Accuracy of fine needle aspiration cytology in the pathological typing of non-small cell lung cancer.

BACKGROUND: Histological typing of non-small cell lung cancer (NSCLC) has an increasing clinical relevance due to the emerging differences in medical treatment between squamous and nonsquamous tumors. However, most NSCLCs are diagnosed in an advanced stage, and the diagnosis is often obtained exclusively by cytology either exfoliative or following fine needle aspiration. We investigated the accuracy of fine needle aspiration cytology (FNAC) in NSCLC typing as compared with histology. METHODS: Over the period 2000-2009, 1182 transbronchial needle aspirate or transthoracic needle aspirate samples were obtained from patients with suspicious thoracic lesions. In 474 patients, a cytological diagnosis of primary NSCLC was obtained, and 186 (39%) of them (108 transbronchial needle aspirates and 78 transthoracic needle aspirates) received a parallel or subsequent histologic diagnosis on endoscopic biopsy (112) or surgery (74). RESULTS: At cytology, 158 (85%) NSCLC cases were typed (89 adenocarcinoma and 69 squamous cell carcinoma), while 28 (15%) were classified as NSCLC not otherwise specified. At histology, 183 (98%) cases were typed (109 adenocarcinoma, 69 squamous cell carcinoma, 3 adenosquamous carcinoma, and 2 large cell carcinoma), and only 3 (2%) were classified as NSCLC not otherwise specified. Cytological and histological typing was concordant in 137 of 156 (88%) cases (K = 0.755; p < 0.001). The positive predictive value of FNAC in typing NSCLC was 92% for adenocarcinoma and 82% for squamous cell carcinoma. CONCLUSION: FNAC in expert hands is fairly accurate for typing NSCLC and can be regarded as an acceptable procedure for diagnostic and medical treatment planning purposes in most NSCLC cases, especially when more invasive approaches are unfeasible. In poorly differentiated and doubtful cases, the use of ancillary techniques, such as immunocytochemistry, may be required to improve the diagnostic yield.

Accuracy and relative value of bone marrow aspiration in the detection of lymphoid infiltration in non-Hodgkin lymphoma.

AIMS AND BACKGROUND: In hematologic malignancies, bone marrow aspiration is considered complementary to bone marrow biopsy for the detection of tumor infiltration. The present study evaluated the accuracy of bone marrow aspiration and the relative contributions of bone marrow aspiration and bone marrow biopsy in detecting bone marrow involvement by non-Hodgkin lymphomas. METHODS AND STUDY DESIGN: We compared 51 simultaneous marrow aspirates and core biopsies from non-Hodgkin lymphoma patients for sensitivity, specificity, concordance, quality and clinical relevance. RESULTS: The agreement level of bone marrow biopsy and bone marrow aspiration was 80%, and the overall sensitivity and specificity for bone marrow aspiration were 69% and 86%, respectively. When considering only the indolent non-Hodgkin lymphoma samples, the sensitivity of bone marrow aspiration was 82% and the specificity was 85%, whereas the sensitivity and specificity were 40% and 86%, respectively, in the aggressive non-Hodgkin lymphoma specimens. Five cases (10%) were reported in which bone marrow biopsy did not detect lymphoid infiltration even though the bone marrow aspiration was positive. In one of these, lymphoid infiltration was documented by a second bone marrow biopsy performed thereafter. CONCLUSIONS: The data from the current study show that bone marrow aspiration is a useful procedure with which to detect bone marrow infiltration by lymphoma. Although it cannot be a substitute for examination of the marrow by core biopsy, the utility of adding an aspirate to bone marrow biopsy is supported by its earlier and easier availability for bone marrow examination, the larger amounts of marrow that can be examined with both procedures, and the percentage, although small, of potentially true-positive bone marrow aspirates with negative biopsies.

Is cytology reliable for epidermal growth factor receptor gene evaluation in non-small cell lung cancer?

BACKGROUND: Epidermal growth factor receptor (EGFR) gene copy number has been proposed as predictor of response to epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer (NSCLC). METHODS: Cytologic and matched histologic samples from 33 primary non-small cell lung cancers were analyzed by fluorescence in situ hybridization (FISH) for epidermal growth factor receptor gene. RESULTS: FISH was positive in 52% and negative in 35% of the 31 matched evaluable samples. Four of 31 (13%) cases were discordant (K = 0.736; p < 0.001). CONCLUSION: Our data support the feasibility and reliability of epidermal growth factor receptor gene assessment by FISH on cytology.

Comparison between epidermal growth factor receptor (EGFR) gene expression in primary non-small cell lung cancer (NSCLC) and in fine-needle aspirates from distant metastatic sites.

PURPOSE: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently found to predict treatment outcome in non-small cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared with primary NSCLC. In all studies FISH have been performed on histologic material. The possibility to perform FISH analysis on cytologic material obtained by fine-needle aspiration from superficial and visceral metastases would allow us to know the real EGFR status avoiding invasive diagnostic procedures. METHODS: EGFR gene copy number was analyzed by FISH on fine-needle aspirates obtained from 31 patients with metastatic NSCLC and the results were compared with those obtained on corresponding paraffin histologic sections from the primary tumor. RESULTS: The feasibility of EGFR FISH on cytology was 90% (28 of 31 patients). EGFR FISH was positive in 61% (17 of 28 patients) of the metastases and in 36% (10 of 28 patients) of the primary tumors. Nine of the 28 cases (32%) were EGFR positive on both primary tumor and metastatic site and 10 (36%) were negative on both primary tumor and metastasis. Nine of the 28 cases (32%) showed discordance of primary tumor versus metastasis (McNemar test; p = 0.041). CONCLUSIONS: EGFR FISH can be reliably assessed on fine-needle aspirates obtained from NSCLC metastases. We found that EGFR gene copy number is discordant between primary NSCLC and the corresponding distant metastatic sites in a significant proportion of cases. These findings should be considered in future studies designed to elucidate the predictive role of EGFR FISH in NSCLC.

HER-2/neu evaluation by fluorescence in situ hybridization on destained cytologic smears from primary and metastatic breast cancer.

OBJECTIVE: To evaluate HER-2/neu amplification by fluorescence in situ hybridization (FISH) (HER-2/neu by FISH) on archival cytologic smears stained with May-Grünwald-Giemsa (MGG) stain. STUDY DESIGN: Cytologic specimens from 69 breast cancer lesions (48 primary and 21 metastatic), stained with MGG stain for routine diagnostic cytology, were destained and subjected to HER-2/neu by FISH. Fifteen of the 69 samples were also evaluated by FISH on paired fresh smears. RESULTS: HER-2/neu by FISH was successfully assayed in 25 of the 48 primary tumors and in 15 of the 21 metastatic lesions, corresponding to an overall feasibility of 58%. These cases had been archived between 1 month and 10 years prior to FISH analysis. Eight of the 25 primary and 5 of the 15 metastatic tumors were amplified. In 15 of the 40 evaluable cases, HER-2/neu was also assessed on the corresponding fresh smears: 8 tumors were amplified and 7 unamplified on both destained MGG and fresh smears. CONCLUSION: HER-2/neu can be detected by FISH on routinely MGG-stained cytologic slides. This approach allows HER-2/neu evaluation whenever histologic sections or fresh cytologic material are not available. In these cases, HER-2/neu assessment on destained cytologic smears plays a role in the selection of targeted therapy.

HER-2/neu amplification by fluorescence in situ hybridization in cytologic samples from distant metastatic sites of breast carcinoma.

BACKGROUND: Amplification of the HER-2/neu oncogene has been proposed as a target for antibody-based therapies and as a predictor of chemoresponsiveness in advanced breast carcinoma. Few studies have concentrated on HER-2/neu gene evaluation by fluorescence in situ hybridization (FISH) on distant metastatic sites and none have been performed on cytologic samples. The current study evaluated HER-2/neu amplification by FISH on cytologic samples obtained from distant metastatic lesions of breast carcinoma to update HER-2/neu characterization through a safe and easier procedure than biopsy. METHODS: Twenty-two cytologic samples from distant metastases (12 hepatic samples, 4 skin samples, 3 pleural samples, and 3 peritoneal samples) were submitted to HER-2/neu evaluation by FISH. Seventeen corresponding primary breast tumors also were evaluated by FISH on paraffin histologic sections or on destained archival cytologic smears. RESULTS: Seven of the 22 metastases (32%) were amplified. Amplification was observed in 4 of the 12 liver metastases, in 1of the 3 ascitic fluid specimens, and in 2 of the 4 skin metastases. In all the three pleural fluid specimens, HER-2/neu was unamplified. Matched results from primary and metastatic lesions were obtained in 14 cases (5 were amplified and 9 were unamplified on both primary and metastatic tumors). CONCLUSIONS: The results of the current study emphasized the feasibility and advantages of two rapid and very informative techniques, such as fine-needle aspiration biopsy and FISH. Both procedures were performed to ascertain the malignant nature of a suspicious lesion and to obtain predictive markers for response. Since the advent of trastuzumab, the characterization of the molecular profile in metastatic breast disease has become increasingly important for targeted therapy selection.

Immunocytochemical evaluation of HER-2/neu on fine-needle aspirates from primary breast carcinomas.

Detection of HER-2/neu alterations is increasingly used in breast cancer patients for therapeutic purposes. This study examines the reliability of HER-2/neu immunocytochemical assessment on 66 cytospin smears obtained by fine-needle aspiration biopsy from breast cancer patients. Results were compared with those obtained by both fluorescence in situ hybridization (FISH) on fine-needle aspirate (FNA) and immunohistochemistry (IHC) on matched histologic section. Concordance between immunocytochemistry (ICC) and FISH was 78% and between ICC and IHC was 84%. Discordance mainly concerned seven unamplified cases that resulted positive by ICC and four cases scored negative by IHC but positive by ICC. Simultaneous assessment of HER-2/neu by ICC, IHC, and FISH was available in 24 cases; the concordance was 75%. In this study, the false positivity of immunocytochemical technique represents the major criticism. In our experience, FISH remains the most objective and powerful technique for HER-2/neu assessment on breast cancer FNAs.

Biological parameters on computed tomography guided fine needle aspiration biopsy from peripheral primary non-small cell lung cancer.

Computed tomography (CT) guided fine needle aspiration biopsy (CT-guided FNAB) represents the procedure of choice for diagnosing peripheral primary lung cancer before surgery. The aim of the present study was to assess the reliability of the immunocytochemical evaluation of biological parameters and DNA flow cytometry on cellular material obtained from non-small cell lung cancer (NSCLC) patients by CT-guided FNAB. Thirty consecutive CT-guided FNABs obtained from NSCLC patients were submitted both to the immunocytochemical evaluation of p53, Ki67, bcl-2 and to flow cytometric DNA analysis. p53, Ki67 and bcl-2 were assessable in 60% (18/30), 53% (16/30) and 48% (10/21) of the cases, respectively. Flow cytometric DNA analysis was performed in 19 out of the 30 cases and 74% (14/19) of the histograms were evaluable. Cytofluorimetric S-phase fraction (SPF), was obtained in 57% (8/14) of the cases. The results of the current study suggest that CT-guided FNAB from primary NSCLC patients may represent an effective practice for the evaluation of biologic parameters and could be useful as a preoperative procedure. The role of neoadjuvant chemotherapy in operable NSCLC is still under debate. We suppose that in the future the presurgical characterization of NSCLC could suggest the opportunity of a neoadjuvant systemic treatment aimed to improve the clinical outcome. Moreover, in locally advanced or metastatic NSCLC immunocytochemistry could help to predict the response to chemotherapy and/or radiotherapy, avoiding ineffective treatments and supporting the development of more rational therapies.