tacrolimus and Mouth-Neoplasms

Oral lichen planus (OLP) is a chronic mucosal condition commonly encountered in clinical dental practice. Lichen planus is believed to represent an abnormal immune response in which epithelial cells are recognized as foreign, secondary to changes in the antigenicity of the cell surface. It has various oral manifestations, the reticular form being the most common. The erosive and atrophic forms of OLP are less common, yet are most likely to cause symptoms. Topical corticosteroids constitute the mainstay of treatment for symptomatic lesions of OLP. Recalcitrant lesions can be treated with systemic steroids or other systemic medications. However, there is only weak evidence that these treatments are superior to placebo. Given reports of a slightly greater risk of squamous cell carcinoma developing in areas of erosive OLP, it is important for clinicians to maintain a high index of suspicion for all intraoral lichenoid lesions. Periodic follow-up of all patients with OLP is recommended.

Topics: Carboxymethylcellulose Sodium; Carcinoma, Squamous Cell; Chronic Disease; Diagnosis, Differential; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Mouth Neoplasms; Precancerous Conditions; Steroids; Tacrolimus

Mucosal melanoma, or so-called mucosal-oral melanoma is a rare but serious diagnostic and therapeutic problem. The "primary mixed" mucocutaneous forms of melanoma, which affect both the mucosa and the adjacent skin, are also particularly problematic and rare. Given that the staging, diagnosis, and treatment of mucosal (oral) melanoma differs from that of cutaneous melanoma, staging in mixed melanoma (primary mucocutaneous melanoma) as well as decisions for each subsequent diagnostic and therapeutic step should be individualized and modified according to the recommendations of the respective two classifications (for cutaneous but also mucosal melanomas), while at the same time or at least to a large extent overlapping with them. In practice, the following paradoxes occur during staging - there are melanomas with the same tumor thickness, but in different stages, which should be treated in a different, consensus-based way. At the same time, it would be appropriate for the surgical interventions to be in accordance with the patient's wishes for minimal trauma/reduced risk of developing facial disproportion. We present the case of a 69-year-old patient with a newly-developed lesion in the area of the mucosa of the upper lip and adjacent skin, which was identified as a primary mucocutaneous form of melanoma after surgical removal. The complex pathogenesis of the disease is discussed herein, emphasizing the role of UV radiation, iatrogenic immunosuppression with mycophenolate mofetil, tacrolimus, and prednisolone (due to severe glomerulonephritis leading to kidney transplantation), as well as the potential possible but speculative pathogenetic role of acetyl salicylic acid, etc. Primary mucosal and mucocutaneous forms of melanoma remain a challenge for clinicians, and steps for their diagnosis and treatment should be an expression of multidisciplinary, consensual solutions.

Topics: Aged; Humans; Melanoma; Mouth Neoplasms; Mycophenolic Acid; Prednisolone; Salicylic Acid; Skin Neoplasms; Tacrolimus

Tacrolimus (TAC, FK506) is a major calcineurin inhibitor and has been commonly used in treatments of patients with organ transplants and immune diseases. Moreover, tacrolimus is recommended by the treatment guidelines for oral potentially malignant disorders (OPMDs) such as oral lichen planus (OLP). However, whether tacrolimus increases the risk of cancer remains controversial. We observed that in a 4-Nitroquinoline N-oxide (4NQO)-induced oral carcinogenesis model, tacrolimus treatment was associated with a significantly lower ratio of cancer formation (52.94% vs. 90%) and a lower proportion of Ki67 and proliferation cell nuclear antigen (PCNA) -positive cells in lesion areas (P < 0.001). Liver, kidney, and lung functions of rats and the tumor immune microenvironment of the tongue were not affected. These observations suggest that tacrolimus blocked oral carcinogenesis through epithelial cell proliferation inhibition, independent of its immunosuppressive effects. As a processing factor, tacrolimus decreased tumor formation and cell proliferation in different stages of oral squamous cell carcinoma (OSCC) progression in vivo and in vitro. Furthermore, we investigated effects on the cell cycle and expression of related proteins. Tacrolimus induced G1/S phase arrest and significantly downregulated the expression of cyclinD1, cyclinE1, and c-Myc. These results suggest that tacrolimus induces G1/S phase arrest via inhibition of cyclinD1, cyclinE1, and c-Myc expression and retards oral cell carcinogenesis in vitro and in vivo. Thus, application of tacrolimus is a safe therapeutic strategy for treating OPMDs.

Topics: 4-Nitroquinoline-1-oxide; Animals; Anticarcinogenic Agents; Carcinogens; Cell Cycle; Cellular Microenvironment; Cyclins; Genes, myc; Ki-67 Antigen; Male; Mice; Mice, Inbred BALB C; Mouth Neoplasms; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Squamous Cell Carcinoma of Head and Neck; Tacrolimus; Xenograft Model Antitumor Assays

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

Topics: Administration, Topical; Biopsy; Candidiasis, Oral; Carcinoma, Squamous Cell; Diagnosis, Differential; Diagnostic Errors; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouth Neoplasms; Surgical Flaps; Tacrolimus

To evaluate disease dynamics, treatment results, and frequency of malignant transformation. Ten-year single center retrospective study. The study included 171 patients, 28-99 years old. Follow-up was 1-16 years. 49.5% exhibited changes in clinical presentation, with 19% yearly increase of probability for type shift. Index of extent (number of oral locations) showed a mean 40% decrease and 94.1% reported improvement. There were significant differences between treated and untreated patients (P=0.012). Patients with or without systemic diseases had identical treatment requirements for oral lesions. The prevalence of SCC was 5.8%. Oral lichen planus constantly changes presentation and extent of involvement. The effect of systemic diseases was insignificant in the present study. There is a clear value for treatment to reduce the extent of lesions. The results indicate that all clinical forms of the disease need to be equally followed since the clinical presentation typically changes over time, while malignant transformation can occur in all forms.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Clobetasol; Dexamethasone; Female; Humans; Lichen Planus, Oral; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Prednisone; Prevalence; Retrospective Studies; Tacrolimus; Tretinoin; Triamcinolone

Oral lichen planus (OLP) is a chronic mucosal disorder of unclear etiology. The mainstay of therapy is topical use of steroids but other immuno-modulating therapies have also been tried. One such example is topical application of tacrolimus. Tacrolimus was in 2000 approved for treatment of atopic dermatitis, but in 2005 a boxed warning was included because of a potential risk of cancer development and for lack of long-term studies of the safety of the drug. The present study describes a patient who in 2003 was diagnosed with OLP and where treatment has included an intermittent use of tacrolimus. Five years after diagnosis, the patient developed a squamous cell carcinoma in the region where tacrolimus had been applied. The possible relationship between the use of tacrolimus and cancer development and rationale to include tacrolimus in OLP treatment is discussed.

Topics: Administration, Buccal; Carcinoma, Squamous Cell; Clobetasol; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouth Neoplasms; Tacrolimus; Triamcinolone Acetonide

The aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant.. A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects.. The results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506.. Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.

Topics: Adult; Calcium Channel Blockers; Candida; Carcinoma, Squamous Cell; Cyclosporine; Drug Therapy, Combination; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mouth Neoplasms; Saliva; Stomatitis, Herpetic; Tacrolimus

Immunosuppression used to avoid graft rejection in solid organ transplantation recipients leads to a variety of side-effects, and an increased rate of infections and de novo malignancies. Oral conditions usually associated with immunosuppressive drugs include fungal and viral infection, and lip lesions, but intra-oral carcinoma has not been reported as having a high incidence. This report deals with a male liver transplant recipient receiving FK506 (5 mg/day) and prednisone (20 mg/day) who was diagnosed with a homogeneous leukoplakia on the floor of the mouth 4 months after transplantation, and 4 months later with a squamous cell carcinoma growth at the site of this lesion. The rapid transformation of the lesion suggests that in patients who display oral premalignant conditions, immunosuppression must be considered as an important risk factor for oral cancer.

Topics: Carcinoma, Squamous Cell; Disease Progression; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Leukoplakia, Oral; Liver Transplantation; Male; Middle Aged; Mouth Neoplasms; Prednisone; Tacrolimus