Multiple Primary Malignancies of the Colon, Stomach, and Kidney in a Patient with Bowel Obstruction Requiring Emergency Surgery: A Case Report

Background

Multiple primary malignancy (MPM) was first reported in the 1900s by Billroth [1] and the definition then was redefined by Warren and Gates [2] as the existence of 2 or more primary malignancies in the same patient. The tumors can be synchronous or metachronous. The North American Association of Central Cancer Registries defines synchronous tumors as those identified less than 6 months apart; tumors diagnosed more than 6 months apart are known as metachronous. Here we describe the case of a 63-year-old man who presented with adenocarcinoma of the colon, gastrointestinal stromal cell tumor (GIST), and renal cell carcinoma (RCC). To our knowledge, this the first reported case in the English literature of synchronous tumors of the colorectum, GIST, and RCC.

Case Report

A 63-year-old man with hypertension who had never undergone surgery presented to our emergency department with a 7-day history of diffuse abdominal pain and constipation. He had smoked a pack of cigarettes a day for the past 45 years. He had no personal or family history of malignancy. Physical examination revealed a distended abdomen and diffuse abdominal tenderness. The results of initial laboratory tests were unremarkable. The patient’s carcinoembryonic antigen level was 4 ng/mL and his cancer antigen 19-9 level was 12 U/mL.

Enhanced computed tomography showed a high-grade large-bowel obstruction with a transitional zone at the splenic flexure, which was suspicious for primary colorectal cancer (CRC) (Figure 1). Two lesions also were seen in the left kidney. A 2.6×2.7×2.7-cm well-rounded, hypodense lesion with high attenuation (66 HU) was present in the mid-pole, and another small 1.5×1.4-cm exophytic cystic lesion with fluid attenuation was present in the lower pole of the left kidney (Figure 2). There were 2 indeterminate small, hypodense lesions in segments 8 and 6 of the liver (Figure 3). No other abdominal masses initially were identified. Renal ultrasonography performed the same day to assess the kidney masses showed a complex cystic lesion in the mid-pole of the left kidney and another simple, exophytic, cortical cyst measuring 1.2 cm (Figure 2).

The patient underwent an urgent exploratory laparotomy, which revealed a splenic flexure mass; it was resected and a primary anastomosis was performed. A partial nephrectomy also was performed for the left renal masses. During intraoperative inspection, a mass was found at the greater curvature of the stomach. It measured approximately 3×3 cm and was hard, round, and had a smooth surface. We elected to do a wedge resection of the stomach to excise the mass.

The pathological evaluation of the colon specimen showed a 4.5×4×1.5-cm, moderately differentiated, invasive adenocarcinoma. The tumor was invading through the muscularis propria into the subserosal adipose tissue and the non-peritonealized pericolic/perirectal soft tissues but did not extend to the serosal surface; there was no regional lymph node metastasis (pT3N0Mx) (Figure 4). No KRAS, NRAS, nor BRAF mutations were identified, nor was there a loss of nuclear expression of MSI/MMR proteins. The left mid-pole kidney lesion was a papillary RCC, Type 1, WHO/ISUP grade I, 3.3 cm in the greatest dimension, with no lymphovascular invasion (pT1aNx Mx) (Figure 5). The patient was found to have a mutation in the PDGFRA gene, which is a member of the type III receptor tyrosine kinase family. The lower-pole lesion was found to be a 1.4-cm papillary, cortical adenoma with cystic changes. The stomach lesion was found to be a GIST, mixed subtype: spindle and epithelioid (pT2NxMx). It was 2.8 cm in greatest dimension, with moderate lymphocytic infiltrate (Figure 6). The tumor was low-grade (1/50 HPF) and had no malignant features, which, along with its size, carried a 1.9% risk for progressive disease [3].

A chest computed tomography (CT) scan performed 4 days after surgery showed bilateral, small, likely benign subpleural nodules and a mixed sclerotic/lytic right 9th rib lesion. Furthermore, magnetic resonance imaging of the liver, performed 1 month postoperatively to evaluate the liver masses, revealed a segment 4A lesion measuring 2×1.7 cm, which was definitely a metastatic lesion from the colon adenocarcinoma, and another benign small cyst in segment 5 (Figure 7). Because the patient had been taken to surgery urgently to relieve his obstruction, his case was discussed at a postoperative tumor board meeting. The plan was to further investigate his liver lesions, to start him on concurrent chemotherapy, and to repeat the CT images in 3 months.

Discussion

MPMs are considered rare and they typically have been described in case reports [4,5] and in reports from registries and centers in different countries [6,7]. The mechanism of development of MPMs is uncertain and likely multifactorial; identified risk factors include previous cancer treatment, diet, smoking, and genetic mutations [8]. Smoking alone is a significant risk for cancer [9], and, together with alcohol intake, has been estimated to account for approximately 35% of all excess risk for MPMs [8]. Most secondary primary tumors have been found to occur in tobacco-related cancer sites, particularly in other digestive organs. This may be due to the similar carcinogenic agents that affect the gastrointestinal system [10,11]. With advances in healthcare systems around the world and the increase in different modalities for diagnosis and management, the life expectancy of the population has increased significantly in the past few decades, according to the World Health Organization [12]. Given the increasing incidence of MPM, individuals who are elderly are at increased risk of developing them [13]. A retrospective study of more than 52 000 patients by Bittorf et al. [6] showed that 2.8% had 3 primary malignancies. Interestingly, the 5-year survival rate for patients with MPMs has been shown to be higher than for those who have solitary malignancies. The reason for that remains unclear.

There are multiple reports in the literature of associated synchronous MPMs. For instance, patients diagnosed with CRC are at a higher risk for RCC than those in the general population, and vice versa [14]. It has been suggested that both neoplasms are associated with genetic predisposition and share a common pathogenic mechanism [14–18]. Synchronous tumors are believed to originate from tissues and organs with a similar embryonic origin [14,19]. This association frequently has been reported with CRC [14].

GIST is another example. It was reported to be associated with different malignant tumors, including RCCs [19–22]. Furthermore, it is known to be part of multiple syndromes, including the Carney triad, Carney-Stratakis syndrome, and neurofibromatosis type 1 (NF1).

Conclusions

The present report describes the first case of MPM of the colon, stomach, and kidney. The diagnoses were made based on the patient’s history, physical examination, and imaging.

Given the broad spectrum of causes for developing MPM, as have been previously discussed, physicians should be attentive to the possibility of new or separate primary malignancies. A high index of suspicion is warranted based on patient history, including age, predisposing risk factors, and family history. Physical examination and different imaging modalities can be employed even if a primary malignancy has been definitively diagnosed.

To date, no management guidelines have been established for MPMs. Therefore, the approach to treatment, screening, and follow-up should be tailored to each individual patient, ideally by a multidisciplinary team.