Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Lin DM. Parathyroid adenoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/parathyroidpthadenoma.html. Accessed June 8th, 2023.
Definition / general
- Benign neoplasm derived from parathyroid parenchymal cells
- Typically involves one gland
Essential features
- Incidence increasing due to biochemical testing
- Diagnosis confirmed by a drop in parathyroid hormone (PTH) after surgical removal
- Atypical parathyroid adenoma displays histology concerning for but not diagnostic of malignancy and requires clinical follow up after excision
- Can be mistaken for thyroid follicular neoplasm by fine needle aspiration
ICD coding
- ICD-10: D35.1 - Benign neoplasm of parathyroid gland
Epidemiology
- Incidence has increased over the past 50 years due to routine biochemical testing
- Accounts for over 85% of cases of primary hyperparathyroidism worldwide (N Engl J Med 2011;365:2389)
- Women more frequently affected than men
- Age range is broad but commonly 30s - 60s (Lloyd: WHO Classification of Tumours of Endocrine Organs, 4th Edition, 2017)
Sites
- Parathyroid gland, inferior glands slightly more common than superior
- Can also occur where ectopic / supernumerary parathyroid tissue may be found (thyroid gland, thymus, retroesophageal area, mediastinum, vagus nerve, carotid sheath)
- Double adenomas can occur, usually involving both superior parathyroid glands (Surg Pathol Clin 2019;12:1007)
Etiology
- Most are sporadic cases of unknown etiology
- Associated syndromes: hyperparathyroidism jaw tumor syndrome (HRPT2 gene germ line mutation), multiple endocrine neoplasia (MEN1 more likely to have adenomas than MEN2A and MEN2B) (Surg Pathol Clin 2019;12:1007)
- Risk factors: radiation exposure, long term lithium therapy (Endocr Rev 2019;40:711, Front Oncol 2019;9:1092)
Clinical features
- Often detected early in asymptomatic patients due to routine serologic testing (see laboratory findings below)
- Symptoms of hyperparathyroidism: nephrolithiasis, osteopenia, osteitis fibrosa cystica, weakness, fatigue and psychiatric disturbances can occur if not detected early
- Rarely presents as a palpable mass (J Med Case Rep 2019;13:332)
Diagnosis
- Various imaging techniques can identify parathyroid nodules, including CT, MRI and ultrasound
- Technetium 99 sestamibi scintigraphy (99mTc) (see radiology description below)
- Intraoperative parathyroid hormone (PTH) rapidly decreases after the abnormal gland is removed
Laboratory
- Serum parathyroid hormone (PTH) and calcium elevated, though usually not as high as in parathyroid carcinoma
- Needle washouts after FNA can be used for PTH measurements (Diagn Cytopathol 2020 Aug 24 [Online ahead of print])
- Hypophosphatemia and hypophosphaturia (J Med Case Rep 2019;13:332)
Radiology description
- Nodule posterior to thyroid gland
- 99mTc sestamibi:
- Sestamibi accumulates in the mitochondria rich oxyphil cells of the parathyroid
- Increased focal uptake may indicate an adenoma (J Nucl Med 1992;33:1801)
Radiology images
Images hosted on other servers:
99mTc MIBI scintigraphy
Prognostic factors
- Normally can be cured by surgical removal but recurrences can happen if not properly localized and excised
- Atypical adenomas are considered tumors of uncertain malignant potential and should be followed up clinically (Surg Pathol Clin 2019;12:1007)
Case reports
- 24 year old pregnant woman with parathyroid adenoma and acute necrotizing pancreatitis (BMC Endocr Disord 2019;19:82)
- 52 year old woman with giant parathyroid adenoma (J Med Case Rep 2019;13:332)
- 54 year old woman with parathyroid lipothymoadenoma (Arch Pathol Lab Med 1993;117:312)
- 56 year old woman with cystic parathyroid adenoma (BMC Endocr Disord 2020;20:53)
- 57 year old man with a parathyroid adenoma (Endocr J 2019;66:379)
- 61 year old woman with retrotracheal parathyroid adenoma (Radiol Case Rep 2020;15:672)
Treatment
- Parathyroidectomy
Clinical images
Images hosted on other servers:
Giant parathyroid adenoma (intraoperative)
Gross description
- Variable size, from < 1 cm to > 10 cm (Rosai: Tumors of the Thyroid and Parathyroid Glands, Series 4)
- Term “microadenoma” has been used to describe tumors measuring < 6 mm
- Weight > 40 mg (Endocr Pathol 2018;29:113)
- Solid yellow / tan, well circumscribed ovoid nodule
- No invasion into adjacent structures
Gross images
Contributed by Mona Kandil, M.D.
Parathyroid adenoma (black arrow) and thyroid
Images hosted on other servers:
Right: parathyroid adenoma;
left: thymoma
Frozen section description
- Identification of parathyroid tissue is usually sufficient for intraoperative management, rather than trying to distinguish adenoma from hyperplasia
Microscopic (histologic) description
- Well circumscribed, frequently with thin fibrous capsule
- Absent or reduced stromal adipocytes
- Compressed nonneoplastic parathyroid tissue may be seen at edge
- Most commonly composed of chief cells (round nucleus, little granular cytoplasm)
- Follicle formation is not rare
- Mitoses and bizarre nuclei (endocrine atypia) may be focally present
- Variants:
- Oxyphilic / oncocytic adenomas: composed entirely of oncocytic cells with abundant, eosinophilic granular cytoplasm (Surg Pathol Clin 2019;12:1007)
- Water clear cell adenoma: cells have clear, glycogen containing cytoplasm (Surg Pathol Clin 2019;12:1007)
- Lipoadenoma (hamartoma): contains stromal (adipose) and parenchymal (usually chief cells) elements; most of the tumor is adipose tissue (Surg Pathol Clin 2019;12:1007)
- Atypical adenoma: contains borderline features concerning for (but not diagnostic of) malignancy (Surg Pathol Clin 2019;12:1007)
- Dense fibrous bands with hemosiderin
- Prominent nuclear atypia with spindled nuclei
- Notable mitotic activity
- Adherence to adjacent tissue
- Necrosis
- Solid or trabecular growth
- No evidence of lymphovascular invasion, perineural invasion, invasion into adjacent structures or metastasis
Microscopic (histologic) images
Contributed by Diana Murro Lin, M.D.
Chief cells
Oxyphil adenoma
Oxyphil cells
Atypical adenoma and thyroid
Atypical adenoma fibrous bands
Virtual slides
Images hosted on other servers:
Parathyroid adenoma
Cytology description
- Cellular aspirates with uniform small cells in sheets, 3D clusters and trabecular arrangements
- Round dark nuclei with smooth nuclear borders and without nucleoli
- Salt and pepper chromatin (Diagn Cytopathol 2020 Aug 24 [Online ahead of print])
- No colloid unless adjacent thyroid tissue is also aspirated
- More monotony than normal thyroid tissue
- Can be mistaken for a thyroid follicular neoplasm (Diagn Cytopathol 2017;45:526)
Cytology images
Contributed by Ayana Suzuki, C.T.
Sheet of chief cells
Images hosted on other servers:
Microfollicular and trabecular arrangement
Positive stains
- Parathyroid hormone, synaptophysin, chromogranin A, GATA3, CAM 5.2, CK7, CK8, CK18 and CK19 (Endocr Pathol 2018;29:113)
- GATA3 (Diagn Cytopathol 2020 Aug 24 [Online ahead of print])
- Polyclonal PAX8 is nonspecific because monoclonal PAX8 is negative in parathyroid (Endocr Pathol 2018;29:91)
- CDC73 (parafibromin)
Negative stains
Electron microscopy description
- Oxyphil cells are mitochondria rich (J Nucl Med 1992;33:1801)
Molecular / cytogenetics description
- CDC73 (HRPT2) in patients with hyperparathyroidism jaw tumor syndrome (Endocr Pathol 2018;29:113)
- MEN1 in multiple endocrine neoplasia and sporadic adenomas
- For fine needle aspiration samples, the Veracyte Afirma Gene Expression Classifier contains a cassette to distinguish parathyroid from thyroid tissue (Diagn Cytopathol 2017;45:526)
- Mutations in CCND1 (cyclin D1), ZFX, EZH2 (Surg Pathol Clin 2019;12:1007)
Videos
Oncocytic adenoma
Parathyroid pathology
Sample pathology report
- Right lower parathyroid, parathyroidectomy:
- Chief cell adenoma, 250 mg
Differential diagnosis
- Histology:
- Parathyroid hyperplasia:
- Typically involves all 4 glands
- Diffuse enlargement rather than nodular growth with compressed rim of normal tissue
- Distinction between hyperplasia and adenoma may be difficult on routine histology and definitive diagnosis is based on intraoperative PTH findings
- Parathyroid carcinoma:
- Definitive evidence of invasion or metastasis (vascular invasion, perineural invasion, invasion into adjacent structure)
- Atypical mitotic figures
- Paraganglioma:
- Parathyroid hyperplasia:
- Cytology:
- Normal thyroid tissue and follicular neoplasms:
- Less defined cell membranes with no visible intracellular lipid droplets (Endocr Pathol 2018;29:113)
- Positive for TTF1 and thyroglobulin and negative for PTH and neuroendocrine markers (Endocr Pathol 2018;29:113)
- Serum calcium and PTH not elevated
- Normal thyroid tissue and follicular neoplasms:
Board review style question #1
What is the best diagnosis for this neck mass?
- Parathyroid adenoma, oxyphil type
- Oncocytoma
- Hurthle cell adenoma
- Granular cell tumor
Board review style answer #1
Board review style question #2
Which of the following features is seen in parathyroid carcinoma but not adenoma?
- Adherence to adjacent thyroid
- Nuclear atypia
- Necrosis
- Perineural invasion
Board review style answer #2
