Parathyroid carcinoma located in the thyroid gland: A case report

Abstract

BACKGROUND

Parathyroid carcinoma (PC) is a difficult-to-diagnose rare disease with low incidence. Relatively accurate preoperative diagnosis is very important in choosing surgical methods and patient prognosis.

CASE SUMMARY

This study reported the clinical diagnosis and treatment of a rare patient with PC located in the thyroid gland and provided a case reference for the diagnosis and treatment of PC. A case of a 64-year-old male patient who presented to our hospital with systemic muscle and joint pain and palpitations is outlined. Subsequently, the patient was admitted to the Department of Nephrology for the treatment of “multiple myeloma nephropathy pending investigation”. The patient was diagnosed with “primary hyperparathyroidism and hypercalcemic crisis” using thyroid color ultrasound.

CONCLUSION

The intraoperative frozen section report considered the parathyroid tumor. Surgical tumor resection was promptly performed, and the diagnosis of PC was confirmed.

Key Words: Parathyroid carcinoma, Surgical resection, Fine needle aspiration, Intraoperative frozen section, Case report

Core Tip: Parathyroid carcinoma (PC) is a difficult-to-diagnose rare disease with low incidence. Relatively accurate preoperative diagnosis is very important in choosing surgical methods and patient prognosis. This study reported a rare patient with PC located in the thyroid gland. Combined with the results of color thyroid ultrasound and intraoperative frozen section, the primary disease of the patient can be confirmed. Accurate preoperative diagnosis is helpful for timely surgical resection of the tumor and improving the therapeutic effect.

INTRODUCTION

Parathyroid carcinoma (PC) is a rare malignant tumor with a relatively low incidence, accounting for < 1% of primary hyperparathyroidism[1]. PC due to ectopic third and fourth parotid glands during embryonic development is even rare, accounting for about 0.2%[2,3]. This case report presents the clinical diagnosis and treatment of a rare intrathyroidal PC.

CASE PRESENTATION

Chief complaints

A 64-year-old male patient presented to the Cardiology Department of our hospital because of “palpitations” that started 2 d before the presentation.

History of present illness

Six months ago, the patient developed systemic arthralgia and bone pain without obvious inducement, which could be relieved after resting at first and then became worse, accompanied by limb muscle weakness, dry mouth, polyuria and polydipsia, occasional nausea, and no obvious vomiting or abdominal distension. Half a month ago, he presented to the orthopedic outpatient department of our hospital and was administered joint nutrition drugs; however, his symptoms were not significantly relieved.

History of past illness

The patient had a 15-year history of hypertension and had stopped taking irbesartan for nearly 6 months, with normal blood pressure.

Personal and family history

The patient had a no family history.

Physical examination

Physical examination results showed a 4 cm × 5 cm mass in the left lobe of the thyroid gland, which was hard and moved with swallowing. Other examination results were normal.

Laboratory examinations

The detection value of cytokeratin 19 fragment was 5.29 ng/mL (normal value < 5.0), and the parathyroid hormone (PTH) value was > 346.90 pmol/L. The blood calcium and 24-h urine calcium values were higher than the normal reference range. Serum creatinine of 241.3 umol/L, uric acid of 573 umol/L, and calcium of 3.76 mmol/L were all higher than the normal range. The outpatient doctor considered “renal insufficiency and multiple myeloma nephropathy pending investigation” and admitted the patient to the nephrology department for calcitonin and furosemide treatment.

Imaging examinations

Colored ultrasonography of the patient’s thyroid and cervical lymph nodes showed a cystic solid mass (mostly solid, possibly with calcification) in the left lobe of the thyroid gland (Figure 1), which was considered “primary hyperparathyroidism and hypercalcemic crisis”.

Figure 1 Colored ultrasound of the thyroid gland and cervical lymph nodes. A-C: The left lobe of the thyroid gland is enlarged, the right lobe is not large, and the echogenicity of glandular tissue is uneven. A mixed echogenic mass of about 38 mm × 30 mm was found in the left lobe of the thyroid, with a clear boundary and regular shape. Several strong echogenic spots of different sizes were observed inside, accompanied by acoustic shadow behind.

Parathyroid scintigraphy (MIBI) revealed a concentration shadow of radioactivity in the left lobe of the thyroid gland (Figure 2). Fine needle aspiration (FNA) cytological smear of thyroid nodules suggested the possibility of papillary thyroid carcinoma (Figure 3).

Figure 2 Parathyroid imaging (MIBI). A-C: A concentrated shadow of radioactivity in the left lobe of the thyroid.

Figure 3 Fine needle aspiration cytological smear of thyroid nodules. A-C: Patches of thyroid follicular epithelium with crowded cells were detected. Some cells showed intranuclear pseudoinclusions, and nuclear furrows were rare. The pathological case was considered papillary thyroid carcinoma.

FINAL DIAGNOSIS

The final diagnosis of the presented case is parathyroid adenoma.

TREATMENT

The patient was initially diagnosed with hypercalcemic crisis and primary hyperparathyroidism, with the possibility of parathyroid adenoma (PA). Patients were treated with diuretics and calcitonin (calcitonin, 100iu, q6h). After the diagnosis, parathyroid tumor resection under general anesthesia + left thyroid isthmus resection + tissue lymph node resection and biopsy of left central cervical tissue were performed. Intraoperative exploration showed an elevated left lobe of the thyroid gland, and a mass of 3.5 cm × 3 cm in size was palpable behind the bulge, with unclear boundary, complete capsule, and hard quality. No obvious mass was found in the right lobe of the thyroid gland, and no enlarged lymph nodes were found locally and beside the cervical vascular sheath. Considering that the left parathyroid tumor was integrated with the left thyroid lobe, parathyroid tumor resection + left thyroid lobe and isthmus resection was finally performed. Intraoperative frozen section report considered a parathyroid tumor.

OUTCOME AND FOLLOW-UP

The serum PTH and calcium indexes decreased to normal values post-resection. The results of the postoperative pathological examination showed that the tumor presented multiple nodules of varying sizes, with abundant interstitial blood vessels, and irregular ribbon-like collagen fibers in the tumor, which were intermittently distributed and crisscrossed (Figure 4A). Simultaneously, pathological examination revealed tumor invasion or breakthrough of the capsule (Figure 4B), vascular and fat invasion (Figure 4C and D), and heterocyst (Figure 4E). Immunohistochemistry showed that PTH was diffusely positive (Figure 4F), with approximately 1% of tumor cells positive for Ki-67 (Figure 4G), and calcitonin staining was negative (Figure 4H).

Figure 4 Pathological findings. A: Fiber separation (10×); B: Capsular invasion (10×); C: Endovascular invasion (10×); D: Fatty infiltration (10×). E: Heterocyst (40×); F: Parathyroid hormone staining (40×); G: Ki67 staining (40×); H: Calcitonin staining (40×).

DISCUSSION

Since Armstrong first reported cases of PC in 1938, about 700 cases of PC have been reported, and only 11 cases of PC located in the thyroid gland have been clearly reported in the literature[4,5]. The clinical symptoms and signs of PC are mainly associated with hypercalcemia caused by primary hyperparathyroidism, recurrent urinary calculus, osteoporosis, pathological fractures, and gastrointestinal and neuropsychiatric symptoms. However, the differentiation between PA and PC is difficult because clinical and laboratory indicators are not specific. Patients with PC usually have higher blood calcium (usually > 14–15 mg/dL) and PTH levels that can exceed the upper normal limit more than 3 to 10 times. On the contrary, PA usually causes only mild to moderate increases in blood calcium and PTH levels[6]. Some studies have found that serum and urine HCG and its highly glycated isomers are abnormally elevated in patients with PC, but not in those with PA; however, more clinical studies are still needed to confirm this[7]. Neck color ultrasonography and MIBI imaging are the first choice for localization diagnosis of parathyroid diseases, which can distinguish and identify normal and ectopic parathyroid tissues, as well as recurrent parathyroid disease, but does not have the specificity to distinguish benign from malignant tumors[8]. CT and magnetic resonance imaging can accurately locate primary tumors and recurrent lesions, which help detect smaller lesions and assess the adhesion and invasion of surrounding tissues and lymph node metastasis.

With the increasing application of FNA in thyroid lesions, B-ultrasound-guided FNA is also of diagnostic value in the clinical suspicion of parathyroid disease. However, because the cytological features of parathyroid and thyroid lesions have many similarities, the parathyroid lesions with FNA in neck masses may be confused with thyroid tumors, especially for parathyroid tissues heterolocated in the thyroid gland, which is more difficult to distinguish. For example, in our case, the cell smear examination indicated papillary thyroid carcinoma after cervical mass FNA. When cytological smear examination alone still cannot distinguish thyroid lesions from parathyroid lesions, the parathyroid hormone indicators can be detected and evaluated with FNA fluid guided by B-ultrasound to help determine the nature of neck lesions, improve the accuracy of B-ultrasound imaging of parathyroid glands, and successfully guide the operation of patients[9-13]. PTH levels were measured in the puncture fluid diluted with saline, and intact plasma PTH levels were measured. The lesion was defined as a parathyroid gland when the PTH concentration in the parathyroid fine-needle biopsy sample was higher than the serum PTH level. The sensitivity and specificity of PTH elution determination by parathyroid fine-needle puncture were 95.5% and 100%[14]. In this case, FNA was performed on the left neck nodule under the B-ultrasound guidance. The cytological smear of FNA suggested the possibility of papillary thyroid cancer. However, the PTH measured when we performed the puncture fluid elution was significantly higher than 3460.90 pmol/L, the PTH measured by contralateral thyroid FNA was 103.40 pmol/L, and the synchronous serum PTH was > 349.6 pmol/L. Therefore, even though the FNA cytological smear at the time suggested the possibility of papillary thyroid cancer, the lesion was still highly suspected to be PC. The patient was advised to undergo surgical treatment as soon as possible, and postoperative pathological results confirmed PC (Figure 4).

PTH elution measurement is a simple and effective method to guide surgeons in the preoperative localization of parathyroid tumors. However, no unified standard and specification has been established. PC is mainly diagnosed by pathologists intra- and postoperatively. Pathologic diagnosis of PC is often difficult. About 80% of PC tumors are well differentiated. Moreover, distinguishing PA from PC based on histomorphological criteria and even from parathyroid gland cells from thyroid cells, was difficult. In this case, the patient was easily misdiagnosed with papillary thyroid cancer. The accuracy of the diagnosis largely depends on the experience of the pathologist. At present, scholars at home and abroad are experiencing difficulties in relying on intraoperative frozen sections to diagnose PC. Immunohistochemistry of tissue sections will be helpful for the diagnosis of PC, and the Ki-67 and cyclin D1 expression will be increased in PC[15]. The decreased P27 expression and increased galectin-3 expression, as well as their association with Ki-67 labeling, help determine the likelihood of malignancy[16]. The CDC73 gene mutation and paraibromin chromosome deletion will also help diagnose PC in the case of ambiguous clinical diagnosis[15,17,18].

CONCLUSION

The diagnosis of PC is difficult but extremely important. The most effective treatment for PC is surgery, which is not sensitive to chemotherapy or radiation. The prognosis of PC greatly varies, with a recurrence rate of > 50% in 2–3 years postoperatively and 33%–82% in 5 years[19]. In the early operation, standard en bloc resection can be performed with good results, which can provide the best chance of cure and long-term survival for patients[20]. Therefore, the early diagnosis of PC, which can even provide clues of PC preoperatively, will have a significant impact on the choice of surgical methods and the prognosis of patients.

ACKNOWLEDGEMENTS

We would like to thank all the authors and relevant staff who have contributed to this study.