Differentiation between hepatic angiomyolipoma and hepatocellular carcinoma in individuals who are not at-risk for hepatocellular carcinoma.

PURPOSE: To develop a practical methodfor differentiating hepatocellular carcinoma (HCC) from angiomyolipoma (AML) in individuals who are not at-risk for HCC. METHOD: We retrospectively enrolled consecutive patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) and pathological confirmation between January 2008 and April 2022. Patients who underwent prior treatment, those with multiple lesions, or those at-risk for HCC were excluded. The training cohort included patients with pathological confirmation between 2008 and 2019, whereas the validation cohort included the remaining cases. Independent reviews of the MRI were performed by two reviewers. Using the clinical and MRI findings, we developed AML-HCC score using Firth's logistic regression in the training cohort, and the diagnostic performance was validated in the validation cohort. RESULTS: Of the 206 patients, 156 were assigned to the training cohort (25 and 131 patients with AML and HCC, respectively) and 50 were assigned to the validation cohort (4 and 46 patients with AML and HCC, respectively). The AML-HCC score was defined as the sum of female (score 1), early draining vein (score 2), T2 homogeneity (score 1), necrosis or severe ischaemia (score -2), and HBP hyperintensity to spleen (score -1). When the AML-HCC score was ≥1, the sensitivity and specificity were 80% and 95% for the training cohort and 100% and 80% for the validation cohort, respectively. CONCLUSIONS: We developed and validated an AML-HCC score to differentiate between AML and HCC in individuals who are not at-risk for HCC, and our model demonstrated good diagnostic performance.

Pituitary Apoplexy After Leuprolide Therapy in a Breast Cancer Patient: A Case Report.

Pituitary apoplexy (PA) is a clinical syndrome resulting from sudden hemorrhage and/or infarction of the pituitary gland. Recent reports documented the development of PA secondary to treatment with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer. A 52-year-old woman visited our emergency room with a severe headache, occurred 1 day prior. She underwent breast-conserving surgery for breast cancer 1 month prior. She was currently undergoing radiation and hormone therapy, consisting of leuprorelin. Brain contrast-enhanced MRI revealed a pituitary adenoma with internal hemorrhage in the sellar and suprasellar areas. Pachymeningeal enhancement was observed along the retroclival and bilateral frontal areas. The patient was diagnosed with PA and aseptic meningitis. The patient underwent total excision via transsphenoidal surgery 8 days after admission. The patient was pathologically diagnosed with a pituitary adenoma with necrosis. On immunochemical staining, the tumor was positive for follicle-stimulating hormone. The follow-up MRI revealed no evidence of residual tumor or an improved pachymeningeal enhancement. She is currently undergoing follow-up at the neurosurgery and endocrinology outpatient departments with no noted complications. In breast cancer patients receiving GnRH agonist therapy, PA may be rare complication.

IL-1ß promotes IL-9-producing Th cell differentiation in IL-2-limiting conditions through the inhibition of BCL6.

IL-9-producing CD4+ T helper cells, termed Th9 cells, differentiate from naïve precursor cells in response to a combination of cytokine and cell surface receptor signals that are elevated in inflamed tissues. After differentiation, Th9 cells accumulate in these tissues where they exacerbate allergic and intestinal disease or enhance anti-parasite and anti-tumor immunity. Previous work indicates that the differentiation of Th9 cells requires the inflammatory cytokines IL-4 and TGF-ß and is also dependent of the T cell growth factor IL-2. While the roles of IL-4 and TGF-ß-mediated signaling are relatively well understood, how IL-2 signaling contributes to Th9 cell differentiation outside of directly inducing the Il9 locus remains less clear. We show here that murine Th9 cells that differentiate in IL-2-limiting conditions exhibit reduced IL-9 production, diminished NF-kB activation and a reduced NF-kB-associated transcriptional signature, suggesting that IL-2 signaling is required for optimal NF-kB activation in Th9 cells. Interestingly, both IL-9 production and the NF-kB transcriptional signature could be rescued by addition of the NF-kB-activating cytokine IL-1ß to IL-2-limiting cultures. IL-1ß was unique among NF-kB-activating factors in its ability to rescue Th9 differentiation as IL-2 deprived Th9 cells selectively induced IL-1R expression and IL-1ß/IL-1R1 signaling enhanced the sensitivity of Th9 cells to limiting amounts of IL-2 by suppressing expression of the Th9 inhibitory factor BCL6. These data shed new light on the intertwined nature of IL-2 and NF-kB signaling pathways in differentiating Th cells and elucidate the potential mechanisms that promote Th9 inflammatory function in IL-2-limiting conditions.

Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease.

CD4 T cells play important roles in promoting protective immunity and autoimmune disease. A great deal of attention has been given to the differentiation and function of subsets of cytokine-producing CD4 T cells (i.e., Th1, Th2, and Th17 cells) in these settings. However, others have also observed the accumulation of granzyme-producing CD4 T cells in tumors and in autoimmune patients that are distinct from their cytokine-producing counterparts. Despite the relatively large numbers of granzyme-producing cells in diseased tissues, their roles in driving disease have remained enigmatic. This review will focus on the phenotype(s) and roles of granzyme-producing CD4 T cells in cancer and autoimmunity. We will also examine how granzyme-producing cells interact with current therapeutics and speculate how they may be targeted during disease.

Granzyme A-producing T helper cells are critical for acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) can occur after hematopoietic cell transplant in patients undergoing treatment for hematological malignancies or inborn errors. Although CD4+ T helper (Th) cells play a major role in aGVHD, the mechanisms by which they contribute, particularly within the intestines, have remained elusive. We have identified a potentially novel subset of Th cells that accumulated in the intestines and produced the serine protease granzyme A (GrA). GrA+ Th cells were distinct from other Th lineages and exhibited a noncytolytic phenotype. In vitro, GrA+ Th cells differentiated in the presence of IL-4, IL-6, and IL-21 and were transcriptionally unique from cells cultured with either IL-4 or the IL-6/IL-21 combination alone. In vivo, both STAT3 and STAT6 were required for GrA+ Th cell differentiation and played roles in maintenance of the lineage identity. Importantly, GrA+ Th cells promoted aGVHD-associated morbidity and mortality and contributed to crypt destruction within intestines but were not required for the beneficial graft-versus-leukemia effect. Our data indicate that GrA+ Th cells represent a distinct Th subset and are critical mediators of aGVHD.

RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells.

Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin+ conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPß. RARα promotes the development of LCs and langerin+ conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations.

Evaluation for fracture patterns around the wrist on three-dimensional extremity computed tomography, especially focused on the triquetrum.

INTRODUCTION: To describe fracture patterns of triquetrum and analyse them according to fracture classifications, anatomy of intrinsic carpal ligaments and comparison with other wrist fractures. METHODS: We retrospectively reviewed 297 three-dimensional extremity computed tomographies (CTs) on wrist fractures from October 2007 to January 2012. We initially classified the fractures according to the involved bones and analyzed them according to the patterns of triquetrum fractures, associated carpal bone fractures and presence of combined distal radius fractures. We also correlated the fracture patterns with the patient's injury patterns. RESULTS: A total of 297 CTs and 291 patients were included (162 males and 129 females; mean age, 47.8 years). There were a total of 131 carpal bone fractures in 102 patients of 102 CTs. Triquetrum fractures were the most commonly observed cases (36 cases/27.5%). For the triquetrum fractures, the following types were observed: 26 dorsal, five volar, two comminuted fractures are observed in triquetrum. Three other triquetrum fractures show combined forms of other carpal bone fractures. For the combined distal radius fractures, 10 dorsal and two volar fractures were shown. Out of 187 distal radius fractures, 20 showed carpal bone fractures (10.7%). There were no differences in injury patterns according to the fracture patterns. The most common pattern of injury was falling on the outstretched hand, followed by fall from height. CONCLUSION: The dorsum of triquetrum is more frequently fractured than the volar aspect. The number of carpal bone fractures among the patients who have distal radius fractures is higher than usual expectation.

Schwannomatosis involving peripheral nerves: a case report.

Schwannomatosis or neurilemmomatosis has been used to describe patients with multiple nonvestibular schwannomas with no other stigmata of neurofibromatosis type-2 (NF-2). In our case, schwannomatosis, multiple schwannomas were present in a 21-yr-old woman with no stigmata or family history of NF-1 or NF-2. She had no evidence of vestibular schwannoma or other intracranial tumors. Multiple peripheral tumors were found in the carotid space of the neck, and soft tissue of posterior shoulder, lower back, ankle and middle mediastinum. All of those tumors were completely limited to the right side of the body. All surgically removed tumor specimens in this patient proved to be schwannomas.