Incidental High-Grade Appendiceal Mucinous Neoplasm

Abstract

Background:

High-grade appendiceal mucinous neoplasm (HAMN) is an uncommon epithelial neoplasm of the appendix, and it is a median risk lesion that can be placed between benign low-grade appendiceal mucinous neoplasm (LAMN) and malignant adenocarcinoma. The diagnosis can be both incidental during surveillance imaging or clinically similar to acute appendicitis, which presents as pain in the right lower quadrant, or local pressure on adjacent organs. It carries the potential to progress to cancer if left untreated. Our aim is to review the literature and to report this rare tumor with outlining its clinical presentation, histologic features, and management.

Case Description:

A 50-year-old man with end-stage renal disease (ESRD) on hemodialysis underwent evaluation for kidney transplantation. A noncontrast CT abdomen revealed an incidental appendiceal mass during routine pretransplant imaging. The patient was asymptomatic with no gastrointestinal complaints. We performed a robotic appendectomy with partial cecectomy. The size of the mass was 10 × 5.5 × 3.5 cm. Pathology confirmed HAMN limited to the appendix, stage pTis (HAMN), with a negative margin and negative lymph nodes involvement pN0. The patient recovered well, and he will be monitored for recurrence while awaiting the renal transplant.

Conclusion:

HAMN is a recently recognized diagnosis. It can progress to an aggressive nature if left untreated. A standard appendectomy is performed for appendix limited lesions with right hemicolectomy in the presence of invasive characteristics. A comprehensive screening and vigilant clinical evaluation are essential before transplantation.

INTRODUCTION

The appendiceal tumors are uncommon, and account for roughly <2% of appendiceal resections.¹ The tumors are categorized as epithelial, neuroendocrine, goblet cell, mesenchymal, and lymphoid subtypes.^2,3 Appendiceal mucinous neoplasms (AMNs) are epithelial tumors, which may vary from benign adenomas to malignant adenocarcinomas. The AMNs are diagnosed in approximately <0.3% of appendiceal resections after the 50s with equal incidence among both males and females.^1,3,4 The mucinous subtypes are subcategorized to low-grade appendiceal mucinous neoplasm (LAMN) and high-grade appendiceal mucinous neoplasm (HAMN).³ The HAMN shows a higher grade dysplastic change, which places it between LAMN and malignant adenocarcinoma.³

The HAMN diagnosis can be both incidental during surveillance imaging or clinically similar to acute appendicitis, which presents with pain in the right lower quadrant, or with local pressure effect on the adjacent structures.⁵ The diagnosis is challenging due to the nonspecific clinical features. Imaging modalities such as ultrasonography, computed tomography (CT) scan, or colonoscopy can show cystic or mucinous appendiceal lesions in addition to appendiceal wall calcification, which is a radiologic sign in approximately 50% of the lesions.^1,6,7 Histopathology is the confirmatory diagnostic tool, which differentiates it from the LAMN and adenocarcinoma. Additionally, a tumor marker measurement such as carcinoembryonic antigen (CEA) and CA 19-9 can be useful in patients with advanced tumor stage.⁸

The surgical approach is guided by the stage of the disease and peritoneal spread. Overall, a standard appendectomy is performed for appendix limited lesions via a minimally invasive or open approach. The right hemicolectomy is performed in cases with the diagnosis of adenocarcinoma, perforation or possibility of lymph node involvement. Lesions limited to the appendix have a favorable outcome, whereas peritoneal spread can lead to pseudomyxoma peritonei (PMP), which carries a higher risk of morbidity.

CASE DESCRIPTION

A 50-year-old African American man with end-stage renal disease (ESRD) and on hemodialysis since Jun 2024, was undergoing a renal transplant evaluation for listing on the United Network for Organ Sharing (UNOS). His past medical history was notable for hypertension, diabetes mellitus, ischaemic heart disease, and intellectual disability. Family history was notable for maternal seizure and paternal heart disease. His physical examination was unremarkable, and his body mass index (BMI) was 27.3 kg/m². As part of the transplant evaluation, a noncontrast CT scan of the abdomen and pelvis revealed an elliptical soft tissue density in the right hemipelvis outlined with a linear calcification, radiographically suggestive of a cystic lesion (Figure 1A). The laboratory tests were performed, and the results are summarized in Table 1. Furthermore, the colonoscopy findings were unremarkable. The patient denied abdominal pain, bowel changes, or other gastrointestinal complaints.

Figure 1.

(A) Noncontrast CT of the abdomen and pelvis. (A) Axial view showing an elliptical soft tissue density mass in the right hemipelvis with linear calcification. (B) The coronal view demonstrates the same mass. (B) Robotic port placement illustration. (C) Intraoperative images of the surgical procedure: (A) identification of the appendicular mass, (B) careful dissection of the mass, (C) stapling the base of the appendix with the cecum, and (D) removal of the mass within an EndoCatch bag.

Table 1.

Laboratory Results

Test	Result	Units	Reference Range
WBC	4.6	10E3/uL	3.1–9.7
Hemoglobin (Hgb)	12.4	g/dL	13.1–16.8
Hematocrit (Hct)	39.7	%	38.2–48.4
Creatinine	8.88	mg/dL	0.66–1.25
Blood urea	42	mg/dL	6–22
Estimated creatinine clearance (drug dosing)	10	mL/min	70–120
Estimated GFR (CKD-EPI)	6.7	mL/min/1.73 m²	>60
Albumin	4.4	g/dL	3.5–5.0
Calcium	8.4	mg/dL	8.6–10.3
Phosphorus	5.2	mg/dL	2.5–4.9
Alkaline phosphatase (ALP)	126	U/L	34–104

The patient’s case was discussed at our multidisciplinary conference, and the patient was scheduled for a robotic appendectomy prior to the renal transplant. Under general anesthesia, he was placed supine, prepped, and draped in a sterile fashion. Furthermore, a pneumoperitoneum was established with a Veress needle, and three 8-mm robotic ports were inserted as per the right hemicolectomy protocol in addition to a 12-mm assistant port to the left side of the umbilicus (Figure 1B). The patient was placed in Trendelenburg position (head down), and the table was rotated to the patient’s left. The XI robotic system was docked in from the patient’s left side, and the mesoappendix was carefully divided with a vessel sealer. Additionally, a robotic endovascular stapler was used, and appendectomy with a segment of cecum was resected for the concern of malignancy, and the intraoperative images are shown in Figure 1C. The specimen, which appeared firm and large (10 × 5.5 × 3.5 cm), was removed in an EndoCatch bag after extension of the extraction site due to the large size, and then the port site was closed (Figure 2A).

Figure 2.

(A) (A) Gross specimen of vermiform appendix with partial cecum (10.0 × 5.5 × 3.5 cm). (B) Specimen cross-section with release of the contents. (C) The contents consist of brown-colored fluid mixed with mucus and evidence of hemorrhage. (B) (A) Low-power photomicrograph demonstrates appendiceal lumen with epithelium replaced by flat mucinous epithelial cells with high-grade dysplastic changes. No invasion into the wall of the appendix is present. (B) High-power photomicrograph illustrates a nuclear enlargement, overlapping, and high-grade dysplastic change.

The specimen was sent to the pathology department for a frozen section evaluation to guide intraoperative decision-making while the patient remained on the table in case a right hemicolectomy was required. The retrieved specimen was opened, and a moderate amount of brown color fluid with mucus was observed, which appeared as old blood (Figure 2A). Pathology reported calcification, mucin, and hemorrhagic material, but no invasive carcinoma and no positive lymph nodes for malignancy. Therefore, hemicolectomy was not performed. As a result, the extraction site was closed with a laparoscopic needle closure system, followed by the closure of the subcutaneous tissue and the skin. The patient tolerated the procedure well and had a minimal blood loss. He recovered and was discharged home on postoperative day one, and he was on a tolerating renal diet.

The final pathology report demonstrated a HAMN confined to lumen and lamina propria, staged as pTis (HAMN) pN0 (0/4 lymph nodes) (Figure 2B). Resection margins were negative, and no mucin was identified on the serosal surface. The postoperative course was without complication, and the patient was placed under surveillance for recurrence while he is awaiting the kidney transplant.

DISCUSSION

The appendiceal tumors are uncommon, and account for <2% of the appendectomies performed.¹ The tumors are categorized as epithelial, neuroendocrine, goblet cell, mesenchymal, and lymphoid subtypes.^1,2 The mucinous tumor group extends from benign LAMN to malignant adenocarcinoma.^2,3 HAMN is within the appendiceal mucinous tumor group, which shows higher grade of dysplastic changes than LAMN.

The clinical presentation is variable. Patients can be clinically silent, and the lesions are identified during surveillance imaging, such as cancer surveillance or organ transplant evaluation, like our case report. When it becomes symptomatic, it is often similar to acute appendicitis, which presents with right lower quadrant pain or local pressure effect on surrounding organs.⁵ Moreover, the appendiceal mass might lead to obstruction of ureter and bowel or perforate and release its mucin in the peritoneal space, which leads to PMP.¹ The variable symptomatology between incidental and symptomatic presentation can mask the disease and delay the diagnosis. Hence, it is prudent to consider a high index of suspicion in the differential diagnoses of abdominopelvic pathologies.

Histologically, the HAMN in our case has features between LAMN and malignant adenocarcinoma. Similar to the LAMN, it shows an expansile growth in the absence of invasion, however, it differs in demonstrating nuclear enlargement, overlapping, and higher-grade dysplastic changes.⁹ While it lacks the infiltrative growth, but it carries the risk of peritoneal spread if the appendix ruptures. At the molecular level, HAMN can carry mutation in multiple genes, which supports its differentiation from the lower grade dysplastic lesions and its potential to switch for a more malignant nature.^2,9

The appendiceal mucinous tumors nomenclature has currently been updated. 2016, the Peritoneal Surface Oncology Group International (PSOGI) named HAMN as a different tumor type, and highlighted the noninvasive nature with higher grade cellular dysplasia, which differentiates the HAMN from the LAMN and malignant adenocarcinoma, as shown in Table 2.¹⁰ In 2019, World Health Organization (WHO) included HAMN into the mucinous tumor group between the LAMN and mucinous adenocarcinoma, as shown in Table 3.¹¹ Additionally, it is recommended to stage the HAMN similar to adenocarcinoma because of its potential to switch for a malignant nature.¹²

Table 2.

Classification of Appendiceal Epithelial Neoplasms (According to PSOGI 2016)¹⁰

Tumor Type	Characteristics
LAMN HAMN	Mucinous tumor in the absence of infiltrative invasion but with one of these criteria: loss of muscularis mucosae, fibrosis of submucosa “Pushing invasion” (expansile or diverticulum-like growth), dissection of acellular mucin in the wall, undulating or flattened epithelial growth, rupture of appendix, mucin and/or cells outside appendix.
Mucinous adenocarcinoma	Mucinous neoplasm with infiltrative invasion (40% of all appendiceal adenocarcinomas).
Mucinous signet ring cell carcinoma	Signet ring cells present >50% of the cells in adenocarcinoma.
Nonmucinous adenocarcinoma	Nonmucinous adenocarcinoma resembling usual colorectal type.

Table 3.

Classification of Appendiceal Neoplasms (According to WHO 2019)¹¹

Appendix Neoplasms	Types
Sessile serrated lesions and adenomas	•
Mucinous neoplasms	Low-grade mucinous neoplasm of the appendix (LAMN) High-grade mucinous neoplasm of the appendix (HAMN)
Adenocarcinomas	Nonmucinous adenocarcinoma (NOS, “not otherwise specified”) Mucinous adenocarcinoma Signet ring cell adenocarcinoma Undifferentiated carcinoma
Goblet cell adenocarcinoma	•
Neuroendocrine neoplasms	Neuroendocrine tumors (NET) Neuroendocrine carcinomas (NEC) Mixed neuroendocrine/non-neuroendocrine neoplasms (MiNEN)

The HAMN management lines depend primarily on the tumor spread and margin status. Overall, appendix limited HAMNs are generally treated with a standard appendectomy, while a more aggressive operation, such as right hemicolectomy combined with cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) are spared for tumors with invasive features, such as positive lymph node, positive margins, and/or peritoneal spread.¹³ Furthermore, long-term surveillance is recommended due to the potential for peritoneal spread, particularly in patients who are immunocompromised, such as transplant candidates. In our patient, the lesion was diagnosed during the pretransplant evaluation as an abdominal mass and was successfully managed with the robotic appendectomy and partial cecectomy. It achieved a complete resection with negative margins and nodes, which avoided a more extensive colectomy.

Due to the recent recognition, the HAMN has remained less characterized.^13,14 The LAMN treatment modalities include standard appendectomy for the cases without appendicular rupture and peritoneal mucin spread, and CRS combined with HIPEC in the presence of appendicular rupture and peritoneal mucin spread.^15–18 Moreover, there are no specific chemotherapy agents during the HIPEC, however, the recommended agents include alkylating cytotoxic agents, such as mitomycin and oxaliplatin.¹⁴ These LAMN-based therapies are currently recommended for the HAMN management as well.¹⁴

>To our knowledge, a few incidental HAMN cases have been reported in the english literature, which are listed in Table 4. It includes the demographic characteristics, clinical presentation, operative findings, and treatments modalities. This summary reinforces the variability of the therapeutic modalities practiced. The surgical approaches range from a standard appendectomy to a more extensive resection. In our case report, we performed a robotic appendectomy, partial cecectomy, and four nodes were retrieved which were negative for malignancy.

Table 4.

Reported Incidental HAMN Cases

Author, Year	Country	Extra-Appendiceal Spread	Demographics and Presentation	Imaging	Technique	Procedure	Pathology/Tumor Size (cm)	Death
Dannaoui et al (2021)19	United States	None	74 years, female, incidental finding during right colonic cancer resection	Unrevealed findings	Open	Extended right hemicolectomy from the terminal ileum to the distal transverse colon with ileocolic anastomosis	High grade, 2	None
Togasaki K et al (2022)20	Japan	None	70 years, female, incidental finding	Cystic lesion	Laparoscopic	Ileocolic resection	High grade	None
Amir et al (2023)21	Saudi Arabia	None	62 years, female, incidental finding presented as renal colic with right flank pain	Mucocele	Laparoscopic	Appendectomy	High grade, 5.8	None
Gamza et al (2024)22	Poland	None	64 years, male, incidental finding during radical prostatectomy	Fluid layer in recto-vesical pouch and interloop space	Robotic assisted	Appendectomy	High grade, pTis R0	None
Fatah et al (2026), present case	United States	None	50 years, male, incidental finding during renal transplant listing preparation	Mucocele	Robotic	Appendectomy + partial cecectomy	High grade, 10 × 5.5 × 3.5	None

CONCLUSION

HAMN is a recently recognized diagnosis, which is a median risk lesion between benign LAMN and malignant adenocarcinoma. A standard appendectomy is performed for appendix limited lesions via a minimally invasive or open approach. The right hemicolectomy is spared for invasive characteristics. It carries the potential to progress to cancer if left untreated. This report showcases the importance of a comprehensive screening and a vigilant clinical evaluation before renal transplantation. Due to the rarity and recent recognition of this condition, further multi-institutional studies are required to address its clinical behavior and management strategies.