Archives of pathology & laboratory medicine
-
Arch. Pathol. Lab. Med. · Jan 2018
ReviewIs There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part I-Colorectal Cancer: Microsatellite Instability, Testing, and Clinical Implications.
- Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker. ⋯ - Although the TNM classification of malignant tumor stage remains the key determinant of CRC prognosis and treatment, there are considerable stage-independent, interindividual differences in clinical outcome and therapy response by patients. In addition, MSI-H status has an important role in CRC management and can be reliably detected by molecular and immunohistochemistry techniques and genetic testing. Efforts must be made to identify whether MSI-H CRC is germline or sporadic to ensure appropriate treatment, accurate prognosis, and risk assessment for relatives. Microsatellite status has been recognized as a good prognostic indicator and is predictive of a poor response to 5-fluorouracil-based chemotherapy and a good response to programmed death ligand-1 inhibitor pembrolizumab in metastatic/refractory MSI-H CRC.
-
Arch. Pathol. Lab. Med. · Jan 2018
ReviewIs There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer.
- The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti-programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability-high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability-high CRC. ⋯ - Exciting success with anti-PD-1/PD-L1 and anticytotoxic T-lymphocyte-associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability-high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti-PD-1 or anti-PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability-high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.
-
Arch. Pathol. Lab. Med. · Jan 2018
ReviewPathology of Chronic Hypersensitivity Pneumonitis: What Is It? What Are the Diagnostic Criteria? Why Do We Care?
- Chronic hypersensitivity pneumonitis (CHP) has emerged from obscurity during the past 15 years and is now recognized as a very common form of fibrosing interstitial pneumonia but one that is frequently misdiagnosed both clinically and on surgical lung biopsy as usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) or fibrotic nonspecific interstitial pneumonia. ⋯ - Upper lobe-predominant fibrosis and/or air-trapping on computed tomography scan are features of CHP but not UIP/IPF; however, radiologic separation is possible in only about 50% of cases. Morphologically, CHP sometimes mimics UIP/IPF, but CHP often shows isolated foci of peribronchiolar (centrilobular) fibrosis, frequently associated with fibroblast foci, and in CHP, fibrosis may bridge from the centrilobular region to another bronchiole, an interlobular septum, or the pleura ("bridging fibrosis"). This set of findings is uncommon in UIP/IPF. In addition, CHP may produce a picture of fibrotic nonspecific interstitial pneumonia. Although giant cells/granulomas are usually present in subacute hypersensitivity pneumonitis, they are much less frequently found in CHP, and their absence does not contradict the diagnosis. This diagnostic separation is clinically important because CHP is treated differently than UIP/IPF is (immunosuppressive agents versus antifibrotic agents); further, there are some data to suggest that removing the patient from antigen exposure improves outcome, and there is evidence that patients with CHP have a much better survival prognosis after lung transplantation than do patients with UIP/IPF. In most cases, accurate diagnosis of CHP requires consultation among clinicians, radiologists, and pathologists.