Successful treatment of squamous cell carcinoma with intralesional methotrexate

Abstract

IntroductionCutaneous squamous cell carcinoma (cSCC) is associated with several risk factors, including sun exposure, advanced age, fair skin, and immunosuppression.1Nehal K.S. Bichakjian C.K. Update on keratinocyte carcinomas.N Engl J Med. 2018; 379: 363-374https://doi.org/10.1056/NEJMra1708701Crossref PubMed Scopus (140) Google Scholar It is the second-most common skin cancer in the United States,2Belbasis L. Stefanaki I. Stratigos A.J. Evangelou E. Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: an umbrella review of meta-analyses.J Dermatol Sci. 2016; 84: 330-339https://doi.org/10.1016/j.jdermsci.2016.09.003Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar with an estimated annual incidence of 700,000 cases,3Karia P.S. Han J. Schmults C.D. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012.J Am Acad Dermatol. 2013; 68: 957-966https://doi.org/10.1016/j.jaad.2012.11.037Abstract Full Text Full Text PDF PubMed Scopus (528) Google Scholar and represents 20% to 50% of skin cancers.4Que S.K.T. Zwald F.O. Schmults C.D. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging.J Am Acad Dermatol. 2018; 78: 237-247https://doi.org/10.1016/j.jaad.2017.08.059Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar While cSCC has a metastatic rate of 2% to 5%,5Baum C.L. Wright A.C. Martinez J.C. et al.A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.J Am Acad Dermatol. 2018; 78: 141-147https://doi.org/10.1016/j.jaad.2017.07.031Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar the rate tends to be higher (7.5%) on the lip vermilion.6Wang D.M. Kraft S. Rohani P. et al.Association of nodal metastasis and mortality with vermilion vs cutaneous lip location in cutaneous squamous cell carcinoma of the lip.JAMA Dermatol. 2018; 154: 701-707https://doi.org/10.1001/jamadermatol.2018.0792Crossref PubMed Scopus (18) Google ScholarThe treatment of choice for cSCC is surgery; however, nonsurgical options are generally reserved for patients who refuse surgery or cannot tolerate a surgical procedure.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar The treatments combining surgery with radiotherapy or chemotherapy showed efficiency only in early-stage and well-defined cSCC.8Ding L.T. Zhao P. Yang M.L. Lv G.Z. Zhao T.L. GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth.Biochem Biophys Res Commun. 2018; 503: 1941-1948https://doi.org/10.1016/j.bbrc.2018.07.139Crossref PubMed Scopus (17) Google ScholarIntralesional 5-fluorouracil, interferon α, and methotrexate have been used sporadically for the treatment of squamous cell carcinoma.9Good L.M. Miller M.D. High W.A. Intralesional agents in the management of cutaneous malignancy: a review.J Am Acad Dermatol. 2011; 64: 413-422https://doi.org/10.1016/j.jaad.2009.12.013Abstract Full Text Full Text PDF PubMed Scopus (79) Google ScholarCase reportA 90-year-old man from Morelia, México, with no significant medical history presented in June 2017 with a 2-cm tumor on the right side of the lower vermilion, extending about 5 mm inside of the oral mucosa. It was indurated and covered by a yellowish crust. The lesion was indolent and had been growing for 18 months. No regional lymphadenopathy was detected on examination (Fig 1).A punch biopsy showed squamous cell carcinoma with moderate pleomorphism and dyskeratosis with oval and polygonal nuclei with an irregular shape. The tumor infiltrated the entire thickness of the dermis, without vascular permeation and without perineural invasion (Fig 2).Fig 2Cutaneous squamous cell carcinoma with dyskeratosis. Well-formed keratinizing structures known as “keratin pearls” were observed on histopathologic examination, as moderate cellular pleomorphism.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Surgical treatment was declined because of the patient’s fear of the cosmetic outcome, so it was decided to treat him with intralesional methotrexate. Methotrexate 25 mg was injected in 1 ml (25 mg) with an insulin needle gauge 30, monthly at 3 separated intervals. The patient had an excellent clinical response with complete resolution (Fig 3). No recurrence was observed at 1 year of follow-up.Fig 3Six months after the first visit, a complete clinical response was observed. No crusty yellowish tumor was observed at the inner border of the lip. ∗Colorized.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Two months after completed treatment, a second biopsy was taken, which revealed mild acanthosis and mild reactive hyperkeratosis in the dermis. An inflammatory process was observed with mature lymphocytes and few plasma cells and hyalinized fibrosis. No residual tumor was observed (Fig 4).Fig 4On follow- up biopsy, no tumor was observed; only hyalinized fibrosis, hyperkeratosis, and inflammatory changes were reported on histopathological examination. ∗Colorized.View Large Image Figure ViewerDownload Hi-res image Download (PPT)DiscussionMethotrexate is a folic-acid analog that irreversibly inhibits the enzyme dihydrofolate reductase, blocking the synthesis of tetrahydrofolate and, ultimately, preventing the formation of thymidine9Good L.M. Miller M.D. High W.A. Intralesional agents in the management of cutaneous malignancy: a review.J Am Acad Dermatol. 2011; 64: 413-422https://doi.org/10.1016/j.jaad.2009.12.013Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar; likewise, it increases WWOX gene expression, which promotes caspase activation and apoptosis of cSCC cells.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google ScholarMany cases and series have reported on its effectiveness in treating keratoacanthoma10Annest N.M. VanBeek M.J. Arpey C.J. Whitaker D.C. Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature.J Am Acad Dermatol. 2007; 56: 989-993https://doi.org/10.1016/j.jaad.2006.12.017Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar; however, data on intralesional methotrexate in patients with cSCC are scarce.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar,11Plascencia-Gomez A. Calderón-Rocher C. Proy-Trujillo H. Moreno-Coutiño G. Neoadjuvant intralesional methotrexate before surgery in squamous cell carcinoma.Dermatol Surg. 2014; 40: 584-586https://doi.org/10.1111/dsu.12455Crossref PubMed Scopus (10) Google Scholar Recently, a small observational retrospective trial comparing intralesional methotrexate plus surgery versus surgery alone demonstrated a reduction in tumor size that subsequently could facilitate surgery.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google ScholarIn this patient, methotrexate was well tolerated, had a quick response, and was easily administrated at a low cost. At this time, surgical treatment remains the treatment of choice. Since the patient refused surgery, an alternative was required. Methotrexate therapy was chosen, which showed very good effectiveness. However, data with a greater number of clinical cases and long-term follow-up examinations are necessary before this therapeutic intervention could be recommended as an optional approach. IntroductionCutaneous squamous cell carcinoma (cSCC) is associated with several risk factors, including sun exposure, advanced age, fair skin, and immunosuppression.1Nehal K.S. Bichakjian C.K. Update on keratinocyte carcinomas.N Engl J Med. 2018; 379: 363-374https://doi.org/10.1056/NEJMra1708701Crossref PubMed Scopus (140) Google Scholar It is the second-most common skin cancer in the United States,2Belbasis L. Stefanaki I. Stratigos A.J. Evangelou E. Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: an umbrella review of meta-analyses.J Dermatol Sci. 2016; 84: 330-339https://doi.org/10.1016/j.jdermsci.2016.09.003Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar with an estimated annual incidence of 700,000 cases,3Karia P.S. Han J. Schmults C.D. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012.J Am Acad Dermatol. 2013; 68: 957-966https://doi.org/10.1016/j.jaad.2012.11.037Abstract Full Text Full Text PDF PubMed Scopus (528) Google Scholar and represents 20% to 50% of skin cancers.4Que S.K.T. Zwald F.O. Schmults C.D. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging.J Am Acad Dermatol. 2018; 78: 237-247https://doi.org/10.1016/j.jaad.2017.08.059Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar While cSCC has a metastatic rate of 2% to 5%,5Baum C.L. Wright A.C. Martinez J.C. et al.A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.J Am Acad Dermatol. 2018; 78: 141-147https://doi.org/10.1016/j.jaad.2017.07.031Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar the rate tends to be higher (7.5%) on the lip vermilion.6Wang D.M. Kraft S. Rohani P. et al.Association of nodal metastasis and mortality with vermilion vs cutaneous lip location in cutaneous squamous cell carcinoma of the lip.JAMA Dermatol. 2018; 154: 701-707https://doi.org/10.1001/jamadermatol.2018.0792Crossref PubMed Scopus (18) Google ScholarThe treatment of choice for cSCC is surgery; however, nonsurgical options are generally reserved for patients who refuse surgery or cannot tolerate a surgical procedure.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar The treatments combining surgery with radiotherapy or chemotherapy showed efficiency only in early-stage and well-defined cSCC.8Ding L.T. Zhao P. Yang M.L. Lv G.Z. Zhao T.L. GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth.Biochem Biophys Res Commun. 2018; 503: 1941-1948https://doi.org/10.1016/j.bbrc.2018.07.139Crossref PubMed Scopus (17) Google ScholarIntralesional 5-fluorouracil, interferon α, and methotrexate have been used sporadically for the treatment of squamous cell carcinoma.9Good L.M. Miller M.D. High W.A. Intralesional agents in the management of cutaneous malignancy: a review.J Am Acad Dermatol. 2011; 64: 413-422https://doi.org/10.1016/j.jaad.2009.12.013Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Cutaneous squamous cell carcinoma (cSCC) is associated with several risk factors, including sun exposure, advanced age, fair skin, and immunosuppression.1Nehal K.S. Bichakjian C.K. Update on keratinocyte carcinomas.N Engl J Med. 2018; 379: 363-374https://doi.org/10.1056/NEJMra1708701Crossref PubMed Scopus (140) Google Scholar It is the second-most common skin cancer in the United States,2Belbasis L. Stefanaki I. Stratigos A.J. Evangelou E. Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: an umbrella review of meta-analyses.J Dermatol Sci. 2016; 84: 330-339https://doi.org/10.1016/j.jdermsci.2016.09.003Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar with an estimated annual incidence of 700,000 cases,3Karia P.S. Han J. Schmults C.D. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012.J Am Acad Dermatol. 2013; 68: 957-966https://doi.org/10.1016/j.jaad.2012.11.037Abstract Full Text Full Text PDF PubMed Scopus (528) Google Scholar and represents 20% to 50% of skin cancers.4Que S.K.T. Zwald F.O. Schmults C.D. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging.J Am Acad Dermatol. 2018; 78: 237-247https://doi.org/10.1016/j.jaad.2017.08.059Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar While cSCC has a metastatic rate of 2% to 5%,5Baum C.L. Wright A.C. Martinez J.C. et al.A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.J Am Acad Dermatol. 2018; 78: 141-147https://doi.org/10.1016/j.jaad.2017.07.031Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar the rate tends to be higher (7.5%) on the lip vermilion.6Wang D.M. Kraft S. Rohani P. et al.Association of nodal metastasis and mortality with vermilion vs cutaneous lip location in cutaneous squamous cell carcinoma of the lip.JAMA Dermatol. 2018; 154: 701-707https://doi.org/10.1001/jamadermatol.2018.0792Crossref PubMed Scopus (18) Google Scholar The treatment of choice for cSCC is surgery; however, nonsurgical options are generally reserved for patients who refuse surgery or cannot tolerate a surgical procedure.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar The treatments combining surgery with radiotherapy or chemotherapy showed efficiency only in early-stage and well-defined cSCC.8Ding L.T. Zhao P. Yang M.L. Lv G.Z. Zhao T.L. GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth.Biochem Biophys Res Commun. 2018; 503: 1941-1948https://doi.org/10.1016/j.bbrc.2018.07.139Crossref PubMed Scopus (17) Google Scholar Intralesional 5-fluorouracil, interferon α, and methotrexate have been used sporadically for the treatment of squamous cell carcinoma.9Good L.M. Miller M.D. High W.A. Intralesional agents in the management of cutaneous malignancy: a review.J Am Acad Dermatol. 2011; 64: 413-422https://doi.org/10.1016/j.jaad.2009.12.013Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Case reportA 90-year-old man from Morelia, México, with no significant medical history presented in June 2017 with a 2-cm tumor on the right side of the lower vermilion, extending about 5 mm inside of the oral mucosa. It was indurated and covered by a yellowish crust. The lesion was indolent and had been growing for 18 months. No regional lymphadenopathy was detected on examination (Fig 1).A punch biopsy showed squamous cell carcinoma with moderate pleomorphism and dyskeratosis with oval and polygonal nuclei with an irregular shape. The tumor infiltrated the entire thickness of the dermis, without vascular permeation and without perineural invasion (Fig 2).Surgical treatment was declined because of the patient’s fear of the cosmetic outcome, so it was decided to treat him with intralesional methotrexate. Methotrexate 25 mg was injected in 1 ml (25 mg) with an insulin needle gauge 30, monthly at 3 separated intervals. The patient had an excellent clinical response with complete resolution (Fig 3). No recurrence was observed at 1 year of follow-up.Fig 3Six months after the first visit, a complete clinical response was observed. No crusty yellowish tumor was observed at the inner border of the lip. ∗Colorized.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Two months after completed treatment, a second biopsy was taken, which revealed mild acanthosis and mild reactive hyperkeratosis in the dermis. An inflammatory process was observed with mature lymphocytes and few plasma cells and hyalinized fibrosis. No residual tumor was observed (Fig 4).Fig 4On follow- up biopsy, no tumor was observed; only hyalinized fibrosis, hyperkeratosis, and inflammatory changes were reported on histopathological examination. ∗Colorized.View Large Image Figure ViewerDownload Hi-res image Download (PPT) A 90-year-old man from Morelia, México, with no significant medical history presented in June 2017 with a 2-cm tumor on the right side of the lower vermilion, extending about 5 mm inside of the oral mucosa. It was indurated and covered by a yellowish crust. The lesion was indolent and had been growing for 18 months. No regional lymphadenopathy was detected on examination (Fig 1). A punch biopsy showed squamous cell carcinoma with moderate pleomorphism and dyskeratosis with oval and polygonal nuclei with an irregular shape. The tumor infiltrated the entire thickness of the dermis, without vascular permeation and without perineural invasion (Fig 2). Surgical treatment was declined because of the patient’s fear of the cosmetic outcome, so it was decided to treat him with intralesional methotrexate. Methotrexate 25 mg was injected in 1 ml (25 mg) with an insulin needle gauge 30, monthly at 3 separated intervals. The patient had an excellent clinical response with complete resolution (Fig 3). No recurrence was observed at 1 year of follow-up. Two months after completed treatment, a second biopsy was taken, which revealed mild acanthosis and mild reactive hyperkeratosis in the dermis. An inflammatory process was observed with mature lymphocytes and few plasma cells and hyalinized fibrosis. No residual tumor was observed (Fig 4). DiscussionMethotrexate is a folic-acid analog that irreversibly inhibits the enzyme dihydrofolate reductase, blocking the synthesis of tetrahydrofolate and, ultimately, preventing the formation of thymidine9Good L.M. Miller M.D. High W.A. Intralesional agents in the management of cutaneous malignancy: a review.J Am Acad Dermatol. 2011; 64: 413-422https://doi.org/10.1016/j.jaad.2009.12.013Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar; likewise, it increases WWOX gene expression, which promotes caspase activation and apoptosis of cSCC cells.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google ScholarMany cases and series have reported on its effectiveness in treating keratoacanthoma10Annest N.M. VanBeek M.J. Arpey C.J. Whitaker D.C. Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature.J Am Acad Dermatol. 2007; 56: 989-993https://doi.org/10.1016/j.jaad.2006.12.017Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar; however, data on intralesional methotrexate in patients with cSCC are scarce.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar,11Plascencia-Gomez A. Calderón-Rocher C. Proy-Trujillo H. Moreno-Coutiño G. Neoadjuvant intralesional methotrexate before surgery in squamous cell carcinoma.Dermatol Surg. 2014; 40: 584-586https://doi.org/10.1111/dsu.12455Crossref PubMed Scopus (10) Google Scholar Recently, a small observational retrospective trial comparing intralesional methotrexate plus surgery versus surgery alone demonstrated a reduction in tumor size that subsequently could facilitate surgery.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google ScholarIn this patient, methotrexate was well tolerated, had a quick response, and was easily administrated at a low cost. At this time, surgical treatment remains the treatment of choice. Since the patient refused surgery, an alternative was required. Methotrexate therapy was chosen, which showed very good effectiveness. However, data with a greater number of clinical cases and long-term follow-up examinations are necessary before this therapeutic intervention could be recommended as an optional approach. Methotrexate is a folic-acid analog that irreversibly inhibits the enzyme dihydrofolate reductase, blocking the synthesis of tetrahydrofolate and, ultimately, preventing the formation of thymidine9Good L.M. Miller M.D. High W.A. Intralesional agents in the management of cutaneous malignancy: a review.J Am Acad Dermatol. 2011; 64: 413-422https://doi.org/10.1016/j.jaad.2009.12.013Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar; likewise, it increases WWOX gene expression, which promotes caspase activation and apoptosis of cSCC cells.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar Many cases and series have reported on its effectiveness in treating keratoacanthoma10Annest N.M. VanBeek M.J. Arpey C.J. Whitaker D.C. Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature.J Am Acad Dermatol. 2007; 56: 989-993https://doi.org/10.1016/j.jaad.2006.12.017Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar; however, data on intralesional methotrexate in patients with cSCC are scarce.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar,11Plascencia-Gomez A. Calderón-Rocher C. Proy-Trujillo H. Moreno-Coutiño G. Neoadjuvant intralesional methotrexate before surgery in squamous cell carcinoma.Dermatol Surg. 2014; 40: 584-586https://doi.org/10.1111/dsu.12455Crossref PubMed Scopus (10) Google Scholar Recently, a small observational retrospective trial comparing intralesional methotrexate plus surgery versus surgery alone demonstrated a reduction in tumor size that subsequently could facilitate surgery.7Salido-Vallejo R. Cuevas-Asencio I. Garnacho-Sucedo G. et al.Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.J Eur Acad Dermatol Venereol. 2016; 30: 1120-1124https://doi.org/10.1111/jdv.13266Crossref PubMed Scopus (20) Google Scholar In this patient, methotrexate was well tolerated, had a quick response, and was easily administrated at a low cost. At this time, surgical treatment remains the treatment of choice. Since the patient refused surgery, an alternative was required. Methotrexate therapy was chosen, which showed very good effectiveness. However, data with a greater number of clinical cases and long-term follow-up examinations are necessary before this therapeutic intervention could be recommended as an optional approach. None disclosed.