Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management

Abstract

Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.

Diagnosis and treatment of liver metastases of parathyroid carcinoma

“…PET/CT is commonly used to detect recurrence or metastasis of malignancies, but its role in PC has not been clearly reported, and only a few case series studies show the benefit of PET scans, especially in the postoperative period, to detect local recurrence and distant metastases, such as subcutaneous recurrence and breast metastasis ( 27 – 29 ). Only one patient’s liver lesion was found by [18F]FDG-PET-CT among all the cases ( 8 ); such results challenge the sensitivity of [18F]FDG in the diagnosis of liver metastases.…”

“…Physiological saline, diuretics, calcitonin, and bisphosphonates are the most commonly used drugs, which have been clinically demonstrated to lower serum calcium but often only temporarily. The calcimimetic drug cinacalcet is another option that combines with calcium-sensing receptors to reduce PTH secretion and control serum calcium ( 29 ). It can be considered for hypercalcemic patients with inoperable PC, incomplete resection of PC lesions, or postoperative recurrence and effectively lowers serum calcium levels in approximately two-thirds of patients ( 36 , 37 ), but unfortunately, our liver metastatic patients have not shown satisfactory outcomes.…”

Role of surgery in the treatment of parathyroid carcinoma

“…Im Rezidivfall kommen bei häufig erschwerter Lokalisierung die Schnittbildgebungen (Computertomographie, CT/ Magnetresonanztomographie, MRT) sowie Ganzkörperaufnahmen (Positronenemissionstomographie-CT, PET-CT) hinzu [13,18]. In Einzelfällen bedarf es eines selektiven Halsvenenkatheters mit Etagenblutentnahme, um den Rezidivtumor zweifelsfrei zu detektieren [19].…”

“…Neueste Fallberichte zeigen v. a. bei disseminiertem oder metastasiertem Krankheitsverlauf eine Behandlungsoption mit einer gegen humanes Parathormon (hPTH) gerichteten Immuntherapie (Anti-hPTH-Immuntherapie) oder den Einsatz von Immuncheckinhibitoren auf [13,45,46]. Als im komplexen Einzelfall sinnvolle Option konnte der Nutzen einer genomischen Profilerstellung gezeigt werden [19,47,48].…”

Commentary: Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management

“…In the issue of March 2021, Lenschow et al reported the case of a 46-year-old woman with recurrent, programmed death-ligand-1 (PD-L1) negative, tumor mutational burden (TMB)-high parathyroid carcinoma (PC), who showed stable disease as her best response on imaging, and a three-fold drop in PTH after treatment with intravenous pembrolizumab (1).…”