Demonstration of Papillomavirus Antigen in Paraffin Sections of Laryngeal Papillomas

A papillomavirus antigen has been identified in tissue sections of laryngeal papillomata removed at endoscopic operations. The demonstration of the papillomavirus antigen was achieved using the peroxidase-anti-peroxidase test of Sternberger after a broadly cross-reactive rabbit antiserum to the papillomavirus capsid antigen was incubated with the tissue sections. The antigen was detected in specimens from 7 of 15 patients with juvenile-onset laryngeal papillomas, but could not be demonstrated in the specimens from 6 patients with adult-onset papillomas. In all, 73 biopsy specimens from 21 patients were selected for study; 18% (11/61) of the sections from the juvenile-onset patients and 0% (0/12) of the sections from the adult-onset patient specimens exhibited the papillomavirus antigen. The presence of the virus antigen did not correlate with the stage of disease, nor with the duration or severity of the illness. The implications of the findings are discussed.     

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.     

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.     

人喉鳞癌裸鼠移植瘤株的建立及平阳霉素治疗的研究

用人喉鳞癌组织直接接种于裸鼠，建立了一株裸鼠移植瘤株，命名为ＨＬＣ＿（１４）（取自Ｈｕ－ｍａｎＬａｒｙｎｇｅａｌＣａｎｃｅｒ）。鼠间传代２５代，历时２年多，生长稳定，潜伏期短，鼠间移植成功率达１００％。光镜和电镜下形态与原发瘤相似，染色体分析显示人类肿瘤染色体特点，免疫组化检测细胞内角蛋白反应阳性，显示为上皮来源的肿瘤。平阳霉素治疗的实验研究表明：平阳霉素对ＨＬＣ＿（１４）有明显的作用，抑制率为９０．７％。     

Microvessel Density and Endothelial Basement Membrane Composition in Laryngeal Squamous Cell Carcinomas

In this retrospective study we morphometrically evaluated the density of small blood vessels (microvessel density; MVD) in laryngeal squamous cell carcinomas (SCC) in order to find out if the vascular density provides relevant information on the biology and prognosis of this tumor type. In addition, we investigated the composition of the endothelial basement membrane (BM) to analyze qualitatively the role of the major BM components during tumor-associated angiogenesis. For the immunohistochemical staining of the blood vessels we used the endothelial cell marker CD31 and the BM was analyzed by immunostaining for the major components collagen-IV, laminin-1 and perlecan. Beneath the normal mucosa a mean of 18 vessels/0.41 mm² was found. Invasive carcinomas showed a significant increase in blood vessel density to 36.3 vessels /0.41 mm² regardless of the degree of tumor cell differentiation. Interestingly, the highest vascular density was found beneath dysplastic, but non-invasive epithelia (45.5 vessels/0.41 mm²), particularly when associated with a strong lymphoplasmacytic cell infiltration. Statistical analysis revealed a highly significant correlation between MVD and the lymphoplasmacytic infiltrate. However, we did not find any significant correlation between MVD and other clinical/biological parameters. Qualitative analysis of the endothelial BM revealed an "earliest" occurrence of laminin-1 in the obviously newly formed vessels, while collagen IV and perlecan occur at more pronounced stages of vessel formation. There was, however, no prognostically relevant information available from endothelial BM analysis. In summary, at present we do not consider the MVD in SCC of the larynx to be a prognostic factor for the individual outcome of the patient.     

Detection of HPV-16-related DNA sequence in laryngeal squamous cell carcinoma]

The gene libraries of laryngeal squamous cell carcinoma (LSCC) and laryngeal papilloma (LP) were screened by hybridization analysis with alpha-32P-labelled HPV-16 DNA under low stringency (Tm = 40 degrees C). It showed that the relative sequences were detected in LSCCs (11/16, 68.8%), but not in LP. The HPV-16-related DNA harbored in negative hybridization lesions were further analysed by polymerase chain reaction to amplify E6/E7 gene of HPV-16-related DNA. The results showed that 1/5 LSCCs and 2/2 LPs, were positive. The data suggest that development of LSCC should be related to the HPV infection, and HPV may be one of the inducers of LSCC.     

喉鳞状细胞癌中骨桥蛋白的表达及其与血管生成的关系

目的 通过探讨骨桥蛋白(OPN)在喉癌中的表达情况及其与喉癌组织中血管的生长的关系,判断OPN是否可作为预测喉癌的标记物.方法 采用免疫组织化学方法检测骨桥蛋白(OPN)、血管内皮生长因子(VEGF)、CD34在60例喉癌组织、20例癌旁组织、20例声带息肉中的表达情况,对入检喉癌病例按国际抗癌协会(UICC)喉癌TNM分类标准(1997)进行临床分型、临床分期,对最后结果进行统计学分析.结果 OPN、VEGF在60例喉癌中表达的阳性率分别是73.3%、73.3%,在20例声带息肉中表达的阳性率是58.8%、53.9%,在20例癌旁组织中的表达的阳性率分别是25.0%、40.0%,喉癌、癌旁、声带息肉组中的MVD值分别是18.16±8.094,6.30±3.041、7.80±3.311,三个因素在喉癌组中的表达高于癌旁组、声带息肉组,且OPN和VEGF在喉癌组中的表达呈正相关,VEGF与CD34在喉癌组中表达也呈正相关,OPN与CD34在喉癌组中表达呈正相关.结论 OPN在喉鳞状细胞癌中呈高表达,可作为喉癌的一个肿瘤标记物,OPN促使喉癌中血管的增生是促使喉癌增生、侵袭及转移的一种机制.     

Management of a Laryngeal Venous Malformation With Nd:YAG Laser and Bleomycin Sclerotherapy

Literature describing neodymium:yttrium-aluminum-garnet (Nd:YAG) photocoagulation and sclerotherapy for laryngeal venous malformations (VMs) is sparse. Here we present a case in which an extensive laryngeal VM in a 28-year-old female was managed through a combination of four serial Nd:YAG laser photocoagulation sessions and four bleomycin injections over the course of 2 years. The treatment plan resulted in resulted in noticeable lesion ablation, mucosalization, and significant improvement in symptoms. To our knowledge, this case is the first instance of bleomycin injection specifically into a laryngeal VM reported in the English medical literature. Laryngoscope, 130:2199–2201, 2020     

Efficacy of Transcutaneous Computed Tomography-Guided Fine Needle Aspiration Biopsy in Patients With Laryngeal Squamous Cell Carcinoma,Probable Failed Radiation Therapy,and Negative Transmucosal Biopsies

For patients with suspected recurrent/persistent laryngeal squamous cell carcinoma (SCC) after external beam radiotherapy (EBRT), routine transmucosal biopsies obtained during direct laryngoscopy may fail to reveal active carcinoma. We evaluated transcutaneous computed tomography-guided fine needle aspiration (CTGFNA) in three consecutive patients who had a persistently fixed true vocal fold after EBRT that had been administered for laryngeal SCC and who had multiple negative transmucosal laryngeal biopsies. All three CTGFNA biopsies were positive, but final pathology confirmed invasive SCC in only one of the three patients. Despite its theoretical advantages, CTGFNA in its present form requires further assessment and/or modification. Laryngoscope, 106:1244-1247, 1996     

A Higher Angiogenin Expression is Associated With a Nonnuclear Maspin Location in Laryngeal Carcinoma

Objectives

In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC).

Methods

Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes.

Results

On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression ≥5.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression ≥5.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041).

Conclusion

Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC.     

原癌基因Pokemon及核转录因子E2F3在喉鳞癌中的表达及其临床意义

目的 探讨POK红系髓性致癌因子(POK erythroid myeloid ontogenic factor,Pokemon)及核转录因子E2F3(E2F transcrip tion factor 3)在喉鳞癌中的表达及其临床意义.方法 采用免疫组化Max Vision二步法观察61例喉鳞癌组织及46例癌旁正常喉黏膜组织中Pokemon及E2F3的表达,并结合患者年龄、性别、原发部位、TNM分期、临床分期及预后之间的关系进行分析.结果 Pokemon及E2F3在喉鳞癌组织中的阳性表达率明显高于癌旁正常喉黏膜组织中的阳性表达率(P<0.001);颈淋巴结转移(N+)、中低分化、临床晚期(Ⅲ+Ⅳ)喉鳞癌患者中Pokemon及E2F3表达强度增强(P<0.05);Pokemon及E2F3阳性表达患者的5年累积生存率较阴性表达患者低(P<0.05).结论 Pokemon与E2F3在喉鳞癌组织中高表达,并与其预后不良相关.两者可能在喉鳞癌发生及恶性进展过程中发挥重要作用,有望成为喉鳞癌发病机制及分子靶向治疗的新指标.     

Second Malignant Neoplasms in Patients Under 40 Years of Age With Laryngeal Cancer

Objectives/Hypothesis To determine the incidence of second malignant neoplasms (SMN) in patients under 40 years of age with invasive squamous cell carcinoma (SCC) of the larynx. Study Design Retrospective. Methods Using a National Cancer Institute tumor registry database encompassing 1973–1996, the incidence of SMN in patients under 40 years of age with laryngeal cancer was determined and compared with that of the registry's older, more traditional laryngeal cancer population. Median follow‐up was 136 months. Results Among the 364 patients under the age of 40 years with laryngeal cancer, 30 (8.2%) had developed a secondary malignancy to date. In comparison, 4876 (21.4%) of 22,786 patients 40 years or older with laryngeal cancer were affected by an SMN. Kaplan‐Meier analysis of the younger cohort projected 3.0%, 6.8%, and 10.7% relative risk of developing a SMN at any site over 5‐, 10‐, and 15‐year periods, respectively, after index tumor diagnosis. Similar results for the older cohort were 14.2%, 28.1%, and 39.4% at 5, 10, and 15 years, respectively. Further Kaplan‐Meier analysis demonstrated at least a fourfold increased risk for the development of secondary upper aerodigestive tract malignancies among older compared with younger patients. Conclusion Patients under 40 years of age with invasive SCC of the larynx are significantly less likely to develop a second malignancy than their older counterparts.     

Laryngeal chondrosarcomas: a clinicopathologic study of 11 cases, including two "dedifferentiated" chondrosarcomas.

Laryngeal chondrosarcomas are uncommon, and those that contain a distinct, nonchondroid, high-grade spindle cell sarcoma (the so-called "dedifferentiated" chondrosarcoma or chondrosarcoma with additional malignant mesenchymal component [CAMMC]) are extremely rare. Laryngeal CAMMC merit special attention, as CAMMC in other sites portends a poor prognosis. Eleven patients with laryngeal chondrosarcomas are reported on; 2 of these patients had CAMMC. On follow-up, 3 of the 11 patients had recurrences. The first had recurrence 4 and 11 years after tumor enucleation; that patient died disease free 2 years after salvage total laryngectomy. The second had recurrence 2 years after partial laryngectomy and was lost to follow-up after salvage total laryngectomy. The last patient recurred 13 years after partial laryngectomy and underwent salvage total laryngectomy; that patient was one of the two who developed CAMMC, and he also developed stomal recurrence of the "dedifferentiated" component 3 years after total laryngectomy. The other 8 patients are disease free after partial laryngectomy (6) or total laryngectomy (2) 10 months to 12 years later (mean: 51 months). This includes the 1 other patient with CAMMC, who is disease free 60 months after total laryngectomy. Laryngeal CAMMC has been shown, in at least one of the two patients, to be associated with a poor outcome. Patients with recurrent laryngeal chondrosarcomas do not have a poorer outcome after salvage total laryngectomy. The authors advocate partial laryngectomy if technically feasible.     

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.     

Severe regional and distant complication of tonsillitis. Case report

The authors describe a 66-year-old male patient treated for angina that was complicated by para- and retropharyngeal phlegmon, mediastinitis and pleuropneumonia. The role of imaging procedures and bacteriological examination was found especially important in establishing the diagnosis and introducing the right treatment. Efficacy of external (transcutaneus) approach to the para- and retropharyngeal space and phlegmon drainage of these spaces preceded with tracheotomy and tonsillectomy was underlined. Surgical treatment was supplemented with multi-component antibiotic therapy and gammaglobulin administration.     

Prognostic Value of EGFR and TGF-α in Early Laryngeal Cancer Treated With Radiotherapy

The purpose of this study was to determine the overexpression of both epidermal growth factor receptor (EGFR) and transforming growth factoralpha(TGF-α) (a ligand of EGFR) in early laryngeal squamous cell carcinoma. In addition, we attempted to evaluate the prognostic values of our findings. Expression of EGFR and TGF-α in tumor tissue was examined immunohistochemically in 68 patients who had been treated with radiotherapy for early laryngeal cancer. Overexpression of the two factors was noted in 42.6% and 55.9%, respectively. No significant differences due to age, tumor size, and location or grade of cancer tissues were seen. Higher survival rates, found in patients with EGFR (-) and TGF-α (-) tumors as compared with those with EGFR (+) and TGF-α (+) (97.4%, 100% and 86.2%, 86.8%, respectively), were not statistically significant. The recurrence rates were similar between EGFR (+) and EGFR (-) (37.9% and 35.9%, respectively). However, the recurrence rate in patients with TGF-α (+) was significantly higher (57.9%) than in those with TGF-α (-) (10%; P<.01). Therefore overexpression of TGF-α may be an important indicator for recurrence in patients with early laryngeal squamous cell carcinoma treated by irradiation. Laryngoscope, 106:884-885, 1996     

The Role of Partial Laryngeal Resection in Current Management of Laryngeal Cancer: a Collective Review

A spectrum of treatment plans and surgical procedures is available for management of early and moderately advanced laryngeal cancer. While the approach of chemotherapy and irradiation, or irradiation alone, followed by total laryngectomy for failure is often employed in practice by present day clinicians, the options of conventional conservation surgery (CCS), transoral endoscopic laser surgery (TLS) and supracricoid partial laryngectomy (SCPL) provide a wide choice of treatments that may help attain the goal of cure with preservation of laryngeal function and integrity of the airway. While CCS has been supplanted for many early-stage lesions by TLS and for more advanced stages by SCPL, centres throughout the world have reported favourable results with CCS, which is often modified to include resection of more extensive tumours than was previously possible. During the past decade a number of extended CCS procedures have been developed for management of glottic tumours involving both vocal cords and the anterior commissure, the paraglottic space and with vocal cord fixation, and for supraglottic tumours involving the glottis or hypopharynx. TLS has proved an effective, minimally invasive and functionally satisfactory procedure for management of suitable T1 and T2 glottic cancers, and stage I-III supraglottic cancers. The procedure may be effectively employed in combination with neck dissection and postoperative radiotherapy when necessary, particularly for moderately advanced supraglottic carcinomas. SCPL has proven effective in management of glottic and supraglottic cancers of all stages, even with involvement of paraglottic space and thyroid cartilage, provided at least one arytenoid unit can be preserved with clear margins. Invasion of cricoid cartilage is the most significant limitation for this procedure. All three surgical approaches have been employed for irradiation failure, but with greatly increased failure and complication rates compared with the results of treatment of non-irradiated patients. Thus a decision to treat laryngeal cancer initially with irradiation may preclude a satisfactory result from partial laryngectomy should radiation fail. The treatment of laryngeal cancer should be individualized according to the size and extent of the tumour, the age and physical condition of the patient, and the skill and experience of the surgeon with various treatment modalities and surgical procedures.     

Tumor Regression Patterns Based on Follow-up Duration in Patients With Head and Neck Squamous Cell Carcinoma Treated With Radiotherapy or Chemoradiotherapy

Objectives

We describe patterns of tumor regression based on follow-up duration after radiotherapy (RT) or chemo-RT in patients with head and neck squamous cell carcinoma.

Methods

Thirty-one patients with head and neck squamous cell carcinoma were included in this study and received definitive RT or chemo-RT. The pattern of primary tumor regression after treatment was evaluated every 1 to 2 months. Predictive factors for the length of time to full regression were also analyzed.

Results

Among all patients, 27 patients showed regression of the primary tumor, 24 patients showed >50% regression, and 15 patients showed total regression. The primary tumor gradually regressed during the course of follow-up. The median time to full regression was 5.2 months (range, 1.3 to 17.9 months). In the 24 patients who showed >50% regression, the rate of >50% regression increased over time as follows: 25.0% at 1 month, 62.5% at 2 months, 75.0% at 3 months, 91.7% at 4 months, and 95.8% at 5 months. Higher total RT dose and shorter RT duration were associated with longer time to full regression.

Conclusion

A substantial number of patients showed continuous regression of the primary tumor for more than 2 months after treatment. The timing for evaluation of tumor regression must be greater than 2 months from the completion of RT or chemo-RT in patients with head and neck squamous cell carcinoma.