A simple sore can lead to limb amputation; metastatic squamous cell carcinoma of the sole in a 22-year-old man

Abstract

Introduction and importance

Squamous cell carcinoma (SCC) is a cancerous tumor that can develop when normal keratinocytes undergo a transformation into invasive cancer cells, typically due to genetic mutations that affect cell growth and differentiation. SCC is frequently found on sun-exposed areas of the skin like the face, ears, neck, and hands, but it is unusual to see it develop on the soles of the feet.

Case report

This case is about a 22-year-old man who came in with a persistent sore on the bottom of his left foot. The patient mentioned sustaining a small injury to his foot about two weeks before seeking medical help, which started off as a minor wound but deteriorated over time. Ultimately, the diagnosis revealed squamous cell carcinoma that had spread to the lungs and lymph nodes.

Discussion

This case highlights the importance of considering the possibility of malignancy in non-healing wounds, even in young patients without known risk factors. The initial presentation of a simple sore that progressed to metastatic SCC underscores the challenges in diagnosing and managing skin cancers in atypical presentations.

Conclusion

This case highlights cancer's aggressiveness and atypical youth presentations, stressing early detection, aggressive treatment, and comprehensive patient support. Continued research is crucial for enhancing disease management.

Highlights

• •SCC can develop in unusual places like the soles, emphasizing the need to consider cancer in wounds that won't heal.
• •This case shows SCC's aggressiveness, with a foot sore turning into metastatic cancer.
• •Early detection and aggressive treatment are key for skin cancer, especially in young patients without risk factors.

1. Introduction

Skin cancers, particularly those originating from keratinocytes, represent a significant health concern, with non-melanoma skin cancers (NMSCs) being the most prevalent form worldwide [1]. These cancers are primarily associated with exposure to ultraviolet (UV) radiation, which can lead to the development of various skin malignancies, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) [2]. SCC is one of the most common types of skin cancer, with an estimated 16,550 new cases and 2700 deaths due to SCC in the United States alone in 2022. However, the incidence of SCC on the soles of the feet is much rarer, making this case particularly noteworthy [3]. While NMSCs are commonly observed in older individuals with a history of chronic sun exposure, their occurrence in younger populations is relatively rare [4].

Squamous cell carcinoma (SCC) is a malignant neoplasm that can arise from the transformation of normal keratinocytes into invasive cancer cells [5]. This transformation is often associated with genetic mutations that disrupt the normal regulation of cell growth and differentiation. SCC can develop on any part of the body but is most commonly found on sun-exposed areas of the skin, such as the face, ears, neck, and hands, but involving soles of feet is much unexpected. While SCC is generally considered less aggressive than melanoma, it can metastasize to other parts of the body, leading to potentially life-threatening complications [6,7].

This report presents a unique case of a 22-year-old man who initially presented with a simple sore on the sole of his foot, which was later diagnosed as metastatic SCC, necessitating limb amputation. The case underscores the importance of early detection and aggressive management of SCC, highlighting the potential for aggressive behavior in atypical presentations. It also emphasizes the need for a comprehensive understanding of the risk factors, pathogenesis, and clinical manifestations of SCC to improve patient outcomes and prevent unnecessary morbidity and mortality. The work has been reported in line with the SCARE 2023 Criteria [8].

2. Case presentation

This case involves a 22-year-old male presenting with a non-healing ulcer on the plantar surface of his left foot. The patient reported a minor injury to the sole of his foot approximately two weeks prior to seeking medical attention, which initially appeared as a small wound but had progressively worsened (Fig. 1). He described the wound as painful and reported difficulty walking due to the discomfort. The patient had no significant medical history, did not smoke, and had no known allergies. He denied any history of chronic health conditions, including diabetes, and reported no family history of skin cancer or other malignancies.

Fig. 1.

Initial advancement of the wound.

2.1. Initial evaluation and management

Upon initial examination, the ulcer was noted to be approximately 2 cm in diameter, with well-defined borders and a purulent discharge. The surrounding skin was erythematous and tender to palpation. The patient was referred to a specialized wound care team for management. The initial treatment plan included modern bandaging techniques and wound care, aiming to promote healing and prevent infection. However, despite these interventions, the wound continued to deteriorate over the course of approximately ten days, expanding in size and becoming increasingly painful (Fig. 2).

Fig. 2.

The wound worsened, growing larger and causing increased discomfort.

2.2. Diagnostic journey and interventions

As the wound failed to respond to standard wound care, the specialized wound care team expressed concern regarding the ulcer's progression and referred the patient to a general hospital for further evaluation. A biopsy of the lesion was recommended to determine the underlying cause of the non-healing ulcer. The pathologist examined the tissue under a microscope and prepared a report detailing several key findings: the overall architecture of the tissue showed disorganized cellular growth with a loss of normal skin structure, indicative of a malignant process. The cellular features included atypical squamous cells characterized by enlarged nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, which are typical of squamous cell carcinoma (SCC). The report assessed the degree of differentiation, noting that well-differentiated SCCs closely resemble normal squamous epithelium, while poorly differentiated SCCs present a more disorganized appearance and tend to be more aggressive. The depth of invasion revealed that the carcinoma had penetrated deeply into the skin layers, necessitating amputation. Furthermore, immunohistochemistry tests were conducted using antibodies against specific proteins such as p63, CK5/6, CK7, and CK20 to confirm the squamous cell origin of the cancer and to exclude other skin malignancies (Fig. 3).

Fig. 3.

Histopathological examination which revealed the presence of squamous cell carcinoma.

Further investigations, including computed tomography (CT) scan, revealed that the cancer had metastasized to the cervical lymph nodes and lungs (Fig. 4). The stage of the SCC was T4N1M1, depending on the exact details of the lymph node involvement and the number of metastatic sites in the lungs. This would place the cancer in Stage IV, which is the most advanced stage and indicates that the cancer has spread beyond the local area to distant parts of the body.

Fig. 4.

The Metastases of the cancer to the lung tissue in Chest CT-scan.

Moreover, the histopathological report of lymph nodes detailed multiple, measuring between 0.5 cm and 3.0 cm, exhibited a firm texture with tan-white cut sections. Microscopic examination revealed a dense infiltrate of atypical epithelioid cells characterized by irregular nuclei and keratin pearl formation, indicative of squamous cell differentiation. Notably, there was significant invasion into the lymph node sinuses and surrounding adipose tissue, with scattered mitotic figures reflecting active tumor growth. Additional histological findings included lymphovascular invasion and extensive necrosis observed in the lymph nodes.

Given the advanced stage of the disease, a multidisciplinary team, including oncologists and surgeons, was convened to discuss the best course of treatment. The decision was made to proceed with surgical resection of the involved lymph nodes and amputation of the left leg to remove the primary tumor (Fig. 5).

Fig. 5.

Amputation of the left leg to remove the primary tumor.

In the preoperative phase, the laboratory findings indicate a slightly elevated white blood cell (WBC) count of 11,000 cells/μL, suggesting a potential inflammatory response, while other components of the complete blood count (CBC), including hemoglobin at 14 g/dL and platelets at 250,000/μL, remain within normal ranges. The comprehensive metabolic panel (CMP) shows stable blood glucose at 85 mg/dL, a blood urea nitrogen (BUN) level of 15 mg/dL, and a creatinine level of 0.9 mg/dL, all indicative of normal kidney and metabolic function, with electrolytes also within normal limits. Liver function tests (LFTs) reveal normal levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin, confirming healthy liver function. The coagulation profile is within normal ranges, with a prothrombin time (PT) of 12 s, an International Normalized Ratio (INR) of 1.1, and a partial thromboplastin time (PTT) of 30 s. Notably, tumor markers reveal elevated levels of squamous cell carcinoma antigen (SCCAg) and cytokeratin 19 fragments (CYFRA 21-1), suggesting a squamous cell origin, while the carcinoembryonic antigen (CEA) remains normal. Additionally, all infection screenings, including HIV, hepatitis B surface antigen (HBsAg), and hepatitis C antibody, are negative, indicating no underlying infectious conditions.

2.3. Post-operative management and outcome

Following the surgical intervention, the patient underwent chemotherapy to address the pulmonary metastases and to prevent the spread of cancer to other parts of the body. The treatment regimen was tailored to the patient's specific needs and involved a combination of cytotoxic drugs aimed at eradicating any remaining cancer cells. The patient's response to chemotherapy was monitored closely through regular imaging studies and clinical assessments. Despite the aggressive nature of the cancer and the advanced stage at diagnosis, the patient's condition has been stable, with no evidence of disease progression. Over the course of 16 months of follow-up, there have been no signs of recurrence, indicating a positive response to the comprehensive treatment strategy. The patient is currently under the care of a multidisciplinary team and continues to be closely monitored for any signs of recurrence, with ongoing support and follow-up care to manage any potential long-term effects of the treatment and to ensure the best possible outcome.

3. Discussion

The case is particularly noteworthy due to the patient's young age and the atypical location of the SCC, which is typically associated with chronic sun exposure and thus more commonly observed in older individuals. SCC can be classified into various types based on the degree of differentiation and histological characteristics. These types include well-differentiated, moderately differentiated, and poorly differentiated SCC, with the latter being more aggressive and associated with a higher risk of metastasis. Additionally, SCC can be categorized as keratinizing or non-keratinizing, depending on the presence of keratin production, and as invasive or in situ, depending on whether the cancer has invaded beyond the epidermis [9].

This discussion will focus on the implications of this case for our understanding of SCC risk factors, pathogenesis, and clinical management, with a particular emphasis on the importance of early detection and aggressive treatment strategies.

3.1. Similar studies

Schwartz reported a case, about a 65-year-old male with a history of cutaneous squamous cell carcinoma (SCC) on his chest, which had metastasized to regional lymph nodes and later to the gastrointestinal tract, specifically within a diverticulum of the sigmoid colon and the jejunum. This was a rare occurrence, as gastrointestinal metastasis from cutaneous SCC was not commonly reported. The patient underwent treatment, including lymph node dissection and chemoradiation, followed by the discovery of the colonic lesion during a routine colonoscopy. Subsequent laparoscopic surgery confirmed metastatic SCC in the colon and small bowel. The patient was then treated with systemic immunotherapy. The authors stressed the importance of considering gastrointestinal involvement in metastatic SCC, even when other imaging suggested remission, and recommended thorough evaluation for synchronous lesions and the potential need for systemic therapy [10].

BOZKURT and CAPI presented two case reports of Marjolin's ulcers, which were chronic wounds with a propensity to transform into squamous cell carcinoma (SCC), leading to amputations of the extremities. The first patient, a 28-year-old male, developed SCC on his left forearm at the site of a previous burn, which necessitated an arm amputation above the elbow. The second patient, a 61-year-old male, had a long-standing ulcer on his left thigh, also originating from a burn scar, which led to a high femur amputation. The article discussed the aggressive nature of these lesions, their tendency to invade deep structures and metastasize, and the importance of early diagnosis and intervention to prevent malignant transformation. The authors emphasized the need for regular follow-up, especially in developing countries, and awareness among surgeons of the potential for Marjolin's ulcers to invade bone, highlighting that these ulcers were not merely precancerous lesions. The article concluded with the importance of patient education and the necessity of biopsy for suspicious lesions [11].

3.2. Risk factors and pathogenesis

The development of SCC in a young individual without significant risk factors, such as chronic sun exposure or immunosuppression, highlights the complexity of SCC pathogenesis [12]. While UV radiation is a well-established risk factor for SCC, other factors, including genetic predisposition, environmental exposure to certain chemicals, and chronic skin injury, may also contribute to the development of this cancer [13]. SCC is a common type of skin cancer that predominantly impacts people with lighter skin. This increased risk is largely attributed to the lower levels of melanin in fair skin, which offers less natural defense against the damaging effects of ultraviolet (UV) radiation from sunlight—one of the main risk factors for SCC. As a result, those with fair skin face a greater likelihood of developing SCC, particularly if they have a background of significant sun exposure or sunburns [14]. The absence of these known risk factors in the presented case suggests that there may be additional, as yet unidentified, risk factors that contribute to SCC development in younger populations [15].

Additionally, contemporary diets often consisting of processed foods might unintentionally lead to higher arsenic exposure for individuals, stemming from contaminated water sources or soil rich in arsenic utilized in agriculture. Considering the ongoing impact of these exposures, younger individuals may face a heightened cancer risk due to their longer lifespans and the body's inflammatory reactions to detrimental lifestyle habits, including smoking, heavy drinking, and lack of physical activity. Consequently, advocating for a well-rounded diet that minimizes carcinogens and fostering a healthier lifestyle are essential strategies for lowering cancer risk and enhancing overall health outcomes among younger populations [16].

Moreover, the rapid progression of the patient's condition from a simple sore to metastatic cancer underscores the aggressive nature of SCC, which can metastasize to regional lymph nodes and distant organs, including the lungs [17]. This case serves as a reminder that SCC, despite its relatively low metastatic rate compared to melanoma, should not be underestimated in its potential for aggressive behavior, particularly in atypical presentations.

3.3. Clinical management and outcome

The standard approach for SCC involves surgery, with radiation or chemotherapy considered for high-risk cases or metastatic conditions. In this specific instance, due to the disease's late-stage diagnosis, a comprehensive treatment plan involving surgical resection, amputation, and chemotherapy was necessary [18]. The stable response of the patient to treatment underscores the significance of a multidisciplinary strategy, especially in advanced SCC cases [19]. This case also sheds light on the complexities of managing SCC in younger patients, who may encounter distinctive challenges post-treatment, necessitating ongoing support and follow-up care, emphasizing the importance of a comprehensive, multidisciplinary patient management approach.

3.4. Implications for clinical practice and research

This case underscores the importance of a high index of suspicion for SCC in all age groups, particularly in atypical presentations. Healthcare providers should be aware of the potential for SCC to develop in younger individuals and should consider early biopsy and referral to a dermatologist or oncologist in cases of non-healing wounds or ulcers, regardless of the patient's age or apparent risk factors [20].

Further research is needed to better understand the risk factors and pathogenesis of SCC in younger populations, including the role of genetic factors, environmental exposures, and other potential risk factors. This knowledge could inform the development of targeted screening and prevention strategies aimed at reducing the incidence and severity of SCC in younger individuals [21].

4. Conclusion

In conclusion, this case illustrates the potential for squamous cell carcinoma to present in an atypical manner, with a simple sore on the sole of the foot as the initial manifestation. The aggressive nature of the disease and the early metastasis highlight the importance of a high index of suspicion among healthcare providers when evaluating non-healing wounds. Early detection and multidisciplinary management are crucial for improving patient outcomes in such cases.

Ethical approval

Ethical clearance was not necessary by Research Committee of Urmia University of Medical Sciences as the format of this paper is a case report.

Funding

This CASE REPORT did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author contribution

Maryam Ebrahimi Dastgerdi (Corresponding author), Navid Faraji, Rasoul Goli: study concept, data collection, writing the paper.

Raheleh pourbahram, Banafsheh Parvaresh, Hassan Alidoust: writing the paper, reviewing and validating the manuscript's credibility.

Guarantor

Navid Faraji

Research registration number

Not applicable.

Conflict of interest statement

Declarations of interest: None.