NIMG-64. TYPE OF BONY INVOLVEMENT PREDICTS GENOMIC SUBGROUP IN SPHENOID WING MENINGIOMAS

OBJECTIVE As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature. METHODS Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as frank tumor invasion (TI), hyperostosis only (HOOs), or both (TI+HO). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Predictive logistic regression models were developed for genomic subgroups based on pre-operative clinical features. RESULTS Among 64 SWMs, 53% had HOO, 9% had TI, and 14% had TI+HO; nine SOMs were identified. Tumors with invasion (i.e., TI or TI+HO) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor NF2 mutations (OR: 27.6; p: 0.004), while hyperostosis only (without frank tumor invasion) were over 4 times more likely to have a TRAF7 mutation (OR: 4.5; p: 0.023). SOMs were a significant predictor of underlying TRAF7 mutation (OR: 10.21; p: 0.004). CONCLUSIONS SWMs with invasion into bone tend to be higher grade and are more likely to be NF2 mutated, while SOMs and those with hyperostosis are associated with TRAF7 variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers.

Frontalis associated intramuscular lipoma: a case report

<p>Lipomas are the most common benign mesenchymal tumours that are composed of adipose tissue. They can occur at any age and can arise in any location, but are more frequently found on the chest, arm, shoulder and thigh. We report a rare case of lipoma attached to the frontalis muscle in a 65 year old male patient. Clinical examination had revealed a 1.5×1.5 cm in size, firm, non-tender, mobile subcutaneous nodule on the right side of the forehead that gradually increased in size over 8 years. Differential diagnosis of lipoma, liposarcoma, epidermal cyst and sebaceous cyst of the forehead were considered. Non-Contrast computed tomography revealed it to be a solitary, localized, circumscribed nodule within the frontalis without any bony involvement. The nodule was surgically removed and the diagnosis of intramuscular lipoma was confirmed on histopathological examination. The postoperative healing was uneventful and one year follow-up did not show recurrence. The prognosis of the rare frontalis associated intramuscular lipoma is good and risk of recurrence is low provided there is complete removal.</p>

Assessing the accuracy of computed tomography in detecting bony invasion and thickness of squamous cell carcinoma of the scalp

Objectives The aim of this study was to ascertain the accuracy of computed tomography (CT) in assessing the presence of bony involvement and thickness of squamous cell carcinoma (SCC) of the scalp. Methods A single-centre retrospective chart review was carried out. Inclusion criteria were scalp SCC, CT between January 2008 and 2018, and the availability of a reference test. Reference tests were either histology, surgical notes or clinical notes. Tabular assessment of accuracy was performed and Student’s t-test, Mann–Whitney U test and Fisher exact test were used in univariable analysis. Accuracy of thickness measurement was calculated using the limits of agreement method, and linear regression was used to examine trend. Results Thirty-nine patients were included. Most patients were male (74.4%), white (97.4%), not immunosuppressed (66.6%) and had poorly differentiated tumours (33.3%). The most common tumour sites were the vertex (28.2%) and temporal region (23.1%). Sensitivity of CT in detecting presence or absence of bony invasion of scalp SCC was 76.9% (95% CI 46.2–94.9%) and specificity was 96.2% (95% CI 80.4-99.9%). Overall accuracy was 89.7% (95% CI 75.8–97.1%), positive predictive value was 90.1% (95% CI 58.7–99.8%) and negative predictive value was 89.3% (95% CI 71.8–97.7%). No significant differences were found comparing patients with an accurate or inaccurate CT scan. Thickness on CT was found to be consistent with histological thickness at the 95% confidence level. Conclusions CT is accurate at assessing the presence of bony involvement and thickness of scalp SCC. This study was limited somewhat by small sample size.

Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings

Background: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently approved for treatment of OSCC. We described the histologic findings in OSCC following neoadjuvant pembrolizumab, including identification of immune-related cell populations and cancer-associated fibroblasts (CAFs).Materials and Methods: Patients with OSCC clinical stages 3 and 4 and a combined PD-L1 score &gt;1 were randomized either to the standard oncologic protocol or to the pembrolizumab arm of MK-3475-689 study for Head and Neck, Lip, and Oral Cavity. The latter were given two standard doses of 200 mg of pembrolizumab, 3 weeks apart, and then underwent surgical oncologic procedure according to the initial stage. Sections from the resection specimens were analyzed for pathological response to pembrolizumab. Various populations of immune-related cells within the tumor microenvironment were characterized by immunohistochemistry, as were the CAFs.Results: Three patients who were randomized to the pembrolizumab study were described. One patient presented with a tongue SCC, the other two had SCC of the mandibular ridge with bony involvement. Only the patient with tongue SCC showed clinical complete response. Microscopically, the tumor was replaced by a granulomatous type of inflammation. Immunohistochemical stains revealed massive T cell rich (CD3+) infiltrate, with approximately equal amounts of CD4+ and CD8+ cells, numerous macrophages of CD68+ and CD163+ phenotypes; no CAFs were identified. The other two patients were regarded as non-responders as at least 50% of the tumor was viable. The tumor microenvironment of these tumors was generally associated with a lesser extent of inflammatory response compared to the tongue tumor, a variable CD4+/CD8+ ratio and presence of CAFs. Neither T regulatory cells (FOXP3+) nor natural killer cells (CD56+, CD57+) were identified in any of the cases.Conclusion: We showed that characterizing the specific populations of immune-related cells and CAFs after treatment with pembrolizumab, may add to our understanding of the tumor-TME interactions in this setting. These findings should be investigated in future studies on a larger number of patients.

Bartonella osteomyelitis versus vertebral sarcoidosis: A tale of two cases

Background Osteomyelitis is an uncommon manifestation of Bartonella henselae. Similarly, bony involvement may occur with sarcoidosis. Even though these are pathologically distinct entities, they can have overlapping imaging manifestations and therefore mimic one another. This is further complicated by the fact that both entities show non-caseating granulomatous inflammation on histopathology. We present two cases with similar imaging findings, with one case eventually diagnosed as Bartonella osteomyelitis, while the other proved to be vertebral sarcoidosis. Both patients exhibited vertebral involvement in common, and improved clinically and radiographically following antibiotics and steroids treatment, respectively. Given the overlapping pathological and imaging manifestations, and the non-specific clinical presentation, these entities may be considered in the differential consideration of each other. The presence of associated findings in such cases may be helpful.

MON-335 Bisphosphonate and Denosumab Refractory Hypercalcemia of Malignancy: What Else Is at Play?

Hypercalcemia of Malignancy has been historically responsive to anti-resorptive agents. However, when multiple mechanisms contribute, it may be difficult to treat with one modality. This case highlights the importance of the work up in treatment of hypercalcemia in a low PTH state. A 44 yo M with h/o high grade metastatic spindle cell neoplasm with skeletal metastasis was admitted with hypercalcemia. He reported some constipation prior to presentation, however denied confusion. His vital signs were notable for HR of 86 bpm and BP of 112/75 mmHg. Labs at admission were remarkable for an uncorrected Ca of 16.1 (8.8-10.3 ng/mL), a phosphorus (Phos) level of 3.3 mg/dL (2.5-4.5 mg/dL), a PTH level of 11 pg/mL (15-65 pg/mL), PTHrP level of 134 pg/mL (14-27 pg/mL), a 25 OH vit D level of 11 ng/mL (30-100 ng/mL), and a BUN/Cr and GFR of 34/2.38 (8-22 mg/dL/0.5-1.3 mg/dL) and 32 ml/min/m2. He was given intranasal calcitonin and ergocalciferol, then received 2mg IV of zolendronic acid, which reduced the patient’s Ca level to a nadir of 6.6 ng/mL in 5 days. On the next admission serum Ca was elevated to 15.7 ng/dL, which did not respond to zolendronic acid. Given that patient’s Ca was refractory to zolendronic acid, denosumab was given but had no response. He then underwent surgery for cord compression and was given dexamethasone (dex) 4mg IV Q6h post-op. His Ca responded quickly to dex, with a nadir to 9.2 ng/dL, however his Ca became elevated after cessation. Given response to dex, vit D 1,25 OH level was sent and was elevated at 94 pg/mL (18-72 pg/mL). In addition, given his inappropriately normal Phos level in the setting of low PTH, FGF23 was sent and came back elevated at 473 RU/mL (&lt;180 RU/mL). This was likely due to increased bone turnover and release of FGF23. He was discharged with a Ca level of 12.5 ng/mL, however was found to have an elevated Ca to 14.9 ng/mL on presentation to clinic. Given concern that Vit D 1,25 OH, PTHrP and direct bony involvement were all contributing to his hypercalcemia, patient was started on IVF and dex IV. His calcium responded 11.5 ng/mL and was then transitioned to PO dexamethasone and plaquenil. The most likely explanation for this phenomenon is malignancy induced cytokine/PAMP release, which stimulates 1-alpha hydroxylase in tumor macrophages to convert 25 OH D to 1,25 OH D. This was supported by his elevated 1,25 OH D level and a decreased 25 OH D, which suggests that 25 OH D was used as substrate by activated macrophages. This case highlights the importance of ancillary work up of hypercalcemia when a patient’s calcium is refractory to standard anti-resorptive therapy. Moreover, it shows the need for a systematic approach when treating hypercalcemia.

Local Delivery of Antibiotics in the Context of Chronic Diabetic Foot Infection with Bony Involvement: A Case Series of 102 Patients

Category: Diabetes Introduction/Purpose: Diabetic foot infection (DFI) is a devastating condition which poses risk to both life and limb. Treatment principles revolve around surgical debridement, dead space management, delivery of both local and systemic antibiotics and soft tissue cover. Dead space management and local antibiotic delivery can be achieved simultaneously by using an antibiotic loaded bone substitute. We report our retrospective case series of patients treated with surgical management involving local antibiotic delivery via calcium sulphate bone substitute (Stimulan™; Biocomposites, Keele, UK). Methods: All patients between January 2015 and June 2018 with DFI and proven bony involvement presenting to our university teaching hospital were treated via our extensive MDT approach. A total of 102 patients were included. Surgical debridement was performed along with simultaneous insertion of 10 ml calcium sulphate with 1 g vancomycin and 240 mg gentamycin. Outcome was classified as resolved, requiring prolonged treatment from other medical (endocrinologist) or surgical (plastic surgery, limb reconstruction) services or salvage surgery in the form of proximal amputation. Results: 45.1% of patients had a partial amputation at the index surgery. 52% had bony debridement and just 2.9% had soft tissue debridement in conjunction with calcium sulphate insertion. The surgical wound was primarily closed in 56.8% of patients. 7 patients had delayed wound closure and 36.2% of patients healed via secondary intention. 74 patients (72.5%) had resolution of their DFI with bony involvement following surgical intervention. 21 (20.6%) patients needed further treatment from allied specialties. 7 (6.9%) patients required salvage surgery in the form of a below knee amputation. There was no correlation between either closure type (2 p-value 0.75) or index surgery type and outcome (2 p-value 0.64). Conclusion: DFI is a difficult clinical scenario to treat effectively. An MDT approach is undoubtedly key to a good outcome. We believe that the use of calcium sulphate can be a useful adjunct at the time of surgical debridement to aid in both dead space management and allow local antibiotic delivery.