Oral carcinoma development after 23 years of renal transplantation

Keywords: Lip neoplasm, Tongue neoplasm, Mouth neoplasm, Kidney transplantation


Renal transplant patients are treated with immunosuppressive drugs that decrease the effectiveness of the immune system, making them more prone to developing cancer. Skin and lip carcinomas are common malignancies encountered after transplantation, whereas oral carcinomas are rare. We report the case of a 51-year-old female Caucasian patient, with no history of smoking, who presented white lesions on the tongue and an ulcerated lesion on the lower lip beginning 4 months prior. Diagnosis of squamous cell carcinoma for both lesions was made following incisional biopsies. Interestingly, the patient reported a renal transplantation 23 years prior, and was maintained on a combination of cyclosporine, mycophenolate sodium and prednisone. The patient also presented a history of several basal and squamous cell carcinomas on sun-exposed areas of the skin. Both lesions were surgically excised. No sign of recurrence or new lesions in the oral cavity have been observed; however, new skin lesions are frequently diagnosed. This case report highlights that oral cancers may occur in transplant patients in the absence of classical risk factors. Thus, clinicians must be aware of the importance of thorough oral examination in transplant patients in routine follow-up.


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How to Cite
Faustino, I., Fernandes, D., Santos-Silva, A., Vargas, P., & Lopes, M. (2019). Oral carcinoma development after 23 years of renal transplantation. Autopsy and Case Reports, 9(4), e2019112. https://doi.org/10.4322/acr.2019.112
Article / Clinical Case Report


Renal transplantation is the treatment of choice for patients with end-stage renal disease, which may improve their survival rate and quality of life.1 , 2 However, renal transplantation also increases the risk of cancer,3 with a 5% to 6% increase in the incidence of cancer when compared to the general population.4 This can be attributed to the alteration of immune surveillance mechanisms due to the chronic use of immunosuppressive therapy and infection by oncogenic viruses.4 - 6 About 13% of transplanted patients develop cancer;7 however, the risk of malignancies is not the same for all types of cancer.8

Cancers of the skin and lip have been described to occur at a higher incidence9 among transplanted patients; however, the incidence of oral carcinomas, especially in the tongue, is scarcely reported in the literature.10 - 14 The current report presents the case of a renal transplant patient who developed multiple carcinomas in the skin with synchronous development of lip and tongue carcinomas, highlighting the importance of oral examination in the follow-up of these patients.


A 51-year-old female patient was referred for evaluation of white lesions on the tongue and ulcerated lesions on the lower lip that had developed over the past 4 months. She denied smoking and consuming alcohol. She had been diagnosed with systemic erythematous lupus (SLE), and lost renal function as a result of lupus nephritis. The patient had undergone renal transplantation 23 years prior, and was on continuous post-transplant immunosuppressive therapy with a combination of cyclosporine, mycophenolate sodium and prednisone.

On physical examination, numerous skin scars were observed due to the surgical removal of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) that developed during immunosuppressive therapy, especially on the upper limbs and face. The lower lip showed an erythematous area with central ulceration. On intraoral examination, a heterogeneous and slightly corrugated white plaque was observed on the ventral surface of the tongue (Figure 1).

Gross view of the lesions at the time of diagnosis. A - Ulcerated lesion on the lower lip. B - White patch on the ventral surface of the tongue.

Figure 1: Gross view of the lesions at the time of diagnosis. A - Ulcerated lesion on the lower lip. B - White patch on the ventral surface of the tongue.

Incisional biopsies of the lip and the tongue were performed under local anesthesia. The diagnosis of SCC was established, and the patient was referred to a head and neck surgeon who surgically removed both lesions (Figure 2).

Histopathological aspects of squamous cell carcinoma. A - Microinvasive tumor of the tongue. B - Tumor cells in the connective tissue of the lower lip.

Figure 2: Histopathological aspects of squamous cell carcinoma. A - Microinvasive tumor of the tongue. B - Tumor cells in the connective tissue of the lower lip.

After 5 years of follow-up, the patient developed SCC on the forearm, hand, neck, finger, scalp, cheek, leg, nose and temporal region. BCCs developed on the nose, thorax, lower eyelid and upper back.

All tumors that had presented since renal transplantation are listed in Table 1.

Table 1:
All tumors presented by the patient from renal transplantation to the time of diagnosis of oral lesions
Number of the tumor Histopathologic Diagnosis Location Years after transplantation
1 SCC Face 8
2 BCC Skin of lower lip 11
3 BCC Skin of lower lip 11
4 SCC Skin of lower lip 12
5 BCC Pre auricular 15
6 BCC Parietal region 15
7 SCC Occipital region 15
8 SCC Skin of lower lip 15
9 SCC Dorsal of hand 15
10 SCC Scalp 16
11 SCC Skin below the eye 17
12 SCC (in situ) Nose (right) 17
13 BCC Nose (left) 17
14 SCC Ventral tongue 18
15 SCC Lower lip 18
16 SCC (in situ) Scalp 18
17 SCC Scalp 18
18 SCC Right hand 19
19 SCC Neck 20
20 SCC IV finger 20
21 SCC Scalp 21
22 SCC Cheek 23
23 BCC Nose 23
24 BCC Forehead 23
25 SCC Leg 23
26 BCC Thorax 23
27 SCC Left arm 23
28 BCC Lower eyelid 23
29 SCC Nose 23
30 BCC Upper back 23
31 SCC Temporal region 23

SCC: squamous cell carcinoma; BCC: basal cell carcinoma.

The patient is on regular follow-up, and no signs of recurrence or new primary tumors in the oral cavity have been observed. However, the patient has undergone removal of several carcinomas (BCCs and SCCs) of the skin, and future biopsies for new lesions on the nose and forehead are scheduled. The patient signed a declaration of consent in accordance with the standard institutional protocol.


Renal transplantation is the ultimate treatment option for kidney failure, aiming to improve the patient’s quality of life. However, there are some complications related to immunosuppressive maintenance therapy, such as increased susceptibility to infections and a higher risk of cardiovascular disease and malignancies.15 The development of cancer is a significant complication of renal transplantation. The higher likelihood of developing cancer4 can be attributed to the maintenance immunosuppressive therapy.16 , 17

Some immunosuppressive drugs may potentiate the action of carcinogens, independent of their effects on immune cells,18 while others are related to cellular changes and the development of malignancies. Cyclosporine inhibits DNA repair and apoptosis in human keratinocytes exposed to UVB radiation,19 , 20 and prednisone may be associated with a higher probability of malignancy by diminishing DNA repair mechanisms.21 Studies22 , 23 suggest that immunosuppressive agents may be involved in the activation of mechanisms of the tumor growth, such as transforming growth factor alpha and vascular endothelial growth factor. Moreover, withdraw of immunosuppressive therapy in case of transplantation failure is associated with an immediate reduction in the risk of some cancers, such as lip cancer, melanoma and non-Hodgkin's lymphoma.23 , 24 The synergic effect between UV radiation and immunosuppressive therapy can be observed in lesions related to sunlight exposure, such as skin and lip cancers.25 In the present report, the patient was under continuous cyclosporin treatment for 23 years in association with mycophenolate sodium and prednisone, and she developed lip and tongue SCCs in addition to multiple skin carcinomas.

Systemic erythematous lupus has been associated with an increased risk of cancer. Nevertheless, the specific cause is not clear, and may be attributed to dysregulation of the immune system or a side effect of the immunosuppressive medication used for treatment.26 A recent systematic review and meta-analysis27 on the risks of cancer development in SLE patients concluded that SLE is associated with an increased risk of cancer in general, particularly hematological, reproductive, digestive and respiratory cancers in women and men. However, lip and tongue cancers were not cited by this study. On the other hand, a clinical case of tongue cancer has been reported in the English literature in a pregnant woman with SLE, who had classic high-risk habits for the development of oral carcinoma, which makes the association with lupus questionable.26

In contrast to SCCs, BCCs are the most common type of skin cancer worldwide. However, skin SCCs can occur up to 25 times more frequently in transplanted patients.28 The association between immunosuppression and sun exposure can be evidenced in our case, as our patient developed multiple skin carcinomas in sun-exposed areas, especially in the head and neck region.

Lip cancer development has also been described as a common consequence of renal transplantation.18 , 25 , 29 , 30 Lip carcinoma is more common in Caucasians chronically exposed to the sunlight, and almost all lip SCCs are associated with areas of actinic cheilitis.18 , 25 , 31 , 32 The patient in our case report presented fair skin and a history of sunlight-exposure with a delayed habit of UV protection. The combination of these factors with immunosuppressive therapy seems to have contributed to the development of these tumors. Interestingly, although lip SCCs are typically associated with severe actinic cheilitis features, such as red spots, white plates, hardening and loss of vermilion border definition, the current patient only had mild actinic cheilitis.

Although SCC of the tongue is the most frequent oral malignancy in the general population, it seems to be rare in renal transplant patients.10 - 14 While tobacco and alcohol consumption are the most important risk factors for these lesions, diet, nutrition, viruses and genetic predisposition have also been associated with SCC.33 In general, oral SCCs are more frequently observed in adult male patients with a heavy smoking habit and alcohol consumption.34 The profile of risk factors for oral SCCs in transplanted patients are different from those of the general population, and to the best of our knowledge, all reports in the English literature do not resemble the traditional pattern of oral SCCs (Table 2).

Table 2:
Reports on oral SCCs in transplanted patients published in the English literature and their respective findings
Author Gender Age (y) Time since renal transplantation (y) Tobacco use Alcohol abuse Immunosuppressive drugs
Lee & Gisser10 Male 26 9 No No Azt / Pred
Meng11 Male 55 7 No No Azt/ Cyc/ Pred
Male 40 11 No No Azt/ Cyc/ Pred
Male 52 11 No No Azt/ Cyc/ Pred
Zhang et al.12 Male 65 8 No No Azt/Cyc/Pred
Malleshappa13 Male 30 9 No No Azt/ Cyc/ Pred
Prakash14 Male 46 11 No No Azt/ Cyc / Steroids
Current case Female 51 23 No No Cyc / Pred / Myc/

Azt: Azathioprine; Pred: Predinisolone; Cyc: Cyclosporine; Myc: Mycophenolate sodium; y: year.

The present report is the only case of a tongue SCC in a female transplanted patient without classical risk factors (tobacco and alcohol) published in the literature. In addition, this case presented a longer post-transplant period for tongue SCC development (23 years) compared to the average of 9.4 years among the reported cases.

After renal transplantation, malignant diseases are more difficult to control, and the surgical principles for early-stage tongue cancer in these cases are similar to advanced-stage cases due to the low immune states that facilitate tumor metastasis and severe infection after surgery.11 The reported patient showed no signs of metastasis or local recurrence, which may be explained by the early diagnosis and, consequently, better prognosis.

In conclusion, Caucasian transplant patients with a history of sunlight exposure have a higher propensity to develop lower lip and skin cancer. In addition, although rare, oral cancer can also be observed in this group of patients, even after a long follow-up period. Thus, clinicians must be aware of the necessity and importance of oral examination of transplanted patients, and a regular and close follow-up should be enforced.

The patient has signed the consent declaration as to the Institutional standard protocol.

How to cite: Faustino ISP, Fernandes DT, Santos-Silva AR, Vargas PA, Lopes MA. Oral carcinoma development after 23 years of renal transplantation. Autops Case Rep [Internet]. 2019 Out-Dec;9(4):e2019112. https://doi.org/10.4322/acr.2019.112

Financial support: None


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