Malakoplakia of the thyroid gland: a case report and review of literature.

Malakoplakia is a rare granulomatous disease that most commonly occurs in the urinary tract. It is characterized by sheets of histiocytes with granular basophilic inclusions and Michaelis-Gutmann bodies. We present an exceedingly rare case of malakoplakia of the thyroid in a 54-year-old Caucasian woman on immunosuppressive therapy for renal transplant performed in 1994.

Opportunities and challenges facing biomarker development for personalized head and neck cancer treatment.

Head and neck oncologists have traditionally relied on clinical tumor features and patient characteristics to guide care of individual patients. As surgical, radiotherapeutic, and systemic treatments have evolved to become more anatomically precise and mechanistically specific, the opportunity for improved cure and functional patient recovery has never been more promising for this historically debilitating cancer. However, personalized treatment must be accompanied by sophisticated patient selection to triage the application of advanced therapies toward ideal patient candidates. In this monograph, we review current progress, investigative themes, and key challenges facing head and neck cancer biomarker development intended to make personalized head and neck cancer treatment a clinical reality.

Prognostic implication of sentinel lymph node biopsy in cutaneous head and neck melanoma.

BACKGROUND: Current therapy for intermediate thickness melanoma involves wide local excision with sentinel lymph node biopsy (SLNB). SLNB provides important prognostic information and immediate regional lymphadenectomy for a positive sentinel lymph node (SLN) may improve survival and identifies patients who are candidates for adjuvant therapy and/or clinical trials. The head and neck site is unique because of its complex lymphatic drainage pattern to multiple nodal basins and because of the risk of site-specific morbidity associated with regional lymphadenectomy when compared to other body sites. The goal of this study is to report the results of SLNB for head and neck cutaneous melanoma in locating the sentinel node and to report on the prognostic implications of SLNB for this cohort of patients. METHODS: A prospectively entered melanoma database was used to review consecutive patients with head and neck cutaneous melanoma undergoing SLNB at Memorial Sloan-Kettering Cancer Center between 1996 and 2007. The database, along with a retrospective chart review, was used to evaluate the success of SLNB at locating an SLN and the success rate of frozen section and permanent section analysis at diagnosing metastatic disease. Recurrence at all sites including the nodal basin and status at last follow-up was recorded. Characteristics of the patients' primary melanoma were included. Descriptive statistics along with univariate and multivariate survival analysis were performed. RESULTS: Between 1996 and 2007, 234 patients with a diagnosis of head and neck cutaneous melanoma underwent SLNB and had at least 1 month of follow-up. At least 1 SLN was identified in 218 of these patients (93%) by lymphoscintigraphy. In 16 patients, no SLN was found. These patients had a much shorter time to recurrence (4.75 months) than either the SLN-positive group (10.7 months) or the SLN-negative group (26.0 months). They had a disease-specific survival (DSS) in between the SLN-positive and SLN-negative group. Of the patients in whom an SLN was identified, 28 patients (12%) had at least 1 positive SLN. Of these, the SLNs of 14 patients (50%) were identified on frozen section; 14 (50%) could only be identified after further sectioning or immunohistochemical analysis postoperatively. Among 190 patients with a negative SLNB, 12 patients had recurrences in the nodal basin. This resulted in a sensitivity of 70%, a negative predictive value of 94%, and a false-negative rate of 30%. The 3-year disease-free survival for SLN-negative and SLN-positive patients was 84% (p < .031) and 58% (p < .102), respectively. The 3-year melanoma-specific survival was 98% (p < .012) and 75% (p < .201), respectively. CONCLUSION: The SLN status is an important predictor of survival. The technique, performed in the head and neck is complex and associated with a high false-negative rate.

In vivo and in vitro models of ionizing radiation to the vocal folds.

BACKGROUND: Radiation therapy (RT) to the head and neck often results in damage to the vocal folds (VF) and surrounding structures. Characterization and treatment of these sequelae is limited, likely due to the lack of experimental models. METHODS: Larynges from rats exposed to 2 fractionation schedules (40 Gy total) were analyzed histologically. In vitro, reactive oxygen species (ROS) synthesis, and transcription of select genes associated with ROS, inflammation, and fibrosis were examined in VF fibroblasts after single-dose radiation. RESULTS: Although radiation-induced histologic alterations are made to VF architecture, 1 fractionation schedule was accompanied by significant morbidity and mortality. In vitro, radiation increased ROS synthesis and inflammatory and profibrotic gene expression. CONCLUSION: Our data suggest that hyperfractionated RT is more tolerable. Utilizing this model, RT-induced histologic aberrations are made to the VF mucosa. In addition, a relationship between radiation, ROS, and inflammatory and fibrotic gene expression was observed in vitro.

Cigarette smoke and reactive oxygen species metabolism: implications for the pathophysiology of Reinke's edema.

OBJECTIVE/HYPOTHESIS: Oxidative damage mediates the lower airway response to cigarette smoke (CS). In the vocal folds, the tissue phenotype is both distinct and largely uncharacterized. We sought to investigate the effects of CS on the oxidative status and fibroblast phenotype in the vocal folds. Specifically, we hypothesized that CS would induce a hypermetabolic fibroblast phenotype and altered oxidative metabolism potentially providing insight into the relationship among CS, Reinke's edema (RE), and malignancy. STUDY DESIGN: In vivo/in vitro. METHODS: Heme oxygenase (HO)-1 gene expression was examined in human tissue. In vitro, the effects of cigarette smoke condensate (CSC) on HO-1 gene expression and secretion was assayed. In addition, CS-mediated intracellular reactive oxygen species synthesis was quantified, and compared to the response in pulmonary fibroblasts (HFL). We then examined the effects of CSC on migration and proliferation in human vocal fold fibroblasts (HVOX). RESULTS: : HO-1 expression was approximately 4-fold higher in RE samples versus vocal fold polyps. CSC induced HO-1 gene expression and secretion in a time- and dose-dependent fashion in vitro. CSC also increased intracellular ROS in both HVOX and HFL. CSC decreased HVOX proliferation and migration in a dose-dependent manner. CONCLUSIONS: These data suggest that the fibroblast phenotype is influenced by smoke. Our data suggest that the antioxidant response in the vocal fold tissue may be one mechanism of chemoprotection, a putative explanation for the observation that RE rarely transforms to malignancy. In addition, CSC does not appear to induce a hypermetabolic fibroblast phenotype as expected.

A model for 532-nanometer pulsed potassium titanyl phosphate (KTP) laser-induced injury in the rat larynx.

OBJECTIVES/HYPOTHESIS: The potassium titanyl phosphate (KTP) laser is emerging as a potentially effective treatment for various vocal fold pathologies. To date, the precise mechanism(s) of action of this wavelength on the layered microarchitecture of the vocal fold remains unknown. The purpose of this study is to develop an in vivo model for the use of the KTP laser in the rat vocal fold and to characterize the potential of this model for future studies. STUDY DESIGN: In vivo survival surgery. METHODS: A model for videoendoscopic visualization and injury to the rat vocal fold was established using a microlaryngoscope and rigid telescope. Unilateral vocal fold injury was induced with the KTP laser at 10 Watts (W) 20 milliseconds (ms) pulse width. Animals were euthanized at 1 day post-treatment. Larynges were subjected to gross visual analysis and histological analyses via hematoxylin and eosin and trichrome staining. RESULTS: Consistent endoscopic visualization and injury was obtained without significant operative morbidity or mortality. The KTP laser caused superficial blanching and minor edema in the vocal fold, which resolved grossly by 24 hours postinjury. A modest inflammatory cell infiltrate was observed 1 day following injury. However, no remarkable alterations to the vocal fold microarchitecture were observed in the acute period. CONCLUSIONS: We propose that this novel model simulates the clinical scenario of laser use for the vocal folds. Use of this model will allow us to further characterize effects, mechanisms, and therapeutic efficacy of this wavelength.

Effects of transforming growth factor-beta1 on human vocal fold fibroblasts.

OBJECTIVES: We studied the effect of transforming growth factor (TGF)-beta on immortalized human vocal fold fibroblasts. METHODS: Normal human vocal fold fibroblasts were subjected to sequential lentiviral transduction with genes for human telomerase (hTERT) and SV40 large T antigen in order to produce an "immortalized" cell line of normal phenotype. After confirmation of vocal fold fibroblast transfection, these cells, referred to as HVOX, were treated with various concentrations of exogenous TGF-beta1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-beta signaling pathway were examined in this cell line. RESULTS: TGF-beta stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutively expressed type I and II TGF-beta receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-beta isoforms. Exogenous TGF-beta1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-beta increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-beta decreased TGF-beta1 gene expression. CONCLUSIONS: Insight into the underlying pathophysiology of vocal fold fibrosis is likely to yield improved therapeutic strategies to mitigate vocal fold scarring. Our data suggest that TGF-beta signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-beta may be a reasonable target for therapies to prevent and/or treat vocal fold fibrosis, given its putative role in both acute and chronic vocal fold injury, as well as its effects on vocal fold fibroblasts.

Incidence of alarplasty in primary and revision rhinoplasty in a private practice setting.

OBJECTIVE: To evaluate the incidence of alarplasty in primary and revision rhinoplasty during a 3-year period. METHODS: We conducted a retrospective medical record review of patients undergoing primary and revision rhinoplasty between January 1, 2004, and December 31, 2006. Patients were divided into the following categories: primary or revision rhinoplasty, alarplasty, and ethnicity. The incidence of alarplasty was calculated and compared for primary vs revision rhinoplasty and for ethnicity. Statistically significant differences were confirmed using the chi(2) test. RESULTS: A total of 168 patients underwent rhinoplasty with minimum follow-up of 6 months; 116 patients had primary rhinoplasty and 52 revision rhinoplasty. All alarplasties were bilateral. Of 50 alarplasties performed, 35 were in the primary group and 15 in the revision group. The incidence of alarplasty was 30.2% in the primary group and 28.8% in the revision group. Nonwhite patients had a higher overall incidence of alarplasty (63.0%) than did white patients (25.4%). Each ethnic category identified had a higher incidence of alarplasty than the white group. CONCLUSIONS: Alarplasty is an important technique in rhinoplasty. The high incidence of alarplasty in revision rhinoplasty procedures suggests that alarplasty is underused by many surgeons currently performing rhinoplasty. One should consider alarplasty for all patients' noses, not just those of nonwhite ethnic rhinoplasty patients.

Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression.

BACKGROUND: Genetic screening studies suggest that genetic changes underlie progression from well differentiated to anaplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. METHODS: Tissue microarrarys (TMAs) were constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41), poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell cycle/apoptosis-related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and p27). RESULTS: p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001). Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression from WDPTC to PDTC to ATC. CONCLUSIONS: These data confirm the presence of increasing genetic complexity with progressive dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and increased proliferative activity being most prevalent in ATC. The data also confirm the intermediate position of PDTC in the classification scheme of thyroid carcinomas.

Recurrent oral herpes simplex virus infection presenting as a tongue mass.

Reactivation of herpes simplex virus resulting in oral infection is common after cardiac transplantation and usually occurs within the first month posttransplant. The clinical presentation, however, may be atypical. We present a case of a 48-year-old female who presented with a large tongue mass 1 year after cardiac transplantation. Outpatient biopsies and viral stains were nondiagnostic. Because of the high suspicion for malignancy, an excisional biopsy was performed in the operating room. Pathologic analysis was consistent with herpes simplex virus type 1 infection. The patient received antiviral therapy with resolution of infection at follow-up.