 years, 75 years, and 77 years, respectively (Table 2). There were 25 cases of sarcoma, 19 of which were Kaposi sarcoma.

All 99 patients with melanoma and lymphoma were white. Fifty-seven patients with sebaceous carcinoma were white. Eighty-nine percent of patients with Kaposi sarcoma and all 6 patients with Merkel cell carcinoma were white.

Melanoma of the eyelid was one third more common in men, while sebaceous carcinoma was 40% more common in women (Table 2). Seventeen (90%) of 19 patients with Kaposi sarcoma were men.

Eleven different lymphoma diagnoses were recorded among the 27 cases that were primary to the eyelid (Table 3). The 2 most common diagnoses were "lymphoma, not otherwise specified" and small-cell, lymphocytic lymphoma. Two patients had T-cell lymphoma: one with mycosis fungoides and the other with a peripheral T-cell lymphoma.

There were 8 types of primary epithelial malignant neoplasms, including 3 sweat gland carcinomas and 4 mucinous adenocarcinomas. No more than 3 cases of any single type of malignant adnexal tumor were reported (Table 1). Six Merkel cell tumors were diagnosed, all in persons older than 73 years (Table 2).

The annual incidence for all non–basal cell and non–squamous cell tumors of the eyelid was 1.8 per million of white population (95% CI, 1.6-2.1 cases per million) older than 20 years. For blacks of the same age, the incidence was 0.3 per million of black population (95% CI, 0.05-0.7 cases per million). The rates for melanoma and sebaceous carcinoma of the eyelid for whites older than 20 years were 0.6 and 0.5 per million, respectively. The incidence of eyelid tumors in blacks did not significantly change after being age-adjusted to the 1987 white population.

COMMENT

The malignant neoplasms of the eyelid reported to the FCDS represent the collective experience of 95 different medical care facilities, 44% of all facilities in the FCDS network. Only 4 medical facilities reported more than 10 cases (range, 1-16 cases). Florida does not require medical facilities to report basal cell or squamous cell carcinoma. The FCDS has captured an estimated 90% of Florida cancer cases according to audits performed by the Program of Cancer Registries of the Centers for Disease Control and Prevention, Atlanta, Ga.15 Their estimate is based on cancer projections from the Surveillance Epidemiology and End Results Program, National Cancer Institute, Bethesda, Md. The North American Assocation of Central Cancer Registries, Sacramento, Calif, estimated 97% completeness of case ascertainment from 1989 through 1993.16 The FCDS began to monitor hospital cancer submissions in 1981. This monitoring process was based on the percentage of completed (observed) submissions compared with expected cancer cases. Case-finding audits are also performed periodically by the FCDS at all institutions to assure completeness of case reporting. The FCDS audits show that microscopic confirmation exists on 99.6% of all cutaneous melanoma diagnoses found in the registry.16 There is always the possibility of underreporting skin cancers, however, because of the difficulty in identifying cases treated in physician's offices and in outpatient treatment facilities.

The incidence of non–basal cell and non–squamous cell carcinoma of the eyelid in Florida from 1981 through 1994 was low. The incidences of the 2 most common tumors in this study (melanoma and sebaceous carcinoma) in whites older than 20 years were just 0.6 and 0.5 per million, respectively. These incidence rates, by comparison, are approximately one tenth that of uveal melanoma, which is regarded as an uncommon malignant neoplasm.17

Several findings in this study deserve additional comment. Only 3 (1.5%) of 206 eyelid tumors in the FCDS were in blacks, a very small proportion considering the black population in Florida in 1990 was nearly 1.6 million.11,12 Patient race was not recorded in only 3 of the 206 persons with eyelid tumors. There was no case of sebaceous carcinoma, cutaneous adenocarcinoma, Merkel cell tumor, or cutaneous lymphoma of the eyelid in a nonwhite patient in the FCDS. Based on Florida census data, the annual incidence for non–basal cell and non–squamous cell carcinomas of the eyelid in blacks older than 20 years is 0.3 cases per million. The relative risk of developing one of these uncommon malignant neoplasms is 6.4 times greater for whites than for blacks (95% CI, 2.1-20.2). Tumor incidence data from Florida show that black race is a strong protective factor for all types of eyelid tumors. Given the morbidity of tumors in this study if left untreated, it is unlikely that the low frequency in blacks represents an artifact of inadequate reporting.

The protective effect of black race has been well established for melanoma and for basal cell and squamous cell carcinoma but is not well recognized for other types of cutaneous malignant neoplasms.1,2,18 Merkel cell tumor at any skin site has rarely been reported in blacks.7 A variety of adnexal tumors of the eyelid have been reported in series from referral centers and data reveal that most affected patients are white.3,19,20 Incidence rates, however, cannot be determined from these studies. An international study showing variation in reported frequency of sebaceous carcinoma by geographic location suggests that a potentially identifiable environmental or genetic factor is involved in the pathogenesis of this cancer.21

Sarcomas are exceptionally rare in the eyelid. Three quarters of the cases in the FCDS were identified as Kaposi sarcoma. Comorbidities are not reported to the FCDS, but the age and sex distribution of Kaposi sarcoma suggests that these cases are probably associated with the acquired immunodeficiency syndrome.

Primary lymphoma was the third most common eyelid tumor in the FCDS. The designation of primary eyelid lymphoma in the FCDS means that lymphoma was initially diagnosed from an eyelid biopsy specimen. The range of reported histologic diagnoses in this study reflects the broad spectrum of B-cell lymphomas known to affect the skin.22,23 All 27 patients with eyelid lymphoma were white. In North America, blacks have a lower incidence of extranodal non-Hodgkin lymphoma than do whites. From 1984 to 1988, data from the Surveillance Epidemiology and End Results Program show that whites have nearly a 3-fold-greater risk of extranodal lymphoma than do blacks.24 This racial difference has been declining since 1974, and has not been analyzed according to anatomic site.24 If the differences in racial predilection for eyelid lymphoma are generalizable to other sun-exposed skin sites, it may be possible to confirm the FCDS findings with studies from other skin sites.

Most non–basal cell and non–squamous cell malignant neoplasms of the eyelid occur in elderly white patients. A growing body of evidence supports the hypothesis that aging and long-term sun damage to the skin can alter the expression of certain genes implicated in cutaneous carcinogenesis.25 Studies of cutaneous photocarcinogenesis have tended to concentrate on basal cell and squamous cell carcinoma and melanoma. Results from this study showing that the incidence of other types of malignant eyelid tumors is significantly lower in blacks supports the hypothesis that increased skin pigmentation confers a protective effect against these tumors.

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Article Information

Accepted for publication September 12, 1997.

The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System under contract to the Florida Department of Health and Rehabilitative Services (HRS), Tallahassee.

The views expressed herein are solely those of the authors and do not necessarily reflect those of the contractor of HRS.

Corresponding author: Curtis E. Margo, MD, MPH, Department of Ophthalmology, 12901 Bruce Downs Blvd, MDC Box 21, Tampa, FL 33612.

References
1.
Lee  JAH Epidemiology of cancers of the skin. Friedman  RJRigel  DSKopf  AWHarris  MNBaker  Deds.Cancer of the Skin. Philadelphia, Pa WB Saunders Co1991;
2.
Scotto  JFears  TFraumeni  JJ The Incidence of Non-Melanoma Skin Cancer in the United States.  Bethesda, Md Public Health Service, National Institutes of Health1981;NIH publication 82-2433
3.
Wright  JDFont  RL Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations. Cancer. 1979;441757- 1769Article
4.
Rao  NAHidayat  AAMcLean  IWZimmerman  LE Sebaceous carcinoma of the ocular adnexa: a clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol. 1982;13113- 122Article
5.
Doxanas  MTGreen  WR Sebaceous gland carcinoma: a review of 40 cases. Arch Ophthalmol. 1984;102245- 249Article
6.
Garner  AKoornneeff  LLevene  ACollin  JRO Malignant melanoma of the eyelid skin: histopathology and behaviour. Br J Ophthalmol. 1985;69180- 186Article
7.
Kivela  TTarkkanen  A The Merkel cell and associated neoplasms in the eyelids and periocular region. Surv Ophthalmol. 1990;35171- 187Article
8.
Percy  CedVan Holten  VedMuire  Ced The International Classification of Diseases for Oncology, Second Edition.  Geneva, Switzerland World Health Organization1990;
9.
Percy  CLedVan Houlten  VedMuir  Ced International Histologic Classification of Tumours.  Geneva, Switzerland World Health Organization1967;
10.
Percy  CLO'Conor  GRies  LGJaffe  ES Non-Hodgkin's lymphoma: application of the International Classification of Disease for Oncology (ICD-O) to the Working Formulation. Cancer. 1984;541435- 1438Article
11.
Office of Budget and Planning, Population Report.  Tallahassee, Fla Office of the Governor1994;
12.
Office of Vital Statistics, Population Report.  Jacksonville, Fla Dept of Health and Human Resources1995;
13.
Not Available, SAS Language and Procedures. Version 6. Cary, NC SAS Institute1989;
14.
Hirsch  RPRiegelman  RK Statistical First Aid: Interpretation of Health Research Data.  Boston, Mass Blackwell Scientific Publishers1992;
15.
Register, Florida Cancer Data System Newsletter. Spring 1996;
16.
Howe  HedLehnherr  Med Cancer Incidence in North America, 1989-1993.  Sacramento, Calif North American Association of Central Cancer Registries1997;
17.
Egan  KMSeddon  JMGlynn  RJGragoudas  ESAlbert  DM Epidemiologic aspects of uveal melanoma. Surv Ophthalmol. 1988;32239- 251Article
18.
Reintgen  DSMcCarty  KM  JrCox  ESeigler  HF Malignant melanoma in black American and white American populations: a comparative review. JAMA. 1982;2481856- 1859Article
19.
Rao  NAMcLean  IWZimmerman  LE Sebaceous carcinoma of the eyelid. Jakobiec  FAed.Ocular and Adnexal Tumors. Birmingham, Ala Aesculapius1978;
20.
Wolfe  JT  IIIYeats  RPWick  MRCampbell  RJWaller  RR Sebaceous carcinoma of the eyelid. Am J Surg Pathol. 1984;8597- 606Article
21.
Ni  CSearl  SSKuo  PK  et al.  Sebaceous cell carcinomas of the ocular adnexa, tumors of the eyelid and orbit: a Chinese-American collaborative study. Int Ophthalmol Clin. 1982;2223- 61Article
22.
Burg  G Cutaneous B-cell lymphomas. J Dermatol Surg Oncol. 1984;10229- 328
23.
Garia  CFWeiss  LMWarnke  RAWood  GS Cutaneous follicular lymphoma. Am J Surg Pathol. 1986;10454- 463Article
24.
Devesa  SSFears  T Non-Hodgkin's lymphoma time trends: United States and international data. Cancer Res. 1992;52(suppl)5432s- 5440s
25.
Gilchest  BAMarjan  GMina  Y Aging and photoaging affect gene expression in cultured human keratinocytes. Arch Dermatol. 1994;13082- 86Article
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