Uncommon metastatic pattern of renal cell carcinoma (simultaneous metastasis to the small intestine and skeletal muscle): A case report

Abstract

BACKGROUND

Metastasis of renal cell carcinoma (RCC) to the skeletal muscle and small bowel is an exceedingly rare occurrence. Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.

CASE SUMMARY

A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies. Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.

CONCLUSION

This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.

Key Words: Clear cell renal cell carcinoma; Renal cell carcinoma; Skeletal muscle metastasis; Small bowel metastasis; Upper gastrointestinal bleeding; Melena; Case report

Core Tip: Renal cell carcinoma is a malignant tumor that can recur despite treatment similar to other malignancies. The recurrence can present itself as a metastatic process. The involvement of two sites simultaneously as metastatic recurrence is quite uncommon, more so for that to be the small intestine and the skeletal muscle (psoas).

INTRODUCTION

Renal cell carcinoma (RCC) is a type of urogenital cancer, accounting for approximately 3% of solid tumors in adults, with peak incidence occurring between ages 60 years and 70 years. RCC is more prevalent and has a higher mortality rate in men than in women[1,2]. Originating from tubular epithelial cells, RCC constitutes around 90% of all adult renal malignancies[3]. Several risk factors, including obesity, hypertension, smoking, chronic kidney disease, and genetic predispositions, contribute to RCC development[3]. RCC often presents with symptoms such as a palpable abdominal mass, hematuria, and flank pain; however, a significant number of cases remain asymptomatic and are incidentally discovered during abdominal imaging performed for unrelated conditions[3].

The mortality rate for RCC ranges between 30% and 40%[3]. Clear cell RCC (ccRCC), the most common subtype, arises from the epithelial cells of the proximal renal tubules and is associated with a poorer prognosis than other subtypes. Mortality from RCC has declined in developed countries, largely due to earlier detection and advanced therapies. RCC metastasizes through hematogenous spread, and at the time of diagnosis, approximately 20%-30% of patients present with metastatic disease. Furthermore, 40% of patients with initially localized disease who undergo nephrectomy with curative intent will eventually develop metastases[2]. Common sites of metastasis include the lungs, bones, and brain, while metastasis to the gastrointestinal (GI) tract, specifically to the stomach and small intestine, is rare[4]. Synchronous metastasis to both the small intestine and skeletal muscle is extremely uncommon and may sometimes represent the initial sign of recurrent RCC. GI tract metastases from RCC can manifest as bleeding, obstruction, perforation, or intussusception[5]. In the current case, the diagnosis was established following an investigation for upper GI bleeding.

Surgery is the preferred treatment for localized, early-stage RCC, whereas advanced or metastatic RCC treatment options include systemic immunotherapy, targeted therapies against vascular endothelial growth factor or mechanistic target of rapamycin, immune checkpoint inhibitors, chemotherapy, radiation, or observation, depending on disease extent and patient-specific factors[6,7].

This report describes the rare occurrence of synchronous metastases to the small intestine and skeletal muscle following a 20-year remission, underscoring the importance of recognizing atypical metastatic patterns. Early suspicion of RCC should be maintained when unusual lesions are identified during skeletal muscle imaging or endoscopy.

CASE PRESENTATION

Chief complaints

A 58-year-old male presented to the Department of Emergency with new-onset worsening abdominal distention, lower extremity edema, right upper quadrant pain, and dyspnea on exertion.

History of present illness

Upon further questioning, he reported three weeks of dark, tarry stools. In the Department of Emergency, he was found to have tachycardia, mild hypotension, and a distended abdomen with ascites.

History of past illness

Patient had a past medical history significant for RCC status post-nephrectomy at age 38 years, hypertension, nonalcoholic steatohepatitis-related liver cirrhosis, and diabetes mellitus.

Personal and family history

No known significant family history.

Physical examination

In the Department of Emergency, he was found to have tachycardia, mild hypotension, and a distended abdomen with ascites.

Laboratory examinations

Laboratory evaluation revealed iron deficiency anemia, with a hemoglobin level of 9.9 g/dL, compared to his baseline of 14.6 g/dL recorded 8 months prior. The gastroenterology team was consulted for further evaluation of melena, suspected upper GI bleeding, and new decompensation of cirrhosis. An ultrasound demonstrated findings consistent with cirrhosis and splenomegaly. Esophagogastroduodenoscopy and colonoscopy revealed a small column of esophageal varices without high-risk stigmata, portal hypertensive gastropathy, and irregular-appearing folds with intermittent oozing in the second portion of the duodenum (Figure 1). Biopsies of the duodenal irregularities revealed metastatic ccRCC (Figure 2).

Figure 1 Intermittently oozing and irregular appearing folds in the duodenum.

Figure 2 Small bowel biopsy showing submucosal metastatic clear cell renal carcinoma, polypoid mucosa with moderate acute and chronic inflammation. A: Hematoxylin and eosin (HE) stain (4 ×); B: HE stain (40 ×).

For further evaluation of the new decompensation and ascites, diagnostic and therapeutic paracentesis was performed. The ascitic fluid was negative for malignancy, and the serum-ascites albumin gradient was consistent with portal hypertension. The patient was started on diuretic therapy with torsemide and spironolactone to address abdominal distention, lower extremity edema, and dyspnea.

Imaging examinations

An abdominal ultrasound with duplex imaging was obtained to evaluate for a new liver mass or portal vein thrombosis as potential causes of the decompensation. While the ultrasound showed a cirrhotic liver and splenomegaly, no liver mass or thrombosis was identified. However, a new left renal mass was noted. Further evaluation with magnetic resonance imaging of the abdomen and pelvis revealed two masses within the left kidney, raising concerns for primary renal malignancy, as well as metastatic lesions in the liver and a 3 cm mass in the right psoas muscle (Figure 3). A subsequent biopsy of the right psoas muscle lesion confirmed metastatic ccRCC, and immunohistochemical staining of the biopsy showed positivity for several markers consistent with RCC (Figure 4). The pathology revealed atypical cells that were hyperchromatic, had mildly irregular nuclei, clear abundant cytoplasm and further testing with markers helped establish the diagnosis.

Figure 3 Abdominal magnetic resonance imaging showing a 3 cm mass within the right psoas muscle.

Figure 4 Mass, right psoas muscle core biopsy showing focal skeletal muscle involvement by atypical cells with hyperchromatic, mildly irregular nuclei, occasional inconspicuous nucleoli and clear abundant cytoplasm associated with a fine vascular network. Findings consistent with metastatic clear cell renal cell carcinoma. A: Hematoxylin and eosin (HE) stain (10 ×); B: HE stain (40 ×).

MULTIDISCIPLINARY EXPERT CONSULTATION

Gastroenterology and oncology team were consulted.

FINAL DIAGNOSIS

Metastatic RCC.

TREATMENT

For management of his anemia due to ongoing bleeding, the patient was administered intravenous iron to replenish iron stores. The medical oncology team was consulted, and the patient was initiated on combination immunotherapy with nivolumab and ipilimumab for treatment of recurrent RCC. He continued follow up as outpatient and eventually pursued hospice due to overall quality of life and no significant response to treatment.

OUTCOME AND FOLLOW-UP

He continued follow up as outpatient and eventually pursued hospice due to overall quality of life and no significant response to treatment.

DISCUSSION

RCC metastasis to the GI tract, though rare, is an important consideration in patients with a history of RCC who present with GI symptoms, particularly after a prolonged remission. RCC typically metastasizes to the lungs, bones, brain and liver, with only a small fraction of cases involving the GI tract, predominantly reported in isolated case reports and case series[4,8]. Metastasis to both the small intestine and skeletal muscle, as observed in this patient, is exceedingly uncommon and underscores the unique metastatic patterns of RCC. Notably, this case occurred after a 20-year remission period, highlighting RCC’s potential for late recurrence and its unpredictable metastatic behavior. Up to 40% of patients without detectable metastasis at the time of initial diagnosis develop metastatic disease following nephrectomy performed with curative intent[2,9]. While the exact mechanism of metachronous metastasis remains unknown, Paget’s ‘seed and soil’ theory is often implicated[10,11].

Despite extensive research, the exact mechanism of RCC metastasis remains unknown. Hematogenous spread, lymphatic dissemination, direct invasion, and procedural implantation have all been implicated, with hematogenous spread thought to be the primary pathway, likely due to the tumor’s hyper-vascular nature[12]. The small intestine, although an unusual site, can be affected through systemic circulation. Skeletal muscle metastasis is similarly uncommon, as skeletal tissue is generally resistant to metastatic seeding[13]. Sun et al[14] reported two cases of RCC metastasizing to skeletal muscle: (1) One involving recurrence in the vastus lateralis muscle; and (2) Another where RCC was first identified as a mass in the right psoas and gluteus maximus muscles. Both cases resulted in death, underscoring the fact that skeletal muscle metastasis in RCC is often a poor prognostic indicator. Metastasis to skeletal muscle is frequently insidious, as patients may remain asymptomatic until the metastatic lesions grow large enough to cause pain and swelling due to mass effect[14,15].

Although the incidence of RCC has increased over the past decade, likely due to advancements in and more frequent use of imaging, mortality has decreased due to developments in therapeutic options[1]. Managing metastatic RCC requires a multidisciplinary approach, often involving both metastasectomy and systemic therapy. Without treatment, the 5-year survival rate for metastatic RCC is less than 20%. However, surgical resection of isolated metastatic lesions can improve 5-year survival rates to 35%-50%[14].

To the best of our knowledge, simultaneous metastasis to both the skeletal muscle and small bowel has not been previously reported. The presence of synchronous metastases in the duodenum and psoas muscle suggests an aggressive recurrence pattern, possibly facilitated by molecular and microenvironmental changes that enabled these atypical sites to support metastatic growth after years of dormancy.

In this case, the patient’s presentation with melena and iron deficiency anemia prompted an evaluation that ultimately led to the diagnosis of GI metastasis. The intermittent oozing and irregular duodenal folds observed on endoscopy, combined with histopathological confirmation of ccRCC, pointed to a metastatic process. Based on case reports that characterize these rare manifestations of RCC, we emphasize the need for heightened awareness of these atypical presentations. This illustrates the importance of a high index of suspicion in patients with prior RCC and GI symptoms, as RCC recurrence may initially mimic common GI pathologies, potentially delaying accurate diagnosis.

CONCLUSION

The unusual presentation of RCC in this case, following two decades of remission, illustrates RCC’s potential for delayed recurrence and the importance of extended surveillance. Although the advent of targeted therapies and immunotherapy has improved outcomes for metastatic RCC, the prognosis for patients with GI tract and muscle involvement is typically poorer. Hence to prevent risk for metastasis, close follow up with oncology and urology is needed to monitor periodically with imaging studies and for any concerning symptoms. This case highlights the importance of lifelong follow-up for RCC survivors, even in the absence of symptoms, to facilitate early detection of late recurrences that may manifest in atypical locations.