Primary renal parenchymal squamous cell carcinoma involving the renal pelvis: a case report and review of the literature

Abstract

Primary squamous cell carcinoma (SCC) of the renal parenchyma represents an exceptionally rare malignancy. We present an SCC case demonstrating renal pelvis invasion, histopathologically confirmed following radical nephrectomy. Postoperative adjuvant chemotherapy was initiated, with subsequent development of pulmonary and adrenal metastases at the 10th-month follow-up. After treatment adjustment, the patient is currently 12 months after the operation and is in good general condition. This case illustrates that a definitive diagnosis of primary renal parenchymal SCC remains achievable despite concomitant renal pelvis involvement, emphasizing the importance of comprehensive histopathological evaluation in such rare presentations.

1. Introduction

Primary squamous cell carcinoma (SCC) of the renal parenchyma is a rare tumor with only ten cases reported. Due to the lack of specificity in clinical manifestations and ancillary tests, some patients are diagnosed at advanced stages, leading to a poor prognosis. In this report, we present a case of primary renal parenchymal SCC with postoperative metastasis. Additionally, we provide a review of the recent relevant literature.

2. Case report

A 66-year-old male patient presented to our institution with loin pain and fever lasting for one week. The patient had a medical history of lumbar disc herniation, hypertension, and right kidney stones and had previously undergone percutaneous nephrolithotomy (PCNL) on the right kidney. Physical examination revealed significant percussion pain in the left renal region, with no other abnormal signs.

On admission, his routine blood test results revealed a white blood cell count (WBC) of 16.00 × 10⁹/L, absolute monocyte count of 0.86 × 10⁹/L, absolute neutrophil count of 13.56 × 10⁹/L, neutrophil percentage of 84.74 %, platelet count (PLT) of 404 × 10⁹/L. Routine urinalysis showed leukocytes 449/μL. Amyloid level was more than 320.00 mg/L. High-sensitivity C-reactive protein (hs-CRP) was 125.01 mg/L. Procalcitonin (PCT) was 0.15 ng/mL. Liver and renal functions were normal. Computed tomography scan showed an enlarged left kidney with hypodense changes in the renal parenchyma. Further contrast-enhanced computed tomography (CECT) scan showed heterogeneous enhancement of the left kidney with disorganization of the renal pelvis and calyces, accompanied by multiple foci of patchy calcification (Fig. 1). This presentation was initially considered to be xanthogranulomatous pyelonephritis (XGP) or tuberculosis; however, a tumor could not be ruled out. Subsequent tuberculin purified protein derivative (PPD) tests were negative, anti-infective therapy was ineffective, and the patient continued to have fever. Further testing of tumor markers showed that Carbohydrate Antigen 19-9 (CA19-9) was 118.20 U/mL, Carbohydrate Antigen 125 (CA125) was 64.40 U/mL, Carcinoembryonic Antigen (CEA) was 5.52 μg/L, and Cytokeratin 19 Fragment 21-1 (CYFRA21-1) was 26.67 ng/mL. Considering the possibility of a left renal tumor, left nephron exploratory surgery was planned, with nephrectomy to be performed if necessary.

Fig. 1.

Abdominal CECT (A) Axial: mild enlargement of the left kidney; the renal pelvis and renal calyces are not clearly shown, with uneven enhancement. (B) Coronal: dilatation of the renal pelvis, with multiple patchy calcifications. (C) Sagittal: disorganization of the renal pelvis and calyces, and dilatation of the renal pelvis.

The patient underwent radical nephrectomy under general anesthesia. Intraoperative examination revealed that the left kidney was significantly enlarged, hardened, and extensively adhered to the surrounding tissues, and no other lesions were seen in the operative field. Gross pathological examination indicated that the resected left kidney measured 12 cm × 7.5 cm × 6.2 cm, while the tumor measured 9.5 cm × 5.7 cm × 5.6 cm. The tumor appeared grayish-white and firm, exhibiting extensive necrosis and calcification on the cut surface (Fig. 2). Histological findings showed a moderately differentiated SCC involving the entire renal parenchyma and part of the renal pelvis, but not affecting the ureteral cut edge or the perinephric fat capsule. Microscopically, normal glomeruli, intercellular bridges, and keratinized debris were observed in the renal parenchyma, with the invasion of the SCC into the renal pelvis (Fig. 3 A and B). No squamous metaplasia of the uroepithelium or carcinoma in situ was identified. A biopsy of the renal hilar lymph nodes was performed, revealing metastasis in 1 out of 17 nodes. Immunohistochemical results showed P63 (+), P40 (+), CK20 (−), GATA3 (some weakly +), Uro (−), RCC (−), Pax8 (mostly +), CD34 and D2-40 (no intravascular cancerous emboli were observed), S100 (nerve bundles +), P53 (approximately 10 % +), CerbB-2 (approximately 3 % +), and Ki-67 (∼30 % in hot spots) (Fig. 3C and D).

Fig. 2.

(A) The size of the resected kidney was 12 cm × 7.5 cm × 6.2 cm. (B) The two-part nephrectomy specimen showed a grayish-white tumor with extensive necrotic calcification on the cut surface.

Fig. 3.

(A) Histologic examination shows moderately differentiated squamous cell carcinoma within the renal parenchyma, with visible normal glomeruli, intercellular bridges, and keratinized fragments (at arrows) (HE staining, 200 × ). (B) Histologic examination shows squamous cell carcinoma gradually invades the renal pelvis from the renal parenchyma. (HE staining, 200 × ). (C) Immunohistochemistry, CK20 negative (200 × ). (D) Immunohistochemistry, Pax8 positive (200 × ).

The postoperative adjuvant chemotherapy regimen was initially a combination of gemcitabine in combination with cisplatin; however, it was changed to gemcitabine monotherapy after 1 cycle because of abnormal renal function. A CECT examination conducted 10 months after surgery suggested the possibility of metastatic tumors in the left adrenal region and the posterior segment of the upper lobe of the lung. A lung puncture biopsy confirmed the tissue pathologically as metastatic renal parenchymal SCC. Immunohistochemistry test results were P40 (+), P63 (+), CK5/6 (+), CK7 (+), P504S (−), GATA3 (partially weak +), CK20 (−), and UROIII (−). Genetic testing revealed no genetic variants and microsatellite stability. After a multidisciplinary discussion, the treatment regimen was adjusted to include albumin-bound paclitaxel in combination with bevacizumab. Currently, 12 months post-surgery, the patient has completed the second stage of 3 cycles of chemotherapy and is in good general condition. The patient will continue to be followed up.

3. Discussion

Primary SCC of the kidney is a rare malignant tumor, accounting for 0.5 %–0.8 % of all renal malignancies. ¹ It includes renal parenchymal SCC and renal pelvic SCC, with the majority being renal pelvic SCC. In contrast, renal parenchymal SCC is extremely rare, with only 10 cases reported so far (Table 1).2, 3, 4, 5, 6, 7, 8, 9, 10 Urolithiasis and hydronephrosis are considered to be predisposing factors for renal SCC.2, 3, 4^,6

Table 1.

Literature report on primary parenchymal squamous cell carcinoma of the kidney.

	Author	Age	Presentation	Location	Treatment	Tumor extent	Renal stone	Involvement of renal pelvis	Chemotherapy	Prognosis
1	Terada2	73	Hematuria and lumbago	Multiple: Bladder, left ureter, and left kidney	Cystectomy and nephroureterectomy	Replacing entire kidney parenchyma	Absent	Absent	Absent	Alive and disease free at 3 months after surgery
2	Kulshreshtha3	60	Weight loss for 3 months	Mid and lower pole of the left kidney	Radical nephrectomy with lymph node dissection	6.5 cm × 5.5 cm, with Gerota's fascia invasion and para-aortic lymph node metastasis (pT4N1)	Absent	Absent	Absent	Alive and disease free at 13 months after surgery
3	Ghosh and Saha4	51	Dull and intermittent flank pain for 5 months	Lower pole of the right kidney	Radical nephrectomy	5.8 cm × 5.5 cm (pT1bN0)	Absent	Absent	Absent	Alive and disease free at 12 months after surgery
4	Sahoo et al.5	50	Right abdomen pain for 6 months	Upper pole of the right kidney	Radical nephrectomy	8.0 cm × 6.0 cm (pT2aNx)	Absent	Absent	Absent	Alive and disease free at 6 months after surgery
5	Wang et al.|6	61	lematuria and lumbago or 2 months	Right kidney	Radical nephrectomy	NA, with perirenal fat invasion (pT3aNx)	Absent	Absent	Absent	Alive and disease free at 1 month after surgery
6	Zhang et al.7	61	Intermittent flank pain for 2 months	Lower pole of the right kidney	Radical nephrectomy	With perirenal fat invasion (pT3aNx)	Absent	Absent	Absent	Alive and disease free at 3 months after surgery
7	Fotovat et al.8	41	Flank pain and dysuria for 3 months	Lower pole of the left kidney	Radical nephrectomy	With perirenal fat invasion and para-aortic lymph node metastasis (pT3aN1)	Present	Absent	Absent	Metastasis to ovary at 8 months after surgery
8	Zhang et al.7	61	Flank pain and weight loss for 2 months	Lower pole of the right kidney	Radical nephrectomy with right hemicolectomy	9.0 cm × 8.0 cm, with ascending colon invasion (pT4N0)	Present	Absent	Absent	Alive and disease free at 5 months after surgery
9	Liang et al.9	52	1 week of renal cyst found in physical examination	Upper pole of the right kidney	Robot-assisted partial nephrectomy	8.3 cm × 8.2 cm × 8.1 cm (pT2aNxM0)	Absent	Absent	Absent	Alive and disease free at 6 months after surgery
10	Zheng et al.10	51	Hematuria and lumbago for 2 weeks	Right kidney	Radical nephrectomy with lymph node dissection	6.0 cm × 6.0 cm, with perirenal fat invasion and para-aortic lymph node metastasis (pT3aN1)	Present	Absent	Absent	Metastasis to Liver and inferior vena cava metastases at 4 months after surgery
11	This study	66	loin pain and fever for 1 week	Left kidney	Radical nephrectomy with lymph node dissection	9.5cm × 5.7cm × 5.6cm, with para-aortic lymph node metastasis (pT2aN1)	Present	Present	Present	Metastasis to the right lung and adrenal region at 10 months after surgery and alive at 12th months

Regarding the histological origin of renal SCC, the prevailing view is that urothelial SCC originates from squamous metaplasia of the urothelium. When identifiable uroepithelial anisotropic hyperplasia or uroepithelial carcinoma in situ (CIS) is present in the tumor tissue, it should be classified as primary uroepithelial carcinoma with squamous metaplasia. However, the presence of significant keratinizing squamous epithelial hyperplasia in the adjacent flattened uroepithelium (especially when accompanied by heterogeneous hyperplasia) supports the diagnosis of primary renal pelvic SCC. Therefore, an important prerequisite for the diagnosis of primary SCC of the renal parenchyma is that the renal pelvis should be histologically normal, ^2,3,7 and primary tumors elsewhere need to be excluded. ^4,7 The review of the literature showed the tumor did not involve the renal pelvis in any of the reported cases. However, the pathology of the patient in this case showed partial renal pelvis involvement, but the authors still preferred the diagnosis of primary renal parenchymal SCC to primary renal pelvic SCC with extensive invasion of the renal parenchyma, mainly based on the following bases: Firstly, pathological histology showed that the entire renal parenchyma was invaded by cancerous tissues, which invaded from the parenchyma to the renal pelvis in a gradual manner, and the absence of uroepithelial heterogeneous proliferation and CIS within the renal pelvic tissues as confirmed by extensive sampling and CIS, immunohistochemistry showed CK20(−), P63 (+), and P40 (+), suggesting non-urinary epithelial squamous carcinoma, while Pax8 (mostly +) and GATA3 (partly weakly +), which were more supportive of renal parenchymal origins; Secondly, the patient developed lung metastasis 8 months after surgery, and its immunohistochemical features matched with the metastatic renal parenchymal tumors; Lastly, although restricted by the lack of positron emission tomography–computed tomography (PET-CT) device, primary tumors from other sites were excluded by whole-body CECT combined with histopathology.

Primary renal parenchymal SCC is often diagnosed late in the disease course due to the absence of characteristic clinical and imaging manifestations. ⁴ The review of the literature revealed that lumbar and abdominal pain are the most common clinical symptoms, while urinary-specific symptoms (e.g., hematuria and dysuria) were present in only four patients. In the present case, the patient exhibited only loin pain and fever, without any typical urinary symptoms. CECT showed mild enlargement of the left kidney, hypodense foci within the renal parenchyma accompanied by stones, and structural irregularities of the renal pelvis and calyces. These findings initially suggested a diagnosis of XGP or tuberculosis. It is worth noting that among the reported cases, there were four instances of patients with combined stones similar to this case. The presence of combined stones, as a characteristic of XGP, typically necessitates a differential diagnosis from primary renal parenchymal cell carcinoma. In addition to CECT, tumor marker tests also provide adjunctive diagnostic value; in this case, the patient exhibited significantly elevated levels of tumor markers. Furthermore, recent studies have highlighted the importance of the squamous cell carcinoma-specific antigen (SCCA) test for diagnosing SCC.10, 11, 12 Although this test was not initially performed in this case, follow-up monitoring showed postoperative SCCA levels between 1.4 and 2.4 ng/mL (normal range: 0–1.5 ng/mL), and a mildly elevated SCCA of 2.1 ng/mL at the time of discovery of the metastases, suggesting the potential adjunctive diagnostic value of this indicator. However, it is essential to emphasize that histopathological examination remains the gold standard for confirming the diagnosis, and the final diagnosis in this case supports this assertion. ⁹

The late diagnostic features of primary renal parenchymal SCC mostly contribute to its poor prognosis. The review of the literature shows that more than half of the patients were diagnosed at pT3 or higher, with four patients having definite lymph node metastases. Radical nephrectomy tends to be the primary treatment, while previous studies have suggested that postoperative chemotherapy has a marginal effect. ^4,7 In the reported literature, only one patient received postoperative chemotherapy and continued treatment after developing metastases 8 months post-surgery, ultimately succumbing to a reaction to the chemotherapy.⁸ In this study, the patient underwent chemotherapy but still presented with metastases in the right lung and adrenal gland region ten months after surgery. After genetic testing and multidisciplinary consultation, he was treated with the anti-VEGF-targeted drug bevacizumab, and the patient's overall condition is now clinically well. This experience suggests that for postoperative patients and those with metastases, although conventional postoperative chemotherapy may not provide direct benefits, chemotherapy and targeted drug therapy remain viable treatment options after surgery. However, their efficacy requires validation through long-term follow-up.

4. Conclusion

Primary renal parenchymal SCC is an extremely rare malignant tumor characterized by nonspecific clinical manifestations and imaging features, which complicate early diagnosis. Consequently, most patients are diagnosed at advanced stages of the disease. Histopathological examination is the gold standard for diagnosis, with the critical factor being the determination of whether the tumor originates from the renal parenchyma or the renal pelvis. Notably, even in cases of the tumor invading the renal pelvis, a diagnosis of primary renal parenchymal SCC may still be possible. Currently, surgical resection is the primary treatment approach and postoperative adjuvant chemotherapy or new targeted drug therapy may be considered. However, the efficacy of these adjuvant treatments requires further validation through long-term follow-up observation.

CRediT authorship contribution statement

Junjun Wu: Writing – review & editing, Writing – original draft, Formal analysis, Data curation, Conceptualization. Lei Wang: Writing – original draft, Formal analysis. Pengpeng Zhao: Writing – review & editing, Formal analysis. Fuxiang Lin: Writing – original draft, Formal analysis. Zhanping Xu: Writing – review & editing.

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.