Circulating hybrid cells predict presence of occult nodal metastases in oral cavity carcinoma.

BACKGROUND: Levels of circulating hybrid cells (CHCs), a newly identified circulating tumor cell (CTC), correlate with disease stage and progression in cancer. We investigated their utility to risk-stratify patients with clinically N0 (cN0) oral cavity squamous cell carcinoma (OCSCC), and to identify patients with occult cervical lymph node metastases (pN+). METHODS: We analyzed peripheral blood samples for CHCs with co-expression of cytokeratin (tumor) and CD45 (leukocyte) from 22 patients with cN0 OCSCC using immunofluorescence microscopy, then correlated levels with pathologic lymph node status. RESULTS: CHC levels exceeded CTCs and correlated with the presence of both clinically overt (p = 0.002) and occult nodal metastases (p = 0.006). CONCLUSIONS: For evaluated cN0 OCSCC patients, those with cN0 → pN+ status harbored elevated CHC levels compared to patients without occult disease. Our findings highlight a promising blood-based biologic assay with potential utility to determine the necessity of surgical neck dissection for staging and treatment.

Mucosal Eosinophilia and Neutrophilia Are Not Associated With QOL or Olfactory Function in Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is often differentiated by histopathologic phenotypes (eosinophilic versus neutrophilic), which may impact disease severity measures and outcomes. As such, it has been suggested that counts of cellular elements be included as part of a standard pathological report following endoscopic sinus surgery (ESS). OBJECTIVES: This cross-sectional study evaluated associations of mucosal eosinophilia and neutrophilia with measures of quality-of-life (QoL) and olfactory function. METHODS: Patients with medically refractory CRS completed the SNOT-22 survey and Brief Smell Identification Test (BSIT) at enrollment. In addition, baseline Lund-Mackay computed tomography (CT) and Lund-Kennedy endoscopy scores were collected. Ethmoid mucosa was biopsied during ESS and reviewed using microscopy to quantify densest infiltrate of eosinophils or neutrophils per high-powered-field (HPF). Eosinophilic CRS (eCRS) and neutrophilic CRS (nCRS), both with and without nasal polyposis (NP), were compared across SNOT-22 and BSIT scores. RESULTS: 77/168 patients demonstrated mucosal eosinophilia (eCRS) while a total of 42/168 patients demonstrated mucosal neutrophilia (nCRS). After adjusting for polyp status, 35/168 had eCRSsNP, 42/168 eCRSwNP, 75/168 non-eCRSsNP, 16/168 non-eCRSwNP. Additionally, 22/161 were noted to have nCRSsNP, 20/161 nCRSwNP, 84/161 non-nCRSwNP, and 35/161 non-nCRSsNP. A small subset of patients demonstrated both eosinophilia and neutrophilia: 14 CRSwNP and 7 CRSsNP. When evaluating average Lund-Mackay Scores (LMS), significant differences existed between non-eCRSsNP and eCRSsNP (p = 0.006). However, after controlling for nasal polyps, eosinophilia did not significantly associate with differences in the Lund-Kennedy Score. Neutrophilia did not significantly associate with any changes in LMS or LKS after controlling for NP. Eosinophilic and neutrophilic histopathologic subtypes did not significantly associate with differences in baseline SNOT-22 or BSIT measures after controlling for NP. CONCLUSION: Neither the presence of mucosal eosinophilia nor mucosal neutrophilia demonstrated significant associations with SNOT-22 quality-of-life or BSIT olfactory function scores when controlling for comorbid nasal polyposis.

Patient-reported sleep outcomes lack association with mucosal eosinophilia or neutrophilia in patients with chronic rhinosinusitis undergoing functional endoscopic sinus surgery.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with sleep dysfunction, but the underlying pathophysiology is poorly understood. The purpose of this study was to determine if mucosal eosinophilia or neutrophilia were associated with sleep dysfunction severity or altered the improvement in sleep dysfunction following functional endoscopic sinus surgery (FESS). METHODS: A total of 104 patients with medically refractory CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP), completed the Pittsburgh Sleep Quality Index (PSQI) before and after FESS. Anterior ethmoid mucosa was collected during FESS and densest infiltrates of eosinophilia and neutrophilia per high-power field (HPF) were determined by microscopy. Eosinophilic (>10 eosinophils/HPF) and neutrophilic (>4 neutrophils/HPF) CRS were then compared to preoperative and postoperative PSQI measures. RESULTS: Of 104 study participants, 88 (85%) reported preoperative PSQI scores consistent with "poor sleep," (PSQI total > 5). The cohort overall demonstrated significant improvement in poor sleep (65%; χ2 = 12.03; p < 0.001) 16.8 ± 5.0 months after FESS. Regardless of nasal polyposis, neither eosinophilic nor neutrophilic CRS was associated with differences in mean postoperative PSQI improvement. However, in patients with neutrophilic CRSsNP, there was a significant relationship between severity of neutrophilia and improvement in sleep latency (R = -0.798, p = 0.003) and sleep efficacy (R = -0.777, p = 0.005). CONCLUSION: Chronic inflammation has been hypothesized to play a pathophysiologic role in sleep dysfunction associated with CRS. This study suggests that in patients with medically refractory CRS, evidence of mucosal eosinophilia and neutrophilia lack strong associations with patient-reported sleep dysfunction or improvements in sleep quality after FESS, overall. However, neutrophilia may impact sleep latency and efficacy in patients with CRSsNP.

Congenital capillary proliferation of the kidney: a distinctive renal vascular lesion of childhood.

Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1). An eighth lesion showed nonspecific findings, which were interpreted as reactive during our review. The remaining 4 cases presented either prenatally, at birth, or shortly after birth and were morphologically similar. These were characterized by a peculiar pattern of capillary proliferation with entrapment of native renal structures, variable amounts of extramedullary hematopoiesis and reactive lymphocytes, foci of infarction and hemorrhage, and the presence of feeding and draining vessels at their periphery. To our knowledge, this represents a previously undescribed congenital vascular lesion involving the kidney, which we have descriptively and provisionally termed congenital capillary proliferation of the kidney (CCPK). While it is unclear whether CCPK represents a malformation or neoplastic proliferation, it shows overlapping features with congenital hemangioma of the liver (solitary congenital hepatic hemangioma) and congenital nonprogressive hemangioma (CNH) of the skin and soft tissue, suggesting a possible common pathogenesis among these 3 entities.

Rheumatoid nodule presenting as a buccal submucosal nodule: A rare presentation of a common disease.

BACKGROUND: Rheumatoid nodules are a common manifestation of rheumatoid arthritis but buccal rheumatoid nodules are extremely rare. The purpose of this study was to report a rare case of a rheumatoid buccal nodule and a review of the literature. METHODS AND RESULTS: This case is about a 79-year-old woman with rheumatoid arthritis who was taking methotrexate and hydroxychloroquine, presenting with an enlarging left buccal submucosal mass. An incisional biopsy showed features consistent with that of a rheumatoid nodule. The mass was managed expectantly and the patient was taken off methotrexate with a marked reduction in the size of the nodule. CONCLUSION: Submucosal rheumatoid nodules of the oral cavity are an extremely rare manifestation of rheumatoid arthritis but should be considered in the differential diagnosis in patients with a history of rheumatoid arthritis presenting with submucosal masses. © 2016 Wiley Periodicals, Head Neck 39: E12-E14, 2017.

Presumed Second Focus of Lung Immunoglobulin G4-Related Disease Found to be Adenocarcinoma.

We describe a patient presenting with bilateral radiologically similar lung lesions initially diagnosed as immunoglobulin (Ig) G4-related disease from biopsy of one lesion, but radiographic changes 6 months later prompted biopsy of the second lesion and showed adenocarcinoma. No case of lung IgG4-related disease and a distant lung malignancy has been previously reported. This is notable because lung IgG4-related disease often manifests in multiple thoracic locations but is diagnosed from a representative biopsy specimen.

Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Expanded criteria for carcinoid liver debulking: Maintaining survival and increasing the number of eligible patients.

BACKGROUND: Cytoreduction of carcinoid liver metastases typically aims for ≥ 90% debulking in patients without extrahepatic disease. Data on the impact of less-restrictive resection criteria and other clinical and tumor-specific factors on outcomes are limited. METHODS: Records of carcinoid patients undergoing liver debulking from 2007 to 2011 were reviewed. Debulking threshold was 70%, extrahepatic disease did not preclude cytoreduction, and positive margins were allowed. Kaplan-Meier liver progression-free (PFS) and disease-specific (DSS) survival were calculated and compared by log-rank analysis and statistical significance of differences in distributions of factors between patient groups was determined by chi-squared analysis. RESULTS: Fifty-two patients were identified. Complete resection of intrahepatic and extrahepatic gross disease was achieved in 12 patients. All primaries reviewed were low grade, but one third of patients had at least one intermediate-grade metastasis. Fifteen patients (29%) had liver progression; median PFS was 72 months. Five-year DSS was 90%, with all deaths from liver failure. Only age was an important prognostic factor for PFS and DSS. Five-year DSS for patients <50 years was 73% and was 97% for patients 50 or older (P = .03). CONCLUSION: The use of expanded criteria for debulking resulted in 90% 5-year DSS. Although younger age portends a poorer prognosis, the favorable PFS and DSS justify also using expanded criteria in this subgroup.

A cross-sectional analysis of the prevalence of Barrett esophagus in otolaryngology patients with laryngeal symptoms.

BACKGROUND: Populations at risk for esophageal adenocarcinoma remain poorly defined. Laryngeal symptoms can be secondary to laryngopharyngeal reflux (LPR) and can occur without associated gastroesophageal reflux symptoms such as heartburn and regurgitation. GOAL: We sought to determine the prevalence of Barrett esophagus (BE) in otolaryngology patients with laryngeal symptoms±typical gastroesophageal reflux disease (GERD) symptoms. STUDY: We performed a cross-sectional study of otolaryngology clinic patients who reported laryngeal symptoms. Symptoms, medications, and exposure histories were obtained. Unsedated transnasal endoscopy was performed. Suspected BE was biopsied and confirmed histologically. Risk factors and prevalence of BE were assessed. RESULTS: Two hundred ninety-five patients were enrolled [73% male, median age 60 y (interquartile range 51 to 68 y)]. The overall prevalence of BE was 11.8% (n=33). Antisecretory medication use was present in 56% (n=156) of patients at enrollment. Compared with patients without BE, patients with BE were more likely to be male (P=0.01) and to report occupational lung injury (P=0.001). Duration, but not severity of laryngeal symptoms, significantly increased the odds of BE (odds ratio, 5.64; 95% confidence interval, 1.28-24.83; for a duration of symptoms >5 y). Of patients with BE, 58% (n=19) had coexisting LPR and GERD symptoms and 30% (n=10) had only LPR symptoms. Presence and size of hiatal hernia and length of columnar-lined esophagus were significant risk factors for BE. CONCLUSIONS: Long-standing laryngeal symptoms are associated with the presence of BE in otolaryngology patients. Patients with chronic laryngeal symptoms and no identifiable ear, nose, or throat etiology for those symptoms may benefit from endoscopic screening regardless of whether typical GERD symptoms are present.

Ethmoid histopathology does not predict olfactory outcomes after endoscopic sinus surgery.

BACKGROUND: Histological inflammation correlates with the degree of baseline olfactory dysfunction in patients with chronic rhinosinusitis (CRS); however, factors associated with improvement in olfactory status after endoscopic sinus surgery (ESS) remain elusive. Our purpose was to compare histopathological findings in CRS patients with olfactory loss and evaluate whether inflammatory markers can predict long-term olfactory improvement after ESS. METHODS: Adult (> or = 18 years) patients with CRS were prospectively enrolled after electing ESS due to failed medical management. Mucosal tissue specimens were collected at the time of surgery and underwent pathological review in a blinded fashion. Subjects completed the 40-item Smell Identification Test (SIT) preoperatively and at least 6 months postoperatively. Multivariate logistic regression was used to identify histological factors associated with postoperative improvement in SIT score. RESULTS: The final cohort was comprised of 101 patients with a mean follow-up of 16.7 +/- 6.0 months. Mean mucosal eosinophil count was higher in patients with hyposmia and anosmia (p < 0.001). Patients with preoperative anosmia were more likely to have greater severity of basement membrane (BM) thickening compared with subjects with hyposmia or normosmia (p = 0.021). In patients with olfactory dysfunction, 54.7% reported olfactory improvement of at least 4 points on postoperative SIT scores. After controlling for nasal polyposis, histological variables were not associated with postoperative improvement in olfaction. CONCLUSION: Patients with severe olfactory dysfunction were more likely to have mucosal eosinophilia and BM thickening on ethmoid histopathological examination compared with normosmic patients. The presence of specific histological inflammatory findings did not, however, predict olfactory improvement after surgery.

Relationship between clinical measures and histopathologic findings in chronic rhinosinusitis.

OBJECTIVE: Describe detailed histopathologic findings from a cohort of patients with chronic rhinosinusitis and evaluate whether histologic measures correlate with baseline clinical factors. STUDY DESIGN: Cross-sectional study with planned data collection. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Adult patients with chronic rhinosinusitis were prospectively enrolled and demographic data and medical comorbidities recorded. Disease severity was measured by computed tomography (CT), endoscopy, Smell Identification Test (SIT), the Chronic Sinusitis Survey, Rhinosinusitis Disability Index, and SF-36 General Health Survey. Mucosal specimens were assessed for the presence of mucosal inflammation, including cellular (eosinophils, neutrophils, lymphocytes, mast cells, plasma cells, macrophages), epithelial (squamous metaplasia, basement membrane thickening, goblet cells), and stromal markers (subepithelial edema, fibrosis). Histopathologic findings were correlated to baseline clinical factors. RESULTS: A total of 147 subjects were enrolled with histologic samples available for review. Presence of inflammatory markers was diverse, with lymphocytes present in 100 percent of subjects, eosinophils in 49.7 percent, and neutrophils found in 0.7 percent. Total eosinophil counts correlated with the presence of nasal polyposis (r = -0.367; P < 0.001), asthma (r = 0.264; P = 0.001), and aspirin intolerance (r = 0.279; P = 0.001). Mucosal eosinophilia correlated with worse disease severity on CT (r = 0.414; P < 0.001), endoscopy (r = 0.376; P < 0.001), and SIT (r = -0.253; P = 0.002), with the highest correlations seen in subgroups without nasal polyps. Histopathologic findings did not significantly correlate with any quality-of-life measure. CONCLUSION: Mucosal eosinophilia correlates with objective disease severity as defined by CT, endoscopy, and SIT scores. Although other histologic markers of inflammation are present, none show similar correlations. The presence of mucosal eosinophils does not correlate with quality-of-life scores.

Cutaneous reactions to chemotherapy: commonly seen, less described, little understood.

Chemotherapeutic and molecularly targeted agents are associated with a wide array of cutaneous toxicities. Despite the variety of toxicities, surprisingly little is understood regarding the pathogenesis underlying these reactions. This article reviews the most common cutaneous toxicities of cytotoxic chemotherapy and molecularly targeted systemic therapy, including extravasation of chemotherapy, with a discussion of the known and postulated underlying mechanisms of action. The need for developing a greater understanding of the basis of these reactions through more detailed study is evident.

Office-based unsedated small-caliber endoscopy is equivalent to conventional sedated endoscopy in screening and surveillance for Barrett's esophagus: a randomized and blinded comparison.

OBJECTIVES: A major limitation to screening and surveillance of Barrett's esophagus is the complexity, expense, and risk associated with sedation for upper endoscopy. This study examines the feasibility, accuracy, and patient acceptability of office-based unsedated endoscopy as an alternative. METHODS: Of 274 eligible adults scheduled for endoscopic screening for gastroesophageal reflux symptoms or surveillance of Barrett's esophagus at a tertiary care center, 121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a randomized crossover study. The two procedures were compared with regard to histological detection of Barrett's esophagus and dysplasia and biopsy size. Patients answered questionnaires assessing the tolerability of the procedures. RESULTS: The prevalence of Barrett's esophagus was 26% using conventional endoscopy and 30% using unsedated endoscopy (P= 0.503). The level of agreement between the two approaches was "moderate" (kappa= 0.591). Each modality detected four cases of low-grade dysplasia with concordance on one case. The tissue samples collected with unsedated endoscopy were smaller than with conventional endoscopy (P < 0.001). The majority of subjects rated their experience with both procedures as being well tolerated with minimal or no difficulty. When asked which procedure they would prefer in the future, 71% (81/114) chose unsedated small-caliber endoscopy. CONCLUSIONS: Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barrett's esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application.