SMARCA4-Deficient NSCLC with Rare Sigmoid Colon and Adrenal Metastases: A Case Report

This case describes a 59-year-old man diagnosed with non-small cell lung cancer (NSCLC) carrying a deletion of the SMARCA4 gene, a subtype of lung cancer in which a chromatin-remodeling gene, part of the SWI/SNF complex that helps control how DNA is packaged and accessed, is lost. He initially presented with hoarseness and shortness of breath.

Imaging performed at presentation showed an irregular mass in the posterior apical segment of the upper lobe of the left lung, together with enlarged mediastinal and left hilar lymph nodes. Separate imaging also showed uneven thickening of the sigmoid colon wall.

Biopsy of the lung mass confirmed non-small cell lung cancer with SMARCA4 gene deletion. The sigmoid colon lesion was later assessed surgically, and pathology confirmed it as a metastasis originating from the lung cancer rather than a separate primary colon tumor.

Initial treatment consisted of chemotherapy combined with immunotherapy plus intensity-modulated radiotherapy directed at the lungs. After follow-up imaging showed progression of the sigmoid colon tumor, the patient underwent laparoscopic radical sigmoid colectomy with regional lymph node dissection. Following detection of a left adrenal gland metastasis two months after surgery, the treatment regimen was changed to a combination of gemcitabine, nedaplatin, bevacizumab, and camrelizumab.

Follow-up CT after the initial chemotherapy/immunotherapy and radiotherapy showed progression in the sigmoid colon tumor. Two months after the colectomy, imaging detected a new metastasis in the left adrenal gland.

After the treatment regimen was adjusted to gemcitabine, nedaplatin, bevacizumab, and camrelizumab, the patient demonstrated a favorable response. As of the most recent reported follow-up, there was no evidence of recurrence or further metastasis.

This case documents a SMARCA4-deficient NSCLC that spread first to mediastinal/hilar lymph nodes and then, unusually, to the sigmoid colon before adrenal involvement, and that showed progression of the colonic lesion despite initial chemo-immunotherapy and thoracic radiotherapy, followed by an apparently favorable response to a switched regimen of gemcitabine, nedaplatin, bevacizumab, and camrelizumab. Preclinical evidence makes the aggressive, multi-site behavior biologically plausible: BRG1/SMARCA4 is a recurrently inactivated tumor suppressor in lung cancer, and mouse/cell-line models link its loss to increased invasive and migratory capacity and an intrinsically pro-metastatic phenotype. These findings come from animal and cell-line systems, however, and were not designed to explain organ-specific tropism; none of the cited work addresses why a SMARCA4-deficient lung tumor would seed the sigmoid colon, a site epidemiological studies describe as a rare destination for lung cancer metastasis in general, in contrast to the adrenal gland, a comparatively common site. The apparent response to the camrelizumab-containing regimen invites a hypothesis that SWI/SNF loss created a more immunogenic, PD-L1-high, high-mutational-burden tumor state, a pattern reported in some human NSCLC cohorts. This hypothesis is directly challenged by other cohort data showing that SMARCA4 alterations often co-occur with STK11/KEAP1 mutations linked to checkpoint-inhibitor resistance, and that SMARCA4/SWI/SNF-altered NSCLC as a group shows heterogeneous, sometimes inferior, responses to checkpoint blockade. Because this patient's PD-L1 status, tumor mutational burden, and STK11/KEAP1 status were not reported, it is not possible to determine from the available evidence whether SMARCA4 loss meaningfully contributed to the observed treatment response, or whether the outcome instead reflects the specific four-drug combination or disease biology unrelated to SMARCA4.

The clinical course raises two separate biological questions that this evidence set addresses with differing confidence. The first is whether SMARCA4 loss plausibly explains the tumor's aggressive, multi-organ spread. Here the preclinical literature is reasonably consistent: chromatin remodeling disruption from BRG1/SMARCA4 loss is repeatedly associated, across independent mouse and cell-line models, with increased invasiveness and early metastatic features, giving a coherent, if indirect, mechanistic account for aggressive spread in general terms. The second, less settled question is whether SMARCA4 loss explains this tumor's specific choice of metastatic sites or its treatment response. On organotropism, the evidence available is entirely general: it documents that colonic metastasis from lung cancer is rare and adrenal metastasis comparatively common, and offers a general pre-metastatic-niche framework for why some organs are more permissive than others, but none of it examines whether SMARCA4 status changes an NSCLC tumor's organotropic preferences. The sigmoid colon lesion is therefore documented as unusual, but its biological explanation remains open. On treatment response, the evidence is genuinely mixed rather than supportive of a clean story. Associations between SWI/SNF loss and PD-L1/tumor mutational burden offer one candidate mechanism for immunotherapy benefit, but multiple independent cohort analyses describe SMARCA4-altered NSCLC as having heterogeneous, and at times inferior, outcomes to checkpoint inhibition, particularly when STK11/KEAP1 co-mutations are present, a status not reported for this patient. A mechanistic study in a different tumor type additionally illustrates that loss of related SWI/SNF subunits can impair rather than help antitumor immunity, underscoring that chromatin remodeling loss is not a monolithic event with one predictable immunological consequence. Separately, proposed chemoresistance mechanisms tied to BRG1/SMARCA4-altered chromatin state offer a plausible, though untested-in-this-regimen, explanation for why the sigmoid colon tumor progressed under initial chemo-immunotherapy and radiotherapy before responding to the later four-drug combination. Overall, the case is consistent with, but does not confirm, a role for SMARCA4 loss in driving this tumor's aggressiveness; it does not provide evidence sufficient to attribute the favorable late treatment response specifically to SMARCA4 status, and it leaves the mechanism of gastrointestinal metastatic tropism unresolved.

This analysis is based on a single published case report, which by design cannot establish causal relationships between SMARCA4 status and either the metastatic pattern or the treatment response observed; a single patient's course may reflect chance, unmeasured co-mutations, or regimen-specific effects rather than generalizable SMARCA4-driven biology. Key molecular details that would help interpret the case, including PD-L1 expression, tumor mutational burden, and STK11/KEAP1 co-mutation status, were not reported, limiting reconciliation of conflicting human-cohort evidence on SMARCA4 and immunotherapy outcomes. No formal TNM stage was given in the source. Much of the mechanistic evidence connecting SMARCA4 loss to invasiveness, metastasis, and chemoresistance derives from mouse models and cell lines, which may not reproduce human tumor behavior or organ-specific tropism. The evidence search underlying this analysis was scoped to sources addressing SMARCA4 biology, SWI/SNF complex function, and lung cancer metastatic patterns; it does not constitute an exhaustive systematic review, and additional relevant literature may exist outside the reviewed evidence map.

The published source does not include a patient-reported perspective, quality-of-life assessment, or first-person account of the diagnosis and treatment course.