Prognostic significance of regulators of cell cycle and apoptosis, p16(INK4a), p53, and bcl-2 in primary mucosal melanomas of the head and neck.

Abnormalities in cell cycle regulation, tumor suppressor gene functions and apoptosis are frequent events in tumorigenesis. Their role in the pathogenesis and prognosis of primary mucosal melanomas (MM) of the upper aerodigestive tract remains unknown. Sixty-four patients (40 men, 24 women, median age 64 years) with MM were included in this study; 32 had tumors in the nasal/paranasal cavities, 28 in the oral cavity and 4 in the pharynx. Archival tissues from 47 initial mucosal tumors, 17 mucosal recurrences, and 13 nodal/distant metastases were subjected to immunohistochemistry using antibodies against p16, p53, and bcl-2. The results were correlated with histological features and survival data. Expressions of p16, p53, and bcl-2 proteins were seen in 25% (N=19/76), 21% (N=16/76), and 74% (N=56/76) of all tumors, respectively. bcl-2 expression in the initial tumors was associated with significantly longer overall and disease specific survival (3.3 vs. 1.5 years, P ≤ 0.05). Expression of p16 was increasingly lost, from 32% in initial tumors to 12% in recurrent and 15% in metastatic tumors (P=0.06). Tumors comprised of undifferentiated cells were significantly more p53 positive than epithelioid or spindle cells (80% vs. 33%, P=0.02). Expression of these markers did not correlate with necrosis, or vascular and/or deep tissue invasion. Expression of bcl-2 is associated with better survival in MM. Loss of p16 was seen with tumor progression whereas aberrant p53 expression was frequent in undifferentiated tumor cells.

Validation of a novel method for measuring waist circumference.

Though seemingly an easy procedure to perform, there is no universally accepted approach to the measurement of waist circumference (WC) in the clinical setting. Measurement of WC can be affected by a myriad of factors including patient movement or position changes, poor positioning of the measuring tape or differences in tension applied to the tape by the clinician. Changes in any one of these factors can reduce the validity and reliability of the measurement. This is of particular importance in clinical trials where changes in WC represent a therapeutic endpoint. Recognition of the need for a more standardized and reliable means to perform WC measurement led to the development of a novel, validated technique. The Height of Iliac Crest (HIC) method uses a standardized technique that increases the reliability of measurement by minimizing some of the weaknesses and variations of previous methods. The purpose of the following study was to validate the accuracy and reproducibly of the HIC method for obtaining WC measurement data. This study demonstrates that accurate and reproducible results can be obtained through the application of the HIC method for measuring waist circumference.

Design and simulation study of the immunization Data Quality Audit (DQA).

The goal of the Data Quality Audit (DQA) is to assess whether the Global Alliance for Vaccines and Immunization-funded countries are adequately reporting the number of diphtheria-tetanus-pertussis immunizations given, on which the "shares" are awarded. Given that this sampling design is a modified two-stage cluster sample (modified because a stratified, rather than a simple, random sample of health facilities is obtained from the selected clusters); the formula for the calculation of the standard error for the estimate is unknown. An approximated standard error has been proposed, and the first goal of this simulation is to assess the accuracy of the standard error. Results from the simulations based on hypothetical populations were found not to be representative of the actual DQAs that were conducted. Additional simulations were then conducted on the actual DQA data to better access the precision of the DQ with both the original and the increased sample sizes.

Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression.

BACKGROUND: Treatment-resistant depression (TRD) is a long-term, disabling illness. We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with standard care. METHOD: This 2-year prospective, multicenter, observational study (patients enrolled from January 2001 through July 2004) tracked the outcomes of 124 patients with treatment-resistant, nonpsychotic major depressive disorder (N = 109) or bipolar depressed phase disorder (N = 15) who received treatment as usual (TAU) (i.e., any therapeutic regimen agreed to by patients and psychiatrists, including medications, electroconvulsive therapy [ECT], and psychotherapy). Treatments could be adjusted, started, and stopped as necessary. The primary outcome, treatment response, was defined a priori as > or = 50% improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR-30). Remission was defined as an IDS-SR-30 score of < or = 14. The Medical Outcomes Study (MOS) 36-item Short Form Health Survey (SF-36) was used to monitor quality-of-life changes. RESULTS: The 12- and 24-month IDS-SR-30 response rates were 11.6% (13/112) and 18.4% (19/103), respectively. Of the 13 responders at 12 months, only 5 were responders at 24 months. The 12- and 24-month IDS-SR-30 remission rates were 3.6% (4/112) and 7.8% (8/103), respectively. Only 1 of the 4 12-month remitters was also a remitter at 24 months. The SF-36 indicated globally poor quality of life in this sample. CONCLUSIONS: Despite the wide range of treatment options available for depression, the response rates, remission rates, and quality-of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU.

Patterns of care among adolescents with malignancy in Ohio.

Adolescents with malignancy represent a unique population in oncology that traditionally has received care at a variety of institutions. Recent data have shown that clinical trial involvement and patient outcomes in this age group may be influenced by the type of hospital at which they are treated. This article examines factors influencing the location of treatment of patients aged 15 to 19 years from selected areas in Ohio. Patients 15 to 19 years of age with malignancy from the selected 45 counties between 1996 and 1999 were identified from the Ohio Cancer Incidence and Surveillance System database. Factors analyzed included specific diagnosis, age, race, and treating institution. A total of 169 patients were identified, with 46.7% treated at pediatric institutions, 24.8% at adult academic centers, and 28.5% at community hospitals. Diagnosis influenced treatment location: leukemias, central nervous system tumors, and sarcomas were treated more often at pediatric hospitals, whereas melanoma was more often treated at adult academic centers. Patient age and distance from an academic center were also found to affect the location of treatment. Specific diagnosis, age, and geographic location influence the site of treatment of adolescent patients. Efforts to improve survival and increase enrollment in clinical trials must take these factors into account.

Screening for children's exposure to environmental tobacco smoke in a pediatric primary care setting.

BACKGROUND: The American Academy of Pediatrics (Elk Grove Village, Ill) has recommended that pediatricians assess their patients' environmental tobacco smoke (ETS) exposure, but the specific questions most likely to identify children with high ETS exposure are not known. Cotinine is a nicotine metabolite, present in hair, that can be used to quantify months of ETS exposure. OBJECTIVE: To develop a brief screening tool that will accurately predict ETS exposure as defined by child hair cotinine level. METHODS: We compared the performance of a series of easily administered screening questions regarding home ETS exposure to child hair cotinine levels. Subjects were a convenience sample of healthy children aged 2 weeks to 3 years of both self-reported smokers and nonsmokers. RESULTS: Hair samples and questionnaire data were obtained from 291 children. Based on clinical applicability and statistical significance, 3 questions ("Does the mother smoke?", "Do others smoke?", and "Do others smoke inside?") were selected as a valid screening tool to determine children's ETS exposure risk. Maternal report of smoking outside only or smoking few cigarettes per day had no impact on child hair cotinine levels. CONCLUSIONS: It was possible to derive a simple, specific, and valid screening tool that can be used in pediatric offices to identify children at risk for ETS exposure. Further research is needed to test this tool prospectively.

Baseline bone mineral density of the total lumbar spine may predict for chemotherapy-induced ovarian failure.

Age at treatment and the total cumulative dose of cyclophosphamide are established predictors of chemotherapy-induced ovarian failure in premenopausal women with breast cancer. In a prospective trial of 49 women receiving adjuvant chemotherapy, we sought to identify whether other factors including family history of osteoporosis, lifestyle factors, reproductive hormones, bone turnover markers, or bone mineral density (BMD) of the hip or total spine measured before (baseline) and 6 months after chemotherapy increased the risk of ovarian failure. Univariate logistic regression analyses were used to identify the variables related to the risk of ovarian failure, and a multivariate logistic regression model was used to find the best of predictors of ovarian failure among the variables. In the multivariate model a higher total spine BMD at baseline (OR=6.0, p=0.02, 95% CI 1.4-27.3), and a 10% change in estradiol (E2) from baseline to six months (OR=0.80, p=0.02, 95% CI 0.67-0.97) were predictive of ovarian failure adjusted for age. In particular, as total spine BMD at baseline increases by 0.1 g/cm2 the odds of developing chemotherapy-induced ovarian failure increases by 6-fold. The multivariate model provides a good fit to the data (GOF p-value=0.8852), and provides excellent discrimination between those women who will and will not develop ovarian failure (Area under ROC=0.9487). If confirmed in larger data sets, using baseline spinal BMD to identify women who are at higher risk of developing ovarian failure independent of their age would be of value.

Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck.

BACKGROUND: Cancer testis antigens (CTAs) are T-cell-defined tumor-associated antigens encoded by the genes and gene families such as MAGE, NY-ESO-1, and others. Their expression in a wide variety of malignant neoplasms but absence in all normal adult tissue except testicular germ cells makes them attractive targets for immunotherapy of cancer. Primary mucosal melanomas of the head and neck (HNMM) are rare aggressive malignant tumors that are usually difficult to treat. CTAs may provide useful targets for therapy; however, their expression in HNMM is not known. METHODS: We analyzed 40 initial, 15 recurrent, and 15 metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30; sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with monoclonal antibodies 57B, CT7-33, and ES121 to the following CTAs: MAGE-A4, CT7 (MAGE-C1), and NY-ESO-1, respectively. RESULTS: CT7, MAGE-A4, and NY-ESO-1 expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the tumors expressing at least one of the CTAs. CT7 and MAGE-A4 were significantly more frequently expressed in tumors composed of epithelioid cells than spindle cells (p = .05). CTA expression did not correlate with disease progression, overall survival, and disease-specific survival. CONCLUSIONS: CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy. The expression does not seem to have prognostic significance.

Comparison between malignant and nonmalignant splenic masses in dogs using contrast-enhanced computed tomography.

The ability of computed tomography (CT) to distinguish malignant from nonmalignant splenic masses was evaluated in 21 dogs with 24 masses. CT scans of the abdomen were performed pre- and postintravenous contrast medium administration before splenectomy or euthanasia. Splenic masses were evaluated objectively based on Hounsfield units (HU) and volume. Subjective criteria included location within the spleen (head, body, or tail), margination, homogeneity, and attenuation compared to the remaining splenic parenchyma. Characteristics of malignant and nonmalignant masses were compared. The nonmalignant masses were divided into splenic hematomas and nodular hyperplasia for further analysis. Fourteen (58.3%) of the masses were nonmalignant; 10 (41.7%) were malignant. Malignant splenic masses had significantly lower attenuation values, measured in HU, than nonmalignant splenic masses, on both pre- and postcontrast images (P<0.05). On postcontrast images, there was a significant difference in attenuation characteristics among all three subsets of splenic masses (malignant, hematoma, hyperplasia), with nodular hyperplasia having the highest HU values (90.3), hematomas having intermediate HU values (62.5), and malignant splenic masses having the lowest HU values (40.1). A receiver operator characteristic curve of postcontrast medium HU values revealed 55 as the best threshold value to distinguish malignant from nonmalignant masses, with those less than the threshold value being malignant. Abdominal CT is a useful diagnostic imaging modality for evaluation of focal canine splenic masses, with a significant difference in imaging characteristics between malignant and nonmalignant masses.

Digital fluoroscopic excretory urography, digital fluoroscopic urethrography, helical computed tomography, and cystoscopy in 24 dogs with suspected ureteral ectopia.

The purpose of this study was to determine the diagnostic utility of helical computed tomography (CT) for the diagnosis of ectopic ureters in the dog and to compare these findings with those of digital fluoroscopic excretory urography and digital fluoroscopic urethrography. Ureteral ectopia was confirmed or disproved based on findings from cystoscopy and exploratory surgery or postmortem examination. Of 24 dogs (20 female, 4 male) evaluated, 17 had ureteral ectopia. Digital fluoroscopic excretory urography and CT correctly identified ureteral ectopic status and site of ureteral ectopia (P < .05). Urethrography did not reliably detect ureteral ectopia. No false-positive diagnoses of ureteral ectopia were made in any of the imaging studies. Cystoscopic findings significantly agreed with findings during surgery in determining ureteral ectopic status and ectopic ureter site. One false-positive cystoscopic diagnosis of unilateral ureteral ectopia was made in a male dog. Kappa statistics showed better agreement between CT and both cystoscopy and surgical or postmortem examination findings with regard to presence and site of ureteral ectopia compared with other imaging techniques. CT was more useful than other established diagnostic imaging techniques for diagnosing canine ureteral ectopia.

Computed tomographic densitometry of normal feline thyroid glands.

We studied the computed tomographic (CT) appearance and determined Hounsfield units (HU) for normal thyroid tissue in eight cats. Helical CT images (2 mm collimation) were acquired from cranial aspect of the second cervical vertebra (C2) through caudal aspect of the fourth cervical vertebra (C4). Data were acquired before contrast medium administration (n = 7), after delayed contrast medium enhancement (n = 8), and immediately after contrast medium enhancement after a second dose of contrast medium (n = 8). Attenuation of thyroid tissue was compared with surrounding tissues. Before contrast medium enhancement, thyroid tissue was hyperattenuating to the surrounding soft tissues. After delayed contrast medium enhancement, thyroid tissue was hyperattenuating to surrounding soft tissues and isoattenuating to contrast medium-laden blood vessels. Immediately after contrast medium enhancement, thyroid tissue was hyperattenuating to surrounding soft tissues and hypoattenuating to contrast medium-laden blood vessels. The thyroid glands were dorsolateral to the trachea, ovoid, and displayed homogenous contrast medium enhancement. Circular regions of interest were drawn on the right and left thyroid lobes. Densitometric data of thyroid tissue were as follows: precontrast medium enhancement, 123.2 HU (95% CI: 119.4-127.1 HU); delayed contrast medium enhancement, 132.1 HU (95% CI: 127.4-136.8 HU); immediate postcontrast medium enhancement, 168.5 HU (95% CI: 163-173.9 HU). Normal feline thyroid tissue is easily detected using CT without contrast medium enhancement. This information may be useful for CT evaluation of abnormal feline thyroid glands.

Leg tourniquets modify the on-kinetics of oxygen uptake during cycle exercise.

PURPOSE: Obstructive cardiovascular disease decelerates the on-kinetics of the body's oxygen uptake rate (VO2), either by reducing the O2 delivery or by degrading the exercise capacity of skeletal muscle. This study sought to determine whether obstructed blood flow decelerates the on-kinetics of VO2 by reducing O2 delivery. METHODS: Breath-by-breath measurements of VO2 were studied in eight healthy youth (age, 16.5 +/- 0.6 years) during two-legged square-wave exercise on the cycle ergometer. The square protocol was 5 minutes of unloaded exercise followed by an immediate increase to 5 minutes of loaded exercise at 78 +/- 5 W. In the experimental trials, thigh cuffs were inflated 30 seconds before the onset of loaded exercise. Control trials replicated the square-wave exercise with deflated thigh cuffs. RESULTS: The on-kinetics of VO2 were biphasic in the control trial and triphasic in the experimental trial. Experimental VO2 was significantly higher than control values in the final 90 seconds of exercise (P<.05). CONCLUSIONS: The difference between experimental and control VO2 was attributable to inflated thigh cuffs. At no time was experimental VO2 significantly lower than control VO2. The clinical implication of the results is that skeletal myopathy, not reduced blood flow, is essential for decelerating the VO2 on-kinetics of patients with obstructive vascular disease. The warranted conclusion is that square-wave exercise with inflated thigh cuffs stimulates a third phase of VO2 on-kinetics.

Height loss and osteoporosis of the hip.

Osteoporosis of the hip is associated with hip fracture, a devastating outcome on both an individual and aggregate basis. Height loss is a frequent manifestation of vertebral osteoporosis and is simple to evaluate in the clinical setting. The goal of this study was to determine whether height loss is significantly associated with low bone mineral density at the femur, using a retrospective review of cross-sectional data from 2108 women referred for a bone density scan. Collected data included self-reported maximum adult height, current height, and total hip bone mineral density, along with other demographic and risk factor information. We then investigated the relationship between height loss and osteoporosis using multinomial logistic regression modeling. We found that height loss of 2 in. or more is a highly significant predictor of osteoporosis at the hip. In particular, the odds women had osteoporosis at the hip, as determined by total hip bone mineral density, increased 4.4 times (95% confidence interval, 2.6-7.4) if the women had lost > or = 2 but < 3 in. of height. In addition, women with at least 3 in. of height loss had odds of osteoporosis of the hip that were 9.6 times greater (95% confidence interval, 4.8-19.2) than women with less than an inch of height loss. These odds ratios were adjusted for the confounding variables of age, weight, and maximum adult height. Our findings suggest loss of height may be an important clue in detecting osteoporosis of the hip, implying that evaluation of height loss should be routine in the outpatient setting.

Active and passive tobacco smoke exposure: a comparison of maternal and child hair cotinine levels.

The objective of this study was to compare tobacco smoke exposure in mothers and their healthy children less than 3 years old using hair cotinine (HC) levels as an objective long-term measure of exposure. Hair samples were obtained from mother/child pairs recruited from the Columbus Children's Hospital Primary Care Center, and were analyzed by radioimmunoassay to compare HC levels. Mothers were both self-reported smokers and nonsmokers. Contributing and confounding variables were assessed based on questionnaires completed by participants. Exclusion criteria for children were prematurity and presence of chronic cardiopulmonary disease. Hair samples and questionnaires were obtained from 104 mother/child pairs. Child and maternal HC levels were correlated for both self-reported maternal smokers (R2 = .13, p < .013) and self-reported maternal nonsmokers (R2 = .54, p < 001). Child HC levels were higher than maternal HC levels (1.18 ng/mg vs. .78 ng/mg, p < .001). Children of nonsmokers had higher HC levels than their mothers (.77 ng/mg vs. .35 ng/mg, p < .001), while HC levels of smokers and their children were no different (1.91 ng/mg vs. 1.92 ng/mg, p = .978). The relationship between child and maternal HC did not differ by child age, gender, or race. In conclusion, environmental tobacco smoke exposure in young children as reflected by HC is higher than expected based on prior studies of biomarkers and passive tobacco smoke exposure in adult nonsmokers.

Older women with breast carcinoma are less likely to receive adjuvant chemotherapy: evidence of possible age bias?

BACKGROUND: Older women with breast carcinoma are less likely than younger women to receive adjuvant chemotherapy. The authors hypothesized that after controlling for confounders (i.e., variables related to both age and chemotherapy use) and effect modifiers (i.e., variables that have a significant interaction with age), age would become a less significant factor for predicting adjuvant chemotherapy use. METHODS: Data on 480 women with localized breast carcinoma were entered into the National Comprehensive Cancer Network database at The Ohio State University Medical Center. Women were divided into 3 groups: women age < 50 years (n = 143 [30%]), women ages 50-65 years (n = 216 [45%]), and women age > 65 years (n = 121 [25%]). Chi-square and Wilcoxon rank sum tests were used for univariate analyses of the variables of interest, and logistic regression was used for multivariate analyses. RESULTS: After adjustment for confounders (stage, tumor size, progesterone receptor status, and lymph node involvement) and effect modifiers (namely, estrogen receptor [ER] status), the odds of not receiving chemotherapy for women ages 50-65 years and women age > 65 years with ER-positive breast carcinoma were approximately 6 (odds ratio [OR], 6.4; 95% confidence interval [CI], 3.1-13.3; P < 0.001) and 62 (OR, 62.4; 95% CI, 21.8-178.7; P < 0.001) times greater, respectively, than the odds for women age < 50 years. Women ages 50-65 years with ER-negative breast carcinoma were not significantly different from women age < 50 years with respect to chemotherapy use (OR, 1.9; 95% CI, 0.5-7.3; P = 0.374). However, the odds of not receiving chemotherapy for women age > 65 years with ER-negative breast carcinoma were 7 times (OR, 6.7; 95% CI, 1.5-30.6; P = 0.013) greater than the odds for women age < 50 years. CONCLUSIONS: The results of the current study indicate that based on older age alone, women are less likely to receive adjuvant chemotherapy. In addition, the results suggest that age bias may contribute to undertreatment and lack of accrual of older women into clinical trials.

Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract.

OBJECTIVE: Primary mucosal melanomas are rare tumors. We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor. METHODS: Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa. RESULTS: The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively). The former had a remarkable male predilection (28 men, 8 women), while the latter affected both sexes equally (29 men, 30 women). The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P =.008) and were more frequently amelanotic (14 vs 12, P =.049) than sinonasal melanomas. The sinonasal melanomas were frequently thicker (median thickness, 9 vs 2.6 mm), polypoid (29 vs none), ulcerated (57 vs 20), and necrotic (57 vs 14) than oral melanoma (P <.001). Pseudopapillary architecture was more frequent in sinonasal melanomas (16 tumors vs none, P <.001), and desmoplastic melanomas were more frequent in the oral mucosa (6 vs 1, P =.005). Sinonasal melanoma showed vascular and deep tissue invasion more frequently than oral melanoma; however, no significant difference in disease-specific survival was noted (median survival, 2.8 years vs 3.0 years; 5-year survival, 37% vs 35%, respectively). CONCLUSION: Sinonasal melanomas demonstrated aggressive morphologic features significantly more frequently than oral melanomas; however, prognosis remained similar in both groups.

Evaluation of an ear cleanser for the treatment of infectious otitis externa in dogs.

Thirty-one ears (16 dogs) with otitis externa originating from bacterial or yeast infections were enrolled in a study to evaluate the in vivo efficacy of an ear cleanser containing 2.5% lactic acid and 0.1% salicylic acid for the treatment of infectious otitis externa. The affected ears were treated with the ear cleanser twice daily for 2 weeks and evaluated after 1 and 2 weeks of treatment. The ear cleanser was effective in resolution of infection in 67.7% of the ears, and clinical signs of infectious otitis externa were significantly reduced within 2 weeks.

Effect of phosphate binders on supplemental iron absorption in healthy subjects.

A single-dose, prospective, randomized, four-treatment, four-period crossover study was conducted to determine the acute effect of therapeutically equivalent doses of three commonly used phosphate binders on oral iron absorption. Twenty-three healthy subjects received 65 mg of elemental iron alone and with each phosphate binder (calcium carbonate 3000 mg, calcium acetate 2668 mg, or sevelamer HCl 2821 mg). Area under the change in plasma iron concentration-time curve over 6 hours postdosing was measured. ANOVA was used to assess the statistical significance of differences in iron absorption among the treatments. The relative bioavailability of iron administered with each phosphate binder compared to iron administered alone was estimated. The relative iron bioavailabilities (95% confidence intervals) for the calcium carbonate, calcium acetate, and sevelamer HCI treatments were 0.81 (0.70, 0.94), 0.73 (0.63, 0.85), and 0.90 (0.78, 1.05), respectively. Thus, single doses of both calcium-based phosphate binders significantly reduced single-dose iron absorption, while sevelamer HCl did not.

Prognostic factors for malignant melanoma of the squamous mucosa of the head and neck.

Primary malignant melanomas of the squamous mucosa of the head and neck are rare. To learn more about the prognostic significance of various histologic parameters we examined the pathologic features of squamous mucosa from 40 patients seen at a single institution and correlated them with clinical outcome. Follow-up information was available on 37 patients. Thirty-five were treated with surgical resection and two were treated with radiotherapy. Twenty-six were dead at follow-up. Twenty-one of them died of disease. The interval between diagnosis and death ranged from 1 month to 16.5 years (median survival, 2.4 years). Eleven patients were alive at 4 months to 19.5 years after the diagnosis: six of them with disease and five of them free of disease (mean follow-up, 3.5 years). Predictors of poor survival by univariate analysis were the presence of vascular invasion (overall survival, p = 0.007; disease-specific survival, p = 0.01), a polymorphous tumor cell population (overall survival, p = 0.007; disease-specific survival, p = 0.008), and necrosis (overall survival, p = 0.007; disease-specific survival, p = 0.056). However, because these three parameters were associated with each other, none of them remained of independent predictive value for outcome by multivariate analysis. No prognostic significance was found for tumor thickness, level of invasion, ulceration, mitotic index, or nerve/nerve sheath involvement. Thus, the histologic parameters relevant for the prognosis of squamous mucosa differ significantly from those of cutaneous melanomas.