Fine-needle aspiration cytology for parotid lesions, can we avoid surgery?

OBJECTIVE: Salivary gland neoplasms are rare tumours, with most arising in the parotid gland. Fine-needle aspiration cytology (FNAC) is a common method for preoperative evaluation of parotid masses, although its usefulness is controversial. This study was designed to evaluate the accuracy of FNAC in a large cohort of patients, with emphasis on diagnosis of benign tumours and especially Warthin tumour which can be managed conservatively. STUDY DESIGN: Retrospective case series with chart review. SETTING: Tertiary medical centre. SUBJECTS AND METHODS: From 1991 to 2014, all patients 18 or older with both preoperative FNAC and postoperative pathology report were included. Patients with a history of head and neck malignancy or chronic sialoadenitis and patients who had undergone prior oncological treatment were excluded. RESULTS: 470 patients were available for analysis. Overall accuracy was 82.6%. Positive predictive value (PPV) varied between 88.6% and 94.3% for pleomorphic adenoma and 77.1%-100% for Warthin tumour, with values varying depending on different characteristics of patients (eg age, smoking status). For pathologically proven malignant tumours, the FNAC diagnosis was benign or non-diagnostic in 26% of the cases. CONCLUSION: Fine-needle aspiration cytology has limited utility in confirming a benign diagnosis of a parotid mass for most patients, although for some subpopulations, the PPV may be high enough to defer surgery.

Parathyroid adenoma: a comprehensive biochemical and histological correlative study.

OBJECTIVE: To investigate the controversial relationship between preoperative calcium and parathyroid hormone levels and the dimensions and histological features of parathyroid adenoma in patients with primary hyperparathyroidism. STUDY DESIGN: Historical cohort. SETTING: Tertiary medical centre. SUBJECTS AND METHODS: Clinical and tumour-related data were collected from the medical files of all patients who underwent parathyroidectomy for primary hyperparathyroidism in 1996-2012. Preoperative blood parathyroid hormone and calcium levels and urine calcium levels were correlated with the size, weight and volume of the parathyroid adenoma. Pathohistological features were determined in a representative sample of archived paraffin-embedded sections and analysed by calcium or parathyroid hormone level (high/low) and adenoma weight (high/low). RESULTS: A total of 378 patients were included. There was a statistically significant direct correlation of preoperative calcium and parathyroid hormone levels with tumour dimensions and of tumour weight and chief-cell percentage. At a preoperative calcium level >11.5 mg/dL and parathyroid hormone (PTH) level >165 mg/dL, we predict that the adenoma would measure more than 2.7 g, 2.18 cm and volume of 3.59 cm3 . CONCLUSIONS: In patients with primary hyperparathyroidism, preoperative calcium and PTH levels may be predictive of parathyroid adenoma dimensions.

Inflammation following invasive procedures for Warthin's tumour: A retrospective case series.

OBJECTIVE: To determine the risk of inflammation associated with fine-needle aspiration during evaluation of Warthin's tumour. DESIGN: Retrospective case series. SETTING: Tertiary medical centre. PARTICIPANTS: All patients who underwent fine-needle aspiration followed by parotidectomy between 1992 and 2009 for the diagnosis/evaluation of a parotid gland tumour. MAIN OUTCOME MEASURE: Rate of fine-needle-aspiration-related parotitis in patients with Warthin's tumour or other parotid pathologies. RESULTS: A total of 593 parotidectomies were performed in 553 patients during the study period, 96 (16.2%) for Warthin's tumour (study group) and 497 for other parotid-related pathologies (control group). Parotid gland inflammation following fine-needle aspiration was observed in 16 cases in the study group (16.7%) and eight (1.6%) in the control group (P<.001). On multivariate regression analysis, parotitis following fine-needle aspiration was more common in patients with Warthin's tumour than other parotid-related pathologies even after adjustment for possible confounders (P<.007). Signs of inflammation were noted during surgery in six cases in the study group (6.3%) and none in the control group (P<.001); respective rates of postoperative inflammation (wound infection) were 1.04% and 3.3% (P=NS). Management of parotitis consisted of hospitalisation and systemic antibiotic therapy. CONCLUSIONS: Warthin's tumour is associated with a tenfold higher risk of inflammation compared to other parotid tumours following invasive procedures. Clinicians should be alert to this complication in order to initiate proper treatment and patients must be properly counselled.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research.

BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

Thyroid surgery in the elderly.

BACKGROUND: The increase in life expectancy combined with the relatively high incidence of thyroid disease requiring surgery in the elderly has raised questions concerning the appropriate management of the older patient. AIM: Evaluation of the surgical management and outcome of thyroid disease requiring surgery in elderly patients. METHODS: We performed a retrospective cohort study, in which the medical charts of 2,239 patients who underwent total thyroidectomy or hemithyroidectomy between 1995 and 2011 in a tertiary medical center were reviewed for clinical, disease-related, operative and outcome measures. Findings were analyzed between the patients aged more than 75 years for whom complete information was available (n = 255) and a control group of 100 patients aged 40-60 years matched for sex and extent of surgery. RESULTS: The prevalence of comorbidities was significantly higher in the elderly. Presenting symptoms were similar in the two groups; in approximately 25% of both groups thyroid cancer was an incidental finding. There were no between-group differences in surgery duration, time to anesthesia induction, recovery time from anesthesia, or rate of postoperative complications. Hospitalization was 3 days longer on average in the older group. Malignancy rates and distribution of histologic subtypes were similar in the two groups, although the older group presented with significantly higher rates of advanced disease stage and larger tumors. There were no differences in recurrence rate both locoregional and distant metastases. However, a higher proportion of older patients failed to achieve cure. CONCLUSION: Although older patients with thyroid disease have more comorbidities and advanced disease, there is no practical difference in their operative management and surgical outcome compared to younger patients. Surgery should not be deferred solely on the basis of age in the presence of compelling indications; rather, the decision should be based on individual risk-benefit analysis.

Predicting facial nerve invasion by parotid gland carcinoma and outcome of facial reanimation.

We sought to define risk factors for facial nerve involvement in parotid gland carcinoma and assess the outcome of facial nerve reanimation. Medical records were reviewed of 66 patients who underwent surgery for parotid carcinoma in 2000­2007 at a tertiary hospital. Patient and tumor characteristics were compared between patients with and without facial nerve involvement and were analyzed on their influence on functional outcome following reanimation. Facial nerve involvement was verified intraoperatively in 24 patients, of whom 16 underwent reanimation during ablative surgery. Deep lobe invasion was significantly associated with intraoperative finding of facial nerve involvement. Tumors larger than 4 cm and salivary duct carcinoma had an obvious trend for facial nerve involvement. House-Brackmann score at 12 months was 3-4 in most patients. Deep lobe involvement and large tumor size may identify patients at risk of facial nerve involvement. Reanimation is associated with good functional outcome regardless of patient's age.

The impact of positive resection margins in partial laryngectomy for advanced laryngeal carcinomas and radiation failures.

OBJECTIVES: To investigate the prognostic significance of positive margin and disease course in partial laryngectomy for advanced laryngeal carcinoma and radiation failure. DESIGN: Retrospective case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Patients who underwent partial laryngectomy for advanced laryngeal carcinoma or for radiation failure with at least 2 years of follow-up. MAIN OUTCOME MEASURES: Margin status versus primary treatment and salvage treatment versus disease-free survival and overall survival. RESULTS: Twenty nine patients with sufficient follow-up data were found. Twelve patients had histological positive margin. Five of the 12 patients with a histological positive margin failed surgery as did four patients with clear margins. A positive margin had no effect on disease-free survival (P = 0.287) but was associated with poorer overall survival (P = 0.051). Of 11 patients treated primarily with surgery, recurrence was documented in one of eight with a positive margin and none of three with clear margins. Of 18 patients who underwent surgery secondary to radiation failure, recurrence was documented in all four with a positive margin and 4 of 14 with negative margins. Extended frontolateral resection, performed only in radiation failures, was associated with worse disease-free survival. CONCLUSIONS: Non-irradiated patients with involvement of a single margin after partial laryngectomy may be spared total laryngectomy if adjuvant radiation is administered. Patients who fail radiation should undergo radical partial laryngectomy, with conversion to total laryngectomy in those with a positive margin.

Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome.

OBJECTIVE: To assess the possible effect of young age on clinical behaviour and survival outcome of squamous cell carcinoma of the oral tongue. DESIGN: Retrospective, case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Eighty-five patients with oral tongue squamous cell carcinoma with at least 2 years of follow-up. MAIN OUTCOME MEASUREMENTS: Clinical and histopathological staging, disease-free survival, disease-specific survival and overall survival. RESULTS: Eleven patients (13%) were younger than 30 years. Compared to the older patients, they had a significantly worse N stage (P = 0.041), more perineural invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with distant metastases, versus 35%, nearly all locoregional) and mortality (100% of treatment failures versus 73%). There were no significant between-group differences in 5-year disease-free, disease-specific, and overall survival. CONCLUSION: In this study, patients younger than 30 years of age presented with advanced tumour stages and with a different failure pattern compared to the older age group. This may be attributable to age-related biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could not be established.

Salivary analysis of oral cancer biomarkers.

BACKGROUND: Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing. METHODS: We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death. RESULTS: Five markers increased in cancer patients by 39-246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (P< or =0.01). Three markers decreased by 16-29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (P< or =0.01). Increase in salivary carbonyls was profound (by 246%, P=0.012); alterations in CycD1 (87% increase, P=0.000006) and Maspin (29% decrease, P=0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively. CONCLUSION: The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.

Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P<.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

Oral ofloxacin as treatment of malignant external otitis: a study of 17 cases.

Seventeen patients with malignant external otitis were treated with oral ofloxacin. Their mean age was 69 years. Seven of the patients were diabetic. Pseudomonas aeruginosa, sensitive to ofloxacin (Kirby-Bauer method, inhibition zone greater than or equal to 22 mm), was isolated from the external auditory canal in all patients. Ofloxacin (200 mg b.i.d.) was given to the patients for 12 to 39 days. Two patients also received additional parenteral antibiotic therapy. Subjective and objective improvement occurred in all patients during treatment, and complete resolution was documented in all patients, with one exception. Only one patient suffered recurrence 2 weeks after discontinuation of antimicrobial therapy. The results of our study suggest that oral ofloxacin is an effective treatment for malignant external otitis caused by Pseudomonas aeruginosa.

The free vascularized flap and the flap plate options: comparative results of reconstruction of lateral mandibular defects.

OBJECTIVES/HYPOTHESIS: Reconstruction of the mandible and oral cavity after segmental resection is a challenging surgical problem. Although osteocutaneous free flaps are generally accepted to be optimal for reconstruction of anterior defects, the need for bony reconstruction for a pure lateral mandibular defect remains controversial. STUDY DESIGN: A retrospective study. METHODS: A retrospective comparative study of short- and long-term outcomes of three different reconstruction techniques for lateral defects was performed. In total, 57 patients were included, of whom 27 had a plate and pedicled pectoralis major myocutaneous flap (PMMF group), 16 had a plate and free radial forearm flap (FRFF group), and 14 had an osteocutaneous free flap. Functionality, flap failure, and complications were scored. RESULTS: Plates had to be removed in 7 of the 27 patients in the PMMF group and 2 of the 16 in the FRFF group; none of the 14 osteocutaneous free flaps failed. The difference was of borderline statistical significance (P = .055). Longterm functional outcome revealed no statistically significant difference in oral deglutition (P = .76) or in facial contour (P = .36). Oral continence was significantly better in patients in the FRFF group (88%) as compared with the PMMF group (52%) or the osteocutaneous free flap group (43%) (P = .02). On the other hand, the results for speech favored the osteocutaneous free flap group; 13 of 14 patients (92.9%) had a normal score compared with 12 of 16 patients (75%) in the FRFF group and 17 of 27 (63%) in the PMMF group. However, this represented a borderline statistically significant result (P = .06). CONCLUSIONS: For lateral mandibular defects, the osteocutaneous free flap is reliable and durable in the long term. However, in a selected group of patients either of the two flap-plate options is a viable reconstructive option.

Intravascular papillary endothelial hyperplasia in the maxillary sinus. A benign lesion that may be mistaken for angiosarcoma.

Intravascular papillary endothelial hyperplasia is a vascular benign lesion bearing some similarities to malignant angiosarcoma. To the best of our knowledge, it has never been described within the paranasal sinuses. A case of such a lesion within the maxillary sinus appearing in a 17-year-old boy who presented with unilateral facial pains and proptosis is reported. The lesion, despite its benign nature, extended to the ethmoidal cells and nasal cavity and pressed the floor of the orbit. Clinically and histopathologically it may be mistaken for an angiosarcoma. An awareness of this similarity and the features in which it differs from angiosarcoma will prevent incorrect diagnosis and inappropriate treatment.

Significance of DNA ploidy in the treatment of T1 glottic carcinoma.

OBJECTIVE: To assess the role of DNA ploidy as a predictor of radioresistance in T1 glottic carcinoma. DESIGN: Case-control study. Flow cytometric DNA ploidy measurements were performed on formalin-fixed paraffin-embedded tumor specimens from 15 patients with T1 glottic laryngeal carcinomas in whom radiotherapy had failed and from a matched group of 15 patients in whom an identical radiotherapy regimen was curative. Analysis of DNA content was performed blind to outcome of treatment. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Thirty patients with clinically staged T1, N0, M0 glottic carcinoma. INTERVENTION: All patients received radiation to the larynx through opposed lateral ports at a total dose of 64 to 70 Gy. RESULTS: Ten diploid and five aneuploid histograms were found in the resistant group, and six diploid and nine aneuploid histograms were found in the radiosensitive group. This difference was not statistically significant. A trend toward a higher relapse rate after radiotherapy (62.5%) among patients with diploid tumor compared with those with aneuploid tumor (35.7%) was noted. CONCLUSIONS: DNA ploidy did not predict response to radiotherapy in patients with T1 glottic cancer, probably because of the small number of patients. A trend toward lower risk of local recurrence after radiotherapy in aneuploid tumors was noted. A larger prospective study is needed to assess the value of DNA ploidy in the treatment of early laryngeal cancer.

Tumor angiogenesis as a prognostic factor in early oral tongue cancer.

OBJECTIVE: To evaluate the relationship between tumor angiogenesis and the subsequent development of cervical node metastases in patients with stage 1 carcinoma of the oral tongue. METHODS: The study group consisted of 25 patients with T1 carcinoma with no evidence of neck disease at presentation. Paraffin blocks from 10 patients, in whom neck node metastases were found shortly after surgery, were stained for factor VIII and compared with those from 10 randomly chosen patients in whom no evidence of recurrent disease was observed during prolonged followup. Microvessels were counted in each group. RESULTS: The microvessel counts correlated with metastatic disease. The mean +/- SD count was 103.41 +/- 40.72 per X 250 field in the patients with positive lymph node metastases and 50.03 +/- 13.74 per X 250 field in those with no lymph node metastases during follow-up (P < or = .05). CONCLUSIONS: The number of microvessels per X 250 field in the area of most intensive neovascularization in early oral tongue carcinoma may be an independent predictor of nodal metastases. Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early oral tongue carcinoma for aggressive therapy.

Oromandibular reconstruction with the fibular free flap. Analysis of 50 consecutive flaps.

OBJECTIVE: To evaluate the results and functional outcome associated with fibular free flap reconstruction of orofacial and mandibular defects. DESIGN: We conducted a retrospective analysis of 50 consecutive fibular free flaps during a 3-year period. Forty patients were available for follow-up, which ranged from 4 to 39 months. SETTING: Academic tertiary care referral medical center. PATIENTS: Fifty consecutive mandibular reconstructions using the fibular free flap were performed on 47 patients. Thirty-five patients (74%) underwent primary reconstruction. Sixty-six percent of the mandibular defects were anterior or combined anterolateral types; the remainder were pure lateral defects. In 38 patients (81%), a skin paddle was included with the flap to provide either a mucosal lining or skin cover, whereas in only 9 patients (19%), bone was used alone. MAIN OUTCOME MEASURES: Factors reflecting functional properties and processes as well as complications of the upper aerodigestive tract were evaluated clinically and radiographically. RESULTS: Four flaps required reexploration as emergencies, and none were successfully salvaged (8.5% failure). Three patients underwent further free vascularized fibula transfer with 1 failure. During follow-up, swallowing was normal in 25 patients (64%), oral continence was normal or almost normal in 26 patients (67%), and speech was normal or easily intelligible in 35 patients (90%). Aesthetic results were excellent or acceptable in 37 patients (95%). CONCLUSIONS: Our results reveal that the vascularized fibular free flap is very suitable with an excellent success rate for reconstructing both the composite or simple long-spanned mandibular defect. The overlying skin island is reliable and provides lining or coverage for intraoral and extraoral defects. Superior functional cosmetic results are expected in the majority of patients, while donor site morbidity is minimal.

Comparison of nuclear DNA content in locally invasive and noninvasive papillary carcinoma of the thyroid gland.

Extrathyroidal invasion of papillary carcinoma of the thyroid gland has a very bad prognosis. A retrospective study was performed on 40 specimens from patients with papillary carcinoma of the thyroid gland to find out whether DNA ploidy correlated with aggressive tumor behavior. The nuclear DNA content of 20 locally aggressive papillary thyroid carcinomas was studied by flow cytometry. The results were compared with those of a matched control group of 20 patients with noninvasive papillary tumors. Forty percent of the tumors with spread to extrathyroid tissue were aneuploid, whereas all the tumors without such extension were diploid. This difference was statistically significant (p < 0.003). The data suggest that the differentiation of locally noninvasive and invasive papillary thyroid carcinomas may be potentially possible by nuclear DNA determination.