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Atypical parathyroid adenoma

Case contributed by Mikkaela McCormack
Diagnosis certain

Presentation

Several weeks of unexpected fatigue and lethargy. Upon questioning, her doctor elicited the additional symptoms of generalized joint aching and a vague abdominal discomfort, along with appetite loss and minor unintentional weight loss. Initial blood tests revealed an elevated calcium and additional testing showed a high PTH level and low phosphorous. Following sestamibi and CT, the patient progressed to surgery and a frozen section was received in the lab.

Patient Data

Age: 55 years
Gender: Female
pathology

Macroscopic and Microscopic Findings

The specimen consists of a 1.20g, 12 mm well circumscribed tumor with peripheral fibrous capsule, composed of solid sheets of parathyroid epithelial oncocytic cells showing a vaguely organoid architecture without interspersed fat and showing a scant amount of peripheral normal appearing parathyroid gland.  Tumor cells are medium in size with rounded to ovoid nuclei and a moderate amount of oncocytic cytoplasm.  Thick, hyalinised fibrous stromal band traverse the lesion.  There is no tumor cell necrosis or hemorrhage.  There is no significant mitotic activity.

20x H&E: Low-power view shows sheets of parathyroid cells with a peripheral fibrous capsule and traversing hyalinised fibrous bands.  Normal surrounding parenchymal tissue is not seen in this section. 

40x H&E: Medium-power view showing hyalinised bands, with epithelial cells displaying acinar architectural patterns which are subtly visible at this power. 

100x H&E: Closer view. 

200x H&E: This high power view highlights the bland, monomorphous and mitotically inactive appearance of the parathyroid cells. 

Immunohistochemistry

A galectin-3 (Gal-3) immunohistochemical stain was performed, which was negative.

Case Discussion

The presence of a fibrous capsule and traversing thick, hyalinised fibrous bands seen in this case are not usually seen within a regular parathyroid adenoma and are a noted feature of atypical parathyroid adenoma, along with a solid and trabecular growth pattern and scattered mitotic figures. 

Parathyroid carcinoma vs atypical parathyroid adenoma

Parathyroid carcinoma
The definitive diagnosis of parathyroid carcinoma is the presence of metastatic disease or localized invasion into surrounding structures. Histological features of parathyroid carcinoma include:

  • capsule invasion and involvement of surrounding structures
  • lymphovascular/perineural invasion
  • elevated mitotic rate with atypical mitotic figures

Atypical parathyroid adenoma
Atypical adenomas lack the definitive evidence of parathyroid carcinoma but display some abnormal features:

  • thick hyalinised fibrous bands
  • incomplete capsular invasion
  • prominent trabecular growth pattern
  • necrosis (real, tumor-associated necrosis)
  • increased mitotic rate (>1/10 hpf) - uncommon

Note: Adenomas likely need to show more than just one abnormal feature to be designated as 'atypical', with some suggesting 2+ to qualify for a diagnosis.

Immunohistochemistry
PTH is a great stain to determine the parathyroid nature of the cells. There are not any definitive or diagnostic immunohistochemical stains you can use to distinguish between benign and malignant (or potentially malignant) parathyroid neoplasms, however, the following have been used in research settings:

Adenoma (vs 'normal'): neurofilament, GFAP, vimentin, less intense PTH and chromogranin
Parathyroid Carcinoma: Ki67, galectin-3, cyclin D1, bcl2, MDM2

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