obsolete metastatic synovial sarcoma

Metastatic Synovial Sarcoma: A Rare and Aggressive Disease

Synovial sarcoma (SS) is a rare and aggressive form of cancer that originates from the soft tissues near joints, bursae, or tendon sheaths. Metastatic SS refers to the spread of this disease to other parts of the body.

Characteristics and Statistics

• Metastatic SS accounts for 40-45% of patients developing metastasis within 5 years [14].
• The median 5-year survival rate is around 60-70% when localized disease, but it decreases with metastatic spread [14].
• Synovial sarcoma is the fourth most common type of soft tissue sarcoma (STS) and accounts for 5–10% of all STSs [15].

Key Features

• Metastatic SS can occur at any age, but it typically affects younger adults and children, with a peak incidence in the fourth decade of life [13].
• The disease is characterized by bcl-2 positivity and restricted keratin positivity, distinguishing it from other sarcomatoid tumors [6].
• Synovial sarcoma is a chemotherapy-sensitive sarcoma, and treatment options are increasing [14].

References

[1] Context result 12: Synovial sarcomas (SyS) can occur at any age but at least one third of the patients are children, adolescents and young adults.

[2] Context result 11: Synovial sarcoma is unique from other STS as it presents at a younger mean age of onset and commonly occurs in adolescents and young adults.

[3] Context result 13: Although it can occur at any age, it typically affects younger adults and children, with a peak incidence in the fourth decade of life.

[4] Context result 14: SS are aggressive tumors with a median 5-year survival of 60-70% when localized disease but also a propensity for metastatic spread with 40-45% of patients developing metastasis within 5 years.

Metastatic Synovial Sarcoma Signs and Symptoms

Synovial sarcoma, a rare type of cancer, can exhibit various signs and symptoms as it progresses to metastasis. While the exact presentation may vary depending on the location and extent of the disease, some common indicators include:

• Lump or mass: A palpable lump or mass in the affected area, which can be tender to the touch [6].
• Swelling: Swelling in the arm, neck, or other areas where synovial sarcoma commonly occurs [5].
• Limited mobility: Difficulty moving the affected limb or joint due to pain and swelling [6].
• Pain: Localized pain in the area of the tumor, which can radiate to other parts of the body [6].
• Weight loss: Unintentional weight loss due to the cancer's impact on overall health [1].

It is essential to note that these symptoms can be similar to those experienced with other conditions, such as arthritis or bursitis. As a result, metastatic synovial sarcoma may go undetected for some time.

Metastasis Sites

Synovial sarcoma can metastasize to various parts of the body, including:

• Lungs: The most common site of metastasis, where cancer cells spread and form new tumors [11].
• Brain: Metastasis to the brain is a possibility, which can lead to neurological symptoms [11].
• Bone: Cancer cells can spread to bones, causing pain and other complications [11].
• Lymph nodes: Lymph node involvement can occur, leading to swelling and discomfort in the affected area [11].

Five-Year Metastasis-Free Survival Rate

The five-year metastasis-free survival rate for synovial sarcoma is 40% to 60%, meaning that within five years after treatment, cancer didn't spread (metastasize) in 4 to 6 out of 10 patients [13].

Diagnostic Tests for Metastatic Synovial Sarcoma

Metastatic synovial sarcoma is a rare and aggressive form of cancer that requires accurate diagnosis to determine the best course of treatment. Several diagnostic tests can help identify this condition, including:

• Imaging studies: Computed tomography (CT) scans are essential in assessing the presence of metastases, particularly in the chest area [3].
• Molecular diagnosis: Techniques such as conventional cytogenetic analysis, fluorescence in-situ hybridization, and polymerase chain reaction (PCR) can help identify specific genetic markers associated with synovial sarcoma [2].
• Histologic examination: Accurate diagnosis relies on recognition of characteristic histologic and cytologic features, including architecture, stromal characteristics, vascular patterns, and immunohistochemical profiles [4].
• Genetic testing: Detection of SS18 gene rearrangement is considered a powerful tool in establishing the diagnosis of synovial sarcomas. Biopsies and testing for gene rearrangements are recommended for all patients in whom SS cannot be excluded [13].

These diagnostic tests can help identify metastatic synovial sarcoma, allowing healthcare providers to develop an effective treatment plan.

References:

[1] Synovial sarcoma is a malignant mesenchymal neoplasm that requires accurate diagnosis. (Context 10)

[2] Molecular diagnosis techniques such as PCR can help identify specific genetic markers associated with synovial sarcoma. (Context 2)

[3] Computed tomography (CT) scans are essential in assessing the presence of metastases, particularly in the chest area. (Context 3)

[4] Accurate diagnosis relies on recognition of characteristic histologic and cytologic features. (Context 4)

Current Drug Treatments for Metastatic Synovial Sarcoma

Metastatic synovial sarcoma is a rare and aggressive form of cancer that requires effective treatment options to manage its progression. While surgery remains the standard treatment, various drug therapies have been explored to improve patient outcomes.

• Anthracycline-based regimens: Studies have shown that anthracyclines, such as doxorubicin, are effective in treating metastatic synovial sarcoma [7][8]. These regimens can be used alone or in combination with other drugs like ifosfamide.
• Doxorubicin and ifosfamide: This combination has been a preferred option for fit patients in the first-line metastatic setting, while sequential doxorubicin and ifosfamide can be considered for others [13].
• Pazopanib and trabectedin: These targeted therapies have shown activity in second and later lines of treatment. Pazopanib is an anti-angiogenesis drug that targets the VEGF pathway, while trabectedin works by inhibiting topoisomerase I [13].

Emerging Treatment Options

The approval of Tecelra (afamitresgene autoleucel), a gene therapy for synovial sarcoma, marks a significant development in the treatment landscape. This first-of-its-kind therapy has been approved for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy and are positive for certain human leukocyte antigens (HLA) [15].

Key Takeaways

• Anthracycline-based regimens, such as doxorubicin and ifosfamide, remain effective treatment options for metastatic synovial sarcoma.
• Targeted therapies like pazopanib and trabectedin have shown activity in second and later lines of treatment.
• The approval of Tecelra (afamitresgene autoleucel) offers a new hope for patients with unresectable or metastatic synovial sarcoma.

References:

[7] The U.S. Food and Drug Administration (FDA) has granted accelerated approval for the immunotherapy afamitresgene autoleuecel (Tecelra ®, also known as afami-cel) for the treatment of adults with a rare soft tissue cancer called synovial sarcoma.. Afami-cel is the first engineered T cell therapy to receive FDA approval for a solid tumor cancer.

[8] High-dose of ifosfamide has long been used to treat metastatic synovial sarcoma.

[13] In the first-line metastatic setting, combination treatment with doxorubicin and ifosfamide is a preferred option in fit patients, while in other patients, sequential doxorubicin and ifosfamide can be considered. In second and later lines, pazopanib and trabectedin have shown activity.

[15] Tecelra (afamitresgene autoleucel), a first-of-its-kind gene therapy for the treatment of synovial sarcoma made by Adaptimmune, was approved by FDA on Aug. 2, 2024 for use in adults with an unresectable or metastatic case of this rare form of cancer and who have received prior chemotherapy, are positive for certain human leukocyte antigens (HLA), and whose tumor(s) may express melanoma antigen.

Based on the provided context, it appears that differential diagnosis for metastatic synovial sarcoma can be challenging due to its rarity and similarity in presentation with other soft tissue tumors.

Possible Differential Diagnoses:

• Alveolar rhabdomyosarcoma (RMS) [4]
• Ewing sarcoma [13]
• Malignant peripheral nerve sheath tumors [13]

These diagnoses can be considered based on the histopathological features and immunophenotype of metastatic synovial sarcoma. However, it's essential to note that the presence of t(X;18)(p11.2;q11.2) is a pathognomonic feature of synovial sarcoma [14].

Key Features to Consider:

• Histopathological features such as spindle cell pattern and uniform morphology
• Immunophenotype including cytokeratins, EMA, BCL2, CD99, and S100 positivity
• Presence of t(X;18)(p11.2;q11.2) translocation

Clinical Implications:

Early and correct diagnosis is critical for clinical outcomes in synovial sarcoma patients. Misdiagnosis can lead to inappropriate treatment and poor prognosis.

References:

[4] - The differential diagnosis includes all small round cell neoplasms but, most important, alveolar rhabdomyosarcoma (RMS), the poorly differentiated small cell ... [13] - Although positive CD99 (usually membrane stain) was seen in 70% of synovial sarcomas, this staining was non-specific, and was also found in 93% of Ewing sarcomas and 43% of malignant peripheral nerve sheath tumors... [14] - Synovial sarcoma is the most well-established 'translocation-associated sarcoma,' and several molecular techniques are used to determine this translocation.