ABSTRACT Genetic tests for lung cancer, such as the Oncomine Dx Target Test (ODxTT), are essential for patient management, and require RNA and DNA of sufficient quality and quantity from formalin‐fixed paraffin‐embedded (FFPE) samples. ODxTT fails due to poor nucleic acid preservation. Although enhancing the penetration of formalin into tissues improves nucleic acid preservation, the clinical utility of negative‐pressure fixation methods remains unclear. Therefore, we investigated whether the negative‐pressure fixation method using a vacuum fixation device improves ODxTT success rates and the quality of nucleic acids in FFPE samples from lung and other cancers, and examined the underlying mechanisms. The ODxTT success rate was higher with the negative‐pressure fixation method than with the conventional method (96.5% vs. 81.2%), accompanied by increased RNA quality and yield; however, no marked differences were observed in DNA. RNA deteriorated more rapidly than DNA in resected mouse liver tissues, indicating that RNA is more labile than DNA during cold ischemia. Furthermore, in FFPE samples from colon, pancreatic, and prostate cancers, negative‐pressure fixation consistently improved RNA DV200. These results indicate that the negative‐pressure fixation method improves ODxTT success by accelerating formalin penetration, which may suppress RNase‐mediated RNA degradation and preserve RNA quality.
ABSTRACT This study clarifies the distinct clinicopathological and molecular features of amphicrine pancreatic carcinoma (AmpCA) through a case analysis and literature review. We present a case of AmpCA in a 73‐year‐old female, characterized by co‐expression of acinar cell markers and neuroendocrine markers within individual tumor cells. Molecular profiling revealed high‐risk mutations in KRAS G12V, TP53 , and RB1 , along with a high Ki‐67 index (85%). Literature comparison confirms that AmpCA exhibits a unique bidirectional, single‐cell differentiation pattern, fundamentally distinguishing it from the bicellular composition of mixed neuroendocrine‐non‐neuroendocrine neoplasms (MiNEN). We conclude that AmpCA is a distinct malignant entity requiring specific diagnostic criteria, and its molecular profile suggests potential for targeted therapies.
ABSTRACT Undifferentiated carcinoma (UC) is a rare, highly aggressive subtype of pancreatic cancer; UC with rhabdoid features (UCRF) is particularly associated with poor prognosis. This study aimed to compare clinicopathologic characteristics and outcomes of UC between groups of patients defined by presence versus absence of RF. We retrospectively reviewed patients diagnosed with UC by EUS‐guided tissue acquisition from 2017 to 2024. Histologically, 11 patients were classified as anaplastic UC and two had UC with osteoclast‐like giant cell. Six patients had UCRF. Only 2 patients underwent surgery, while 8 received chemotherapy; 5 of these were treated with gemcitabine plus nab‐paclitaxel. One patient (17%) in the UCRF group was INI‐1–negative. CK7 was positive in 3 UCRF patients (50%) and in all 7 UC patients without RF. In the overall cohort, median OS showed no statistically significant difference between UCRF and UC without RF (3.9 vs. 12.9 months; log‐rank p = 0.188). However, after excluding two patients with UCOGC, Kaplan–Meier analysis demonstrated a significantly shorter OS in UCRF ( p = 0.009). These findings suggest that RF represents a potential adverse prognostic factor in pancreatic UC. Further studies are warranted to clarify biologic significance and treatment implications of RF in pancreatic UC.
ABSTRACT Ancillary assays, including BAP1 (BRCA‐1‐associated protein 1), MTAP (methylthioadenosine phosphorylase), and Merlin immunohistochemistry (IHC), are effective in discriminating pleural mesothelioma (PM) from reactive mesothelial proliferations (RMP). IHC of Merlin, a protein product of the neurofibromin 2 gene, was most recently developed. Our previous study suggested uneven occurrence of Merlin loss within PM tissues. This was further investigated here in a total of 41 tissues of PM obtained from seven institutions. Partial or diffuse Merlin loss was detected with excellent interobserver agreement (kappa: 0.82). Of the 34 PM cases with interobserver consensus, partial and diffuse loss of Merlin expression were each observed in 13 cases (38%). PM with partial Merlin loss exhibited either discrete or intermingled spatial distribution of Merlin‐lost cells. BAP1 or MTAP showed partial loss in none or only 5% of PM cases, respectively. The diagnostic sensitivity for PM was enhanced to 91% with addition of diffuse and partial Merlin loss to a combination of BAP1 and MTAP loss while maintaining 100% specificity. Although detection of Merlin loss as well as BAP1 and MTAP losses is effective for distinguishing PM from RMP, pathologists should be familiar with partial Merlin loss when interpreting Merlin IHC results.
ABSTRACT Anti‐glomerular basement membrane (anti‐GBM) disease may coexist with antineutrophil cytoplasmic antibodies (ANCA), a clinicopathologic entity termed double‐positive disease, in which diffuse alveolar hemorrhage (DAH) is common but histologic confirmation of pulmonary capillaritis remains difficult. A 93‐year‐old woman presented with rapidly progressive renal failure, and serologic evaluation revealed markedly elevated myeloperoxidase (MPO)‐ANCA and anti‐GBM antibody levels. Despite corticosteroid therapy, the patient died of progressive renal failure. At autopsy, the kidneys demonstrated diffuse crescentic glomerulonephritis with linear IgG deposition along the glomerular basement membrane, consistent with anti‐GBM nephritis, together with multiple cortical scars composed of clusters of globally sclerotic glomeruli and interstitial fibrosis. The lungs exhibited DAH with focal neutrophilic infiltration along the alveolar septa, accompanied by focal destruction of capillary walls with subtle leukocytoclasia. Immunohistochemical analysis using epithelial marker (cytokeratin AE1/AE3), endothelial markers (CD31, CD34, and ERG), and platelet markers (CD61 and CD42b) highlighted alveolar epithelial injury, loss of endothelial continuity, and extravascular platelet deposition, respectively, in areas where capillaritis was suspected. Spatial concordance of these findings supported the presence of structural injury associated with pulmonary capillaritis. This case highlights the diagnostic importance of rigorous histopathologic assessment complemented by combined immunohistochemistry in patients with DAH.
