Koichi Yoshida,2 Masaru Hagiwara,3. Naohiro Kajiwara,2 Tatsuo Ohira,1. Jun Matsubayashi,4 Toshitaka Nagao,4. Norihiko Ikeda1 1General Thoracic Surgery, ...
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P3.01-027 3D Telomere Nuclear Organization to Distinguish Multiple Synchronous Lung Adenocarcinoma from Metastatic Lung Adenocarcinoma Topic: Morphology Nathalie Bastien,1 Oumar Samassékou,2 Michèle Orain,1 Sabine Mai,3 Philippe Joubert1 1 Department of Pathology, Quebec Heart and Lung Institute, Quebec/QC/Canada, 23D Signatures Inc., Winnipeg/AB/Canada, 3Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg/AB/Canada Background: Lung cancer is the leading cause of cancerrelated mortality. Adenocarcinoma (AC) representing 50% of diagnosed lung cancer. At diagnosis, 25% of pulmonary AC present as multicentric lesions and an half are considered synchronous AC (SLA) while the remaining represents intrapulmonary metastases (MAC) from a primary lung AC. Surgical resection is the treatment of choice for SLA and the outcome of the patients is generally good. On the other hand, intrapulmonary metastases (MAC) are related lesions associated with a poor prognosis and generally not amenable to surgical therapy. There is currently no way to distinguish SLA from MAC without analyzing a surgical specimen from each lesion, which is rarely possible. It is then likely that a significant proportion of patients with multiple AC do not get the appropriate treatment. There is therefore an urgent need to develop molecular tools to classify multicentric lesions. Genomic instability is one of the drivers of metastases, and the alteration of telomeric nuclear organization (TNO) is a predictor of genomic instability and tumor progression. Our hypothesis is that the profile of TNO can discriminate SLA from MAC. Methods: We assessed the parameters defining 3D-TNO using 3D quantitative fluorescence in situ hybridization, 3D imaging and 3D-TNO analyses on formalin-fixed paraffin-embedded tissue sections from 10 patients with SLA or MAC. For each patient, were analyzed two lesions: primary and metastatic lesions for MAC and two different primary tumors for SLA. The following 3D-TNO parameters were evaluated: 1) number of telomere (telomere signals), 2) telomere length (telomere signal intensities), 3) number of telomere aggregates (telomere clusters), 4) telomere distribution within a nucleus and 5) nuclear volume. Results: Firstly, we compared 3D-TNO of cancer cells between MAC and SLA and found that four of the five parameters defining 3D-TNO showed statistical difference
Journal of Thoracic Oncology
Vol. 12 No. 1S
between the two pathological groups. Secondly, for each patient, we did pairwise comparison of parameters defining 3D-TNO between the two lesions. For the patients presenting MAC, we found that metastatic lesions had higher telomere aggregates than primary lesions. The comparison of the number of telomere aggregates did not display statistical difference between the two primary tumors from SLA. Conclusion: This study shows that the number of telomere aggregates is a powerful discriminative parameter that can reliably distinguish patients with SLA from patients with MAC. Our results suggest that 3D-TNO signature has the potential to provide a molecular tool that can eventually be implemented in a clinical setting. Keywords: Telomeres, lung adenocarcinoma, Multicentric lesions
P3.01-028 Comparison of Touch Imprint Cytology and Section Histopathology in the Diagnostic of the Small Peripheral Lung Tumors Topic: Morphology Masatoshi Kakihana,1 Junichi Maeda,2 Koichi Yoshida,2 Masaru Hagiwara,3 Naohiro Kajiwara,2 Tatsuo Ohira,1 Jun Matsubayashi,4 Toshitaka Nagao,4 Norihiko Ikeda1 1General Thoracic Surgery, Tokyo Medical University, Tokyo/Japan, 2General Thotacic Surgery, Tokyo Medical University, Tokyo/Japan, 3General Thoracic Surgery, Tokyo Medical University Hospital, Tokyo/Japan, 4Departments of Anatomic Pathology, Tokyo Medical University, Tokyo/Japan Background: There have been some reports on transbronchial biopsy (TBB) through endobronchial ultrasonography with a guide sheath (EBUS-GS) for diagnostic sampling of small-sized tumors which showing groundglass opacity (GGO) on chest CT. However, technique such as EBUS-GS is limited in their ability to diagnose such small lung tumors. The discussion about the cytological features of small tumors with GGO in detail is necessary. We evaluated about the association of the cytological features with the histological examination using the surgically resected specimen. 140 patients, age between 23e86 years old, who showed clinical and radiological signs of peripheral lung tumors below 3.0cm in diameter, underwent surgical resection at our institution between 2013 and 2015.
January 2017
Methods: Imprints or touch preparation and squash smears preparation were prepared from the unfixed, fresh sample in 140 cases. Papanicolaou’s stain was employed in all cases. To make the squash smears preparation, the slides are drawn apart away from each other, in the direction of the long axis of the slide. Tissue fragments taken from surgical specimen were fixed with 10% neutral buffered formalin and stained with hematoxylin and eosin (H&E). Results: By histological examination (in the 140 cases), the diagnostic of lung cancer was given with the establishing of the histological type. In 110 cases (78.6%) of the cases diagnosed as adenocarcinoma, in 21 cases (15%) squamous cell carcinoma, in 4 cases (2.9%) was neuroendocrine tumors, and one case each of adenosquamous carcinoma, pleomorphic carcinoma and pleomorphic sarcoma. In 84 of the 110 cases (76.3%), the result of imprint cytological examination was adenocarcinoma. In the 110 pathological diagnosed as adenocarcinoma cases, 52 patients (47.2%) are below 2.0cm in size. Tumor stamps of small sized adenocarcinoma are characterized by moderate cellularity and are composed of atypical cells arranged in small flat sheets. The nuclei are generally round, slightly hyperchromatic with small nucleoli. Conclusion: Our data indicate the fact that the cytological examination on stamps from surgical material offers a very high percentage of positive results, close to the histological one. But in the tumor size less than 1.0cm, the establishing of the histological type of lung cancer is more difficult by cytological examination. Despite this, the cytology may be extremely useful in diagnose of the small peripheral tumors. The cytological characteristics of small peripheral adenocarcinoma were little reference to the differentiation at the cellular level. Our findings indicated that the presence of several nucleoli and granular chromatin densely are the factors of adenocarcinoma. Keywords: trans endoscopic lung biopsy, imprint cytology, ground-glass opacity (GGO)
P3.01-029 Cases Demonstrating Spread Through Air Spaces (STAS) Reflects Invasive Growth and Not an Artifact Topic: Morphology Shaohua Lu,1 Natasha Rekhtman,1 Takashi Eguchi,2 David Jones,2 Prasad Adusumilli,2 William Travis1 1 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York/NY/United States of America,
Abstracts
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Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York/NY/United States of America Background: STAS is defined as a pattern of tumor cell spread in the lung parenchyma beyond the edge of a lung cancer. It has been postulated that this is an ex vivo artifact due to the force of knife with the premise that STAS is clinically unimportant and it should be ignored like true artifacts. Methods: We present three cases providing evidence that STAS is not an artifact and is clinically relevant. Results: Case 1: 68F underwent wedge resection of a left upper lobe (LUL) lung adenocarcinoma. During the surgical procedure the surgeon did not cut across the tumor, but sent a separate wedge biopsy as an additional margin. The latter wedge contained an 8 mm focus of adenocarcinoma consisting almost entirely of a STAS pattern with a 1mm area of acinar growth. Case 2: 66M underwent RUL wedge resection in August 2013 for a 1.3 cm lung adenocarcinoma. The resection margin was positive with only STAS in the margin. In the absence of any clinical sign of recurrence or metastases, a completion right upper lobectomy was performed revealing three separate foci of residual adenocarcinoma including 1.5 and 1.0 mm acinar areas and a 0.5 mm focus of STAS with N1 and N2 lymph node metastases. Adjuvant chemotherapy and radiation were given. In 2014, the patient developed multiple bilateral nodules and in November underwent LUL wedge resection that showed three foci of adenocarcinoma with a STAS predominant pattern. In July 2016, the patient remains on chemotherapy with slowly growing bilateral nodules. Case 3: A 77M presented with pneumonia and bilateral ground glass opacities with focal consolidation. A biopsy, originally interpreted as benign, showed diffuse involvement by adenocarcinoma with a STAS predominant pattern. The morphology does not explain the consolidation seen on CT indicating the surgeon did not cut across the main tumor area. Conclusion: We present three cases which provide evidence that STAS is not an artifact that should be ignored. In two cases the extensive STAS predominant pattern was not a knife cutting artifact because the main tumor was not cut either by the surgeon or pathologist. In the third case, STAS was the only pattern of tumor identified at a wedge resection margin. If this had been ignored, the residual and metastatic tumor would not have been identified delaying introduction of chemotherapy. These findings support the concept that STAS is a clinically important invasive pattern and not an artifact. Keywords: Spread Through Air Spaces, Invasive pattern, Artifact, Cases
