Paraganglioma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

• There is limited information about the historical perspective of [disease name].

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• [Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].

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The following are a few famous cases of [disease name]:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Asem Juhani, M.D.[2]

Pheochromocytomas and paragnagliomas (collectively referred to as PPGLs) are rare tumors that originate from chromaffin cells in the adrenal medulla (pheochromocytoma) and extra-adrenal neural ganglia (paraganglioma). These tumors can be biochemically active (producing catecholamines) or silent. PPGLs can also be classified as either sporadic or familial, with association extablished to several familial syndromes.

PPGLs can be either benign or malignant. However, the definition of malignancy is established by the presence of metastasis as benign and malignant tumors in this category are indistinguishable in their histological and biochemical characteristics. Extent of spread of tumor is another factor that classifies PPGLs, putting them into the categories of local, regional and metastatic.

There are several way to classify pheochromocytomas and paragangliomas (PPGLs), including:

PPGLs may be classified according to their site of origin into:

• Pheochromocytoma: tumor originates from chromaffin cells in the adrenal medulla. (80-85%)
• Paraganglioma: tumor originates from chromaffin cells in extra-adrenal neural ganglia. (15-20%) These can have a sympathetic origin (sympathetic chain in thorax, abdomen and pelvis) or a parasympathetic origin (in neck, head and skull base).

Both pheochromocytomas and paragangliomas may be classified into 3 subcategories based on spread:

• Local.
• Regional.
• Metastatic.

These 3 categories share the same histological and biochemical characteristics. Metastasis is considered the definition of malignancy in PPGLs. Non-metastatic PPGLs are considered benign.

Most PPGLs are biochemically active, producing varying amounts of catecholamines like epinephrine, norepinephrine and dopamine, but rarely, they can be biochemically silent.

For pheochromocytomas (adrenal tumors) , the split is halfway between tumors with adrenergic phenotype and those with a noradrenergic phenotype (half adrenergic, half noradrenergic). Paragangliomas (extra-adrenal tumors) that arise from sympathetic ganglia produce noradrenaline (predominantly or even exclusively), while those in the head and base of skull don’t usually produce catecholamines save for some dopamine and its metabolite 3-methoxytyramine.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

PPGLs arise from chromaffin cells in the adrenal medulla or in extra-adrenal neural ganglia. PPGLs are related to several hereditary syndromes and many of the sporadic cases present germline mutations. Chromaffin cells are involved in the production of catecholamines, hence, these tumors can be biochemically active.

The normal physiology of [name of process] can be understood as follows:

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• [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
• The progression to [disease name] usually involves the [molecular pathway].
• The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics play an important part in PPGL pathogenesis.

[Disease name] is transmitted in [mode of genetic transmission] pattern.

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Genes involved in the pathogenesis of [disease name] include:

• [Gene1]
• [Gene2]
• [Gene3]

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The development of [disease name] is the result of multiple genetic mutations such as:

• [Mutation 1]
• [Mutation 2]
• [Mutation 3]

Conditions associated with [disease name] include:

• [Condition 1]
• [Condition 2]
• [Condition 3]

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Disease name] may be caused by [cause1], [cause2], or [cause3].

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Common causes of [disease] include [cause1], [cause2], and [cause3].

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The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

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The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

• Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of disease name, however complications resulting from untreated disease name is common.
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Common causes of [disease name] may include:

• [Cause1]
• [Cause2]
• [Cause3]

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• [Disease name] is caused by an infection with [pathogen name].
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Less common causes of [disease name] include:

• [Cause1]
• [Cause2]
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• [Disease name] is caused by a mutation in the [gene name] gene.

List the causes of the disease in alphabetical order:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2]

Paraganglioma must be differentiated from carcinoid tumor, neuroendocrine carcinoma, medullary thyroid carcinoma, middle ear adenoma, and meningioma.

Paraganglioma should be differentiated from other tuomrs such as:

• Carcinoid tumor
• Neuroendocrine carcinoma
• Medullary thyroid carcinoma
• Middle ear adenoma
• Meningioma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

• The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
• In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

• The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
• In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
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• In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate/mortality rate of [number range]%.
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

There are no established risk factors for [disease name].

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The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

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Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

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Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

• Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
• Common risk factors in the development of [disease name] include:
  • [Risk factor 1]
  • [Risk factor 2]
  • [Risk factor 3]

• Less common risk factors in the development of [disease name] include:
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  • [Risk factor 2]
  • [Risk factor 3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

There is insufficient evidence to recommend routine screening for [disease/malignancy].

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According to the [guideline name], screening for [disease name] is not recommended.

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According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

There is insufficient evidence to recommend routine screening for [disease/malignancy].

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According to the [guideline name], screening for [disease name] is not recommended.

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According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with:

• [Condition 1]
• [Condition 2]
• [Condition 3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

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Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

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Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

• The symptoms of (disease name) usually develop in the first/ second/ third decade of life, and start with symptoms such as ___.
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• If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

• Common complications of [disease name] include:
  • [Complication 1]
  • [Complication 2]
  • [Complication 3]

• Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [–]%.
• Depending on the extent of the [tumor/disease progression] at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent.
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