Case report

Dr. Martellucci

We present a case of Caucasian 36-year-old man, presenting the Emergency Department (ED) after performing blood test for asthenia, revealing a severe anemia (hemoglobin 6.1 g/dL), associated with iron deficiency, increased C-Reactive protein (CRP) levels, erythro-sedimentation rate, altered liver enzymes (AST and ALT), increased number of platelets (more than one million/mm3). Hypocholesterolemia, hypotriglyceridemia, and high direct hyperbilirubinemia were also present.

The patient referred only tiredness and the absence of evident bleeding. The work activity was personal trainer and in clinical history: diagnosis of Marcus Gunn syndrome and abuse of anabolic androgenic steroids for body building for 9 years. The patient denied smoking and alcohol intake, as well as exposure to environmental toxicants. The family history was negative for cardio-pulmonary diseases, as well as cancer and diabetes. In ED the vital parameters were within normal range. Cardiac and thoracic physical examination were without alterations. The abdomen was difficult to evaluate due to hypertrophy of the rectus abdominis muscles. The blood tests confirmed the severe anemia, and showed high levels of CRP (21 times above the normal values), AST, ALT, gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), abnormal platelets values and high direct bilirubinemia (1.74 mg/dL). Pseudocholinesterase was reduced and the SARS Cov-2 swab (RT-PCR) resulted negative. A blood transfusion and abdominal CT were performed. The CT scan performed at the ED showed a voluminous (15 cm) neoformation localized in the middle and upper third of the right kidney with inhomogeneous appearance due to the presence of colliquative areas, calcifications and no clear signs of active bleeding in the lesion. In addition, the radiologist described a significantly enlarged steatotic liver with an hypervascular nodular neoformation (15 mm) (IV hepatic segment) presenting with rapid washout. The patient was transfused with additional two units of blood and again after 4 days. The saturation of transferrin was 8.4% and reticulocytes, after transfusion, were 131.000 cells/mm3, with aptoglobine levels within normal range.

Dr. Melena

Upon admission to our Internal Medicine Unit, the patient was in stable clinical condition, with fever (37.8 °C) and heart rate of 110 bpm. Hepatomegaly was detected at physical examination. For the presence of fever, blood cultures were requested, resulting negative. Additional blood tests were normal with exception of increased tumor antigen CA 15.3, transaminases, the presence of iron deficiency and thrombocytosis.

Considering the steroids abuse, an echocardiography, a total body CT scan and an abdominal MRI were performed. The patient was the transfused several times in our Unit (due to hemoglobin levels below 8 g/dL). The echocardiography, performed due to the high prevalence of cardiovascular risk and testosterone [1], showed: left ventricle of dimensions at the upper limits with increased wall thickness. Preserved ejection fraction. A dilatation of the left atrium. Mild to moderate mitral insufficiency. Mild tricuspid insufficiency. The CT scan (Fig. 1) confirmed the right renal neoformation and an enlarged left kidney with preserved cortico-medullary structure and hepatomegaly with a longitudinal diameter of 37 cm. In the liver three nodular formations (max 15 mm) in the III, IV and VI segments with enhancement in the arterial phase and washout in the venous and late phases (excluding thrombosis, which is often associated with cancer [2, 3]) were described compatible with transient hepatic attenuation differences (THAD), a hepatic perfusion anomaly [4] as also confirmed by MRI (Fig. 2).

Fig. 1
figure 1

CT scan (axial) showing the large right renal mass

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Fig. 2
figure 2

MRI image (abdomen) confirming the right renal mass and the presence of hepatomegaly

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Dr. Assanto and Prof. Molfino

After an interdisciplinary meeting, including internists, radiologist, abdominal surgeon, urologist and oncologist, nephrectomy was indicated as the primary treatment for the patient. Gastroscopy and colonoscopy, before surgery, excluded gastrointestinal bleeding. At Urology Unit total right nephrectomy and hepatic lesions biopsy, during surgery, were performed, without complications. Histological examination confirmed a clear-cell renal carcinoma (ccRC) with no vascular or capsular invasion and the liver biopsy revealed a hepatocellular adenoma. The patient was then discharged in good condition with subsequent outpatient follow-up.

Discussion

Prof. Molfino, Dr. Giovannetti, and Prof. Muscaritoli

Renal cell carcinoma accounts for approximately 2.4% of all malignancies among the adult’s population [5].

The ccRC accounts for approximately 60% of malignant renal neoplasms. Several environmental factors have been identified as contributing causes of the disease, including cigarette smoking, obesity, and hypertension [6, 7], and age like in other type cancers [8].

National and international guidelines do not include steroids abuse as risk factor for renal cancer [9, 10], but some cases of prolonged abuse of steroids associated with ccRC are available in the literature.

Dr. Martellucci

Body builders often assume very high doses of anabolic steroids—even much higher than patient on hormonal replacement therapy for hypogonadism—determining testicular function’s suppression with a decrease in testosterone serum concentration and an increase in estrogens with potential tumor-inducing effects [11]. The association between cancer and use of anabolic androgenic steroids has been described in hepatocellular and prostatic cancers and also with Wilm’s tumor [11] but there is no evidence of a direct association with renal cancer. It has been suggested that patients with a preexisting condition, such as an adenoma, the action of steroids could determine malignant transformation [11, 12]. In particular, authors described only few cases of clear-cell renal cancer in body builders exposed to chronic steroids’ abuse (ranging from 20 months to 15 years of steroids abuse) presenting often with hematuria and anemia as initial symptoms [11, 13, 14].

All the authors

Renal cell carcinomas occur more frequently in adults older than 60 years. Besides the well-known risk factors (previously indicated), some genetic alterations in younger adults and in pediatric population have been reported [7]. The majority of RCC in the general population is sporadic, whereas those occurring in children and young individuals are often determined by specific germline gene mutations [7]. Analgesics have been also associated with higher risk to develop RCC, including aspirin and acetominophen [7]. Therefore, nowadays strategies aimed at reducing RRC risk should be focused on the improvement of both environment and behavioral factors and at managing the associated comorbidities to avoid complications.

The description of our clinical case adds an important information on a possible dangerous and life-threatening association between steroids abuse and renal cancer. We strongly advice to study and clarify the link between abuse of anabolic androgenic steroids and cancer transformation, specifically renal carcinomas in younger adults.