Squamous Cell Carcinoma Treated With Intralesional Methotrexate: Report of a Case
Sancheza DCV, Gonzalezb LGV, Hernandezc LM and Moreno GC
Published on: 2022-05-07
Squamous cell carcinoma (SSC) is the second most common cutaneous malignancy. Some reports have mentioned the use of intralesional methotrexate as a neoadjuvant therapy to reduce the tumor´s size and enable a smaller surgical defect and reconstruction area. Among the multiple advantages of this approach, some stand out, like bypassing the systemic side effects of chemotherapy that present when administered PO or IV. Methotrexate is one of the most used drugs for skin SCC. Its intralesional administration allows a satisfactory pharmaceutical concentration level (>104 ) in the tumoral cells, turning them more sensitive to the cytotoxic effect causing tissue necrosis, thus reducing the tumors mass and enabeling a better surgical outcome.
KeywordsIntralesional Methotrexate; Squamous Cell Carcinoma; Cardiovascular Risk
Squamous cell carcinoma (SSC) is the second most common cutaneous malignancy. Some reports have mentioned the use of intralesional methotrexate as a neoadjuvant therapy to reduce the tumor´s size and enable a smaller surgical defect and reconstruction area. Among the multiple advantages of this approach, some stand out, like bypassing the systemic side effects of chemotherapy that present when administered PO or IV. Methotrexate is one of the most used drugs for skin SCC. Its intralesional administration allows a satisfactory pharmaceutical concentration level (>104 ) in the tumoral cells, turning them more sensitive to the cytotoxic effect causing tissue necrosis, thus reducing the tumors mass and enabeling a better surgical outcome. Methotrexate (MTX) is a folic acid analog that irreversibly inhibits the enzyme dihydrofolate, and ultimately, preventing formation fo thymidine. Liquid formulations are affordable and widely available. MTX is renally excreted, and base on this exprience, the autors recommend a baseline complete blood cell count and assessment fo renal function before use fo intralesional MTX, with a follow-up complete blood cell count 1 wedd after the first injection[1-13]. The use of agentes such as 5-FU5 or Interferon α-2b6 has been described. Intralesional 5-FU to treat SCC is not a new concept. Klein et al reported use of this modality in 1692. Intralesional methotrexate( MTX) offers several advantages over intraregional 5-FU, including: fewer injections with a longer interval between injections, lesser cost; and no need for a local anesthetic before MTX injection, as the injections engenders lesser pain than 5-FU. Furthermore MTX increases the WWOX gene expression and promotes the caspases activation, inducing apoptosis of the squamous carcinoma cells. Locally, infiltration achieves higher MTX intracellular concentration in cSCC cells, which are >104 times more sensitive to the cytotoic effect of MTX [2,14,15]. Despite the lack of clinical trials or clinical guides for the intralesional use of methotrexate, few case reports have been published, where they have administered 40 mg of methotrexate divided in two doses one week apart, and another report mentions complete remission and this way, no surgery was necessary.
Female 83 year-old patient attended to consultation for having a tumour on the posterior side of the right leg, vegetate, of 2.5 cm in diameter and refers that she noticed it 6 months ago [Figure 1].
Figure 1: The posterior side of the right leg, vegetates, of 2.5 cm in diameter. and refers that she noticed it 6 months ago.
Figure 2: A 5mm punch reported moderately differentiated squamous cell carcinoma.
Figure 3: Because of the high cardiovascular risk, surgery was not the first option, so she was offered the intraregional application of 25 mg methotrexate monthly in four occasions.
Figure 4: She was summoned one month after for a clinical and possibly a histolgical evaluation, but she failed to attend. One year later, she returned for another dermatoses, with the SCC completely cleared.
Intralesional chemotherapy with methotrexate is used for tumor reduction prior to surgical removal, thus, reducing the size of the defect, and allowing an easier sugical management, enabeling easier reconstruction and a better cosmetic result. So, despite the surgery still being the gold standard for squamous cell carcinoma management, the neoadjuvant therapy can be extremely beneficial with efficacy of intralesional methotrexate being reported up to 88.9% after weekly injections for two-four weeks, with a dosage between 12.5-25 mg per infiltration. No abnormalities in laboratoy tests have been indentified, and after an average of 2.8 years of follow-up, lesions have not recurred . This is used safely to treat keratoacanthoma with 92% complete response rate. It has algo been shown to be useful as a neoadjuvant to surgery for keratoacanthoma, although there have been no reports on intralesional use un invasive SCC, but as a neodjuvante to surgery, it could be useful for reducing the size of the tumor and so improving patients´s possibilities for surgery and reducing the numbrer of complications. Plascencia-Gomez et al reported a case of an 81 year-old man with squamous cell carcinoma of the lower lip, He received three injections of the drug, with doses ranging from 17.5 to 25mg, with a dramatically reduced the tumor size , allowing a smaller surgical defect that could be repaired using a flap. The final histopathology report corroborated this, nothig the rudction fo the epitheliomatous structures and the presence of the inflammatory response .Immunohistochemistry (IHC) is a method for detecting the location of proteins and other antigens in tissue sections using antibodies. Though less quantitative tan other immunoassays such as western blottting or ELISA, IHC shows where proteins are expressed in the context of intact tissue. This is especially useful for assessing the progression anda best treatment options of diseases such as cancer. In general, IHC data provide a valuable prespective that can help interpret data obtained using other methods.To this moment, the patient has not presented any systemic or local side effects.
After evaluating this patient´s progress, we conclude that neoadjuvant intralesional methotrexate is a helpful aid prior to the surgical procedure where, reducing the tumor´s size improves the surgical success and reduces possible complications.This medical approach provides good response in quick size reduction of the tumor, and is a low cost option. Methotrexate is well torated, acts promptly, it is easy to use and has low in cost ($18 USD for three doses).
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