Relationship of Human Papillomavirus to Schneiderian Papillomas

Objectives/Hypothesis: To classify a large group of Schneiderian papillomas (SPs) into their histologic subtypes and to determine the incidence of human papillomavirus (HPV) in each subtype. Study Design: Pathologic review and polymerase chain reaction–based (PCR-based) examination of archived tissue. Methods: Slides of 114 tumors diagnosed as Schneiderian, inverting, fungiform, or cylindric cell papillomas, or any associated carcinomas, were examined by a head and neck pathologist. Using PCR, consensus primers for the L1 region of HPV were used to determine the presence of HPV in the tumors. This was also performed on normal turbinate control specimens. Results: Eighty-two (78%) were the inverting subtype, 21 (20%) the fungiform subtype, and 2 (2%) the cylindric cell type. Nine tumors were diagnosed as either verrucous or squamous cell carcinoma. Eighty-eight percent of the tumors had DNA of sufficient quality to be amplified using PCR. Of these, 5 of 69 (6.8%) inverting, 17 of 17 (100%) fungiform, and 0 of 2 cylindric cell papillomas were positive for HPV. One of nine (11.1%) cancers was positive for HPV. No normal turbinate tissue contained HPV. HPV types 6b and 11 accounted for all cases of fungiform papillomas. Of the five HPV-positive inverting papillomas, three had HPV type 11 and two had HPV type 16. The single carcinoma containing HPV contained HPV type 18. Conclusions: The histologic subtype of SPs is important, as their etiologies appear to be different. HPV 6b and 11 appear to be involved in all cases of fungiform papillomas but are only rarely involved in cases of inverting or cylindric cell papillomas. HPV 16 may rarely play a role in cases of inverting papillomas, and HPV 16 and 18 may be involved in a subset of cases of carcinomas originating in an inverting papilloma.     

Coinfection of HPV-11 and HPV-16 in a Case of Laryngeal Squamous Papillomas With Severe Dysplasia

Human papillomavirus (HPV) types 6 and 11 have been associated with benign laryngeal papilloma, while HPV-16 is occasionally associated with laryngeal carcinoma. In this study, a case of laryngeal squamous papillomas with severe dysplasia was evaluated for the presence of HPV infection. The biopsy specimens were taken from a 58-year-old female patient at two different time points 3 months apart. Architecturally, the tumor showed papillary configuration reminiscent of squamous papilloma. Cytologically, the lesion showed morphologic features characteristic of severe squamous epithelial dysplasia. HPV infection was determined by DNA in situ hybridization using type-specific HPV-DNA probes. HPV-11 probes demonstrated homogeneous nuclear staining, suggesting productive viral replication. In contrast, HPV-16 probe produced a speckled pattern, suggesting HPV-16 DNA integration. Normal laryngeal epithelium did not yield specific hybridization. The presence of HPV-11 and HPV-16 was confirmed by PCR using HPV type-specific primers. Immunocytochemical staining was performed to detect Ki-67, a proliferation marker, and p53. Ki-67 expression was demonstrated throughout the whole thickness of epithelium. Staining for p53 was negative. This study suggests that multiple HPV infections can occur in the same lesion and that HPV-16 infection and its DNA integration may contribute to the occurrence of severe dysplasia in the lesion described.     

Detection and Typing of Human Papillomavirus DNA in Benign and Malignant Tumours of Laryngeal Epithelium

The role of human papillomaviruses (HPV) in laryngeal squamous cell carcinoma has not yet been established. Thirty-three cases of laryngeal squamous cell carcinoma were analysed for the presence of HPV DNA and compared with 25 cases of normal larynx and 29 cases of laryngeal squamous papilloma in their positivity index. The presence of HPV DNA was analysed by using L1 consensus primers and also by primers specific for the E7 gene of HPV types 16 and 18. Four normal laryngeal samples (16%) were positive for HPV DNA against the 24 samples (82%) (p<0.001) found for laryngeal papilloma and 16 (48.5%) (p<0.05) found for laryngeal squamous cell carcinoma. HPV 16 was the type most frequently found in laryngeal carcinoma samples. Our results support an etiologic role for this type of HPV in the pathogenesis of laryngeal carcinoma.     

增殖细胞核抗原在喉上皮癌前病变中的表达及意义

用免疫组化技术对１１例喉上皮单纯性增生（ＳＨＥ），３２例非典型性增生（ＡＨＥ）及４２例喉鳞状细胞癌（ＬＳＣＣ）的增殖细胞核抗原（ＰＣＮＡ）表达进行了原位检测。结果表明；在ＳＨＥ、ＡＨＥ及ＬＳＣＣ中，ＰＣＮＡ指数分别为９．５７％、２７．３３％、６８．０５％，差异极有显著性意义（Ｐ＜０．００１）。在轻、中、重度ＡＨＥ中，ＰＣＮＡ指数分别为１３．７９％、３０．８４％、３９．９４％，差异有非常显著性意义（Ｐ＜０．０１）。提示ＰＣＮＡ表达程度与非典型性增生程度密切相关，是反映细胞增殖状态的生物标志，ＰＣＮＡ组化研究有助于认识喉癌前病变的本质，发展趋势及喉癌的早期诊断。     

Sinonasal Papillomas: Clinicopathologic Review of 40 Patients With Inverted and Oncocytic Schneiderian Papillomas

Objective To evaluate the pathological features and variations of sinonasal inverted and oncocytic papillomas and correlate the microscopic findings with the clinical behavior. Study Design A retrospective review and pathological assessment. Methods A retrospective review and pathological assessment were performed on 40 patients with a diagnosis of inverted papilloma treated by the senior author (w.l.) between 1994 and 2001. Results Forty cases were identified and reviewed. Seven patients developed recurrences (18%), and four underwent malignant transformations (10%). Pathological assessment revealed 34 (85%) inverted papillomas and 6 (15%) oncocytic schneiderian papillomas. Dysplasia was present in 26 cases (65%), including 9 cases (22%) of high‐grade dysplasia (moderate to severe). Metaplasia of the sinonasal mucosa adjacent to inverted papillomas and oncocytic schneiderian papillomas was seen in 18 (45%) cases. Recurrence developed in two patients with oncocytic schneiderian papillomas (33%) and five patients with inverted papillomas (15%). Four cases (10%) of carcinoma ex papilloma were seen; one arose from oncocytic schneiderian papilloma (17%), and three arose from inverted papilloma (9%). Oncocytic schneiderian papilloma was more often mixed with typical inverted papilloma, rather than presenting in its pure form. Conclusions Although oncocytic schneiderian papilloma is uncommon relative to inverted papilloma, the results suggest that they have higher rates of both recurrence and malignant transformation. The common admixture of oncocytic schneiderian papilloma with inverted papilloma speaks for a common etiological factor of these two lesions. A larger number of cases for analysis would be necessary to confirm the trend noted in our data. Nonetheless, pathological findings consistent with oncocytic schneiderian papilloma should be explicit in any classification system and justify aggressive treatment and careful postoperative surveillance.     

Detection of Human Papillomavirus in Laryngeal Squamous Dysplasia and Carcinoma. An In Situ Hybridization and Signal Amplification Study

We examined the presence of human papillomavirus (HPV) DNA in 65 cases of laryngeal squamous dysplasia and carcinomas using in situ hybridization with signal amplification in paraffin sections. Hybridization was performed with biotynilated DNA probes for HPV 6/11, 16/18, 31/33 and wide-spectrum HPV (6, 11, 16, 30, 31, 45, 51 and 52). HPV DNA was found in 7 cases of the total sample (10.7%); it was also found in 4 out of 45 (8.8%) cases of invasive carcinoma and in 5 out of 33 (15.5%) cases of squamous dysplasia. Morphological signs suggestive of HPV infection were observed in 35.5% of our sample but they were not related to HPV DNA positivity. In conclusion, HPV probably plays little, if any, role in laryngeal carcinogenesis among the population studied.     

Ki-67 As a Prognostic Marker in Adenoid Cystic Carcinoma Assessed With the Monoclonal Antibody MIB1 in Paraffin Sections

The monoclonal antibody MIB1 recognizing the Ki-67 antigen in formalin-fixed, paraffin-embedded tissue was used to study the proliferative activity in 44 adenoid cystic carcinomas of the salivary glands. The antigen expression was compared with clinical factors, histopathological grading, and prognosis. The Ki-67 value was significantly higher in tumors from patients suffering from treatment failure than in nonfailures (P < 0.001). The Ki-67 expression was also higher in tumors exhibiting areas more than 30% of the solid growth pattern and higher in sinonasal tumors than in other locations. By Cox regression analysis, Ki-67 more than 4% was the strongest prognostic indicator (P <0.005). Clinical stage and violation of surgical margins were also found to be independent significant prognostic indicators. We conclude that Ki-67 expression estimated by the use of MIB1 is a powerful tool for predicting the short-term prognosis for patients with adenoid cystic carcinoma.     

Identification of p53 and Human Papilloma Virus in Schneiderian Papillomas

Schneiderian papilloma of the nose is an unusual neoplasm with the propensity for local tissue destruction, recurrence, and malignant degeneration. Human papilloma virus (HPV) is related to a subset of sinonasal papillomas and has been implicated in the pathogenesis of cancer by interaction with the host p53 protein. Detection of p53 and HPV could be clinically useful as tumor markers for lesions with oncogenic potential. Thirty specimens for p53 were studied and nine (30%) stained positive. HPV was detected in six (20%). In the presence of p53, an odds ratio for carcinoma was 1.19:1, or 19% higher than expected. In the presence of HPV the odds ratio for carcinoma was 11.5:1, or 11.5 times higher than expected. In the presence of HPV an odds ratio for finding an elevated amount of p53 was 2.2:1. The data support the hypothesis that HPV and p53 may interact in a novel manner and elevate the risk for neoplasia.     

Intraoperative Identification of Laryngeal Nerves With Laryngeal Electromyography

The laryngeal nerves are at risk during thyroid surgery, and several techniques have been described for their intraoperative identification to minimize potential damage. Nerve protection is based on the electromyographic recording from the muscles innervated by the laryngeal nerves, and that electrical activity is picked up by various techniques. We evaluated an electrode attachment to the endotracheal tube that provides a stable method for continuous recording of the laryngeal electromyogram. In addition, we tested various modalities of electrical stimulation in the region where the nerves are located, identified the most reliable evoked electromyographic activity, and characterized the wave form and latency. The results, obtained in 28 patients scheduled for thyroid and parathyroid surgery, indicate that the technique of recording from electrodes attached to the endotracheal tube is safe and reliable. Insulated bipolar forceps or a monopolar electrode was used to deliver low-voltage pulses (1 to 3 V) at 1 to 2 pulses/s generated by either battery-operated or optically isolated stimulators. The most unequivocal recordings were obtained with the monitoring equipment set to the nerve-conduction velocity modality, with the sweep set at 2 msec/cm. The technique clearly differentiated the evoked electromyographic responses obtained from the superior or recurrent laryngeal nerve and was easily performed with no perioperative complications.     

选择性喉返神经吻合术治疗喉麻痹的实验研究

目的 研究不同神经源分别支配受损喉返神经内收及外展肌支的神经肌电表现。方法 将实验组犬左喉返神经完全切断，再将其外展肌支及内收肌支分别同期与同侧膈神经支及颈袢胸舌肌支吻合，吻合术后6个月分别用神经电图仪、光镜、电镜及直达喉镜等方法全面检测甲杓肌与环杓后肌神经肌电活动情况，所得数据用统计学方法进行分析。结果 吻合术后6个月，喉内收及外展肌均出现动作电位波，其甲杓肌潜伏期与术前比较无差异，甲杓肌神经传导速度已恢复正常，环杓后肌神经传导速度稍慢。结论 选择性喉返神经吻合术最大限度地从生理及解剖上避免了吻合术后喉内肌的联带运动问题，达到了预期目的。     

Papillomas of the larynx and pharynx: Two case reports

Two unusual cases of papillomas are presented: the first is that of a young boy with extensive papillomas of the larynx who was treated successfully without tracheotomy using endolaryngeal surgery and steroids at the time of each procedure. This case adds to the clinical evidence that the most probable cause of juvenile papillomas is a virus, since the mother had condyloma acuminata during pregnancy and at term. The second case is that of a young girl with rapidly recurring papillomas of the mouth and pharynx who was treated successfully with an autogenous vaccine and cryosurgery after other measures failed. This case demonstrates the effectiveness of cryosurgery in the treatment of papillomas and the possible efficacy of the autogenous vaccine suggests a viral etiology for papillomas of the pharynx and larynx.     

Correlation of Laryngeal Chemoreflex Severity With Laryngeal Muscle Response

Objectives: To examine the relationship between the severity of the laryngeal chemoreflex (LCR) and the pattern of laryngeal muscle activity during an LCR-induced apnea. Methods: The laryngeal mucosa of 20 piglets aged 17 to 20 days was stimulated under both hypoxic and normoxic conditions. Respiration, blood pressure, and activity of the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were monitored during the LCR-induced apnea. Results: Hypoxemia resulted in a shorter average apnea duration but a greater degree of hypotension. All piglets recovered spontaneously following normoxic LCR stimulation. Hypoxic stimulation resulted in two divergent apneic responses: transient with a spontaneous recovery (17 piglets) or profound requiring resuscitation (three piglets). An increase in TA muscle activity and a decrease in PCA muscle activity was the most common response to LCR stimulation. The response of the TA and PCA muscles was maintained in piglets destined for spontaneous recovery. Decreasing TA activity and increasing PCA activity correlated with the development of a profound response. Conclusions: The piglet demonstrates two distinct responses to hypoxic laryngeal chemostimulation that correlate with the activity of the intrinsic laryngeal muscles. Failure to maintain the activity of the TA and PCA muscles during a profound response is associated with the development of severe cardiovascular instability. This study suggests that the critical event involving the LCR is the development of complications secondary to hypoxia.     

Laryngeal carcinoma in brothers

The most important etiologic factors of laryngeal carcinoma are tobacco smoking and heavy drinking as well as precancerous changes of laryngeal mucosa. The significance of genetic or family factor is still not explained. Two brothers, 45 and 48 years old, in which supraglottic carcinomas were diagnosed, are presented. The tumor localisation was the same in both brothers. In each of the patients supraglottic horizontal laryngectomy and neck dissection were performed. In one brother 5-year disease free survival was obtained, in second the distant and regional metastases were cause of death after two years.     

小儿喉乳头状瘤31例临床小结

报告３１例小儿喉乳头状瘤的病例资料。本病特点：病情发展快，病变范围广，声门下发生率高，气管切开率高和绝少癌变。认为似不应以手术次数作为分型依据；术前要对肿瘤精确定位和明确范围；术中应用激光消除残存瘤组织和止血，可获较好疗效；术后密切随访观察，及时发现和处理复发病例。     

Laryngeal growth in infancy

Growth of the cricoid ring in infants is studied. In the first two weeks of life a small ring seems correlated with the fact of early infant death. Therefore we suggest that mortuary specimens at this age are not a reliable guide to the size of the cricoid in thriving infants. Rates of growth from ages of two weeks to three years are given for the specimens examined. Comparison with similar measurements carried out in England show that the specimens collected here were systematically smaller for a given age.