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Questions and Answers
What is the primary origin of paragangliomas?
What is the primary origin of paragangliomas?
Which of the following sites is most commonly associated with extra-adrenal paragangliomas?
Which of the following sites is most commonly associated with extra-adrenal paragangliomas?
Which mutation is most frequently associated with head and neck paragangliomas?
Which mutation is most frequently associated with head and neck paragangliomas?
Which enzyme complex is the SDH enzyme associated with?
Which enzyme complex is the SDH enzyme associated with?
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What is the consequence of mutations in any of the SDH gene subunits?
What is the consequence of mutations in any of the SDH gene subunits?
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Which type of mutations account for most cases of SDH deficiency in head and neck paragangliomas?
Which type of mutations account for most cases of SDH deficiency in head and neck paragangliomas?
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Which of the following statements is true regarding the prevalence of SDH mutations?
Which of the following statements is true regarding the prevalence of SDH mutations?
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What role does the SDH complex play within mitochondria?
What role does the SDH complex play within mitochondria?
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What histological feature in paragangliomas is NOT typically associated with malignancy?
What histological feature in paragangliomas is NOT typically associated with malignancy?
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Which type of morphology may be seen in paragangliomas that could potentially mimic small cell carcinoma?
Which type of morphology may be seen in paragangliomas that could potentially mimic small cell carcinoma?
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What characterizes the sustentacular cells in paragangliomas?
What characterizes the sustentacular cells in paragangliomas?
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Which immunohistochemical marker is NOT consistently positive in paragangliomas?
Which immunohistochemical marker is NOT consistently positive in paragangliomas?
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Which pattern of paraganglioma may show extensive fibrosis that obscures the classic nested arrangement?
Which pattern of paraganglioma may show extensive fibrosis that obscures the classic nested arrangement?
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What is the consequence of loss of expression of SDHB in paragangliomas?
What is the consequence of loss of expression of SDHB in paragangliomas?
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Which feature is a common pitfall for diagnosis in paragangliomas?
Which feature is a common pitfall for diagnosis in paragangliomas?
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Which of the following features is NOT commonly observed in paragangliomas associated with SDH deficiency?
Which of the following features is NOT commonly observed in paragangliomas associated with SDH deficiency?
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Which of the following cytomorphological characteristics is associated with paragangliomas?
Which of the following cytomorphological characteristics is associated with paragangliomas?
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What is a common characteristic feature observed in paragangliomas?
What is a common characteristic feature observed in paragangliomas?
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In which location can paragangliomas be particularly challenging to diagnose?
In which location can paragangliomas be particularly challenging to diagnose?
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Which of the following is true regarding necrosis in paragangliomas?
Which of the following is true regarding necrosis in paragangliomas?
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What feature indicates the indolent nature of most paragangliomas despite their sclerotic features?
What feature indicates the indolent nature of most paragangliomas despite their sclerotic features?
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Which gene is primarily associated with the majority of paragangliomas in patients with hereditary paragangliomatosis?
Which gene is primarily associated with the majority of paragangliomas in patients with hereditary paragangliomatosis?
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What is the most common location for extra-adrenal paragangliomas?
What is the most common location for extra-adrenal paragangliomas?
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Which syndrome is characterized by paragangliomas and gastrointestinal stromal tumors?
Which syndrome is characterized by paragangliomas and gastrointestinal stromal tumors?
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Which mutation appears to exhibit paternal transmission suggestive of imprinting?
Which mutation appears to exhibit paternal transmission suggestive of imprinting?
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Which imaging modality is likely to show an enhancing mass in a characteristic location associated with paragangliomas?
Which imaging modality is likely to show an enhancing mass in a characteristic location associated with paragangliomas?
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What condition is often associated with paragangliomas due to mutations in the RET gene?
What condition is often associated with paragangliomas due to mutations in the RET gene?
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Which of the following describes the sex distribution of patients affected by paragangliomas?
Which of the following describes the sex distribution of patients affected by paragangliomas?
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What is the primary treatment option for paragangliomas that can lead to a good prognosis if completely resected?
What is the primary treatment option for paragangliomas that can lead to a good prognosis if completely resected?
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Which symptoms may indicate the presence of a paraganglioma in the middle ear?
Which symptoms may indicate the presence of a paraganglioma in the middle ear?
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What percentage of hereditary paragangliomatosis cases are associated with multiple paragangliomas?
What percentage of hereditary paragangliomatosis cases are associated with multiple paragangliomas?
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Which imaging finding is indicative of a paraganglioma in angiography?
Which imaging finding is indicative of a paraganglioma in angiography?
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Which genetic abnormality is linked to both paragangliomas and renal cell carcinoma?
Which genetic abnormality is linked to both paragangliomas and renal cell carcinoma?
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In which age group are paragangliomas most commonly found?
In which age group are paragangliomas most commonly found?
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What is a potential complication of fine needle aspiration (FNA) of paraganglioma?
What is a potential complication of fine needle aspiration (FNA) of paraganglioma?
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Which immunohistochemical stain is negative in paraganglioma but positive in many other tumors?
Which immunohistochemical stain is negative in paraganglioma but positive in many other tumors?
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What feature assists in the differential diagnosis of paraganglioma from schwannoma?
What feature assists in the differential diagnosis of paraganglioma from schwannoma?
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Which tumor is characterized by positive staining for keratin, unlike paraganglioma?
Which tumor is characterized by positive staining for keratin, unlike paraganglioma?
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What is one of the primary treatments for paragangliomas?
What is one of the primary treatments for paragangliomas?
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What risk does surgical treatment of paraganglioma pose?
What risk does surgical treatment of paraganglioma pose?
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What is the estimated 5-year survival rate for patients with paraganglioma if recurrence or metastasis occurs?
What is the estimated 5-year survival rate for patients with paraganglioma if recurrence or metastasis occurs?
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In laryngeal paraganglioma, which feature may complicate its differentiation from small cell carcinoma?
In laryngeal paraganglioma, which feature may complicate its differentiation from small cell carcinoma?
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What is the estimated doubling time of paragangliomas?
What is the estimated doubling time of paragangliomas?
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Which marker is used to help identify sustentacular cells in paraganglioma?
Which marker is used to help identify sustentacular cells in paraganglioma?
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What condition might a functional paraganglioma lead to if manipulated during a procedure?
What condition might a functional paraganglioma lead to if manipulated during a procedure?
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Which of the following neuroendocrine tumors could paraganglioma be differentiated from based on negative expression of keratin?
Which of the following neuroendocrine tumors could paraganglioma be differentiated from based on negative expression of keratin?
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What is the incidence rate of malignant paragangliomas in the head and neck region?
What is the incidence rate of malignant paragangliomas in the head and neck region?
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Which clinical approach is emphasized for patients with benign paragangliomas?
Which clinical approach is emphasized for patients with benign paragangliomas?
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What is the characteristic feature of paragangliomas as observed on magnetic resonance imaging (MRI)?
What is the characteristic feature of paragangliomas as observed on magnetic resonance imaging (MRI)?
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Which imaging modality is particularly useful for demonstrating pronounced tumor vascularity of paragangliomas during surgical planning?
Which imaging modality is particularly useful for demonstrating pronounced tumor vascularity of paragangliomas during surgical planning?
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What pathological findings are characteristic of a paraganglioma?
What pathological findings are characteristic of a paraganglioma?
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In which classification system are paragangliomas graded based on their surgical findings?
In which classification system are paragangliomas graded based on their surgical findings?
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Which immunohistochemical markers are typically positive in the chief cells of paragangliomas?
Which immunohistochemical markers are typically positive in the chief cells of paragangliomas?
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What size in centimeters is typically noted for carotid body tumors?
What size in centimeters is typically noted for carotid body tumors?
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Which of the following findings is NOT indicative of malignancy in paragangliomas?
Which of the following findings is NOT indicative of malignancy in paragangliomas?
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What clinical symptoms are associated with functional extra-adrenal paragangliomas due to catecholamine secretion?
What clinical symptoms are associated with functional extra-adrenal paragangliomas due to catecholamine secretion?
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What distinctive pattern may be observed microscopically in paragangliomas, informing their diagnosis?
What distinctive pattern may be observed microscopically in paragangliomas, informing their diagnosis?
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Which anatomical location is NOT commonly associated with paragangliomas?
Which anatomical location is NOT commonly associated with paragangliomas?
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Which feature is characteristic of the gross findings in a paraganglioma compared to other tumors?
Which feature is characteristic of the gross findings in a paraganglioma compared to other tumors?
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Which diagnostic tool is used primarily to aid in localization of paragangliomas, especially in cases of occult or familial forms?
Which diagnostic tool is used primarily to aid in localization of paragangliomas, especially in cases of occult or familial forms?
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What type of cells are the chief cells in paragangliomas characterized by?
What type of cells are the chief cells in paragangliomas characterized by?
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What diagnostic feature is evident in carotid body paragangliomas as seen on angiography?
What diagnostic feature is evident in carotid body paragangliomas as seen on angiography?
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What percentage of malignant paragangliomas is estimated to be located in the head and neck region?
What percentage of malignant paragangliomas is estimated to be located in the head and neck region?
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Which characteristic is less likely in patients with inherited syndromes compared to those with sporadic disease?
Which characteristic is less likely in patients with inherited syndromes compared to those with sporadic disease?
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Which of the following imaging studies may be useful for identifying functional tumors?
Which of the following imaging studies may be useful for identifying functional tumors?
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What is the typical clinical behavior of malignant paragangliomas despite the presence of metastasis?
What is the typical clinical behavior of malignant paragangliomas despite the presence of metastasis?
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What is the most common site for metastatic disease in malignant paragangliomas?
What is the most common site for metastatic disease in malignant paragangliomas?
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Which histological feature is commonly associated with malignant behavior in paragangliomas?
Which histological feature is commonly associated with malignant behavior in paragangliomas?
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What is a useful immunohistochemical marker indicating malignancy in paragangliomas?
What is a useful immunohistochemical marker indicating malignancy in paragangliomas?
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Which of the following treatments is considered the primary approach for metastatic malignant paraganglioma?
Which of the following treatments is considered the primary approach for metastatic malignant paraganglioma?
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What percentage of patients with malignant paragangliomas is estimated to experience recurrences or metastases?
What percentage of patients with malignant paragangliomas is estimated to experience recurrences or metastases?
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Which of the following findings is not typically associated with malignant paragangliomas?
Which of the following findings is not typically associated with malignant paragangliomas?
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Which age group is most commonly affected by malignant paragangliomas?
Which age group is most commonly affected by malignant paragangliomas?
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What immunohistochemical profile is expected in malignant paragangliomas?
What immunohistochemical profile is expected in malignant paragangliomas?
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Which of the following differential diagnoses may resemble a malignant paraganglioma?
Which of the following differential diagnoses may resemble a malignant paraganglioma?
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In patients with symptomatic malignancies, what biochemical marker is monitored to identify recurrence?
In patients with symptomatic malignancies, what biochemical marker is monitored to identify recurrence?
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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.
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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.
