A 52-year-old man was referred to our hospital because of a growing left renal tumor. A contrast-enhanced CT scan revealed the presence of a 93-mm tumor in the upper pole of the left kidney (Fig. a,b) with tumor thrombus observed in the left renal vein (Fig. c). The tumor was gradually enhanced from the corticomedullary phase to the excretory phase. Enlarged lymph nodes were present at the left external iliac lesion; they were extra-regional lymph nodes and no other distant metastasis was observed (Fig. d). We diagnosed him as having left RCC classified as cT3aN0M1.\nOpen radical nephrectomy and dissection of left-sided pelvic lymph nodes were performed. The tumor and lymph nodes were examined macroscopically and microscopically. Macroscopically, a 80 × 80-mm, gray–whitish and solid tumor with necrotic tissue was located in the upper pole of the resected left kidney. Microscopically, the tumor consisted of a tubular and partly papillary structure (Fig. a). The neoplastic cells were cuboidal with eosinophilic cytoplasm. The Fuhrman nuclear grading system is used to describe the RMTSCC., This case was classified as Fuhrman nuclear grade 3 (Fig. b). The tumor was invaded into left renal vein, and metastatic lymph nodes were found at the left external iliac area (Fig. c). Fascicular growth with spindle cells and mucin stained by Alcian blue stain were found (Fig. a). Immunohistochemical findings showed the neoplastic cells to be diffusely positive for AMACR (Fig. b) and CK 7 (Fig. c). CD 10 was negative in the neoplastic cells (Fig. d). Although Ki-67 and p53 were negative in the neoplastic cells with low nuclear grade, they were positive in the neoplastic cells with high nuclear grade (Fig. e,f). We subsequently diagnosed him as having left RMTSCC classified as pT3aN0M1.\nThree months after nephrectomy, a PET-CT scan showed metastasis at the second lumbar vertebra with a maximum standard uptake value of 5.7 (data not shown). Six months after nephrectomy, vertebrectomy was performed for metastasis at the second lumbar vertebra. The pathological findings showed metastasis of the RMTSCC to the second lumbar vertebra. Nine months after nephrectomy, another PET-CT scan showed two 10-mm lymph nodes at the left internal iliac lesion with a maximum standard uptake value of 5.1 (data not shown). These were not regional lymph nodes of RCC, but he was not suffering from other causative diseases such as prostate or rectal cancer. Therefore, we diagnosed these lymph nodes as metastasis of RMTSCC. We are planning on administration of tyrosine kinase inhibitor.
In June 2019, a 53-year-old man was admitted to a local hospital due to a palpable “right neck mass”. He had no fever, dizziness, fatigue, abdominal pain, backache, frequent urination, urgency, or changes in urine color. There was no other positive clinical sign on physical examination. No family history of hereditary diseases was detected. After surgical resection, a metastatic squamous cell carcinoma was diagnosed pathologically (, left panel). In the following PET-CT (Positron Emission Tomography-Computed Tomography) scan showed nodular iso-density foci in the upper pole of the left kidney, with a diameter of about 28.5 mm, SUVmax value of 8.3, increased FDG (fluorodeoxyglucose) metabolism, indicative of malignant lesions, and semi-oval infarct foci in the center of the right kidney. On July 29, 2019, renal puncture was performed, and the pathological diagnosis was epithelial tumor based on the immunohistochemical positive results of relevant markers. SPECT/CT (Single Photon Emission Computed Tomography) showed no obvious abnormalities in blood flow perfusion, uptake and excretion in both kidneys.\nFor further surgical treatment, the patient was transferred to our hospital on August 12, 2019. The renal artery CTA (Computed 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 (). The local boundary was unclear from the adjacent renal parenchyma. It was slightly protruded on the surface of the renal parenchyma, and the lesion was slightly uneven and enhanced by enhanced scan. There was no obvious abnormality in the diagnosis of bilateral renal artery CTA. Kidney magnetic resonance imaging (MRI) confirmed a 2.9 * 1.5 cm circular abnormal signal lesion in the middle of the right kidney and a 3.6 cm diameter circular abnormal signal lesion in the upper pole of the left kidney, which was isointense on T1-weighted imaging (T1WI), a low signal area on fST2WI, and hyperintense on DWI. The signal of the ADC map was reduced, and a slight uneven enhancement was seen by enhanced scan. Based on the above findings, the possible diagnosis was a malignant tumor of the kidney.\nOn August 19, 2019, a laparoscopic radical nephrectomy (left) was performed under general anesthesia. On December 12, 2019, the patient was admitted to the hospital due to a “right kidney mass”. After completing the relevant examinations, the “Da Vinci Robot-Assisted Laparoscopic Partial Right Nephrectomy” was successfully performed. No complication was observed and the patient was discharged six days after surgery. The patient’s condition currently remains stable. PET-CT scan re-examination found no local recurrence or distant metastasis one year after the operation.\nHistological 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 (, middle panel). Microscopy examination of the partial nephrectomy of the right kidney revealed a papillary renal cell carcinoma (PRCC) (, right panel). The histological morphology and immunohistochemical results of renal tumor were different from those of neck tumor. PAX8 staining showed positive expression ().\nTo further investigate their genetic characteristics, whole exome sequencing (WES) was performed separately. A total of 304 putative somatic variants of 225 genes were identified in neck tumor tissues, of which 10 were identified as driver gene mutations, including CDKN2A, KMT2D and NSD1 mutations that are common drivers of head and neck squamous cell carcinoma (HNSC) (). 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 ( and ). The three lesions have both private and shared mutation genes shown in . Similarly, 51, 58 and 47 shared gene variants were detected respectively between left & right kidney, left kidney& neck, and right kidney & neck. Thirty-eight common mutated genes were shared in all three tumor tissues. For the driver gene mutations, the right nephropathy foci shared one driver gene mutation with the left kidney (WT1) and the neck lesions (CREBBP), respectively. But no driver mutated gene was shared in all three tissues ().\nIn addition, a clonal evolution analysis was performed to examine the heterogeneity of tumor evolution among different lesions. We used a previously reported hierarchical Bayesian clustering model () to define clones and subclones based on clusters of SNVs sharing similar cancer cell fractions (CCF). CCF distributions are shown in . These clones and subclones were shared between the spatially distinct lesions. Correspondent clonal components also existed in different lesions, especially some driver gene mutations, such as NFKB2, WT1, GTF2I, etc. The clone evolution analysis showed that the clone components of the initial left renal primary lesion and the final cervical squamous cell carcinoma lesion were different. 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 (). Therefore, the primary clones in the metastatic lesions may not be derived from the primary clones in the left kidney tumor. Instead, they may have originated from the subclones generated before the diagnosis. Some driver gene variants detected in clones with different lesions were unique and some were shared. The putative dynamic mutation profiles during the disease course are represented in . These results can serve as a strong complement to histopathological findings, suggesting that these lesions may have evolved from the original focus, although there are differences in the pathological morphology of different lesions.