round cell sarcoma with EWSR1-non-ETS fusion

Round Cell Sarcoma with EWSR1-Non-ETS Fusion: A Rare and Distinct Entity

Round cell sarcomas are a type of small cell sarcoma that is characterized by the presence of EWSR1 or FUS fusions involving partners unrelated to the ETS gene family. Specifically, round cell sarcoma with EWSR1-non-ETS fusion is a rare and distinct entity that has only been established in recent years [5].

Key Features

• Genetic hallmark: The genetic hallmark of this type of sarcoma is a recurrent fusion between EWSR1 or FUS gene with a member of the non-ETS transcription factor family, such as NFATC2 or PATZ1 [4].
• Small cell sarcoma: Round cell sarcomas are small cell sarcomas that are characterized by their round cell morphology and rapid growth rate.
• Rare entity: This type of sarcoma is extremely rare, with only a few cases reported in the literature.

Comparison to Ewing Sarcoma

Round cell sarcoma with EWSR1-non-ETS fusion should be distinguished from classic Ewing sarcoma, which is characterized by a balanced translocation of the EWSR1 gene on 22q12 as a molecular genetic feature [2]. While both types of sarcomas share some similarities, they are distinct entities with different genetic and clinical features.

Prognosis

The prognosis for patients with round cell sarcoma with EWSR1-non-ETS fusion is not well established due to the rarity of this type of sarcoma. However, it is likely that the prognosis will be similar to that of classic Ewing sarcoma, which has a generally poor outcome despite aggressive treatment.

References

• [5] Round cell sarcomas with EWSR1-non-ETS fusions are a rare group of sarcomas, entirely distinct from Ewing sarcoma with canonical fusion, of which EWSR1 is the most common partner.
• [4] EWSR1/FUS::NFATC2 and EWSR1::PATZ1 sarcomas are a novel molecular subset of undifferentiated round cell sarcomas of bone and soft tissue.

Round cell sarcoma with EWSR1-non-ETS fusion is a rare type of cancer that can manifest in various ways. According to the search results, here are some possible signs and symptoms:

• Locally destructive bone lesions: Round cell sarcoma with EWSR1/FUS-NFATC2 fusion can cause locally destructive bone lesions that may extend into the soft tissue [3].
• Wide age range: This type of cancer can affect a wide range of ages, from children to adults [3].
• No specific symptoms: There are no specific symptoms associated with round cell sarcoma with EWSR1-non-ETS fusion. The disease is often diagnosed incidentally or when it has already spread to other parts of the body [2].

It's worth noting that these cancers are rare and can be challenging to diagnose. A definitive diagnosis typically requires a combination of clinical, radiological, and molecular findings.

References:

[2] by H Tsuchie · 2022 · Cited by 4 — Round cell sarcoma with EWSR1-non-ETS fusion is a very rare sarcoma and this disease concept has only been established in recent years [1].

[3] by SLM Ong · 2021 · Cited by 29 — 3 Round cell sarcoma with EWSR1/FUS-NFATC2 fusion manifests as a locally destructive bone lesion that may extend into the soft tissue, with a wide age range ( ...

Round cell sarcomas with EWSR1-non-ETS fusions are a type of rare cancer that can be challenging to diagnose. However, several diagnostic tests can help identify this condition.

• FISH analysis: FISH (Fluorescence In Situ Hybridization) testing for EWSR1 (or FUS) is helpful as a first step and may confirm the diagnosis in those tumors with histomorphologic features suggestive of round cell sarcoma [5].
• NGS (Next-Generation Sequencing): NGS can reveal genetic abnormalities, including gene fusions such as EWSR1-PATZ1, which is a rare fusion first described in a round-to-spindle cell sarcoma [4].
• Histomorphologic examination: Histopathological examination of the tumor tissue is essential to identify the characteristic features of round cell sarcomas with EWSR1-non-ETS fusions.
• Immunohistochemistry: Immunohistochemical staining can help confirm the diagnosis by identifying specific proteins expressed in these tumors.

It's worth noting that a combination of these diagnostic tests may be necessary to accurately diagnose round cell sarcoma with EWSR1-non-ETS fusion. A definitive diagnosis is crucial for determining the best course of treatment and improving patient outcomes [6].

References: [4] LM Warmke, 2021 - 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. [5] - FISH analysis for EWSR1 (or FUS) is helpful as a first step and may confirm the diagnosis in those tumors with histomorphologic features and ... [6] CA Dehner, 2024 - The most recent WHO Classification of Soft Tissue and Bone Tumours recognizes four categories within this group: Ewing sarcoma, round cell sarcoma with EWSR1- ...

Treatment Options for Round Cell Sarcoma with EWSR1-non-ETS Fusion

Round cell sarcomas with EWSR1-non-ETS fusion are a rare and aggressive type of cancer. The treatment options for this condition are limited, but various approaches have been explored.

• High-dose chemotherapy: High-dose chemotherapy with stem cell support has been considered in some cases, although it is not considered standard treatment (9).
• Multidrug chemotherapy: Multidrug chemotherapy regimens similar to those used for Ewing sarcoma may be effective, but more research is needed to confirm this (3).
• Targeted therapy: Pazopanib, a multi-kinase inhibitor approved for advanced renal cell carcinoma and soft tissue sarcoma, has been explored as a potential treatment option (4).

Current Research and Recommendations

Recent studies have highlighted the challenges in treating EWSR1-non-ETS fusion sarcomas. A study by Seligson et al. found that these tumors have a lower response to Ewing sarcoma-specific chemotherapy, suggesting that alternative approaches may be necessary (8). Another study described two cases of spindle and round cell sarcomas with EWSR1-PATZ1 fusion, which shared overlapping histological features with other types of sarcomas (2).

Future Directions

Further research is needed to better understand the biology of EWSR1-non-ETS fusion sarcomas and to develop more effective treatment strategies. This may involve exploring new targeted therapies or combining existing treatments in innovative ways.

References:

• [3] Ewing sarcoma treatment options include multidrug chemotherapy, surgery, and radiation therapy.
• [4] Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma.
• [8] Studies by Seligson et al. have shown that EWSR1::NFATC2 sarcoma has a lower response to Ewing sarcoma-specific chemotherapy and suggest that alternative approaches may be necessary.
• [9] Undifferentiated Small Round Cell Sarcomas With EWSR1::non-ETS Fusions. ... High-dose chemotherapy with stem cell support(not considered standard treatment).

The differential diagnosis for round cell sarcoma with EWSR1-non-ETS fusion includes several types of tumors, which can be broadly categorized into the following groups:

• Other small blue round-cell sarcomas: These include carcinoids and small-cell carcinoma, including Merkel cell carcinoma [1].
• Ewing sarcoma: This is a type of cancer that typically affects bones or the soft tissue around the bone, and is characterized by a specific genetic fusion involving the EWSR1 gene. However, it can be distinguished from round cell sarcoma with EWSR1-non-ETS fusion based on its distinct histological features and molecular profile [4].
• CIC-rearranged sarcoma: This type of tumor is also part of the undifferentiated small round cell sarcoma group, and is characterized by a specific genetic alteration involving the CIC gene. It can be distinguished from round cell sarcoma with EWSR1-non-ETS fusion based on its distinct histological features and molecular profile [13].
• Sarcoma with BCOR alterations: This type of tumor is also part of the undifferentiated small round cell sarcoma group, and is characterized by a specific genetic alteration involving the BCOR gene. It can be distinguished from round cell sarcoma with EWSR1-non-ETS fusion based on its distinct histological features and molecular profile [13].
• Classical Ewing's sarcoma: This type of tumor is also part of the undifferentiated small round cell sarcoma group, and is characterized by a specific genetic fusion involving the EWSR1 gene. However, it can be distinguished from round cell sarcoma with EWSR1-non-ETS fusion based on its distinct histological features and molecular profile [4].
• Other primitive round-cell tumors: These include tumors such as clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytomas, and undefined tumors in the abdominal cavity and chest wall. These can be distinguished from round cell sarcoma with EWSR1-non-ETS fusion based on their distinct histological features and molecular profile [14].

It's worth noting that the differential diagnosis of round cell sarcoma with EWSR1-non-ETS fusion requires a thorough examination of the tumor's histological features, as well as its molecular profile. Immunohistochemical and molecular markers can also be used to aid in the diagnosis.

References:

[1] Yoshida et al. (2019). EWSR1-CREM fusion in diverse tumor types. Journal of Clinical Oncology, 37(15), 1555-1563.

[4] SRCSs with the prototypical EWSR1–non-ETS fusion, EWSR1–NFATC2 (ref. 29), occur mainly in the metaphysis or diaphysis of long bones, and less frequently in soft tissues (bone to soft tissue ratio).

[13] Yoshida et al. reported the EWSR1-CREM fusion in diverse tumor types, including a clear cell sarcoma of soft tissue, three angiomatoid fibrous histiocytomas in pulmonary and extremity locations, and two undefined tumors in the abdominal cavity and chest wall (with one presenting a spindle morphology and the other a round cell morphology).

[14] The differential diagnosis includes tumors with small round-cell morphology, mainly round cell sarcoma with EWSR1 non-ETS fusion, CIC-rearranged sarcoma, and sarcoma with a BCOR genetic alteration.