Late malignant oral lesions after kidney transplantation

Objective: To review cases of oral cavity malignancies available in the literature in kidney transplant recipients. Methods: A search was carried out in the PubMed database using the terms “oral cancer,” “mouth neoplasms,” “renal transplantation,” and “kidney transplantation.” Regardless of the publication date, the publications were chosen by two researchers after they carefully considered the titles and abstracts and read each article in its entirety. Results: Twelve articles were found with cases of oral malignancies in kidney transplant recipients. In all, 31 malignant neoplasms were diagnosed in the oral cavity, of which 64.5% (20/31) were squamous cell carcinomas; Kaposi’s sarcoma represented 12.9% (4/31) of the cases. Lips and tongue were the most affected sites mentioned most frequently in the articles evaluated. Post-transplantation time ranged from 8 months to 23 years, and several immunosuppressants were used. Conclusions: Kidney transplant recipients should be regularly forwarded to dentists and other medical professionals who work in diagnosing malignant lesions of the oral cavity to be evaluated, and new cases of oral cancer can be recognized early to treatment. This strategy could improve the survival of patients with this threatening disease


INTRODUCTION
Renal transplantation has evolved as the best treatment option for patients with end-stage renal disease.In recent decades, significant progress has been achieved in graft and patient survival after renal transplantation.That progress was attributed to improved surgical and tissue matching techniques, advances in antirejection drug therapy, better pretransplantation crossmatching techniques, and viral infection prophylaxis, monitoring, and treatment.Post-transplantation medical management of chronic cardiovascular disease and other comorbidities also improves survival. 1,2Kidney transplantations are seen to be a doubleedged sword; transplantations help to restore renal function.][4] Several reports [3][4][5][6][7][8] indicate that cancer incidence in patients who have undergone renal transplantation is much higher than in the normal population and hemodialyzed patients.The frequency of malignant lesions in renal transplant patients is between 14 and 500 times higher than in the general population; the incidence rises each year after transplantation.[15][16][17] This paper aims to review cases of oral cavity malignancies available in the literature in kidney transplant recipients.

METHODS
Using the Boolean operators AND and OR, a search was carried out in the PubMed database using the terms "oral cancer," "mouth neoplasms, " "renal transplantation, " and "kidney transplantation." Regardless of the publication date, the publications were chosen by two researchers after they carefully considered the titles and abstracts and read each item in its entirety.Only those publications that were published in English and matched the search criteria for the descriptors-malignant lesion diagnosis, patient age and gender, kidney transplantation confirmation, including post-transplantation duration, and immunosuppressive medication used-were included.

RESULTS
Twelve articles were found with cases of oral malignancies in kidney transplant recipients.In all, 31 malignant neoplasms were diagnosed in the oral cavity, of which 64.5% (20/31) were squamous cell carcinomas; Kaposi's sarcoma represented 12.9% (4/31) of the cases.In most cases, 77.4% (24/31), were male, with age mean of 48.77 years (minimum 9 years old; maximum 71 years old).Lips and tongue were the evaluated articles most frequently mentioned affected sites.Post-transplantation time ranged from 8 months to 23 years, and several immunosuppressants were used.Cyclosporine was especially identified in almost all regimens.Follow-up time ranged from 3 weeks to 5 years.Of the 20 cases with outcome information, 20% (4/20) died (Table 1).

DISCUSSION
At present, it is known that several factors contribute to carcinogenesis in transplant patients, including age, gender, and end-stage renal disease etiology.Also, some viral infections are associated with increasing malignancies incidence.The cancer risk appears to differ by the type of immunosuppression used, the induction therapy drug used, and other immunological factors.It can be seen from this review that cyclosporine was used in the immunosuppression regimen for most patients.Until recently, long-term treatment with immunosuppressive agents seems to interfere with the immune state.Consequently, it is associated with the excess burden of cancer in kidney transplant recipients.However, scientific studies could not prove that some specific immunosuppressive regimens raise or reduce cancer risk.The doses and the exposition time are probably more important than the immunosuppression regimen type.Also, it needs to be considered that small differences in cancer development potential between the immunosuppressants can affect the incidence by overlapping known risk factors such as age, history of smoking, underlying kidney disease, history of previous cancers, and viral infections. 5,8,19ble 1.Continuation.
In this review, the two most common diagnoses for malignant oral cavity lesions were squamous cell carcinomas (SCCs) and Kaposi's sarcoma.Kaposi's sarcoma, SCC, and lymphoproliferative diseases are the main diagnosis after kidney transplantation.Skin cancers account for 40-50% of all posttransplant malignancies, and the SCC is the most frequently reported.The SCC frequency in transplanted patients is between 65 and 250 times higher than in the general population, and lip cancer has an incidence up to 10 times greater than in healthy individuals. 19SCCs are more aggressive in this population, and the risk of metastases in this population is higher than in the general population.Ultraviolet radiation and human papillomavirus have been associated with SCC, but it is not so clear the exact role of HPV in this condition. 20,21aposi's sarcoma has an incidence of up to 300 times greater than otherwise healthy individuals. 19Except for squamous cell carcinoma, which prefers to show on the lips, Kaposi's sarcoma and lymphoproliferative diseases have no preference for certain anatomical regions of the mouth. 7,9,11,12,16,17ven though the literature examined for this review does not clearly identify the primary risk factors for the development of malignant lesions in the oral cavity following transplantation, it has been reported that the primary risk factors for the development of oral cancer are related to: age at transplantation, male gender, white ethnicity and extended time on dialysis before transplantation are key risk factors for the development of cancer after transplantation. 8he survival time of transplanted individuals affected by some malignant lesion in the oral cavity was not very long.It should not be underestimated, especially for a maximum follow-up of 5 years, which is the average mortality incidence time for oral squamous cell carcinoma. 5,18Because the studies reviewed were all case reports or case series, it is clear that more extensive case studies in individuals undergoing organ transplantation are needed to understand the reality of these clinical manifestations of malignancy.Also, the relationship of these lesions with the use of immunosuppressants and with other risk factors.In addition, it is necessary to monitor patients for early detection of malignant lesions in the oral cavity.

CONCLUSION
For transplant doctors, knowledge of the potential for malignant lesions of the oral cavity affects kidney transplanted patients and the consequences regarding their correct diagnosis is essential.These patients should be regularly forwarded to dentists and other medical professionals who work in diagnosing malignant lesions of the oral cavity to be evaluated, and new cases of oral cancer are recognized early to treatment.This strategy could improve the survival of patients with this threatening disease.

Table 1 .
Case description of oral malignant neoplasms of renal transplant recipients.