Clinical Impact of Pathological Features Including the Ki-67 Labeling Index on Diagnosis and Prognosis of Adult and Pediatric Adrenocortical Tumors.

Adrenocortical tumors (ACT) in the adult and pediatric population are generally considered distinct entities due to differences in molecular events related to tumorigenesis, clinical presentation, and outcome. Furthermore, pathological criteria used for diagnosis and prognostication of ACT in adults are usually inadequate for predicting the biological behavior of ACT in children. Here, we analyzed 146 adult and 44 pediatric (< 15y/o) ACT with long-term clinical follow-up and furthered current evidence on the clinical and pathological differences between pediatric and adult tumors. Predilection for female over male gender was observed in both cohorts, but more so in adults (84% vs. 61%, p = 0.003). Cushing syndrome was more frequent in adults (p < 0.001), whereas virilization, either isolated (p < 0.001) or combined to Cushing (p = 0.047), was more common in children. The Ki67 labelling index (LI) of pediatric adenomas and carcinomas was much higher than their corresponding tumors in adults (p < 0.001). Despite these differences, pathological analyses including the evaluation of Ki67 greatly improved patient prognostication in both age cohorts. Indeed, increased Weiss scores and Ki67 indexes correlated with poor overall- and disease-free survival in adult patients with carcinoma. Among the proliferative indexes tested, Ki67 LI ≥ 10% showed the highest hazard ratio (HR) for recurrence and the Ki67 LI ≥ 3% showed the highest HR for survival. In pediatric tumors, the Wieneke score (p < 0.001) and the Ki67 LI (p < 0.001) showed high accuracy for predicting biological behavior, and increased scores/indexes correlated with worse overall and disease-free survival. In this age cohort, Ki67 LI < 10% was able to rule out malignant behavior, whereas Ki67 LI ≥ 15% may be used to predict the patients with higher risks of recurrence and/or poor outcome.

External validation of the AJCC Cancer Staging Manual, 8th edition, in an independent cohort of oral cancer patients.

OBJECTIVES: To evaluate the new American Joint Committee on Cancer (AJCC) cancer staging manual (8th edition) in an independent cohort of patients surgically treated for oral squamous cell carcinoma in order to determine whether the upstaging of pT and pN classification was indicative of a worse prognosis. METHODS: A cohort of 298 patients was analyzed retrospectively. RESULTS: Of these patients, 22.8% received an upstaging when the depth of invasion was included into the pT classification. Similarly, 29.2% of them were upstaged when extracapsular extension was added to pN classification. Twenty-eight of 68 patients (41.2%) that received an upstaging of pT classification died, and 23 (33.8%) experienced disease recurrence compared to 98/229 (42.8%) and 68/229 (29.7%), respectively, for those with the same pT during follow-up. With regard to pN classification, 70.6% of upstaged patients (60/85) died, and 50.6% (43/85) developed recurrence of the disease compared to 63/205 (30.7%) and 42/205 (20.5%), respectively, for those with the same pN during follow-up. Patients who were upstaged in pT classification presented a worse DFS (51.1% versus 80.4%, P=0.007) and OS (31.5% versus 58.6%, P=0.017). Similarly, those that were upstaged in pN classification presented a worse DFS (17.1% versus 61.2%, P=0.001) and OS (8.5% versus 37.9%, P<0.001). CONCLUSION: The new AJCC cancer staging manual (8th edition) allows a better stratification of oral SCC patients. By including the depth of invasion to the pT classification and extranodal extension to the pN classification, a worse disease-free and overall survival was assessed for these patients.

DEATH RELATED TO PULMONARY METASTASIS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

OBJECTIVE: The purpose of the present study was to investigate the predictive factors for shorter disease-specific survival in patients with pulmonary disease secondary to differentiated thyroid cancer (DTC). METHODS: This was a retrospective cohort study conducted over a 5-year period that included 54 patients with pulmonary disease secondary to DTC during the follow-up. Among these patients, 13 (24.1%) died from the disease. Dedifferentiation characteristics were identified at pathological examination of the metastatic disease (lymph node or distant metastases) and was defined as the abrupt transformation of a well-differentiated tumor into high-grade morphology lacking the original distinct histologic characteristics. RESULTS: Tumor dedifferentiation marked by cellular aberrations and radioiodine (RAI) therapy resistance occurred in 5 (9.3%) patients. Four of them died due to pulmonary progression (80.0%), and the median survival of this group was 30 months compared to 279 months in the patients without dedifferentiation. The cumulative disease-specific survival was 20.0% in the patients with dedifferentiation during the follow-up versus 46.1% among the cases without this condition (P = .003, log-rank test). Moreover, dedifferentiation was independently associated with shorter disease-specific survival (hazard ratio [HR] = 31.607; 95% confidence interval [CI]: 4.815-207.478; P<.0001, Cox regression model) as were age over 45 years (HR = 10.904; 95% CI: 1.145-103.853; P = .038) and male sex (HR = 4.210; 95% CI: 1.056-16.783; P = .042). CONCLUSION: DTC patients with pulmonary disease exhibited shorter disease-specific survival, particularly those who developed tumor dedifferentiation, and these patients require special attention during follow-up. ABBREVIATIONS: CI = confidence interval DTC = differentiated thyroid cancer FTC = follicular thyroid carcinoma HR = hazard ratio IQR = interquartile range LN = lymph node LR = likelihood ratio PTC = papillary thyroid carcinoma RAI = radioiodine pTNM = pathologic tumor-node-metastasis stage system.

Tumor thickness as a predictive factor of lymph node metastasis and disease recurrence in T1N0 and T2N0 squamous cell carcinoma of the oral tongue.

OBJECTIVE: The aim of the study was to compare the thickness of primary tumors with the frequency of nodal metastases and survival in patients surgically treated for T1/T2N0 oral tongue squamous cell carcinoma. STUDY DESIGN: This is a retrospective longitudinal study with 74 patients. RESULTS: None of the patients with a tumor thickness (TT) ≤ 7 mm presented with nodal metastasis, whereas 25 of the patients with a TT > 7 mm (51.0%) developed metastases (P < .0001). Multivariate analysis showed that TT > 7 mm was a risk factor for occult nodal metastasis (odds ratio = 8.7; P = .002) with 81.9% accuracy. TT > 10 mm was also a predictive factor of worse disease-free survival in these patients (hazard ratio = 12.2; P = .003). CONCLUSIONS: Tumor thickness of greater than 7 mm is predictive of a higher incidence of lymph node metastasis, and a TT > 10 mm is predictive of worse disease-free survival in squamous cell carcinoma of the oral tongue.

Primary bone lymphoma in 24 patients treated between 1955 and 1999.

The authors present their experience in the treatment of 24 patients with primary bone lymphoma. Eighty-one patients treated between 1955 and 1999 were evaluated, and 57 were excluded because of misdiagnosis. The male to female ratio was 7:5 and the median age was 38.5 years (range, 18-69 years). Two patients had human immunodeficiency virus. Seventeen patients had intermediate-grade lymphomas (Working Formulation), nine patients had centroblastic subtype (Kiel), and 22 patients had B immunophenotype. Nine patients had combined treatment with chemotherapy and radiation therapy, and nine patients had chemotherapy alone. The mean followup was 13.2 years (range, 1.5-37.3 years). Three patients had surgery, two because of subtrochanteric fractures (one patient had closed reduction and internal fixation and the other patient had resection and endoprosthesis reconstruction). The third patient presented with myelocompression at the thoracic level, and he had decompression surgery. Only one patient had radiation therapy and two patients had no treatment. There have been no local recurrences in 17 patients (70.8%). Seven patients (29.2%) died with evidence of disease within a followup of 11 months. The results of the current study showed that patients with primary bone lymphoma have a good prognosis when they are treated with chemotherapy, regardless of whether radiation therapy was given. Surgery usually is appropriate for patients with fractures.