Parathyromatosis: The Pathogenic Background (Post-Parathyroidectomy Seeding or Exceptional Embryologic Remnant) and the Importance of a Fine Clinical Index for Recurrent Primary Hyperparathyroidism (a Narrative Review).

Background: Parathyromatosis, an exceptional clinical and pathological entity, involves multiple small nodules of hyper-functional parathyroid tissue scattered throughout the neck and/or mediastinum, in relationship with a prior parathyroidectomy (mostly) or embryologic remnant. Since its first identification in 1975, many aspects of this condition have remained a matter of debate. Objective: We introduce an updated perspective on parathyromatosis covering the main clinical points for everyday practice, from diagnosis to management, as well as the current level of pathogenic understanding. Methods: A narrative review. Results: A total of 22 patients were identified, with the following characteristics: an age range of 33-68 (mean 46.18) years; 4/22 subjects <40 years; female-to-male ratio = 14:8. Of the 22 subjects, 21 had undergone previous parathyroidectomy for primary (n = 14) or secondary (n = 7) hyperparathyroidism. One case was a surgically naïve patient. Analysis of the surgical procedures (seeding circumstances) revealed the following: parathyroid cyst removal, left/right parathyroidectomy; removal of 3.5 parathyroids ± self-transplantation, VATS for mediastinal parathyroid tumours. Parathyroidectomy was accompanied by thyroid surgery (n = 3 patients), specifically hemi-thyroidectomy, partial left-thyroid lobectomy, and partial thyroidectomy. The shortest timeframe from parathyroidectomy to parathyromatosis-related hyperparathyroidism recognition was 1 year, and the longest was 17 years. The highest number of previous surgeries was four. The recognition of parathyromatosis was due to the clinical picture of associated hyperparathyroidism, except for in 2/21 cases with incidental detection. The implant sites coincided with the prior surgical area, but also with unusual locations (clavicle, pleura, mediastinum, sternocleidomastoid muscle and forearm, thyroid). The imaging evaluation included ultrasound plus CT plus 99m-Tc sestamibi scintigraphy, as well as (variable rates) neck MRI, SPECT/CT, 11-Choline PET-CT, Gallium-68 DOTATATE, and 4D CT. Surgery implied serial procedures in some cases (e.g., up to seven). The surgery spectrum largely varied, including not only cervicotomy, but also thoracoscopy, VATS, pericardial adipose tissue excision and thymectomy, etc. Conclusions: Awareness remains a key factor when approaching such an unusual ailment underlying little-understood pathogenic loops, which, if left unrecognized and untreated, might impair patients' quality of life and the overall parathyroid disease burden.