Timothy H. Phelps

Molecular etiology of second primary tumors in contralateral tonsils of human papillomavirus-associated index tonsillar carcinomas.

OBJECTIVES For patients with tobacco-related head and neck squamous cell carcinoma (HNSCC), the occurrence of a second primary tumor (SPT) is an ominous development that is attributed to a field cancerization effect and portends a poor clinical outcome. The goal of this study was to determine whether patients with human papillomavirus (HPV)-related index tonsillar carcinomas can also develop SPTs in the contralateral tonsil, and to discern the molecular etiology of HPV-related tumor multifocality. MATERIALS AND METHODS The surgical pathology archives of The Johns Hopkins Hospital were searched for all patients with primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil. The HPV-16 E6 exon was sequenced from each independent cancer site to determine whether the tumor pairs harbored the same or a different HPV-16 variant. RESULTS Four patients with bilateral HPV-related tonsillar carcinomas were identified. In every case, the HPV DNA sequences derived from the index tumor and corresponding SPT were 100% concordant, indicating that the index and SPTs were caused by the same HPV-16 variant. CONCLUSION For the small subset of patients with tonsillar carcinomas who develop SPTs in the contralateral tonsil, the index case and the SPT consistently harbored the same HPV variant. This finding suggests that HPV-related tumor multi-focality can be attributed either to independent inoculation events by the same virus, or by migration of HPV-infected cells from a single inoculation site to other regions of Waldeyers ring.

Ultrastructural evidence of cell-mediated endothelial cell injury in cardiac transplant-related accelerated arteriosclerosis

Accelerated arteriosclerosis secondary to chronic allograft rejection is a major long-term complication of heart transplantation. Accelerated arteriosclerosis has been associated with an endothelialitis, and the majority of the involved inflammatory cells are T lymphocytes and macrophages. Coronary arteries from six heart allograft recipients with transplant-related arteriosclerosis were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Four hearts were explants from heart transplant recipients with severe accelerated arteriosclerosis who were undergoing retransplantation, and two were obtained from autopsied recipients. The patients ranged in age from 6 to 60 years (mean, 44 years). The graft survival for these six hearts ranged from 1.4 to 5.6 years (mean, 4.3 years). Lymphocytes, macrophages, and smooth muscle cells were identified by TEM in the intimas of all the vessels examined. The lymphocytes were often in contact with macrophages or in close proximity to injured endothelial cells. Areas of endothelial injury were characterized by vacuolization of endothelial cells and partial denudation of the endothelium with fibrin deposition. SEM also revealed endothelial cell injury with disorganization of the endothelium and gaps between endothelial cells. Leukocytes and platelets were often noted in these gaps. These findings suggest that accelerated arteriosclerosis in heart transplant recipients is associated with an accumulation of macrophages, lymphocytes, and smooth muscle cells in the intima as well as with lymphocyte-directed endothelial injury.

Parturitional Injury of the Head and Neck

Parturitional injuries refer to injuries sustained during and secondary to fetal delivery. The skull, brain, and head and neck regions are frequently involved. Accurate differentiation and classification of the various injuries is essential for treatment, prognosis, and parental counseling. In this review, we discuss the various “bumps and lumps” that maybe encountered along the neonatal skull as well as the most frequent calvarial and intracranial parturitional injuries. In addition, a short discussion of the most common head and neck, facial, and spinal lesions is included. Various mimickers and risk factors are also presented.

Soft Tissue, Nerves, and Muscle

Soft tissue resections are often complex specimens containing soft tissues, skin, and sometimes even bone. The general approach to these specimens is a simple one, and it parallels that outlined for complex head and neck specimens in Chapter 6. First, identify the various components of the specimen (soft tissue, bone, and skin). Second, think of each component as a geometric shape. Third, approach each component separately. Fourth, look for relationships between any lesions and each component.

Non-neoplastic Intestinal Disease

Proper tissue orientation is a critical part of the histologic evaluation of biopsies of the gastrointestinal tract. Tissue orientation is a two-step process that involves the coordinated actions of the endoscopist and the histotechnologist. The endoscopist should mount the biopsy mucosal side up on an appropriate solid surface (e.g., filter paper) and place it in fixative. This first step should be done immediately, in the endoscopy suite, so that the specimen does not dry out en route to the surgical pathology laboratory. The histotechnologist can then embed and cut the biopsy specimen perpendicular to the mounting surface. If the specimen is free floating, great care must be taken to identify the mucosal surface for proper embedding. Multiple sections should be cut from each tissue block for histologic evaluation. Step sections are preferred to serial sections so that intervening unstained sections are available for special stains as needed.

Neoplastic Intestinal Disease

Polyps of the gastrointestinal tract are usually removed endoscopically by a single incision at the base of the polyp stalk. Although these specimens lack the size and complexity of more extended bowel resections, they are delicate structures that require meticulous processing. First, obtain relevant clinical information such as the patient’s history, the endoscopic findings, and the anatomic site from which the polyp was removed. Next, turn your attention to the specimen itself. The polypectomy specimen poses three important questions to the surgical pathologist: (1) Are adenomatous changes present? (2) Is infiltrating carcinoma present, and if it is, does it infiltrate into the stalk? (3)Do any of the neoplastic changes extend to the resection margin at the base of the stalk? Clearly, the polypectomy specimen must be carefully oriented and processed so that these issues can be addressed.

Heart Valves and Vessels

For years, almost all valvular heart disease has been ascribed to chronic rheumatic heart disease. As a result, excised heart valves are frequently the most neglected specimens in the surgical pathology laboratory. Failure to pay appropriate attention to resected valves can be a disservice to the patient. Careful examination of heart valves not only will help in the clinical management of these patients, but may also help in the development of improved prosthetic heart valves.