Prognostic significance of immunohistochemical classification utilizing biopsy specimens in patients with extensive-disease small-cell lung cancer treated with first-line chemotherapy and immune checkpoint inhibitors.

PURPOSE: Although immune checkpoint inhibitors (ICIs), together with cytotoxic chemotherapy (chemoimmunotherapy), have been adapted for the initial treatment of extensive-disease small-cell lung cancer (ED-SCLC), they have achieved limited success. In ED-SCLC, a subtype of SCLC, the expression of immune-related molecules and clinical data are not well understood in relation to ICI treatment efficiency. METHODS: We examined lung biopsy specimens from patients diagnosed with ED-SCLC treated with chemoimmunotherapy or chemotherapy. SCLC subtype, expression of HLA class I, and infiltration of CD8-positive cells were examined using immunohistochemistry (IHC). Subsequently, the association between clinical factors, IHC results, and progression-free survival or overall survival was assessed. RESULTS: Most of the cases showed the achaete-scute homolog 1 (ASCL1) subtype. Among the 75 SCLC cases, 29 expressed high levels of HLA class I, while 46 showed low levels or a negative result; 33 patients were characterized as CD8-high, whereas 42 were CD8-low. In the chemoimmunotherapy cohort, multivariate analysis revealed a correlation between CD8-high and improved survival. Specifically, patients in the CD8-high group of the chemoimmunotherapy cohort experienced enhanced survival compared to those in the chemotherapy cohort, which was attributed to ICI addition. IHC subtype analysis demonstrated a survival advantage in the SCLC-I and SCLC-A groups when ICI was combined with chemotherapy compared to chemotherapy alone. CONCLUSION: Our study highlights the predictive value of IHC-classified subtypes and CD8-positive cell infiltration in estimating outcomes for patients with ED-SCLC treated with chemoimmunotherapy as a first-line therapy. These findings have practical implications for daily clinical assessments and treatment decisions.

Transbronchial cryobiopsy for small peripheral pulmonary lesions using endobronchial ultrasonography and an ultrathin bronchoscope.

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.

Assessment of H3K27me3 immunohistochemistry and combination of NF1 and p16 deletions by fluorescence in situ hybridization in the differential diagnosis of malignant peripheral nerve sheath tumor and its histological mimics.

BACKGROUND: A definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging, especially in cases without neurofibromatosis 1 (NF1), because MPNST lacks specific markers on immunohistochemistry (IHC). METHODS: We performed IHC for histone 3 trimethylated on lysine 27 (H3K27me3) and evaluated the percentage of cells with H3K27me3 loss using measured values at 10% intervals, categorized as complete loss (100% of tumor cells lost staining), partial loss (10% to 90% of tumor cells lost staining), and intact (no tumor cells lost staining). We conducted fluorescence in situ hybridization (FISH) for NF1 and p16 deletions comparing 55 MPNSTs and 35 non-MPNSTs, consisting of 9 synovial sarcomas (SSs), 8 leiomyosarcomas (LMSs), 10 myxofibrosarcomas (MFSs), and 8 undifferentiated pleomorphic sarcomas (UPSs). We assessed the percentage of cells with homozygous and heterozygous deletions and defined "deletion" if the percentage of either the NF1 or p16 deletion signals was greater than 50% of tumor cells. RESULTS: Among the 55 MPNSTs, 23 (42%) showed complete H3K27me3 loss and 32 (58%) exhibited partial loss or intact. One each of the 9 SSs (11%), 8 LMSs (12%), and 8 UPSs (12%) showed complete H3K27me3 loss and many non-MPNSTs exhibited intact or partial H3K27me3 loss. Among the 55 MPNSTs, 33 (60%) and 44 (80%) showed NF1 or p16 deletion, respectively. Co-deletion of NF1 and p16 was observed in 29 (53%) MPNSTs. Among the 23 MPNTSs showing H3K27me3 complete loss, 18 (78%) and 20 (87%) exhibited NF1 or p16 deletion, respectively. Among the 32 MPNSTs with H3K27me3 partial loss or intact, 15 (47%) and 24 (75%) exhibited NF1 or p16 deletion, respectively. The frequency of NF1 and/or p16 deletion tended to be lower in non-MPNSTs than in MPNSTs. Approximately 90% of MPNSTs included cases with H3K27me3 complete loss and cases showing H3K27me3 partial loss or intact with NF1 and/or p16 deletion. Approximately 50% of MPNSTs showed co-deletion of NF1 and p16 regardless of H3K27me3 loss. CONCLUSIONS: FISH for NF1 and p16 deletions, frequently observed in high-grade MPNSTs, might be a useful ancillary diagnostic tool for differentiating MPNST from other mimicking spindle cell and pleomorphic sarcomas.

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

BACKGROUND: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs. CASE PRESENTATION: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred. CONCLUSIONS: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.