Faculty Bibliography
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309
Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors
INTRODUCTION: The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs. METHODS: Tumor tissues from 23 patients with WHO Type B2/B3 thymoma (n = 12) and thymic carcinoma (n = 11) were identified and clinical outcomes were annotated. The expression of membranous PD-L1 on tumor cells, CD3+ and CD8+ tumor infiltrating lymphocytes (TILs), co-stimulatory (CD137, GITR, ICOS), and co-inhibitory immune checkpoint molecules (PD-1, CTLA-4, TIM-3) were assessed semi-quantitatively using immunohistochemistry. RESULTS: PD-L1 positivity (>/= 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p<0.01), and was associated with longer overall survival (p = 0.02). TIM-3 and GITR were expressed in all TETs, including 18/23 and 12/23 with at least moderate/high expression, respectively. Moderate/high CD137 expression correlated with CD8+ (p = 0.01) and moderate/high GITR expression co-associated with PD-1 (p = 0.043). CONCLUSIONS: TETs are characterized by frequent PD-L1 expression and PD-L1 is associated with improved survival, suggesting PD-L1 signaling may be biologically important in TETs. Robust expression of markers of immune activation and immunotherapeutic target molecules in TETs emphasizes the potential for development of anti-PD-1/PD-L1 therapies.
PMCID:5542609
PMID: 28771603
ISSN: 1932-6203
CID: 2681252
Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research
Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.
PMCID:5564448
PMID: 28777142
ISSN: 1533-4031
CID: 2663752
Spectrum of Subsolid Pulmonary Nodules and Overdiagnosis
PMID: 28734396
ISSN: 1558-4658
CID: 2650492
Rapidly Progressive Cavitary Lung Disease Due To Concurrent Mycobacterium Avium Infection And Eosinophilic Pneumonia [Meeting Abstract]
ISI:000400372503461
ISSN: 1535-4970
CID: 2591072
Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study [Meeting Abstract]
ISI:000394467302564
ISSN: 1530-0285
CID: 2517662
Live Digital Telepathology Enables Rapid Remote Frozen Section Diagnosis and Cytology Adequacy Assessment by Subspecialists [Meeting Abstract]
ISI:000394467302170
ISSN: 1530-0285
CID: 2517622
Live Digital Telepathology Enables Rapid Remote Frozen Section Diagnosis and Cytology Adequacy Assessment by Subspecialists [Meeting Abstract]
ISI:000393724402076
ISSN: 1530-0307
CID: 2506802
Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study [Meeting Abstract]
ISI:000393724402474
ISSN: 1530-0307
CID: 2506842
The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases
INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise kappa scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, kappa scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.
PMID: 27998793
ISSN: 1556-1380
CID: 2464252
Unusual late presentation of metastatic extrathoracic thymoma to gastrohepatic lymph node treated by surgical resection
In advanced stages, thymic tumors tend to spread locally. Distant metastatic disease is rare. We present the first report of single metastatic abdominal lymph node in a 37-year-old female patient and 5 years after an extrapleural pneumonectomy for stage IV thymoma followed by radiotherapy with no other evidence of abdominal disease successfully treated by robotic surgical resection.
PMID: 26620540
ISSN: 1863-6713
CID: 2410672
