Pulmonary carcinoid tumour is a neuroendocrine tumour of the lung.

There are two types:

- Typical pulmonary carcinoid tumour

- Atypical pulmonary carcinoid tumour

Atypical pulmonary carcinoid tumour is a subtype of pulmonary carcinoid tumor. It is an uncommon low-grade malignant lung mass that is most often in the central airways of the lung. It is also known as "atypical lung carcinoid tumour", " atypical lung carcinoid" or "moderately differentiated neuroendocrine carcinoma".

It is a more aggressive than typical carcinoid tumors: nodal metastases in 70% vs. 5%. The 5 year survival is 49-69%.

Atypical carcinoid tumors have increased mitotic activity (2-10 per 10 HPF), nuclear pleomorphism or foci of necrosis.

Lung carcinoids typically present with a cough or hemoptysis. Findings may closely mimic malignant tumours of the lung, i.e. lung cancer.

Typical pulmonary carcinoid tumour is a subtype of pulmonary carcinoid tumour. It is an uncommon low-grade malignant lung mass that is most often in the central airways of the lung.

It is also known as typical lung carcinoid tumour, lung carcinoid, and typical lung carcinoid.

Pulmonary neuroendocrine tumor are classified according to tumoral grade:

- Low grade pulmonary neuroendocrine tumor: Typical pulmonary carcinoid tumour (TC; low-grade);

- Intermediate-grade pulmonary neuroendocrine tumor: Atypical pulmonary carcinoid tumour (AC; intermediate-grade)

- High-grade pulmonary neuroendocrine tumor

- Small cell lung cancer (SCLC)

- Large cell neuroendocrine carcinoma (LCNEC of the lung)

Low-grade nodular neuroendocrine proliferations ≥ 0.5 cm are classified as carcinoid tumors and smaller ones are called pulmonary tumorlets.

When neuroendocrine cell hyperplasia and tumorlets are extensive, they represent the rare preinvasive lesion for carcinoids known as "diffuse idiopathic pulmonary neuroendocrine cell hyperplasia".

Both LCNEC and SCLC can demonstrate histologic heterogeneity with other major histologic types of lung carcinoma, such as pulmonary adenocarcinoma or pulmonary squamous cell carcinoma, but is not characteristic of TC or AC.

Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.

Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical pulmonary carcinoid tumor and intermediate-grade atypical pulmonary carcinoid tumor to the high-grade pulmonary large cell neuroendocrine carcinoma (LCNEC) and pulmonary small cell carcinoma (SCLC), with significant clinical, epidemiologic and genetic differences.

"Lung tumors" are neoplastic tumors of the lung These include:

Primary tumors of the lung/pulmonary system:

- Bronchial leiomyoma, a rare, benign tumor

- Lung cancer, the term commonly used to refer to "carcinoma of the lung"

- Pulmonary carcinoid tumor

- Pleuropulmonary blastoma

- Neuroendocrine tumors of the lung

- Lymphomas of the lung.

- Sarcomas of the lung.

- Some rare vascular tumors of the lung

Non-lung tumors which may grow into the lungs:

- Mediastinal tumors

- Pleural tumors

Metastasis or secondary tumors/neoplasms with other origin:

- Metastasis to the lung

While most carcinoids are asymptomatic through the natural lifetime and are discovered only upon surgery for unrelated reasons (so-called "coincidental carcinoids"), all carcinoids are considered to have malignant potential.

About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:

- Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonin's growth-promoting effect on cardiac myocytes,[14] a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve.

- Diarrhea

- Wheezing

- Abdominal cramping

- Peripheral edema

The outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea.

This constellation of symptoms is called "carcinoid syndrome" or (if acute) "carcinoid crisis". Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating sites of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.

They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most common affected area is the respiratory tract, with 28% of all cases — per PAN-SEER data (1973 – 1999). The rectum is also a common site.

Carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome.

Carcinoid tumors are the most common malignant tumor of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach. They are known to grow in the liver, but this finding is usually a manifestation of metastatic disease from a primary carcinoid occurring elsewhere in the body. They have a very slow growth rate compared to most malignant tumors. The median age at diagnosis for all patients with neuroendocrine tumors is 63 years.

Synonyms for FA include well differentiated fetal adenocarcinoma, high-grade fetal adenocarcinoma, pulmonary adenocarcinoma

of fetal type, and pulmonary endodermal tumour resembling fetal lung.

FA can produce repeated hemoptysis, possibly related to cavitation of the tumor.

Other presenting symptoms described have included: flu-like syndrome with cough and fever,

Aside from cancer general symptoms such as malaise, fever, weight loss and fatigue, Pancoast tumour can include a complete Horner's syndrome in severe cases: miosis (constriction of the pupils), anhidrosis (lack of sweating), ptosis (drooping of the eyelid) and enophthalmos (sunken eyeball). In progressive cases, the brachial plexus is also affected, causing pain and weakness in the muscles of the arm and hand with a symptomatology typical of thoracic outlet syndrome. The tumour can also compress the recurrent laryngeal nerve and from this a hoarse voice and bovine cough may occur.

In superior vena cava syndrome, obstruction of the superior vena cava by a tumour (mass effect) causes facial swelling cyanosis and dilatation of the veins of the head and neck.

A Pancoast tumor is an apical tumour that is typically found in conjunction with a smoking history. The clinical signs and symptoms can be confused with neurovascular compromise at the level of the superior thoracic aperture. The patient's smoking history, rapid onset of clinical signs and symptoms and pleuritic pain can suggest an apical tumour. A Pancoast tumor can give rise to both Pancoast syndrome and Horner's syndrome. When the brachial plexus roots are involved it will produce Pancoast syndrome; involvement of sympathetic fibres as they exit the cord at T1 and ascend to the superior cervical ganglion will produce Horner's syndrome.

This particular variant of lung cancer is usually asymptomatic and is found after chest x-rays are taken for other reasons. Hemoptysis is seen occasionally and, in some cases, distal obstruction of bronchi by blood clots or mucus plugs produces cough and/or infection. Lesions often enlarge and progress slowly, over many years.

The 1999 World Health Organization classification system defined MCACL as a cystic adenocarcinoma with copious mucin production that, histologically, resembles (the more common) mucus-producing cystadenocarcinomas originating in the ovary, breast and pancreas. The 2004 revision of the WHO classification noted that the tumors tend to be well circumscribed by a partial fibrous tissue capsule with central cystic change and copious mucin pooling. The thin, fibrous wall circumscribing the tumor is highly characteristic of this lesion. It can sometimes occur within a pulmonary bronchocele, and this tumor entity should be kept in mind after identification of a bronchocele with suspicious or non-prototypical imaging characteristics.

Microscopically, the neoplastic epithelial cells tend to grow along the alveolar walls, in a fashion similar to the mucinous variant of bronchioloalveolar carcinoma, a more common form of adenocarcinoma.

Hemoptysis is seen occasionally.

Positron Emission Tomography (PET) scanning can be of assistance in diagnosing MCACL, as these lesions show intense uptake, typically in the wall of the tumor.

CA 19-9 has been reported to be elevated in MCACL.

Differential diagnosis of MCACL includes secondary metastatic cystadenocarcinomatous lesions, particularly from the pancreas or ovary, mucoepidermoid carcinoma, and pulmonary mucinous bronchioloalveolar carcinoma. The mouse monoclonal antibody 1D3, developed to detect a high molecular weight mucin found in a number of cystic malignancies of various organs, may be of use in differentiating primary mucinous cystadenocarcinoma of the lung from metastatic lung tumors due to mucinous cystic lesions of the uterus and pancreas, as well as those primary in the colon and stomach.

Mucinous cystadenocarcinoma of the lung (MCACL) is a very rare malignant mucus-producing neoplasm arising from the uncontrolled growth of transformed epithelial cells originating in lung tissue.

Lung cancer is an extremely heterogeneous family of malignant neoplasms, with well over 50 different histological variants recognized under the 4th revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Because these variants have differing genetic, biological, and clinical properties, including response to treatment, correct classification of lung cancer cases are necessary to assure that lung cancer patients receive optimum management.

The WHO-2004 scheme groups lung carcinomas into 8 major types:

- Squamous cell carcinoma

- Small cell carcinoma

- Adenocarcinoma

- Large cell carcinoma

- Adenosquamous carcinoma

- Sarcomatoid carcinoma

- Carcinoid tumor

- Salivary gland-like carcinoma

EMECL is considered a subtype of salivary gland-like carcinoma, tumors so named because their histological appearance and characteristics closely resemble malignant neoplasms arising in the major and minor salivary glands.

Adenocarcinomas are highly heterogeneous tumors. Several major histological subtypes are currently recognized by the WHO and IASLC/ATS/ERS

- Non-invasive or minimally invasive adenocarcinoma

- Adenocarcinoma in situ of the lung (Bronchioalveolar carcinoma)

- Minimally invasive adenocarcinoma of the lung

- Invasive adenocarcinoma

- Acinar predominant adenocarcinoma

- Papillary predominant adenocarcinoma

- Micropapillary predominant adenocarcinoma

- Solid predominant adenocarcinoma

- Invasive mucinous adenocarcinoma

In as many as 80% of tumors that are extensively sampled, components of more than one of these subtypes will be recognized. In such cases, resected tumors should be classified by comprehensive histological subtyping. Using increments of 5% to describe the amount of each subtype present, the predominant subtype is used to classify the whole tumor. The predominant subtype is prognostic for survival after complete resection.

Signet ring and clear cell adenocarcinoma are no longer histological subtypes, but rather cytological features that can occur in tumour cells of multiple histological subtypes, most often solid adenocarcinoma.

Some variants are not clearly recognized by the WHO and IASLC/ATS/ERS classification:

- Enteric adenocarcinoma of the lung

- Cribriform adenocarcinoma of the lung

A Pancoast tumor is a tumor of the pulmonary apex. It is a type of lung cancer defined primarily by its location situated at the top end of either the right or left lung. It typically spreads to nearby tissues such as the ribs and vertebrae. Most Pancoast tumors are non-small cell cancers.

The growing tumor can cause compression of a brachiocephalic vein, subclavian artery, phrenic nerve, recurrent laryngeal nerve, vagus nerve, or, characteristically, compression of a sympathetic ganglion (the superior cervical ganglion), resulting in a range of symptoms known as Horner's syndrome.

Pancoast tumors are named for Henry Pancoast, a US radiologist, who described them in 1924 and 1932.

GCCs have an aggressive course compared to other appendiceal neuroendocrine tumours.

In WHO-2004, BACs are one of four specific histologic subtypes of lung adenocarcinoma, along with acinar adenocarcinoma, papillary adenocarcinoma, and solid adenocarcinoma with mucin production. However, approximately 80% of adenocarcinomas are found to contain two (or more) of these four subtypes. Multiphasic tumors such as these are classified into a fifth "subtype", termed adenocarcinoma with mixed subtypes.

There are other classification systems that have been proposed for lung cancers, including BACs and other forms of adenocarcinoma. The Noguchi classification system for small adenocarcinomas has received considerable attention, particularly in Japan, but has not been nearly as widely applied and recognized as the WHO system.

Like other forms of lung carcinoma, BAC possesses unique clinical and pathological features, prognosis, and responses to different treatments.

Carcinoids most commonly affect the small bowel, particularly the ileum, and are the most common malignancy of the appendix. Many carcinoids are asymptomatic and are discovered only upon surgery for unrelated causes. These coincidental carcinoids are common; one study found that one person in ten has them. Many tumors do not cause symptoms even when they have metastasized. Other tumors even if very small can produce adverse effects by secreting hormones.

Ten per cent (10%) or less of carcinoids, primarily some midgut carcinoids, secrete excessive levels of a range of hormones, most notably serotonin (5-HT) or substance P, causing a constellation of symptoms called carcinoid syndrome:

- flushing

- diarrhea

- asthma or wheezing

- congestive heart failure (CHF)

- abdominal cramping

- peripheral edema

- heart palpitations

A carcinoid crisis with profound flushing, bronchospasm, tachycardia, and widely and rapidly fluctuating blood pressure can occur if large amounts of hormone are acutely secreted, which is occasionally triggered by factors such as diet, alcohol, surgery chemotherapy, embolization therapy or radiofrequency ablation.

Chronic exposure to high levels of serotonin causes thickening of the heart valves, particularly the tricuspid and the pulmonic valves, and over a long period can lead to congestive heart failure. However, valve replacement is rarely needed. The excessive outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency, and thus pellagra, which is associated with dermatitis, dementia, and diarrhea. Many other hormones can be secreted by some of these tumors, most commonly growth hormone that can cause acromegaly, or cortisol, that can cause Cushing's syndrome.

Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. Bowel obstruction can occur, sometimes due to fibrosing effects of NET secretory products with an intense desmoplastic reaction at the tumor site, or of the mesentery.

Conceptually, there are two main types of NET within this category: those which arise from the gastrointestinal (GI) system and those that arise from the pancreas. In usage, the term "carcinoid" has often been applied to both, although sometimes it is restrictively applied to NETs of GI origin (as herein), or alternatively to those tumors which secrete functional hormones or polypeptides associated with clinical symptoms, as discussed.

The carcinoid syndrome occurs in approximately 5% of carcinoid tumors and

becomes manifest when vasoactive substances from the tumors enter the systemic circulation escaping hepatic degradation. Interestingly, if the primary tumor is from the GI tract (hence releasing serotonin into the hepatic portal circulation), carcinoid syndrome generally does not occur until the disease is so advanced that it overwhelms the liver's ability to metabolize the released serotonin.

- Flushing: The most important clinical finding is flushing of the skin, usually of the head and the upper part of thorax.

- Diarrhea: When the diarrhea is intense and explosive, it may lead to electrolyte disturbance and dehydration.

- Abdominal pain: Due to desmoplastic reaction of the mesentery or hepatic metastases.

- Bronchoconstriction, which may be histamine-induced, affects a smaller number of patients and often accompanies flushing.

- Secondary restrictive cardiomyopathy: About 50% of patients have cardiac abnormalities classically of the restrictive-type caused by serotonin-induced fibrosis of the valvular endocardium, notably the tricuspid and pulmonary valves, called cardiac fibrosis. This results in a heart with normal rhythm and contractility, but reduced preload and end-diastolic volume. "TIPS" is an acronym for Tricuspid Insufficiency, Pulmonary Stenosis (fibrosis of tricuspid and pulmonary valves).

- Nausea and Vomiting

In situ pulmonary adenocarcinoma (AIS), previously called "Bronchioloalveolar carcinoma" (BAC), is a term describing certain variants of lung cancer arising in the distal bronchioles or alveoli that initially exhibit a specific non-invasive growth pattern. BAC is a type of non-small-cell lung cancer (NSCLC). AIS is defined as a small (≤3 cm) solitary tumour with pure alveolar epithelial appearance (lepidic growth), lacking any invasion of the interstitium. If completely resected, the prognosis of surgically treated AIS is 100%.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a subtype of pneumocytic hyperplasia (hyperplasia of pneumocytes lining pulmonary alveoli).

Several synonymous terms have been done for this entity: adenomatoid proliferation of alveolar epithelium, papillary alveolar hamartoma, multifocal alveolar hyperplasia, multinodular pneumocyte hyperplasia.

These multifocal lesions are observed in tuberous sclerosis, and can be associated with lymphangioleiomyomatosis and perivascular epithelioid cell tumour (PEComa or clear cell "sugar tumor")).

It can be diagnosed through lung biopsy using thoracoscopy.

Nearly 40% of lung cancers in the US are adenocarcinoma, which usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"), adenocarcinoma is the most common form of lung cancer. Its incidence has been increasing in many developed Western nations in the past few decades, where it has become the most common major type of lung cancer in smokers (replacing squamous cell lung carcinoma) and in lifelong nonsmokers. According to the Nurses' Health Study, the risk of adenocarcinoma of the lung increases substantially after a long duration of previous tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.4 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 5.

This cancer usually is seen peripherally in the lungs, as opposed to small cell lung cancer and squamous cell lung cancer, which both tend to be more centrally located, although it may also occur as central lesions. For unknown reasons, it often arises in relation to peripheral lung scars. The current theory is that the scar probably occurred secondary to the tumor, rather than causing the tumor. The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women. The peripheral location of adenocarcinoma in the lungs may be due to the use of filters in cigarettes which prevent the larger particles from entering the lung. Deeper inhalation of cigarette smoke results in peripheral lesions that are often the case in adenocarcinomas of the lung. Generally, adenocarcinomas grow more slowly and form smaller masses than the other subtypes. However, they tend to form metastases widely at an early stage. Adenocarcinoma is a non-small cell lung carcinoma, and as such, it is not as responsive to radiation therapy as is small cell lung carcinoma, but is rather treated surgically, for example by pneumonectomy or lobectomy.