round cell sarcoma with EWSR1-PATZ1 gene fusion

Round Cell Sarcoma with EWSR1-PATZ1 Gene Fusion: A Rare and Distinct Entity

Round cell sarcomas with EWSR1-PATZ1 gene fusion are a rare and distinct entity of tumors separate from prototypical Ewing sarcoma [5]. These tumors are characterized by the presence of an EWSR1-PATZ1 gene fusion, which is a rare fusion first described in a round-to-spindle cell sarcoma [3].

Clinical Features

The clinical features of round cell sarcomas with EWSR1-PATZ1 gene fusion are not well established due to their rarity. However, they have been reported to occur in the soft tissues and bone, with a predilection for thoracoabdominal soft tissues [8]. The tumors can present as spindle or round cell neoplasms, and may exhibit abundant intratumoral fibrosis and polyphenotypic differentiation, mimicking a range of other sarcomas [2].

Molecular Characteristics

The EWSR1-PATZ1 gene fusion is a result of a chromosomal translocation that fuses the EWSR1 gene with the PATZ1 gene. This fusion has been identified in fewer than 20 cases of round cell sarcoma, and is considered a rare molecular subset of undifferentiated round cell sarcomas [7].

Diagnostic Challenges

The diagnosis of round cell sarcomas with EWSR1-PATZ1 gene fusion can be challenging due to their rarity and overlapping clinical features with other sarcomas. A final diagnosis may require molecular testing, such as next-generation sequencing (NGS), to reveal the presence of the EWSR1-PATZ1 gene fusion [3].

References

• [5] KW Park et al., "Round cell sarcoma with EWSR1-PATZ1 fusion represent a rare distinct entity of tumors separate from prototypical Ewing sarcoma."
• [2] A Chougule et al., "EWSR1-PATZ1 fusion positive spindle and round cell sarcomas show abundant intratumoral fibrosis and polyphenotypic differentiation, thus mimicking a range of other sarcomas."
• [3] LM Warmke et al., "A final diagnosis was reached when NGS revealed an EWSR1-PATZ1 gene fusion, a rare fusion first described in a round-to-spindle cell sarcoma by Mastrangelo et al."
• [7] I Machado et al., "EWSR1/FUS::NFATC2 and EWSR1::PATZ1 sarcomas are a novel molecular subset of undifferentiated round cell sarcomas of bone and soft tissue."

Round cell sarcomas with EWSR1-PATZ1 gene fusion are a rare type of cancer that can manifest in various ways. According to the search results, here are some signs and symptoms associated with this condition:

• Painful bone lesions: These tumors often present as painful, locally destructive bone lesions that may invade surrounding soft tissues [2].
• Frequent pain: The sarcomas can be frequently painful, which is a notable symptom of EWSR1-NFATC2 and FUS-NFATC2 sarcomas [2].
• Locally destructive growth: The tumors tend to grow locally and can cause destruction of surrounding bone and soft tissues.
• Polyphenotypic differentiation: Round cell sarcomas with EWSR1-PATZ1 fusion are known to exhibit polyphenotypic differentiation, meaning they can show both neural and myogenic differentiation on immunohistochemistry [12].

It's essential to note that these symptoms may vary depending on the individual case and the specific location of the tumor. If you or someone you know is experiencing any unusual symptoms, it's crucial to consult a medical professional for proper evaluation and diagnosis.

References: [2] - Symptoms of EWSR1-NFATC2 and FUS-NFATC2 sarcomas. [12] - Histology features of round cell sarcomas with EWSR1-PATZ1 fusion.

Diagnostic Challenges and Approaches for Round Cell Sarcoma with EWSR1-PATZ1 Gene Fusion

The diagnosis of round cell sarcomas, particularly those harboring the EWSR1-PATZ1 gene fusion, can be challenging due to their rarity and overlapping morphological features with other tumor types. Various diagnostic tests have been employed to identify this specific subtype.

• Fluorescence In Situ Hybridization (FISH): While FISH has been used to detect the EWSR1-PATZ1 gene fusion, its sensitivity and specificity may be limited, as highlighted by recent studies [2].
• Next-Generation Sequencing (NGS): NGS has emerged as a powerful tool for identifying tumor-specific genetic alterations, including the EWSR1-PATZ1 gene fusion. This approach can provide a definitive diagnosis when used in conjunction with clinical and pathological findings [3].
• Molecular Diagnostics: The identification of characteristic oncogenic fusions, such as EWSR1-PATZ1, is crucial for diagnosing sarcoma subtypes, including small round blue cell tumors [6].

Key Considerations

• Further studies are required to improve the diagnostic accuracy and understanding of this rare tumor subtype.
• A multidisciplinary approach, involving clinical, pathological, and molecular evaluation, is essential for accurate diagnosis and management.

References:

[1] A Chougule · 2019 · Cited by 67 [2] Jan 18, 2021 [3] by LM Warmke · 2021 · Cited by 4 [6] by JA Bridge · 2019 · Cited by 93

Treatment Options for Round Cell Sarcoma with EWSR1-PATZ1 Gene Fusion

Round cell sarcomas with EWSR1-PATZ1 gene fusion are rare and aggressive tumors that require a multidisciplinary approach to treatment. The following treatment options have been reported in the literature:

• Surgery: Surgical resection is often the primary treatment for localized disease [5]. However, complete surgical resection may not be possible due to the infiltrative nature of these tumors [8].
• Multidrug Chemotherapy: Chemotherapy is a common treatment approach for round cell sarcomas with EWSR1-PATZ1 gene fusion [3]. The use of multidrug chemotherapy regimens has been reported in several case studies.
• Radiation Therapy: Radiation therapy may be used as an adjunct to surgery or as a standalone treatment for locally advanced or metastatic disease [6].
• Neoadjuvant Chemoradiation: Neoadjuvant chemoradiation has been used in some cases to downstage the tumor before surgical resection [4].

Current Challenges and Future Directions

Despite advances in treatment, round cell sarcomas with EWSR1-PATZ1 gene fusion remain a significant clinical challenge. The lack of standard therapy for locally advanced or metastatic disease is a major concern [7]. Further research is needed to develop effective treatment strategies for these patients.

References:

[3] Ewing sarcoma treatment options include multidrug chemotherapy, surgery, and radiation therapy. Treatment approaches titrate therapeutic effectiveness based on tumor characteristics and patient factors. [4] A final diagnosis was reached when NGS revealed an EWSR1-PATZ1 gene fusion, a rare fusion first described in a round-to-spindle cell sarcoma by Mastrangelo et al., which showed infiltrative growth, and the patient subsequently underwent surgical excision of the tumor and right neck lymph node dissection followed by adjuvant chemoradiation. [5] All but 1 patient received complete surgical resection; 7 were also treated with neoadjuvant chemo/radiotherapy. All cases showed typical histopathological features of Ewing sarcoma, including a high mitotic rate and the presence of Homer-Wright rosettes. [6] In general, local disease is managed via surgical resection; however, at present, there is no standard therapy for locally advanced or metastatic disease. Here, the patient underwent neoadjuvant chemoradiation followed by surgical resection. [7] However, currently, there is no standard therapy for locally advanced or metastatic disease. To the best of our knowledge, no previous case report has precisely described the treatment approach used in this case. [8] The EWSR1::PATZ1 fusion was initially described in isolated case reports and a small series of aggressive round-cell sarcomas, which showed infiltrative growth, and the patient subsequently underwent surgical excision of the tumor.

The differential diagnosis for round cell sarcoma with EWSR1-PATZ1 gene fusion includes other small round cell tumors, such as classical Ewing's sarcoma.

• Classical Ewing's sarcoma is a key differential diagnosis, and it can be morphologically similar to EWSR1/PATZ1 fusion sarcoma [9][10].
• Sarcomas with BCOR alterations not infrequently show a spindle cell pattern and should be considered in the differential diagnosis of synovial sarcoma and malignant peripheral nerve sheath tumors [11].
• Other small round cell tumors, such as alveolar rhabdomyosarcoma, neuroblastoma, and lymphomas, may also need to be ruled out in the differential diagnosis.

It's worth noting that molecular diagnostics play a crucial role in distinguishing between these entities. The identification of characteristic oncogenic fusions, such as EWSR1-PATZ1, can help guide the differential diagnosis [12].

References: [9] Liu L, et al. (2024). Cited by 2 — The most important differential diagnosis for EWSR1/FUS::NFATC2 sarcoma is classical Ewing's sarcoma. [10] Cote GM, Choy E, et al. Spindle and round cell sarcoma with EWSR1-PATZ1 gene fusion: a sarcoma with polyphenotypic differentiation...and genomic features of EWSR1-PATZ1 fusion sarcoma. Mod Pathol, 32... [11] Sarcomas with BCOR alterations not infrequently show a spindle cell pattern and should be considered in the differential diagnosis of synovial sarcoma and malignant peripheral nerve sheath tumors. [12] Molecular diagnostics of sarcoma subtypes commonly involve the identification of characteristic oncogenic fusions. EWSR1-PATZ1 is a rare fusion partnering in sarcoma, with few cases reported in...