PMC9706001_01
CT scan images of neck and hematoxylin-eosin (HE) staining of three tumors (x100). (A) A 66 mmx54 mm round soft tissue mass shadow in the left neck. (B) Further contrast-enhanced CT scan showed ring enhancement. (C) CT scan image of neck at 6 months post-treatment. (D) CT scan image of neck at 10 months post-treatment. (E) HE staining of rectal mucinous adenocarcinoma, (F) prostate adenocarcinoma, and (G) undifferentiated sarcoma of the left neck. Solid arrows indicate tumor masses; dashed arrows indicate significant tumor regression.
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Figure 1A ), supraclavicular area and superior mediastinum, with multiple enlarged lymph nodes around, and the trachea, thyroid and esophagus were pushed to the right, with local tracheal narrowing. Further contrast-enhanced CT scans showed ring enhancement ( Figure 1B ), and a lack of clear demarcation between the mass and the esophageal wall. More specifically, the surgical pathology confirmed a diagnosis of rectal mucinous adenocarcinoma ( Figure 1E ), while the tumor invaded through the muscularis propria and into the adipose tissue outside the intestinal wall (pT3), without tumor vascular thrombus or perineural invasion around the tumor, with negative surgical margins. The pathological diagnosis of prostate biopsy revealed prostate adenocarcinoma with Gleason 3 + 4 ( Figure 1F ). Microscopically, tumor cells displayed striking atypia and epithelioid morphology, infiltrating into skeletal muscle, without lymph node structure detected ( Figure 1G ). Reassuringly, significant regression of the left neck tumor was observed after two cycles of treatment, and the curative effect was evaluated as partial response (PR) according to the RECIST criteria and then maintained the state of PR during a follow-up of 14 months, which further supported our diagnosis ( Figures 1C, D ).
Immunohistochemical staining for DNA mismatch repair proteins (MMR proteins MSH6, MSH2, MLH1, and PMS2) of three tumors (x100). (A-D) Absence of MSH6 and MSH2 staining, and positive staining for MLH1 and PMS2 in the rectal mucinous adenocarcinoma; (E-H) Absence of MSH6 and MSH2 staining, and positive staining for MLH1 and PMS2 in the prostate adenocarcinoma; (I-L) Absence of MSH6 and MSH2 staining, and positive staining for MLH1 and PMS2 in the undifferentiated sarcoma of left neck.
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Immunohistochemistry showed complete loss of MSH2 and MSH6 expression but normal MLH1 and PMS2 expression ( Figure 2 ). NGS result of MSH2 also showed that tumor tissues had higher mutation abundance than the control (84% vs 48%, respectively) ( Supplementary Figure S2 ). Immunohistochemistry showed complete loss of MSH2 and MSH6 expression but normal MLH1 and PMS2 expression ( Figure 2 ). As expected, dMMR was also confirmed by immunohistochemical staining, consistent with the phenotypes of rectal mucinous adenocarcinoma and prostate adenocarcinoma ( Figure 2 ).
Timeline scheme of the major clinical event of the patient.
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For more details, see  Supplementary Figure S3 . The timeline scheme of the major clinical event of the patient is represented in  Figure 3 .