Bronchial adenoma D38.1

Synonyms

Basal cell carcinoma; carcinoid;

First Describer

In 1831, Laennec was the first to describe bronchial adenoma. Kramer coined the term "bronchial adenoma" in 1930. A detailed description was published by Wessler and Rabin in 1932 (Doerr 1969).

Bronchial mucinous adenoma (BMGA), a benign rare tumor of the tracheobronchial mucous glands, was first described by Müller in 1882 (Oliveira 2017).

The first bronchoplastic surgery of an adenoma was performed by Price Thomas in 1956 (Krajc 2013).

A bronchial adenoma is a semimalignant tumor of the bronchial tubes, which is a potential neoplasm (Kasper 2015) and can be neuroendocrine active.

Nowadays, the term "bronchial adenoma" is generally no longer used. It has been changed to "bronchial carcinoid tumors (BCT)" (Mashaal 2022).

The staging is based on the TNM classification for lung cancer:

• Stage I: localized
• Stage II: hilar lymph node involvement
• Stage III: mediastinal lymph node involvement
• Stage IV: liver metastases (Kaifi 2015).

In the literature, very different divisions of a bronchial adenoma can be found.

Various semimalignant tumors of the bronchial system are grouped under the generic term "bronchial adenoma". Müller (1995) gives the following subdivision:

• pleomorphic adenomas (mixed tumors)
• monomorphic adenomas:
  • cystadenomas
  • Oncocytomas
  • Clear cell tumors

Emminger (2010) differentiates between:

• bronchus carcinoid (BCT)
• Papillomas
• Cylindromas (Emminger 2010)

Reiser (2013) considers a bronchial adenoma to be a tumor entity that is histologically subdivided into:

• carcinoids (>80%)
• Cylindromas (>10%):
  • adenoid cystic carcinoma
  • mucoepidermoid carcinoma (Reiser 2013).

WHO- classification includes 4 categories:

• typical carcinoid (1 - 2 % of all lung tumors)
• atypical carcinoid (0.1 - 0.2 % of all lung tumors)
• small cell carcinoma (9.8 % of all lung tumors)
• large cell neuroendocrine carcinoma (0.3 % of all lung tumors)

(Kasper 2015)

According to Mashaal (2022), we now differentiate only:

• 1. typical carcinoid tumors.

In this case, the tumor suppression markers - mutations of the p53, BCL2 or BAX genes - are missing.

• 2. Untypical carcinoid tumors.

In this type, tumor suppression marker mutations exist (Mashaal 2022).

Of the bronchial tumors, approximately 5-10% are benign or semimalignant. Bronchial adenomas form the largest subgroup with 75 % (Heberer 2013). According to Mashaal (2022), BCT accounts for 1 - 2 % of all lung tumors .

Bronchial adenoma is particularly common between the 3rd and 4th decades of life (Herold 2022). It affects men and women with equal frequency. However, males are affected approximately 1 decade earlier than females (Mashaal 2022).

BCT, which occurs congenitally as part of MEN 1 syndrome, occurs in approximately 8% of affected individuals and is predominantly found in females (sex ratio 4:1).

(Kasper 2015)

In most cases, a BCT is an endobronchial lesion, but up to 20% may develop from peripheral pulmonary nodules.

Environmental factors such as smoking or environmental toxins do not play a role in the development. However, there are cases associated with congenital endocrine neoplasia type 1 (MEN- 1) (Kasper 2015 / Mashaal 2022).

A BCT develops from the Kulchitsky cells of the bronchial mucosa or from the cartilaginous epithelium of the tracheobronchial tree. It has an endocrine function and can secrete peptide hormones and neuroamines such as ACTH, bradykinin, serotonin, and somatostatin (Mashaal 2022).

It is often centrally located and grows slowly toward the clearing of a bronchus (Herold 2022).

Only about 25% of patients are symptomatic (Mashaal 2022). The adenoma is not infrequently discovered as an incidental finding during X-ray examinations (Emminger 2010).

Otherwise, the following symptoms may exist:

• productive and nonproductive cough
• wheezing as in bronchial asthma
• chest pain (about 40%) (Mashaal 2022)
• Hemoptysis: these occur in about 25-50% of patients (Mashaal 2022).
• recurrent pneumonia (Herold 2022)
• Increasing dyspnea (Zhu 2018).
• Cushing's syndrome (Mashaal 2022).

Differentiation between typical and atypical BCTs is performed by biopsies obtained by bronchoscopy and by specific immunostaining. If it is an atypical carcinoid, imaging studies are indicated to look for metastases (Mashaal 2022).

X-ray thorax

• Bronchial obstruction
• Atelectasis (in 40 % [Mashaal 2022])
• Signs of pneumonia (Herold 2022)
• Formation of bronchiectasis with increasing fibrosis (Vogl 2011)
• central lesion (in about 25 %)
• peripheral single nodules in the periphery of the lung in about 20 % (Mashaal 2022)

CT / MRI

Both examinations are well suited for the detection of a BCT (Kasper 2015).

CT additionally serves to identify smaller lesion of the tracheobronchial tree. In highly vascularized lesions, contrast enhancement and / or calcification is found. The so-called bronchial tree sign (bronchial triangle sign) - first described by Coruh 2020 - is used to differentiate from hamartomas (rare benign tumors of the lung [Curran 2013]).

HR- CT

• Bronchiectasis

HR- Ct is the best examination to detect bronchiectasis: sensitivity > 95%, specificity 93 - 100% (Vogl 2011).

Bronchoscopy

Because BCT is often a central lesion, bronchoscopy is the most effective diagnostic tool (Mashaal 2022).

• Serotonin (Emminger 2010)
• ACTH
• Chromogranin A in serum

Urinalysis:

• 5- hydroxyindoleacetic acid (Mashaal 2022).

Histologically, BCT resembles carcinoid tumors of the intestine. They consist of small, roundish, uniform cells that have formed nests or strands.

90% of BCTs are well differentiated, and approximately 10% of atypical ones show more severe pleomorphism. Atypical BCTs show a higher tendency to invade lymphatic vessels (Mashaal 2022).

• bronchial asthma
• malignant tumors of the lung such as:
  • Adenocarcinoma
  • large cell carcinoma
  • small cell carcinoma
  • squamous cell carcinoma (see lung carcinoma)
• benign changes of the lung such as:
  • infectious granulomatous lesions
  • vascular causes such as:
    • arteriovenous malformations
    • hematomas
    • pulmonary infarcts
    • pulmonary varices
  • inflammatory causes such as:
    • granulomatosis with polyangiitis
    • rheumatic nodules
    • sarcoidosis
• amyloidoma
• round atelectasis
• localized fluid
• intrapulmonary lymph nodes
• mucoid impaction
• aspirated foreign body (Mashaal 2022)

• Carcinoid crisis
• Carcinoid syndrome
• Cushing's syndrome
• Metastases

In about 15% of cases, metastases develop. These are often found in the liver, bones, adrenal glands and brain (Mashaal 2022).

A bronchial adenoma should be resected promptly after diagnosis. Emminger (2010) still describes growth as slow, but the tumors can lead to bronchial stenosis (such as the papillomas), be endocrine active (such as the bronchial carcinoid), and malignantly degenerate (such as the cylindromas and bronchial carcinoid). However, according to Mashaal (2022), they can sometimes grow rapidly and be much more aggressive overall than previously thought.

The treatment approach in stage IV (see "Classification" above) is somewhat different. Here, surgical resection alone is not sufficient.

Interventional radiotherapy should be performed preoperatively. In addition, somatostatin analogues are used for:

- reduction of the tumor mass

- positive effect on symptomatic treatment of neurosecretory effects

- alleviation of symptoms

- stabilization of tumor growth for several years (Mashaal 2022).

Similarly, chemotherapeutic agents such as temozolomide and thalidomide, which are currently still in clinical trials, have shown therapeutic benefits.

Other chemotherapy options such as radioisotope-labeled peptide receptor therapy with 131- MIBG, 90 Y- DOTA- TOC, or 177 Lu-DOTA- TOC have also shown good results in clinical trials to date.

Clinical trials with tyrosine kinase antibodies and inhibitors of mammalian mTOR receptors are currently in testing (Mashaal 2022).

Complete surgical resection is the treatment of choice. As a rule, neuroendocrine symptoms also disappear after surgery (Mashaal 2022).

The prognosis of BCT depends on several factors:

• the severity of the intrabronchial obstruction
• the ability to metastasize
• the total production of vasoactive amines (Mashaal 2022).

The prognosis of a typical BCT is good. Survival rates are 92% at 5 years and 88% at 10 years.

For atypical BCTs, the prognosis is worse, ranging from 69% based on 5-year survival and 24-52% based on 10-year survival (Mashaal 2022).

After complete surgical resection, the overall prognosis is better (Mashaal 2022).

Recurrences are extremely rare in typical carcinoids, but more likely in atypical carcinoids, which certainly contributes to the poorer prognosis in the latter (Mashaal 2022).

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