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L. Ampollini
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-062 - Impact of the Tissue Distribution of Subpopulations of TILs and PD-L1 Expression on the Clinical Outcome of NSCLC (ID 5715)
14:30 - 14:30 | Author(s): L. Ampollini
- Abstract
Background:
The number and function of tumor infiltrating lymphocytes (TILs) represent an important prognostic factor in cancer. Among the multiple immune escape mechanisms triggered by cancer, the PD-1/PD-L1 checkpoint seems to play a central role. Accordingly, PD-1/PD-L1 inhibitors have shown significant clinical results in multiresistant NSCLC. However, the role of this immune checkpoint on tumor biology and clinical outcome remains to be determined. To this end, the number and distribution of subpopulations of TILs together with the quantification of PD-L1 expression were immunohistochemically assessed in NSCLC and their impact on patients survival evaluated.
Methods:
Histologic sections from 106 NSCLC (46 ADC,60 SCC) were morphometrically analysed after immunohistochemical assessment of the incidence of CD3+, CD8+ and PD-1+ TILs and their proximal or distal location with respect to neoplastic cells. A comparative evaluation between immuneperoxidase and immunofluorescence (IF) on control tissues and on serial sections from the same cases was undertaken using three different anti-PD-L1 antibodies (clones:28-8,SP142 and M4420). Following suitability criteria, PD-L1 was measured by confocal quantitative IF. Neoplastic and stromal expression of PD-L1 was ascertained by the simultaneous IF detection of Cytokeratin (CK). Morphometric data and clinical records were subjected to Kaplan Meier estimation.
Results:
The gradient of lymphocyte subsets according to their hierarchical phenotype was maintained in both NSCLC, however, the number of CD3[+] TILs was 1.8-fold higher in ADC vs SCC in the presence of similar density of CD8[+] and PD-1[+ ]cells. EGFR and K-RAS mutations conditioned the ADC immune microenvironment by altering CD8[+] and PD-1[+] distribution. High intra- and inter-patients variability in PD-L1 levels was expectedly observed although the average value in SCC samples was higher compared to ADC . K-RAS and to a less extent EGFR mutations were associated with a lower PD-L1 expression. Significant PD-L1 labelling of stromal cells was present in 10% of cases. Interestingly, a lower expression of CK in cells with high PD-L1 signal and the occasional presence of neoplastic plugs overexpressing PD-L1 and lacking CK were documented. Although the number of TILs and PD-L1 levels tended to positively correlate with OS in the entire population of NSCLC, in the individulal cohort of ADC and SCC patients only low number of intratumor PD-1[+] lymphocytes was statistically associated with a significant increased (>10months) OS.
Conclusion:
High levels of PD-L1 and reduction of its cellular target are associated with improved clinical outcome in NSCLC suggesting that adoption by TILs of local escape from PD-L1 pressure delays tumor progression.
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-036 - Giant Primary Dedifferentiated Liposarcoma of the Anterior Mediastinum: An Extremely Rare Occurrence (ID 4031)
14:30 - 14:30 | Author(s): L. Ampollini
- Abstract
Background:
To present an extremely rare case of giant primary dedifferentiated liposarcoma of the anterior mediastinum.
Methods:
A 70-year-old male presented for persistent dyspnoea. Chest CT-scan showed a huge well-defined solid mass with a fatty tissue component in the anterosuperior mediastinum (Fig.1A). The tumour caused a wide displacement of the right lung and mediastinal organs with no signs of invasion. PET-CT scan showed a unique uptake of the mediastinal mass (Suv max=4.6). A surgical resection was proposed. A right emiclamshell incision was performed. On exploration, a huge mass of the anterior mediastinum causing the compression of the right lung, pericardium and great vessels was observed; no sign of adjacent organs invasion was found. The tumour was radically resected and the patient was discharged uneventfully after 6 days. The patient denied any adjuvant therapy. No evidence of recurrence has been identified as of 16 months postoperatively.
Results:
Macroscopically, the smooth, lobulated, well demarcated, yellowish-white mass weighed 2102g and measured 27x23x13cm (Fig.1B). Microscopically, the tumour presented a dedifferentiated component characterized by spindle cells organized in a fascicular pattern with abundant stroma and necrosis (Fig.1C) and a second component of lipoma-like well-differentiated liposarcoma (Fig.1D). Figure 1E showed both components. The spindle cells displayed a moderate degree of nuclear atypia, with moderate to marked levels of pleomorphism and cellularity. The spindle cells resulted positive for desmin and SMA and had an elevated proliferative index (Ki67=50%) (Fig.1F). Immunohistochemically, tumour cells of both components were positive for CDK4 (Fig.1G) MDM2 (Fig.1H) and negative for myoglobin, EMA, S-100. Given that, a final pathological diagnosis of primary dedifferentiated liposarcoma of the mediastinum was disclosed. Figure 1
Conclusion:
Primary dedifferentiated liposarcoma of the mediastinum is extremely rare. Chemotherapy and radiotherapy seems to be ineffective; radical surgical resection represents the best therapeutic modality. A closed and long-term follow-up is required because of the high risk of recurrence.
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P2.04-037 - Solitary Fibrous Tumor of the Pleura Associated with Severe Hypoglicemia: The Doege-Potter Syndrome (ID 4058)
14:30 - 14:30 | Author(s): L. Ampollini
- Abstract
Background:
to present an extremely rare case of Doege-Potter Syndrome (DPS).
Methods:
a 66 years-old man, non-smoker, was admitted for disorientation and confusional state. Blood tests showed a severe hypoglycemia (30 mg/dl); the patient was not diabetic and did not take antihyperglycemic agents. An extremely low values of insulin and C-peptide was also found. A chest CT-scan showed a 20x16cm lobulated mass occupying the right hemithorax (Figure 1A). FDG-PET showed a unique uptake of the lesion (SUVmax 2.5). After a multidisciplinary discussion, a surgical resection was proposed. The lesion of pleural origin was radically resected through a right posterolateral thoracotomy. From the 1st postoperative day, the blood glucose levels were normal; the patient was discharged on the 5th postoperative day uneventfully.
Results:
the mass measured 26x18x12cm, presented polylobate margins, elastic consistency and grayish-white color (Figure 1B). Microscopically, a mesenchymal neoplasm characterized by spindle cells with moderate atypia, hyperchromasia and nuclear pleomorphism, organized in a fascicular pattern was found (Figure 1C). A moderate deposition of collagen extracellular matrix, with areas of hyaline involution and foci of necrosis was evident (Figure 1D). The mitotic index was 9x10 HPF. Immunohistochemically, tumor cells were positive for CD34, CD99, BCL-2, vimentin, desmin, IGF1-R, IGF-2, Ki67 (15%) and negative for EMA, smooth muscle actin, cytokeratin pool, c-kit, DOG-1, myogenin, calretinin, S100. Considering these histopathologic features, a diagnosis of malignant solitary fibrous tumor of the pleura was made. After 18 months, the patient is in good condition and free of disease. Figure 1
Conclusion:
DPS is a paraneoplastic syndrome characterized by severe hypoglycemia associated with a solitary fibrous tumor of the pleura. Surgical therapy is the gold standard, providing also the resolution of hypoglycemic crisis. Close follow-up and blood glucose monitoring is essential, especially in patients suffering from the malignant variant of this rare pleural tumor.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-004 - Exceptional Evolution of Benign Metastasizing Leiomyomas of the Lung (ID 4028)
14:30 - 14:30 | Author(s): L. Ampollini
- Abstract
Background:
to describe an exceptional case of malignant transformation of benign metastasizing leiomyomas (BML) of the lung.
Methods:
a 62-year-old woman presented for radiological finding of multiple bilateral pulmonary nodules. Nine years before, she underwent hysterectomy for uterine leiomyoma. After pulmonary biopsy, a diagnosis of BML was made. Subsequently, a surgical resection of the right pulmonary nodules was performed; histopathological examinations confirmed the diagnosis of BML (Ki67=1%; strong expression of estrogen and progesterone receptor as depicted in Fig.1C-E). The patient was put on anastrazole therapy but an increase of the left pulmonary nodules was observed. Therefore, a surgical resection of the left nodules was carried out; final pathological examination confirmed BML. Three years later, a chest CT-scan showed bilateral pulmonary relapses; tamoxifen was started but it was ineffective. Then, a surgical resection of the right pulmonary nodules was performed (Fig.1A-B). The patient was discharged uneventfully on postoperative day 5.
Results:
macroscopically, the nodules had whitish and yellowish colour, smooth margins, with tense-elastic consistency. Microscopically, an intersecting bundles of spindle cells with moderate nuclear atypia organized in a fascicular pattern were clearly evident (Fig.1F). The mitotic activity was more pronounced than previous histological samples (up to 10 mitoses/10HPF). Immunohistochemical studies showed positivity for smooth-muscle actin, desmin, and negativity for HMB-45, CD34, and TTF-1; Ki-67=20% (Fig.1G). Estrogen and progesterone receptor were weakly positive (Fig.1H). Based on the current criteria, a diagnosis of low-grade leiomyosarcoma was made. The patient denied the contralateral surgical resection. Eighteen months later the chest CT-scan revealed bilateral pulmonary nodules; she is currently under megesterol acetate treatment. Figure 1
Conclusion:
BML of the lung is a rare pathological condition with a usually indolent clinical course. Although it’s exceptional, an evolution towards a low grade leiomyosarcoma should be considered in the natural history of the disease.
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-012 - Tumor-Infiltrating Lymphocytes, PDL-1, BAP-1, VEGFR-2 and IGF-1R Expression in Malignant Pleural Mesothelioma (ID 4142)
14:30 - 14:30 | Author(s): L. Ampollini
- Abstract
Background:
to investigate whether there was any relationship between survival and the expression of tumor infiltrating lymphocytes (TILs), programmed cell-death-ligand-1 (PDL-1), BAP-1 (BRCA1-Associated Protein 1), VEGFR-2 (vascular endothelial growth factor receptor 2) and IGF-1R (Insulin-Like Growth Factor 1 Receptor) in malignant pleural mesothelioma (MPM).
Methods:
63 cases of MPM were identified. All tissues were obtained at the time of diagnosis. There were 40 males; mean age was 70.4 years. 34 patients were smokers and 40 had a certain history of asbestos exposure. All histological slides were revised; there were 30 epithelioid subtypes, 20 biphasics and 13 sarcomatoids. The presence of TILs was scored as absent, weak, moderate and strong according to a quantitative assessment on hematoxylin and eosin slides. The expression of BAP-1, VEGFR-2, PDL-1 and IGF-1R was analyzed by immunohistochemistry. The impact of asbestos exposure, tobacco consumption and histological subtypes on survival were also assessed. The survival analysis was analyzed by Kaplan Meier curve.
Results:
TILs were present in 89% of cases and were found to be a favorable prognostic factor (p=0.009) although related with histological subtypes (p=0.008). The absence of TILs was higher in biphasic and sarcomatoid subtypes (90.9%, 30/33) compared to epithelioid MPM (53.3%, 16/30 p<0.001). Median survival in TILs and non-TILs patients was 28 months and 11 months, respectively. The expression of PDL-1 in tumor cells (cut-off: 10%, p=0.028) and VEGFR-2 in TILs (p=0.003) were related with survival, but they were differently expressed in histological subtypes. Using a logistic regression model, TILs, PDL-1 and VEGFR-2 in TILs correctly classified 21/30 epithelioid subtypes (70%) and 29/33 biphasic and sarcomatoid subtypes (87.9%). IGF-1R was overexpressed in 82% of the tumors (21 epitheliods and 31 sarcomatoids) and in 25% of TILs (7 epitheliods and 3 sarcomatoids) and was a favorable prognostic factor (p=0.023) independently of the histological subtype. Median survival was 4 and 13 months in patients not overexpressing and overexpressing IGF-1R, respectively. In a Cox regression model including both IGF-1R and histological subtype, IGF-1R remained significant [p=0.006, HR=0.41 (0.20-0.84)]. Tobacco, asbestos exposure, age and BAP-1 expression were not significantly related with survival.
Conclusion:
the histological subtype is an important prognostic factor in MPM and it’s related to different histological markers: the presence of TILs, PDL-1 and VEGFR-2 in TILs. Moreover, the overexpression of IGF-1R is an independent favorable prognostic factor. Therefore, histological markers may improve the prognostic assessment of MPM and provide mechanistic clues for new therapeutic strategies.
