Rira Hoshi

Clinicopathological findings of non-small-cell lung cancer with high serum progastrin-releasing peptide concentrations

Although progastrin-releasing peptide (proGRP) is used as a serum tumor marker for small cell lung cancer (SCLC), high serum pro-GRP concentrations are observed in some non-small-cell lung cancers (NSCLCs). The characteristics of these NSCLCs are not well known. To determine the clinicopathological features of NSCLC in patients with elevated serum proGRP concentrations, serum proGRP values were assessed in 654 advanced lung cancer patients, and positive (>46pg/mL) NSCLC specimens were subjected to cytological and histopathological reevaluation. Serum proGRP concentrations were positive in 34 of 421 NSCLC patients (8.1%) and 186 of 233 SCLC patients (80%). Histological subtypes of the 34 NSCLC patients at diagnosis were 20 adenocarcinomas, 5 squamous cell carcinomas, 4 large cell carcinomas, and 5 large cell neuroendocrine carcinomas. Six of 27 cytology specimens contained characteristic neuroendocrine morphology. Immunohistochemical analysis showed that 11 of 17 tumors were positive for neuroendocrine markers (64.7%). Twenty of 34 serum proGRP-positive NSCLC patients received platinum-based chemotherapy, and the response rate was 55.0%. These results suggest that serum proGRP-positive NSCLCs may have neuroendocrine differentiation. In addition, serum proGRP-positive NSCLCs may have clinical characteristics that are different from other NSCLCs.

Discriminant Model for Cytologic Distinction of Large Cell Neuroendocrine Carcinoma from Small Cell Carcinoma of the Lung

Background: To establish cytologic criteria for pulmonary large cell neuroendocrine carcinoma (LCNEC), we developed and evaluated a discriminant model for cytologic differential diagnosis between LCNEC and small cell lung carcinoma (SCLC). Methods: Aspiration cytologic and/or imprint smears from 29 LCNEC cases were reviewed in comparison with 26 SCLC cases. We selected the following parameters for assessment: background, cellular arrangement, cell clusters, cell cohesion, arrangements, cell dimensions areas, the presence of cytoplasm and/or prominent nucleoli, nuclear features, mitosis, naked nuclei, and nuclear streaking. To demonstrate the utility of differences in frequencies of cytologic parameters for LCNECs and SCLCs, a discriminant model was developed and evaluated. Results: Among the cytologic parameters investigated, large clusters (consisting of ≥60 tumor cells) with tight cohesion and small tumor cells (showing ≤120 &mgr;m2) without prominent nucleoli on each case were particular focuses of attention, because statistically significant differences with good power were evident between the LCNEC and SCLC groups for their frequencies (p < 0.0001). On the basis of variation in plotted location on scatter plots, a discriminant model for LCNEC and SCLC was made and evaluated by logistic discriminant analysis. Sensitivity, specificity, and accuracy were all 100%. With leave-one-out cross validation, the predicted error rate of the discriminant model for new cases was 0.00545. Conclusion: Our model based on the cytologic features of large cell clusters with tight cohesion and of small tumor cells without prominent nucleoli should be a useful aid for distinction between LCNECs and SCLCs.

Prognosis of non-small-cell lung cancer patients with positive pleural lavage cytology

OBJECTIVES Positive pleural lavage cytology (PLC) is considered as a precursor condition of pleural dissemination (PD) or malignant pleural effusion (PE), and one of the poor prognostic factors in surgically resected non-small-cell lung cancer (NSCLC) patients. Although PD and PE are classified as M1a, PLC does not contribute to the tumour, node and metastasis (TNM) classification of the Union Internationale Contre le Cancer. This study aimed to evaluate the prognostic effect of positive PLC status in surgically resected NSCLC patients compared with PD and/or PE. We also aimed to consider the contribution of positive PLC status to the TNM classification. METHODS We reviewed 1572 consecutive patients with completely resected NSCLC, and analysed the relationship between PLC status, other clinicopathological factors and prognosis. The survival rates of 45 patients with PD and/or PE were also investigated. RESULTS Positive preresection PLC (pre-PLC) status was observed in 56 patients. Pre-PLC status was significantly associated with other clinicopathological factors. Positive pre-PLC patients exhibited a worse 5-year overall survival (50.6%) compared with negative pre-PLC patients (78.0%), but better survival than PD and/or PE patients (21.0%). Prognosis of positive pre-PLC patients was equal to that of pT3, negative pre-PLC patients; survival equality was observed when patients were stratified according to pN0, pN1 and pN2. CONCLUSIONS Positive pre-PLC had the significant prognostic effect in surgically resected NSCLC patients. However, it is not a contraindication for surgical resection, unlike PD and/or PE. Our data suggest that positive pre-PLC should be classified as pT3 in next TNM classification.

Cytology of pulmonary adenocarcinomas showing enteric differentiation.

OBJECTIVE To evaluate cytologic differences between primary pulmonary adenocarcinomas showing enteric differentiation (PAED) primary pulmonary adenocarcinomas of ordinary structure (PAC) and pulmonary metastases from colorectal carcinomas (MCR). STUDY DESIGN During an 18-year period (1986-2003), cytologic materials were obtained from 5 PAEDs confirmed by pathologic examination of surgically resected specimens at the Cancer Institute Hospital. Aspiration cytologic and/or imprint smears of routine samples stained by the Papanicolaou method from the PAED cases were reviewed in comparison with 10 cases each of PAC showing a tubular pattern and MCR. RESULTS The aspiration biopsy cytology and imprints showed similar features. Abundant necrotic debris in the background was recognized in a majority of all cases independent of the group. None to slight overlapping of tumor cells and less frequent palisading or glandular arrangements were characteristic features of PAED, significantly differing from MCR. Moreover, differences in nuclear features were evident as follows: in the MCR group, nuclear chromatin was hyperchromatic and coarsely condensed, and there were prominent nucleoli, whereas a slightly hyperchromatic pattern with some small to enlarged nucleoli was typical of PAED and PAC cases. CONCLUSION Although diagnosis of PAED by routine cytology is difficult due to the features of the lesion, differential diagnosis between PAED, PAC and MCR is a possible using conventional cytologic criteria.

Association of cytologic micropapillary clusters in cytology samples with lymphatic spread in clinical stage I lung adenocarcinomas.

OBJECTIVE Cytologic micropapillary clusters (MPCs) are round, three-dimensional and cohesive clusters of lung cancer cells with a pseudopapillary configuration. Recently, we demonstrated that MPCs from early stage lung adenocarcinomas can be considered as useful aids to assessing prognosis. We here demonstrate that stage I lung adenocarcinomas found to be positive for MPCs in preoperative cytologic approaches are high risk for lymphatic spread. METHODS The clinicopathologic characteristics, metastatic status of dissected lymph nodes, vascular infiltration and presence of MPCs in preoperative cytologic specimens in 209 patients with clinical stage I lung adenocarcinomas undergoing complete surgical resection during 2004-2006 were reviewed. RESULTS Thirty-eight patients (18%) had positive MPC findings; 21 patients with clinical stage IA and 17 with stage IB. Significant associations with postoperative stages IA and IB, frequent lymph node metastasis and venous infiltration on pathologic examination were observed (P<0.05). In particular, 50% of clinical stage I patients with MPCs demonstrated advance in the postoperative stage of disease. CONCLUSIONS MPCs may be a manifestation of aggressive behavior, as evidenced by frequent lymph node metastasis, of clinical stage I lung adenocarcinomas. Preoperative cytologic detection of MPCs, therefore, should alert the surgeon to the probability of lymph node metastases.

Implications for Differential Diagnosis of Lung Cancer-Associated Lymphadenopathy in Lymphoepithelioid Cell Lymphoma (Lennert's Lymphoma) Arising Simultaneously with Lung Cancer

BACKGROUND Lymphoepithelioid cell lymphoma (LCL) is a rare morphologic variant of peripheral T-cell lymphoma, and its cytologic features have not been well characterized. We describe details from fine needle aspiration cytology (FNAC) of LCL in a patient simultaneously suffering from lung cancer, in whom extensive lymph node metastasis was suspected clinically. CASE A 54-year-old man had a lung nodule diagnosed as an adenocarcinoma by biopsy. 18F-fluoro-deoxyglucose positron emission tomography showed high uptake in the lung nodule as well as interlobar, supraclavicular and axillary lymph nodes. FNAC from interlobar and supraclavicular lymph nodes revealed abundant lymphoid cells intermingled with epithelioid cell clusters. Most lymphoid cells were small, with teardrop-shaped nuclei. Occasionally, large lymphoid cells with hyperconvoluted nuclei and prominent nucleoli were observed. An extensive sarcoid reaction was suspected on cytology, and lobectomy was performed. LCL with lung adenocarcinoma was diagnosed on the immunohistochemical findings. CONCLUSION Detailed observation of lymphoid cells with FNAC is important even in patients with lung cancer and massive regional lymphadenopathy. Presence ofa teardrop nuclear shape and nuclear irregularities of lymphoid cells provides important information for cytologic diagnosis of LCL when epithelioid cell clusters are evident.

Cytomorphologic differentiation between large cell neuroendocrine carcinoma and small cell carcinoma of the lung

目的:肺大細胞神経内分泌癌 (LCNEC) と肺小細胞癌 (SCLC) の鑑別を目的とし, それらの細胞像を比較検討した.対象と方法:対象は摘出材料の組織学的検索にてLCNECと診断された22例とSCLC, intermediatetype (IMT) 20例. それらの経気管支針穿刺および摘出材料の捺印標本を用い, 細胞集塊, 細胞の出現様式, 細胞の大きさおよび性状について比較検討した.結果:LCNECは構成細胞数が60個以上の大型集塊での出現が目立ち, その集塊は辺縁の結合性が強く柵状配列がみられた. SCLCは散在性での出現が多く, 集塊で出現してもその結合性は弱かった. LCNECはSCLCと比較して, 細胞面積が120μm2で核小体の目立たない腫瘍細胞の出現率が低かった.結論:今回LCNECとSCLCとの鑑別点として, 出現形式, 集塊の構成細胞数集塊辺縁の結合性および配列, 核小体の目立たない小型腫瘍細胞の出現頻度が重要であることが示された. これらの細胞所見からLCNECとSCLCの細胞学的診断は可能であると考えられる.

Cytomorphologic investigation of atypical adenomatous hyperplasia of the lung

目的:肺異型腺腫様過形成 (AAH) と高分化腺癌 (AD) の鑑別を目的とし, それらの細胞像を比較検討した.対象と方法:対象は組織学的にhigh-grade AAHと診断された4例と高分化腺癌8例, それらの捺印標本を用い, 細胞の出現様式, 細胞と核の大きさと長さおよび性状について比較検討した.結果:1. AAHの集塊は構成細胞数が20個前後で平面的であり, 細胞数が60個以上の大型集塊や重積性のある集塊はみられなかった.2. AAH細胞はAD細胞と比較すると小型でN/C比は低く, また, 立方状でライトグリーン淡染性の細胞質を有し, 高円柱状細胞の混在や泡沫状細胞は認めなかった.3. AAHの核はADの核と比較すると小型楕円形で, 核形不整はごく少数ないしはみられなかった.4. AAHの核内細胞質封入体の出現率はADより低く, 2核細胞の出現率は高かった.結論:従来の報告に加えて, 今回AAHとADとの鑑別点として, 集塊の構成細胞数, 細胞の形状, 細胞質の性状についての新しい知見を得た.これらの細胞所見の特徴からAAHの細胞学的推定診断は可能になると考えられる.

A case of epithelioid hemangioendothelioma of the soft tissue.

60歳, 女性の腋窩部に発生した類上皮血管内皮腫の1例を経験し, その細胞像について鑑別診断を中心に検討した.腫瘍細胞は主に乳頭状ないし平面状の上皮様細胞結合を示す集塊として出現していた. その細胞質には病理組織学的に特徴とされている大小の細胞質内空胞がみられた他に, 核には溝や, 核内細胞質封入像様の構造がみられた. 鑑別すべき腫瘍に上皮様細胞結合を示す腫瘍, 核溝や核内細胞質封入像様の構造がみられる腫瘍, 細胞質に空胞様の構造がみられる腫瘍があげられるが, 核, 細胞質双方に所見を合わせもっている腫瘍は少なく, 腫瘍の出現様式, 核所見, 細胞質所見を合わせて検討することで, 本腫瘍を推定診断することが可能ではないかと思われた.