Flow cytometric analysis of DNA content in laryngeal cancer

DNA content was measured by flow-cytometric analysis in 30 paraffin embedded sections from patients with laryngeal squamous cell carcinoma. The morphological characteristics and N staging of the tumours as registered in their clinical charts were correlated with their DNA content. Eighty per cent of the tumours were found to have a predominantly aneuploid distribution of DNA values. There was no correlation between the N stage of the tumour or degree of cell differentiation and DNA content. A multiploid pattern correlates with non-metastatic laryngeal tumours and we suggest that this pattern may be a good indicator for biological activity.     

Flow cytometric analysis of DNA content in paraffin-embedded tissue in head and neck cancer--evaluation of malignant potential and carcinogenic process of nasoparanasal tumor

Flow cytometric analysis of DNA content from paraffin-embedded material has become an important diagnostic and prognostic method in clinical pathology and investigative oncology. We analyzed nuclear DNA content in order to detect possible alternations in DNA histogram as an indicator of malignant potential and carcinogenic process of head and neck tumor. DNA histograms were evaluated by three parameters; DNA aneuploidy, S + G2M% : rate of S and G2 + M phase cells as a parameter for growth kinetics, and polyploid%: rate of more than tetraploid cells as a parameter of nuclear atypia. We took a simple method for the selection of tumor area in paraffin blocks using a consecutive section stained with hematoxylin-eosin as a diagnostic guideline. This technique can be used either to enrich the sample to be analyzed with aimed area or to analyze histopathologically different compartments of the tumor. We compared the result of fresh and fixed specimens in 20 materials. DNA aneuploidy was found in both specimens of the same two carcinomas and there was a close relationship between them in S + G2M% (p less than 0.01) and polyploid% (p less than 0.05). We studied two cases of maxillary carcinoma with coexisting inverted papilloma as precancerous lesion. In one case S + G2M% and polyploid% were 16%, 1.15% in nasoparanasal papilloma, 20.5%, 4.0% in papilloma with atypia, and 33%, 8.25% in carcinoma, respectively. In the other case those were 3%, 0.1% in transitional papilloma, 8%, 0.9% in inverted papilloma, and 13%, 4.0% in carcinoma, respectively. There was positive correlation between these two parameters and histopathological grade. Finally we analyzed nuclear DNA content from fixed specimens in three groups; 33 papillomas, 15 maxillary carcinomas and 23 normal epithelia. Mean values of S + G2M% and polyploid% were as follows: 2.1%, 2.6% in normal epithelia, 19.6%, 8.9% in papillomas, and 34.8%, 18.1% in carcinomas. There was statistical significance between three groups (p less than 0.01). DNA aneuploidy was only found in 6 of 15 carcinomas (40%). The results demonstrated that S + G2M% and polyploid% were significantly compared with the histopathological grade of atypia and DNA aneuploidy was a marker of carcinoma. We suggest that DNA histogram is a good indicator for biological activity and that the increased S + G2M% and polyploid% may indicate carcinogenic process. We also suggest that tumor progression may lead to acquired genetic variability and DNA aneuploidy.     

Flow cytometric analysis of nuclear DNA content in oral leukoplakia

DNA ploidy has been studied in 31 paraffin-embedded specimens of oral leukoplakia and in 10 specimens of oral leukoplakia that have undergone malignant transformation after a 5-year observation period. Three out of 31 specimens (9.7%) showed an aneuploid DNA pattern, with DNA indices of 1.17, 1.28 and 1.32. It was not possible to establish a statistically significant difference of DNA ploidy related to the presence or absence of dysplasia. One out of the 10 oral leukoplakias that underwent malignant transformations had a multiploid pattern with DNA indices of 1.44 and 2.37. In this study the DNA index has not proved to be of value in the identification of dysplastic leukoplakia among the non-dysplastic ones.     

DNA content in laryngeal keratosis, laryngeal cancer and normal laryngeal epithelium

The DNA content in laryngeal precancerous lesion, laryngeal keratosis, laryngeal carcinoma and normal laryngeal epithelium had been measured in order to study the relationship between histopathologic picture and DNA content. The results showed that the DNA content in keratotic tissue increased to varying degrees as compared with the normal tissue. The DNA content in laryngeal cancer increased distinctly, being much higher than that in normal and keratotic tissues.     

Flow cytometric analysis of DNA content and Ki-67-positive fractions in the diagnosis of salivary gland tumors

To explore the utility of flow cytometry (FCM) for the diagnosis of histopathology of salivary gland tumors, fresh materials taken at surgery from 23 Warthin’s tumors, 57 pleomorphic adenomas, and 14 malignant tumors were analyzed for DNA ploidy and proliferative cell activities, including S-phase fraction (SPF), G2- plus M-phase fraction (G2M), and Ki-67-positive fraction. To facilitate this study, glands were taken from all major salivary sites and minor glands in the head and neck. DNA aneuploidy was not detected in the benign tumors. Nine of 14 malignant tumors showed DNA aneuploidy. The percentage of SPF or G2M of the malignant tumors was significantly higher than those of the benign tumors. The percentage of Ki-67-positive fraction of pleomorphic adenomas was comparable to that of malignant tumors and was significantly higher than that of Warthin’s tumors. Ki-67 of 20% as a cut-off had a sensitivity of 88%, specificity of 100%, and accuracy of 91% for differentiating pleomorphic adenomas from Warthin’s tumors. In analyzing DNA content and proliferative activities by FCM, we could distinguish among the three major histopathologies of salivary gland tumors. Warthin’s tumors showed low SPF+G2M with low Ki-67, pleomorphic adenomas had low SPF+G2M with high Ki-67, and malignant tumor showed high SPF+G2M with high Ki-67. The high percentage of the Ki-67-positive fraction seen in pleomorphic adenomas may reflect their potential biological aggressiveness manifested as tumor recurrence or malignant transformation. Received: 26 June 1997 / Accepted: 5 November 1997     

Measurement of nuclear DNA content of laryngeal carcinoma and determination of estrogen receptor (ER) level in laryngeal cancer cells

In 39 patients with laryngeal carcinoma, nuclear DNA content was measured, and the ER in cancer cells of 23 cases determined. The following results were obtained: 1. For all laryngeal carcinomas, there were two patterns-diploid and non-diploid carcinomas. The majority (27/39) belonged to the non-diploid pattern. 2. The laryngeal carcinomas of non-diploid pattern or with higher level of DNA content were easily metastasized to cervical nodes. This kind of cancers were more often seen in clinically advanced cases. Patients with these carcinomas, judged by the results of one-year's follow-up, had poor prognosis. 3. Carcinomas with diploid pattern or with lower level of DNA content had the tendency to become ER positive. The cervical node metastases was more easily taking place in ER negative carcinomas. Some indirect relationship between DNA content and ER in laryngeal cancers may exist.     

头颈部非霍奇金淋巴瘤25例临床分析

目的：探讨25例头颈部非霍奇金淋巴瘤(NHL)的临床表现、分期、分型及治疗方法。方法：对我院2000年3月-2004年4月间治疗的25例头颈部NHL进行回顾性分析。结果：25例中,首犯咽淋巴环11例,鼻腔8例,鼻窦1例,颈淋巴结4例,腮腺1例。鼻腔、鼻窦已有3例死亡。结论：根据头颈部NHL的首犯部位、肿瘤分期、组织学分型进行恰当的治疗,可提高治愈率。     

The role of second opinion pathology in the management of lesions of the head and neck

PURPOSE OF REVIEW: Medical error is a common problem, and its human cost in terms of disability, suffering, and death is stunning. Steps toward reducing medical error will require the identification of mistake-prone practices within a complex health care system. Erroneous pathologic diagnosis has been identified as one source of error. This review was undertaken to assess the magnitude of diagnostic imprecision in lesions of the head and neck, and to address the validity of mandatory review of pathology material for patients who are referred from one institution to another for management of tumors involving the head and neck. RECENT FINDINGS: Mandatory second opinion pathology consistently uncovers discrepancies across all major organ systems and has a profound impact on management and prognosis. Site-specific studies have implicated the head and neck as a high-risk area that is prone to diagnostic error. Diagnostic discrepancy rates have ranged from 1 to 53% for surgical pathology studies and from 17 to 60% for cytopathology studies. Major changes (affecting treatment or prognosis) occur in 5 to 7% of surgical pathology cases. The thyroid is consistently identified as a site that is particularly prone to diagnostic discrepancies; and no specific head and neck sites are immune to diagnostic error. SUMMARY: Limited studies addressing the site-specific impact of second opinion pathology implicate the head and neck as a high-risk area that is prone to major changes in diagnoses. Accordingly, mandatory second opinion pathology makes good clinical and risk management sense for all patients referred to head and neck surgery or oncology services before a major therapeutic endeavor is undertaken.     

Monoclonal antibodies (Mabs) in head and neck cancer

The development of monoclonal antibodies (Mabs) represents a major contribution of immunology to the study of head and neck cancer. The interest of the otolaryngologist in this new field is quite recent, but our knowledge of cancer and other immunoproliferative disorders will exponentially expand with the characterization of tumor-associated antigens of squamous cell carcinomas. The author reviews briefly the technique for producing monoclonal antibodies and presents an overview of the application of Mabs to clinical medicine, oncology and, more specifically, head and neck cancer. Very few contributions have been made in head and neck cancer, but the field of Mabs will significantly alter our diagnostic and therapeutic armamentarium.     

头颈部肿瘤DNA的定量分析

目的：探讨细胞定量学分析在诊断头颈部肿瘤中的意义。方法：应用全自动细胞图像分析仪测定23例头颈部恶性肿瘤和20例良性病变患者的细胞核DNA指数(DI)、S期细胞分数(SPF)、细胞增殖指数(PI)和DNA大于5c的核的比率(5c Ex)。结果：细胞定量分析和常规细胞学检查的阳性率分别为76．92％和50．00％，SPF、PI和5c Ex在恶性病变组分别为14，05％、19.59％和1．59％，SPF和PI在肿瘤部位的细胞增生程度高，与瘤旁1cm和手术切缘处存在明显不同。结论：全自动细胞图像分析仪的细胞定量诊断阳性率较常规细胞学检查明显提高，异倍体率、SPF、PI和5c Ex指标在诊断头颈部肿瘤、估计肿瘤的生物学恶性程度和评估手术范围等临床工作中有一定参考价值。     

Flow cytometric analysis of DNA ploidy in nasosinal papilloma]

Using paraffin embedded specimens taken from 32 patients with histologically benign nasosinal papillomas, we conducted nuclear DNA analysis by flow cytometry and studied the biological degree of malignancy in this disease. Aneuploidy, which is frequently observed in malignant tumors was not seen in any of these nasosinal papilloma cases. Age did not affect either S+G2M % or polyploid %, two parameters that reflect cell proliferation capacity. Both parameters, S+G2M % and polyploid %, were higher in inverted papillomas which are more likely to become malignant than epithelial papillomas. In recurrent cases of nasosinal papilloma both S+G2M % and polyploid % were higher than in nonrecurrent cases. Moreover, the polyploid % was significantly different, supporting speculation that this can be used as a parameter for predicting recurrence of nasosinal papilloma.     

Survival in second primary malignancies of patients with head and neck cancer

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.     

Panendoscopy and synchronous second primary tumors in head and neck cancer patients

Endoscopy techniques are used to diagnose and to determine the extent and exact location of malignancies in the head and neck region, bronchial tree and esophagus. Panendoscopy is used to find the primary tumor in the case of metastatic disease from unknown primaries or to detect a simultaneous second primary tumor at the time of diagnosis of a malignancy in the upper aerodigestive tract (UADT). The value of panendoscopy has been debated lately because of the relatively small proportion of malignant findings and because of the lack of convincing data concerning its effect on survival rates. However, despite the relatively low proportion of positive findings, their significance is often crucial for the individual patient. The significant number of late metachronous, second primaries, especially in the lungs, also emphasizes the importance of follow-up endoscopies. This study consists of 203 consecutive patients with squamous cell cancer (SCC) of the upper aerodigestive tract who underwent panendoscopy in Turku University Central Hospital as part of the initial diagnostic workup from 1992–1999. Eight patients with synchronous second primaries were found to represent a prevalence of 3.9%, and in addition, 19 patients with metachronous tumors were diagnosed. In the case reports we illustrate the importance of some of these findings.     

(Chemo-) prevention of second tumors in patients with head and neck neoplasms

This review discusses the possible role of chemoprevention in the improvement of survival rates and the prevention of secondary primary tumours in patients with head and neck cancer. Chemoprevention is a new treatment that is especially promising for high risk groups. The fear that the advantages of this treatment will be outweighed by the disadvantages of side-effects and toxicity has not been confirmed by current studies. Randomized studies are needed to show whether chemoprevention can reduce the frequency of second primary tumours.     

Fibro-osseous lesions of the head and neck

Review and classification of fibro-osseous lesions of the head and neck is presented. The common denominator to all these pathologic entities is replacement of normal bone with fibrous tissue.