Metastatic Appendiceal Carcinoma Diagnosed in an Asymptomatic Patient With Incidental Thyroid Mass on Routine Examination

CASE REPORT

A 77-year-old Caucasian man with a history of 60 pack-years of smoking, hypertension, and multiple resected basal cell carcinomas of the skin was seen in the office for a regular medical checkup. He was noted to have a left carotid artery bruit and subsequently had a magnetic resonance angiogram (MRA) that showed a mass in the left lobe of the thyroid causing compression and displacement of the trachea. A left-lobe thyroidectomy was performed, showing a goitrous gland and a 6-mm focus of adenocarcinoma. A staging computed tomographic (CT) scan showed multiple liver lesions but did not show the primary tumor. He then underwent a radiographic guided core biopsy of the liver showing metastatic adenocarcinoma with morphologic and immunophenotypic profiles of colorectal or pancreatobiliary origin. Carcinoembryonic antigen (CEA) and CA19-9 were very high at 557 ng/mL (normal level=0-2.5 ng/ml) and 616 U/mL (normal level=0-37 U/ml), respectively. A work-up was performed for an unknown primary adenocarcinoma with a positron emission tomographic (PET) scan that showed intense metabolic activity in the neck, liver, and right lower quadrant (Figure 1).

Figure 1.

PET scan at diagnosis showing focal metabolic activity in the thyroid and the subcarinal and infrahilar lymph nodes, along with multiple foci of intense metabolic activity in the liver. Intense metabolic activity was present in the right lower quadrant within a soft tissue mass 4 cm in diameter that was contiguous with the posterior wall of the cecum.

Further gastrointestinal (GI) evaluation with endoscopy showed a lesion in the terminal ileum into the cecum, with an appendiceal adenocarcinoma in the biopsy. There were no other synchronous or metachronous neoplasms in the GI tract.

The patient was treated with FOLFOX with bevacizumab and completed 6 cycles over 6 months. His follow-up PET scan showed, after 6 months of chemotherapy, partial metabolic responses in the mediastinal lymph nodes, the hepatic metastases, and the appendiceal lesions (Figure 2). CEA and CA19-9 decreased to 62 ng/mL and 49 U/mL, respectively. After 6 months, he developed oxaliplatin-induced neuropathy, and his regimen was changed to FOLFIRI plus bevacizumab. At this writing, the patient has completed 9 months of therapy. He remains very stable clinically and has shown excellent response to chemotherapy.

Figure 2.

A restaging PET scan after 6 months of diagnosis showing positive therapeutic response in the mediastinal lymph nodes, in hepatic metastases, and within the primary appendiceal region.

DISCUSSION

Adenocarcinoma of the appendix is very rare and is usually discovered in a surgical specimen.¹The incidence of appendiceal adenocarcinoma ranges from 0.11% to 0.80% in appendectomy specimens.^2–5 It constitutes <0.5% of all gastrointestinal neoplasms. Presenting symptoms can include right lower quadrant pain, appendicitis, early satiety, and changes in bowel habits or abdominal distention. According to the Surveillance, Epidemiology and End Results program, the incidence of appendiceal malignancies in the United States is 0.12 cases per 1,000,000 people per year, with adenocarcinoma accounting for the largest subset (37%) of total cases.⁶ Histologic typing predicts the extent of disease: mucinous adenocarcinoma with metastases at the time of diagnosis in 71% of cases, and colonic adenocarcinoma with metastases at the time of diagnosis in 83% of cases.⁶

Adenocarcinoma of the appendix has the tendency to metastasize both hematogenously and lymphatically.⁷ A recent review of thyroid metastases found that the most commonly reported nonthyroid malignancy (NTM) leading to clinically discovered metastases to the thyroid are renal cell, lung, colorectal, and breast carcinomas.⁸ Of the NTMs that metastasize, 1.9% of those found in the thyroid gland were from an unknown primary malignancy.⁸

The clinical incidence of metastasis to the thyroid has been reported in 1.4% to 3% of all patients operated on for suspected thyroid malignancy.^8–10 However, rates of up to 24% have been reported in autopsy series of patients who died of cancer.¹¹ Metastatic deposits occur in the thyroid gland due to vascular or lymphatic spread. It has been postulated that the rich vasculature of the goitrous thyroid makes it particularly susceptible.¹² However, some have suggested that the rapid flow of blood through the gland reduces the likelihood of metastatic deposits.⁸

CEA, CA19-9, and CA-125 are potential tumor markers in epithelial appendiceal neoplasms. One or any combination of them can be elevated in 60% of patients.¹³

Diagnosis of appendiceal cancer by endoscopy is very rare. Even in advanced cases, a negative colonoscopy is common.¹⁴ PET and CT are helpful tools in detecting lesions of the appendiceal region.

Cytoreductive surgery (CRS) and/or hyperthermic intraperitoneal chemotherapy (HIPEC) is the first-line treatment for appendiceal cancer. For patients like ours, who were ineligible for CRS and HIPEC because of extraperitoneal metastatic disease, systemic chemotherapy is a reasonable option. Strong data on the role of systemic chemotherapy in metastatic appendiceal cancer are lacking because most of the available data come from retrospective studies¹⁵ and also because of the diversity of histology and the lack of a clear consensus in reporting and describing appendiceal cancer. As the appendix is considered part of the colon, appendiceal tumors have historically been treated with colorectal cancer regimens, although their natural history, biology, and outcomes are different.¹⁶

The National Comprehensive Cancer Network (NCCN) colorectal cancer (CRC) database showed that treatment of metastatic appendiceal carcinoma incorporates agents used for colorectal cancer: FOLFOX, with or without bevacizumab; FOLFIRI; or single-agent fluoropyridine. A study from the NCCN 2005–2010 database showed a 46% response rate, median progression-free survival of 1 year, and overall survival of 2.1 years in metastatic appendiceal cancer treated with systemic chemotherapy, which is comparable to progression-free survival achieved in the treatment of metastatic colorectal cancer.¹⁷

CONCLUSION

The case presented here highlights the need to be cognizant of unusual primary sites in secondary thyroid cancer. Metastases from the appendix should always be considered in the differential diagnosis of the secondary thyroid lesion, although it is very rare. Appendiceal cancer with extraperitoneal metastasis can be treated with the same systemic chemotherapy as is used in the treatment of colorectal cancer.