Organizing pneumonia resembling disease progression in a non-small-cell lung cancer patient receiving ceritinib: A case report.

RATIONALE: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), a distinct molecular entity, is highly sensitive to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib or ceritinib. Interstitial lung disease is a rare (1.2%) pulmonary toxicity that can result from ALK TKIs, however, organizing pneumonia has not been reported to date. PATIENT CONCERNS: A 45-year-old Korean female with ALK-rearranged metastatic lung adenocarcinoma underwent ceritinib treatment and exhibited a partial response, until she developed organizing pneumonia resembling disease progression. DIAGNOSES: Multiple rebiopsies confirmed the involvement of organizing pneumonia in the pathology. INTERVENTIONS: Ceritinib was stopped and the patient was treated with intravenous antibiotics followed by oral antibiotics for two weeks. OUTCOMES: After recovering from organizing pneumonia, ceritinib was successfully rechallenged and the patient attained a complete response. LESSONS: When a new mass-like lesion develops in the lungs of responding patients, benign lung conditions, including organizing pneumonia should be considered in differential diagnoses.

Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features, although the proportion of discordant subtypes is low. The microsatellite-unstable colorectal cancers of the same CIMP status tended to exhibit different clinicopathological features depending on MLH1 methylation status.