Heather M. Brown

Gene Expression Profiling in Squamous Cell Carcinoma of the Oral Cavity Shows Abnormalities in Several Signaling Pathways

Objectives/Hypothesis: To examine gene expression profiles in squamous cell carcinoma of the oral cavity (oral SCC) compared with histologically matched normal tissue.

Expression of focal adhesion kinase and phosphorylated focal adhesion kinase in squamous cell carcinoma of the larynx

Objectives: Focal adhesion kinase (FAK) is overexpressed in a variety of human cancers including those derived from the oral cavity. The purpose of this work is to determine the expression patterns of FAK and its activated form, FAK pY397, in squamous cell carcinoma of the larynx and to correlate FAK expression with tumor differentiation and clinical parameters. Study Design: A retrospective study using archival tissue. Methods: Thirty‐five paraffin embedded tissue specimens of laryngeal carcinoma were obtained from the Department of Pathology at the University of Florida College of Medicine. Immunohistochemical staining of the specimens for FAK and activated phospho‐FAK (FAK pY397) was performed. Intensity of staining, distribution of staining, and percentage of cells stained was determined by one pathologist. Results: There was a statistically significant correlation between FAK staining intensity and tumor differentiation. Poorly differentiated tumors stained more intensely than moderately differentiated tumors (P < .001). There was no correlation between FAK pY397 staining and differentiation (P = .163). However, FAK pY397 staining was unexpectedly found in the nuclei of many specimens. FAK was present in the basal layer of cells within nontransformed squamous mucosa derived from tonsillectomy specimens and in blood vessels. A small amount of FAK pY397 was also localized to blood vessels in nontransformed squamous mucosa. Conclusion: FAK and phospho‐FAK are overexpressed in squamous cell carcinoma of the larynx. FAK expression correlates with differentiation. Future investigations will examine the potential of FAK and FAK pY397 expression both as a prognostic indicator and a point of therapeutic inhibition.

The Adequacy of Gross Pathological Examination of Routine Tonsils and Adenoids in Patients 21 Years Old and Younger

Most hospitals microscopically examine all routine tonsil and adenoid specimens from healthy pediatric patients with recurrent infections or obstructive sleep apnea. Concern over missing the rare unsuspected, significant diagnosis propagates this practice. Careful gross examination for asymmetry and clinical findings should obviate the need for routine microscopic examination of tonsil and adenoid specimens in patients age 21 years and younger. A retrospective study was conducted using the SNOMED database of 4070 patients age 21 years or younger who underwent tonsillectomy and/or adenoidectomy between 1970 and July 2001 at the University of Florida. The age distribution of the study group was 0 to 5 years (52%), 6 to 12 years (37%), and 13 to 21 years (11%). Specimens consisted of tonsils only (15%), tonsils and adenoids (40%), and adenoids only (45%). Clinically significant diagnoses were diagnoses that impacted the care of patients and included malignancies and some infections. Non-clinically significant diagnoses included normal, acute or chronic tonsillitis, and tonsillar hyperplasia. Clinically significant pathological processes were seen in the tonsil or adenoid specimens of 3 of the 4070 patients. These 3 cases included a 2-year-old male with Burkitts lymphoma, a 19-year-old male with non-Hodgkins lymphoma (small noncleaved cell, non-Burkitts type), and an 11-year-old male with a probable viral process but in whom a lymphoma could not be absolutely excluded. All 3 of these patients had signs and symptoms, including significant cervical lymphadenopathy, meriting microscopic analysis of the specimens. In conclusion, microscopic examination of all routine tonsils and adenoids for individuals 21 years or younger is not indicated. Gross examination is still recommended. Clinical suspicion and specimen asymmetry should be used to determine when thorough histological examination is merited.

Chlamydial infection induces host cytokinesis failure at abscission.

Chlamydia trachomatis is an obligate intracellular bacteria and the infectious agent responsible for the sexually transmitted disease Chlamydia. Infection with Chlamydia can lead to serious health sequelae such as pelvic inflammatory disease and reproductive tract scarring contributing to infertility and ectopic pregnancies. Additionally, chlamydial infections have been epidemiologically linked to cervical cancer in patients with a prior human papilomavirus (HPV) infection. Chlamydial infection of cultured cells causes multinucleation, a potential pathway for chromosomal instability. Two mechanisms that are known to initiate multinucleation are cell fusion and cytokinesis failure. This study demonstrates that multinucleation of the host cell by Chlamydia is entirely due to cytokinesis failure. Moreover, cytokinesis failure is due in part to the chlamydial effector CPAF acting as an anaphase promoting complex mimic causing cells to exit mitosis with unaligned and unattached chromosomes. These lagging and missegregated chromosomes inhibit cytokinesis by blocking abscission, the final stage of cytokinesis.

Multinucleation during C. trachomatis infections is caused by the contribution of two effector pathways.

Chlamydia trachomatis is an obligate intracellular bacterial pathogen and the second leading cause of sexually transmitted infections in the US. Infections cause significant morbidity and can lead to serious reproductive sequelae, including an epidemiological link to increased rates of reproductive cancers. One of the overt changes that infected cells exhibit is the development of genomic instability leading to multinucleation. Here we demonstrate that the induction of multinucleation is not conserved equally across chlamydial species; C. trachomatis L2 caused high levels of multinucleation, C. muridarum intermediate levels, and C. caviae had very modest effects on multinucleation. Our data show that at least two effector pathways together cause genomic instability during infection leading to multinucleation. We find that the highly conserved chlamydial protease CPAF is a key effector for one of these pathways. CPAF secretion is required for the loss of centrosome duplication regulation as well as inducing early mitotic exit. The second effector pathway involves the induction of centrosome position errors. This function is not conserved in three chlamydial species tested. Together these two pathways contribute to the induction of high levels of genomic instability and multinucleation seen in C. trachomatis infections.

Cytology of secondary vulvar Paget's disease of urothelial origin: A case report

BACKGROUND Primary cutaneous Pagets disease of the vulva is an intraepithelial adenocarcinoma most likely arising from a cutaneous stem cell with sweat gland epithelial differentiation or can be of sweat gland origin. Primary vulvar Pagets disease, however, can be mimicked by an internal noncutaneous neoplasm htat has extended to secondarily involve the vulva. Most commonly, this is due to an anal or rectal adenocarcinoma or a urothelial carcinoma. These malignancies may be detected in a vaginal or vulvar cytologic smear. CASE An 81-year-old woman with a past history of urothelial carcinoma in situ of the bladder presented severalyears subsequent to treatment for bladder cancer with extensive vulvar and vaginal disease, clinically interpreted as primary vulvar Pagets disease involving the vagina. Vaginal cytology showed a high grade malignancy. The patient subsequently underwent radical (total deep) vulvectomy and vaginal excision. Subsequent investigation of her bladder showed recurrent urothelial carcinoma in situ with extensive spread to the vagina and vulva, simulating primary cutaneous vulvar Pagets disease. CONCLUSION It is important to recognize secondary vulvar Pagets disease, although uncommon, because of the difference in therapy for primary and secondary vulvar Pagets disease. Certain cytologic characteristics in a vaginal or vulvar smear in a patient with suspected vulvar Pagets disease may aid in distinguishing them.

Utility of Image Guided Surgery in the Diagnosis of Pterygopalatine Fossa Lesions

Objectives To describe the utility of image guided surgery in the diagnosis of pterygopalatine fossa lesions and to discuss the varied pathologic diagnoses from this area.

Diagnosis of clinically unsuspected extrapulmonary tuberculosis by fine needle aspiration: a case report.

BACKGROUND Mycobacterium tuberculosis (MTb) infection remains the cause of higher morbidity and mortality than any other infectious disease in the world. Intact cellular immunity is necessary to resist the disease, and therefore the AIDS epidemic has greatly contributed to the resurgence of MTb. Depending on the degree of immunosuppression, the presentation of MTb in patients with AIDS can be atypical and difficult to diagnose as compared to the classical presentation of MTb in the nonimmunocompromised population. CASE A patient who was not known to be HIV positive had a clinical picture of extensive abdominal and pelvic lymphadenopathy without chest radiographic abnormalities. The diagnosis of MTb was made by fine needle aspiration (FNA) of a pelvic lymph node. CONCLUSION Miliary tuberculosis associated with AIDS may have an unusual clinical presentation and unusual cytologic features on ENA.

Pathology and Classification Of Thyroid Carcinoma

Figure 1 presents a system for classifying thyroid cancer based on differences in the cell of origin of the tumor, the presence of cytologic features of neoplasia, and growth morphology. Medullary cancers arise from the parafollicular C-cells whereas all other thyroid carcinomas arise from follicular epithelium. This explains why medullary thyroid carcinoma is positive by immunohistochemical staining for calcitonin andwhymedullary carcinoma never concentrates radioiodine. The nomenclature for thyroid cancer of follicular epithelial cell origin can be confusing because the term “follicular” is used in three different ways. All thyroid carcinomas other than medullary carcinoma are follicular tumors because they arise from epithelial cells of the thyroid follicle. The term follicular also describes the architectural growth pattern of a tumor, for example, the follicular variant of papillary carcinoma. Finally, follicular carcinoma is a distinct tumor.