Faculty Bibliography

OBJECTIVE:Acinic cell carcinoma (AciCC) is a rare, usually low-grade salivary malignancy. Evidence on rates of lymph node metastases (LNMs) is limited in pediatric patients and varies significantly (4%-45%) in adults. We set out to determine and compare rates of LNMs in pediatric and adult AciCC and to analyze their impact on survival, using the National Cancer Database. STUDY DESIGN/METHODS:Historical cohort study. SETTING/METHODS:National Cancer Database. METHODS:All AciCCs of the major salivary glands with complete clinical and pathologic nodal staging were selected between 2010 and 2016. Patient demographics, tumor characteristics, treatment, and survival were analyzed. Univariable and multivariable regression were performed to determine factors associated with LNMs and survival. RESULTS:< .001) were associated with LNM in adult patients. CONCLUSION/CONCLUSIONS:LNMs in AciCC of the major salivary glands are rare in children and adults. However, high-grade and T3-T4 tumors are associated with an increased risk of LNM. LNM is associated with worse survival.

OBJECTIVE:To present a rare case of a middle ear capillary hemangioma in an adult. PATIENT/METHODS:A 31-year-old woman with a 6-month history of left ear fullness, pressure, tinnitus, and progressive hearing loss. INTERVENTION/METHODS:Endoscopic laser-assisted resection. MAIN OUTCOME MEASURES/METHODS:Clinical, radiographic, and histopathological findings of a capillary hemangioma. RESULTS:Otoscopy revealed an erythematous and slightly pulsating multilobulated middle ear retrotympanic mass. Her audiogram demonstrated a left-sided mixed hearing loss with air-conduction thresholds in the severe-to-profound range. Computed tomography (CT) imaging was significant for total opacification of the left middle ear and mastoid air cells. She underwent a combined endoscopic transcanal and transmastoid excision of the mass with ossicular chain reconstruction. A KTP laser was used to ablate and shrink down the periphery of the lesion. Pathology of the specimen was consistent with a capillary hemangioma. The patient's pulsatile tinnitus and spontaneous vertigo resolved postoperatively. CONCLUSIONS:Capillary hemangiomas are an uncommon cause of vascular middle ear lesions in adults and typically present with symptoms of aural fullness, pulsatile tinnitus, conductive hearing loss, otalgia, and vertigo. Surgery resection provides definitive treatment and the use of laser ablation techniques can allow for hemostasis and excellent visualization.

Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS.

Myopericytomas are uncommon tumors defined by their round to spindle shaped cells often arranged in a concentric pattern of perivascular growth. They are typically well-circumscribed, nodular, slow-growing lesions that occur in the soft tissue of the extremities. Here, we present a 30-year-old female with a 2.4 cm myopericytoma occurring in the deep lobe of the parotid gland. The diagnosis was made with detailed histopathologic and immunohistochemical findings and positive identification of the specific mutation for PDGFRβ p.Asp666Lys by next generation sequencing (NGS). This is the first case report of a parotid myopericytoma with a genetic testing that shows a particular mutation that has been linked to myopericytomatosis.

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR₂) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR₂. We report here a role for cathepsin S in PAR₂-dependent cancer pain. We report that cathepsin S was more active in human oral SCC than matched normal tissue, and in an orthotopic xenograft tongue cancer model than normal tongue. The multiplex immunolocalization of cathepsin S in human oral cancers suggests that carcinoma and macrophages generate cathepsin S in the oral cancer microenvironment. After cheek or paw injection, cathepsin S evoked nociception in wild-type mice but not in mice lacking PAR₂ in Na_v1.8-positive neurons (Par₂Na_v1.8), nor in mice treated with LY3000328 or an endogenous cathepsin S inhibitor (cystatin C). The human oral SCC cell line (HSC-3) with homozygous deletion of the gene for cathepsin S (CTSS) with CRISPR/Cas9 provoked significantly less mechanical allodynia and thermal hyperalgesia, as did those treated with LY3000328, compared to the control cancer mice. Our results indicate that cathepsin S is activated in oral SCC, and that cathepsin S contributes to cancer pain through PAR₂ on neurons.

Introduction: TERT promoter mutations in thyroid carcinoma suggest worse prognosis based on findings of a small number of studies. Additionally, pathologic features and clinical behavior of indeterminate thyroid nodules (ITN) with TERT promoter mutations remain less studied. Our study aims to explore the clinicopathologic features of ITN with TERT promoter mutations.
Material(s) and Method(s): A search conducted in our electronic medical record between 2015-2018 identified 18 cases with indeterminate thyroid fine-needle aspiration (FNA) cytology (Bethesda Class III, IV, and V) and a TERT mutation on molecular testing. 17 patients underwent thyroidectomy and were the subjects of this study.
Result(s): The mean age was 65 (range 38-83) with a female to male ratio of 9:8. The FNA Bethesda diagnoses were Class III in 9, IV in 8, and V in 1. Majority of patients who underwent thyroidectomy had malignant nodules (14,78%). Thyroidectomy diagnoses included classic PTC (5,29%), FVPTC (5,29%), follicular variant of papillary carcinoma (3,17%), poorly differentiated thyroid carcinoma (1, 6%), follicular adenoma (2,11%) and NIFTP (1,6%). Additional alterations were present in 11 cases, including NRAS(6), KRAS(2), and BRAF V600E (3). Of three cases with concurrent BRAF V600E mutation, two were metastatic, and one had tall cell features. Of two follicular adenoma cases, one had a concomitant NRAS mutation, and the other displayed negative results on Afirma testing. Malignant cases tended to occur in older patients, the majority exhibited follicular architecture, frequent oncocytic morphology, and higher pathologic stage (pT3 in 92%, pT2 in 8%).
Conclusion(s): Most TERT promoter mutations in ITN cytology are associated with high risk of malignancy and these malignancies are associated with unfavorable features such as advanced stage, capsular/vascular invasion, and metastatic disease. Few TERT promoter mutations have a benign outcome. Further studies on ITNs with TERT mutations are needed to determine the optimal management of these nodules.
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