Biopsy specimens are subjected to an expanding portfolio of assays that regularly include mutation profiling via next-generation sequencing (NGS). Specimens derived via fine-needle aspiration, a common biopsy technique, are subjected to a variety of cytopreparatory methods compared with surgical biopsies that are almost uniformly processed as formalin-fixed, paraffin-embedded tissue. Therefore, the fine-needle aspiration-derived specimens most commonly accepted for molecular analysis are cell blocks (CBs), because they are processed most similarly to surgical biopsy tissue. However, CB preparations are fraught with challenges that risk unsuccessful sequencing and repeat biopsies, with the potential to further increase health care costs and delay clinical care. The diversity of cytopreparations and the resource-intensive clinical validation of NGS pose significant challenges to more consistent use of non-CB (NCB) cytology specimens. As part of clinical validation of a targeted NGS assay, DNA subjected to nine cytopreparatory methods was evaluated for sequencing performance and was shown to be uniformly acceptable for clinical NGS. Of the 379 clinical cases analyzed after validation, the majority (56%) were derived from NCB cytology specimens. This specimen class had the lowest DNA insufficiency rate (1.5%) and showed equivalent sequencing performance to surgical and CB formalin-fixed, paraffin-embedded tissue. NCB cytology specimens are valuable sources of tumor nucleic acid and are the preferred specimen type for clinical NGS at our institution.
In select cases where additional tissue may be needed, sampling with a 19-G EBUS needle following standard aspiration with a 22-G needle results in an increase in diagnostic yield.
Anaplastic lymphoma kinase (ALK) gene rearrangements are present in ∼5% of non-small-cell lung cancers (NSCLCs). These rearrangements occur because of a chromosomal inversion within the short arm of Chromosome 2, which results in the formation of the echinoderm microtubule-associated protein-like 4 (EML4)–ALK fusion oncogene. Whereas NSCLC transformation to SCLC is a rare phenomenon described in epidermal growth factor receptor (EGFR) mutant cancers primarily after treatment with targeted therapy, it is exceedingly rare in ALK-rearranged adenocarcinomas. It is currently unclear what the therapeutic significance of the rearrangement is in this transformed tumor as there is a paucity of medical literature describing follow-up care and outcomes of patients in this rare scenario. We describe a unique case in which a patient with ALK-rearranged adenocarcinoma underwent small-cell transformation at a metastatic site with retained ALK rearrangement and was provided clinical follow-up after treatment with second-generation tyrosine kinase inhibiter (TKI) therapy.
An increasing spectrum and number of opportunistic fungal pathogens have been reported to cause disease in humans over the past decade. Disseminated phaeohyphomycoses caused by rare dematiaceous molds in immunocompromised patients have a high mortality rate and are increasingly reported in the literature. Early diagnosis of disseminated phaehyphomycosis is critical especially in neutropenic patients but can be hindered by the low sensitivity of fungal blood cultures and low clinical suspicion. Cutaneous manifestations are often the earliest sign of disease and conducting a thorough skin exam in febrile neutropenic patients can lead to more rapid diagnosis and initiation of treatment. PCR amplification and sequencing of mold RNA extracted from paraffin-embedded tissue can be useful for diagnosing rare fungal infections when negative fungal cultures preclude morphologic diagnosis. Effective treatment for disseminated phaehyphomycosis is lacking and there is a need to report experiences with the use of newer antifungals.
is a major contributor to morbidity and mortality in the United States. Methods for identifying the organism in stool include molecular platforms, enzyme immunoassays (EIAs) for toxin, and culture. Controversy persists over whether molecular tests are too sensitive at identifying , and there are questions about how additional laboratory information could inform clinical management and reduce over treatment. The aim of this study was to assess whether clinical factors are related to the toxin status of patients and whether information about toxin status could potentially inform clinical management of patients. A total of 201 PCR-positive stool samples from adult patients at our institution underwent EIA toxin testing. Clinical and laboratory data were collected, and the percentage of PCR-positive/EIA-positive (PCR/EIA) patients and PCR and EIA-negative (PCR/EIA) patients was calculated. Of the 201 samples, 47% were EIA positive and 53% were EIA negative. Although PCR/EIA patients were more likely to have had a prior infection ( = 0.015), there was no statistical difference between the additional data collected that correlated with a positive EIA result. We were unable to show that patients with an EIA result had worse clinical parameters than those with EIA results and concluded that establishing a testing algorithm that included both PCR and EIA testing would not change the clinical management of patients at our hospital.
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