PMC8350481_01
(A) The initial cervical biopsy (100x magnification) demonstrated extensive mitotic activity, high-grade nuclei with hyperchromasia and nuclear molding, scant cytoplasm, and ill-defined cell borders, all characteristic of small-cell carcinoma. (B) The carcinoma was diffusely positive for chromogranin (100x magnification) and synaptophysin (not pictured). (C) Positron Emission Tomography/Computed Tomography (PET/CT) scan at the time of diagnosis that showed evidence of cervical disease, multiple hepatic metastases, and right adrenal gland metastasis.
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The carcinoma cells express neuroendocrine markers synaptophysin and chromogranin ( Figures 1A, B ). MRI and PET/CT imaging, which was positive for uptake in the cervix region. Metastases in the liver and right adrenal gland were also noted ( Figure 1C ), leading to the final diagnosis of stage IV invasive high-grade small cell NEC of the cervix.
(A) PET/CT scan after completing chemoradiation therapy showed no evidence of disease. (B) At the time of diagnosis of recurrent disease, brain MRI and CT scan of the abdomen confirming brain metastasis and multiple hepatic metastatic disease.
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The patient received four additional cycles of the aforementioned carboplatin and etoposide and then underwent a repeat PET/CT scan, which demonstrated complete interval resolution of the previously seen hypermetabolic cervical mass, hepatic mass, and adrenal mass ( Figure 2A ). She underwent imaging, which demonstrated an interval development of hepatic and right adrenal metastatic disease ( Figure 2B , right), as well as a heterogeneously enhancing 2.9 cm likely intra-axial mass involving the right temporal lobe ( Figure 2B , left).
A schematic representation showing treatment course and timeline.
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The family selected hospice care, and the patient expired 15 months after the initial diagnosis ( Figure 3 ).
(A) sCNA at three different time points (left panels) with copy number (log2 ratio) indicated on the y-axis and chromosome on the x-axis. PET/CT images corresponding to the time of liquid biopsy collections (right panels). (B) Diagrammatic representation of the serial trend of tumor fraction at diagnosis, during treatment, and at the time of recurrence. (C) A descriptive comparison of selected gene-level copy number data between time of diagnosis and time of recurrence. -2/-1/0/1/2 refer for homozygous deletion, heterozygous deletion, copy neutral, low gain, and high amplification, respectively.
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TFx was 2.5%. Then 5 months later, she had another evaluation, and her TFx was 36%. This was consistent with the diagnosis of recurrent disease that was evident by imaging, confirming recurrent brain, multiple hepatic, and right adrenal metastasis ( Figures 4A, B ). We sought to investigate sCNA to see if there is a difference between the primary and recurrent disease and if there are interval changes. sCNA at the time of recurrence was comparable with that at the time of initial diagnosis, but with higher amplitude, especially for amplification ( Figure 4A ). Similarly, genes-level copy number data were comparable too with evidence of additional gains at the time of recurrence as evident in selected genes that correspond to certain pathways like PI3K/AKT, RAS/RAF, DNA-damage response, MYC/MCL, TP53, RB1, and others ( Figure 4C ).