Multi-detector computed tomography (MDCT) evaluation of synchronous renal cell carcinoma and other solid malignancies

Multiple primary malignant neoplasms (MPMNs) became more prevalent as the population aged and medical technology progressed. The purpose of this research was to review the findings of multidetector computed tomography (MDCT) in synchronous renal cell carcinoma and other solid tumors. 31 individuals with synchronous renal cell carcinoma and additional solid cancers were included in this retrospective analysis. CT scanning was carried out using 64 MDCT scanners. All sixty-two malignancies were undergoing pathological assessment. Out of 685 patients with renal cell carcinoma, 31 individuals were identified with another primary solid cancer that occurred concurrently. All of our instances were pathologically verified. In all 31 individuals, clear renal cell carcinoma was found. The most frequent extra-renal malignancies were hepatocellular carcinoma (10/31), followed by breast carcinoma (4/31), non-Hodgkin lymphoma (4/31), bronchogenic carcinoma (3/31), colonic carcinoma (3/31), prostatic carcinoma (2/31), urinary bladder carcinoma (1/31), periampullary carcinoma (1/31), mucoepidermoid carcinoma (1/31) and skin squamous cell carcinoma (1/31) as well as malignant hemangioendothelioma (1/31). MDCT scanning was an accurate imaging method for diagnosing synchronous renal cell carcinoma and other solid tumors. Even in the face of numerous cancers, the goal of therapy in cancer patients must always be curative. During the pretreatment examination, the potential of synchronous double malignancies with renal cell carcinoma should be explored.


Background
Renal cell carcinoma (RCC) was the 17th most prevalent malignancy, accounting for 2.2% of all malignancies diagnosed worldwide in 2018 [1]. The number of people diagnosed with second primary cancer has risen due to newly established diagnostic imaging technologies and advances in the treatment of common cancer [2]. Warren and Gates established the diagnostic criteria for numerous primary malignancies. At the current moment, these conditions are still approved [3]. A single patient with several primary cancers accounts for 0.7%-11% of all carcinomas [4]. Renal cell carcinoma patients are at risk of developing additional synchronous primary cancers. Few case reports of synchronous renal cell carcinoma and other malignancies [5][6][7]. Up to our knowledge, this is the most extensive study in the MDCT examination of synchronous renal cell carcinoma and other solid cancers in the literature. To enhance the prognosis of renal cell cancer patients, a careful preoperative examination is suggested. In this retrospective analysis, we reviewed the multidetector computed tomography (MDCT) results of 31 patients with synchronous renal cell carcinoma and other solid tumors. El-Badrawy Egypt J Radiol Nucl Med (2022) 53:75

Patients
The institutional research ethics review committee authorized the present study. Due to the retrospective nature of this investigation, the patient's informed permission was not obtained. All consecutive patients with renal cell carcinoma were included in this retrospective research treated at our institution from November 2006 to September 2019. Patients' files were reviewed, and 31 patients identified with double primary malignancies as per Warren and Gates criteria were further analyzed. All thirty-one patients had ultrasonography. Pathological diagnoses of all sixty-two malignancies were confirmed in all 31 cases. Although; characteristic CT findings were detected on all 31 patients, a needle biopsy was done to exclude the possibility of metastases and confirm the histopathological diagnosis. During a metastatic workup for other cancers, twenty individuals with RCC were discovered by chance. Sixteen patients with stage T1a and four patients with stage T1b.
Except for case number 21, all primary renal cell carcinomas and other synchronous cancers were discovered simultaneously. This patient underwent a right nephrectomy two years before. During follow-up CT scanning, there was a local mass at the operative bed of the right kidney with malignant para-aortic lymphadenopathy and pulmonary mass with malignant mediastinal lymphadenopathy. Needle biopsies were taken from local recurrent mass and lung mass. Both biopsies underwent immune histochemical staining and revealed local clear renal cell and bronchogenic carcinomas. The existence of two malignant tumors, proven histopathological, with distinct histology in the two sites, was the inclusion criterion for our patients. Individuals who did not have definitive histopathological confirmation of each tumor were excluded, as were patients whose second tumor was thought to be a metastasis of the first. Table 1 contains patient age at the time of each tumor diagnosis, gender, location of origin, histology, and clinical stage. Tumor node metastasis (TNM) staging by the American Joint Committee on Cancer (AJCC) was the most often used cancer staging method. The AJCC has undergone several revisions, and its 8th version is already in use by practicing physicians [8]. As a result, it has become the staging system in the present study. The Barcelona Clinic Liver Cancer (BCLC) staging system is the most often utilized for hepatocellular carcinoma (HCC) therapy [9]. As a result, our research has become the HCC staging method. Warren and Gates' criteria for synchronous double primary cancers were now widely recognized [3].

CT technique
The 64 MDCT scanner was used to do whole-body and triphasic abdominal CT scanning (Brilliance 64; Philips Healthcare, Best, The Netherlands). The unenhanced and contrast-enhanced triphasic investigations were obtained with a slice thickness of 3 mm. For the abdominal examination, arterial and delayed phases were used. The portal phase was completed for the whole body. The contrastenhanced investigation used 100 ml of non-ionic contrast medium (ioversol, Optiray 350, Mallinckrodt) at a flow rate of 5 ml/sec. During all stages of the computed tomography test, patients were asked to hold their breath. Automated bolus monitoring at the lower thoracic aorta level to guarantee proper timing in an arterial phase. The whole-body portal venous phase was done with a 55-60 s effective delay following the commencement of the contrast injection. The abdominal examination was done in the delayed phase, with an effective delay of 3-6 min. Post-processing was carried out on all images using the workstation [Extended Brilliance Workspace V3.5.0.2254] (EBW). The images were seen in three different settings: lung, soft tissue, and bone. Ten individuals had their CT results confirmed by an MRI.

Image interpretation
The images were looked at the density, size, and the number of lesions, as well as vascular encasement, lymph node involvement, and other organ involvement in the abdomen, as well as metastatic spread. The whole body was scanned with a CT scanner to check for any lymph node groupings, organs, bone, or lung metastases that may have occurred. All renal cell carcinomas and other synchronous solid malignancies were assessed for local, lymphatic, hematogenous, and transcoelomic spread if suspected according to the primary site of the tumor. Size, organ origin, internal architecture, local invasion, vascular encasement, calcifications as well as the presence of metastases were all analyzed. All 62 cancers were assessed for tumor staging (Table 1).

Results
To detect extra-renal primary tumors, we used the Warren and Gates criteria. Thirty-one instances (4.5%) of the 685 patients with renal cell carcinoma satisfied the inclusion criteria for synchronous extra-renal original malignancy [3]. There were 21 males and ten women (mean age, 63 year; range, 36-80 years). Hepatitis C virus was found in 17 of the individuals. Hepatitis C and B viruses were found in six cases.
All sixty-two tumors were accurately characterized, evaluated, and staged. MDCT accurately predicted the second primary vs. metastases in all patients. Clear renal  (Fig. 3). Twenty-two of the 31 extra-renal tumors were intra-abdominal (ten hepatocellular carcinomas, four lymphomas, three colonic carcinomas, two prostatic carcinomas, and one for each urinary bladder carcinoma, periampullary carcinoma, and malignant hemangioendothelioma). The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging; the renal cell carcinoma was stage I (26 patients), III (4 patients), and local tumor recurrent with para-aortic malignant lymphadenopathy (1 patient).
The BCLC staging method classified the HCC as stage A (6 patients), B (3 patients), and C (1 patient). Breast  1 64-year-old male patient with a history of chronic liver disease presented with hematuria. a, b Initially, an unenhanced MDCT scan due to high serum creatinine (contra-indication for contrast study) revealed an ill-defined right liver lobe (thin arrow) and right renal mass (arrow). c, d T2 magnetic resonance image revealed hepatic focal lesion (star) (pathologically proved HCC) and right renal mass (arrow) (pathologically proved RCC). The patient underwent a right nephrectomy. e-g MDCT scan after nephrectomy showed right liver lobe mass (asterisk) with enhancement on arterial phase and washout in portal phase (characteristic of HCC) with right nephrectomy

Discussion
Synchronous primary multiple cancers were tumors that coincide or within six months of one another [10]. Warren and Gates presented the diagnostic criteria for multiple primary cancers [3]. These criteria are: (a) each cancer was malignant; (b) Each tumor has its unique set of pathological characteristics; (c) Each tumor must be unique; and (d) the chance of one tumor becoming a metastasis of another must be ruled out. The development of improved diagnostic techniques and the aging of the population has contributed to the increased occurrence of several primary malignant neoplasms (MPMNs) [11]. Early detection of synchronous secondary tumors in malignant patients is critical for appropriate therapy. Renal cell carcinoma (RCC) was the majority fatal of all urologic tumors, accounting for 90% of adult renal cancers. [12]. Clear renal cell carcinoma is about 70% of RCC [13]. All our 31 renal cell carcinomas were clear cell subtypes. The biopsy is recommended to characterize renal tumor histology and other solid malignancies to validate the initial tumor's histology origin [14,15]. Our study's sixty-two cancers were all histopathological evaluated.
In the present study, the median age was 63 years. This is consistent with earlier findings indicating that elderly age is a risk factor for the development of primary, secondary cancers [16]. According to Motzer et al. [2011], the average age at diagnosis of RCC is 65 years, with the majority of patients in their sixth to eighth decade of life, and men are two to three times more affected than females [17]. This coincides with our result as the male gender was (21/31).
Renal cell carcinoma (RCC) incidence has significantly raised in recent decades as a result of the increased usage of modern and accurate abdominal imaging methods [18]. In general, incidentally discovered renal cell cancers were smaller in size [19]. Upon the increased use of imaging modalities for various medical conditions, an increasing proportion of incidental renal cell carcinomas were being identified [14,18]. This is consistent with our findings since renal cell carcinoma was discovered by chance in 20 of 31 individuals. There were 16 T1a (stage I) patients and 4 T1b individuals (stage I).
Most synchronous cancers were discovered during the preoperative workup, and the majority were found in the intra-abdominal cavity [20]. This is consistent with our findings since synchronous extra-renal primary cancers were abdominal malignancy (22/31 patients).
MDCT is a noninvasive and reliable imaging technology that is extensively used in ordinary clinical practice to identify, characterize, and stage renal masses. [21,22]. MDCT is an excellent tool for evaluating synchronous primary solid double cancers [23][24][25][26][27][28][29]. This is consistent with our findings since MDCT properly identified all sixty-two cancers. The radiological findings of renal cell carcinoma in the multiple primary malignancies were similar to that of RCC-alone patients.
The frequency of the second extra-renal primary malignancy site in RCC patients differs depending on the geographical distribution of the study [30][31][32]. The incidence of renal cell carcinoma was detected during whole-body CT, monitoring for lung cancer, colorectal cancer, and coronary artery disease was 0.21% [30]. RCC is associated with various primary cancers, including prostate, bladder, lung, breast, colon, and rectal cancers, malignant melanomas, and non-lymphomas Hodgkin's (NHL) [31]. Piccinini et al. discovered six cases of RCC that were discovered by chance during the first staging workup of a rhinopharyngeal carcinoma, stomach cancer, Waldenström's disease, NHL, and breast cancer [32]. According to our findings, the most prevalent extra-renal malignancy is HCC (10/31). The second most common extra-renal malignancies are breast carcinoma (4/31) and lymphoma (4/31). Of these eighteen patients, fourteen patients have hepatitis C, and four patients have hepatitis C and B viruses. This is consistent with earlier research that linked hepatitis virus to an increase in the incidence of HCC, breast cancer, and lymphoma. [33][34][35]. The next extra-renal malignancies are bronchogenic carcinoma (3/31) and colonic carcinoma (3/31). This difference may be due to the relatively small number of cases and due to the geographical setting.
Renal cell carcinoma should be evaluated thoroughly. Detection of synchronous second primary malignancy with renal cell carcinoma is crucial for patient management. Early proper diagnosis of this condition is essential to avoid erroneous disease progression and subsequent palliative treatment rather than curative therapy differentiating a synchronous second primary malignancy from metastatic disease by MDCT seems to be a novel idea for both radiologists and clinicians.