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A paraganglioma is rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). About 97% are benign and cured by surgical removal; the remaining 3% are malignant because they are able to produce distant metastases. "Paraganglioma" is now the most-widely accepted term for these lesions, that have been also described as: glomus tumor, chemodectoma, perithelioma, fibroangioma, and sympathetic nevi.^[1]

Cellular origin and classification[edit]

Paragangliomas originate from paraganglia in chromaffin-negative glomus cells derived from the embryonic neural crest, functioning as part of the sympathetic nervous system (a branch of the autonomic nervous system). These cells normally act as special chemoreceptors located along blood vessels, particularly in the carotid bodies (at the bifurcation of the common carotid artery in the neck) and in aortic bodies (near the aortic arch).

Accordingly, paragangliomas are categorised as originating from a neural cell line in the World Health Organization classification of neuroendocrine tumors. In the categorization proposed by Wick, paragangliomas belong to group II.^[2] Given the fact that they originate from cells of the orthosympathetic system, paragangliomas are closely related to pheochromocytomas, which however are chromaffin-positive.

Clinical presentation[edit]

Most paragangliomas are either asymptomatic or present as a painless mass. While all contain neurosecretory granules, only in 1–3% of cases is secretion of hormones such as catecholamines abundant enough to be clinically significant; in that case manifestations often resemble those of pheochromocytomas.

Inheritance[edit]

About 75% of paragangliomas are sporadic; the remaining 25% are hereditary (and have an increased likelihood of being multiple and of developing at an earlier age). Mutations of the genes for the succinate dehydrogenase, SDHD (previously known as PGL1), SDHA, SDHC (previously PGL3) and SDHB have been identified as causing familial head and neck paragangliomas. Mutations of SDHB play an important role in familial adrenal pheochromocytoma and extra-adrenal paraganglioma (of abdomen and thorax), although there is considerable overlap in the types of tumors associated with SDHB and SDHD gene mutations. Paragangliomas may also occur in MEN type 2A and 2B. They are seen in at a higher incidence in people living at high altitude. Other genes related to familiar paraganglioma are SDHAF2, VHL, NF1^{[disambiguation needed]}, TMEM127 and MAX.

Pathology[edit]

Mediastinal paraganglioma. The cut surface of a 3.9 x 3.5 x 2.5 cm tumor is triangular, with a bulging peripheral portion and a somewhat fibrotic center. It was surrounded by the heart, left lower lobe of the lung, aorta, esophagus, and diaphragm, and had been 1.8 cm in diameter 7 years before.

Micrograph of a carotid body tumor with the characteristic Zellballen. H&E stain.

The paragangliomas appear grossly as sharply circumscribed polypoid masses and they have a firm to rubbery consistency. They are highly vascular tumors and may have a deep red color.

On microscopic inspection, the tumor cells are readily recognized. Individual tumor cells are polygonal to oval and are arranged in distinctive cell balls, called Zellballen.^[3] These cell balls are separated by fibrovascular stroma and surrounded by sustentacular cells.

By light microscopy, the differential diagnosis includes related neuroendocrine tumors, such as carcinoid tumor, neuroendocrine carcinoma, and medullary carcinoma of the thyroid.

With immunohistochemistry, the chief cells located in the cell balls are positive for chromogranin, synaptophysin, neuron specific enolase, serotonin, neurofilament and Neural cell adhesion molecule; they are S-100 protein negative. The sustentacular cells are S-100 positive and focally positive for glial fibrillary acidic protein. By histochemistry, the paraganglioma cells are argyrophilic, periodic acid Schiff negative, mucicarmine negative, and argentaffin negative.

Sites of origin[edit]

About 85% of paragangliomas develop in the abdomen; only 12% develop in the chest and 3% in the head and neck region (the latter are the most likely to be symptomatic). While most are single, rare multiple cases occur (usually in a hereditary syndrome). Paragangliomas are described by their site of origin and are often given special names:-

Carotid paraganglioma (carotid body tumor): Is the most common of the head and neck paragangliomas. It usually presents as a painless neck mass, but larger tumors may cause cranial nerve palsies, usually of the vagus nerve and hypoglossal nerve.
Glomus tympanicum and Glomus jugulare: Both commonly present as a middle ear mass resulting in tinnitus (in 80%) and hearing loss (in 60%). The cranial nerves of the jugular foramen may be compressed, resulting swallowing difficulty, or ipsilateral weakness of the upper trapezius and sternocleiodomastoid muscles (from compression of the spinal accessory nerve). These patients present with a reddish bulge behind an intact ear drum. This condition is also known as the "Red drum". On application of pressure to the external ear canal with the help of a pneumatic ear speculum the mass could be seen to blanch. This sign is known as "Brown's sign".
Vagal paraganglioma: These are the least common of the head and neck paragangliomas. They usually present as a painless neck mass, but may result in dysphagia and hoarseness.
Pulmonary paraganglioma: These occur in the lung and may be either single or multiple.^[4]

Other sites: Rare sites of involvement are the larynx, nasal cavity, paranasal sinuses, thyroid gland, and the thoracic inlet, as well as the bladder in extremely rare cases.

Treatment[edit]

The main treatment modalities are surgery, embolization^[5] and radiotherapy.^[6]

Additional images[edit]

Micrograph of a carotid body tumor.
Glomus Jugulare Tumor.
Ectopic functional paraganglioma (glomus jugulare) in a patient with VHL. T2 weighted MRI at the same location demonstrates a high signal mass consistent with a paraganglioma. Extra adrenal paragangliomas can be found in VHL (arrow).
S100 immunostain highlighting the sustentacular cells in a paraganglioma.

References[edit]

^ Rao AB,et al (1999). "Paragangliomas of the Head and Neck: Radiologic-Pathologic Correlation". Radiographics 119: 1605–32. PMID 10555678.
^ Wick MR (2000). "Neuroendocrine neoplasia. Current concepts". Am. J. Clin. Pathol. 113 (3): 331–5. doi:10.1309/ETJ3-QBUK-13QD-J8FP. PMID 10705811.
^ Kairi-Vassilatou E, Argeitis J, Nika H, Grapsa D, Smyrniotis V, Kondi-Pafiti A (2007). "Malignant paraganglioma of the urinary bladder in a 44-year-old female: clinicopathological and immunohistochemical study of a rare entity and literature review". Eur. J. Gynaecol. Oncol. 28 (2): 149–51. PMID 17479683.
^ da Silva, RA; Gross JL, Haddad FJ et al. (February 2006). "Primary pulmonary paraganglioma: case report and literature review". Clinics (São Paulo) 61 (1): 83–86. doi:10.1590/S1807-59322006000100015. PMID 16532231. Cite uses deprecated parameters (help)
^ Carlsen CS, Godballe C, Krogdahl AS, Edal AL (2003). "Malignant vagal paraganglioma: report of a case treated with embolization and surgery". Auris, nasus, larynx 30 (4): 443–6. doi:10.1016/S0385-8146(03)00066-X. PMID 14656575.
^ Pitiakoudis M, Koukourakis M, Tsaroucha A, Manavis J, Polychronidis A, Simopoulos C (2004). "Malignant retroperitoneal paraganglioma treated with concurrent radiotherapy and chemotherapy". Clinical oncology (Royal College of Radiologists (Great Britain)) 16 (8): 580–1. PMID 15630855.

External links[edit]

Clinical Trial information for patients with Paraganglioma
(Description with pictures)
GeneReviews/NCBI/NIH/UW entry on Hereditary Paraganglioma-Pheochromocytoma Syndromes
(Bilateral Carotid Paraganglioma)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 傍神経節腫：疫学、臨床症状、診断、および組織学的検査 paragangliomas epidemiology clinical presentation diagnosis and histology
2. 傍神経節腫：限局性疾患の治療 paragangliomas treatment of locoregional disease
3. 傍神経節腫および褐色細胞腫：悪性疾患のマネージメント paraganglioma and pheochromocytoma management of malignant disease
4. 遺伝的疾患における褐色細胞腫 pheochromocytoma in genetic disorders
5. 小児における褐色細胞腫 pheochromocytoma in children

English Journal

Radiation dose to the fetus from [18F]-FDG administration during the second trimester of pregnancy.

Zanotti-Fregonara P, Koroscil TM, Mantil J, Satter M.Source* Molecular Imaging Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD; † Wright State University Boonshoft School of Medicine, Dayton, OH; ‡ Department of Nuclear Medicine/PET, Kettering Medical Center, Dayton, OH.
Health physics.Health Phys.2012 Feb;102(2):217-9.
ABSTRACT-: The authors estimated the fetal radiation dose from [F]-FDG in a rare case of a woman who underwent a PET/CT scan during the second trimester of pregnancy. The patient, a 27-y-old female with a paraganglioma, received 181.3 MBq [F]-FDG. From the concentrations of radioactivity measured on
PMID 22217594

18F-DOPA PET/CT biodistribution consideration in 107 consecutive patients with neuroendocrine tumours.

Chondrogiannis S, Grassetto G, Marzola MC, Rampin L, Massaro A, Bellan E, Ferretti A, Mazza A, Al-Nahhas A, Rubello D.SourceaDepartment of Nuclear Medicine, PET/CT Center bDepartment of Medical Physics cDepartment of Internal Medicine, Santa Maria della Misericordia Hospital Rovigo, Rovigo, Italy dDepartment of Nuclear Medicine, Hammersmith Hospital, London, UK.
Nuclear medicine communications.Nucl Med Commun.2012 Feb;33(2):179-84.
OBJECTIVE: L-6-Fluoro 3,4-dihydroxyphenylalanine (F-DOPA), an amino acid-based radiopharmaceutical, is increasingly being used in the detection and management of neuroendocrine tumours. Knowledge of the normal biodistribution of this radiopharmaceutical is essential for the proper interpretation of
PMID 22083098

Management of a giant thoracic hypervascular paraspinal ganglioma.

Nawaz MA, Samarage M, O'Neill K, Punjabi P.SourceDepartment of Cardiothoracic Surgery, Hammersmith Hospital NHS, London, United Kingdom.
The Annals of thoracic surgery.Ann Thorac Surg.2012 Jan;93(1):e7-8.
We report a rare occurrence of a large primary nonfunctioning paraganglioma of the thoracic spine in a 76-year-old man who underwent successful multimodality treatment by preoperative angiographic embolization and debulking through a lateral transthoracic surgical approach.Copyright © 2012 The Soci
PMID 22186487

Japanese Journal

腹腔鏡下に切除した後腹膜血管平滑筋腫の1例

坂田綾子,槙山和秀,野口剛,佐野太,中井川昇,矢尾正祐,中山崇,山中正二,窪田吉信
泌尿器科紀要 58(2), 75-78, 2012-02
… These radiographic findings suggested a retroperitoneal tumor such as paraganglioma, angioma. …
NAID 120003988249

Low-dose 123I-metaiodobenzylguanidine diagnostic scan is inferior to 131I-metaiodobenzylguanidine posttreatment scan in detection of malignant pheochromocytoma and paraganglioma

Kayano Daiki,Taki Junichi,Fukuoka Makoto,Wakabayashi Hiroshi,Inaki Anri,Nakamura Ayane,Kinuya Seigo
Nuclear Medicine Communications 32(10), 941-946, 2011-10
… OBJECTIVE: We assessed the lesion detectability of low-dose diagnostic 123I-metaiodobenzylguanidine (MIBG) whole-body scans obtained at 6 and 24 h compared with posttreatment 131I-MIBG whole-body scans in malignant pheochromocytoma and paraganglioma. … METHODS: Scintigrams obtained in 15 patients with malignant pheochromocytoma and paraganglioma were retrospectively analyzed. …
NAID 120003386976

Related Pictures

★リンクテーブル★

リンク元	「褐色細胞腫」「傍神経節腫」
拡張検索	「extra-adrenal paraganglioma」「nonchromaffin paraganglioma」「gangliocytic paraganglioma」

「褐色細胞腫」

Paraganglioma
	Classification and external resources
	; Micrograph of a carotid body tumor (a type of paraganglioma).
ICD-10	C75.4, C75.5, D35.5, D35.6, D44.6, D44.7
ICD-9	194.5, 194.6, 227.5, 227.6, 237.3
ICD-O:	M8680/0 - M8693/9
DiseasesDB	33480
eMedicine	med/2994
MeSH	D010235

　　[★]

英: pheochromocytoma PC, phaeochromocytoma
同: クロム親和細胞腫 chromaffin cell tumor chromaffinoma
関: 副腎外褐色細胞腫、傍神経節腫 paraganglioma。アドレナリン受容体

概念

副腎髄質や傍神経節などのクロム親和性細胞から発生する腫瘍。
カテコールアミン分泌する

病型

臨床像：発作型・持続型
腫瘍発生様式：散発性、家族性(10%)　：　:*家族性発生のものはMEN2の可能性あり。
発生部位：副腎原発(90%)(片側性、両側性(10%))、副腎外発生(10%)
腫瘍の数：単発性、多発性(10%)
腫瘍の正常：良性、悪性(10%)

病因

10% disease

embfc　←　なんか適当な語呂にして

extraadrenal：副腎外10%
malignancy：悪性10%
bilateral：両側10%
familial：家族性10%
child：小児10%

疫学

20-40歳

遺伝形式

常染色体優性遺伝

原因となる遺伝子

Location	Phenotype	Phenotype	Gene/Locus	Gene/Locus
Location	Phenotype	MIM number	Gene/Locus	MIM number
1p36.22	Pheochromocytoma	171300	KIF1B	605995
1p36.13	Pheochromocytoma	171300	SDHB	185470
2q11.2	{Pheochromocytoma, susceptibility to}	171300	TMEM127	613403
3p25.3	Pheochromocytoma	171300	VHL	608537
5p13.2	{Pheochromocytoma, modifier of}	171300	GDNF	600837
10q11.21	Pheochromocytoma	171300	RET	164761
11q23.1	Pheochromocytoma	171300	SDHD	602690
14q23.3	{Pheochromocytoma, susceptibility to}	171300	MAX	154950

病態生理

起立性低血圧：慢性的な血管収縮により体液が減少して生じやすくなる。また、慢性的なカテコラミン過剰により自律神経の血圧調節能力低下。

病理

悪性褐色細胞腫ではコハク酸脱水素酵素サブユニットB(SDHB)遺伝子に変異が存在するものがある。

症状

カテコールアミンの過剰分泌による症状
高血圧、頭痛、発汗、動悸・頻脈、高血糖　→　5H
起立性低血圧、起立性めまい、蒼白、不安・神経過敏、体重減少

YN.D-69

HT,HM,HG,Hhidr,Head

高血圧

α1作用により末梢血管収縮。
β1作用によりレニン分泌

代謝亢進

高血糖

α2作用：インスリン分泌抑制
β2作用：肝臓によるグリコーゲン分解

頭痛

発汗

代謝亢進による体温上昇に対して発汗により体温の上昇を補償することがメカニズムと思われる。
甲状腺機能亢進症と同じメカニズムに基づく。さらに、脱共役蛋白質の活性化によるものと思う(成長ホルモン#)。

検査

血液検査：カテコラミン、クロモグラニンA
尿検査　：カテコラミン、クロモグラニンA、バニリルマンデル酸、メタネフリン、ノルメタネフリン
薬物負荷検査：

画像検査

MRI：病変はT2 high
CT：出血・壊死部位は低吸収
シンチ：副腎シンチグラム：131I-MIBGの取り込みを見る。

検査禁忌

副腎静脈造影、副腎静脈サンプリング　　←　　褐色細胞腫の場合に高血圧クリーゼの恐れ

診断

治療

薬物療法と手術療法がある。

薬物療法

αβ遮断薬

手術療法

αブロッカー(プラゾシン)とβブロッカーを併用、あるいはαβ遮断薬(ラベタロール)を使用し血圧を安定させてから手術を行う。手術は静脈結紮を先に行いカテコラミンの体循環への流入を防ぐ。
腹腔鏡下副腎摘除術

禁忌となる薬物

グルカゴン：以下のような目的でグルカゴンが用いられるが、褐色細胞腫の患者においては「カテコールアミンの遊離を刺激して、急激な血圧の上昇を招くおそれがあ」ため、禁忌

成長ホルモン分泌能検査、インスリノーマの診断、肝糖原検査、低血糖時の救急処置、消化管のX線および内視鏡検査の前処置

β受容体遮断薬：α受容体遮断薬と併用することなしに単独で用いるのは禁忌。α受容体の血管収縮作用を相対的に増強させるため、逆に血圧が上昇してしまう危険がある。(QB.D-289)

参考

1. PHEOCHROMOCYTOMA - OMIM

http://omim.org/entry/171300

国試

104A044、101A022

「傍神経節腫」

　　[★]

英: paraganglioma
同: 副神経節細胞腫
関: 神経節細胞傍神経節腫、褐色細胞腫、クロム親和細胞腫

「extra-adrenal paraganglioma」

　　[★]

副腎外傍神経節腫、副腎外褐色細胞腫

関: chemodectoma、extra-adrenal pheochromocytoma、nonchromaffin paraganglioma

「nonchromaffin paraganglioma」

　　[★]

非クロム親和性傍神経節腫

関: chemodectoma、extra-adrenal paraganglioma

「gangliocytic paraganglioma」

　　[★]

神経節細胞傍神経節腫

関: paraganglioma

[pmid10555678-1] Rao AB,et al (1999). "Paragangliomas of the Head and Neck: Radiologic-Pathologic Correlation". Radiographics 119: 1605–32. PMID 10555678.

[pmid10705811-2] Wick MR (2000). "Neuroendocrine neoplasia. Current concepts". Am. J. Clin. Pathol. 113 (3): 331–5. doi:10.1309/ETJ3-QBUK-13QD-J8FP. PMID 10705811.

[pmid17479683-3] Kairi-Vassilatou E, Argeitis J, Nika H, Grapsa D, Smyrniotis V, Kondi-Pafiti A (2007). "Malignant paraganglioma of the urinary bladder in a 44-year-old female: clinicopathological and immunohistochemical study of a rare entity and literature review". Eur. J. Gynaecol. Oncol. 28 (2): 149–51. PMID 17479683.

[da_Silva-4] Silva, RA; Gross JL, Haddad FJ et al. (February 2006). "Primary pulmonary paraganglioma: case report and literature review". Clinics (São Paulo) 61 (1): 83–86. doi:10.1590/S1807-59322006000100015. PMID 16532231. Cite uses deprecated parameters (help)

[pmid14656575-5] Carlsen CS, Godballe C, Krogdahl AS, Edal AL (2003). "Malignant vagal paraganglioma: report of a case treated with embolization and surgery". Auris, nasus, larynx 30 (4): 443–6. doi:10.1016/S0385-8146(03)00066-X. PMID 14656575.

[pmid15630855-6] Pitiakoudis M, Koukourakis M, Tsaroucha A, Manavis J, Polychronidis A, Simopoulos C (2004). "Malignant retroperitoneal paraganglioma treated with concurrent radiotherapy and chemotherapy". Clinical oncology (Royal College of Radiologists (Great Britain)) 16 (8): 580–1. PMID 15630855.

Paraganglioma
Classification and external resources
Micrograph of a carotid body tumor (a type of paraganglioma).
ICD-10	C75.4, C75.5, D35.5, D35.6, D44.6, D44.7
ICD-9	194.5, 194.6, 227.5, 227.6, 237.3
ICD-O:	M8680/0 - M8693/9
DiseasesDB	33480
eMedicine	med/2994
MeSH	D010235

匿名

検索

案内

paraganglioma