Paragangliomas Overview

Questions and Answers

What is the primary origin of paragangliomas?

Mesodermal tissue

Epithelial cells

Endodermal tissue

Neural crest (correct)

Which of the following sites is most commonly associated with extra-adrenal paragangliomas?

Urinary bladder

Carotid body (correct)

Pancreas

Adrenal gland

Which mutation is most frequently associated with head and neck paragangliomas?

SDHB

SDHC

SDHA

SDHD (correct)

Which enzyme complex is the SDH enzyme associated with?

Tricarboxylic acid cycle Signup and view all the answers

What is the consequence of mutations in any of the SDH gene subunits?

Dysfunction of the entire SDH complex Signup and view all the answers

Which type of mutations account for most cases of SDH deficiency in head and neck paragangliomas?

Germline mutations Signup and view all the answers

Which of the following statements is true regarding the prevalence of SDH mutations?

Up to half of all paragangliomas have SDH mutations. Signup and view all the answers

What role does the SDH complex play within mitochondria?

Oxidizes succinate to fumarate Signup and view all the answers

What histological feature in paragangliomas is NOT typically associated with malignancy?

Sparse atypical mitoses Signup and view all the answers

Which type of morphology may be seen in paragangliomas that could potentially mimic small cell carcinoma?

Sclerosing variants Signup and view all the answers

What characterizes the sustentacular cells in paragangliomas?

They stain uniformly for S100 protein Signup and view all the answers

Which immunohistochemical marker is NOT consistently positive in paragangliomas?

Neurofilament Signup and view all the answers

Which pattern of paraganglioma may show extensive fibrosis that obscures the classic nested arrangement?

Sclerosing variants Signup and view all the answers

What is the consequence of loss of expression of SDHB in paragangliomas?

Reflects dysfunction of the entire SDH complex Signup and view all the answers

Which feature is a common pitfall for diagnosis in paragangliomas?

Fragmentation of tumor nests Signup and view all the answers

Which of the following features is NOT commonly observed in paragangliomas associated with SDH deficiency?

Presence of keratin markers Signup and view all the answers

Which of the following cytomorphological characteristics is associated with paragangliomas?

Presence of clear cell changes Signup and view all the answers

What is a common characteristic feature observed in paragangliomas?

Supporting sustentacular cells Signup and view all the answers

In which location can paragangliomas be particularly challenging to diagnose?

Middle ear Signup and view all the answers

Which of the following is true regarding necrosis in paragangliomas?

It may be observed in embolized tumors Signup and view all the answers

What feature indicates the indolent nature of most paragangliomas despite their sclerotic features?

Higher rates of recurrence Signup and view all the answers

Which gene is primarily associated with the majority of paragangliomas in patients with hereditary paragangliomatosis?

SDHD Signup and view all the answers

What is the most common location for extra-adrenal paragangliomas?

Carotid body Signup and view all the answers

Which syndrome is characterized by paragangliomas and gastrointestinal stromal tumors?

Carney-Stratakis Syndrome Signup and view all the answers

Which mutation appears to exhibit paternal transmission suggestive of imprinting?

SDHD Signup and view all the answers

Which imaging modality is likely to show an enhancing mass in a characteristic location associated with paragangliomas?

Computed Tomography (CT) Signup and view all the answers

What condition is often associated with paragangliomas due to mutations in the RET gene?

Multiple Endocrine Neoplasia Type 2A (MEN2A) Signup and view all the answers

Which of the following describes the sex distribution of patients affected by paragangliomas?

Females more frequently than males Signup and view all the answers

What is the primary treatment option for paragangliomas that can lead to a good prognosis if completely resected?

Surgery Signup and view all the answers

Which symptoms may indicate the presence of a paraganglioma in the middle ear?

Tinnitus and hearing loss Signup and view all the answers

What percentage of hereditary paragangliomatosis cases are associated with multiple paragangliomas?

90%-100% Signup and view all the answers

Which imaging finding is indicative of a paraganglioma in angiography?

Splaying of the internal and external carotid arteries with tumor blush Signup and view all the answers

Which genetic abnormality is linked to both paragangliomas and renal cell carcinoma?

VHL gene mutation Signup and view all the answers

In which age group are paragangliomas most commonly found?

Fifth to sixth decades Signup and view all the answers

What is a potential complication of fine needle aspiration (FNA) of paraganglioma?

Induced hypertensive crisis Signup and view all the answers

Which immunohistochemical stain is negative in paraganglioma but positive in many other tumors?

Cytokeratin Signup and view all the answers

What feature assists in the differential diagnosis of paraganglioma from schwannoma?

Expression of S100 protein Signup and view all the answers

Which tumor is characterized by positive staining for keratin, unlike paraganglioma?

Hyalinizing trabecular tumor of the thyroid Signup and view all the answers

What is one of the primary treatments for paragangliomas?

Surgical resection Signup and view all the answers

What risk does surgical treatment of paraganglioma pose?

Cranial nerve injury Signup and view all the answers

What is the estimated 5-year survival rate for patients with paraganglioma if recurrence or metastasis occurs?

60% Signup and view all the answers

In laryngeal paraganglioma, which feature may complicate its differentiation from small cell carcinoma?

Increased nuclear pleomorphism Signup and view all the answers

What is the estimated doubling time of paragangliomas?

7 years Signup and view all the answers

Which marker is used to help identify sustentacular cells in paraganglioma?

S100 protein Signup and view all the answers

What condition might a functional paraganglioma lead to if manipulated during a procedure?

Hemorrhage Signup and view all the answers

Which of the following neuroendocrine tumors could paraganglioma be differentiated from based on negative expression of keratin?

Medullary thyroid carcinoma Signup and view all the answers

What is the incidence rate of malignant paragangliomas in the head and neck region?

2% to 19% Signup and view all the answers

Which clinical approach is emphasized for patients with benign paragangliomas?

Lifetime clinical follow-up Signup and view all the answers

What is the characteristic feature of paragangliomas as observed on magnetic resonance imaging (MRI)?

A 'salt and pepper' pattern on T2-weighted scans Signup and view all the answers

Which imaging modality is particularly useful for demonstrating pronounced tumor vascularity of paragangliomas during surgical planning?

Angiography Signup and view all the answers

What pathological findings are characteristic of a paraganglioma?

Organized nests of tumor cells called 'zellballen' Signup and view all the answers

In which classification system are paragangliomas graded based on their surgical findings?

Shamblin staging system Signup and view all the answers

Which immunohistochemical markers are typically positive in the chief cells of paragangliomas?

Chromogranin and synaptophysin Signup and view all the answers

What size in centimeters is typically noted for carotid body tumors?

3.8 cm Signup and view all the answers

Which of the following findings is NOT indicative of malignancy in paragangliomas?

High nuclear to cytoplasmic ratio Signup and view all the answers

What clinical symptoms are associated with functional extra-adrenal paragangliomas due to catecholamine secretion?

Headache and palpitations Signup and view all the answers

What distinctive pattern may be observed microscopically in paragangliomas, informing their diagnosis?

Zellballen pattern with fibrovascular stroma Signup and view all the answers

Which anatomical location is NOT commonly associated with paragangliomas?

Pneumothorax Signup and view all the answers

Which feature is characteristic of the gross findings in a paraganglioma compared to other tumors?

Presence of a fibrous pseudocapsule Signup and view all the answers

Which diagnostic tool is used primarily to aid in localization of paragangliomas, especially in cases of occult or familial forms?

123I-MIBG scan Signup and view all the answers

What type of cells are the chief cells in paragangliomas characterized by?

Polygonal cells with granular cytoplasm Signup and view all the answers

What diagnostic feature is evident in carotid body paragangliomas as seen on angiography?

Splaying of internal and external carotid arteries Signup and view all the answers

What percentage of malignant paragangliomas is estimated to be located in the head and neck region?

2% to 19% Signup and view all the answers

Which characteristic is less likely in patients with inherited syndromes compared to those with sporadic disease?

Development of malignancies Signup and view all the answers

Which of the following imaging studies may be useful for identifying functional tumors?

123I-MIBG studies Signup and view all the answers

What is the typical clinical behavior of malignant paragangliomas despite the presence of metastasis?

Indolent and prolonged clinical course Signup and view all the answers

What is the most common site for metastatic disease in malignant paragangliomas?

Liver Signup and view all the answers

Which histological feature is commonly associated with malignant behavior in paragangliomas?

Significant necrosis and hemorrhage Signup and view all the answers

What is a useful immunohistochemical marker indicating malignancy in paragangliomas?

Loss of SDHB expression Signup and view all the answers

Which of the following treatments is considered the primary approach for metastatic malignant paraganglioma?

Surgery (debulking) Signup and view all the answers

What percentage of patients with malignant paragangliomas is estimated to experience recurrences or metastases?

Up to 50% Signup and view all the answers

Which of the following findings is not typically associated with malignant paragangliomas?

Well-established histologic criteria for malignancy Signup and view all the answers

Which age group is most commonly affected by malignant paragangliomas?

Individuals in their 40s to 50s Signup and view all the answers

What immunohistochemical profile is expected in malignant paragangliomas?

Positive for synaptophysin and chromogranin Signup and view all the answers

Which of the following differential diagnoses may resemble a malignant paraganglioma?

Atypical carcinoid tumor Signup and view all the answers

In patients with symptomatic malignancies, what biochemical marker is monitored to identify recurrence?

Catecholamines Signup and view all the answers

Study Notes

Extra-Adrenal Paragangliomas

Originates from paraganglia along sympathetic and parasympathetic chains; common sites: carotid body, jugulotympanic body, orbit, nasopharynx, larynx, vagal body, paraspinal chain, urinary bladder, organ of Zuckerkandl.
Distinct from pheochromocytomas, which arise in adrenal glands; head and neck is the most frequent site for extra-adrenal paragangliomas.

Genetics

Tumors arise sporadically or linked to hereditary tumor syndromes.
Up to 50% have succinate dehydrogenase (SDH) mutations; at least 30% of head and neck paragangliomas possess these mutations.
SDH is crucial for metabolism, catalyzing the oxidation of succinate to fumarate; consists of four subunits (SDHA, SDHB, SDHC, SDHD).
Germline mutations most common in SDHD, related to multifocality and hereditary paraganglioma-pheochromocytoma syndrome (HPGL/PCC).
Genetic syndromes associated include VHL, NF1, RET, Carney-Stratakis syndrome.

Incidence and Impact

Incidence estimated at 0.2-1 per 100,000; carotid body is most common site (60%).
Generally presents as a slowly growing, painless mass; symptoms vary by location (e.g., tinnitus, hearing loss).
Bilateral, multiple, or malignant cases found in 10%; 50% may be familial.

Imaging and Diagnosis

Common imaging modalities: CT, MRI, angiography, 123I-MIBG scans.
CT reveals enhancing masses; MRI shows hyperintense T2-weighted images and “salt and pepper” patterns.
Angiographic features include splaying of carotid arteries, diagnostic for carotid body paragangliomas.

Prognosis and Treatment

Prognosis good with complete resection; indolent growth potential can lead to recurrence years later.
Treatment options include surgery, preoperative adrenergic blockage, and/or embolization.

Pathology Overview

Gross findings: gray to hemorrhagic masses, average size 3.8 cm (up to 10 cm).
Microscopic findings include organoid nests ("zellballen") of polygonal cells, granular cytoplasm, and fibrovascular stroma.
Immunohistochemistry: positive for chromogranin, synaptophysin, NSE; presence of sustentacular cells marked by S100 protein.

Differential Diagnosis

Must distinguish from various tumors based on location: includes middle ear adenoma, meningioma, and schwannoma.
Sclerosing variants may resemble malignancies but tend to have indolent behavior.

Ancillary Studies

Ultrastructural characteristics show dense-core neurosecretory granules.
Immunohistochemical staining important for identifying SDH deficiency and distinguishing specific mutations.
Fine needle aspiration (FNA) is generally avoided due to risks of hemorrhage and complications.

Clinical Features and Patient Demographics

Head and neck paragangliomas affect females more frequently (5:1 ratio), primarily in the 5th-6th decades of life.
Nonfunctional in 96%; few produce catecholamines, presenting with systemic symptoms (e.g., palpitations, hypertension) if functional.### Tumor Cell Characteristics
Tumor cells appear singly or in clusters, forming acini (pseudorosettes).
Cells exhibit polygonal shapes, varying sizes, and irregularly shaped nuclei with pale cytoplasm.
Presence of binucleated, multinucleated, or giant cells is common.

Differential Diagnosis of Paraganglioma

Differential depends on tumor location, particularly in the middle ear or neck.
Middle ear paraganglioma may resemble:
- Middle ear adenoma, ceruminous adenoma, meningioma, schwannoma, or renal cell carcinoma metastasis.
Immunohistochemistry is essential for distinguishing these tumors:
- Paraganglioma is negative for keratin and epithelial membrane antigen (EMA), aiding in differentiation.
- S100 protein identifies sustentacular cells in paraganglioma.

Immunohistochemical Markers

Chromogranin and synaptophysin positive in both paraganglioma and other neuroendocrine tumors.
S100 protein positive in sustentacular cells of paraganglioma, negative in other tumors.
SDHB expression loss indicates paraganglioma; retained in other tumors.
Cytokeratin and EMA positive in other tumors but negative in paraganglioma.

Tumors in Vagal and Carotid Body Locations

Must differentiate from:
- Medullary thyroid carcinoma, hyalinizing trabecular tumor, parathyroid adenoma.
Medullary thyroid carcinoma is positive for keratin and calcitonin; distinguishing features include receptor positivity patterns.

Laryngeal Paraganglioma

Very rare; differential also includes carcinoid tumors and secondary neuroendocrine tumors.
Differentiation is complicated when tumor shows sclerosing features.

Clinical Characteristics

Paragangliomas are generally indolent with good clinical outcomes, especially if sporadic.
Estimated 7-year doubling time; overall recurrence rate is around 5%.
Surgery is the standard treatment, but evaluated based on individual patient factors.
Preoperative treatment may include α- and β-blockers.

Malignant Paraganglioma

Rarity: 2% to 19% in head and neck locations; most found abdominally.
Malignancy defined by metastatic presence; histology alone insufficient for diagnosis.
Common metastatic sites include regional lymph nodes, bones, liver, and lungs.

Prognosis for Malignant Forms

Clinical course tends to be prolonged and indolent; less than 50% have a 10-year survival rate.
Functional tumors facilitate monitoring through biochemical means.
Treatment may involve surgery, radiation, and radiolabeled analogs.

Pathological Features of Malignant Paragangliomas

Generally large with potential necrosis and hemorrhage.
Histological features may resemble benign tumors; no established criteria for malignancy.
Key indicators of malignancy include extensive capsular invasion, high mitotic figures, and pleomorphism.

Ancillary Studies

No definitive markers for malignancy; however, loss of S100 protein and high Ki-67 labeling suggest malignacy risk.
Differential diagnosis is crucial due to potential mimicry with other neuroendocrine tumors.

Summary Notes on Management

Constant monitoring for recurrence and metastasis is necessary for all paraganglioma patients.
Treatment approaches should be individualized based on the clinical scenario, including potential complications from surgery.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz focuses on extra-adrenal paragangliomas, highlighting their origin from paraganglia along sympathetic and parasympathetic chains. It covers various tumor sites, including the carotid body and urinary bladder, while distinguishing them from adrenal pheochromocytomas.