Spindle cell carcinoma of the gingiva: report of an autopsy case

An autopsied case of an 80-year-old man with spindle cell carcinoma of the gingiva is reported. The tumor was polypoid and mostly composed of a sarcomatous proliferation of spindle cells with a small focus of squamous cell carcinoma at the stalk portion. The carcinoma metastasized to a cervical lymph node, lungs and pleura with extension to the diaphragm. In the metastatic lymph node, the squamous cell component was more prominent than the spindle cell one, while only anaplastic pleomorphic carcinoma cells were found in the lungs. The spindle or anaplastic cells were immunohistochemically positive for vimentin and carci-noembryonic antigen (CEA) but not for other epithelial antigens. We have concluded that the sarcomatoid component arose from the oral squamous cell carcinoma by a metaplastic process. This is the first case report of an oral spindle cell carcinoma examined by autopsy.     

Brain perfusion SPECT in neuro-Behçet’s disease: Discordance between Tc-99m-HMPAO and Tc-99m-ECD

A patient with neuro-Behçet’s disease was studied with both Tc-99m-HMPAO and Tc-99m-ECD brain perfusion SPECT during the same time period. In Tc-99m-HMPAO SPECT, focal high uptake was observed in the left basal ganglia where MRI depicted abnormal signal intensity. Conversely, Tc-99m-ECD SPECT did not show corresponding high uptake, but demonstrated rather low uptake in contrast to the Tc-99m-HMPAO SPECT. This case suggests that Tc-99m-HMPAO and Tc-99m-ECD may show discordant distribution in inflammatory brain disease such as neuro-Behçet’s disease.     

Changes of peripheral blood lymphocyte subsets in a long-term survivor with advanced renal cell carcinoma

We present the case of an 11-year survivor with advanced renal cell carcinoma (T4N2M1). This patient received long-term interferon-alpha (IFN-α)-based immunotherapy. Measurement of peripheral blood lymphocyte subsets suggested that reduction of the IFN-α dose might be associated with a marked increase of cytotoxic T cells, suppressor T cells, activated suppressor/cytotoxic T cells, and natural killer cells among the peripheral blood lymphocytes.     

Hepatocellular carcinoma occurring in a Crohn��s disease patient

We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn’s disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the non-neoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was no evidence of liver cirrhosis or primary sclerosing cholangitis. Only nine cases of HCC in CD patients have been reported previously in the English-language literature. Eight of 10 cases (including the present case) had received azathioprine treatment, and four of these cases also showed FHG, which is considered a preneoplastic liver lesion, within the non-neoplastic liver. Although the precise mechanism of the development of HCC in CD patients is controversial, these results suggest that azathioprine therapy and FHG in the non-neoplastic liver contribute to the development of HCC. These findings also indicate that it is important to survey CD patients treated with prolonged azathioprine therapy for potential liver tumors.     

The Effect of LKB1 Activity on the Sensitivity to PI3K/mTOR Inhibition in Non–Small Cell Lung Cancer

IntroductionLiver kinase B1 (LKB1), also called serine/threonine kinase 11 (STK11), is a tumor suppressor that functions as master regulator of cell growth, metabolism, survival, and polarity. Approximately 30% to 35% of patients with NSCLC possess inactivated liver kinase B1 gene (LKB1), and these patients respond poorly to anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy. Therefore, novel therapies targeting NSCLC with LKB1 loss are needed.MethodsWe used a new in silico signaling analysis method to identify the potential therapeutic targets and reposition drugs by integrating gene expression data with the Kyoto Encyclopedia of Genes and Genomes signaling pathways. LKB1 wild-type and LKB1-deficient NSCLC cell lines, including knockout clones generated by clustered regularly interspaced short pallindromic repeats–Cas9, were treated with inhibitors of mechanistic target of rapamycin kinase (mTOR) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and a dual inhibitor.ResultsIn silico experiments showed that inhibition of both mTOR and PI3K can be synergistically effective in LKB1-deficient NSCLC. In vitro and in vivo experiments showed the synergistic effect of mTOR inhibition and PI3K inhibition in LKB1-mutant NSCLC cell lines. The sensitivity to dual inhibition of mTOR and PI3K is higher in LKB1-mutant cell lines than in wild-type cell lines. A higher compensatory increase in Akt phosphorylation after rapamycin treatment of LKB1-deficient cells than after rapamycin treatment of LKB1 wild-type cells is responsible for the synergistic effect of mTOR and PI3K inhibition. Dual inhibition of mTOR and PI3K resulted in a greater decrease in protein expression of cell cycle–regulating proteins in LKB1 knockout cells than in LKB1 wild-type cells.ConclusionDual molecular targeted therapy for mTOR and PI3K may be a promising therapeutic strategy in the specific population of patients with lung cancer with LKB1 loss.