Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is characterized by clonal proliferation of predominantly CD4+ T cells with localization to the skin.1 Mycosis fungoides typically affects older adults with a male to female ratio of 2:1 but also can occur in children and younger adults.2,3 Known as the great imitator, the manifestations of MF can be variable with considerable clinical and pathologic overlap with benign inflammatory skin diseases, rendering definitive diagnosis challenging.4-7 The early stages of classic MF manifest as pruritic erythematous patches and plaques with variable scaling that can progress in later stages to ulceration and tumors.8 Histopathologically, classic MF is characterized by epidermotropic proliferation of small- to intermediate-sized pleomorphic lymphocytes with cerebriform nuclei and a haloed appearance; intraepidermal nests of atypical lymphocytes known as Pautrier microabscesses occasionally are observed.5 Mycosis fungoides typically follows an indolent clinical course, with advanced-stage MF portending a poor prognosis.9,10 Current treatment is focused on halting disease progression, with topical therapies, phototherapy, and radiation therapy as the standard therapies for early-stage MF.11-13 For advanced-stage MF, treatment may include systemic therapies such as interferon alfa and oral retinoids along with chemotherapies for more refractive cases.14 Allogenic hematopoietic cell transplantation is the only curative treatment.11
Current staging guidelines for MF do not address anatomic location as there is little known about its impact on patient outcomes.11,15 Due to the indolent nature of MF leading to diagnostic challenges, the exact frequency of each primary disease site for MF also remains unclear, though the suggested incidence of MF of the head and neck ranges from 30% to 70%.16,17 Involvement of the head and neck16,18 or external ear and external auditory canal19 is associated with worse prognosis. The purpose of this study was to examine the impact of anatomic location of primary disease site on survival in MF.
Methods
The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database includes patient records from 18 registries and encompasses approximately 48% of the US population.20 Using SEER*STAT software (version 8.4.0.1), we conducted a search of patients diagnosed with MF (International Classification of Diseases for Oncology, Third Edition [ICD-O-3] histologic code 9700/3 [mycosis fungoides]) between 2000 and 2019. For inclusion in the study, patients were required to have a known age, specified primary site, and a known cause of death (if applicable). Patients with known Sézary syndrome (SS)—an aggressive form of CTCL that is characterized by the presence of clonally related neoplastic T cells in the skin, lymph nodes, and peripheral blood—were not included because the World Health Organization/European Organisation for Research and Treatment of Cancer considers SS and MF to be separate entities1,15; SS does not necessarily arise from preexisting MF and is associated with markedly poorer survival. This study was exempt from institutional review board approval because the data were publicly available and anonymized.
Data Collection—For age at diagnosis, patients were divided into the following categories: younger than 40 years, 40 to 59 years, 60 to 79 years, and 80 years and older. Demographics, tumor characteristics, and surgical management (if applicable) were obtained for each patient. The designations of chemotherapy and radiation treatment in the SEER database are not reliable and prone to false negatives. As such, these were excluded from analysis.
The primary outcomes of interest were overall survival (OS) and disease-specific survival (DSS), which were calculated as time from MF diagnosis to death. Although OS included all patients who died of any cause, DSS only included patients who died of MF.
Statistical Analysis—Demographics (age, sex, race, ethnicity), tumor characteristics (tumor size, primary site, T stage, lymph node involvement, metastasis), and surgical management (if applicable) were summarized. Overall survival and DSS were calculated using Kaplan-Meier analysis. Univariate and multivariable Cox proportional hazards regression models were generated to determine which prognostic factors for MF were associated with poorer OS and DSS. Only statistically significant variables in the univariate analysis were used to construct the multivariable analysis. Hazard ratios (HRs) and their associated 95% CIs were reported. Incidence rates were calculated and age adjusted to the 2000 US standard population. The SEER JoinPoint Regression program was used to determine the annual percent change (APC)—change in incidence rate over time. P<.05 was considered statistically significant. All statistical analyses were conducted with R version 4.0.2.