S-1 eliminates MDSCs and enhances the efficacy of PD-1 blockade via regulation of tumor-derived Bv8 and S100A8 in thoracic tumor.

Myeloid-derived suppressor cells (MDSCs) have been known to play a pivotal role in the induction of immune tolerance, which limits the benefits of immune checkpoint inhibitors (ICIs). Recent studies revealed that several chemotherapeutic agents decreased tumor-infiltrating MDSCs. Therefore, combination therapy with cytotoxic chemotherapeutic agents and ICIs was approved for first-line treatment for lung cancer. However, the impact of chemotherapeutic agents on MDSCs and an optimal partner of ICIs has not been fully investigated in thoracic tumors, including lung cancer and malignant pleural mesothelioma. In the present study, we found that treatment with 5-FU and its oral formulation, S-1, suppressed tumor progression and inhibited the accumulation of MDSCs in thoracic tumor-bearing mice. Tumor-infiltrating T cells and dendritic cells were significantly expanded in S-1-treated mice. 5-FU suppressed the ability of tumor cells to recruit MDSCs, while it did not suppress the survival and differentiation of mouse MDSCs in vitro. We also revealed that 5-FU or S-1 significantly downregulated the expression of tumor-derived Bv8 and S100A8. The knockdown of Bv8 or S100A8 in tumor cells suppressed tumor growth and MDSC recruitment in vivo. Furthermore, in comparison with pemetrexed, administration of S-1 improved the synergistic therapeutic efficacy of anti-PD-1 antibodies with or without carboplatin. Our findings revealed a novel mechanism wherein S-1 primed a favorable tumor microenvironment to provide the rationale for combination therapy with S-1 and ICIs as the optimal therapy for thoracic cancer.

Lactate Dehydrogenase and its clinical significance in pancreatic and thoracic cancers.

The energy metabolism of tumor cells is considered one of the hallmarks of cancer because it is different from normal cells and mainly consists of aerobic glycolysis, fatty acid oxidation, and glutaminolysis. It is about one hundred years ago since Warburg observed that cancer cells prefer aerobic glycolysis even in normoxic conditions, favoring their high proliferation rate. A pivotal enzyme driving this phenomenon is lactate dehydrogenase (LDH), and this review describes prognostic and therapeutic opportunities associated with this enzyme, focussing on tumors with limited therapeutic strategies and life expectancy (i.e., pancreatic and thoracic cancers). Expression levels of LDH-A in pancreatic cancer tissues correlate with clinicopathological features: LDH-A is overexpressed during pancreatic carcinogenesis and showed significantly higher expression in more aggressive tumors. Similarly, LDH levels are a marker of negative prognosis in patients with both adenocarcinoma or squamous cell lung carcinoma, as well as in malignant pleural mesothelioma. Additionally, serum LDH levels may play a key role in the clinical management of these diseases because they are associated with tissue damage induced by tumor burden. Lastly, we discuss the promising results of strategies targeting LDH as a treatment strategy, reporting recent preclinical and translational studies supporting the use of LDH-inhibitors in combinations with current/novel chemotherapeutics that can synergistically target the oxygenated cells present in the tumor.

Immunohistochemical Expression of Choline Acetyltransferase and Catecholamine-Synthesizing Enzymes in Head-and-Neck and Thoracoabdominal Paragangliomas and Pheochromocytomas.

Paragangliomas (PGLs) are neural-crest-derived, non-epithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. Head-and-neck PGLs (HNPGLs) have been recognized as nonchromaffin, nonfunctional, parasympathetic tumors. By contrast, thoracoabdominal paragangliomas and pheochromocytomas (PPGLs) are chromaffin, functional, sympathetic tumors. Although HNPGLs and PPGLs have the same histological structure, the zellballen pattern, composed of chief and sustentacular cells surrounded by abundant capillaries, the pathobiological differences between these types of PGLs remain unclarified. To determine the phenotypic features of these PGLs, we performed an immunohistochemical study using specific antibodies against choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, and enzymes for the catecholamine-synthesis, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH), in 34 HNPGLs from 31 patients, 12 thoracoabdominal PGLs from 12 patients, and 26 pheochromocytomas from 22 patients. The expression of ChAT, TH, and DBH was 100%, 23%, and 10% in the HNPGLs; 12%, 100%, and 100% in the pheochromocytomas; and 25%, 67%, and 100% in the thoracoabdominal PGLs, respectively. These results designate HNPGLs as acetylcholine-producing parasympathetic tumors, in contrast to PPGLs being catecholamine-producing tumors. The other most frequently used neuroendocrine markers are synaptophysin and chromogranin A expressed 100% and 80%, respectively, and synaptophysin was superior to chromogranin A in HNPGLs. This is the first report of HNPGLs being acetylcholine-producing tumors. Immunohistochemistry of ChAT could be greatly useful for pathologic diagnosis of HNPGL. Whether measurement of acetylcholine levels in the blood or urine could be a tumor marker of HNPGLs should be investigated soon.

Thoracic mesenchymal malignant tumors and programed cell death ligand-1 status: Clinicopathologic and prognostic analysis of eight pulmonary sarcomatoid carcinomas and eight malignant mesotheliomas.

BACKGROUND: The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. METHODS: From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated. RESULTS: PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not. CONCLUSION: The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.

Superficial CD34-Positive Fibroblastic Tumor on the Chest Wall of an 8-Year-Old Girl: A Case Report and Literature Review.

This study reports a case of superficial CD34-positive fibroblastic tumor (SCPFT) in a child and analyze the major known clinicopathological features of SCPFT and other skin mesenchymal tumors, contributing to an accurate diagnosis of this rare disease. We summarize the clinicopathologic features of an 8-year-old girl who was diagnosed with SCPFT and 46 previously reported SCPFT cases. Post-operative histopathologic examination of the current case showed the tumor lesion was well-circumscribed; tumor cells were spindled-to-polygonal with a fascicular pattern; most nuclei displayed hyperchromasia and low mitotic rate; intranuclear pseudoinclusions could be found; and abundant eosinophilic cytoplasm and partial myxoid stroma were observed. Immunohistochemistry revealed strong and diffuse CD34-positivity, vimentin staining positively but no S-100, SMA, NSE, CD31, desmin, cytokeratin, STAT6, ß-catenin, MDM2, or ERG expression. The Ki-67 and CD68 labeling indexes were approximately 1%. There were no rearrangements of PDGFB or PRDM10 tested by FISH. After surgical resection, the patient had no signs of recurrence or metastasis at a 6-month follow-up. The present case is the first that describes SCPFT in children and has significant clinical implications. SCPFT should be differentiated from other skin mesenchymal tumors. The presented compilation of all so far published SCPFT cases will help in diagnosing successfully SCPFT and increasing awareness of this tumor to guide clinical practice.

Review of SMARCA4 (BRG1)-deficient carcinomas following a malignant pleural effusion specimen confounded by reduced claudin-4 expression.

SMARCA4-deficient neoplasms are recently characterized high-grade malignancies associated with a poor prognosis. The SMARCA4 gene encodes BRG1, which is part of the SWI/SNF complex. SMARCA4-deficient neoplasms have an undifferentiated, often rhabdoid morphology, and demonstrate loss of BRG1 nuclear expression on immunohistochemistry. These neoplasms have become increasingly recognized and diagnosed in tissue specimens, but their features in cytologic specimens are poorly defined in the literature. The review is introduced by a diagnostically challenging case of a SMARCA4-deficient carcinoma involving a pleural fluid specimen in which the carcinoma cells demonstrated greatly reduced claudin-4 expression in the setting of strong, diffuse BerEP4 expression. Most of the malignant cells also demonstrated positive cytoplasmic staining for PAS and all were PAS-diastase negative, suggesting that the cytoplasm contained glycogen granules.

Management of Multiple Secreting Paragangliomas in a Succinate Dehydrogenase Subunit D (SDHD) Variant Carrier.

Management of functional intrathoracic sympathetic paragangliomas in succinate dehydrogenase subunit D (SDHD) mutation carriers is challenging, and there is no uniform guideline for treatment to date. The risks of potential malignant behavior and long-term cardiovascular morbidity have to be weighed against the risks of treatment complications. We report the multidisciplinary and shared decision-making approach that resulted in successful surgical removal of 3 paragangliomas in a SDHD mutation carrier.

The Roles of Neuropilin 2/VEGF-C Axis in a Series of Recurrent Lymphangioma.

INTRODUCTION: Vascular endothelial growth factor (VEGF) and its receptor act as a major contributor to lymphangioma, but their role on nonrecurrent and recurrent lymphangiomas remain unclear. We aim to investigate those factors in the generation of recurrent lymphangioma. MATERIALS AND METHODS: Patients diagnosed with lymphangioma from January 2005 to December 2012 in our hospital were collected and divided into nonrecurrent and recurrent lymphangiomas. The clinical characteristics including age, sex, symptoms, location, and size of lymphangioma were collected. Surgical resection samples were collected for histology, protein and mRNA detection of VEGF-C, VEGF receptor-3 (VEGFR-3), and neuropilin 2 (Nrp2). Follow-ups including lymphangioma recurrent and the local symptoms such as ulcer were reviewed. RESULTS: A total of 80 patients aged from 5 months to 12 years were enrolled in this study, 51 patients had no recurrence and other 29 patients suffered from recurrent lymphangioma. There was no significant difference in demographic data and clinical characters between the two groups (p > 0.05). Immunohistochemistry staining showed that VEGFR-3 remained unchanged between nonrecurrent and recurrent lymphangiomas (p > 0.05), and VEGF-C and Nrp2 were significantly increased in recurrent lymphangioma compared with nonrecurrent lymphangioma (p < 0.05). The same expression trend was proved as detected by protein and mRNA levels. CONCLUSION: The VEGF-C/Nrp2 axis was significantly increased in the recurrent lymphangioma, indicating that VEGF-C/Nrp2 targeted therapy may serve as a potential therapeutic strategy for recurrent lymphangioma.

Insulinoma-associated Protein 1 (INSM1) in Thoracic Tumors is Less Sensitive but More Specific Compared With Synaptophysin, Chromogranin A, and CD56.

OBJECTIVE: Recognition of neuroendocrine differentiation is important for tumor classification and treatment stratification. To detect and confirm neuroendocrine differentiation, a combination of morphology and immunohistochemistry is often required. In this regard, synaptophysin, chromogranin A, and CD56 are established immunohistochemical markers. Insulinoma-associated protein 1 (INSM1) has been suggested as a novel stand-alone marker with the potential to replace the current standard panel. In this study, we compared the sensitivity and specificity of INSM1 and established markers. MATERIALS AND METHODS: A cohort of 493 lung tumors including 112 typical, 39 atypical carcinoids, 77 large cell neuroendocrine carcinomas, 144 small cell lung cancers, 30 thoracic paragangliomas, 47 adenocarcinomas, and 44 squamous cell carcinomas were selected and tissue microarrays were constructed. Synaptophysin, chromogranin A, CD56, and INSM1 were stained on all cases and evaluated manually as well as with an analysis software. Positivity was defined as ≥1% stained tumor cells in at least 1 of 2 cores per patient. RESULTS: INSM1 was positive in 305 of 402 tumors with expected neuroendocrine differentiation (typical and atypical carcinoids, large cell neuroendocrine carcinomas, small cell lung cancers, and paraganglioma; sensitivity: 76%). INSM1 was negative in all but 1 of 91 analyzed non-neuroendocrine tumors (adenocarcinomas, squamous cell carcinomas; specificity: 99%). All conventional markers, as well as their combination, had a higher sensitivity (97%) and a lower specificity (78%) for neuroendocrine differentiation compared with INSM1. CONCLUSIONS: Although INSM1 might be a meaningful adjunct in the differential diagnosis of neuroendocrine neoplasias, a general uncritical vote for replacing the traditional markers by INSM1 may not be justified.

Cytopathological Features of SMARCA4-Deficient Thoracic Sarcoma: Report of 2 Cases and Review of the Literature.

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity of thoracic sarcomas with an undifferentiated rhabdoid morphology and SMARCA4 inactivation. Regardless of some reports about the histopathological findings so far, there have been only a few reports about the cytological features. In this article, we present the pathological features of 2 SMARCA4-DTS cases, including the cytological findings. Histopathologically, the tumor cells showed atypical loosely cohesive large epithelioid cells focally with geographic necrosis. Some cells were characterized by rhabdoid cells. Both patients showed intrathoracic masses with a history of smoking, and loss of SMARCA4 expression was confirmed with histopathological specimens. Immunohistochemically, tumor cells of both cases were at least focally positive for cytokeratin, CD34, CD99, synaptophysin, SOX2, and SALL4. In addition, tumor cells demonstrated significantly reduced expression of BRG1/SMARCA4 and SMARCA2. In conclusion, SMARCA4-DTS should be taken into consideration in the differential diagnosis of tumors with undifferentiated rhabdoid morphology involving the thoracic region.

[Perioperative Venous Thromboembolism (VTE) Prophylaxis in Thoracic Cancer Patients: Chinese Experts Consensus - Interpretation of Perioperative Hypercoagulable State].

Venous thromboembolism (VTE) is a common perioperative complication of lung cancer and a major cause of unexpected death in hospital. The clinical risk factors of VTE include: patients' factors (advanced age, obesity, etc.), tumor-related factors (classification, staging, etc.), treatment-related factors (chemotherapy, surgery, etc.). In addition, tumor cells express cancer procoagulant (CP), tissue factor (TF), inflammatory factors or activate platelets, inflammatory cells and other related cells, directly or indirectly activate the coagulation process, and cause blood hypercoagulable state, thus promote the occurrence of VTE. At the same time, the relevant biomarkers can also reflect the perioperative coagulation status of patients, which is helpful to more accurately identify high-risk subgroups to establish more accurate and targeted anticoagulation strategies to prevent thrombosis in lung cancer patients.

[Perioperative Venous Thromboembolism (VTE) Prophylaxis in Thoracic Cancer Patients: Chinese Experts Consensus - Interpretation of Clinical Significance of D-dimer].

The risk of perioperative venous thromboembolism (VTE) is pretty high in thoracic cancer patients. Perioperative VTE influences the recovery of patients after operation and quality of life in the future, even seriously leading to death. To strengthen the knowledge and attention of thoracic surgeons on perioperative VTE in thoracic cancer patients, China National Research Collaborative Group on VTE in Thoracic Surgery released the edition of VTE prophalaxis in thoracic cancer patients: Chinese experts consensus in 2018. This article is to interpret the diagnostic value and risk prediction value of D-dimer in VTE in detail, and briefly introduce the role of other biomarkers in VTE of tumor patients. The consensus interpretation aims to deepen the understanding of thoracic surgeons on the clinical significance of D-dimer in VTE.

Furosemide versus mannitol in Japanese patients with thoracic malignancy who received cisplatin-based chemotherapy using short hydration: study protocol for a randomised controlled trial.

INTRODUCTION: Cisplatin (CDDP) is a key drug for various thoracic malignancies. To avoid renal toxicity of CDDP, mannitol is routinely used, but it sometimes causes phlebitis which damages patients' quality of life. Furosemide is another widely used option for diuresis administered more quickly. To date, previous comparisons of these diuretics have lacked statistical significance owing to study design. We therefore undertake a randomised phase II comparative study of furosemide and mannitol in CDDP-based chemotherapy using short hydration. METHODS AND ANALYSIS: This is a two-arm, prospective, randomised, single-centre, open-label phase II study. The primary endpoint is set as the proportion of patients who experienced any grade of 'creatinine increase' using the Common Terminology Criteria for Adverse Events V.4.0, during the first cycle. Secondary endpoints are: the proportion of patients who experienced ≥grade 2 of creatinine increase during the first cycle, any grade and ≥grade 2 of creatinine increase after the completion of fourth cycle, and the proportion of patients with phlebitis. Enrolled in this trial will be 105 patients. ETHICS AND DISSEMINATION: This study was approved by the Wakayama Medical University Institutional Review Board on 30 March 2018 study (approval number: 2258). Patients have been enrolled since May 2018. As the study will complete accrual in March 2021, results will be published by 2021. This study will provide important information about the utility of furosemide compared with mannitol to protect against nephrotoxicity. TRIAL REGISTRATION NUMBER: UMIN000031910.

Dual-input tracer kinetic modeling of dynamic contrast-enhanced MRI in thoracic malignancies.

Pulmonary perfusion with dynamic contrast-enhanced (DCE-) MRI is typically assessed using a single-input tracer kinetic model. Preliminary studies based on perfusion CT are indicating that dual-input perfusion modeling of lung tumors may be clinically valuable as lung tumors have a dual blood supply from the pulmonary and aortic system. This study aimed to investigate the feasibility of fitting dual-input tracer kinetic models to DCE-MRI datasets of thoracic malignancies, including malignant pleural mesothelioma (MPM) and nonsmall cell lung cancer (NSCLC), by comparing them to single-input (pulmonary or systemic arterial input) tracer kinetic models for the voxel-level analysis within the tumor with respect to goodness-of-fit statistics. Fifteen patients (five MPM, ten NSCLC) underwent DCE-MRI prior to radiotherapy. DCE-MRI data were analyzed using five different single- or dual-input tracer kinetic models: Tofts-Kety (TK), extended TK (ETK), two compartment exchange (2CX), adiabatic approximation to the tissue homogeneity (AATH) and distributed parameter (DP) models. The pulmonary blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), fractional interstitial volume (vI ), and volume transfer constant (KTrans ) were calculated for both single- and dual-input models. The pulmonary arterial flow fraction (γ), pulmonary arterial blood flow (BFPA ) and systemic arterial blood flow (BFA ) were additionally calculated for only dual-input models. The competing models were ranked and their Akaike weights were calculated for each voxel according to corrected Akaike information criterion (cAIC). The optimal model was chosen based on the lowest cAIC value. In both types of tumors, all five dual-input models yielded lower cAIC values than their corresponding single-input models. The 2CX model was the best-fitted model and most optimal in describing tracer kinetic behavior to assess microvascular properties in both MPM and NSCLC. The dual-input 2CX-model-derived BFA was the most significant parameter in differentiating adenocarcinoma from squamous cell carcinoma histology for NSCLC patients.

Severe Hepatotoxicity of Mithramycin Therapy Caused by Altered Expression of Hepatocellular Bile Transporters.

Mithramycin demonstrates preclinical anticancer activity, but its therapeutic dose is limited by the development of hepatotoxicity that remains poorly characterized. A pharmacogenomics characterization of mithramycin-induced transaminitis revealed that hepatotoxicity is associated with germline variants in genes involved in bile disposition: ABCB4 (multidrug resistance 3) rs2302387 and ABCB11 [bile salt export pump (BSEP)] rs4668115 reduce transporter expression (P < 0.05) and were associated with ≥grade 3 transaminitis developing 24 hours after the third infusion of mithramycin (25 mcg/kg, 6 hours/infusion, every day ×7, every 28 days; P < 0.0040). A similar relationship was observed in a pediatric cohort. We therefore undertook to characterize the mechanism of mithramycin-induced acute transaminitis. As mithramycin affects cellular response to bile acid treatment by altering the expression of multiple bile transporters (e.g., ABCB4, ABCB11, sodium/taurocholate cotransporting polypeptide, organic solute transporter α/ß) in several cell lines [Huh7, HepaRG, HepaRG BSEP (-/-)] and primary human hepatocytes, we hypothesized that mithramycin inhibited bile-mediated activation of the farnesoid X receptor (FXR). FXR was downregulated in all hepatocyte cell lines and primary human hepatocytes (P < 0.0001), and mithramycin inhibited chenodeoxycholic acid- and GW4046-induced FXR-galactose-induced gene 4 luciferase reporter activity (P < 0.001). Mithramycin promoted glycochenodeoxycholic acid-induced cytotoxicity in ABCB11 (-/-) cells and increased the overall intracellular concentration of bile acids in primary human hepatocytes grown in sandwich culture (P < 0.01). Mithramycin is a FXR expression and FXR transactivation inhibitor that inhibits bile flow and potentiates bile-induced cellular toxicity, particularly in cells with low ABCB11 function. These results suggest that mithramycin causes hepatotoxicity through derangement of bile acid disposition; results also suggest that pharmacogenomic markers may be useful to identify patients who may tolerate higher mithramycin doses. SIGNIFICANCE STATEMENT: The present study characterizes a novel mechanism of drug-induced hepatotoxicity in which mithramycin not only alters farnesoid X receptor (FXR) and small heterodimer partner gene expression but also inhibits bile acid binding to FXR, resulting in deregulation of cellular bile homeostasis. Two novel single-nucleotide polymorphisms in bile flow transporters are associated with mithramycin-induced liver function test elevations, and the present results are the rationale for a genotype-directed clinical trial using mithramycin in patients with thoracic malignancies.

[Giant Solitary Fibrous Tumor Associated with Loss of Consciousness by Hypoglycemic Attack].

We herein report a rare case of solitary fibrous tumor (SFT) producing high-molecular-weight insulin-like growth factor Ⅱ(big IGF-Ⅱ). A 51-year-old woman with a large mass in the right thorax suffered from repeated loss of consciousness due to hypoglycemic attack. A hematological examination revealed low values of serum insulin and C-peptide despite her hypoglycemia. We therefore regarded her giant thoracic tumor as the cause of the hypoglycemic attack. She underwent resection of the tumor and was diagnosed with SFT pathologically. After the surgery, her blood sugar level stabilized immediately, and she has had no hypoglycemic attacks since. Although we identified big IGF-Ⅱ in a preoperative serum sample by a Western immunoblot analysis, it was not detected after surgical resection. Positivity for big IGF-Ⅱ was observed in the tumor cells by immunohistochemical staining. We therefore concluded that big IGF-Ⅱ produced by the SFT caused the hypoglycemic attack in this patient.

Transcriptome profiling of caspase-2 deficient EµMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling.

Caspase-2 is a highly conserved cysteine protease with roles in apoptosis and tumor suppression. Our recent findings have also demonstrated that the tumor suppression function of caspase-2 is context specific. In particular, while caspase-2 deficiency augments lymphoma development in the EµMyc mouse model, it leads to delayed neuroblastoma development in Th-MYCN mice. However, it is unclear how caspase-2 mediates these differential outcomes. Here we utilized RNA sequencing to define the transcriptomic changes caused by caspase-2 (Casp2-/-) deficiency in tumors from EµMyc and Th-MYCN mice. We describe key changes in both lymphoma and neuroblastoma-associated genes and identified differential expression of the EGF-like domain-containing gene, Megf6, in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2-/- tumors that are strongly associated with neuroblastoma outcome, with roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In contrast, we found that key changes in gene expression in the EµMyc/Casp2-/- tumors, are associated with increased immune signaling and T-cell infiltration previously associated with more aggressive lymphoma progression. In addition, Rap1 signaling pathway was uniquely enriched in Casp2 deficient EµMyc tumors. Our findings suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues.

Fibroelastic pseudotumor elastofibroma dorsi detected by 18F-FDG PET/CT scan and by postherapy radioiodine SPECT/CT. / Seudotumor fibroelástico elastofibroma dorsi detectado por 18F-FDG PET/TC y por 131I SPECT/TC posterapia.

Radioiodine uptake in the thyroid tissue, metastasis of differentiated thyroid cancer (DTC), and in other tissues, depends on the expression of sodium-iodide symporter (NIS). Vascular permeability, effusions, inflammation, and other mechanisms may also play a role in the accumulation of radioactive iodine. A 63-year-old woman underwent radioiodine therapy, as well as a post-therapy whole-body scan, as she was suspected of having lung metastasis from thyroid carcinoma. The scan not only showed uptake at the lung metastasis but also a faint diffuse bilateral uptake in the posterior thorax. On SPECT/CT this uptake was located in a known Elastofibroma Dorsi (ED) previously diagnosed by contrast CT and viewed in a FDG PET/CT. The radioiodine uptake in ED, especially if typical, is not a diagnostic problem in SPECT/CT study, but can be misleading in a study limited to a few planar images, particularly if the uptake occurs asymmetrically, or ED is located in a unsuspected area.