Is a Carcinoid Tumor Cancer?

What a carcinoid is

It is an old name for a neuroendocrine tumor, which grows from neuroendocrine cells in the wall of organs, most often in the digestive tract. These cells produce hormone-like substances, including serotonin. The word “carcinoid” meant “carcinoma-like”, and for a long time it was used for tumors that grow more slowly than ordinary cancer.

The current WHO classification of digestive system tumors divides neuroendocrine neoplasms into well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Mixed tumors, which contain both a neuroendocrine and a non-neuroendocrine component, form a separate group^[1]. That is why a modern report usually says “neuroendocrine tumor” with its grade instead of “carcinoid”.

For bowel neuroendocrine tumors, their work-up and treatment, see the page on neuroendocrine tumors.

Is a carcinoid cancer or not?

It is not considered benign: a neuroendocrine tumor can spread. At the same time, neuroendocrine tumors differ enormously. A small appendix tumor found by chance after an appendectomy and a small bowel tumor with liver metastases share the same name, but their outlook and treatment are completely different.

A neuroendocrine carcinoma, by contrast, is an aggressive malignant tumor that grows fast and is treated differently from neuroendocrine tumors^[1][5]. That is why the grade and differentiation in the pathology report matter more than the name.

What G1, G2, G3 and Ki-67 mean

The grade shows how fast the tumor cells divide. It is based on the Ki-67 index, the proportion of dividing cells, and on the number of mitoses per 2 mm² of tissue^[1]:

• G1 — Ki-67 below 3% and fewer than 2 mitoses: the slowest-growing tumor;
• G2 — Ki-67 3–20% or 2–20 mitoses;
• G3 — Ki-67 above 20% or more than 20 mitoses: the tumor is well differentiated but divides fast;
• neuroendocrine carcinoma — a poorly differentiated tumor with high proliferative activity. It is told apart from G3 by the appearance of its cells, not by Ki-67 alone.

If Ki-67 and the mitotic count point to different grades, the higher grade is assigned^[1][5]. For example, Ki-67 of 2% with 3 mitoses is G2, not G1. Treatment cannot be planned without the Ki-67 index and grade^[5], so if the report does not include them, it is worth asking for the slides to be reassessed.

Appendix carcinoid

It is usually found by chance in a removed appendix, and in most cases removing the appendix is enough. Whether another operation is needed depends mainly on the size and risk features^[3]:

• up to 1 cm — removing the appendix is usually enough;
• 1–2 cm — if the tumor has been removed completely, a second operation is usually not needed. It is discussed case by case, mainly when the tumor grade is high;
• over 2 cm — a right hemicolectomy is indicated, that is, removal of the right half of the colon with its lymph nodes; in young patients a smaller operation is sometimes possible;
• if tumor is found at the resection margin, further surgery is discussed whatever the size.

Rectal carcinoid

These are usually small G1 tumors that can be removed endoscopically if the right technique is used^[4]. Before removal, the size, depth of invasion and lymph nodes are assessed with endoscopic ultrasound, and pelvic MRI is added for tumors of 1 cm or more, G2–G3 tumors or suspected lymph node involvement. Management by size is as follows^[4]:

• up to and including 1 cm — endoscopic removal;
• over 1 cm and up to 2 cm — the decision is made by a multidisciplinary team after a full work-up: endoscopic or transanal removal, or surgery;
• 2 cm or more, or with involved lymph nodes — surgery as for rectal cancer, with removal of the mesorectum.

If the tumor was removed during a routine colonoscopy without knowing it was a neuroendocrine tumor, it is important to check whether it was removed completely. This decides whether further treatment is needed^[4].

Small bowel carcinoid

Small bowel tumors often cause only vague abdominal pain and are frequently found when the lymph nodes are already involved^[5]. A large mass of involved lymph nodes in the mesentery can cause bowel obstruction or impair the blood supply to the bowel. That is why removing the affected segment of bowel together with its mesentery is usually considered even when there are metastases, mainly to prevent these complications: whether such surgery prolongs survival is not clearly established^[5]. In selected patients, liver metastases are also operated on. The decision is made by a multidisciplinary team.

Carcinoid syndrome

It is chronic diarrhea and/or episodes of skin flushing together with raised levels of serotonin or its breakdown product 5-HIAA^[2]. Not everyone develops it: in recent data, it occurs in 19–35% of patients with neuroendocrine tumors^[2].

Carcinoid syndrome usually means the tumor has already spread: at least 87% of patients with it have liver metastases, although the syndrome sometimes occurs without them^[2]. Rarely, over time, it can damage the valves of the right side of the heart, so these patients need a heart check, including echocardiography^[2]. Similar symptoms can have other causes, so they need to be investigated rather than put down to the syndrome.

What to do if your report says “carcinoid”

1. Check the pathology reportIt should state the grade (G1–G3), the Ki-67 index, the mitotic count and, if the tumor was removed, the margin status. If these are missing, ask for the slides to be reassessed.
2. Have the tests your doctor ordersWhat is needed depends on the tumor location: CT or MRI, endoscopic ultrasound, PET-CT with somatostatin analogues, a 5-HIAA test.
3. Do not judge by the name“Carcinoid” means neither “nothing to worry about” nor “a death sentence”. What matters is the grade, size, location and spread.
4. Show your results to a surgeonSend your pathology report and scans: the online consultation is free. We discuss a treatment plan after a full work-up and a multidisciplinary team review.

Sources

1. Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76(2):182–188. PMID 31433515
2. Grozinsky-Glasberg S, Davar J, Hofland J, et al. European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease. J Neuroendocrinol. 2022;34(7):e13146. PMID 35613326
3. Kaltsas G, Walter T, Knigge U, et al. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for appendiceal neuroendocrine tumours (aNET). J Neuroendocrinol. 2023;35(10):e13332. PMID 37682701
4. Rinke A, Ambrosini V, Dromain C, et al. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours. J Neuroendocrinol. 2023;35(6):e13309. PMID 37345509
5. Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(7):844–860. PMID 32272208

This article is for general information and does not replace a consultation: the treatment plan is based on your pathology and test results.