Induced phase separation of mutant NF2 imprisons the cGAS-STING machinery to abrogate antitumor immunity.

Missense mutations of the tumor suppressor Neurofibromin 2 (NF2/Merlin/schwannomin) result in sporadic to frequent occurrences of tumorigenesis in multiple organs. However, the underlying pathogenicity of NF2-related tumorigenesis remains mostly unknown. Here we found that NF2 facilitated innate immunity by regulating YAP/TAZ-mediated TBK1 inhibition. Unexpectedly, patient-derived individual mutations in the FERM domain of NF2 (NF2m) converted NF2 into a potent suppressor of cGAS-STING signaling. Mechanistically, NF2m gained extreme associations with IRF3 and TBK1 and, upon innate nucleic acid sensing, was directly induced by the activated IRF3 to form cellular condensates, which contained the PP2A complex, to eliminate TBK1 activation. Accordingly, NF2m robustly suppressed STING-initiated antitumor immunity in cancer cell-autonomous and -nonautonomous murine models, and NF2m-IRF3 condensates were evident in human vestibular schwannomas. Our study reports phase separation-mediated quiescence of cGAS-STING signaling by a mutant tumor suppressor and reveals gain-of-function pathogenesis for NF2-related tumors by regulating antitumor immunity.

Kikuchi disease with an exuberant proliferation of large T-cells: a study of 25 cases that can mimic T-Cell lymphoma.

Exuberant large T-cell proliferations in Kikuchi disease can potentially be misdiagnosed as lymphoma. In this study, we explore their clinicopathological features and summarize key points that can be used to distinguish them from T-cell lymphoma. The cohort consisted of 25 cases of Kikuchi disease with an exuberant large T-cell proliferation, which, in part, mimicked lymphoma. The median age was 25 years with a female:male ratio of 4:1. By B-scan ultrasonography, patients presented with either isolated lymphadenopathy (68%) involving the cervical and axillary regions or generalized lymphadenopathy (32%). Histologically, lymph nodes showed paracortical and interfollicular expansion by sheets of large cells associated with karyorrhectic debris. Histiocytes and plasmacytoid dendritic cells were present in the background. No case showed complete effacement of lymph node architecture. The large cells were CD8-positive cytotoxic T-cells with a high proliferation rate. These T-cells showed decreased BCL-2 in 17 (68%) cases. CD5 expression was decreased in 10 (40%) cases. Histiocytes in the background were positive for myeloperoxidase. Clonal TRG and/or TRB rearrangements were detected in 2 of 10 (20%) cases. In conclusion, large T-cell proliferations in Kikuchi disease can be alarming at the morphologic and immunophenotypic levels and need to be distinguished from T-cell lymphoma. Clinical features helpful in the differential diagnosis include young patients and lymphadenopathy involving the cervical and axillary regions. Major pathologic features helpful in this differential diagnosis include partial involvement of the lymph node and the presence of karyorrhectic debris, crescent-shaped histiocytes, and/or loose aggregates of plasmacytoid dendritic cells.

Case Report: Multiple Ocular Manifestations Assisted in the Diagnosis of Systemic Sarcoidosis.

SIGNIFICANCE: Sarcoidosis is a variable, multisystem granulomatous disease, which can affect many organs including the lungs, lymph nodes, and eyes. It is difficult to differentiate sarcoidosis and tuberculosis because of their similar clinical and pathological features. PURPOSE: This study aimed to describe a sarcoidosis case with typical ocular and systemic manifestations combined with suspected tuberculosis infection. CASE REPORT: A 30-year-old Chinese man, initially diagnosed with tuberculosis, presented with typical ocular sarcoidosis during antituberculosis therapy. The ocular surface, anterior chamber, anterior chamber angle, ciliary body, vitreous, optic disc, and lacrimal gland of the patient all exhibited manifestations of sarcoidosis, although optic disc involvement has rarely been reported. Typical ocular sarcoidosis manifestations and positive responses to corticosteroid therapy of the patient helped us reach the diagnosis of systemic sarcoidosis. The patient was followed up for 48 months and showed significant improvement of miliary nodules and lymph nodes in both lungs. However, the appearance of uveitis in the right eye persisted because of nonadherence to steroid treatment. CONCLUSIONS: This case shows the importance of ophthalmic evaluation in the diagnosis and management of sarcoidosis and supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis.

A study of using carbon nanoparticles to improve lymph nodes staging for laparoscopic-assisted radical right hemicolectomy in colon cancer.

PURPOSE: This study aimed to analyze and evaluate the feasibility of using carbon nanoparticles (CNs) to track lymph nodes (LNs) metastases in right colon tumors, especially for patients who underwent laparoscopic-assisted radical right hemicolectomy. METHOD: A total of 99 patients were enrolled in this retrospective study between November 2015 and September 2017 (control group n = 47). One day before surgery, 1 ml of CNs suspension was injected into the submucosal layer around the site of the primary lesions by colonoscopy. Then complete mesocolic excision (CME) of laparoscopic right hemicolectomy was performed. CNs-stained LNs were identified and counted from all dissected LNs after surgery. RESULTS: The dates showed that the number of total harvested LNs and the number of positive patients in the experimental group increased significantly compared with the control group (respectively, P < 0.01 and P < 0.05). The increase of positive percentage shifted some patients toward higher stage, although the total number of positive LNs changed a little bit. In addition, the duration for pathologist to dissect LNs became shorter (26.4 vs. 31.1 min, P < 0.05). CONCLUSION: Therefore, the CNs are not only a good tattoo in laparoscopic-assisted operation, but could be regarded as a better pathological evaluating tool for tumor treatment.

'Ectopic' suprasellar type IIa PRL-secreting pituitary adenoma.

BACKGROUND: Ectopic pituitary adenomas (EPAs) are rare, and the suprasellar cistern seems to be the most common location. At this time, no detailed original classification, diagnosis, or treatment protocols for suprasellar pituitary adenomas (SPAs) have been described. CASE DESCRIPTION: A 19-year-old man showed visual disturbances and lack of libido for 3 years, he suffered a sharp decline in vision with only light perception in the last week. Magnetic resonance imaging scans revealed a large suprasellar cystic lesion with a normal pituitary in the sella turcica. Endocrinological findings showed an extremely high prolactin level of 1250 ng/mL. Because of the sharp decline in vision, the patient underwent total removal of the suprasellar lesion using a transfrontal interhemispheric approach. The tumor pedicle originated in the lower pituitary stalk without any connection to the anterior pituitary gland in the sella turcica, while the diaphragma sellae was incomplete. Clinical and endocrinological cure criteria were fulfilled and postoperative pathology confirmed a prolactin-secreting pituitary adenoma. CONCLUSION: Ectopic suprasellar pituitary adenomas (ESPAs) are extremely rare intracranial extracerebral tumors. SPAs can be classified into three types according to their origin and their relationship with surrounding tissue. Only type III is theoretically a true ectopic, based on previous reports. Thus, ESPAs are uncommon compared to other EPAs. Our case is the first reported case of a type IIa 'E'SPA and the first description of this subtype classification until now. The pars tuberalis may be different from the pars distalis, and each subtype of adenohypophyseal cells may have different migration characteristics, which leads to different proportions of each hormone-secreting subtype in SPAs and EPAs. Transsphenoidal surgery is minimally invasive, but transcranial surgery may remain a universal option for the treatment of suprasellar lesions.

Case report: Moderate therapeutic response to Bevacizumab in late-onset Labrune syndrome.

Labrune syndrome (LS) is caused by SNORD118 gene mutations with a particular neuroimaging of white matter disease, intracranial calcification, and cysts. There was no effective treatment until now. An 18-year-old man with infancy-onset LS was first treated with vascular endothelial growth factor (VEGF) inhibitor Bevacizumab for 1 year, resulting in significant clinical and radiological improvements. We adopted a similar regimen in a patient with late-onset LS and demonstrated moderate cognitive improvements but without changes in imaging. As such, Bevacizumab could potentially be clinically effective in adult-onset LS with great safety.

Mucinous cystadenoma with calcification arising from renal pelvis radiologically resembled renal calculus with hydronephrosis: report of a rare case and review of the literature.

Primary mucinous cystic tumors occurring in the renal pelvis or the entire pyelocaliceal system are uncommon. Most are mucinous cystadenomas and less frequently mucinous cystadenocarcinomas. In fact, the publications on these neoplasms are limited to a few cases. Because mucinous cystadenomas of kidney are exceedingly rare, little is known about their natural history, pathogenesis and clinicopathologic features. Herein, we describe 1 case of mucinous cystadenoma arising from the renal pelvis with calcification, which resembled hydronephrosis with renal calculus radiologically. The patient presented with a history of intermittent dull pain on the right waist since 10 years ago. He had no history of removing urinary calculus or long-standing chronic infection in urinary system. The histopathology was unique since the inner surface of the cyst was covered by a mucinous epithelium connected to a urothelium, a transition from nonneoplastic urothelium to mucinous epithelium was demonstrated by immunohistochemical staining for GATA-binding protein 3 (GATA3). This suggests that mucinous cystadenoma of renal pelvis, like its malignant counterpart, maybe arises in foci of metaplastic mucinous areas.