Multifocal Digital Squamous Cell Carcinoma With Sarcoma Differentiation: A Case Report

Introduction

Sarcomatoid refers to poorly differentiated squamous cell carcinomas with sarcoma-like histological characteristics [1]. Sarcomatoid squamous cell carcinoma is a specific subtype of squamous cell carcinoma. Its histological characteristics are characterized by a bidirectional differentiation pattern: on the one hand, there are malignant epithelial components, evolving from dysplasia to invasive carcinoma, and on the other hand, there are significant sarcomatoid changes in the stroma, featuring highly atypical spindle cell proliferation [2]. The World Health Organization classification clearly distinguishes between “spindle cell squamous cell carcinoma” (with minimal or absent epithelial components) and “sarcomatoid squamous cell carcinoma” (exhibiting prominent epithelial features). However, as demonstrated in this case, these 2 tumor types frequently exhibit overlap in clinical presentation and histological characteristics, effectively forming a continuum of highly aggressive epithelial malignancies [3]. This tumor has been given various names in the literature, including but not limited to spindle cell type squamous cell carcinoma, pleomorphic carcinoma, pseudosarcomatous carcinoma, and sarcomatoid carcinoma, reflecting its complex morphological spectrum. Sarcomatoid squamous cell carcinoma can develop in various anatomical sites, including the aerodigestive tract, salivary glands, breast, skin, urogenital system, and gastrointestinal tract [4].

The sarcomatoid subtype of cutaneous squamous cell carcinoma is extremely rare in clinical practice and has an indeterminate etiology; its clinical presentation varies according to anatomical site [5]. Due to its unique nomenclature system, complex histological features, and extremely low incidence rate, this lesion often poses challenges in clinical diagnosis and treatment strategy selection. Hypotheses regarding the etiology primarily involve the epithelial-mesenchymal transition process, driven by multiple factors, including carcinogenic effects triggered by chronic inflammatory responses and viral infections, leading to tumor cells exhibiting a highly invasive spindle cell morphology [6]. Typically, cutaneous squamous cell carcinoma predominantly affects older adults (with an average age of onset between 60 and 70 years). However, the present case demonstrates the occurrence of the disease in a younger male patient, which is widely recognized as a significant adverse factor for prognosis [7,8].

This report aims to examine a rare case of multifocal digital lesions, highlighting the potential risks of misdiagnosis during the diagnostic process. It further indicates that squamous cell carcinoma retains significant aggressiveness even after combined therapy, underscoring the need for heightened vigilance regarding its inherent threat. Additionally, the report emphasizes the importance of implementing early radical interventions for this high-risk patient population to enhance treatment efficacy and improve prognosis [9]. Therefore, we report a rare case of multifocal digital sarcomatoid squamous cell carcinoma in a young man to highlight these diagnostic and therapeutic challenges. The patient developed multiple primary squamous cell carcinomas on both hands and a sarcomatoid differentiation feature on the third finger of the right hand.

Case Report

TIMELINE SUMMARY:

The patient’s disease evolved as follows. Chronic inflammatory and squamous lesions appeared on multiple digits over a 2-year period. A distinct polypoid lesion (on R3) developed approximately 12 months prior to presentation and underwent rapid growth acceleration in the last 2 months before the patient sought definitive care.

The patient’s medical history showed that he had no history of chronic diseases, such as hypertension or diabetes, nor any history of surgery. He reported no history of chronic alcohol consumption or immunosuppression. The patient reported no weight loss over the past 2 years. He started smoking when he was in his teens and had a smoking history of over 30 years, smoking half a pack of cigarettes every day. Pain management during the course of the disease was primarily supportive, including over-the-counter and prescribed oral analgesics.

Physical examination showed that all fingers except the thumbs and the right fifth finger were affected. There was a raised lump on the third finger of the right hand that was pink in color and fragile, with areas of bleeding and necrosis. It was soft in texture, smooth on the surface, and showed no temperature changes. Radiographs of the hand bilaterally showed destruction of the bone tissue of the fingers and no signs of osteomyelitis (Figure 1B). As part of the further investigation, magnetic resonance imaging (MRI) was conducted on the bilateral hand lesions (Figure 1C).

To establish a clear diagnosis, the patient was taken to the operating room for a biopsy. Focal biopsy of the right index finger revealed epithelial widening, impaired layer formation, pleomorphic cells and nuclei, and numerous atypical mitoses. Immunohistochemical testing for the proliferation marker Ki-67 showed positive staining in approximately 30% of the epidermis. Pathologic sections showed no invasion of the basement membrane by proliferating keratinocytes. Pathologic findings were consistent with the diagnosis of squamous cell carcinoma in situ. A pathological examination on the tumor lesion on the right middle finger was performed. The mass showed significant hyperplasia of squamous epithelium under the microscope, accompanied by obvious abnormal keratinization (including excessive keratinization and incomplete keratinization), with the epithelial foot extending and widening in some areas and observed focal erosion. There was patchy necrosis in the interstitial with inflammatory exudation. In the dermis, atypical spindle-shaped cells showed clustered or diffuse proliferation, suggesting the presence of potential mesenchymal-derived tumor components (Figure 1D). The immunohistochemical staining results showed the tumor cells expressed smooth muscle actin and vimentin and showed focal expressions of cytokeratin, desmin, and p40 protein. Cluster of differentiation 34 and p63 were negative. The spindle cell component was distinguished from true sarcomas, such as leiomyosarcoma or fibrosarcoma, by its coexistence with typical squamous cell carcinoma and a characteristic immunohistochemistry profile (vimentin+, focal cytokeratin+, and p63-), confirming an epithelial origin with divergent mesenchymal differentiation. This profile helped rule out malignant melanoma and primary spindle cell sarcoma.

After comprehensive evaluation by positron emission tomography–computed tomography, it was determined that no distant metastatic lesions were detected in this patient. All regional lymph nodes were within the normal size range, and no signs of tumor metastasis were observed (Figure 1E).

After a pathological biopsy, a clear diagnosis was made and the overall condition was fully evaluated. The patient’s condition was communicated and a surgical plan was formulated. As the patient repeatedly experienced ulceration and pain in the second finger of the right hand, a finger amputation surgery was requested. Additionally, a lesion expansion resection of the sarcomatoid carcinoma in the third finger of the right hand was performed. For the remaining fingers, curettage surgeries were conducted, followed by photodynamic therapy (Figure 1F).

Based on the pathological and imaging findings, the patient underwent surgical excision of the primary lesions on the left index and middle fingers, followed by topical 5-aminolevulinic acid–mediated photodynamic therapy for the remaining low-grade lesions. The sarcomatoid lesion on the right third finger was initially excised. Pathological confirmation indicated that all excisional margins (both the non-sarcomatoid and sarcomatoid lesions) were free of tumor (R0 resection). Postoperative wound healing was generally satisfactory. However, due to the high-risk pathology and subsequent local recurrence 3 months later, the patient was advised to undergo amputation of the right third finger. The patient completed the planned 4 sessions of photodynamic therapy and tolerated the treatment well, with localized pain during irradiation being the only reported adverse event.

The histopathological examination revealed moderately differentiated squamous cell carcinoma involving multiple digits bilaterally (Figure 1H). The left second finger demonstrated squamous epithelial hyperplasia with marked hyperkeratosis and parakeratosis containing inflammatory necrotic exudate, showing focal high-grade dysplasia with small invasive foci. Similar dysplastic changes were observed in the left fourth and fifth fingers with papillary squamous hyperplasia. The right second and fourth fingers exhibited moderately differentiated squamous cell carcinoma, with the former showing perineural invasion but no lymphovascular involvement. Notably, the right third finger presented a spindle cell malignant neoplasm immunohistochemically consistent with sarcomatoid carcinoma. All bony resection margins remained free of neoplasia, and no lymphovascular invasion was detected in the sarcomatoid component (Table 2).

After 3 months of treatment, a follow-up examination was conducted. The lesion on the finger that had undergone excision showed local recurrence (Figure 1G). Three months after the surgery, the patient was followed up. Ulcerative lesions were observed in the second, third, fourth, and fifth fingers of the left hand, as well as the fourth finger of the right hand. Following the detection of local recurrence, the patient declined further surgical intervention. He specifically expressed a profound fear of permanent disfigurement and was concerned that further amputations would severely affect his livelihood and ability to work as a construction worker. Subsequently, the patient was lost to follow-up.

Discussion

Sarcomatoid carcinoma is a subtype of squamous cell carcinoma with dual differentiation: conventional squamous cell carcinoma components and a sarcomatoid area of atypical spindle cells. Sarcomatoid (spindle cell) carcinoma is a specific histological subtype of squamous cell carcinoma. Its typical feature is that the tumor cells exhibit spindle-shaped sarcomatoid morphological changes. This type of tumor is commonly found in internal organ systems. Commonly affected sites include the respiratory system (eg, lungs), digestive system (eg, esophagus), urinary system (eg, bladder, kidneys), and endocrine organs (eg, thyroid), while cases originating from the skin are extremely rare in clinical practice [10].

Sarcomatoid carcinoma, a biphasic malignant tumor, exhibits greater aggressiveness than does conventional squamous cell carcinoma, which is attributed to its sarcomatoid component. Current evidence suggests an epithelial origin for this neoplasm, with the spindle cell morphology arising through divergent differentiation [11].

The risk factors for cutaneous sarcomatoid carcinoma include immunosuppression, previous radiotherapy, smoking, and alcohol consumption. Long-term sun exposure and exposure to toxins are also risk factors for skin involvement [12]. Our patient had a history of smoking, did not consume alcohol, and had no previous history of radiotherapy.

Clinically, cutaneous sarcoma usually occurs on the skin that has been damaged by sunlight and presents as nodular lesions of varying sizes, often accompanied by ulcers. The duration of these tumors ranges from several months to several years, and changes usually occur early on. The lesions typically manifest as ulcerated nodules, with sizes ranging from 7 to 50 mm. Unlike carcinomas that occur in internal organs, those that mainly occur on the skin do not seem to be necessarily associated with a high mortality rate [13,14].

Sarcomatoid carcinoma, as a specific subtype of squamous cell carcinoma, needs to be differentiated from various tumors with spindle cell morphology during pathological diagnosis. The term cutaneous sarcoma encompasses multiple primary malignant tumors of mesenchymal origin in the skin, including leiomyosarcoma, rhabdomyosarcoma, and fibrosarcoma. During clinical diagnosis, it is essential to clearly differentiate these from squamous cell carcinoma to ensure diagnostic accuracy and the appropriate formulation of subsequent treatment plans [15]. These lesions to be distinguished include, but are not limited to, reactive proliferative lesions, such as nodular fasciitis; mesenchymal malignant tumors, such as smooth muscle sarcoma, rhabdomyosarcoma, and fibrosarcoma; neurogenic tumors, such as malignant peripheral nerve sheath tumors; and certain epithelial tumors with spindle cell differentiation, such as spindle cell melanoma and synovial sarcoma. The diagnostic and therapeutic challenges become particularly pronounced when the squamous cell carcinoma component is significantly diminished or obscured by ulcerative changes or necrotic tissue. Accurate diagnosis often requires a comprehensive judgment based on histological features, immunohistochemical markers, and molecular detection results.

The pathological diagnosis of sarcomatoid carcinoma presents significant challenges. Its histological features are dominated by the proliferation of spindle-shaped or polymorphic cells, often lacking clear epithelial differentiation characteristics, making it difficult to distinguish it from primary spindle cell sarcoma, malignant melanoma, and reactive spindle cell lesions under the optical microscope. At this point, immunohistochemical detection holds crucial diagnostic value [16].

Commonly used epithelial differentiation markers include cytokeratin, p63 (a marker specific to squamous cells), epithelial membrane antigen, and carcinoembryonic antigen. Mesenchymal markers are mainly vimentin, supplemented by myogenic markers (desmin, smooth muscle actin) and neurogenic markers (S-100 protein) [17,18]. The diagnosis requires comprehensive consideration: squamous cell carcinoma typically expresses cytokeratin and p63, while sarcomatoid carcinoma typically shows positive for vimentin and negative for other specific markers [19].

A clear differentiation can be achieved only through a systematic analysis of the expression profiles of multiple markers. This differential diagnosis process requires particular attention to the correlation between histological morphology and immunophenotype, and a comprehensive judgment should be made in combination with clinical manifestations.

The standardized local treatment protocol for cutaneous squamous cell carcinoma should ensure the complete eradication of all lesional tissues, rather than merely extending the excision of the primary and metastatic foci [5,20]. Clinically, it is recommended to perform a circumferential resection with a 10-mm safety margin, accompanied by deep tissue excision including the fascial layer [10]. Radiotherapy presents a therapeutic paradox – although implicated in sarcomatoid tumorigenesis, it remains a viable option for patients with surgical contraindications, incomplete resections, or nodal involvement at diagnosis.

In this case, the patient underwent photodynamic therapy targeting residual low-grade malignant lesions. Although photodynamic therapy is a well-established noninvasive treatment strategy widely used for squamous cell carcinoma in situ and superficial invasive squamous cell carcinoma, its efficacy remains limited in managing high-grade or deeply invasive lesions, such as subepidermal squamous cell carcinoma [21]. Following combined therapy, recurrence occurred at the subepidermal squamous cell carcinoma site, further highlighting the pronounced resistance of such tumors to non-curative treatments. However, some studies suggest that in certain situations, these adjuvant treatment methods may need to be considered [22]. Additionally, immunotherapy, particularly PD-1 inhibitors, has garnered significant attention in the treatment of advanced cutaneous squamous cell carcinoma. Given the disease’s high mutational burden and aggressive nature, immunotherapy demonstrates considerable potential as a key focus for future research. It holds promise as a vital adjuvant treatment strategy for patients at high risk or with inoperable lesions, further advancing clinical practice and innovation in this field [23,24]. This disease is a rare clinical malignant tumor, and its specific pathogenesis has not yet been clarified. The early symptoms are often atypical, and the overall clinical prognosis is poor [10].

Adverse prognostic indicators in sarcomatoid carcinoma include prolonged course (>3 years), large tumor size (>2 cm), recent growth acceleration, multifocal involvement, and younger age at presentation (<65 years) [5,25]. The unique clinical manifestations of the present case – multiple squamous cell lesions in the fingers accompanied by an isolated and aggressive squamous cell carcinoma transformation – provide important clinical and pathological insights in the relevant field, and also highlight several key challenges [26]. First, multiple low-grade malignant squamous cell lesions were observed in the fingers, with a background of long-term exposure to high-risk factors such as sun exposure and smoking. This situation fully supports the theory that the hand area is prone to malignant transformation and creates a high-risk foundation for subsequent malignant transformation. The localized sarcomatoid differentiation limited to the third finger reflects the possibility of a highly invasive pathological evolution in this local area. Second, although the surgery achieved R0 resection and was supplemented by photodynamic therapy, the squamous cell carcinoma still showed a rapid recurrence trend within 3 months, highlighting the significant biological invasiveness of this subtype of tumor [9]. At the same time, this indicates that non-curative treatment methods such as photodynamic therapy have certain limitations in controlling thick and highly malignant spindle cell malignant tumors, emphasizing the necessity of adopting active early treatment strategies (such as amputation) for high-risk patients with digital squamous cell carcinoma [21]. Moreover, this case further suggests the risk of high-grade transformation in multifocal digital squamous cell carcinoma, especially for patients younger than 50 years old with multiple lesions, which may imply that this subgroup of patients requires systemic or neoadjuvant treatment to improve prognosis [23].

Given the aggressive nature of this disease, clinicians should fully inform patients of the high risk of skin squamous cell carcinoma at the early stage of diagnosis, and recommend initiating a comprehensive treatment plan that includes assessment of local lesions, examination of regional lymph nodes, and analysis of overall condition. It is recommended to adopt a multidisciplinary collaboration model to make individualized treatment decisions to ensure timely intervention [12].

Conclusions

This case highlights that digital sarcomatoid squamous cell carcinoma is highly aggressive and prone to early recurrence, necessitating extensive resection and close follow-up from the outset. Its diagnostic complexity and poor prognosis underscore the need for complementary biomarkers and a low threshold for radical intervention in patients with high risk.