Use of a Novel Polymer in an Animal Model of Head and Neck Squamous Cell Carcinoma.

Objective To evaluate the adverse effects and therapeutic efficacy of our biocompatible polymer platform delivering targeted local therapy of cytokine CCL21 and cisplatin in a partially resected xenograft animal model of head and neck squamous cell carcinoma. In addition, to evaluate the efficacy of cotreatment with radiotherapy and assess the biocompatibility of the cisplatin-eluting polymer in the murine neck. Study Design Experimental animal study. Setting Academic research laboratory. Subjects and Methods SCCVII/SF cell injection established head and neck squamous cell carcinoma tumors in C3H/HeJ mice. Subjects underwent surgery, and a chemokine-eluting polymer was implanted into the resected site. Subjects treated with cisplatin received radiation or no radiation, and tissue was harvested after 8 weeks to assess polymer biocompatibility. Results Our results with the polymer platform significantly ( P < .05) reduced SCCVII/SF tumor size in C3H/HeJ mice with cisplatin (49% ± 8.7%, Δ3.4 ± 0.6 cm3 [95% CI]), CCL21 (42% ± 4.8%, Δ3.5 ± 0.4 cm3), and cisplatin/CCL21 dual-agent polymer (82% ± 4.4%, Δ8.0 ± 0.4 cm3) as compared with controls. Cisplatin polymer with high-dose (16 Gy) and low-dose (4 Gy) radiation reduced tumor mass (respectively, 92% ± 7.2%, Δ6.1 ± 0.5 cm3; 85% ± 7.4%, Δ5.7 ± 0.5 cm3) as compared with the reduction from high-dose radiotherapy alone (70% ± 7.9%, Δ4.7 ± 0.5 cm3). No significant toxicity or inflammation was noted on histopathology after radiotherapy and cisplatin-eluting polymer treatment. Conclusion Cisplatin, CCL21, and cisplatin/CCL21 dual-agent polymer all exhibit significant antitumor effects and decrease tumor burden. Moreover, combination cisplatin polymer with radiotherapy may permit a decrease in intensity of radiation therapy in patients having received the cisplatin polymer. Histopathologic analysis suggests that the polymer is free from significant adverse effects in this model and warrants clinical trial.

Intraosseous mucoepidermoid carcinoma: Outcome review.

OBJECTIVE: Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma. STUDY DESIGN: Retrospective review of institutional case records and literature. METHODS: This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck. RESULTS: Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer. CONCLUSION: This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1083-1092, 2018.

Dynamic Optical Contrast Imaging.

The variable location and indistinct features of parathyroid glands can make their intraoperative identification challenging. Currently, there exists no routine use of localization methods during surgery. Dynamic optical contrast imaging (DOCI) leverages a novel realization of temporally dependent measurements of tissue autofluorescence that allows the acquisition of specific tissue properties. A prospective series of patients with primary hyperparathyroidism was examined. Parathyroid lesions and surrounding tissues were collected; fluorescence decay images were acquired via DOCI. Ex vivo samples (81 patients) were processed for histologic assessment. DOCI extracts relative fluorescence decay information in a surgically relevant field of view with a clinically accessible acquisition time <2 minutes. Analysis of DOCI revealed microscopic characterization sufficient for tissue type identification consistent with histology ( P < .05). DOCI is capable of efficiently distinguishing parathyroid tissue from adjacent tissues. Such an intraoperative tool would be transformative, helping surgeons to identify lesions, preserve healthy tissue, and improve patient outcomes.

Dynamic optical contrast imaging as a novel modality for rapidly distinguishing head and neck squamous cell carcinoma from surrounding normal tissue.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are debilitating diseases for which a patient's prognosis depends heavily on complete tumor resection. Currently, the surgeon's fingers determine the location of tissue margins. This study evaluated the diagnostic utility of a novel imaging modality, dynamic optical contrast imaging (DOCI), in the detection of HNSCC. This system generates contrast by illuminating the tissue with pulsed light and detecting variations in endogenous fluorophore lifetimes. METHODS: A total of 47 fresh ex vivo samples from 15 patients were imaged with the DOCI system immediately after surgical resection. DOCI maps were analyzed to determine the statistical significance of contrast between tumors and adjacent nonmalignant tissue. Pilot intraoperative clinical data were also acquired. RESULTS: Statistical significance (P < .05) between muscle and tumor was established for 10 of 10 emission wavelengths, between collagen and tumor for 8 of 10 emission wavelengths, and between fat and tumor for 2 of 10 wavelengths. The system extracted relative fluorescence decay information in a surgically relevant field of view in <2 minutes. CONCLUSIONS: This study demonstrates the feasibility of using DOCI to rapidly and accurately distinguish HNSCC from surrounding normal tissue. An analysis of DOCI images revealed microscopic characterization sufficient for tissue-type identification consistent with histology. Such an intraoperative tool would be transformative by allowing the rapid delineation of tumor tissue from nontumor tissue and thus maximizing the efficacy of resection and improving patient outcomes. Cancer 2017;123:879-86. © 2016 American Cancer Society.

p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma.

BACKGROUND: In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC). METHODS: Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used. RESULTS: p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail. p38 binds to and stabilizes p38IP, a subunit of histone SPT3-TAF9-GCN5 acetyltransferase (STAGA), resulting in enhanced transcription of Snail. p38 shRNA HNSCC cell lines show a less invasive phenotype in a spheroid model. In clinical HNSCC samples, p38 interacting protein (p38IP) is significantly increased compared to adjacent normal tissue. An inverse relationship between p38, p38IP and E-cadherin is demonstrated. CONCLUSIONS: Herein we provide the first report that p38-p38IP is required for the Snail-induced E-cadherin down-regulation and cell invasion in HNSCC.

Clinicopathological and Targeted Exome Gene Features of a Patient with Metastatic Acinic Cell Carcinoma of the Parotid Gland Harboring an ARID2 Nonsense Mutation and CDKN2A/B Deletion.

We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC). A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism. Tumor staging was pT4 N0 MX. Immunohistochemistry staining showed pankeratin (+), CD56 (-), and a Ki67 proliferation index of 15%. Upon microscopic inspection, 49 local lymph nodes resected during parotidectomy were negative for cancer cells. Targeted sequencing of the primary tumor revealed deletions of CDKN2A and CDKN2B, a nonsense mutation in ARID2, and single missense mutations of unknown significance in nine other genes. Despite postoperative localized radiation treatment, follow-up whole body PET/CT scan showed lung, soft tissue, bone, and liver metastases. The patient expired 9 months after resection of the primary tumor.

Invasive fungal sinusitis in a healthy athlete due to long-term anabolic steroid use.

Invasive fungal rhinosinusitis is a potentially fatal infection that affects immunocompromised patients. Prognosis is generally poor despite aggressive medical and surgical treatments. We present the first reported case of invasive fungal sinusitis in a healthy 18-year-old male athlete who was taking anabolic androgenic steroids (AAS). The effects of excessive AAS use on the immune system are not fully understood, but there may be consequences at supraphysiological concentrations. This case demonstrates potential immunomodulatory effects of anabolic steroids and highlights a previously unknown cause of invasive fungal sinusitis.

COX-(2) overexpression in sinonasal inverted papilloma.

BACKGROUND: Inverted papilloma (IP) is a benign, but locally aggressive neoplasm of the nasal cavity and paranasal sinuses. The mainstay of treatment of IP is surgical resection, but high rates of tumor recurrence have been reported. Cyclo-oxygenase-2 (COX-2) has been found to be overexpressed in many tumors and has been used successfully as a therapeutic target. The goal of this study is to highlight COX-2 expression in IP. METHODS: Immunohistochemistry for COX-2 was performed on IP samples obtained during surgical resection between January 2012 and June 2013. The intensity of staining was evaluated by 2 head and neck pathologists blinded to the clinical features and outcomes. A positive stain was defined as having 10% or more of tumor cells exhibiting immunoreactivity. RESULTS: The study includes 13 tumor samples from 7 females and 6 males. Mean age was 54.5 (range, 18-81) years. Tumor locations included: nasal septum (1), ethmoid (3), sphenoid (4), and maxillary (5) sinuses. No tumors demonstrated malignancy or dysplasia. Five (38%) of the 13 IP samples stained strongly positive for COX-2, and 3 of 13 (23%) stained weakly positive. There were no clinical differences in patients that stained strongly or weakly for COX-2. CONCLUSION: COX-2 overexpression was identified in 62% of cases of IP in this study, and strongly positive in 38% of cases. Larger studies are necessary to identify the true incidence of COX-2 expression for this tumor. Pharmaceuticals targeting COX-2 may eventually provide an additional therapeutic option for select cases of recurrent or unresectable IP.

Primary small cell carcinoma of the lung initially presenting as a breast mass: a fine-needle aspiration diagnosis.

The incidence of metastases to the breast from extramammary sites is relatively low compared with the incidence of primary breast carcinoma. Primary sites which have a predilection for metastases to the breast include, in the order of decreasing frequency, malignant melanoma, lymphoma, lung carcinoma, ovarian carcinoma, and soft tissue sarcoma, followed by gastrointestinal and genitourinary primaries. Most lung primaries metastasizing to breast represent adenocarcinoma. Other types of lung carcinoma, including small cell carcinoma, are relatively rare. We report a case of lung small cell carcinoma metastasizing to the breast and initially presenting with a breast mass in a 50-year-old female. The tumor was first diagnosed on a fine-needle aspiration biopsy specimen (FNAB) from the breast lesion and subsequently supported by core biopsy. A discussion of the differential diagnoses to consider on FNAB follows. Because of the difference in treatment for primary small cell carcinoma of breast versus primary small cell carcinoma of the lung, as well as the difference in prognosis for both malignancies, determining the site of primary malignancy is crucial to adequate patient care.