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We present an exceedingly rare case of chondromyxoid fibroma of the nasal cavity and palate. This rare tumor usually occurs in the metaphyses of the long bones. Our patient's tumor was diagnosed by biopsy, and it was resected en bloc. At the 2-year follow-up, the patient was doing well with no signs of recurrence. We review the pathologic characteristics, differential diagnosis, and treatment of chondromyxoid fibroma of the nasal cavity.

Purpose: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer., Experimental Design: miRNA arrays were done on normal lung tissues and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells. Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal-malignant human lung tissue bank., Results: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung tissues. Individual overexpression of miR-34c, miR-145, and miR-142-5p in ED-1 and ED-2 cells markedly repressed cell growth. Anti-miR cotransfections antagonized this inhibition. The miR-34c target, cyclin E, was repressed by miR-34c transfection and provided a mechanism for observed growth suppression., Conclusions: miR-34c, miR-145, and miR-142-5p were repressed in murine and human lung cancers. Transfection of each miRNA significantly repressed lung cancer cell growth. Thus, these miRNAs were growth suppressive and are proposed to exert antineoplastic effects in the lung.

Cyclin E is a critical G(1)-S cell cycle regulator aberrantly expressed in bronchial premalignancy and lung cancer. Cyclin E expression negatively affects lung cancer prognosis. Its role in lung carcinogenesis was explored. Retroviral cyclin E transduction promoted pulmonary epithelial cell growth, and small interfering RNA targeting of cyclin E repressed this growth. Murine transgenic lines were engineered to mimic aberrant cyclin E expression in the lung. Wild-type and proteasome degradation-resistant human cyclin E transgenic lines were independently driven by the human surfactant C (SP-C) promoter. Chromosome instability (CIN), pulmonary dysplasia, sonic hedgehog (Shh) pathway activation, adenocarcinomas, and metastases occurred. Notably, high expression of degradation-resistant cyclin E frequently caused dysplasia and multiple lung adenocarcinomas. Thus, recapitulation of aberrant cyclin E expression as seen in human premalignant and malignant lung lesions reproduces in the mouse frequent features of lung carcinogenesis, including CIN, Shh pathway activation, dysplasia, single or multiple lung cancers, or presence of metastases. This article reports unique mouse lung cancer models that replicate many carcinogenic changes found in patients. These models provide insights into the carcinogenesis process and implicate cyclin E as a therapeutic target in the lung.

Tobacco carcinogen treatment of immortalized human bronchial epithelial (HBE) cells has uncovered novel targets for cancer chemoprevention. Experiments were conducted with HBE cells and independent treatments with tobacco carcinogens along with the chemopreventive agent all-trans-retinoic acid (RA). That work highlighted D-type and E-type cyclins as novel molecular pharmacologic targets of several chemopreventive agents. G1 cyclins are often aberrantly expressed in bronchial preneoplasia and lung cancers. This implicated these species as targets for clinical cancer chemoprevention. Retinoid regulation mechanisms of D-type cyclins in lung cancer chemoprevention have been comprehensively explored. Retinoid chemoprevention has been mechanistically linked to proteasomal degradation of cyclin D1 and cyclin D3. Threonine 286 mutation stabilized cyclin D1, implicating phosphorylation in this retinoid chemoprevention. Studies with a phospho-specific anti-cyclin D1 antibody confirmed this hypothesis. Glycogen synthase kinase (GSK) inhibitors established a role for this kinase in the retinoid regulation of cyclin D1, but not cyclin D3. Involvement of D-type cyclins in this chemoprevention was shown using small interfering RNAs (siRNAs). Gene profiling experiments highlighted the E1-like ubiquitin-activating enzyme (UBE1L) in the retinoid regulation of cyclin D1. Proof of principle trials have translated these studies into the clinic and established that chemopreventive agents can target D-type cyclins. These findings have been built upon with a targeted combination regimen that cooperatively affects D-type cyclins. Taken together, these preclinical and clinical findings strongly implicate these cyclins as novel molecular pharmacological targets for cancer chemoprevention.

Background: Negative resection margins are likely the most important prognostic factor for a patient with a head and neck squamous cell carcinoma. Frozen-section evaluation allows a positive margin to be corrected before surgical closure and reconstruction. A final pathology report is later issued after examination of all resected tissues. The accuracy of the final pathology report relies on accuracy in the preceding steps. The current process of margin reporting in head and neck cancer resections was studied to reveal possible waste and error in the system., Methods: Two hundred pathologists were surveyed about their center's current process of frozen-section margin evaluation. The authors of the current study used the membership log of the North American Society of Head and Neck Pathology and the list of the top 50 US cancer centers according to US News and World Report. The authors analyzed the process of frozen-section procedure using Toyota industry principles of quality improvement., Results: The majority of surgeons send small fragments of tissue from the surgical defect cavity. Many pathologists receive small unoriented tissue fragments. Many resample all or most of the margins for the final pathology report without anatomic orientation from the surgeon. Other pathologists do not sample any margins., Conclusions: Final margin reporting redundancy and waste is due mainly to lack of anatomic correlation at interdisciplinary hand-offs. Oversampling and undersampling of margins may be occurring, and the accuracy of the final pathology report may be compromised. There is currently no consensus on how to best submit tissue for frozen-section evaluation of head and neck resection margins., (Copyright 2006 American Cancer Society.)

Context: The differentiation of pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma is a difficult and frequently encountered distinction, especially in biopsy specimens from head and neck mucosa. The problem is compounded by inflamed and often poorly oriented tissue sections., Objective: To distinguish pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma, utilizing a panel of antibodies to various epithelial and stromal elements (p53, matrix metalloproteinase 1, E-cadherin, and collagen IV) that has been shown to be useful in differentiating intestinal adenomas with invasive adenocarcinoma from displaced adenomatous epithelium., Design: Thirty-three archival specimens (16 squamous cell carcinoma [12 with invasion and 4 with microinvasion] and 17 pseudoepitheliomatous hyperplasia) from head and neck mucosal locations were immunostained and examined by the authors., Results: We found increased nuclear staining of the invasive tumor cells with p53. There was decreased staining within invasive tumor nests with E-cadherin. There was highly significant increased staining within tumor cells and adjacent stroma with matrix metalloproteinase 1 (P < .001). The only antibody in our panel that did not show a reliable staining pattern was collagen IV. It appeared fragmented in benign inflamed and malignant areas and therefore was not useful., Conclusions: p53, matrix metalloproteinase 1, and E-cadherin showed significant staining trends independent of inflammation and suboptimal tissue orientation. Although a properly oriented hematoxylin-eosin-stained section was our gold standard, we found this immunoperoxidase panel useful as a diagnostic adjunct in difficult cases.

Agammaglobulinemia is the most common primary immunodeficiency, with an incidence of approximately 1 in 250,000 males in the United States. These patients are at risk for frequent recurrent infections, which may become fatal if untreated. Patients have increased susceptibility to encapsulated pyogenic bacteria. Haemophilus influenzae is second only to Streptococcus pneumoniae as the bacteria most frequently implicated in infections in these patients. We present a case involving an adolescent boy with X-linked agammaglobulinemia and H influenzae cervical adenopathy, confirmed twice by culture. We correlate the clinical, microbiologic, and histologic findings. Owing to the severity of infections in this population, surgical intervention is more common than in the immunocompetent population. This description may help the pathologist in considering a differential diagnosis when examining a diagnostic lymph node biopsy in these patients.

Objective and Importance: Hemangiopericytoma is a rare tumor of the central nervous system, most often found supratentorially. Thirty-nine cases within the spinal column, of which five were intradural, have been reported. To date, no magnetic resonance imaging descriptions of intradural hemangiopericytomas have been published. This article is the first report of an intradural hemangiopericytoma of the lumbar spine and the first magnetic resonance imaging description of such a lesion., Clinical Presentation: A 31-year-old man presented with progressive bilateral leg paresthesia and increased lower extremity cramping and fatigue during a period of several months. This progressed to urinary urgency, frequency, and sexual dysfunction. A neurological examination revealed no motor or sensory deficits. Gadolinium-enhanced magnetic resonance imaging of the lumbar spine revealed a centrally located intradural mass posterior to the L4 vertebral body., Technique: The patient underwent a laminectomy of L4 and partial laminectomy of L3 with complete en bloc resection of the tumor. A discrete, intradural, red-appearing lesion was found and resected en bloc. Pathological findings were consistent with hemangiopericytoma., Conclusion: Intradural hemangiopericytomas, although rare, cannot be differentiated from other, more benign tumors. Spinal hemangiopericytomas ideally should be resected en bloc to reduce operative blood loss and potentially increase disease-free survival time. Despite total surgical resection of these benign-seeming lesions, the high recurrence rate mandates close follow-up and consideration of adjuvant therapy.