Distinct multiplex immunofluorescence-based immune and stromal marker expression profile of subcutaneously metastatic...

The SMARCA4 gene encodes the BRG1 protein, a key component of the switch (SWI)/sucrose nonfermenting (SNF) chromatin remodeling complex, and its loss has been implicated in the pathogenesis of various tumors. SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare, rapidly progressive, and highly aggressive subtype that is associated with a poor prognosis, with subcutaneous metastasis being one of its uncommon distant-spread phenotypes. The tumor microenvironment (TME) of SMARCA4-UT is closely associated with tumor metastasis and immunotherapeutic response, but the expression profiles of key immune and stromal markers in subcutaneous metastatic lesions have not been clarified.

A 49-year-old male patient with a history of heavy smoking experienced an insidious onset of symptoms, including a painful left lower-limb mass, dyspnea, chest tightness, and hoarseness. Diagnosis of SMARCA4-UT was confirmed by genetic testing of cancer and immunohistochemistry. The patient received four cycles of tislelizumab combined with albumin-bound paclitaxel and carboplatin, followed by four cycles of tislelizumab monotherapy maintenance. Multiplex immunofluorescence (mIF) staining was performed on the subcutaneous metastatic lesion tissue of the left lower limb to detect the expression patterns of six target molecules [CD20, CD56, CD8, programmed cell death protein 1 (PD-1), CD68, and pan-CK], with ZEN software (Zeiss) being used for qualitative and quantitative analysis. The patient's general condition improved significantly after treatment; dyspnea, chest tightness, and left lower-limb pain were resolved; and the best therapeutic response was partial response. mIF staining revealed varying intensities of positive signals for all six target markers in the subcutaneous metastatic lesion: CD56, PD-1, and pan-CK exhibited high expression, while CD8, CD68, and CD20 exhibited low expression.

SMARCA4-UT has an insidious onset and a diversity of metastatic sites, which can easily result in misdiagnosis, and genetic testing of cancer and immunostaining for SMARCA4 are crucial for achieving an accurate diagnosis. The distinct marker expression profile in subcutaneous metastatic lesions (high CD56, PD-1, and pan-CK expression with low CD8, CD68, and CD20 expression) reflects the unique TME of SMARCA4-UT, which may be related to its metastatic potential and immunotherapeutic response. Chemotherapy combined with immunotherapy shows promising efficacy in the treatment of SMARCA4-UT, and the mIF-based marker profile may provide a potential basis for optimizing individualized treatment strategies.