miR-211 expression in human oral squamous cell carcinoma (OSCC) has been implicated in poor patient survival. To investigate the oncogenic roles of miR-211, we generated K14-EGFP-miR-211 transgenic mice tagged with GFP. Induction of oral carcinogenesis in transgenic mice using 4-nitroquinoline 1-oxide (4NQO) resulted in more extensive and severe tongue tumorigenesis compared with control animals. We found that 4NQO and arecoline upregulated miR-211 expression in OSCC cells. In silico and experimental evidence further revealed that miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities in OSCC cells and was drastically downregulated in tumor tissues. We used GeneChip analysis and bioinformatic algorithms to identify transcriptional targets of TCF12 and confirmed through reporter and ChIP assays that family with sequence similarity 213, member A (FAM213A), a peroxiredoxin-like antioxidative protein, was repressed transcriptionally by TCF12. FAM213A silencing in OSCC cells diminished oncogenic activity, reduced the ALDH1-positive cell population, and increased reactive oxygen species. TCF12 and FAM213A expression was correlated inversely in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients bearing tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment downregulated TCF12 and upregulated FAM213A by modulating miR-211 both in vitro and in vivo Overall, our findings develop a mouse model that recapitulates the molecular and histopathologic alterations of human OSCC pathogenesis and highlight a new miRNA-mediated oncogenic mechanism. Cancer Res; 76(16); 4872-86. ©2016 AACR.

https://cancerres.aacrjournals.org/content/canres/76/16/4872.full.pdf

MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity.

Giant cell tumor of bone is a benign albeit aggressive tumor commonly affecting the bones of the knee. Patients with these tumors present with pain, swelling, and inability to bear weight on the involved extremity. These destructive tumors typically arise in the metaphyseal region of the long bones in individuals in the second, third, and fourth generations of life. Histologically, the multinucleated giant cells are the hallmark of the lesion, easily recognized on histological review, which recently have become therapeutic targets for medical management of the disease. For decades, surgical management has been the primary treatment for giant cell tumor of the bone. Some tumors can be treated with excision and filling of the osseous void with bone cement or allograft. This is an effective treatment option with a low to moderate risk of local recurrence while preserving limb function. For more destructive tumors, wide excision and reconstruction with prosthetic, structural allograft or combined allograft prosthetic components are utilized. Advances in medical management of the disease have also demonstrated promise as an effective treatment; however, its use has usually been limited to the treatment of metastatic disease, recurrent disease or when advanced local disease would require surgical treatment felt to be overly morbid.

Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options.

INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma

Purpose of reviewGiant cell tumor of bone (GCTB) is an uncommon benign primary bone tumor, consisting of receptor activator of nuclear factor kappa-B (RANK) expressing reactive osteoclast-like giant cells and neoplastic spindle-shaped cells. Denosumab was approved by FDA in 2013 and by EMA in 2014 t

Challenges of denosumab in giant cell tumor of bone, and other giant cell-rich tumors of bone

Mesenchymal Tumors with EWSR1 Gene Rearrangements.

Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone.

/pdf/two-cases-of-sarcoma-arising-in-giant-cell-tumor-of-bone-478qv4krjj.pdf

Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab

Extraskeletal myxoid chondrosarcoma with a t(9;16)(q22;p11.2) resulting in a NR4A3-FUS fusion

Bizarre parosteal osteochondromatous proliferation: a new cytogenetic subgroup characterized by inversion of chromosome 7.

Case. This case report describes the operative management of 16-year-old male with a symptomatic chondroblastoma of the distal femur with breach of the chondral surface. Following appropriate imaging and core needle biopsy, the diagnosis was confirmed histologically. The patient then underwent intralesional curettage and osteochondral allograft reconstruction of the defect. At one-year follow-up the patient was pain-free and has obtained excellent range of motion. There is radiographic evidence of allograft incorporation and no evidence of local recurrence. Conclusion. Osteochondral allograft reconstruction is an effective option following marginal resection and curettage of chondroblastoma involving the chondral surface of the distal femur.

/pdf/chondroblastoma-of-the-knee-treated-with-resection-and-3o8p9rjgrh.pdf

Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction

Context.— Pathology studies using convolutional neural networks (CNNs) have focused on neoplasms, while studies in inflammatory pathology are rare. We previously demonstrated a CNN differentiates reactive gastropathy, Helicobacter pylori gastritis (HPG), and normal gastric mucosa. Objective.— To determine whether a CNN can differentiate the following 2 gastric inflammatory patterns: autoimmune gastritis (AG) and HPG. Design.— Gold standard diagnoses were blindly established by 2 gastrointestinal (GI) pathologists. One hundred eighty-seven cases were scanned for analysis by HALO-AI. All levels and tissue fragments per slide were included for analysis. The cases were randomized, 112 (60%; 60 HPG, 52 AG) in the training set and 75 (40%; 40 HPG, 35 AG) in the test set. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The test set was blindly reviewed by pathologists with different levels of GI pathology expertise as follows: 2 GI pathologists, 2 general surgical pathologists, and 2 residents. Each pathologist rendered their preferred diagnosis, HPG or AG. Results.— At the HALO-AI AD percentage cutoff of 50% or more, the CNN results were 100% concordant with the gold standard diagnoses. On average, autoimmune gastritis cases had 84.7% HALO-AI autoimmune gastritis AD and HP cases had 87.3% HALO-AI HP AD. The GI pathologists, general anatomic pathologists, and residents were on average, 100%, 86%, and 57% concordant with the gold standard diagnoses, respectively. Conclusions.— A CNN can distinguish between cases of HPG and autoimmune gastritis with accuracy equal to GI pathologists.

/pdf/a-deep-learning-convolutional-neural-network-can-c0nz0beq6o.pdf

A Deep Learning Convolutional Neural Network Can Differentiate Between Helicobacter Pylori Gastritis and Autoimmune Gastritis With Results Comparable to Gastrointestinal Pathologists.

Cory Broehm

Papers

Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab

Extraskeletal myxoid chondrosarcoma with a t(9;16)(q22;p11.2) resulting in a NR4A3-FUS fusion

Bizarre parosteal osteochondromatous proliferation: a new cytogenetic subgroup characterized by inversion of chromosome 7.

Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction

A Deep Learning Convolutional Neural Network Can Differentiate Between Helicobacter Pylori Gastritis and Autoimmune Gastritis With Results Comparable to Gastrointestinal Pathologists.