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