Goblet cell adenocarcinoma of the appendix: A case report of three cases

Abstract

Introduction and importance

Appendiceal goblet cell adenocarcinoma is in 0.3–0.9 % of appendectomy specimens. There is still controversy regarding whether surgery with dissection or additional resection is necessary for goblet cell adenocarcinoma and whether adjuvant chemotherapy is practical. We present three cases of goblet cell adenocarcinomas.

Case presentation

Case 1: A 30-year-old woman was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells and tumour infiltration into the subserosa. The patient underwent laparoscopic ileocecal resection, and the main lymph nodes at the root of the feeding vessels were removed. Case 2: A 50-year-old man was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells; malignant cells were found at the surgical resection margins. The patient underwent laparoscopic ileocolic resection. Case 3: A 60-year-old man undergoing treatment for malignant melanoma. He was diagnosed with appendicitis associated with an appendiceal tumour, and emergency laparoscopic caecal resection was performed and diagnosed as goblet cell adenocarcinoma. We decided to prioritize treatment for malignant melanoma, and the patient is under follow-up for goblet cell adenocarcinoma and no metastasis was detected.

Clinical discussion

We performed additional resection in two case of goblet cell adenocarcinoma. Diagnosing appendiceal goblet cell adenocarcinoma is difficult, and the prognosis of patients with positive lymph nodes is poor. Surgical treatment should be considered for the advanced stages of this disease.

Conclusion

Goblet cell adenocarcinoma, diagnosed after appendectomy, additional resection including lymph node dissection may provide a long-term prognosis.

Highlights

• •We present three cases of goblet cell adenocarcinomas.
• •Positive lymph nodes in appendiceal tumours decrease long-term survival.
• •Surgery and lymph node dissection should be considered for advanced stages.

1. Introduction

Appendiceal goblet cell adenocarcinoma, formerly known as a goblet cell carcinoid, is a tumour that histopathologically resembles both carcinoids and adenocarcinomas. It is considered more malignant than ordinary carcinoids. Appendiceal goblet cell adenocarcinoma is found in 0.3–0.9 % of appendectomy specimens [1]. There is still controversy regarding whether surgery with dissection or additional resection is necessary for goblet cell adenocarcinoma and whether adjuvant chemotherapy is practical. In this article, we report three cases of goblet cell adenocarcinoma diagnosed after surgery for appendicitis, as well as a review of the literature.

This case series has been reported in line with the PROCESS guidelines [2].

2. Presentation of case

2.1. Case 1

A 30-year-old woman presented with abdominal pain. The patient was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells and tumour infiltration into the subserosa. Goblet-like cells stained positive for alcian blue, chromogranin A, and Ki-67 (5–6 %). No malignant cells were observed at the resection margins. She was consulted in our hospital at 30 days after initial operation. On the 40th day, CT showed no metastasis or recurrence. The diagnosis was goblet cell adenocarcinoma T3N0M0 StageIIA. 75 days after the appendicectomy, the patient underwent laparoscopic ileocecal resection with D3 lymph node dissection, which is defined as the removal of the main lymph nodes at the root of the feeding vessels (ileocolic vessels). No atypical cells suggestive of a tumour were found in the resected specimen, including the lymph nodes. Eight years have passed since additional resection, and the patient remains alive and recurrence-free.

2.2. Case 2

A 50-year-old man presented to our hospital with lower abdominal pain. His abdomen was obese and soft, with focal peritonitis in the right lower quadrant, positive rebound tenderness, and guarding to palpation. Laboratory evaluation revealed mild leukocytosis (white blood cell count up to 16,000/μL). Abdominal CT revealed that the appendix was swollen to approximately 18 mm in diameter with partial wall disruption. Effusion of ascites was observed in the Douglas fossa. The patient underwent laparoscopic appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells, which had alcian blue-positive mucus and stained positive for CKAE1/AE3, synaptophysin, chromogranin A, and CDX-2. These cells were found on the subserosa, were mostly infiltrated by individual cells, and were considered to have a high-grade pattern. Malignant cells were observed at the surgical resection margins (Fig. 1). On 30 days after the initial operation, CT showed no metastasis or recurrence. 41 days after the appendicectomy, the patient underwent laparoscopic ileocolic resection with D3 lymph node dissection. The root of the ileocolic artery was dissected medically, and lymph nodes were dissected along the left border of the superior mesenteric vein (Fig. 2). Pathologically, there were a few goblet-like dysmorphic cells proliferating in a small mass within the muscular layer of the ileum with alcian blue-positive mucus, indicating CKAE/AE3(+). No malignant cells were found at the resection margins, and there was no lymph node metastasis. The final diagnosis was pT3N0M0 pStage IIA. The patient was under observation and did not undergo postoperative adjuvant chemotherapy.

Fig. 1.

A: Histopathological evaluation showing a malignant neoplasm with goblet-like cells. Goblet-like cells were found on the subserosa, mostly infiltrated by individual cells, and considered to have a high-grade pattern (HE ×4).

B: Goblet cells are positive for alcian blue-PAS (×4).

C: Goblet cells are positive for CKAE1/AE3 immunostaining (×4).

D: Malignant cells are found at the surgical resection margins. Arrows indicate goblet cells (HE ×20). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2.

Intraoperative findings

The root of the ileocolic vein and superior mesenteric vein are exposed, and lymph node dissection is performed on the left border of the superior mesenteric vein.

2.3. Case 3

A 60-year-old man presented to our Department of Dermatology as an outpatient for postoperative chemotherapy for malignant melanoma. The patient was referred to our department because of elevated c-reactive protein in blood tests and suspicious findings of appendicitis on contrast-enhanced abdominal CT. The patient presented with lower right abdominal pain. The CT showed an enlarged 15-mm appendix with a thickened wall and fluid retention in the lumen. The base of the appendix was stained darkly on contrast-enhanced CT performed 6 months earlier, and a tumour could not have been ruled out (Fig. 3a and b). Based on the findings of contrast-enhanced CT, appendicitis associated with an appendiceal tumour was suspected, and emergency laparoscopic caecal resection was performed (Fig. 4). Histopathological evaluation revealed a malignant neoplasm with goblet-like cells. Malignant cells with nest formation were found from the mucosa to subserosa. The malignant cells were positive for cytokeratin CAM-5.2, synaptophysin, and chromogranin A. Appendiceal goblet cell adenocarcinoma was diagnosed. These goblet-like cells exhibited perineural invasion. Surgical resection margins were negative for malignant cells. As pathological examination revealed goblet cell adenocarcinoma and pT3, additional ileal resection was planned. However, preoperative chest CT showed a mass in the right lung, which was suspected to be the pulmonary metastasis of a malignant melanoma. We decided to prioritize treatment for malignant melanoma, and the patient is under follow-up for goblet cell adenocarcinoma without treatment by the time of writing this study.

Fig. 3.

a: Contrast-enhanced CT scan of the abdomen at the onset of acute appendicitis. The appendix is enlarged with a thickened wall, fluid accumulation in the lumen, and elevated periapical fatty tissue concentration. No calculus is present in the lumen.

b: Contrast-enhanced CT scan of the abdomen (6 months before the onset of acute appendicitis). A contrast effect is observed at the base of the appendix.

Fig. 4.

Resected specimen

The appendix was enlarged. The arrows indicate the wall thickness of the appendix.

3. Discussion

Goblet cell adenocarcinoma is a rare tumour that almost exclusively affects the appendix. In the 2019 World Health Organization classification update, goblet cell adenocarcinoma was reclassified as goblet cell adenocarcinoma of the appendix as it is recognised to have predominantly mucin secreting cells and a minor neuroendocrine component [3]. Goblet cell adenocarcinoma is a biologically aggressive lesion that is more similar to adenocarcinomas than to typical carcinoid tumours [4]. Appendiceal goblet cell adenocarcinoma is found in 0.3–0.9 % of appendectomy specimens [1] and approximately 14–19 % of primary appendiceal cancer specimens. The mean age at diagnosis is 58 years, and there is no significant difference in incidence between men and women [5]. Similar to most tumours of the appendix, goblet cell adenocarcinoma frequently presents with acute abdominal pain and clinical findings of the appendicitis in 50–60 % of cases [6], [7], [8]. It is often diagnosed incidentally during appendectomy or ileocecal resection and is confirmed by surgical pathology. However, depending on its size, the tumour may cause bowel obstruction by infiltrating the terminal ileum. In cases of metastases to the lower abdomen and pelvis, vague abdominal symptoms are commonly the first reported feature and are often overlooked by primary care physicians [9]. In cases 1 and 2, the preoperative diagnosis was acute appendicitis, and postoperative pathological examination revealed goblet cell adenocarcinoma. In case 3, contrast-enhanced CT performed before the onset of acute appendicitis showed a dark-stained image at the base of the appendix, suggesting the possibility of an appendiceal tumour. Because the findings were suspicious for a tumour intraoperatively, appendectomy was performed, and the surgical resection margins were negative for malignant cells. It is essential to accurately diagnose goblet cell adenocarcinoma as it is more aggressive in nature than typical carcinoid tumours. The prognosis of patients with goblet cell adenocarcinoma at the early stages is good but much poorer at advanced stages. At the time of diagnosis, 11.2 % of patients had distant metastasis, 3.6 % had ovarian metastasis, and 1 % had peritoneal dissemination. The 5-year overall data based on the American Joint Committee of Cancer (TNM) staging system is 100 % for stage I, 76 % for stage II, 22 % for stage III, and 14 % for stage IV [10]. Webb et al. studied 4435 patients with goblet cell adenocarcinoma and found lymph node metastasis in 21.9 % of patients, excluding those with unknown lymph node metastasis. Positive lymph nodes in appendiceal tumours are associated with decreased long-term survival. Webb et al. reported a relatively good 5-year survival rate of 86 % in patients with no lymph node metastasis in goblet cell adenocarcinoma but a 42 % decrease in the 5-year survival rate in node-positive cases and a poor prognosis in node-positive cases [11].

Both North American and European Neuroendocrine Tumour Societies recommend right hemicolectomy as standard first-line treatment for goblet cell adenocarcinoma even after appendectomy due to the high risk of metastasis and improvements in prognosis [7], [12], [13].Pham et al. reported that right hemicolectomy and attendant mesenteric nodal resection are recommended for (1) T3/4 disease, which has a high recurrence rate (30 % for T3 and 70 % for T4) or nodal involvement, (2) direct caecal extension, and (3) clinically positive mesenteric nodes [10]. Additional resection was planned for cases 1–3 because of serosal invasion. Furthermore, Case 2 showed positive resection margins and suspected lymph node metastasis. Moreover, postoperative chemotherapy is recommended for patients with positive lymph nodes; however, some reports indicate that adjuvant chemotherapy does not improve survival, and chemotherapy has not yet been established [11]. In Case 1, no lymph node metastasis was found after additional resection, and long-term survival was achieved without postoperative chemotherapy. In Case 2, additional resection was performed, and although the resection margins were negative, a small number of atypical cells were found in the intrinsic muscle layer within the ileum. No postoperative chemotherapy was administered, and the patient is currently under observation by the time of writing this study. In case 3, we decided not to perform an additional resection because the patient had malignant melanoma.

4. Conclusion

Diagnosing appendiceal goblet cell adenocarcinoma is difficult. If goblet cell adenocarcinoma is diagnosed after appendectomy, additional resection, including lymph node dissection, may provide a long-term prognosis.

Consent

Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

Ethical Approval was provided by the authors institution.

Funding

None.

Author contribution

Nami Kiyosawa, Makoto Koyama, Yusuke Miyagawa, Masato Kitazawa, Shigeo Tokumaru were performed surgery and perioperative treatment. Yuji Soejima reviewed critically the manuscript.

Guarantor

Dr. Yuji Soejima

Research registration number

I don't have my UIN.

Conflict of interest statement

None.

Abbreviations

CT

computed tomography