Faculty Bibliography

BACKGROUND: Plexiform neurofibroma is a relatively common but potentially devastating manifestation of neurofibromatosis type 1 (NF1). Surgical management is the mainstay of therapy, but within the head and neck region it is limited by the infiltrating nature of these tumors, inherent operative morbidity, and high rate of regrowth. METHOD: We describe a case of a 7-year-old girl with neurofibromatosis type 1 and a massive facial plexiform neurofibroma with the aim of emphasizing the treatment and timing issues involved in the management of this difficult problem. A MEDLINE search (1966 through December 2000) was carried out, and pertinent literature on the subject was reviewed. RESULT: The patient described in this case report was carefully observed for a period of 6 years from diagnosis before surgical excision of the tumor was undertaken with an uneventful recovery. CONCLUSION: Surgical management remains the mainstay of treatment for these locally invasive tumors, but functional disturbances are almost inevitable in resecting substantial tumors involving the head and neck region. The indication and timing of surgery in pediatric patients therefore needs to be carefully weighed against the physical and psychologic consequences of treatment

Granulosa cell tumor is almost exclusively an ovarian tumor. Rare cases of granulosa cell tumor have been reported involving the testes. We report a testicular gonadal stromal tumor with granulosa cell differentiation in a 54-year-old white man. The tumor was discovered by an ultrasound evaluation for left hydrocele. The patient was clinically asymptomatic. On frozen section, the initial impression was a malignant lymphoma. Final histology on the orchiectomy specimen showed a gonadal stromal tumor with granulosa cell features. Immunohistochemical studies excluded malignant lymphoma and germ cell tumors, consistent with a stromal tumor. This case report illustrates the challenges for the pathologist in making an accurate diagnosis in unusual testicular tumors

The author's current perspective of blepharoplasty is a product of a 30-year evolution in treating the aging eyelid. A review of the literature highlighting the most recent techniques can provide the reader with state of the art thinking by many authors on the subject. Some-times, however, a single surgeon's lifetime experience with a surgical procedure also can be insightful. The article details the author's experience with blepharoplasty

OBJECTIVE: To present an unusual case of recurrent facial palsy resulting from acute leukemic infiltration of the parotid gland. STUDY DESIGN: Case report. METHODS: An 11-year-old boy who had been treated for acute lymphoblastic leukemia (ALL) from 3 to 6 years of age presented with intermittent left facial nerve palsy with concurrent ipsilateral parotid fullness. The initial findings at diagnosis and workup are presented, and the disease progression and resolution with therapy are documented. RESULTS: The patient had been off therapy when this finding developed. A workup for central and viral etiologies for the facial palsy was unrevealing. Biopsy of the parotid gland demonstrated a lymphoblastic leukemic infiltrate. The patient was placed on a chemotherapy protocol for relapsed leukemia, resulting in complete resolution of the facial palsy. CONCLUSION: Isolated facial nerve dysfunction, albeit rare, has been documented as a sign of central nervous system involvement in leukemia, but until now this presentation has not been described in the setting of leukemic relapse presenting with acute infiltration of the parotid gland

The clinical and aspiration cytologic details of a case of temporomandibular joint pigmented villonodular synovitis are presented and correlated with imaging, surgical, histopathologic, and clinical follow-up findings; the origin of such lesions is discussed. The lesion originally presented in a 36-year-old, otherwise healthy, white man as a unilateral mass involving the temporal fossa and temporomandibular joint region. The tumor's extent was defined by magnetic resonance imaging and computed tomographic scan; there was destruction of the temporomandibular joint and erosion of the temporal cranial bones by a lesion whose maximum dimensions were estimated by imaging to be 2.75 x 3.25 cm. The lesion was initially sampled and classified by computed tomography-guided fine-needle aspiration biopsy. Following complete resection, the original diagnosis was confirmed with both hematoxylin-eosin-stained paraffin sections and immunohistochemical staining. The patient remains free of disease 7 years postoperatively.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

Interleukin 2 (IL-2) and interleukin 12 (IL-12) have potent anti-tumour activity as single agent therapy against several different murine and human tumours. Combining these cytokines may result in improved therapeutic effectiveness, however, the toxicity associated with simultaneous administration is prohibitive. This study was designed to determine the specific histopathologic changes associated with combination therapy. Mice were treated with 5 days of interleukin-2, interleukin-12, or both using standard doses and schedules. Histologic specimens were prepared from all internal organs on a daily basis to identify specific pathologic abnormalities. Treatment with interleukin-2, interleukin-12, or both resulted in pathologic insult to the liver and gastrointestinal tract. Mild lymphoplasmacytic infiltrates were seen in the liver. The most significant pathology was seen in the large bowel and consisted of apoptosis of colonic epithelial cells. While recovery of injured gastrointestinal mucosa occurred in mice treated with interleukin-2 or interleukin-12 alone, combination therapy resulted in death before recovery was possible. Combination interleukin-2 and interleukin-12 therapy results in irreversible injury of the colon as manifested by increased epithelial cell apoptosis and death in mice. Understanding the pathologic changes associated with combination cytokine therapy may lead to strategies that prevent toxicity while maintaining therapeutic effects.

A method is presented for analyzing cochlear implant stimulations and typical representations used in simulations. Filtered "white-noise" bands are modulated using sinusoids, representing differing stimulation channels. These representations, along with their corresponding envelopes, are used to generate neural activation patterns (NAPs), which represent "normal-hearing" responses in the auditory nerve to these stimuli. Additionally, NAPs are generated to represent the neural activity induced by cochlear implant stimulation strategies, assuming exponential rolloff from the electrodes. The mean squared error is measured between NAPs both directly, and after compensation for perceptual resolution. Results suggest that the noise-band approximation of the CIS implant signal actually has more in common with the original source than with the implant stimulation patterns.