Spindle cell carcinoma (SCC) is a rare and aggressive form of cancer that arises from epithelial cells, the tissue that lines the surface of organs and the body. Carcinomas typically consist of rounded or polygonal cells, but SCC is defined by its highly unusual cell shape. This malignancy is characterized by cells that have elongated, slender nuclei and a fusiform appearance, leading to the name “spindle cell.” This cellular morphology is often associated with a high-grade malignancy, meaning the tumor tends to grow and spread quickly.
The Unique Nature of Spindle Cell Carcinoma
Spindle cell carcinoma is most often categorized as a variant of squamous cell carcinoma, the most common type of cancer in many epithelial tissues. The defining feature is the presence of cells that have undergone “sarcomatoid differentiation,” making the epithelial cancer cells look like those found in sarcomas, which are cancers of mesenchymal tissues like bone, fat, or muscle. The tumor cells in SCC are long and narrow, resembling the spindle shape of fibroblasts or smooth muscle cells. This transformation is believed to be a form of aggressive dedifferentiation, where the epithelial cells lose their original characteristics and adopt a more primitive, mesenchymal-like phenotype.
The pathology is often described as biphasic, meaning the tumor may contain both the classic epithelial component and the transformed spindle cell component, though sometimes only the spindle cells are evident in the biopsy. The spindle component often displays significant cellular irregularity, rapid cell division, and may be haphazardly arranged, helping pathologists distinguish it from true sarcomas. The aggressive nature of this cellular change contributes to the generally poorer prognosis associated with SCC compared to conventional squamous cell carcinoma.
Common Sites of Development and Associated Risk Factors
Spindle cell carcinoma can arise in almost any part of the body lined by epithelial tissue, but it shows a strong predilection for the upper aerodigestive tract. The head and neck region is a frequent site, with the larynx (voice box) and the oral cavity being particularly common primary locations. Less common sites include the skin, lungs, esophagus, and even the breast or kidney.
For SCCs arising in the head and neck, the primary risk factors are strongly linked to lifestyle exposures, mirroring those for conventional squamous cell carcinoma. These include prolonged tobacco use and excessive alcohol consumption. Another established risk factor is a history of prior radiation treatment for other cancers in that region. Cutaneous SCC, which is found on the skin, is often associated with chronic sun damage, chronic inflammation, or previous radiation exposure to the skin.
Identifying and Confirming the Diagnosis
The diagnosis of spindle cell carcinoma is often complicated because its microscopic appearance closely mimics true sarcomas and other non-carcinoma spindle cell lesions. The diagnostic process begins with a biopsy, where a tissue sample is removed for examination under a microscope. Initial imaging scans, such as computed tomography (CT) or magnetic resonance imaging (MRI), are also performed to determine the tumor’s size, extent of local invasion, and whether it has spread to other areas of the body.
The definitive confirmation requires specialized laboratory techniques, most notably Immunohistochemistry (IHC). IHC uses antibodies to identify specific proteins within the tumor cells. To confirm that the spindle-shaped cells are epithelial (carcinoma) rather than mesenchymal (sarcoma), the cells must stain positive for epithelial markers. The most important of these markers are cytokeratins, a family of proteins characteristic of epithelial tissue, which confirms the tumor’s epithelial lineage despite its sarcomatoid appearance.
The pathologist must also ensure the tumor cells are negative for markers associated with other spindle cell malignancies, such as S-100 protein (indicating melanoma) or desmin (indicating a muscle-related sarcoma). While the spindle cells may also express mesenchymal markers like vimentin, the co-expression of cytokeratins is the distinguishing feature that confirms the diagnosis of spindle cell carcinoma.
Therapeutic Strategies for Spindle Cell Carcinoma
The primary and most effective treatment is typically surgical resection with wide, clear margins. The goal of surgery is to remove the entire tumor along with a surrounding border of healthy tissue to ensure that no cancerous cells are left behind. Due to the tumor’s tendency for local recurrence and its size at presentation, the extent of the surgery can vary significantly, ranging from local excision to more radical procedures.
Adjuvant therapies are often used following surgery to reduce the risk of the cancer returning. Radiation therapy is a common adjuvant treatment, particularly for tumors located in the head and neck region, where it targets any microscopic cancer cells remaining in the area. The role of chemotherapy is less clear and is generally reserved for advanced cases where the cancer has metastasized to distant sites or when the tumor is unresectable. Treatment decisions usually involve a multidisciplinary team of specialists, including surgeons, oncologists, and radiation oncologists, to develop an individualized strategy for management.