Plasma growth differentiation factor-15 is an independent marker for aggressive disease in endometrial cancer.

OBJECTIVE: Better biomarkers are needed in order to identify patients with endometrial carcinoma at risk of recurrence and who may profit from a more aggressive treatment regimen. Our objective was to explore the applicability of plasma growth differentiation factor 15 (GDF-15) as a marker for recurrent disease, as well as a marker for poor prognosis and lymph node metastases. METHODS: EDTA-blood samples were obtained from 235 patients with endometrial cancer before primary surgery. For 36 of these patients, matching blood samples were collected at time of recurrence. Blood samples were also collected from 78 patients with endometrial hyperplasia. Plasma GDF-15 was measured by an enzyme-linked immunosorbent assay (ELISA). Preoperative pelvic MRI scans for 141 patients were investigated in parallel for imaging variables. RESULTS: Preoperative plasma level of GDF-15 was significantly higher for patients who experienced recurrence (1780 ng/L; 95% CI; 518-9475 ng/L) than for patients who did not develop recurrent disease (1236 ng/L; 95% CI; 307-7030 ng/L) (p<0.001). Plasma levels of GDF-15 at recurrence (2818 ng/L, 95% CI 2088-3548 ng/L) were significantly higher than plasma levels of GDF-15 measured at time of primary diagnosis (1857 ng/L, 95% CI; 1317-2398 ng/L) (p = 0.001). High plasma level GDF-15 independently predicts recurrent disease (OR = 3.14; 95% CI 2.10-4.76) and lymph node metastases (OR = 2.64; 95% CI 1.52-4.61). Patients with high plasma level of GDF-15 had significantly larger tumor volume (p = 0.008). CONCLUSION: Elevated plasma level of GDF-15 is associated with aggressive disease and lymph node metastasis in endometrial carcinoma. GDF-15 may be helpful in indicating recurrent disease.

Abnormal Muscularization of Intra-acinar Pulmonary Arteries in Two Cases Presenting as Sudden Infant Death.

Abnormal muscularization of acinar arteries is the hallmark of persistent pulmonary hypertension of newborn (PPHN), an uncommon disease with high rate of morbidity and mortality. PPHN presents with signs of respiratory distress immediately following birth. We herein report 2 cases presenting as a witnessed sudden unexpected death in the late neonatal period, preceded by respiratory deterioration and in whom the presence of abnormal muscularization of the acinar pulmonary arteries was reminiscent of PPHN. The significance of this report is twofold: to increase the awareness among pediatricians and pathologists of this feature that can present in some cases of Sudden Unexpected Death in Infancy/Sudden Infant Death Syndrome, and to highlight the importance of performing a thorough autopsy in order to identify the abnormality.

Primitive neuroectodermal tumour of the kidney with vena caval and atrial tumour thrombus: a case report.

INTRODUCTION: Renal primitive neuroectodermal tumour is an extremely rare malignancy. CASE PRESENTATION: A 21-year-old woman presented with microscopic haematuria, a palpable right loin mass, dyspnoea, dizziness and fatigue. Initial ultrasound scan of the kidneys revealed an 11 cm right renal mass with venous extension into the inferior vena cava. Computed tomography of the thorax and abdomen revealed an extension of the large renal mass into the right renal vein, inferior vena cava and up to the right atrium. A small paracaval lymph node was noted and three small metastatic nodules were identified within the lung parenchyma. The patient underwent a radical nephrectomy and inferior vena caval tumour (level IV) thrombectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Immunohistochemical staining of the specimen showed a highly specific cluster of differentiation (CD) 99, thus confirming the diagnosis of a primitive neuroectodermal tumour. CONCLUSION: It is important that a renal primitive neuroectodermal tumour be considered, particularly in young patients with a renal mass and extensive thrombus.

Carcinoma ex benign pleomorphic adenoma of the parotid gland.

BACKGROUND: Carcinoma in pleomorphic salivary adenoma is a common histologic subtype of primary parotid malignancy. METHODS: In this study, 28 patients (predominantly male) with histologically diagnosed carcinoma in pleomorphic salivary adenoma presenting over 10 years were retrospectively reviewed. RESULTS: Only 25 percent of patients had a previously treated pleomorphic salivary adenoma. Although the presenting features suggested malignancy in some cases, overall they were nonspecific, overlapping with the presentation of benign disease. Preoperative investigations included fine needle aspiration cytology, which was only 29-percent sensitive, and computed tomography and/or magnetic resonance imaging. There were 14 superficial and 12 total or radical parotidectomies. The facial nerve was resected en bloc with the tumor in nine cases and immediately reconstructed with good reanimation results in patients with recent-onset facial paresis. Only 44 percent of patients had a complete histologic tumor clearance, and this was the most significant determinant of survival (p < 0.01, log-rank analysis). The locoregional control rate was 66 percent at 5 years, but recurrent disease proved invariably fatal. Five-year disease-specific survival was 44 percent with a high rate of disease-specific mortality (87 percent). CONCLUSIONS: Carcinoma in pleomorphic salivary adenoma is very difficult to diagnose preoperatively. Fine needle aspiration cytology had a disappointingly low sensitivity for this tumor, potentially misdirecting surgical management. While good locoregional disease control could be achieved with surgery and radiotherapy, carcinoma in pleomorphic salivary adenoma was shown to be aggressive with a high disease-specific rate of mortality. Given that incomplete tumor resection was the most important prognostic factor, a high index of clinical suspicion, radical ablative surgery, and immediate soft-tissue and nerve reconstruction for proven cases are advocated.

Iris melanocyte numbers in Asian, African American, and Caucasian irides.

PURPOSE: The anatomical basis for iris color has long been a controversial issue in ophthalmology. Recent studies demonstrated that in Caucasians, blue-eyed, gray-eyed, and hazel-eyed individuals have comparable numbers of iris melanocytes. The present investigation was carried out to compare melanocyte numbers in the irides of Asian, African American, and Caucasian brown-eyed individuals. METHODS: Paraffin-embedded sections from 71 brown-colored irides were incubated with rabbit anti-cow antibody against S100a, linked with an FITC conjugate antibody, and counterstained with Evans blue. Cells were counted under a fluorescence microscope and scored as melanocytes or other cells. Cell number, density, and iris area were calculated for each specimen. RESULTS: Caucasian and African American irides had comparable mean total melanocyte numbers. Asian irides had fewer total melanocytes than African American (P = .042) and Caucasian (P = .001) irides and smaller total number of cells (ie, melanocytes plus other cells) than African American (P = .054) or Caucasian (P = .009) irides. CONCLUSIONS: There is a statistically significant smaller mean total melanocyte number and mean total cellularity in Asian irides as compared to Caucasian and African American irides. This difference appears to be due to the combination of smaller iris area and lower melanocyte density in the Asian irides. The possibility exists that this may be a factor in ethnic variations in certain ocular diseases.