DNA flow cytometry of thyroid neoplasms

Mechanically dispersed cell suspensions from 23 thyroid lesions were studied by acridine orange flow cytometry. Eight of 14 carcinomas (three papillary, two medullary, two Hürthle cell, and one follicular) manifested abnormal DNA indices ranging from 0.6 to 2.0. Six carcinomas (four papillary and two medullary) were diploid. Four patients having papillary carcinomas with diploid DNA content were young women whose clinical course of disease was indolent. Three papillary carcinomas with abnormal DNA content were found in older men with clinically aggressive disease. One benign adenomatoid nodule displayed a small population with a low-degree hyperdiploid stemline (DNA index = 1.1) with low proliferative activity. Differentiation between clinically indolent and aggressive carcinomas may be possible by nuclear DNA determination, but further work is needed to determine the importance of proliferative activity in thyroid carcinoma.     

DNA ploidy in papillary carcinoma of the thyroid gland in children and adolescents

OBJECTIVE: To evaluate DNA ploidy in papillary thyroid carcinoma in children in correlation to the clinical course of the disease. METHODS: Flow cytometric DNA ploidy measurements were performed on formalin-fixed, paraffin-embedded tumor specimens from 14 children and 14 adult patients with papillary carcinoma of the thyroid gland. Analysis of DNA content was performed blind to patient's age and clinical presentation. RESULTS: Seven patients presented with cervical metastasis, one patient had distal metastasis and four patients had local invasion. All patients underwent total thyroidectomy. Seven children underwent bilateral modified neck dissection. Twenty-five tumors expressed diploid DNA content. No statistically significant difference in DNA content was observed between the tumors from child and adult patients. No correlation was found between DNA content and aggressive presentation in the pediatric group. CONCLUSION: Our primary results indicate that diploid DNA content is common in papillary thyroid carcinoma in children and aggressive clinical presentation is not associated with DNA aneuploidy. Larger prospective studies and long-term clinical follow-up is warranted to document the clinical significance of these observations.     

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.     

Nuclear ploidy in neuroendocrine neoplasms of the larynx.

Seventeen neuroendocrine neoplasms of the larynx were examined for DNA ploidy. Twelve tumours were atypical carcinoids, four paragangliomas and one a small cell neuroendocrine carcinoma. Seven atypical carcinoids were aneuploid, one diploid and one tetraploid, with metastasis being aneuploid. In three cases only skin metastases were available for study, which were aneuploid. The small cell neuroendocrine carcinoma was aneuploid. Two of the paragangliomas were aneuploid and two diploid. Like other sites, neuroendocrine neoplasms of the larynx have a high rate of aneuploidy. Determination of DNA ploidy did not provide useful diagnostic or prognostic information.     

DNA含量及细胞核形态参数测定在甲状腺肿瘤中的应用价值

本文应用图像分析技术 ,对我院 1 996～ 1 998年住院手术治疗的 68例甲状腺癌 ( thyroidcarcinoma,TC)、2 0例甲状腺腺瘤 ( adenoma,AD)、6例腺瘤伴乳头状增生 ( adenoma and popillary,APP)进行了 DNA含量及细胞核形态参数检测。结果显示 :DNA指数、DNA倍体及细胞核形态参数三种检测 ,TC与 AD组对比有显著性差异 ( P <0 .0 1 ) ,TC组与 APP组对比也有明显差异 ( P <0 .0 5)。它提示用针吸病理检查同时追加上述三种检测 ,将是术前鉴别诊断的参数之一。探讨了这三种检测结果与甲状腺癌预后因素的关系及潜在的应用价值。     

Horner's syndrome and thyroid neoplasms

Although thyroid goiter is a common condition, it rarely results in Horner's syndrome. We report a case of a patient with an intrathoracic multinodular goiter complicated by Horner's syndrome. Benign thyroid disease was confirmed pathologically, and the patient's symptoms improved after surgery. In the literature, the major cause of Horner's syndrome is neoplasia, with malignant lesions being twice as frequent as benign tumors. An extensive review of the literature demonstrates a different repartition for thyroid neoplasia: including our case, 38 cases of Horner's syndrome secondary to a benign thyroid tumor are described, against only 8 cases caused by a thyroid carcinoma. We conclude that contrary to the commonly held opinion, Horner's syndrome is more often due to benign thyroid diseases than to thyroid malignancies.     

Hurthle cell neoplasms of the thyroid

OBJECTIVES/HYPOTHESIS: Hurthle cell tumors are a variant of follicular cell neoplasms. The purpose of the study was to determine the reliability of intraoperative frozen-section analysis for diagnosing Hurthle cell carcinoma and Hurthle cell neoplasm and to evaluate age, gender, and tumor size differences in the incidence of Hurthle cell carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: The records of all patients undergoing thyroid surgery at Long Island Jewish Medical Center (Long Island Campus of the Albert Einstein College of Medicine, New Hyde Park, NY) from 1990 to 2000 were reviewed. Patients were identified whose final pathological finding was Hurthle cell neoplasm or Hurthle cell carcinoma. Age at diagnosis, gender, tumor size, and correlation between frozen-section analysis and final pathological finding was determined. RESULTS: One hundred sixteen patients had Hurthle cell tumors on final pathological finding (49 had Hurthle cell carcinoma and 67 had Hurthle cell neoplasm). Eleven of these patients had incidental papillary carcinoma. There were 24 men and 92 women. Sixty-seven percent of the men (16 of 24) and 36% of the women (33 of 92) had Hurthle cell carcinoma on final pathological finding. The mean ages for Hurthle cell neoplasm and Hurthle cell carcinoma groups were 53 (median age, 50 y) and 58 years (median age, 61 y), respectively. One hundred eleven patients had intraoperative frozen-section analysis. Of the 49 patients with Hurthle cell carcinoma, 9 (19%) were diagnosed by frozen-section analysis, 36 (75%) had indeterminate frozen-section analysis, 3 (6%) were discovered to have papillary carcinoma on frozen-section analysis, and 1 did not have a frozen-section analysis. Multivariate analysis indicated that size correlated with malignancy and that gender did not (P =.0015). CONCLUSIONS: In the study population, only 19% of patients were discovered to have Hurthle cell carcinoma on frozen-section analysis. Sixty-seven percent of men with Hurthle cell neoplasm had malignancies, compared with 36% of women, and this difference was statistically significant.     

Prognostic significance of DNA ploidy in mucoepidermoid carcinoma

Thirty-four mucoepidermoid carcinomas were studied retrospectively with regard to histological and clinical parameters. In 28 of the tumors DNA patterns were also assessed using flow cytometry. Twenty-two of the 28 tumors (79%) were DNA diploid and 6 (21%) DNA aneuploid. Two tumors (7%) showed intratumoral DNA as indicated by different stemlines in specimens investigated from different parts of the tumor. DNA ploidy correlated significantly with cervical lymph node status (P < 0.01), but not with tumor size or histological grade. The mean S-phase value was 2.7% and was significantly higher in aneuploid samples than in diploid ones (P < 0.05). The recurrence rate was significantly lower for patients with stage I and II tumor compared with those with stage III and IV disease (P < 0.01). Five aneuploid tumors showed significantly higher recurrence rates (5/6) than the diploid ones (1/22) (P < 0.01). In univariate analysis for survival, only N stage tumor (P < 0.05) and tumor DNA ploidy (P < 0.0003) had significant prognostic influence. Thus, DNA ploidy seems to be a valuable parameter for evaluating the biological behavior of mucoepidermoid carcinomas of the salivary glands.     

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.     

DNA ploidy and proliferative activity in salivary gland tumours]

DNA ploidy and S-Phase fraction (SPF) of 279 salivary gland tumours were analysed using high-resolution DNA flow cytometry. All 229 benign neoplasms were diploid while 12 of 50 malignant tumours showed cell populations with aneuploid DNA content. The SPF values of diploid malignancies were significantly higher if compared with pleomorphic adenomas but did not differ from that of the zystadenolymphoma (Warthin tumour) group. While aneuploidy represents a distinct indicator of malignancy SPF values are of minor relevance for dignity assessment in salivary gland tumours.     

Ultrasonography a useful adjunctive in management of thyroid neoplasms

Fine needle aspiration cytology has been the gold standard of diagnosis in case of thyroid neoplasm. However ultrasonography of thyroid neoplasm is a useful guide for an operating thyroid surgeon. We in our study evaluated patients of thyroid neoplasm with USG thyroid & studied its role in the therapeutic management of neoplasm. In our study of 10 patients of thyroid neoplasm we found USG of the thyroid neoplasm as a valuable guide in management.     

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.     

Chemosensitivity and DNA ploidy in head and neck squamous cell carcinomas.

The succinate dehydrogenase activity and cellular DNA content of human head and neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy status were compared with histologic differentiation. The average decrease of enzyme activity in the poorly differentiated squamous cell carcinomas was significantly greater than that of well- and moderately differentiated squamous cell carcinomas. Statistically significant differences were also noted with relation to the original site of the primary tumor. The chemosensitivity of a tumor with DNA aneuploidy tended to be lower among the well- and moderately differentiated squamous cell carcinomas and higher among the poorly differentiated type. We conclude from this study that simultaneous analysis of the chemosensitivity and DNA ploidy will aid not only in selecting effective antitumor drugs but also in predicting changes in cellular characteristics during the course of disease.     

Hürthle cell neoplasms of the thyroid

The approach to Hürthle cell neoplasms of the thyroid gland remains controversial because there is no consensus on the criteria used to establish malignancy. Invasion into the thyroid capsule, blood vessels, and contiguous structures in the neck and lymph nodes, or distant metastases establishes malignancy. Benign Hürthle cell lesions should be treated with total lobectomy and isthmusectomy. Total thyroidectomy is the recommended treatment for malignant Hürthle cell lesions.     

DNA ploidy and S phase in relation to metastases of pharyngolaryngeal epidermoid carcinoma

Lymph node metastases in pharyngolaryngeal squamous-cell carcinoma are the clinical finding that most precisely condition prognosis. Sometimes the presence of subclinical metastases modifies the initial therapeutic strategy because they are not detected by physical exploration or imaging techniques. We tried to establish a relationship between the tumor's intrinsic aggressiveness and the development of metastases through tumoral DNA damage. Aneuploidy and the S phase were more frequent in tumors of the larynx, particularly supraglottic tumors, that developed lymph node metastases (72%) than in diploid tumors with a normal S phase (18%). In pharyngeal tumors, no differences could be established because most were aneuploid with a high S phase and metastases. Flow cytometry is highly sensitive, but not sufficiently specific for routine clinical use. However, it is a useful point of departure for our line of research, which will continue with a search for more specific genetic or molecular markers of metastases among the general DNA abnormalities.     

甲状腺微小癌临床分析

目的 探讨甲状腺微小癌的诊断方法和治疗原则.方法 对1984年9月～2002年9月收治的82例甲状腺微小癌总结分析.结果 75例(91.5%)患者在术前或术中得以明确诊断,所有病例均行手术治疗,5例因复发和转移二次手术,1例死亡.结论 对可疑病例行必要辅助检查,有助于提高甲状腺微小癌诊断率.甲状腺患侧腺叶切除,术前或术中证实有淋巴结转移者行颈淋巴清扫术,是合适的治疗方法.     

Quantitation of DNA ploidy in squamous intraepithelial neoplasia of the laryngeal glottis

The DNA contents in 56 laryngeal glottic biopsy specimens with a spectrum of squamous intraepithelial neoplastic (SIN) changes were evaluated by image analysis. A combination of DNA histogram features were used to define abnormal DNA-containing cell populations that were interpreted as representing intraepithelial neoplastic transformation. Eighteen biopsy specimens were classified as dysplasia/keratosis and graded SIN I, six (33%) of which were aneuploid. Eighteen (78%) of 23 biopsy specimens graded SIN II were aneuploid, and all 15 biopsy specimens graded SIN III had abnormal quantities of nuclear DNA. Twelve biopsy specimens (six of SIN II grade and six of SIN III grade) were considered to represent keratinizing forms of dysplasia, and all 12 (100%) were found to contain increased (aneuploid) quantities of DNA. We conclude that the proposed SIN-grading scheme for laryngeal epithelial abnormalities exhibits strong correlations with nuclear DNA content. In addition, aneuploidy was observed in all SIN II- and SIN III-graded biopsy specimens with prominent keratinization.