Outcomes of SWI/SNF complex-deficient sinonasal carcinomas in a Southeast Asian cohort.

BACKGROUND: SWI/SNF complex-deficient sinonasal carcinomas are rare, genetically distinct, and aggressive entities. METHODS: SMARCB1 and SMARCA4 immunohistochemistry was retrospectively performed on a cohort of undifferentiated, poorly differentiated, and poorly defined sinonasal carcinomas. Survival outcomes were compared between SMARCB1/SMARCA4 (SWI/SNF complex)-deficient and -retained groups. RESULTS: Eight SWI/SNF complex-deficient (six SMARCB1-deficient, two SMARCA4-deficient) cases were identified among 47 patients over 12 years. Triple-modality treatment was more frequently utilized in SWI/SNF complex-deficient carcinomas than in SWI/SNF complex-retained carcinomas (71.4% vs. 11.8%, p = 0.001). After a median follow-up of 21.3 (IQR 9.9-56.0) months, SWI/SNF complex-deficient sinonasal carcinomas showed comparable recurrence rates (57.1% vs. 52.9%, p = 0.839), time-to-recurrence (7.3 [IQR 6.6-8.3] vs. 9.1 [IQR 3.9-17.4] months, p = 0.531), and overall survival (17.7 [IQR 11.8-67.0] vs. 21.6 [IQR 8.9-56.0] months, p = 0.835) compared to SWI/SNF complex-retained sinonasal carcinomas. CONCLUSION: Triple-modality treatment may improve survival in SWI/SNF complex-deficient sinonasal carcinomas.

Chromium- and Metal-Reductant-Free Asymmetric Nozaki-Hiyama-Kishi (NHK) Reaction Enabled by Metallaphotoredox Catalysis.

Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki-Hiyama-Kishi (NHK) reaction is a widely used method for the synthesis of allylic alcohols, it suffers from drawbacks such as the use of toxic chromium salts, high amounts of metal reductants, and poor enantiocontrol. To address these limitations, we present a novel approach involving a metallaphotoredox-catalyzed asymmetric NHK reaction for the production of chiral allylic alcohols. This method marries alkenyl (pseudo)halides with aldehydes, leveraging a synergistic blend of a chiral nickel catalyst and a photocatalyst. This innovative technique enables both oxidative addition and insertion just using nickel, diverging significantly from the conventional NHK reaction pathway mediated by nickel and chromium salts. The adoption of this methodology holds immense promise for crafting a spectrum of intricate compounds, particularly those of significance in pharmaceuticals. Detailed experimental investigations have shed light on the metallaphotoredox process, further enhancing our understanding and enabling further advancements.

Primary Epithelioid Angiosarcoma of the Submandibular Gland-A Case Report with Histology-Cytology Correlation and Comprehensive Molecular Analysis.

BACKGROUND: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized. METHODS AND RESULTS: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization. CONCLUSION: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.

A Case of Parathyroid Carcinoma in Renal Hyperparathyroidism.

Introduction: Parathyroid carcinoma is a rare malignant endocrine tumor that is usually associated with primary hyperparathyroidism. The coexistence of parathyroid carcinoma and renal hyperparathyroidism is a rare phenomenon. Hence, we present a case of parathyroid carcinoma in a patient with tertiary hyperparathyroidism. Case Presentation: Our patient is a 31-year-old woman with a past medical history of end-stage renal failure (ESRF), on hemodialysis for the past 18 years. She was referred by her nephrologist to the endocrine surgery department for consideration of parathyroidectomy in view of long-standing tertiary hyperparathyroidism complicated by hypercalcemia. Bedside ultrasonography scan (US) of the thyroid revealed three parathyroid glands and a hypoechoic right lower pole thyroid nodule with central calcification. Fine-needle aspiration cytology was performed for the suspected thyroid nodule on the same day, which eventually yielded a follicular lesion of undetermined significance. A right hemithyroidectomy and total parathyroidectomy with deltoid implantation was performed. Intraoperative exploration revealed that the thyroid nodule noted at initial US was found to be the right superior parathyroid gland invading into the right thyroid itself. The right superior parathyroid gland was excised en bloc with the right hemithyroidectomy. Post-operatively, the patient was hypocalcemic but was discharged well on post-operative day 5. Histopathological diagnosis of the right hemithyroidectomy specimen containing the right superior parathyroid gland was consistent with that of parathyroid carcinoma. Conclusion: Parathyroid carcinoma is a rare entity that is difficult to diagnose. In patients with ESRF, the presence of concurrent tertiary hyperparathyroidism makes this even more challenging.

Ocular Crystal-Storing Histiocytosis with Co-existing MALT Lymphoma-A Rare Case with Cytologic and Heretofore Not Reported Findings on Frozen Section.

BACKGROUND: Crystal-storing histiocytosis (CSH) is a rare disorder which most commonly occurs in the setting of concurrent lymphoproliferative disease. Morphologically, it consists of aggregates of histiocytes containing eosinophilic crystalline material, which in most cases is composed of aggregated abnormal light chains. METHODS: Using histomorphology, immunohistochemistry and in situ hybridization, the authors characterize a rare case of orbital CSH associated with extranodal marginal zone (MALT) lymphoma and report for the first time the frozen section features of CSH. RESULTS: The frozen section featured plump histiocytes with ample weakly basophilic to grayish cytoplasm with a microvacuolated appearance and focal stippling. These features stand in contrast with the formalin-fixed, paraffin embedded histomorphological appearance of aggregates of plump histiocytes with densely eosinophilic crystalline cytoplasmic material. CONCLUSION: CSH is a challenging diagnosis to make on frozen section. The artifacts that preclude its recognition, as well as differential diagnoses of this entity in the head and neck are discussed.

The Challenge of "Monomorphic" Mucoepidermoid Carcinoma-Report of a Rare Case with Pure Spindle-Clear Cell Morphology.

BACKGROUND: Mucoepidermoid carcinoma is a malignant salivary gland tumor which, in most cases, is composed of variable proportions of mucous, epidermoid, and intermediate cells. METHODS: We report a case of parapharyngeal mucoepidermoid carcinoma with highly unusual ("monomorphic") light microscopic features as well as atypical immunohistochemical properties. Molecular analysis was performed using the TruSight RNA fusion panel. RESULTS: The tumor featured heretofore undescribed histopathological features: sheets and nests composed of monomorphic neoplastic (plump spindle to epithelioid) cells with no mucous, intermediate, glandular/columnar, or any other cell type identified. The neoplastic cells displayed variable clear cell change and only expressed cytokeratin 7. Despite this non-classical morphology, the presence of the classical CRTC1::MAML2 fusion was demonstrated. CONCLUSIONS: Mucoepidermoid carcinoma featuring a uniform ("monomorphic") population of neoplastic cells is a novel observation. A confident diagnosis of mucoepidermoid carcinoma can be made upon detection of the CRTC1/3::MAML2 fusion. Our case increases the spectrum of histopathological appearances that mucoepidermoid carcinoma may display.

Impact of new talent settlement policy on housing prices: Evidence from 70 large and medium-sized Chinese cities.

Since 2017, Chinese cities have set off a wave of talent migration, with major cities joining the talent war and issuing new talent settlement policies that might stimulate the real estate market through the inflow and outflow of human capital. However, the effects of new talent settlement policies on housing prices have not been extensively studied. This study used a difference-in-differences model to examine the causal effects of new talent settlement policies on housing prices in China based on data from 70 large and medium-sized cities. The results showed that new talent settlement policies had positive effects on housing prices, and the effects revealed pronounced regional heterogeneity: they were more significant in the eastern region, first-tier, and new first-tier cities, and varied across major migration zones. Further, the varying policy tools in the new talent settlement policies had disparate effects on housing prices. Thus, we recommend that new talent settlement policies must be coordinated with the goals of real estate regulation and reasonable regional standards, and that the policy tools should be tailored according to the actual conditions of cities.

Oncocytic low-grade myoepithelial carcinoma ex pleomorphic adenoma - A rare case illustrating key learning points.

BACKGROUND: Oncocytic myoepithelial carcinoma ex pleomorphic adenoma neoplastic is a rare neoplastic event and may not display overt malignant radiological features. METHODS: Using routine histopathology and immunohistochemistry, we characterize a case of low-grade oncocytic carcinoma ex pleomorphic adenoma. RESULTS: The tumor arose in the left parotid gland in a 59 year old female. Computed tomography (CT) imaging demonstrated a well-defined, lobulated, enhancing lesion with relative central stellate hypoenhancement. Histologically, the tumor displayed a multi-nodular, non-destructive, invasive pattern, low mitotic activity (one mitotic figure per 10 high power fields) and a small remnant focus of pleomorphic adenoma. The neoplastic cells showed significant expression of cytokeratin 5/6, S-100 protein, smooth muscle actin and p63. CONCLUSION: Low-grade oncocytic carcinoma ex pleomorphic adenoma is a challenging histopathological diagnosis which can be established with use of immunohistochemistry, generous tumor sampling and recognition of the multi-nodular, non-destructive, pattern of invasion. In the absence of clear-cut tumor encroachment into external structures, its malignant nature may not be easily identified on pre-operative imaging.

The Microbiome of Meibomian Gland Secretions from Patients with Internal Hordeolum Treated with Hypochlorous Acid Eyelid Wipes.

OBJECTIVE: The aims of our experiment were to compare the microorganisms in meibomian gland secretions from patients with internal hordeolum before and after treatment using hypochlorous acid eyelid wipes, to elucidate the mechanism underlying hypochlorous acid eyelid wipe treatment of internal hordeolum. METHODS: This was a prospective, matched-pair study. A total of eight patients with internal hordeolum who attended the ophthalmology clinic of our hospital from April to August 2020 were included. Meibomian gland secretions were collected from subjects before treatment (Group A) and from patients cured after eyelid cleaning with hypochlorous acid eyelid wipes for 7 days (Group B). Samples were submitted to 16S rRNA high-throughput sequencing, and the resulting data were analyzed to compare the differences in the structure and composition of meibomian gland secretion microbial flora before and after treatment of internal hordeolum. RESULTS: A total of 2127 operational taxonomic units were obtained from the two groups of samples, and there was no significant difference in alpha diversity before and after eyelid cleaning. At the phylum level, there was no significant difference between the two groups. The predominant phyla in Group A included the following: Firmicutes (32.78% ± 20.16%), Proteobacteria (26.73% ± 7.49%), Acidobacteria (10.58% ± 11.45%), Bacteroidetes (9.05% ± 6.63%), Actinobacteria (8.48% ±1.77%), and Chloroflexi (3.15% ± 3.12%), while those in Group B were the following: Proteobacteria (31.86% ± 9.69%), Firmicutes (29.07% ± 24.20%), Acidobacteria (11.33% ± 7.53%), Actinobacteria (7.10% ± 1.98%), Bacteroidetes (5.39% ± 5.17%), and Chloroflexi (3.89% ± 3.67%). Starting from the class level, significant differences in microbial communities were detected before and after eyelid cleaning (P < 0.05). Linear discriminant analysis effect size analysis showed the core flora in Group A microbiome comprising Actinobacteria, Staphylococcus, Staphylococcaceae, Staphylococcus aureus, Ruminococcacea UCg-014, Ruminococcacea-UCG-014, Halomonadaceae, Neisseria, Methylobacterium, Frankiales, and Neisseria sicca, while those in Group B microbial were Streptococcus sp., Blautia, Bifidobacterium pseudocatenulatum, Subdoligranulum, Subdoligranulum variabile, Faecalibacterium, and Faecalibacterium prausnitzii. CONCLUSION: Eyelid cleaning with hypochlorous acid eyelid wipes does not change the biodiversity in the meibomian gland secretions of patients with internal hordeolum. Hypochlorous acid eyelid wipes may affect the internal hordeolum through broad-spectrum antibacterial action to effectively reduce the relative abundance of symbiotic pathogens, such as Staphylococcus, Neisseria, Actinomycetes, and Ruminococcus and increase that of Faecalibacterium prausnitzii and other symbiotic probiotics with anti-inflammatory effects.

Resolution of (R,S)-1-(4-methoxyphenyl)ethanol by lipase-catalyzed stereoselective transesterification and the process optimization.

An efficient lipase-catalyzed stereoselective transesterification reaction system was established for resolution of 1-(4-methoxyphenyl)ethanol (MOPE) enantiomers. A series of lipases were tested and compared. The immobilized lipase Novozym 40086 is selected as the best choice. The effects of organic solvent, acyl donor, time and temperature on substrate conversion (c), and optical purity of the remaining substrate (eeS ) were investigated. Response surface methodology and central composite design were employed to evaluate the effect of some important factors and to optimize the process. Under the optimized conditions including solvent of n-hexane, acyl donor of vinyl acetate, temperature of 35°C, substrate molar ratio of 1:6, enzyme dosage of 20 mg, and reaction time of 2.5 h, eeS of 99.87% with c of 56.71% is achieved. The use of alkane solvent and immobilized enzyme, the mild reaction conditions, and the reduced reaction time make the system promising in industrial application.

Epithelioid Sarcoma of the External Auditory Canal: An Uncommon Tumor at an Unusual Site and a Brief Overview of the Literature.

We present a case (41 years old pregnant female) with epithelioid sarcoma arising in the left external auditory canal. On immunohistochemistry, the tumor cell diffusely expressed cytokeratins and showed patchy expression of ERG and CD34. The neoplastic cells demonstrated uniform loss of INI1-expression. Epithelioid sarcoma arising in the external auditory canal is rare. Awareness that ES may rarely arise at unusual sites is of critical importance in order to apply a broad enough panel in the immunohistochemical study, so a misdiagnosis of carcinoma can be avoided.

Cardiac sarcoma attached to pacemaker lead.

BACKGROUND AND AIM: Cardiac sarcoma is a rare condition and may mimic atrial myxoma. We present a case report of a man with a cardiac sarcoma. METHOD: Case report presentation. RESULTS: A 68-year-old man with a permanent pacemaker presented to us with a 4-month history of breathlessness. Echocardiography revealed a large right atrial mass adherent to the pacemaker lead and a provisional diagnosis of atrial myxoma was made based on echocardiographic appearance. A 60 x 30 x 30 mm irregular lobulated tumour was surgically resected from the right atrium. Upon histopathologic examination, the tumour was consistent with an undifferentiated pleomorphic sarcoma. CONCLUSION: Cardiac sarcomas have an extremely poor prognosis and more unfortunately this man developed a surgical site infection and died of acute mediastinitis. We discuss the presentation, imaging and current surgical approaches to cardiac sarcoma. Curative treatment is currently limited for this disease.

(Mammary Analogue) Secretory Carcinoma of the Nasal Cavity: Report of a Rare Case with p63 and DOG1 Expression and Uncommon Exon 4-Exon 14 ETV6-NTRK3 Fusion Diagnosed with Next Generation Sequencing.

We present a 72 years old male with a left nasal cavity (mammary analogue) secretory carcinoma (SC) which exhibited classical morphological features on light microscopical examination, diffuse strong S100 and mammoglobin positivity on immunohistochemistry, and ETV6-NTRK3 gene fusion on next generation sequencing (NGS) analysis. Unusual features of this tumor are expression of p63 and DOG1 on immunohistochemistry and the atypical junction between Exon 4 of the ETV6 gene and Exon 14 of the NTRK3 gene.

Cervical Myxoid Solitary Fibrous Tumor: Report of an Unusual Variant and a Brief Overview of the Literature.

We present a 49 year old female with a diagnostically challenging myxoid solitary fibrous tumor arising in the soft tissue of the neck. The tumor was diffusely positive for CD34 and STAT6 on immunohistochemistry.

Detection of Clinical Mesenchymal Cancer Cells from Bladder Wash Urine for Real-Time Detection and Prognosis.

Bladder cancer (BC) is a disease that requires lifelong surveillance due to its high recurrence rate. An efficient method for the non-invasive rapid monitoring of patient prognosis and downstream phenotype characterization is warranted. Here, we develop an integrated procedure to detect aggressive mesenchymal exfoliated bladder cancer cells (EBCCs) from patients in a label-free manner. Using a combination of filtration and inertial focusing principles, the procedure allowed the focusing of EBCCs in a single stream-line for high-throughput separation from other urine components such as large squamous cells and blood cells using a microfluidic sorting device. Characterization of enriched cells can be completed within hours, suggesting a potential utility for real-time detection. We also demonstrate high efficiency of cancer cell recovery (93.3 ± 4.8%) and specific retrieval of various epithelial to mesenchymal transition (EMT) phenotype cell fractions from respective outlets of the microfluidic device. EMT is closely associated with metastasis, drug resistance and tumor-initiating potential. This procedure is validated with clinical samples, and further demonstrate the efficacy of bladder wash procedure to reduce EBCCs counts over time. Overall, the uniqueness of a rapid and non-invasive method permitting the separation of different EMT phenotypes shows high potential for clinical utility. We expect this approach will better facilitate the routine screening procedure in BC and greatly enhance personalized treatment.

Primary Tonsillar Epithelioid Follicular Dendritic Cell Sarcoma: Report of a Rare Case Mimicking Undifferentiated Carcinoma and a Brief Review of the Literature.

We present a 52 years old male with a left tonsillar follicular dendritic cell sarcoma with prominent epithelioid features that on light microscopical examination bore a striking resemblance to a lymphoepithelial or undifferentiated carcinoma. The tumor was immunohistochemically positive for CD21 and CD35 and negative for cytokeratins. Two distinct histopathological features (both present in our case) that may serve as clues to the correct diagnosis on light microscopical examination were formation of ectatic pseudovascular spaces lined by malignant cells and the presence of non-neoplastic multinucleated giant cells. Familiarity with the above-mentioned morphological clues, and awareness that this tumour may occur in anatomical sites outside the lymph node, are essential for accurate diagnosis.

Molecular profiling of different glioma specimens from an Ollier disease patient suggests a multifocal disease process in the setting of IDH mosaicism.

Ollier disease (OD) and Maffucci syndrome are rare conditions due to a post-zygotic somatic mutation that results in mosaicism. In addition to enchondromas and hemangiomas, some of these patients also develop other unrelated tumors, such as gliomas, that harbor IDH mutations, suggesting that an IDH mutation is a common genetic event in the tumorigenesis in this group of patients. We illustrate an interesting case of multifocal IDH-mutant astrocytomas in an OD patient with 8 years of follow-up. We first demonstrated identical IDH mutations in the brain tumor samples from various locations in this patient, but different 1p,19q results by fluorescent in-situ hybridization, different whole genome copy number profiles by OncoScan analysis, and a discrepant IDH2M131I mutation unique to one tumor, supporting a multifocal disease process in the setting of somatic IDH mosaicism.

Thymoma: a clinicopathological correlation of 1470 cases.

We present 1470 surgical resections for thymoma identified in the pathology files of 14 institutions from 11 countries with the purpose of determining and correlating a simplified histological classification of thymoma and pathological staging with clinical outcome. The study population was composed of 720 men and 750 women between the ages of 12 and 86 years (average, 54.8 years). Clinically, 137 patients (17%) had a history of myasthenia gravis, 31 patients (3.8%) of other autoimmune disease, and 55 (6.8%) patients of another neoplastic process. Surgical resection was performed in all patients. Histologically, 1284 (87.13%) cases were thymomas (World Health Organization types A, B1, and B2, and mixed histologies), and 186 (12.7%) were atypical thymomas (World Health Organization type B3). Of the entire group, 630 (42.9%) were encapsulated thymomas, and 840 (57.9%) were invasive thymomas in different stages. Follow-up information was obtained in 1339 (91%) patients, who subsequently were analyzed by univariate and multivariate statistical analysis. Follow-up ranging from 1 to 384 months was obtained (mean, 69.2 months) showing tumor recurrence in 136 patients (10.1%), whereas 227 died: 64 (28.2%) due to tumor and 163 (71.8%) due to other causes. Statistical analysis shows that separation of these tumors into thymoma and atypical thymoma is statistically significant (P = .001), whereas tumor staging into categories of encapsulated, minimally invasive, and invasion into adjacent organs offers a meaningful clinical assessment with a P = .038. Our findings suggest that our simplified histological schema and pathological staging system are excellent predictors of clinical outcome.