CLINICAL REPORT
551 ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Metastasis Risk of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Immunocompetent Patients
Roel E. GENDERS 1, Joris A. J. OSINGA 1, Elise E. TROMP 1, Peter O’ ROURKE 2, Jan N. BOUWES BAVINCK 1 and Elsemieke I.
PLASMEIJER 1, 3 1
Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands, 2 Statistics Unit, and 3 Cancer and Population studies, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Organ transplant recipients( OTRs) have a high incidence of cutaneous squamous cell carcinoma( cSCC), and immunosuppression has been reported to be an important risk factor for metastasis. The aim of this study was to identify the metastasis risk over a 10- year period for 593 patients with cSCC, of whom 134 were OTR and 459 were immunocompetent. Metastasis incidence rate was 1,046( 95 % confidence interval( 95 % CI) 524 – 2,096) per 100,000 person years in OTR and 656( 95 % CI; 388 – 1,107) in immunocompetent patients, yielding an incidence rate ratio of 1.6( 95 % CI 0.67 – 3.81). In OTRs head / neck location, older age at transplantation and older age at diagnosis of first cSCC were associated with metastatic risk, and 7 out of 8 metastasized tumours were smaller than 2 cm. In immunocompetent patients tumour size and tumour depth were associated with metastasis. In conclusion, we were not able to demonstrate an increased incidence rate of metastasis in OTRs compared with immunocompetent patients. However, OTRs and immunocompetent patients differed with regard to risk factors for metastasis.
Key words: organ transplant recipients; cutaneous squamous cell carcinoma; metastasis; immunocompetent.
Accepted Feb 5, 2018; Epub ahead of print Feb 6, 2018 Acta Derm Venereol 2018; 98: 551 – 555.
Corr: Roel E. Genders, Department of Dermatology Leiden University Medical Centre, Albinusdreef 2, NL-2333 ZA Leiden, The Netherlands. E- mail: r. e. genders @ lumc. nl
Cutaneous squamous cell carcinoma( cSCC) is the second most frequent form of keratinocyte carcinoma( KC)( 1, 2). The incidence of cSCC varies globally, with a higher incidence closer to the equator. In Finland the reported incidence for men is 6 per 100,000 person years and for women 4 per 100,000 person years. In Australia, these numbers are reported to be 1,035 and 472 per 100,000 person years, respectively( 3, 4).
The incidence of cSCC metastasis varies, with higher incidence often reported from tertiary hospitals( 5 – 10). The risk of developing metastasis from low-risk cSCC in the general population is between 0.5 % and 5 %, but may be as high as 45 % in high-risk cSCC, i. e. tumours located on the lip and ear, large tumours and recurrent tumours( 5, 11, 12).
The risk of developing cSCC in organ transplant recipients( OTRs) is 40 – 250 times increased compared with the general population( 13). In some reports, it has been suggested that cSCC in OTRs frequently exhibit aggressive behaviour irrespective of size, that in-transit metastases are more frequent, and that cSCC in OTRs have a worse prognosis than cSCC in immunocompetent patients( 14, 15). Between 5 % and 23 % of all patients with metastatic cSCC, have been reported to be immunosuppressed, many of whom were OTR, and therefore immunosuppression has been reported to be a risk factor for metastasis( 16 – 18).
In clinical practice, it is difficult to identify high-risk cSCC and to detect metastasis at an early stage, both in immunosuppressed and immunocompetent patients( 19 – 21). Tumour size, Clark’ s level, Breslow’ s thickness, degree of differentiation, perineural invasion and location are associated with the development of metastasis( 22). Staging systems are developed to help determine highrisk tumours( 23 – 25). The American Joint Committee on Cancer( AJCC) classification is the most commonly used staging system, and is subject to regular modifications. Since 2010 the AJCC classification is based on several high-risk features of cSCC( 23). Though immunosuppression is mentioned as a risk factor, it does not influence tumour stage in any of the staging systems.
OTR are subject to lifelong immunosuppressive therapy and therefore are an ideal population with regard to analysing the influence of immunosuppression on cSCC metastatic behaviour. Comparative studies between OTR and immunocompetent patients focusing on the metastasis risk of cSCC are scarce. The aim of this study was to identify the risk of cSCC metastasis in a defined cohort of OTRs and immunocompetent patients, calculated both per patient as well as per individual tumour.
METHODS
For this retrospective study, all consecutive patients with primary cSCC who were diagnosed from January 2004 to December 2013 were identified from the institutional oncology database of Leiden University Medical Centre. Each patient’ s medical record was cross-checked with pathology records of cSCC in the same period. Missing patients and / or tumours were added to the database manually. Each tumour was given its own record; one individual patient could have had more records in case of multiple primary
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2901 Acta Derm Venereol 2018; 98: 551 – 555