PMC8354027_01
(A) Pathological examination of cervical mass revealed squamous cell carcinoma (left panel); pathological findings for the renal tumor were a mixed pattern of mucinous tubular and spindle cell carcinoma (MTSCC) with papillary adenoma in the left kidney (middle panel); and a papillary renal cell carcinoma (PRCC) in the right kidney (right panel). (B) Neoplastic cells in the neck and left kidney showed negative and positive staining for PAX8, respectively.
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After surgical resection, a metastatic squamous cell carcinoma was diagnosed pathologically (Figure 1A, left panel). Histological examination of the radical nephrectomy specimen of the left kidney showed a mixed pattern of mucinous tubular and spindle cell carcinoma (MTSCC) with papillary adenoma (Figure 1A, middle panel). Microscopy examination of the partial nephrectomy of the right kidney revealed a papillary renal cell carcinoma (PRCC) (Figure 1A, right panel). PAX8 staining showed positive expression (Figure 1B). Similarly, the WES results of renal tumor samples revealed 361 somatic variants in 219 genes in the left kidney and 270 somatic variants in 207 genes in right kidney, including five and four driver gene variants, respectively (Figure 3 and Supplementary Figure 1).
Abdomen CT scan with contrast media. Circular iso-density lesions of about 4.4 * 4.2 cm in the upper left kidney (arrow) and an oblong iso-density foci of about 3.4 * 2.1 cm in the middle of the right kidney (arrow).
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Tomographic Angiography) results showed an oblong iso-density foci of about 3.4 * 2.1 cm in the middle of the right kidney, and a 4.4 * 4.2 cm-like circular iso-density lesion in the upper left kidney (Figure 2). The local boundary was unclear from the adjacent renal parenchyma.
Similarity among different lesions based on somatic mutation analysis. (A) Venn diagram illustrating the distributions of genetic mutation in different lesions [left kidney (Tkl) vs right kidney (Tkr) vs neck (Tn)]. (B) Venn diagram illustrating the distributions of driver genetic mutation in different lesions [left kidney (Tkl) vs right kidney (Tkr) vs neck (Tn)].
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Similarly, the WES results of renal tumor samples revealed 361 somatic variants in 219 genes in the left kidney and 270 somatic variants in 207 genes in right kidney, including five and four driver gene variants, respectively (Figure 3 and Supplementary Figure 1). The three lesions have both private and shared mutation genes shown in Figure 3. But no driver mutated gene was shared in all three tissues (Figure 3B).
Analysis of heterogeneity between different lesions. (A) Two-dimensional analysis of tumor subclonal architecture in right kidney (Tkr) and left kidney (Tkl); and (B) in neck (Tn) vs. left kidney (Tkl); and (C) in neck (Tn) vs. right kidney (Tkr). These subclones were shared between the spatially distinct lesions.
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CCF distributions are shown in Figure 4.
Fish plots constructed by timescape. Colors indicate different clones. Driver genes detected in the clones are shown. Tkl, left kidney tumor; Tkr, right kidney tumor; Tn, neck tumor.
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The left renal tumor was mainly composed of clones 3, 4, and 7, the right renal tumor was mainly composed of clones 2, 3, and 6, while the cervical mass was mainly composed of clones 4 and 6 (Figure 5). The putative dynamic mutation profiles during the disease course are represented in Figure 5.