Publications by authors named "Diana Bell"

185 Publications

Non-functional water clear cell parathyroid carcinoma masquerading as medullary thyroid carcinoma.

Ann Diagn Pathol 2021 Jul 15;54:151791. Epub 2021 Jul 15.

Department of Pathology, The University of Texas MD Anderson Cancer, United States of America; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer, United States of America. Electronic address:

Parathyroid carcinoma is a rare neuroendocrine tumor. Non-functional parathyroid carcinomas are exceedingly rare neoplasms which generally present at an advanced disease stage, and occasionally can masquerade as medullary thyroid carcinoma.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151791DOI Listing
July 2021

Metagenomic identification of a new sarbecovirus from horseshoe bats in Europe.

Sci Rep 2021 07 19;11(1):14723. Epub 2021 Jul 19.

Centre for Ecology, Evolution and Conservation, School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.

The source of the COVID-19 pandemic is unknown, but the natural host of the progenitor sarbecovirus is thought to be Asian horseshoe (rhinolophid) bats. We identified and sequenced a novel sarbecovirus (RhGB01) from a British horseshoe bat, at the western extreme of the rhinolophid range. Our results extend both the geographic and species ranges of sarbecoviruses and suggest their presence throughout the horseshoe bat distribution. Within the spike protein receptor binding domain, but excluding the receptor binding motif, RhGB01 has a 77% (SARS-CoV-2) and 81% (SARS-CoV) amino acid homology. While apparently lacking hACE2 binding ability, and hence unlikely to be zoonotic without mutation, RhGB01 presents opportunity for SARS-CoV-2 and other sarbecovirus homologous recombination. Our findings highlight that the natural distribution of sarbecoviruses and opportunities for recombination through intermediate host co-infection are underestimated. Preventing transmission of SARS-CoV-2 to bats is critical with the current global mass vaccination campaign against this virus.
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http://dx.doi.org/10.1038/s41598-021-94011-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289822PMC
July 2021

Long-Term Outcomes of Olfactory Neuroblastoma: MD Anderson Cancer Center Experience and Review of the Literature.

Laryngoscope 2021 Jul 17. Epub 2021 Jul 17.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.

Objectives/hypothesis: Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis.

Study Design: Retrospective study.

Methods: A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival.

Results: Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P = .003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival.

Conclusion: ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance.

Level Of Evidence: Level 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29732DOI Listing
July 2021

Imaging of the Thyroid: Practical Approach.

Neuroimaging Clin N Am 2021 Aug;31(3):265-284

Department of Neuroradiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street Unit 1482, Houston, TX 77030, USA.

Imaging evaluation of the thyroid gland spans a plethora of modalities, including ultrasound imaging, cross-sectional studies, and nuclear medicine techniques. The overlapping of clinical and imaging findings of benign and malignant thyroid disease can make interpretation a complex undertaking. We aim to review and simplify the vast current literature and provide a practical approach to the imaging of thyroid disease for application in daily practice. Our approach highlights the keys to differentiating and diagnosing common benign and malignant disease affecting the thyroid gland.
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http://dx.doi.org/10.1016/j.nic.2021.04.008DOI Listing
August 2021

Pembrolizumab in Patients with Refractory Cutaneous Squamous Cell Carcinoma: A Phase II Trial.

Adv Ther 2021 Jul 9. Epub 2021 Jul 9.

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Introduction: Patients with advanced cutaneous squamous cell carcinoma (CSCC) have a poor prognosis. Blocking the PD-1-PD-L1 axis has shown promising activity in this patient population. We assessed the safety and antitumor activity of PD-1 inhibitor pembrolizumab in patients with refractory advanced CSCC.

Methods: This was a prespecified subgroup analysis of patients with advanced CSCC who enrolled in an open-label, phase II clinical trial for pembrolizumab in patients with refractory rare cancers during 2016-2018. Patients received pembrolizumab 200 mg intravenously every 21 days until progressive disease, unacceptable adverse event, or completion of 24 months of treatment. The primary endpoint was nonprogression rate (NPR) at 27 weeks; secondary endpoints included safety, objective response rate (ORR) per irRECIST, clinical benefit rate (CBR), progression-free survival, and overall survival.

Results: Twenty patients with refractory CSCC enrolled; 19 were evaluable for efficacy. Median follow-up time was 44.1 months. The NPR at 27 weeks was 37% (95% CI 0.16-0.62). Three patients had a complete response (CR), three had a partial response, and one had stable disease, for an ORR of 32% and a CBR of 37%; median duration of response was 27.3 months. All three patients with a CR remained free of recurrence at the time of writing. Severe treatment-related adverse events (grade ≥ 3) occurred in 10% of patients (2/20). PD-L1 expression was not correlated with response to pembrolizumab.

Conclusion: A long-term follow-up confirms pembrolizumab's antitumor activity and safety profile in patients with refractory CSCC. Patients with a CR may experience cure.

Trial Registration: ClinicalTrials.gov, NCT02721732, Registered March 29, 2016.
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http://dx.doi.org/10.1007/s12325-021-01807-6DOI Listing
July 2021

Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck.

Clin Cancer Res 2021 Jun 29. Epub 2021 Jun 29.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence.

Patients And Methods: Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response.

Results: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR ( = 11) or MPR ( = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8 T-cell cluster enriched in patients with pCR.

Conclusions: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0585DOI Listing
June 2021

Novel anaplastic thyroid cancer PDXs and cell lines: Expanding preclinical models of genetic diversity.

J Clin Endocrinol Metab 2021 Jun 19. Epub 2021 Jun 19.

Departments of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: Anaplastic thyroid cancer (ATC) is a rare, aggressive, and deadly disease. Robust pre-clinical thyroid cancer models are needed to adequately develop and study novel therapeutic agents. Patient-derived xenograft (PDX) models may resemble patient tumors by recapitulating key genetic alterations and gene expression patterns, making them excellent pre-clinical models for drug response evaluation. We developed distinct ATC PDX models concurrently with cell lines and characterized them in vitro and in vivo.

Materials & Methods: Fresh thyroid tumor from patients with a preoperative diagnosis of ATC was surgically collected and divided for concurrent cell line and PDX model development. Cell lines were created by generating single cells through enzymatic digestion. PDX models were developed following direct subcutaneous implantation of fresh tumor on the flank of immune compromised/athymic mice.

Results: Six ATC PDX models and four cell lines were developed with distinct genetic profiles. Mutational characterization showed one BRAF/TP53/CDKN2A, one BRAF/CDKN2A, one BRAF/TP53, one TP53 only, one TERT-promoter/HRAS, and one TERT-promoter/KRAS/TP53/NF2/NFE2L2 mutated phenotype. H&E staining comparing the PDX models to the original patient surgical specimens show remarkable resemblance, while immunohistochemistry stains for important biomarkers were in full concordance (Cytokeratin, TTF-1, PAX8, BRAF). Short tandem repeats DNA fingerprinting analysis of all PDX models and cell lines showed strong concordance with the original tumor. PDX successful establishment rate was 32%.

Conclusion: We have developed and characterized six novel ATC PDX models with four matching cell lines. Each PDX model harbors a distinct genetic profile, making them excellent tools for pre-clinical therapeutic trials.
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http://dx.doi.org/10.1210/clinem/dgab453DOI Listing
June 2021

A High-Throughput Approach to Identify Effective Systemic Agents for the Treatment of Anaplastic Thyroid Carcinoma.

J Clin Endocrinol Metab 2021 Jun 12. Epub 2021 Jun 12.

Department of Head and Neck surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Despite the use of aggressive multimodality treatment, most anaplastic thyroid carcinoma (ATC) patients die within a year of diagnosis. Although the combination of BRAF and MEK inhibitors has recently been approved for use in BRAF-mutated ATC, they remain effective in a minority of patients who are likely to develop drug resistance. There remains a critical clinical need for effective systemic agents for ATC with a reasonable toxicity profile to allow for rapid translational development.

Methods & Methods: Twelve human thyroid cancer cell lines with comprehensive genomic characterization were used in a high-throughput screening (HTS) of 257 compounds to select agents with maximal growth inhibition. Cell proliferation, colony formation, orthotopic thyroid models, and patient-derived xenograft models (PDX) were used to validate the selected agents.

Results: Seventeen compounds were effective and docetaxel, LBH-589, and pralatrexate were selected for additional in vitro and in vivo analysis as they have been previously approved by the FDA for other cancers. Significant tumor growth inhibition (TGI) was detected in all tested models treated with LBH-589; pralatrexate demonstrated significant TGI in the orthotopic papillary thyroid carcinoma model and two PDX models; docetaxel demonstrated significant TGI only in the context of mutant TP53.

Conclusions: HTS identified classes of systemic agents which demonstrate preferential effectiveness against aggressive thyroid cancers, particularly those with mutant TP53. Preclinical validation in both orthotopic and PDX models, which are accurate in vivo models mimicking tumor microenvironment, may support initiation of early phase clinical trials in non-BRAF mutated or refractory to BRAF/MEK inhibition ATC.
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http://dx.doi.org/10.1210/clinem/dgab424DOI Listing
June 2021

Delay to surgery after neoadjuvant chemotherapy in head and neck squamous cell carcinoma affects oncologic outcomes.

Cancer 2021 Jun 25;127(12):1984-1992. Epub 2021 Feb 25.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Neoadjuvant chemotherapy (NAC) is used in head and neck squamous cell carcinoma (HNSCC) for downstaging advanced disease and decreasing distant metastasis (DM). To the authors' knowledge, no study has specifically examined the impact of a delayed time to surgery (TTS) after NAC on oncologic outcomes. They thus aimed to identify a cutoff for TTS after NAC and its effect on survival indices.

Methods: This was a retrospective review of all patients with HNSCC receiving NAC followed by surgery with curative intent between March 2016 and March 2019 at the MD Anderson Cancer Center. Receiver operating characteristic analysis was used to identify a cutoff for TTS, and this cutoff was used to analyze the overall survival (OS), locoregional recurrence rate, DM-free rate, and disease-free survival (DFS). A multivariate Cox regression analysis was performed.

Results: One hundred one patients were analyzed with a median follow-up of 24.7 months. The 3-year OS and locoregional recurrence rates did not differ with a TTS ≥ 34 days. However, the 3-year DM-free rate was significantly worse (56% vs 90%; P = .001) in the group with a TTS ≥ 34 days, and the 3-year DFS was significantly lower (26% vs 64%; P = .006). In a multivariate analysis, a TTS ≥ 34 days (hazard ratio [HR], 4.92; 95% confidence interval [CI], 1.84-13.13) and extracapsular extension (HR, 3.01; 95% CI, 1.13-8.00) were significant independent predictors of a poorer DM-free rate. Weight loss > 10% (HR, 5.53; 95% CI, 1.02-30.24) was the only independent predictor for a TTS ≥ 34 days.

Conclusions: Emphasis should be placed on early definitive locoregional treatment after NAC, particularly in patients who do not respond to NAC. There is a need to validate these findings and establish new benchmarks for the interval between NAC and surgery.
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http://dx.doi.org/10.1002/cncr.33471DOI Listing
June 2021

The tumor immune contexture of salivary duct carcinoma.

Head Neck 2021 04 11;43(4):1213-1219. Epub 2021 Feb 11.

Department of Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Background: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations.

Methods: We extracted clinical data and performed immunohistochemistry for AR, AR-V7, HER-2, PD-L1, LAG-3, and tumor-infiltrating immune cells.

Results: We included 17 patients. Age ranged from 42 to 85 years old; HER-2 was overexpressed or amplified in 65%. AR was positive in 88% of patients, while AR-V7 was positive in 13% by IHC. We found low scores of immune infiltration and a PD-L1 expression in 53%. We found no clinically significant association between biomarkers and survival outcomes.

Conclusion: In this small series of SDC, biomarkers do not seem to correlate with disease biology, although they provide additional treatment options. SDC may harbor a different immune profile compared to other subtypes, with an indication of T-cell dysfunction.
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http://dx.doi.org/10.1002/hed.26587DOI Listing
April 2021

Targeting of CD40 and PD-L1 Pathways Inhibits Progression of Oral Premalignant Lesions in a Carcinogen-induced Model of Oral Squamous Cell Carcinoma.

Cancer Prev Res (Phila) 2021 Mar 4;14(3):313-324. Epub 2020 Dec 4.

Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

We have previously demonstrated that PD-1 blockade decreased the incidence of high-grade dysplasia in a carcinogen-induced murine model of oral squamous cell carcinoma (OSCC). It remains unknown, however, whether there are additional factors involved in escape from immune surveillance that could serve as additional targets for immunoprevention. We performed this study to further characterize the immune landscape of oral premalignant lesions (OPL) and determine the impact of targeting of the PD-1, CTLA-4, CD40, or OX40 pathways on the development of OPLs and oral carcinomas in the 4-nitroquinoline 1-oxide model. The immune pathways were targeted using mAbs or, in the case of the PD-1/PD-L1 pathway, using PD-L1-knockout (PD-L1) mice. After intervention, tongues and cervical lymph nodes were harvested and analyzed for malignant progression and modulation of the immune milieu, respectively. Targeting of CD40 with an agonist mAb was the most effective treatment to reduce transition of OPLs to OSCC; PD-1 alone or in combination with CTLA-4 inhibition, or PD-L1, also reduced progression of OPLs to OSCC, albeit to a lesser extent. Distinct patterns of immune system modulation were observed for the CD40 agonists compared with blockade of the PD-1/PD-L1 axis with or without CTLA-4 blockade; CD40 agonist generated a lasting expansion of experienced/memory cytotoxic T lymphocytes and M1 macrophages, whereas PD-1/CTLA-4 blockade resulted in a pronounced depletion of regulatory T cells among other changes. These data suggest that distinct approaches may be used for targeting different steps in the development of OSCC, and that CD40 agonists merit investigation as potential immunoprevention agents in this setting. PREVENTION RELEVANCE: PD-1/PD-L1 pathway blockade, as well as activation of the CD40 pathway, were able to prevent OPL progression into invasive OSCC in a murine model. A distinct pattern of immune modulation was observed when either the CD40 or the PD-1/PD-L1 pathways were targeted.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0418DOI Listing
March 2021

Sinonasal analogue HPV related breast multiphenotypic carcinoma, a report of a case with the first description in the breast.

Diagn Pathol 2020 Nov 20;15(1):137. Epub 2020 Nov 20.

UT MD Anderson Cancer Center, 1515 Holcombe Blvd Box 85, Houston, TX, 77030, USA.

Background: High grade basal-like breast carcinomas are triple negative, express basal cytokeratins, and are known for the overall poor prognosis and aggressive behavior. HPV related multiphenotypic sino-nasal carcinoma has overlapping histology with basal-like breast carcinomas, but carry the defining feature of association with high risk HPV.

Case Presentation: We present a case of a perimenopausal woman with a non-healing ulcerated lesion involving the nipple and breast following a trauma. Biopsy performed showed an HPV-positive basal-like carcinoma with squamous differentiation involving the breast, analogous to multiphenotypic carcinoma previously described in the sinonasal tract.

Conclusion: This is the first report of a case of a high- risk HPV related basal-like carcinoma with squamous differentiation, described in the literature. We highlight the morphology and immunophenotype of this lesion and its recognition when compared to other multiphenotypic lesions of the breast, and suggest that pathologists should consider HPV evaluation when encountering similar basal-like tumors involving the breast.
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http://dx.doi.org/10.1186/s13000-020-01050-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678216PMC
November 2020

Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets.

Clin Cancer Res 2021 Feb 10;27(3):852-864. Epub 2020 Nov 10.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Salivary gland adenoid cystic carcinoma (ACC) has heterogeneous clinical behavior. Currently, all patients are treated uniformly, and no standard-of-care systemic therapy exists for metastatic ACC. We conducted an integrated proteogenomic analyses of ACC tumors to identify dysregulated pathways and propose a classification with therapeutic implications.

Experimental Design: RNA/DNA sequencing of 54 flash-frozen salivary ACCs and reverse phase protein array (RPPA) in 38 specimens were performed, with validation by Western blotting and/or IHC. Three independent ACC cohorts were used for validation.

Results: Both unbiased RNA sequencing (RNA-seq) and RPPA analysis revealed two molecular subtypes: ACC-I (37%) and ACC-II (63%). ACC-I had strong upregulation of , MYC target genes, and mRNA splicing, enrichment of -activating mutations, and dramatically worse prognosis. ACC-II exhibited upregulation of and receptor tyrosine kinases (AXL, MET, and EGFR) and less aggressive clinical course. TP63 and MYC were sufficient to assign tumors to ACC subtypes, which was validated in one independent cohort by IHC and two additional independent cohorts by RNA-seq. Furthermore, IHC staining for MYC and P63 protein levels can be used to identify ACC subtypes, enabling rapid clinical deployment to guide therapeutic decisions. Our data suggest a model in which ACC-I is driven by MYC signaling through either NOTCH mutations or direct amplification, which in turn suppress P63 signaling observed in ACC-II, producing unique therapeutic vulnerabilities for each subtype.

Conclusions: Cooccurrence of multiple actionable protein/pathways alterations in each subtype indicates unique therapeutic vulnerabilities and opportunities for optimal combination therapy for this understudied and heterogeneous disease.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854509PMC
February 2021

von Ebner's glands intercalated duct adenocarcinoma with PALB2 gene mutation.

Ann Diagn Pathol 2020 Dec 5;49:151637. Epub 2020 Oct 5.

Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States of America; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States of America. Electronic address:

Secretory carcinoma of the salivary glands is a distinct entity with distinct morphologic features, immunohistochemical profile and molecular alterations. It mainly affects middle aged individuals with slight male predominance and parotid gland is the most common site of involvement. Although ETV6-NTRK3 gene fusion is considered pathognomonic for secretory carcinoma, advances in molecular profiling of this tumor have led to the discovery of novel ETV6 fusion partners and gene mutations. Herein, we describe a case of an adenocarcinoma of intercalated duct origin favor secretory carcinoma, in a unique location of von Ebner's glands of mobile tongue in a 40-year-old Caucasian female. Aside from being in a unique location, the tumor showed somatic mutation for PALB2 gene which has not been described so far in secretory carcinoma. Discovery of novel fusions and mutations have therapeutic implications with respect to targeted therapy.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151637DOI Listing
December 2020

TRPS1: a highly sensitive and specific marker for breast carcinoma, especially for triple-negative breast cancer.

Mod Pathol 2021 04 3;34(4):710-719. Epub 2020 Oct 3.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
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http://dx.doi.org/10.1038/s41379-020-00692-8DOI Listing
April 2021

Clinical Implication of Diagnostic and Histopathologic Discrepancies in Sinonasal Malignancies.

Laryngoscope 2021 05 18;131(5):E1468-E1475. Epub 2020 Sep 18.

Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.

Objectives: To evaluate the incidence of histopathologic diagnostic discrepancy for patients referred to our institution, identify pathologies susceptible to diagnostic error, and assess the impact on survival of histopathologic diagnostic discrepancies.

Methods: Three hundred ninety-seven patients with sinonasal cancers were identified, and discordance between the outside pathologic report and MD Anderson Cancer Center pathologic report was assessed. Overall survival and disease-specific survival were analyzed using Kaplan-Meier and log rank methods.

Results: Discordance of major histopathologic diagnoses was present in 24% (97 of 397) of reports, with sinonasal undifferentiated carcinoma, sarcoma, neuroendocrine carcinoma, and poorly differentiated carcinoma pathologies having the highest change in diagnosis (P < .01). A further 61% (244 of 397) had minor changes such as histologic grade, subtype, or stage, with sarcoma and neuroendocrine carcinoma pathologies being most susceptible to change (P < .02). Overall, the 5-year overall survival (OS) and disease-specific survival (DSS) was reduced in patients with a major change in histopathologic diagnosis (59.2% vs. 70.2% (P = .02) and 72.9% vs. 81.2% (P = .02), respectively). Furthermore, patients with a major change in diagnosis and prior treatment experienced a significant reduction in 5-year OS (61.9% vs. 70.4%, P = .03 < .01) and DSS (72.4% vs. 81.5%, P = .04).

Conclusion: Histopathological diagnosis of sinonasal tumors is complex and challenging given the rarity of the disease. Obtaining the correct diagnosis is important for treatment selection and survival. In histologies prone to misdiagnoses, obtaining a second opinion from experienced head and neck pathologists at a high-volume institution may potentially lead to a change in treatment recommendations that could result in improved survival in patients with sinonasal malignancies.

Level Of Evidence: 4 Laryngoscope, 131:E1468-E1475, 2021.
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http://dx.doi.org/10.1002/lary.29102DOI Listing
May 2021

High-grade sinonasal carcinomas and surveillance of differential expression in immune related transcriptome.

Ann Diagn Pathol 2020 Dec 7;49:151622. Epub 2020 Sep 7.

Department Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States of America.

The skull base is the location of a wide variety of malignant tumors. Among them is sinonasal undifferentiated carcinoma (SNUC), a highly aggressive sinonasal neoplasm that was recently reclassified into subgroups of high-grade carcinomas with unique genomic events (e.g., SMARC-deficient carcinoma, nuclear protein in testis NUT carcinoma). Other high-grade carcinomas in this location are neuroendocrine carcinomas, sinonasal adenocarcinomas, and teratocarcinosarcomas. Given the rarity of these tumors, little transcriptomic data is available. The aim of this study was to characterize the immune-oncology gene expression profile in SNUC and other high-grade sinonasal carcinomas. Next-generation sequencing was performed in 30 high-grade sinonasal carcinoma samples using the HTG EdgeSeq Precision Immuno-Oncology Panel. Ingenuity pathway analysis was performed to understand the immunobiology, signaling, and functional perturbations during tumor development. The samples were divided into 3 groups: 21 SNUCs and SMARC-deficient sinonasal carcinomas; 5 high-grade neuroendocrine carcinomas (HGNECs), with small cell and large cell variants; and 4 high-grade sinonasal carcinomas (HGSNCs) of mixed histology (1 NUT carcinoma, 1 teratocarcinosarcoma, and 2 sinonasal adenocarcinomas). PRAME and ASCL1 emerged as upregulated transcripts with strong protein validation for SNUC and HGNEC; other upregulated candidates EZH2 and BRCA1 offer consideration for alternative targeted therapy, and downregulation of major histocompatibility complex molecules and chemokines represent another hurdle in the development of effective immunotherapy. This immune-oncology gene expression analysis of 3 groups of high-grade sinonasal carcinoma with emphasis on SNUC identified a number of differentially expressed transcripts reflecting effects on tumorigenesis. Identification of immune pathways should be further investigated for possible integration of immunotherapy into a multidisciplinary approach to these cancers and personalized treatment.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151622DOI Listing
December 2020

Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma.

Cancers (Basel) 2020 Aug 27;12(9). Epub 2020 Aug 27.

Department of Internal Medicine, Division of Molecular Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.

Acinic cell carcinoma (AcCC) is a morphologically distinctive salivary gland malignancy often associated with chromosome rearrangements leading to overexpression of the NR4A3 transcription factor. However, little is known about how NR4A3 contributes to AcCC biology. Detailed RNA-sequencing of 21 archived AcCC samples revealed fusion reads arising from recurrent t(4;9), t(9;12), t(8;9) or t(2;4) chromosomal translocations, which positioned highly active enhancers adjacent to the promoter of the gene or the closely related gene, resulting in their aberrant overexpression. Transcriptome analyses revealed several distinct subgroups of AcCC tumors, including a subgroup that overexpressed both and . A poor survival subset of the tumors with high-grade transformation expressed and as well as , an oncogene that is the major driver in a different type of salivary gland tumor, adenoid cystic carcinoma. The combination of and showed cooperativity in regulating a distinct set of genes. In addition, the ligand binding domain of NR4A3 directly bound the Myb DNA binding domain. Transformation assays indicated that, while overexpressed NR4A3 was sufficient to generate transformed colonies, the combination of NR4A3 plus Myb was more potent, leading to anchorage-independent growth and increased cellular invasiveness. The results confirm that and are the main driver genes of AcCC and suggest that concurrent overexpression of and defines a subset of AcCC patients with high-grade transformation that display exceptionally poor outcome.
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http://dx.doi.org/10.3390/cancers12092433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565926PMC
August 2020

Neuroendocrine Carcinoma and Sinonasal Undifferentiated Carcinoma.

Adv Otorhinolaryngol 2020 30;84:168-184. Epub 2020 Jul 30.

Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA,

Sinonasal malignancies are uncommon, representing 1% of all neoplasms. A wide spectrum of malignant neoplasms arise from the sinonasal and skull base regions; the majority of these tumors are poorly or undifferentiated tumors manifesting overlapping features that result in diagnostic challenges. Sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC) are types of sinonasal neuroendocrine tumor, together with olfactory neuroblastoma. They share overlapping clinical, radiological, and histopathological features, albeit with variability in behavior and prognosis between each other. The literature is at variance regarding the appropriate management strategy of these tumors due to their rarity and difficulty in establishing the correct diagnosis. In recent years progress has been made in the diagnostic techniques and treatment strategies implemented for these tumors. Here we provide a comprehensive review of the recent literature, focusing on the recent advances in histopathological and ancillary diagnosis, and different treatment options for SNEC and SNUC.
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http://dx.doi.org/10.1159/000457936DOI Listing
June 2021

Prognostic factors for local recurrence and survival and impact of local treatments on survival in lacrimal gland carcinoma.

Br J Ophthalmol 2021 06 17;105(6):768-774. Epub 2020 Jul 17.

Orbital Oncology & Ophthalmic Plastic Surgery, Department of Plastic Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

Background/aims: To identify prognostic factors for local recurrence, distant metastasis and disease-specific survival (DSS) for lacrimal gland carcinoma.

Methods: All consecutive patients with lacrimal gland carcinoma treated from January 1998 through December 2018 were included. Log-rank tests and univariate Cox proportional hazards regression models were used to study risk factors and survival.

Results: Overall, 55 patients were included in this study, and 5 patients were excluded from the survival analysis. Median age was 46 years (range: 10-76). 43 patients (78%) had adenoid cystic carcinoma (ACC). 31 patients (56%) had T2 disease at presentation. 28 patients (51%) underwent orbital exenteration with or without adjuvant radiotherapy or chemoradiation, 26 (47%) underwent eye-sparing surgery with or without adjuvant radiotherapy or chemoradiation, and 1 received palliative chemoradiation. 11 patients (22%) experienced local recurrence; 14 (29%) experienced distant metastasis. Five- and 10-year local-recurrence-free survival rates were 0.71 (95% CI 0.58 to 0.88), and 5- and 10-year distant-metastasis-free survival rates were 0.67 (95% CI 0.53 to 0.85) and 0.49 (95% CI 0.30 to 0.81), respectively. There was no significant difference in risks of local recurrence, distant metastasis or DSS between ACC patients who had orbital exenteration and those who had eye-sparing surgery. Perineural invasion was negatively associated with local-recurrence-free survival (p=0.02). Among patients with ACC, basaloid/solid histologic type was associated with significantly worse DSS than non-basaloid/solid histologic type (p<0.01).

Conclusions: For lacrimal gland carcinoma, orbital exenteration with adjuvant therapy and eye-sparing surgery with adjuvant therapy are associated with similar recurrence outcomes. Eye-sparing surgery is associated with better DSS. Perineural invasion is a risk factor for local recurrence. ACC with basaloid/solid subtype correlates with worse DSS.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316142DOI Listing
June 2021

Surgical management of carcinomas of the infratemporal fossa and skull base: patterns of failure and predictors of long-term outcomes.

J Neurosurg 2020 Jun 12;134(5):1392-1398. Epub 2020 Jun 12.

4Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Objective: Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma.

Methods: All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors' institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes.

Results: Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence.

Conclusions: The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.
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http://dx.doi.org/10.3171/2020.3.JNS192630DOI Listing
June 2020

Malignant Mixed Tumor (Carcinoma Ex Pleomorphic Adenoma) of the Lacrimal Gland.

Ophthalmic Plast Reconstr Surg 2020 Sep/Oct;36(5):497-502

Orbital Oncology & Ophthalmic Plastic Surgery, Department of Plastic Surgery.

Purpose: To review the clinical presentation, treatment, and prognosis of patients with malignant mixed tumor (carcinoma ex pleomorphic adenoma) of the lacrimal gland.

Methods: Clinical records and radiographic images were reviewed for patients with malignant mixed tumor of the lacrimal gland treated at the center during 2008-2019.

Results: The study included 9 patients (6 men, 3 women) aged 17-66 years (median age, 56 years). Six had primary malignant mixed tumor with no history of orbital lesions, and 3 had previously been diagnosed with pleomorphic adenoma. Tumor, Node, Metastasis classification per the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual were T1aN0M0 in 2 patients, T2aN0M0 in 3 patients, T4bN0M0 in 2 patients, and T4cN0M0 in 2 patients. Two patients underwent orbital exenteration, 6 patients underwent eye-sparing surgery, and 1 patient had an unresectable tumor because of cavernous sinus extension. All patients received radiotherapy (intensity-modulated radiotherapy in 3 and proton therapy in 6). All patients received chemotherapy, 8 concurrently with radiotherapy and 1 after radiotherapy. The median follow-up time was 70 months. At last contact, 6 patients were alive without evidence of disease; 2 had died of disease, 1 of distant metastasis, and the other of cavernous sinus invasion.

Conclusions: The findings suggest that de novo malignant mixed tumor of the lacrimal gland is more common than disease that results from transformation after incomplete resection of lacrimal gland pleomorphic adenoma. Most cases can be treated with eye-sparing surgery and radiation unless skull base extension is present.
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http://dx.doi.org/10.1097/IOP.0000000000001625DOI Listing
March 2021

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8 Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

Clin Cancer Res 2020 07 8;26(13):3211-3219. Epub 2020 Apr 8.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: In oropharyngeal squamous cell carcinoma (OPC), high CD8 tumor-infiltrating lymphocyte (CD8TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8TIL density, safety, and efficacy in patients with OPC.

Patients And Methods: Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes.

Results: Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment ( = 0.97; 95% CI: -1.07-2.28). In each group, 6 patients (43%, 95% CI: 17.66-71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8TIL change in patients with a MPR was seen ( = 0.059; 95% CI: -0.33-3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence.

Conclusions: Durvalumab + tremelimumab did not increase CD8TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3977DOI Listing
July 2020

Epithelioid rhabdomyosarcoma: Report of the first case in the jaw.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Nov 12;130(5):e308-e315. Epub 2020 Mar 12.

Universidade Federal de Minas Gerais, School of Dentistry, Department of Oral Surgery and Pathology, Belo Horizonte, Minas Gerais, Brazil.

Objectives: Epithelioid rhabdomyosarcoma (EpiRMS) is a novel morphologically distinct variant of rhabdomyosarcoma, with an unusually challenging microscopic diagnosis. The occurrence of rhabdomyosarcomas in the jaws is extremely rare. This study presents the first case of EpiRMS in the jaw (mandible) and a literature review of the previous 35 cases of EpiRMS.

Study Design: Here, we report a case of EpiRMS affecting an 18-year-old male patient. Clinical, imaging, microscopic, and immunohistochemical features are discussed and previously reported cases of EpiRMS are reviewed.

Results: An 18-year-old male patient presented with an exophytic sessile growth on the buccal gingiva, and orthopantomography revealed irregular bone loss. Microscopic analysis showed a large number of cells with epithelioid appearance. Immunohistochemistry staining was positive for desmin, myogenin, MyoD1, smooth muscle actin, h-caldesmon, INI-1, and AE1-AE3. The patient's disease was staged as T4aN1M0 and was treated with surgical excision combined with chemotherapy.

Conclusions: The occurrence of RMS in the mandible is rare, and this is the first case of EpiRMS in the jaw. EpiRMS is an unusual histologic subtype that mimics other sarcomas and epithelial malignancies, making diagnosis a challenge. A specific immunohistochemistry panel aids in the diagnosis. EpiRMS has an aggressive course and an unfavorable prognosis.
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http://dx.doi.org/10.1016/j.oooo.2020.01.004DOI Listing
November 2020

Uncommon tumors of temporomandibular joint: An institutional experience and review.

Head Neck 2020 08 10;42(8):1859-1873. Epub 2020 Feb 10.

Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Background: The temporomandibular joint (TMJ) harbors a myriad of pathologic alterations including arthritides and benign and malignant neoplasms.

Methods: Herein, we describe our institutional experience of some uncommon and unusual synovial pathologies of the TMJ along with a review of literature. We searched through the archives of department of pathology and institutional electronic medical record for specimens of TMJ between 1999 and 2019. Hematoxylin and eosin slides were reviewed and data (final diagnosis, age, gender, clinical presentation, tumor size, treatment modality, recurrence, and vital status) were collected.

Results: A total of seven cases were identified including four cases of synovial chrondromatosis; and one case each of tenosynovial giant cell tumor, localized type, tenosynovial giant cell tumor, diffuse type, and synovial sarcoma.

Conclusions: The article emphasizes on the clinical, radiologic, pathologic, and molecular features of these uncommon entities. The differential diagnosis of each entity is also discussed. Current updates in the management are also reviewed.
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http://dx.doi.org/10.1002/hed.26106DOI Listing
August 2020

Incidental 18F-Fluciclovine Uptake in a Warthin Tumor of the Parotid Gland in a Patient Undergoing PET/CT Imaging for Biochemical Recurrent Prostate Cancer.

Clin Nucl Med 2020 Apr;45(4):e208-e210

The University of Texas MD Anderson Cancer Center, Houston, TX.

A 67-year-old asymptomatic man with biochemical recurrent prostate cancer underwent F-fluciclovine PET/CT for restaging to determine subsequent treatment strategy. PET/CT images were obtained from the proximal thighs to the vertex of the skull, after the intravenous administration of 362.6 MBq (9.8 mCi) of F-fluciclovine. PET/CT imaging demonstrated a focus of abnormally increased F-fluciclovine uptake corresponding to a small nodularity in the left parotid gland. Subsequent ultrasound-guided fine-needle aspiration biopsy of the lesion revealed histopathology compatible with a benign Warthin tumor.
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http://dx.doi.org/10.1097/RLU.0000000000002938DOI Listing
April 2020

Response rates and survival to systemic therapy after immune checkpoint inhibitor failure in recurrent/metastatic head and neck squamous cell carcinoma.

Oral Oncol 2020 02 19;101:104523. Epub 2019 Dec 19.

Department of Thoracic, Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, United States. Electronic address:

Objectives: Prior reports have demonstrated a potential enhancement in overall response rate (ORR) to chemotherapy after exposure to immunotherapy. The goal of this study was to evaluate the ORR and survival to chemotherapy and/or targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients who progressed on immune checkpoint inhibitors (ICI).

Materials And Methods: We retrospectively collected clinical and pathologic data from patients with recurrent/metastatic HNSCC who progressed on ICI and subsequently received chemotherapy or targeted therapy. ORR was assessed by RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results: A total of 43 patients met criteria for inclusion. The majority were male (91%) and former smokers (60%). Most patients received ICI as first-line (58.14%); the vast majority was platinum exposed (90.7%). The ORR to ICI was 21%. The ORR to systemic therapy before ICI was 47%, and the ORR after ICI failure was 42%. After progression on ICI, the median PFS and OS on the subsequent line of therapy were 4.2 and 8.4 months respectively.

Conclusion: In our cohort of recurrent/metastatic HNSCC patients, the ORR and OS to systemic therapy after progression on ICI were higher than historical controls for second-line or beyond. Further investigations are warranted to better characterize optimal sequencing and combination strategies.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104523DOI Listing
February 2020

Surgical management of non melanoma skin cancer of the head and neck.

Oral Oncol 2020 01 9;100:104485. Epub 2019 Dec 9.

Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, United States. Electronic address:

Non-melanoma skin cancer (NMSC) is the most common malignancy in the world and is reaching epidemic proportions. The most common types of NMSC include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The head and neck is the most common site for NMSC, and surgery remains the mainstay of treatment. We review the etiology, risk factors, pathogenesis as well as the preoperative, operative, and postoperative considerations in the management of NMSC. Multidisciplinary evaluation and attention to each of these phases is imperative for favorable oncologic and functional patient outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104485DOI Listing
January 2020

Association of Immunosuppression With Outcomes of Patients With Cutaneous Squamous Cell Carcinoma of the Head and Neck.

JAMA Otolaryngol Head Neck Surg 2020 02;146(2):128-135

Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston.

Importance: Patients with immunosuppression have a higher incidence of cutaneous squamous cell carcinoma (cSCC) and often present with more aggressive, multifocal disease.

Objectives: To determine the risks for mortality in patients with cSCC and immunosuppression compared with nonimmunosuppression and to compare the difference in mortality risk based on the cause of immunocompromise.

Design, Setting, And Participants: This retrospective cohort study of patients with cSCC of the head and neck recruited participants from a tertiary cancer care center. Patients who underwent no treatment, wide local excision, or biopsy of the lesions were eligible for inclusion from January 1, 1995, to September 30, 2015. Data were analyzed from March 21, 2018, to April 4, 2019.

Exposures: Immunocompromise, defined as having solid organ transplant, stem cell transplant, hematopoetic malignant disease, autoimmune disease requiring treatment with immunosuppressive therapy, type 1 or 2 diabetes treated with insulin, HIV or AIDS, or other hematoproliferative disorder.

Main Outcomes And Measures: Patients were divided into 2 groups according to their immune status (immunosuppression vs no immunosuppression). The primary outcome measure was disease-specific survival. A Cox proportional hazards regression model was used to determine the association of immune status with disease outcome.

Results: A total of 796 patients (680 men [85.4%]; median age, 69 [range, 27-98] years), including 147 with and 649 without immunosuppression (IS and non-IS groups, respectively), constituted the final cohort. In the IS group, 77 (52.4%) had diabetes, 39 (26.5%) had lymphoma or leukemia, 25 (17.0%) had an organ or stem cell transplant, and 3 (2.0%) had HIV. Five-year disease-specific survival was 68.2% in the IS group compared with 84.1% in the non-IS group (difference, 15.9%; 95% CI, 3.5%-27.4%). Immunosuppression was independently associated with worse disease-specific survival (hazard ratio, 2.32; 95% CI, 1.53-3.50).

Conclusions And Relevance: This study's findings suggest that immunosuppression is independently associated with a worse outcome in cSCC, with a 2.32 times increased risk of disease-specific death after adjusting for age, history of skin cancer, recurrent or persistent disease status, disease stage, and treatment.
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http://dx.doi.org/10.1001/jamaoto.2019.3751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902183PMC
February 2020

Pan-Trk immunohistochemistry reliably identifies ETV6-NTRK3 fusion in secretory carcinoma of the salivary gland.

Virchows Arch 2020 Feb 19;476(2):295-305. Epub 2019 Aug 19.

Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Secretory carcinoma of the salivary gland is a newly recognized entity that morphologically resembles breast secretory carcinoma and has a characteristic t(12;15)(p13;q25) ETV6-NTRK3 translocation. Fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) analyses can detect the ETV6-NTRK3 fusion; however, both tests are expensive and not widely available. In this study, we aimed to determine whether pan-Trk immunohistochemistry (IHC) could detect ETV6-NTRK3 fusions as reliably as RT-PCR and FISH. We performed pan-Trk IHC in 70 salivary gland cancer samples, including secretory carcinomas, acinic cell carcinomas, and hybrid carcinomas. Nineteen tumors exhibited positive pan-Trk staining, including 16 secretory carcinomas, 2 hybrid carcinomas with a secretory carcinoma component, and 1 acinic cell carcinoma. Pan-Trk IHC staining was localized in the nucleus in 16 (84.2%) cases and in the cytoplasm and/or membrane in 3 (15.8%) cases. RT-PCR analysis for the ETV6-NTRK3 transcript was conducted in 45 samples; the fusion transcript was present in 11 of 12 secretory carcinomas and absent in 32 acinic cell carcinomas and 1 mucoepidermoid carcinoma. Pan-Trk IHC was positive in 10 of 11 salivary tumors that were positive for ETV6-NTRK3 by RT-PCR and negative in all 34 tumors that were negative for the fusion by RT-PCR. Therefore, in comparison with RT-PCR, pan-Trk IHC had a sensitivity of 90.9% and specificity of 100%. In conclusion, our data showed that pan-Trk IHC is a reasonable screening test for diagnosing secretory carcinoma of the salivary gland.
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http://dx.doi.org/10.1007/s00428-019-02640-7DOI Listing
February 2020
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