CD33+ CD14- phenotype is characteristic of multinuclear osteoclast-like cells in giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a benign bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. GCTB is composed of uniformly distributed osteoclastic giant cells, thought to originate from the fusion of monocyte-macrophage lineage cells, in a background consisting of mononuclear rounded cells and spindle-shaped cells. Several reports showed the specific expression of markers, such as CD14 on the mononuclear rounded cell population, however, lacking osteoclastic giant cells. Blood monocytes that were CD14+, CD33+, or CD14+/CD33+ have also been shown to be programmed as pre-osteoclasts. The macrophage marker CD33 is expressed earlier than CD14 in macrophage maturation, whereas CD14 is expressed longer than CD33. The aim of this study was to investigate CD14/CD33 expression profiles in GCTB. Nineteen GCTB tumor samples of 19 patients were studied. Immunofluorescent analyses were performed with monoclonal antibodies against CD14, CD33, RANK, and CD51. To unambiguously further prove the expression of these molecules, quantitative RT-PCR was used with subsequent sequencing of its products. All samples showed similar immunoreactivity profiles. The mononuclear rounded cell population was positive for RANK, CD51, CD14, and CD33. The osteoclastic giant cell population expressed RANK and CD51, as well as CD33, but was consistently negative for CD14 expression. The CD14 and CD33 profiles were confirmed by quantitative RT-PCR. These RT-PCR products were sequence verified. Osteoclasts in GCTB are the result of fusion of CD33-expressing pre-osteoclasts that further fuse with CD14+ mononuclear cells. Although these results reflect a static rather than a dynamic spectrum, we strongly believe that osteoclastogenesis seems not to be the exclusive result of fusion of intratumoral CD14+ mononuclear cells. Moreover, CD33-modulated osteoclastogenesis opens up the possibility for novel therapeutic directions.

Esophageal endoscopic ultrasound with fine-needle aspiration with an on-site cytopathologist: high accuracy for the diagnosis of mediastinal lymphadenopathy.

STUDY OBJECTIVES: To analyze the accuracy of esophageal endoscopic ultrasound (EUS) with real-time, guided fine-needle aspiration (EUS-FNA) with an on-site cytopathologist in patients with (presumed) lung cancer presenting with mediastinal lymphadenopathy (ML) or a suspect left adrenal gland (LAG). DESIGN: A single-center prospective study. PATIENTS: Sixty-seven outpatients with (presumed) lung cancer with ML or a suspect LAG on either CT and/or positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) scan. INTERVENTIONS: All patients underwent EUS-FNA under conscious sedation. A cytopathologist was present during all procedures. MEASUREMENTS: EUS with and without fine-needle aspiration (FNA) as compared to FDG-PET was evaluated for accuracy in diagnosing cancer, safety, and rate of avoidance for further surgery. RESULTS: Of 67 consecutive patients (56 men; median age, 64 years), malignant ML or LAG were found in 47 patients (70.1%). In 20 patients (29.9%) without EUS-FNA proof of malignancy, confirmation was obtained by surgical procedure in 13 patients (sarcoidosis [n = 5], infection [n = 1], lung cancer [n = 7]) or by clinical follow-up in 5 patients suggesting benign disease. Sixty-five patients were included in the calculation of test characteristics. With malignancy as an end point, the accuracy for EUS-FNA was 100%. This was better than EUS without FNA (accuracy, 75.4%; p < 0.001) or FDG-PET (accuracy, 75.0% [n = 28]; p = 0.0011). When using final histopathologic diagnosis as an end point, the accuracy of EUS-FNA was 92.3%, since EUS-FNA was unable to show noncaseating granulomas in those patients with sarcoidosis diagnosed after mediastinoscopy. Related to the presence of the in situ cytopathologist, there were no inconclusive samples. No adverse events were recorded, and 67.7% of surgical interventions were avoided following EUS-FNA. CONCLUSIONS: The accuracy in this series of EUS-FNA with cytopathologist-assisted rapid on-site evaluation is high. The technique is safe and greatly reduces the number of surgical interventions.

The role of biological markers as predictors of response to preoperative chemotherapy in large primary breast cancer.

The aim of this prospective study was to evaluate biological markers, their correlation with response and outcome, and the change in these markers under the influence of preoperative chemotherapy (PCT) in patients with a large primary breast cancer. One hundred and thirty-five women were treated with PCT, followed by locoregional therapy and adjuvant treatment. Estrogen receptor (ER), progesterone receptor (PgR), HER-2, p53, and cathepsin D were determined by immunohistochemistry (IHC) before and after PCT. The overall response (OR) was 70% and the pathologic complete response (pCR) was 13%. Forty-four percent of the patients could be offered breast-conserving surgery (BCS). At a median follow-up of 50 mo the overall survival is 82% and the disease-free survival is 70%. No local recurrence (LR) has developed following BCS. Invasive ductal carcinoma (IDC) was more frequently ER-negative and HER-2-positive than invasive lobular carcinoma (ILC). P53-negative and ER-negative patients seemed to be more chemosensitive compared to p53-positive patients (74% vs 53%) and ER-positive patients (75% vs 65%), but this difference did not reach statistical significance. A trend toward higher complete pathologic remission rate was seen for ER-negative patients (p = 0.0609). PgR, HER-2, and cathepsin D were not related to response. The pattern of biological markers did not change with PCT, making repeated determination useless.