Clinical course of atypical parathyroid neoplasm with soft tissue extension

The American Joint Committee on Cancer (AJCC) TNM staging system defines atypical parathyroid neoplasia (APN) as tumor in situ (Tis) and reserves the definition of parathyroid carcinoma (PC) to parathyroid tumor with invasion into surrounding structures. Because the parathyroid gland has no true capsule, "extension" with APN versus microscopic "invasion" of surrounding soft tissue can be difficult and confusing for clinicians. We aimed to determine the clinical course of atypical parathyroid neoplasm with and without soft tissue extension and parathyroid carcinoma with only soft tissue invasion (pT1) and to report the outcomes.

Following an IRB-approved protocol, we identified all patients treated for parathyroid neoplasm or cancer at our single tertiary care cancer center from 1990 to 2021. We excluded all patients with evidence of clinical or pathologic gross invasion into surrounding structures (pT2 or higher), lymph node involvement, or metastatic disease. By definition, this excluded all cases where the distinction was clinically evident to the surgeon at the time of the operation based on finding a hard, firm, sticky, or discolored parathyroid gland. Only patients with pathologic T1 (pT1) parathyroid carcinoma or APN were included. All pathologic examinations were independently re-reviewed by a single designated expert senior endocrine pathologist. The definition of APN strictly followed the WHO definition of a clinically worrisome lesion having features including fibrous bands or increased mitotic rate, necrosis, or trabecular growth that did not meet robust criteria for frank invasion. Pathologic T1 disease was defined as invasion limited to soft tissue. Analyses were performed using R version 4.0.2 and Jamovi.

Of all PC patients at our institution, only 71 met the strict inclusion criteria of APN or pT1. Forty-four patients had pT1 disease and 27 had APN: 12 of the APN had soft tissue extension, and 15 had no soft tissue extension. The groups were similar with regard to age at diagnosis (p = 0.328). The average follow-up duration was 84 months from initial surgical intervention. Of the 12 with APN, one patient (1/12; 8%) with soft tissue extension recurred, developed distant metastases, and subsequently died during follow up. Of the 44 patients with pT1 PC, six developed distant metastases and 13 (13/44; 30%) died during the follow-up period. One patient with APN and soft tissue extension recurred and died and no patient with APN and no soft tissue extension died.

Patients with APN and extension into soft tissue have a clinical course similar to that of APN without soft tissue extension. APN with soft tissue extension is a different disease from pT1 disease with invasion of soft tissue. The pTis classification appears justified for APN with and without soft tissue extension.