Malignant Transformation of Metaplastic Thymoma into High-Grade Sarcomatoid Carcinoma: A Case Report.

The correlation of histogenesis between metaplastic thymoma and thymic sarcomatoid carcinoma is unclear. We report a case of metaplastic thymoma transformed into high-grade sarcomatoid carcinoma. A 64 × 54 × 32 mm anterior mediastinal mass in a 61-year-old woman microscopically consisted mainly of classic metaplastic thymoma, with the center dominated by high-grade sarcomatoid carcinoma. In some areas, both epithelial and spindle cell components of the metaplastic thymoma showed increased cellular atypia, mitotic activity, and focal necrosis and gradually transformed into the polygonal/pleomorphic and spindle cell components of sarcomatoid carcinoma. Immunohistochemically, the characteristics of the polygonal/pleomorphic sarcomatoid cells were similar to those of the epithelial component of metaplastic thymoma, while the spindle sarcomatoid cells were more similar to the spindle cells component of metaplastic thymoma. The Ki-67 index was less than 5% in the metaplastic thymoma areas but up to 70% in the sarcomatoid carcinoma area. Radical operation and postoperative radiotherapy were performed. Multifocal relapses at the pleura occurred 13 months after surgery.

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer.

Background: The present study aimed to evaluate the effects of concomitant proton pump inhibitor (PPI) use on immune checkpoint inhibitor (ICI) efficacy among advanced cancer patients. Methods and Materials: A systematic literature search of electronic database was performed to identify all potential reports. Then, meta-analyses were conducted to obtain pooled HRs with 95% CIs, which reveal the influence of PPI use on PFS and OS in patients receiving ICI treatment. Results: A total of 7 studies with 3,647 advanced cancer patients fulfilled the inclusion criteria. The impact of PPI use was then evaluated on 3,340 patients for PFS and 3,647 patients for OS. Concomitant PPI use has a detrimental effect on the efficacy of ICIs that PPI use increased the risk of progression by 28% (HR = 1.28, 95% CI 1.17-1.40; I2 = 31.3%, Q test P = .21) when compared to those not receiving PPIs. Similarly, the meta-analysis showed that PPI use was also associated with shorter OS of advanced cancer patients receiving ICIs that PPI use increased risk of death by 39% (HR = 1.39, 95% CI 1.26-1.54; I2 = 36.5%, Q test P = .16). Sensitivity analysis showed that the pooled HRs were constant after excluding one study at a time, and no significant publication biases were detected. Conclusion: The meta-analysis suggested that concomitant PPI use is significantly associated with low clinical benefit in ICI treatment, revealing a significantly reduced PFS and OS in advanced cancer patients receiving ICIs who are also exposed to PPI.

HER2 Splice Site Mutation c.1899-1G>A as the Potential Acquired Resistance to Trastuzumab in a Patient with HER2-Positive Gastric Adenocarcinoma.

The addition of trastuzumab to chemotherapy regimen is the standard of care for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer; however, most patients eventually acquire trastuzumab resistance. Although some resistance mechanisms to trastuzumab-based regimens have been proposed, further understanding is required for developing therapeutic strategies to overcome the resistance. In the present work, we attempted to determine the possible resistance mechanism to trastuzumab in a patient with HER2-positive stage IV gastric adenocarcinoma. In this study, we first report the nucleotide change c.1899-1G>A at the intron 15 acceptor splice site promoting exon 16 deletion of HER2 as the potential mechanism of trastuzumab resistance in HER2-positive gastric adenocarcinoma. KEY POINTS: The combination of trastuzumab with chemotherapy is considered to be the standard therapy for HER2-positive advanced gastric cancer (GC), but most of the patients eventually acquire trastuzumab resistance. The mechanisms of resistance to trastuzumab in GC are poorly characterized. To the best of the authors' knowledge, this study is the first to implicate HER2 c.1899-1G>A, which results in exon 16 skpping, as the acquired resistance mechanism to trastuzumab in HER2-positive gastric adenocarcinoma. This work provides insights into the potential molecular mechanism of trastuzumab resistance, which is crucial in developing effective therapeutic strategies for HER2-positive GC patients refractory to trastuzumab.

GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis.

Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.