Clinical and Pathologic Features Associated With Invasive Breast Carcinoma With 2018 American Society of Clinical Oncology/College of American Pathologists In Situ Hybridization Group 2 Results (Human Epidermal Growth Factor Receptor 2 [HER2]/Chromosome 17 Centromere [CEP17] Ratio ≥2.0 and Average HER2 Copy Number <4.0).

CONTEXT.­: The American Society of Clinical Oncology/College of American Pathologists updated the human epidermal growth factor receptor 2 (HER2) breast carcinoma testing guideline in 2018 to address issues from uncommon HER2 fluorescence in situ hybridization (FISH) results. Based on the 2013 American Society of Clinical Oncology/College of American Pathologists guideline, cases wherein the HER2/chromosome 17 centromere (CEP17) ratio of 2.0 or more with an average HER2 copy number of less than 4.0 were considered in situ hybridization (ISH) positive. Under the 2018 guideline, such cases are classified as ISH Group 2 and are no longer considered eligible for anti-HER2 therapy when the corresponding HER2 immunohistochemistry result is 0, 1+, or 2+. OBJECTIVE.­: To assess the clinical, pathologic, and treatment aspects of patients with ISH Group 2 results. DESIGN.­: We retrospectively reviewed HER2 FISH results at our center between January 2012 and December 2014 and identified and characterized cases with ISH Group 2 results. RESULTS.­: Thirty-nine cases with ISH Group 2 results from 39 patients were reviewed. Twenty of 39 (51%) patients received anti-HER2 therapy. Patients treated with HER2-targeted therapy were less likely to have hormone receptor-positive tumors, compared with patients without anti-HER2 treatment, though not significantly (P = .30). The only significant difference between the 2 patient groups was receipt of cytotoxic chemotherapy treatment (P < .001). Overall, clinical outcome was similar between the 2 groups (P > .99). CONCLUSIONS.­: This retrospective study with median follow-up of at least 6 years shows patients with ISH Group 2 tumors had similar clinical outcomes, irrespective of HER2-targeted therapy. Further analysis in the prospective setting would provide valuable data that would potentially inform clinical decision making.

Pseudofungi in an Immunocompromised Patient with Breast Cancer and COVID-19.

Herein, we present a case of a male patient with breast cancer and a recent history of COVID-19 pneumonia, diagnosed with pseudofungi on pathological examination of lymph nodes after mastectomy. Pseudofungi are septate hyphae-like structures that morphologically mimic fungal elements despite the absence of true mycosis and thus predispose to overtreatment if not properly identified. We report a review of similar cases involving this diagnostic mimicker in the literature.

Oncolytic Herpes Simplex Virus Prevents Premalignant Lesions from Progressing to Cancer.

Early detection and timely treatment of precancerous lesions are hallmarks of successful strategies to prevent deaths due to cancer. Oncolytic viruses are a group of promising anti-cancer agents with wide-ranging experimental and clinical efficacy against solid tumors. Previously, we have shown that NV1066, an oncolytic herpes simplex-1 virus encoding enhanced green fluorescent protein, selectively infects, replicates in, and kills various cancer types. In this study, we sought to determine whether this oncolytic agent can treat precancerous lesions to prevent cancer formation. Using an oral chemical carcinogenesis model in hamsters, we assessed the ability of NV1066 to infect precancerous and cancerous lesions. NV1066 consistently infected dysplastic cells, carcinoma in situ, and squamous cell carcinoma. Animals receiving an intramucosal injection of NV1066 for 7 weeks showed significantly fewer (3-fold) and smaller (4-fold) lesions compared to animals that did not receive viral treatment. Results indicate that infectivity might be dependent on the herpes simplex virus 1 receptor, nectin-1. This study demonstrates that not only can NV1066 treat oral squamous cell carcinoma, but it can also infect and treat premalignant lesions, thus delaying cancer progression. Overall, our study shows the potential of the oncolytic virus NV1066 as a cancer prevention tool.

Data Set for the Reporting of Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Standardized, synoptic pathologic reporting for tumors greatly improves communication among clinicians, patients, and researchers, supporting prognostication and comparison about patient outcomes across institutions and countries. The International Collaboration on Cancer Reporting is a nonprofit organization whose mission is to develop evidence-based, universally available surgical pathology reporting data sets. Within the head and neck region, lymph node excisions and neck dissections are frequently performed as part of the management of head and neck cancers arising from the mucosal sites (sinonasal tract, nasopharynx, oropharynx, hypopharynx, oral cavity, and larynx) along with bone tumors, skin cancers, melanomas, and other tumor categories. The type of specimen, exact location (lymph node level), laterality, and orientation (by suture or diagram) are essential to accurate classification. There are significant staging differences for each anatomic site within the head and neck when lymph node sampling is considered, most importantly related to human papillomavirus-associated oropharyngeal carcinomas and mucosal melanomas. Number, size, and site of affected lymph nodes, including guidelines on determining the size of tumor deposits and the presence of extranodal extension and soft tissue metastasis, are presented in the context of prognostication. This review elaborates on each of the elements included in the data set for Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours.

Data Set for the Reporting of Carcinomas of the Nasopharynx and Oropharynx: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic data collection across institutions and countries to guide cancer care in the future. An expert panel was convened to identify the minimum data set of elements that should be included in cancer reporting from tumors of the nasopharynx and oropharynx. Specifically, there has been a significant change in practice as a result of identifying oncogenic viruses, including human papillomavirus and Epstein-Barr virus, because they preferentially affect the oropharynx and nasopharynx, respectively. For these anatomic sites, when viral association is taken into account, usually reported elements of in situ versus invasive tumor, depth of invasion, and degree of differentiation are no longer applicable. Thus, guidance about human papillomavirus testing in oropharyngeal carcinomas and Epstein-Barr virus testing in nasopharyngeal carcinomas is highlighted. Further, the clinical and the pathologic differences in staging as proposed by the 8th edition of the Union for International Cancer Control are incorporated into the discussion, pointing out several areas of continued study and further elaboration. A summary of the International Collaboration on Cancer Reporting guidelines for oropharyngeal and nasopharyngeal carcinomas is presented, along with discussion of the salient evidence and practical issues.

Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence.

Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations. A high incidence of chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 was identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared with the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.Conclusions: These data support a model, whereby fatal NAT cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and chromosome 1q gain highlight their likely association with tumor virulence. Clin Cancer Res; 23(19); 5970-80. ©2017 AACR.

Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma.

BACKGROUND: An objective definition of clinically relevant extracapsular nodal spread (ECS) in head and neck squamous cell carcinoma (SCC) is unavailable. METHODS: Pathologic review of 245 pathologically positive oral cavity SCC neck dissection specimens was performed. The presence/absence of ECS, its extent (in millimeters), and multiple nodal and primary tumor risk factors were related to disease-specific survival (DSS) at a follow-up of 73 months. RESULTS: ECS was detected in 109 patients (44%). DSS was significantly better for patients without ECS than patients with ECS. Time-dependent receiver operator curve (ROC) analysis identified a prognostic cutoff for ECS extent at 1.7 mm. In multivariate analyses, DSS was significantly lower for patients with major ECS compared with patients with minor ECS, but not significantly different between patients with minor ECS and patients without ECS. CONCLUSION: ECS is clinically relevant in oral cavity SCC when it has extended more than 1.7 mm beyond the nodal capsule. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1192-E1199, 2016.

Association between Hyperprolactinemia and Granulomatous Mastitis.

Granulomatous mastitis (GM) is a relatively uncommon inflammatory breast lesion with multiple suggested etiologies. Although most GM cases show association with lactation and pregnancy, a minority of cases have been linked to hyperprolactinemia caused by either dopamine antagonist medications or with intracranial lesions, such as pituitary adenoma. The goal of this study is to review the GM cases reported in the literature with a specific emphasis on those cases associated with hyperprolactinemia and prolactinomas and to identify cases of GM seen at the Cleveland Clinic Florida which demonstrate co-occurrences of GM and intracranial lesions. CoPath and Epic data bases at Cleveland Clinic Florida were searched for cases describing inflammatory breast lesions in patients with pituitary pathology. Chart reviews were conducted and pertinent medical history was extracted for case reports. H&E-stained paraffin-embedded sections retrieved from Cleveland Clinic Florida pathology storage were evaluated by light microscopy. Four cases showing a co-occurrence of GM and hyperprolactinemia were consequently identified. A prolactin-secreting pituitary adenoma was present in two of the three GM cases. The third case demonstrated a concomitant craniopharyngioma, which was also associated with a rise in serum prolactin. This phenomenon was presumably attributable to compression, resulting in compromised transport of dopamine to the adenohypophysis and subsequent disinhibition of prolactin secretion by lactotrophs. The fourth patient with GM had a similar history of elevated prolactin. Classical histopathological features of GM were found in all four cases, including noncaseating granulomas, multinucleated giant cells, epithelioid histiocytes, and chronic inflammation. Intriguingly, complete resolution of inflammatory breast lesions along with normalization of prolactin levels occurred following the surgical excision of the craniopharyngioma, suggesting that intracranial lesion-induced hyperprolactinemia might be directly causal in GM. Therefore, the authors would suggest screening for pituitary tumors and evaluate prolactin levels in the workup of GM patients without a recent history of lactation and pregnancy and no other identified etiology.

Giant cystic degeneration of a uterine leiomyoma in a patient with autosomal dominant polycystic kidney disease.

OBJECTIVE: To report the management of a large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease (ADPKD). DESIGN: Case Report. SETTING: Cleveland Clinic Florida, Department of Gynecology, Section of Minimally Invasive Gynecologic surgery, Weston Florida. PATIENTS: A 52-year old woman with ADPKD with a large abdominal mass, abnormal uterine bleeding and symptomatic anemia. Imaging revealed a giant intramural cystic lesion of the uterus compressing the inferior vena cava. INTERVENTIONS: Uterine artery embolization and blood transfusion followed by a computed tomography guided cyst aspiration were performed on admission to alleviate anemia and abdominal pain and distension. Total laparoscopic hysterectomy with bilateral salpingectomy was performed in an outpatient setting. MAIN OUTCOME MEASURES: Management of large cystic degeneration of leiomyoma. RESULTS: Normal recovery from definitive surgery. Surgical pathology confirmed a benign, cystically dilated leiomyoma. CONCLUSION: This case demonstrates the management of giant intramural cyst lesion of the uterus using a minimally invasive surgical approach, as opposed to emergency surgery via laparotomy. CAPSULE: Large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease, in which step-wise treatments allows successful minimally invasive hysterectomy.

Undetectable Thyroglobulin Levels in Poorly Differentiated Thyroid Carcinoma Patients Free of Macroscopic Disease After Initial Treatment: Are They Useful?

BACKGROUND: Predictive role of undetectable thyroglobulin (Tg) in patients with poorly differentiated thyroid carcinoma (PDTC) is unclear. Our goal was to report on Tg levels following total thyroidectomy and adjuvant RAI in PDTC patients and to correlate Tg levels with recurrence. METHODS: Forty patients with PDTC with no distant metastases at presentation (M0) and managed by total thyroidectomy and adjuvant RAI were identified from a database of 91 PDTC patients. Of these, 31 patients had Tg values recorded and formed the basis of our analysis. A nonstimulated Tg level <1 ng/ml was used as a cutoff point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ (2) test. Recurrence-free survival (RFS) stratified by postop Tg level was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Twenty patients had undetectable Tg (<1 ng/ml) and 11 had detectable Tg (≥1 ng/ml; range 2-129 ng/ml) following surgery. After adjuvant RAI, 24 patients had undetectable Tg (<1 ng/ml) and 7 had detectable Tg (≥1 ng/ml; range 1-57 ng/ml). Patients with undetectable Tg were less likely to have pathologically positive margins compared to those with detectable Tg (33 vs. 72 % respectively; p = 0.03). Patients with undetectable Tg levels had better 5-year regional control and distant control than patients with detectable Tg level (5-year regional recurrence-free survival 96 vs. 69 %; p = 0.03; 5-year distant recurrence-free survival 96 vs. 46 %, p = 0.11). CONCLUSION: Postoperative thyroglobulin levels in subset of patients with PDTC appear to have predictive value for recurrence. Patients with undetectable Tg have a low rate of recurrence.

Variation in infection prevention practices in dialysis facilities: results from the national opportunity to improve infection control in ESRD (End-Stage Renal Disease) project.

OBJECTIVE To observe patient care across hemodialysis facilities enrolled in the National Opportunity to Improve Infection Control in ESRD (end-stage renal disease) (NOTICE) project in order to evaluate adherence to evidence-based practices aimed at prevention of infection. SETTING AND PARTICIPANTS Thirty-four hemodialysis facilities were randomly selected from among 772 facilities in 4 end-stage renal disease participating networks. Facility selection was stratified on dialysis organization affiliation, size, socioeconomic status, and urban/rural status. MEASUREMENTS Trained infection control evaluators used an infection control worksheet to observe 73 distinct infection control practices at the hemodialysis facilities, from October 1, 2011, through January 31, 2012. RESULTS There was considerable variation in infection control practices across enrolled facilities. Overall adherence to recommended practices was 68% (range, 45%-92%) across all facilities. Overall adherence to expected hand hygiene practice was 72% (range, 10%-100%). Compliance to hand hygiene before and after procedures was high; however, during procedures hand hygiene compliance averaged 58%. Use of chlorhexidine as the specific agent for exit site care was 19% overall but varied from 0% to 35% by facility type. The 8 checklists varied in the frequency of perfect performance from 0% for meeting every item on the checklist for disinfection practices to 22% on the arteriovenous access practices at initiation. CONCLUSIONS Our findings suggest that there are many areas for improvement in hand hygiene and other infection prevention practices in end-stage renal disease. These NOTICE project findings will help inform the development of a larger quality improvement initiative at dialysis facilities.

Patient and family member needs during the perioperative period.

PURPOSE: The purpose of this study was to determine the needs and experiences of patients and family members throughout the entire perioperative experience. DESIGN AND METHODS: Using a descriptive study design, a convenience sample of patients and family members were surveyed about their needs and how well those needs were met during the perioperative period. Survey questions were adapted from valid and reliable patient and family needs surveys. Rank order of patient and family needs were determined based on average item scores. FINDINGS: A total of 68 patients and 63 family members were surveyed over an 8-month period. Patient needs with the highest scores were related to pain and/or nausea management, having information about the condition after surgery, and treatment with respect and dignity. Family member needs with the highest scores were related to communication with the surgeon after the procedure, opportunities to ask questions and address concerns with hospital staff, and receiving information about the surgical procedure itself before coming to the hospital. Patients and family members perceived that their needs were met most of the time. CONCLUSIONS: Results of this survey identify the needs of patients and family members throughout the perioperative time period.

Dr. Andrew Huvos (1934-2006) retrospective: a tribute to the pathologist and the man.

Andrew G. Huvos was born in communist Budapest, Hungary, in March of 1934. At twenty-four he immigrated to New York City, working as a cytotechnologist at Delafield Hospital. Dr. Huvos attended the University of Gottingen Medical School in Germany, where he was awarded his MD degree. He completed a 1-year internship at New York Hospital, going on to Residency at Delafield Hospital and Fellowship at Presbyterian Hospital. Dr. Huvos ascended through the ranks to Attending Pathologist and Member at Memorial Hospital for Cancer and Allied diseases, at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. Concurrently, he was appointed to Weill Medical College of Cornell University, where he was Professor of Pathology for over two decades. Dr. Huvos was an editorial referee for over half a dozen highly esteemed publications, including the New England Journal of Medicine and Cancer. He trained over a thousand oncological surgical pathology fellows, head and neck fellows, and surgeons. Dr. Huvos spent nearly 40 years at MSKCC and his career was accompanied by his authorship of 388 peer-reviewed publications and eighteen book chapters. His legacy leaves behind a generation of pathologists who have greatly benefited from his tutelage.

Poorly differentiated thyroid carcinoma presenting with gross extrathyroidal extension: 1986-2009 Memorial Sloan-Kettering Cancer Center experience.

PURPOSE: To describe the outcome of patients with poorly differentiated thyroid cancer (PDTC) presenting with gross extrathyroidal extension (ETE). MATERIALS AND METHODS: After obtaining Institutional Review Board approval, we performed a retrospective review of a consecutive series of thyroid cancer patients treated by primary surgical resection with or without adjuvant therapy at Memorial Sloan-Kettering Cancer Center from 1986 to 2009. Out of 91 PDTC patients, 27 (30%) had gross ETE (T4a), and they formed the basis of our study. Of 27 patients, 52% were women. The median age was 70 years (range 27-87 years). Ten patients (37%) presented with distant metastases; four to bone, three to lung, and three to both bone and lung. All patients had extended total thyroidectomy, except two who had subtotal thyroidectomy. Twenty patients (74%) had central compartment neck dissection and 11 also had lateral neck dissection. Four patients had pN0, six (30%) pN1a, and 10 (50%) pN1b neck disease. Twenty-one patients (77%) had adjuvant therapy: 15 (55%) radioactive iodine (RAI) only, three (11%) postoperative external beam radiation (EBRT) only, and three (11%) had both RAI and EBRT. Overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and regional recurrence-free survival (RRFS) were calculated by the Kaplan Meier method. RESULTS: The median follow-up time was 57 months (range 1-197 months). The 5 year OS and DSS were 47% and 49%, respectively. This poor outcome was due to distant metastatic disease; 10 patients had distant metastases at presentation and a further six developed distant metastases during follow-up. Locoregional control was good with 5-year LRFS and RRFS of 70% and 62%, respectively. Overall, eight patients (30%) had recurrences: two had distant alone, two regional, two regional and distant, one local and distant, and one had local, regional, and distant recurrence. CONCLUSION: Aggressive surgery in patients with PDTC showing gross ETE resulted in satisfactory locoregional control. Due to the small proportion of patients who received EBRT (22%), it is not possible to analyze its benefit on locoregional control. Of significance is the observation that the majority of patients (60%) who presented with or subsequently developed distant metastases eventually died of distant disease. New systemic therapies to target distant metastatic disease are required for improvements in outcome.

Long-term regional control and survival in patients with "low-risk," early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation: the importance of tumor thickness.

BACKGROUND: The objectives of this study were to determine the incidence of locoregional failure in patients with low-risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation. METHODS: A combined database of patients with OTSCC who received treatment at Memorial Sloan-Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1-T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient-related, tumor-related, and treatment-related characteristics were recorded. Local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. RESULTS: At a median follow-up of 66 months (range 1-171 months), the 5-year rates of local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥ 4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence-free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥ 4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease-specific survival compared with those who did not (33% vs 97%; P < .0001). CONCLUSIONS: Patients with low-risk, pathologic T1-T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥ 4 mm thick.

A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage III/IVB head and neck squamous cell cancer.

BACKGROUND: For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. METHODS: Planned treatment consisted of definitive intensity-modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m(2) on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2-year progression-free survival (PFS), and overall survival (OS) was a secondary endpoint. RESULTS: Forty-two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27-75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow-up was approximately 31.8 months (range, <3 to 51 months). The 2-year PFS rate was 75.9% (95% confidence interval, 63.9%-90.1%), and the 2-year OS rate was 88% (95% confidence interval, 78.6%-98.4%). Among 32 patients for whom post-treatment Head and Neck Performance Status Scores were obtained (median, 5.6 months after completing radiation therapy), scores of 100 for eating, speech, and diet, respectively, were recorded among 75%, 84%, and 50% of patients. BACKGROUND: The addition of bevacizumab to high-dose cisplatin plus IMRT did not appear to increase toxicity to unacceptable levels among patients with HNSCC, and the efficacy results were encouraging.

Correlation of a priori DCE-MRI and (1)H-MRS data with molecular markers in neck nodal metastases: Initial analysis.

The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [(1)H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment DCE-MRI and (1)H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the "endogenous marker" of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, (1)H-MRS, and molecular marker data. A significant correlation was observed between DCE-MRI parameter std(k(ep)) and VEGF IHC expression level (rho=0.81, p=0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(K(trans)) and std(v(e)) (rho=-0.71; p=0.004, and rho=-0.73; p=0.003, respectively). Other DCE-MRI, (1)H-MRS and IHC values did not show significant correlation. The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.

Craniofacial surgery for esthesioneuroblastoma: report of an international collaborative study.

Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB. Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients. Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis. Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome.

Viable tumor in postchemoradiation neck dissection specimens as an indicator of poor outcome.

BACKGROUND: The objective of this study was to determine the prognostic significance of viable tumor in postchemoradiation neck dissection specimens in patients with squamous cell carcinoma of the laryngopharynx. METHODS: Retrospective analysis identified 181 patients treated with primary concurrent chemoradiation for carcinoma of the laryngopharynx at Memorial Sloan-Kettering Cancer Center between the years 1995 and 2005. Of these, 56 patients had a comprehensive neck dissection either as a planned or salvage procedure. Neck dissection specimens were analyzed by a single pathologist for the presence of viable tumor. The presence of viable tumor was correlated to the timing of neck dissection after chemoradiation and to tumor response. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined by the Kaplan-Meier method, and correlation to tumor viability was determined with the log-rank test. RESULTS: Nineteen (33%) patients had viable tumor in their neck dissection specimens. Viable tumor was higher in patients who had a less-than-complete response to chemoradiation compared with those who had a complete response (42% vs 25%, p = .1). There was no correlation to timing of neck dissection. The 5-year OS, DSS, and RFS were significantly lower in patients who had viable tumor in their neck dissection specimens (OS 49% vs 93%, p = .0005; DSS 56% versus 93%, p = .003; RFS 40% vs 75%, p = .004). CONCLUSIONS: Patients with viable tumor in postchemoradiation neck dissection specimens had a poorer outcome compared with patients with no viable tumor.

Tissue microarray evidence of association between p16 and phosphorylated eIF4E in tonsillar squamous cell carcinoma.

BACKGROUND: Expression of p16 is a marker for human papillomavirus (HPV)-related carcinogenesis in head and neck cancer. The purpose of this study is to determine if p16 immunoreactivity is associated with aberrant expression of components of the PI3 kinase pathway. METHODS: A tissue microarray (TMA) was constructed for 46 archived tonsillar squamous cell carcinoma specimens. Clinical demographics of these patients were analyzed, and the TMA was interrogated with antibodies directed against p16, phosphorylated Akt(Ser473), phosphorylated S6(Ser240/244), phosphorylated S6(Ser235/236), phosphorylated 4E-BP1(Thr37/46), phosphorylated eIF4E(Ser209), PTEN, p21, and p53. RESULTS: There was a significant correlation between history of tobacco abuse (>10 pack/years) and absence of p16 expression (p = .01). Expression of p16 was significantly associated with immunoreactivity of p21 (p = .02), PTEN (p = .02), and phosphorylated eIF4E (p = .03). There was no evidence of association between p16 status and expression of phosphorylated S6, phosphorylated 4E-BP1, or p53. CONCLUSION: p16 positive tonsillar squamous cell carcinoma is characterized by expression of phosphorylated eIF4E that may occur via a mammalian target of rapamycin (mTOR)-independent mechanism.