Thyroid & parathyroid

Parathyroid malignant

Parathyroid carcinoma


Editorial Board Members: Andrey Bychkov, M.D., Ph.D., Marc Pusztaszeri, M.D.
Mehmet Kefeli, M.D.

Last author update: 24 January 2023
Last staff update: 24 January 2023 (update in progress)

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PubMed Search: Parathyroid carcinoma

Mehmet Kefeli, M.D.
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Cite this page: Kefeli M. Parathyroid carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/parathyroidpthca.html. Accessed February 6th, 2023.
Definition / general
  • Malignant neoplasm originating from parathyroid parenchymal cells
Essential features
  • 90% of patients present with excess parathyroid hormone (PTH)
  • HRPT2 (CDC73) mutation is strongly associated with familial and sporadic parathyroid carcinoma (> 70%)
  • One of the following features is necessary for definitive malignancy diagnosis of parathyroid lesion (Endocr Pathol 2022;33:64):
    • Angioinvasion (vascular invasion)
    • Lymphatic invasion
    • Perineural (intraneural) invasion
    • Invasion of adjacent structures / organs
    • Metastasis
  • Estimated 5 year and 10 year overall survival rates are 78 - 85% and 49 - 70%, respectively (Ann Surg Oncol 2015;22:3990)
Terminology
  • Parathyroid carcinoma
ICD coding
  • ICD-10: C75.0 - malignant neoplasm of parathyroid gland
Epidemiology
  • M = F
  • Mean age of 56 years (range: 15 - 89 years)
  • Usually associated with familial syndromes in younger patients
  • < 1% of cases of primary hyperparathyroidism (J Bone Miner Res 2008;23:1869)
Sites
  • Normal parathyroid gland location
  • Sites of the neck in which parathyroid gland can be seen (e.g., retroesophageal space, mediastinum, thymus and thyroid gland)
Etiology
Clinical features
  • Palpable neck mass (30 - 75%)
  • Symptoms of overt hyperparathyroidism:
    • Bone disease (osteitis fibrosa cystica, osteoporosis, fractures)
    • Renal disease (nephrolithiasis, nephrocalcinosis)
    • Neurocognitive symptoms (fatigue, weight loss, weakness, anxiety, depression, polyuria, polydipsia)
  • Jaw tumor (if associated with HPT JT)
  • Neck pain
  • References: Turk Patoloji Derg 2015;31:80, Endocr Pathol 2022;33:64
Diagnosis
  • One of the following microscopic features is necessary for definitive diagnosis of parathyroid lesion malignancy (Endocr Pathol 2022;33:64):
    • Angioinvasion (vascular invasion)
    • Lymphatic invasion
    • Perineural (intraneural) invasion
    • Invasion of adjacent structures / organs
    • Metastasis
Laboratory
Radiology description
Radiology images

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Xray lytic lesion

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Sestamibi scan

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Bone scan

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Tc MIBI scintigraphy and CT

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Tc MIBI SPECT / CT

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99mTc MIBI SPECT / CT and MRI

Prognostic factors
  • The following microscopic features have been reported with aggressive growth in some parathyroid tumors (Am J Surg Pathol 1993;17:820):
    • Necrosis
    • Macronucleoli
    • > 5 mitoses per 10 mm2
  • Older age at time of diagnosis, larger tumor size and male gender are negative prognostic factors (Ann Surg Oncol 2015;22:3990)
  • Estimated 5 year and 10 year overall survival rates are 78 - 85% and 49 - 70% respectively (Ann Surg Oncol 2015;22:3990)
Case reports
Treatment
Clinical images

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Intraoperative dissection

Gross description
Gross images

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Large size and irregular cut surface

Frozen section description
  • Distinction between parathyroid adenoma and carcinoma is often difficult to make on frozen section if the tumor does not show grossly evident invasion into adjacent structures
Microscopic (histologic) description
  • Nodular and solid growth pattern is common
  • Broad fibrous bands can be present
  • Uniform cells or mild to moderate nuclear atypia
  • Mostly composed of chief cells; however, oxyphil cells and transitional cells can also be seen
  • Nuclear atypia, macronucleoli
  • Increased mitotic activity (> 5/10 mm2) and atypical mitosis may be seen
  • Necrosis can be present
  • One of the following features is necessary for definitive diagnosis of parathyroid lesion malignancy (Endocr Pathol 2022;33:64):
    • Angioinvasion (vascular invasion)
    • Lymphatic invasion
    • Perineural (intraneural) invasion
    • Invasion of adjacent structures / organs
    • Metastasis
Microscopic (histologic) images

Contributed by Mehmet Kefeli, M.D.
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Solid and nodular growth

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Skeletal muscle invasion

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Uniform cytomorphology

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Numerous mitoses

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Prominent nucleoli


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PTH

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GATA3

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Thyroglobulin

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TTF1

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Ki67

Virtual slides

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Parathyroid carcinoma

Cytology description
  • Cellular, composed of cohesive sheets, ribbon-like cords
  • Nuclei are uniform or show mild to moderate atypia
  • Coarsely granular chromatin pattern
  • Prominent nucleoli
  • Cytoplasm is moderately abundant and granular
  • Distinction between parathyroid carcinoma and adenoma is extremely difficult to make on cytology; nuclear pleomorphism, prominent macronucleoli, enlarged uniform hyperchromatic nuclei, mitotic figures favor carcinoma (Diagn Cytopathol 2016;44:688)
Cytology images

Contributed by Mehmet Kefeli, M.D.
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Cohesive clusters and sheets of cells

Positive stains
Negative stains
Molecular / cytogenetics description
Videos

Parathyroid pathology

Sample pathology report
  • Right neck, mass, excision:
    • Parathyroid carcinoma, oxyphilic type (see comment)
    • Comment: There is a cellular malignant tumor with thyroid gland and striated muscle invasion. Tumor cells characterized by eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin and prominent nucleoli. There are 12 mitoses per 10 mm2, some of which show atypical features. Lymphatic and vascular invasion are also seen. Immunohistochemically, the tumor cells show strong expression of PTH, GATA3, chromogranin A and synaptophysin while they are negative with thyroglobulin, TTF1, PAX8, CEA and tyrosine hydroxylase. Ki67 index is 16%. Morphological and immunohistochemical features strongly support parathyroid carcinoma, oxyphilic type. Complete nuclear parafibromin loss is detected, which correlates with HRPT2 (CDC73) mutation and also parafibromin deficient parathyroid neoplasm.
Differential diagnosis
Board review style question #1

    Which of the following is diagnostic for parathyroid carcinoma in a parathyroid lesion?

  1. Broad fibrous bands
  2. Increased mitotic activity (> 5/10 mm2)
  3. Parafibromin loss
  4. Perineural invasion
  5. Tumor cells within the capsule
Board review style answer #1
D. Perineural invasion of tumor cells is diagnostic of malignancy for parathyroid neoplasm. Although the other options are also atypical features and commonly seen in parathyroid carcinoma, based on the 2022 WHO classification one of the following features is required for definitive malignancy diagnosis of the parathyroid lesion: angioinvasion (vascular invasion), lymphatic invasion, perineural (intraneural) invasion, invasion of adjacent structures / organs, metastasis (Endocr Pathol 2022;33:64).

Comment Here

Reference: Parathyroid carcinoma
Board review style question #2
    Which of the following markers is recommended for atypical parathyroid tumors and parathyroid carcinoma in routine practice and may also be associated with the risk of tumor recurrence?

  1. Isocitrate dehydrogenase 1 (IDH1)
  2. Menin
  3. Parafibromin
  4. SMARCB1 / INI1
  5. Succinate dehydrogenase B (SDHB)
Board review style answer #2
C. Parafibromin. Parafibromin is the protein encoded by the tumor suppressor gene HRPT2 (CDC73). Complete loss of nuclear parafibromin immunoreactivity indicates biallelic CDC73 inactivation and requires routine germline CDC73 mutation testing. Based on the 2022 WHO classification, complete nuclear loss of expression of parafibromin is considered parafibromin deficiency. Parafibromin deficient parathyroid neoplasms may show metachronous disease in the other glands and increased recurrence (Endocr Pathol 2022;33:64)

Comment Here

Reference: Parathyroid carcinoma
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