case_images: PMC10516538_01
case_images: The patient case with multiple cancers or gastrointestinal polyps diagnosed over several years. (A) Diagnosis timeline of the patient. (B) The multiple gastric polyps found by gastroscope. (C) The HE staining of breast fibroadenoma tissue. (D-H) The colonoscopy found multiple lesions of cancer and colonic polyps. The HE stain of colonic (I) and rectal (J) cancer tissues. Newly detected gastric polyps (K) found by endoscope and colonic polyps (L, M) in 2020. (N, O) The HE staining of glioblastoma tissue. (P-S) The IHC examination of Ki-67, CD45, Nestin, and beta-catenin.
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case_images: An electronic gastroscope examination revealed dozens of polyps in the gastric fundus, body, and horn ( Figures 1A, B ). Subsequently, the lump was removed, and post-operative pathological testing revealed fibroadenoma ( Figures 1A, C ). Pathological biopsies from the colonoscopy indicated a diagnosis of multiple primary cancers of the colorectum with a stage of IIA (T3N0M0), accompanied by multiple colonic polyposis ( Figure 1A ). To be specific, the relative positions from the anus and the corresponding diagnosis are as follows: 2 cm and 27 cm, low-to-medium differentiated adenocarcinoma; 15 cm, high-grade intraepithelial neoplasia combining partial cancerization; 18 cm, tubulo-papillary structured adenocarcinoma; 30 cm, papillary adenoma; 60 cm, tubular adenoma combining partially mild-to-moderate differentiated atypical hyperplasia; and 65 cm, mixed polyposis ( Figures 1D-J ). In 2020, at the age of 24, the patient was re-admitted to the hospital twice in May and December due to the discovery of hundreds of gastric and colonic polyps ranging in size from 0.3 cm x 0.3 cm to 0.6 cm x 0.8 cm ( Figure 1A ). All polyps were removed through either EMR or argon plasma coagulation based on their sizes ( Figures 1K-M ). Post-operative pathological diagnosis indicated glioblastoma, NOS (WHO grade IV,  Figures 1A, N-S ).
case_images: Detection of an unreported de novo POLD1 L606M germline variant. IGV snapshots of the heterozygous POLD1 variant tested in (A) patient's rectal tissue, (B) patient's glioblastoma tissue, (C) patient's white blood cell, (D) father's white blood cell, and (E) mother's white blood cell.
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case_images: Table S1 ) revealed a heterozygous germline variant in the polymerase domain of POLD1 (c.1816C>A; p.L606M) ( Figures 2A-C ), which had been reported as somatic mutations in ultra-mutated brain, uterine, and endometrial tumors, although no evidence in clinics of the germline POLD1 p.L606M has been published yet. The POLD1 germline variant was not detected from either the paternal or maternal side ( Figures 2D, E ).