Sarcomatoid Carcinoma: Symptoms, Types, Causes and Treatment

Sarcomatoid carcinoma is a rare and aggressive form of cancer that combines features of both carcinoma (epithelial origin) and sarcoma (mesenchymal origin). Its unique biology leads to rapid progression, significant diagnostic challenges, and often limited treatment options. This article provides a comprehensive overview of sarcomatoid carcinoma, including its symptoms, types, causes, and current treatments, drawing on the latest clinical and research evidence.

Symptoms of Sarcomatoid Carcinoma

Sarcomatoid carcinoma can develop in various organs, and its symptoms often depend on the tumor's location and the stage at diagnosis. However, this cancer is notable for its rapid growth and tendency to present at an advanced stage, often leading to systemic symptoms.

Symptom	Organ/System	Typical Presentation	Source
Cough, back pain, weight loss	Lung/Spine	Persistent cough, localized or radiating pain, unintentional weight loss	1 11
Abdominal pain, jaundice, anorexia	Gallbladder/Liver	Upper abdominal pain, yellowing of skin/eyes, decreased appetite	2 9
Diffuse pain, palpable mass, nausea	General (various)	Non-specific, often late-stage findings	2 3 13
Systemic symptoms	Multiple	Fatigue, cachexia, fever	1 3 8 11

Table 1: Key Symptoms

Symptom Profiles by Organ

Sarcomatoid carcinoma’s symptoms are heavily influenced by the tumor’s location:

• Lung: The most common symptoms are persistent cough, hemoptysis (coughing up blood), chest or back pain, and shortness of breath. Patients may also report weight loss and fatigue due to the aggressive nature of the tumor. Occasionally, the cancer may spread to the spine, causing neurological symptoms or severe back pain 1 4 11 13.
• Kidney: Sarcomatoid renal cell carcinoma may cause flank pain, blood in the urine (hematuria), abdominal or back pain, and sometimes a palpable mass. Systemic symptoms like fever, weight loss, and night sweats may be present if the disease is advanced 3 6 8.
• Gallbladder and Liver: Patients may present with abdominal pain, jaundice, anorexia, nausea, and weight loss. A palpable abdominal mass and symptoms related to liver dysfunction (such as cholangitis or sepsis) can also occur, especially if there’s metastatic disease 2 9.
• Other Sites: Sarcomatoid carcinoma can also occur in the skin, bone, breast, thyroid, pancreas, and urinary tract. Local symptoms such as pain, swelling, or the presence of a mass are common, with systemic signs appearing as the disease progresses 1 3.

Systemic Manifestations

Regardless of the organ, advanced sarcomatoid carcinoma frequently causes systemic symptoms such as:

• Profound fatigue
• Unexplained weight loss
• Cachexia (muscle wasting)
• Fever or night sweats

These symptoms often reflect the cancer’s aggressive behavior and high rate of metastasis at diagnosis 1 3 8 11.

Types of Sarcomatoid Carcinoma

Sarcomatoid carcinoma is not a single disease, but rather a group of cancers that share similar histological features. These tumors can arise in various organs, each with multiple subtypes and unique clinical implications.

Type/Subtype	Location	Distinctive Feature	Source
Pulmonary Sarcomatoid Carcinoma (PSC)	Lung	Five histological subgroups (e.g., pleomorphic, giant cell, spindle cell)	1 4 11 13
Sarcomatoid Renal Cell Carcinoma (sRCC)	Kidney	High-grade transformation in all RCC subtypes	3 5 6 7 8 12
Gallbladder Sarcomatoid Carcinoma	Gallbladder	Carcinosarcoma features, highly aggressive	2
Hepatic Sarcomatoid Carcinoma	Liver	Sarcomatoid change in hepatocellular or cholangiocarcinoma	9
Other Sites	Thyroid, Skin, Breast, Bone, Pancreas, Urinary tract	Rare, organ-specific presentations	1

Table 2: Major Types and Subtypes of Sarcomatoid Carcinoma

Pulmonary Sarcomatoid Carcinoma (PSC)

PSC represents a rare, poorly differentiated subset of non-small-cell lung cancer (NSCLC). It is further classified into five histologic subtypes:

• Pleomorphic carcinoma
• Giant cell carcinoma
• Spindle cell carcinoma
• Carcinosarcoma
• Pulmonary blastoma

PSC is characterized by aggressive behavior, frequent metastasis, and poor response to conventional chemotherapy 1 4 11 13.

Sarcomatoid Renal Cell Carcinoma (sRCC)

Sarcomatoid differentiation can occur in any subtype of renal cell carcinoma, including clear cell, papillary, chromophobe, and collecting duct carcinoma 3 6 7. This feature is associated with:

• High-grade transformation
• Poor prognosis
• Elevated rates of metastasis (often to lungs, bones, liver)
• Histologically, the sarcomatoid component may resemble fibrosarcoma, malignant fibrous histiocytoma, or undifferentiated sarcoma 3 7 8.

Gallbladder and Hepatic Sarcomatoid Carcinomas

Gallbladder and liver sarcomatoid carcinomas are exceedingly rare. They often present as carcinosarcomas (with both epithelial and mesenchymal elements) and are almost always diagnosed at an advanced stage, with rapid progression and poor outcomes 2 9.

Other Organ Sites

Sarcomatoid carcinoma can, albeit rarely, originate in:

• Thyroid
• Skin
• Breast
• Bone
• Pancreas
• Urinary tract

These presentations are typically aggressive, with local symptoms determined by the organ of origin and a high likelihood of systemic involvement 1.

Causes of Sarcomatoid Carcinoma

The exact causes of sarcomatoid carcinoma are still being unraveled, but several risk factors and pathogenic mechanisms have been identified. The development of these tumors involves both genetic and environmental factors, as well as unique molecular pathways.

Cause/Factor	Role in Development	Example/Organ	Source
Smoking	Major risk factor	Lung, kidney	1 11 13
Chronic Inflammation	May promote transformation	Gallbladder, liver	2 9
Genetic Mutations	High-grade transformation	TP53, BAP1, MYC	5 9 12
Epithelial-Mesenchymal Transition (EMT)	Drives dedifferentiation	Renal cell carcinoma	6 12
Underlying Carcinoma	Sarcomatoid change occurs in pre-existing carcinoma	RCC, hepatocellular carcinoma	3 6 8 9 12

Table 3: Key Causes and Risk Factors

Environmental and Lifestyle Risk Factors

• Smoking is a well-established risk factor for pulmonary sarcomatoid carcinoma and is also linked to renal cell carcinoma 1 11 13.
• Chronic inflammation (such as that caused by gallstones or chronic hepatitis) may contribute to the development of sarcomatoid carcinoma in the gallbladder and liver 2 9.

Genetic and Molecular Drivers

• Genetic mutations play a central role. TP53 mutations are common in sarcomatoid variants across multiple organs. In sarcomatoid renal cell carcinoma, BAP1 mutations, CDKN2A deletions, and MYC pathway activation have been identified, reflecting aggressive behavior 5 9 12.
• Epithelial-Mesenchymal Transition (EMT): A process where epithelial cells lose their characteristics and gain mesenchymal, migratory features; this is a hallmark of sarcomatoid differentiation in renal cell carcinoma and other organs 6 12.
• Underlying carcinoma: Sarcomatoid change is almost always seen as a high-grade transformation or dedifferentiation within a pre-existing carcinoma (e.g., clear cell or papillary RCC, hepatocellular carcinoma) rather than as a primary tumor 3 6 8 9 12.

Other Considerations

• Immunocompromised states: Although not fully established, there are case reports of sarcomatoid carcinoma in patients with HIV and other immunodeficiencies, suggesting the immune system may play a protective role 1.
• No single driver: Unlike some cancers, sarcomatoid carcinoma does not have a single defining mutation or risk factor; rather, it represents a convergence of high-risk features leading to a particularly aggressive phenotype 5 12.

Treatment of Sarcomatoid Carcinoma

Treating sarcomatoid carcinoma is challenging due to its aggressiveness, resistance to conventional therapies, and advanced stage at presentation. However, new therapeutic avenues are emerging, especially in renal and pulmonary subtypes.

Treatment Approach	Indication	Outcome/Notes	Source
Surgical resection	Localized disease	Best chance for cure, but recurrence common	1 2 6 8 11 13
Chemotherapy	Advanced/metastatic	Limited efficacy, high resistance	2 11 13
Immune checkpoint inhibitors (ICIs)	Advanced/metastatic (esp. RCC)	Improved survival, response rates >50%	5 8 10 12
Targeted therapy	Selected patients	Modest benefit, less effective than ICIs	10 13
Palliative care	Advanced, refractory	Symptom management, quality of life	2 8

Table 4: Treatment Strategies and Their Effectiveness

Surgery

• Localized tumors: Surgical removal (resection, nephrectomy, lobectomy) remains the mainstay for localized disease, offering the best chance for prolonged survival. However, recurrence rates are high due to the aggressive nature of the disease 1 2 6 8 11 13.
• Cytoreductive surgery: In metastatic renal cases, the benefit of removing the primary tumor is debated, especially when distant metastases are present 8.

Chemotherapy

• Limited response: Traditional chemotherapy regimens, including platinum-based combinations, have shown poor efficacy in most sarcomatoid carcinomas, with rapid progression and low overall survival 2 11 13.
• Adjuvant chemotherapy: Some studies suggest adjuvant chemotherapy may benefit surgically treated lung sarcomatoid carcinoma patients, particularly those with advanced stage or positive lymph nodes 13.

Immune Checkpoint Inhibitors (ICIs)

• A breakthrough for renal cell carcinoma: ICIs targeting PD-1/PD-L1 have significantly improved outcomes in sarcomatoid RCC. Response rates can exceed 50%, with some patients achieving complete remission 5 8 10 12.
• Rationale: These tumors often express high levels of PD-L1, making them suitable for immunotherapy 5 8 9 12.
• Lung and other sites: Research is ongoing to establish the role of ICIs in sarcomatoid carcinoma of the lung and other organs.

Targeted Therapy

• Mixed results: Agents such as sunitinib (a VEGF inhibitor) have been used, but with less success in sarcomatoid RCC compared to non-sarcomatoid cases. ICIs are now preferred as first-line therapy for advanced disease 10 13.

Palliative Care

• Symptom management: For patients ineligible for surgery or systemic therapy, palliative care is essential for maintaining quality of life. This may include pain control, management of complications (e.g., jaundice or sepsis), and hospice care 2 8.

Key Considerations

• Multidisciplinary approach: Optimal management requires collaboration among oncologists, surgeons, pathologists, and palliative care teams.
• Clinical trials: Given the rarity and aggressiveness of sarcomatoid carcinoma, enrollment in clinical trials is encouraged to access novel therapies and contribute to knowledge advancement 8 10 12.

Conclusion

Sarcomatoid carcinoma remains one of the most challenging and aggressive cancers encountered in medicine. Its rarity, rapid progression, and poor response to conventional therapies demand a nuanced, evidence-based approach. Here are the main takeaways:

• Symptoms depend on tumor location but commonly include pain, mass effect, and systemic signs like weight loss and fatigue.
• Multiple organ sites: Sarcomatoid carcinoma can arise in the lung, kidney, gallbladder, liver, and other organs, each with distinct subtypes and presentations.
• Underlying causes involve a combination of environmental risk factors (such as smoking and chronic inflammation), high-grade genetic mutations (notably TP53, BAP1), and processes like epithelial-mesenchymal transition.
• Treatment is evolving: Surgery remains first-line for localized disease, but immunotherapy—especially immune checkpoint inhibitors—now offers hope for advanced cases, particularly in renal cell carcinoma. Chemotherapy and targeted therapies have limited success.
• Multidisciplinary care and clinical trials are essential to improve outcomes and discover new therapeutic strategies.

In summary:

• Sarcomatoid carcinoma is rare, aggressive, and often presents late.
• Its symptoms and prognosis vary by site but are universally severe.
• New therapies, particularly immunotherapy, are beginning to change the outlook for some patients.
• Early diagnosis, multidisciplinary management, and research participation are key to improving survival and quality of life.