Tag: parathyroid

Parathyroid carcinoma with spindle cell differentiation (sarcomatoid carcinoma)

Parathyroid carcinoma is a rare neoplasm, accounting for <1% of all malignancies and has a female-to-male ratio of ~1:1. It can be sporadic or familial, with the latter seen in 10-15% of patients with hyperparathyroidism-jaw tumor syndrome (HPT-JT) or in the setting of familial isolated hyperparathyroidism (FIHP). Other etiologies include external radiation to the neck and prolonged chief cell hyperplasia in patients with renal failure and celiac disease.

Clinically, there is excess secretion of parathyroid hormone with calcium levels often >14 mg/dL. Laboratory workup in our patient prior to surgery revealed a calcium level of 14 and a parathyroid hormone level of 600. As a result, many patients show symptoms of fatigue, weakness, weight loss, nausea/vomiting, and polyuria. Unlike parathyroid adenoma, patients often have a palpable neck mass.

Grossly, tumors are often large, variably encapsulated, and ill-defined, involving the surrounding structures. In this patient, the tumor was grossly invading the thyroid and was also attached to the trachea and esophagus. On imaging, he also had multiple nodules in the lung, concerning for metastasis. Histologically, there is evidence of invasive growth involving the adjacent structures, vascular and/or perineural invasion. As in follicular thyroid carcinoma, vascular invasion should be in the surrounding soft tissue and not intratumoral. Tumor cells are often separated by broad fibrous bands. The triad of macronucleoli, >5 mitoses per 50 high-power fields, and necrosis is predictive of aggressive growth. Rarely, as in this case, the tumor cells can have sarcomatoid growth pattern, characterized by marked cytologic atypia and spindle cell morphology. To our knowledge, there are only ~ 5 cases reported in the English literature with this morphology. Among these patients, 3 developed lung metastases and died within 5-7 months of diagnosis.

By immunohistochemistry, the tumor cells are positive for cytokeratins, PTH, GATA3, PAX8, synaptophysin, and chromogranin. Several studies, have shown inactivation of the tumor suppressor gene CDC73 as the major molecular driver in the pathogenesis of parathyroid carcinoma in both sporadic and familial forms.

Most parathyroid carcinomas recur locally, with spread to adjacent structures, such as the thyroid gland, strap muscles and recurrent laryngeal nerve.  Older age, large tumor size, and male sex have been associated with worse overall survival. There is no generally accepted staging system for this tumor.

References

1. Hu L, Xie X. Parathyroid carcinoma with sarcomatoid differentiation: a case report and literature review. Diagn Pathol. 2020 Dec 14;15(1):142. doi: 10.1186/s13000-020-01060-5. PMID: 33317559; PMCID: PMC7737283.
2. Lloyd RV, Osamura RY, Kloppel G, Rosai J. WHO classification of Tumours of Endocrine Organs (4^th edition). IARC: Lyon 2017.
3. Harari A, Waring A, Fernandez-Ranvier G, Hwang J, Suh I, Mitmaker E, Shen W, Gosnell J, Duh QY, Clark O. Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metab. 2011 Dec;96(12):3679-86. doi: 10.1210/jc.2011-1571. Epub 2011 Sep 21. PMID: 21937626.
4. Hu Y, Zhang X, Wang O, Bi Y, Xing X, Cui M, Wang M, Tao W, Liao Q, Zhao Y. The genomic profile of parathyroid carcinoma based on whole-genome sequencing. Int J Cancer. 2020 Nov 1;147(9):2446-2457. doi: 10.1002/ijc.33166. Epub 2020 Jul 24. PMID: 32574388.

Quiz Answers

Q1 = D. Rare recurrence after resection

Q2 = A. True

Parathyroid Lipoadenoma.

Parathyroid lipoadenomas are a rare manifestation of primary hyperparathyroidism. Only a few sporadic cases have been described in the literature. To diagnose this entity, several factors must be considered, both clinical and histological. From the clinical perspective, evidence of primary hyperparathyroidism must exist, typically confirmed preoperatively via serum biochemistry (as in this case), as well as intraoperatively by single gland enlargement. In this case, the other three parathyroid glands were sampled and were appropriately normocellular. Moreover, a post-operative biochemical cure is supportive of the diagnosis.

Histologically, parathyroid lipoadenoma exhibits extensive stromal adipose tissue and small, labyrinth-like nests of parathyroid cells, most often chief cells, arranged in cords or acini. Features of malignancy (invasion) and other atypical features (e.g. necrosis, increased mitotic count, fibrous bands) should be absent. Of note, there is no set definition or proportion of adipose tissue required for a diagnosis of lipoadenoma. However, many use >50% as a rough guide. Importantly, parathyroid glands are normally adipose-rich (~ 50% parenchyma / 50% fat). Assessing only the ratio of parenchymal cells to adipocytes is not necessarily reliable in the diagnostic evaluation of parathyroid disease. Size and weight are also important in defining an abnormal gland, and intraoperative and postoperative biochemical workup distinguishes uniglandular disease (adenoma) from multiglandular disease (hyperplasia).

Recognizing lipoadenoma is important for two reasons: (1) not to mistake it for invasion of parathyroid tissue into adipose tissue (carcinoma); and (2) not to underestimate this abnormal gland as normal, especially on frozen section or if dealing with limited tissue. Pathologic, clinical, and serologic correlation is necessary!

Prognostically, these tumors behave as typical adenomas. There is no documented difference in pre-operative biochemistry. Importantly, confirmed by a recent series, there is no correlation between a patient’s body mass index (BMI) and the formation of a lipoadenoma.

References

• International Agency for Research on Cancer. Lloyd RV et al., eds: WHO classification of tumours of endocrine organs. 4th edition. 2017. International Agency for Research on Cancer: Lyon, France.
• Juhlin CC, et al. “Lipoadenoma of the Parathyroid Gland: Characterization of an Institutional Series Spanning 28 Years.” Endocr Pathol. 2020 Mar 19. doi: 10.1007/s12022-020-09616-3. [Epub ahead of print]
• Hyrcza MD, Sargın P, Mete O. “Parathyroid Lipoadenoma: a Clinicopathological Diagnosis and Possible Trap for the Unaware Pathologist.” Endocr Pathol. 2016 Mar;27(1):34-41. doi: 10.1007/s12022-015-9404-5.

Quiz Answers

Q1 = D. is comparable in terms of prognosis.

Q2 = B. False