Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

Clinical and Radiologic Outcomes After Fenestration and Partial Wall Excision of Idiopathic Intradural Spinal Arachnoid Cysts Presenting with Myelopathy.

BACKGROUND: Intradural spinal arachnoid cysts (ISACs) with associated neurologic deficits are encountered infrequently. Various management strategies have been proposed with minimal data on comparative outcomes. OBJECTIVE: We describe the clinical and radiologic presentation as well as the outcomes of 14 surgically managed patients who presented with an ISAC and associated myelopathy. METHODS: We retrospectively reviewed the clinical course of consecutive patients presenting with neurologic deficits associated with idiopathic ISACs at our institution. The diagnoses were based on preoperative magnetic resonance imaging studies followed by intraoperative and histopathological confirmation. RESULTS: A total of 14 consecutive patients with ISACs (1 cervicothoracic, 12 thoracic, and 1 thoracolumbar) and associated myelopathy were identified. Syringomyelia was noted in 8 patients. All ISACs were treated with cyst fenestration and partial wall resection through a posterior approach. Preoperative neurologic symptoms were noted to be stable or improved in all patients starting at 6-week postoperative follow-up. The median (interquartile range) preoperative mJOA score was 13 (12.0-14.8), whereas the postoperative median score at a mean follow-up of 22 months (range 6-50 months) was 16 (14.0-17.0), which represents a median improvement (ΔmJOA) of 2.0 (1.3-3.0) (P < 0.001). Comparison of ΔmJOA scores between cases without and with associated syrinxes did not reveal a significant difference (P = 0.23). Postoperative magnetic resonance imaging scans revealed spinal cord re-expansion at the level of the ISAC in all cases and either complete or partial syrinx resolution in 7 of 8 cases. CONCLUSIONS: Early treatment with fenestration and partial wall resection allows for cord decompression, syrinx resolution, and gradual resolution of myelopathic symptoms in most cases.

Crospovidone and Microcrystalline Cellulose: A Novel Description of Pharmaceutical Fillers in the Gastrointestinal Tract.

Crospovidone and microcrystalline cellulose (MCC) are pharmaceutical fillers well known in the pulmonary pathology literature. Fillers are inactive substances incorporated into medications to facilitate drug delivery. By examining 545 consecutive gastrointestinal surgical specimens from 302 patients between September 11, 2015 and October 23, 2015, we identified the fillers in 29 specimens from 26 patients. The control group consisted of an equal number of consecutive site-matched specimens collected during this same time. Pertinent clinicopathologic data were analyzed, and 1 case was subject to special stains. To confirm the histologic diagnosis, a variety of fillers and medications common to the patients were processed. The fillers were found in 9% of all patients, and there were no specific clinicopathologic associations. In the gastrointestinal tract, crospovidone is nonbirefringent and has a coral shape with each segment composed of a pink core and purple coat; MCC is brightly birefringent with matchstick shape and clear color. Identical material was seen in the processed crospovidone and MCC powders, as well as oxycodone-acetaminophen and omeprazole tablets. In summary, crospovidone and MCC are common, biologically inert, and they are most often seen in the small bowel. Their presence outside of the luminal bowel may serve as a surrogate marker for perforation. Awareness of their morphology is important to distinguish fillers from parasites, calcifications, and other medications, particularly those linked to mucosal injury. We report the unique histomorphologic profile of these fillers as a helpful diagnostic aide, and caution that the fillers have slightly divergent features when compared with those described in the lung.