case_images: PMC9185004_01
case_images: (a) H&E, PD-L1 expression, and T-cell populations in the 2014 tumor
  biopsy. H&E shows a low-grade glioma, PD-L1 negative, T-CD4 negative and
  with scant perivascular T CD8+ cells. (b) Pedigree depicting the cancer
  history of the patient's family, reflecting an autosomal dominant pattern of
  inheritance. (c) Mismatch-repair protein IHC shows preserved expression of
  MSH2 and MSH6, partial PMS2 expression and complete lack of expression of
  MLH1. (d) Sanger sequence of the patient's peripheral blood lymphocytes
  demonstrating a pathogenic MLH1 mutation [c.1865 T > A
  (p.L622 H)].. CRC, colorectal cancer; HGD, high-grade dysplasia; LGG, low-grade glioma;
  (+), mutation carrier; (-), noncarrier.
case_images: 10.1177_17588359221100863-fig1.jpg
case_images: PMC9185004_01_10.1177_17588359221100863-fig1.jpg
case_images: fig1-17588359221100863
case_images: The patient underwent germline genetic testing that confirmed the carrier status of the pathogenic hMLH1 mutation previously detected in his paternal uncle (Figure 1).
case_images: MRI tumor evolution from initial diagnosis until the end of therapy.. Upper row: A large nonenhancing glioma in the left temporal lobe is seen in
  the MRI from December 2012. A biopsy informed of a grade-II IDH wild-type
  astrocytoma (according to WHO 2007 4th edition that corresponds to an IDH
  wild-type GB according to WHO 2021 5th edition classification of CNS tumors)
  and treatment with single-agent temozolomide was administered for 12 months
  until PD occurred in January 2014. A partial tumor resection was made
  followed by adjuvant RT between April and May 2014. A W&S strategy
  started until February 2015 when due to PD, treatment with FTM was
  administered between February and May 2015, suffering PD.. Treatment with Bevacizumab 10 mg/kg/q2wk was started in June 2015,
  experiencing a rapid and complete/near-complete tumor response after only
  four cycles that was maintained until February 2017, when a W&S strategy
  was began until April 2018, when PD occurred. Yellow arrows indicate the
  tumor in cases of PD. The yellow box indicates the post-contrast MRI from
  May 2015 where the tumor progression was observed. Although radionecrosis
  was also present, the very high perfusion values (VSRr) indicate a
  predominant tumor component. The blue box indicates the post-contrast MRI
  from July 2015, where a major tumor response after bevacizumab can be
  seen.. Lower row: The patient started a rechallenge with bevacizumab 10 mg/kg/q2wk
  in April 2018, showing progressive disease as the best response in June 2018
  but without clinical deterioration until November 2018, when therapy was
  stopped and treatment with nivolumab 3 mg/kg/q2wk started. After four
  cycles, MRI in February 2019 showed progressive disease. Due to concerns of
  a potential PsPD due to an immune-mediated response, a tumor biopsy was
  performed that was reported as GB with a very scant T-cell infiltrate (not
  shown). Given the clinical stability, it was decided to continue nivolumab
  beyond progression. In May 2019, MRI showed an overt radiologic progression
  with clinical deterioration (worsening aphasia and gait instability).
  Treatment with reduced-dose irinotecan (125 mg/m2/q2wk) combined with
  bevacizumab (10 mg/kg/q2wk) was started with significant toxicity (G2
  diarrhea, G3 asthenia) after the first cycle, and the patient and his family
  decided to definitively stop treatment, being transferred to a
  palliative-care facility.. BEV, bevacizumab; CNS, central nervous system; CPT-11, irinotecan; CR,
  complete response; FTM, progressive disease; IDH, isocitrate dehydrogenase;
  MRI, magnetic resonance imaging; Nivo, nivolumab; PD, progressive disease;
  PsPD, pseudoprogression; RT, radiotherapy; SD, stable disease; T1 PC,
  post-contrast T1 image; TMZ, temozolomide; VSRr x 8, perfusion value
  equivalent to eight times that of the normal-appearing contralateral white
  matter; W&S, wait and see.
case_images: 10.1177_17588359221100863-fig2.jpg
case_images: PMC9185004_01_10.1177_17588359221100863-fig2.jpg
case_images: fig2-17588359221100863
case_images: Due to toxicity (grade III asthenia, and grade II diarrhea), however, treatment was permanently discontinued after one single cycle administered in June 2019, and the patient was transferred to hospice for end-of-life care where he died 3 months later (Figure 2).