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Thoracic SMARCA2-deficient But SMARCA4-preserved Tumors With Undifferentiated Morphology Combined With Claudin-4
Akari Iwakoshi1, Eiichi Sasaki2, Mariko Sato3
1Departments of Pathology.
Abstract:
Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized tumor characterized by inactivation of SMARCA4, a SWItch/Sucrose NonFermentable chromatin remodeler, detectable by immunohistochemistry. SMARCA4-UT shows undifferentiated or rhabdoid morphology with claudin-4 negativity. However, thoracic undifferentiated tumors with the same histologic features as SMARCA4-UTs but a preserved SMARCA4 expression have so far been underrecognized. We herein report 3 cases of thoracic undifferentiated tumors with isolated loss of SMARCA2 but retained expression of SMARCA4 and SMARCB1. The present tumors were found in 2 men and 1 woman, 40 to 50 years old. All patients were heavy smokers (≥20 pack-years). The tumors were generally large masses located in the mediastinum, lung>chest wall, or lung and composed of relatively monotonous, round to epithelioid cells with variably rhabdoid cells. Immunohistochemically, the tumors showed claudin-4 negativity with variable expression of cytokeratin. All cases showed highly aggressive clinical behavior with overall survival of 2 to 10 months. These SMARCA2-deficient tumors with preserved SMARCA4 expression appeared to be clinicopathologically indistinguishable from SMARCA4-UTs, except for in their SMARCA4 status. This variant may expand the spectrum of SWItch/Sucrose NonFermentable-deficient undifferentiated tumors of the thoracic region beyond SMARCA4-UT.
Insights
Newly identified thoracic undifferentiated tumors show SMARCA2 deficiency with preserved SMARCA4 expression. These aggressive tumors are clinicopathologically similar to SMARCA4-UTs, expanding the spectrum of SWItch/Sucrose NonFermentable-deficient thoracic tumors.
Area of Science:
- Oncology
- Molecular Pathology
- Genetics
Background:
- Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recognized entity characterized by SMARCA4 inactivation and claudin-4 negativity.
- Undifferentiated thoracic tumors with similar morphology but preserved SMARCA4 expression have been underrecognized.
Observation:
- This report details 3 cases of thoracic undifferentiated tumors with isolated SMARCA2 loss but retained SMARCA4 and SMARCB1 expression.
- Patients were middle-aged heavy smokers presenting with large mediastinal or lung masses.
- Histologically, tumors showed monotonous round to epithelioid cells with rhabdoid features and claudin-4 negativity.
Findings:
- Immunohistochemistry confirmed isolated SMARCA2 deficiency with preserved SMARCA4 expression.
- Tumors exhibited aggressive clinical behavior with short overall survival (2-10 months).
- These SMARCA2-deficient tumors are morphologically and clinically similar to SMARCA4-UTs, differing mainly in SMARCA4 protein status.
Implications:
- This finding expands the spectrum of SWItch/Sucrose NonFermentable (SWI/SNF)-deficient undifferentiated tumors in the thorax.
- Recognizing this SMARCA2-deficient variant is crucial for accurate diagnosis and understanding of thoracic undifferentiated neoplasms.
- Further research is needed to elucidate the specific role of SMARCA2 in thoracic tumorigenesis and its clinical impact.
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