Your pathology report for high grade mucinous neoplasm of the appendix (HAMN)

By Jason Wasserman MD PhD FRCPC
November 24, 2025

A high-grade mucinous neoplasm of the appendix (HAMN) is a tumor made up of mucin-producing cells that line the inside of the appendix. Like low-grade mucinous neoplasms (LAMNs), HAMNs produce large amounts of mucin, which can cause the appendix to enlarge or rupture. However, unlike LAMNs, HAMN cells exhibit high-grade features under the microscope. This means the nuclei look more irregular, the cells divide more quickly, and the tissue has a more aggressive appearance.

HAMN is considered a precancerous or early cancerous condition. Although it may not behave as aggressively as mucinous adenocarcinoma, it is more concerning than LAMN and requires careful evaluation, complete removal, and close follow-up.

Anatomy of the appendix

The appendix is a small pouch located at the beginning of the large intestine. It is lined by glandular cells that can produce mucin. Because the appendix is narrow and enclosed, mucinous tumors can cause the appendix to stretch, thin, or rupture. If the wall breaks, mucin or tumor cells may spill into the abdomen.

What are the symptoms of HAMN?

Some people with HAMN have no symptoms, and the tumor is discovered incidentally during imaging or surgery. When symptoms do occur, they often resemble appendicitis, with lower right abdominal pain, nausea, vomiting, or fever.

If the appendix ruptures or mucin spreads beyond the appendix, symptoms may include:

• Abdominal swelling or fullness.

• A new umbilical hernia.

• A feeling of pressure in the abdomen

• A detectable mass on exam.

Imaging studies may show a dilated, fluid-filled appendix, sometimes with calcium deposits in the wall.

Who gets HAMN?

HAMN is rare. It can occur in adults of any age but is most often diagnosed in middle age or later. Men and women are affected at similar rates. No specific environmental or lifestyle causes have been identified.

What causes a high-grade mucinous neoplasm?

The exact causes remain unknown, but HAMNs often show genetic changes in genes such as KRAS. Unlike LAMNs, GNAS mutations are less common in HAMN. The genetic profile of HAMN differs from that of typical colorectal cancer; mutations in APC, TP53, and SMAD genes are less frequent but may appear in some high-grade tumors.

HAMN is not associated with mismatch repair deficiency, microsatellite instability, or BRAF mutations.

How is this diagnosis made?

HAMN is almost always diagnosed after the appendix has been surgically removed, often because of abdominal pain or a suspected case of appendicitis. A pathologist examines the appendix under the microscope to make the diagnosis.

In HAMN, the normal lining of the appendix is replaced by high-grade mucinous epithelial cells. These cells may form delicate projections, scalloped patterns, or flattened sheets. Compared with LAMN, the nuclei are larger, darker, and more irregular, and there may be many dividing cells, including abnormal (atypical) mitotic figures. Areas of necrosis (dead cells) may be present, and cells may slough into the lumen.

As mucin accumulates, the appendix may become distended, or its wall may become fibrotic or calcified. Mucin can dissect into or through the wall of the appendix, and in some cases, if the appendix ruptures, it may spill into the abdomen. If tumor cells are present in this mucin, there is a risk of developing pseudomyxoma peritonei, a condition in which mucin gradually accumulates throughout the abdominal cavity.

HAMN grows in a pushing pattern, similar to LAMN, meaning it expands outward without deeply destroying surrounding tissue. However, the high-grade appearance of the cells places HAMN between LAMN and invasive mucinous adenocarcinoma on the spectrum of appendiceal tumors. If the tumor shows destructive invasion into the wall or surrounding tissues, it is classified as mucinous adenocarcinoma rather than HAMN.

Tumor extension (depth of spread)

Tumor extension describes how far the mucin or tumor cells have traveled within or beyond the wall of the appendix. This information is essential for determining the pathologic stage and guiding treatment.

HAMNs confined to the inner layers of the appendix (the submucosa and muscularis propria) are staged as pTis, meaning “carcinoma in situ.” These early-stage tumors have not penetrated deeply and generally have a more favorable outlook.

If the tumor reaches the subserosa, the layer beneath the outer surface, the stage becomes pT3. When mucin or tumor cells reach or perforate the serosa, the tumor is staged as pT4a. At this stage, mucin may escape from the appendix.

HAMN that spreads beyond the appendix is staged according to the nature of the mucin:

• pM1a: mucin outside the appendix without tumor cells

• pM1b: mucin-containing tumor cells outside the appendix

Spread beyond the appendix is clinically significant because it may lead to pseudomyxoma peritonei, a condition requiring specialized care.

Margins

A margin is the cut edge of the appendix after removal. The pathologist examines the margin to ensure that the tumor has been entirely removed. A negative margin means no HAMN cells are present at the edge. A positive margin means tumor cells or mucin were present at the cut edge, which may increase the risk of recurrence or peritoneal spread.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Many cancers spread through lymphatic channels into lymph nodes, but HAMN—like LAMN typically spreads by mucin leakage, not by lymphatic spread. Lymph node involvement is rare. If lymph nodes are removed during surgery, the pathologist will examine them to check for tumor cells.

Pathologic stage (pTNM)

HAMN is staged using the same system as invasive appendiceal adenocarcinoma.

• pTis: Tumor confined to inner layers (submucosa/muscularis propria)

• pT3: Tumor reaches the subserosa

• pT4a: Tumor perforates the serosa

• pM1a: Acellular mucin outside the appendix

• pM1b: Mucin-containing tumor cells outside the appendix

This staging system allows doctors to estimate prognosis and plan further treatment.

Prognosis

Because HAMN is rare, long-term data are limited. For tumors confined to the appendix, the prognosis may be similar to LAMN, with excellent outcomes after complete removal. When HAMN spreads into the abdomen, it behaves more like other high-grade mucinous tumors and may require specialized treatment.

The prognosis depends on:

• How far the tumor has spread.

• Whether mucin outside the appendix contains tumor cells.

• The ability to remove all visible disease.

• Whether the tumor shows very high-grade features.

Patients with HAMN that has spread into the abdomen may benefit from a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). This approach has improved survival for many people with peritoneal involvement.

After the diagnosis

Your doctor will review your pathology report to determine whether additional imaging or treatment is needed. If the tumor was confined to the appendix and removed completely, surgery alone may be sufficient. If mucin or tumor cells were found outside the appendix, you may be referred to a surgical oncologist who specializes in managing pseudomyxoma peritonei and other peritoneal diseases. Follow-up may include scans and regular clinical exams.

Questions to ask your doctor

• Was the tumor confined to the appendix or did it spread beyond it?

• Did the mucin outside the appendix contain tumor cells?

• Were the surgical margins clear?

• How was my tumor staged?

• Do I need further imaging, surgery, or HIPEC?

• How often should I be monitored?

• Should I see a specialist in peritoneal surface malignancies?