Cadaveric analysis of autonomic nerve fiber density in posterior nasal, posterolateral nasal, and anterior ethmoid nerves.

KEY POINTS: Autonomic nerve densities were equivalent in posterior nasal (PNN), posterolateral nasal (PLNN), and anterior ethmoid nerves (AEN). Rhinitis studies should explore the utility of PLNN and/or AEN transection over PNN alone.

Glycogenic Acanthosis: An Unusual Cause of Vocal Fold Leukoplakia.

Glycogenic acanthosis is a common benign lesion of the esophagus; however, reports of extra-esophageal manifestations are exceedingly rare. This case represents the first report of laryngeal glycogenic acanthosis found in a living patient, presenting as vocal fold leukoplakia. Glycogenic acanthosis may be considered among the differential diagnoses of conditions presenting as vocal fold leukoplakia. Laryngoscope, 132:1641-1643, 2022.

A Grade I Intracranial Meningioma with Metastasis to Multiple Vertebral Bodies: A Case Report and Literature Review.

World Health Organization (WHO) grade I meningiomas are slow-growing and typically benign brain tumors that can often be easily removed by surgery and rarely become malignant. We report the case of a WHO grade I meningioma in a 67-year-old man with multiple extracranial metastases.

Inverted Papilloma of the Middle Ear and Mastoid Cavity: A Case Report, Literature Review, And Surveillance Proposal.

INTRODUCTION TO THE TOPIC: Inverted papilloma is a rare condition of the middle ear. In this paper, the authors present a case report of a patient at a Midwestern health system with inverted papilloma. To supplement the case report, a literature review was also performed to identify clinical trends predisposing such cases to recurrence, malignant transformation, and response to radiation. In addition, the authors also propose a surveillance algorithm derived from this case and previously published surveillance strategies. CASE REPORT: The authors present a rare case of inverted papilloma of the middle ear. To the authors' knowledge, this is the youngest case presentation (mid-teenage years) of this condition to have been reported in the literature. The patient underwent surgical excision, had recurrence, and has been disease free since revision surgery. SUMMARY OF THE EVIDENCE: Our literature review identified 25 cases previously published with ours being the 26th. An inadequate number of cases exist to abstract statically relevant clinical trends in presentation and tumor behavior. Additionally, no tumor characteristics have been identified that predispose tumors to future malignant transformation. No assessments can be made regarding the benefits of radiation therapy. Most cases to date have been surveyed with a combination of CT, MRI, and clinical follow-up. CONCLUSIONS: Inverted papillomas of the middle ear space are rare. Although this case report adds to the literature, additional cases are needed to draw statistically relevant clinical characteristics and responses to medical and surgical therapy.

Proteomic analysis of oral cavity squamous cell carcinoma specimens identifies patient outcome-associated proteins.

CONTEXT: Global proteomic analysis of oral cavity squamous cell carcinoma was performed to identify changes that reflect patient outcomes. OBJECTIVES: To identify differentially expressed proteins associated with patient outcomes and to explore the use of imaging mass spectrometry as a clinical tool to identify clinically relevant proteins. DESIGN: Two-dimensional separation of digested peptides generated from 43 specimens with high-resolution mass spectrometry identified proteins associated with disease-specific death, distant metastasis, and loco-regional recurrence. RNA expressions had been correlated to protein levels to test transcriptional regulation of clinically relevant proteins. Imaging mass spectrometry explored an alternative platform for assessing clinically relevant proteins that would complement surgical pathologic diagnosis. RESULTS: Seventy-two peptide features were found to be associated with 3 patient outcomes: disease-specific death (9), distant metastasis (16), and loco-regional recurrence (39); 8 of them were associated with multiple outcomes. Functional ontology revealed major changes in cell adhesion and calcium binding. Thirteen RNAs showed strong correlation with their encoded proteins, implying transcriptional control. Reduction of DSP, PKP1, and TRIM29 was associated with significantly shorter time to onset of distant metastasis. Reduction of PKP1 and TRIM29 correlated with poorer disease-specific survival. Additionally, S100A8 and S100A9 reductions were verified for their association with poor prognosis using imaging mass spectrometry, a platform more adaptable for use with surgical pathology. CONCLUSIONS: Using global proteomic analysis, we have identified proteins associated with clinical outcomes. The list of clinically relevant proteins observed will provide a means to develop clinical assays for prognosis and optimizing treatment selection.

Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas.

Small, noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. We used comparisons of global miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in our patient population. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient among 736 miRNAs that were evaluated. This result has been previously observed by other groups; however, we extend this finding with the unique observation that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% CI: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, we found that oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls. We conclude that miR-375 represents a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor's invasive properties.

Cytoplasmic ezrin and moesin correlate with poor survival in head and neck squamous cell carcinoma.

Members of the 4.1 superfamily of proteins, including ezrin, moesin, merlin, and willin regulate many normal physiologic processes such as cellular shape, motility, and proliferation. In addition, they contribute both to tumor development and tumor progression. We reported previously that strong cytoplasmic ezrin expression was independently associated with poorer patient survival. One hundred and thirty-one histologically confirmed primary head and neck squamous cell carcinomas were examined prospectively for cancer progression and survival at a large health care center in the Bronx, NY, USA. Immunohistochemical analysis of ezrin, moesin, merlin, and willin expression in tissue microarray samples of primary head and neck squamous cell carcinoma revealed a significant association of increased cytoplasmic ezrin with poor cancer survival. Global RNA analyses suggest that cancers with high cytoplasmic ezrin have a more invasive phenotype. This study supports our previous findings associating cytoplasmic ezrin with more aggressive behavior and poorer outcome and indicates the need for a multi-institutional study to validate the use of cytoplasmic ezrin as a biomarker for treatment planning in head and neck squamous cell carcinoma.

Electronic tracking of human brain samples for research.

Insight into the pathogenesis of neurodegenerative disorders requires accurately categorized postmortem human brain tissue. This article introduces electronic tissue tracking and management as implemented at New York Brain Bank (NYBB) through processing of the brain at fresh state and storing standardized frozen samples. NYBB tissue tracking uses a relational database to co-register a bar coded, unique sample identifier to unique coordinates in the three-dimensional freezer space, allowing immediate retrieval of stored samples without further dissection. In the 5 years since the inception of NYBB (2002-2007) 560 brains (63,252 fresh frozen samples) were processed and as of 11/2007, 54,242 samples are stored seven freezers occupying 81% of maximum capacity of NYBB. Within the same time period, 1,094 requests were processed and 9,096 samples were disbursed with an average turnaround time of five working days. The NYBB system of brain banking has the following key advantages: (1) The dissection of the brain and the harvest of samples at the fresh state improve their anatomic specificity and quality; (2) samples are ready for immediate disbursement once categorized diagnostically, reducing the time between the receipt of request and disbursement of samples; (3) the methods prevent thaw-refreeze cycles and carving out of regions of interest from frozen tissue, which is cumbersome and deleterious to the both samples and source brains; (4) accurate quantitative data on stored samples according to anatomical regions and distributive diagnosis guides future sample collection and fosters effective use of limited resources.

The spectrum of B-cell non-Hodgkin lymphomas with dual IgH-BCL2 and BCL6 translocations.

Dual IgH/BCL2 and BCL6 translocations are rarely observed in B-cell non-Hodgkin lymphomas (B-NHLs). We investigated the morphologic, phenotypic, and cytogenetic spectrum of B-NHL with such dual translocations. Dual IgH/BCL2 and BCL6 translocations were detected in follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs), representing 6.1% of 132 B-NHLs in our series, including 6 (11%) of 56 FLs (grades 1, 2, and 3a) and 2 (3%) of 76 DLBCLs; 33% of FLs with dual translocations had variant morphologic features. All dual-translocation FLs were CD10+/BCL6+/BCL2+/MUM1-, and the DLBCLs demonstrated "activated" germinal center (CD10+/BCL6+/MUM1+) and non-germinal center (CD10-/BCL6+/MUM1+) phenotypes. BCL6 translocations in all cases involved nonimmunoglobulin genes/loci. Mean chromosome abnormalities in dual-translocation FLs and DLBCLs did not differ from IgH/BCL2 FLs and DLBCLs. Detection of dual translocations predominantly in low-grade FLs suggests that BCL6 abnormalities are acquired early in the histologic evolution of a subset of IgH/BCL2-associated FLs.

Twenty-first century brain banking: practical prerequisites and lessons from the past: the experience of New York Brain Bank, Taub Institute, Columbia University.

Generally accepted methods for processing postmortem brains are lacking, despite the efforts of pioneers in the field, and the growing awareness of the importance of brain banking for investigating the pathogenesis of illnesses unique to humans. Standardizing methods requires compromises, institutional or departmental mindset promoting collaboration, and the willingness to share ideas, information, and samples. A sound balance between competition and institutional interests is needed to best fulfill the tasks entrusted to health care institutions. Thus, a potentially widely accepted protocol design involves tradeoffs. We successfully integrated brain banking within the operation of the department of pathology. We reached a consensus whereby a brain can be utilized for diagnosis, research, and teaching. Thus, routing brains away from residency programs is avoided. The best diagnostic categorization possible is being secured and the yield of samples for research maximized. Thorough technical details pertaining to the actual processing of brains donated for research were recently published. Briefly, one-half of each brain is immersed in formalin for performing the neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state to obtain samples ready for immediate disbursement once categorized diagnostically. The samples are tracked electronically, which is crucial. This important tracking system is described separately in this issue. This report focuses on key lessons learned over the past 25 years of brain banking including successful solutions to originally unforeseen problems.

Twenty-first century brain banking. Processing brains for research: the Columbia University methods.

Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at -160 degrees C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research.

Cytogenetic analysis of B-cell posttransplant lymphoproliferations validates the World Health Organization classification and suggests inclusion of florid follicular hyperplasia as a precursor lesion.

Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized. We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 infectious mononucleosis (IM)-like lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein-Barr virus infection status, and clinical outcome. Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 (c-MYC) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM-like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome. We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD.

Adult-onset nemaline myopathy and monoclonal gammopathy.

A 45-year-old man with severe proximal muscle weakness had findings diagnostic of adult-onset nemaline myopathy. He also had a monoclonal gammopathy. This is the fifth report of adult-onset nemaline myopathy in a patient with monoclonal gammopathy, suggesting that the occurrence of these entities may be more than a chance association. Myocyte-bound immunoglobulin or light chains were not detected and immunotherapy was not effective in this patient. Other causes of adult-onset nemaline myopathy were ruled out, including the most common mutations of sarcomeric thin filament genes.

Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation.

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy. Magnetic resonance imaging indicated focal lesions of the cerebellum and brainstem, and electrodiagnostic studies suggested an axonal neuropathy. Autopsy revealed a flattened small-bowel mucosa with intraepithelial lymphocytosis, a spectrum of degenerative changes of the intra-abdominal and mediastinal lymph nodes, including cavitary degeneration, and splenomegaly. Histologically, the lymph nodes showed pseudocyst formation and lymphocytic vasculitis with fibrinoid necrosis, and sections of the brain exhibited fibrinoid degeneration of small blood vessels, sparse perivascular lymphocytic infiltrates, and perivascular ischemic lesions. Identical T-cell clones were identified in the duodenum, stomach, lymph nodes, and spleen. This patient had an unusual neurological disorder related to a vasculopathy, probably mediated by a circulating neoplastic clone of activated T cells.

Possible regulation of microtubules through destabilization of tubulin.

Chaperones and folding cofactors are known to mediate posttranslational folding of nascent tubulin, thus forming functional dimers. Based on sequence likeness, a novel protein similar to cofactor E, E-like protein (El), was identified. In overexpression experiments El, similar to a subset of folding factors (i.e. cofactors D and E), appears to disrupt functional dimers and target them for destruction by the proteasome. El apparently does not interact with microtubules directly and has no function in the tubulin folding pathway. Suppression of El expression seems to increase the cellular content of stable, posttranslationally modified microtubules by an unknown mechanism. Degradation of functional tubulin dimers as well as the alteration of the cellular content of stable microtubules through El might regulate the distribution and organization of organelles in vivo.

Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients.

The aims of this study were to: (1) assess the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity in depressed patients as measured by single photon emission tomography (SPECT); (2) evaluate the predictive value of brain SPECT on the antidepressant efficacy of rTMS. Patients (n=17) received 1600 rTMS stimuli at a rate of 10 Hz, 5 days per week for 2 weeks to the left dorsolateral prefrontal cortex. Whole brain SPECT data were acquired using Tc99m-Bicisate. Regional cerebral blood flow (rCBF) was correlated with the % change in the 28-item Hamilton Depression Rating Scale Score (Delta-HDRS) and a semiquantitative region of interest (ROI) analysis was conducted. Prior to rTMS there was a significant left-right asymmetry favoring the right, whereas 2 weeks after the rTMS treatment this asymmetry was reversed. The rCBF in limbic structures was negatively correlated with the outcome and rCBF in several neocortical areas was positively correlated. Brain SPECT can provide information about mechanisms of action of rTMS and may have predictive value for the antidepressant efficacy of rTMS.