Parathyromatosis Coexisting with Papillary Thyroid Microcarcinoma

Postoperative clinical, biochemical or histological persistence or recurrences observed in primary and renal hyperparathyroidism are determined by inadequate operations, existence of ectopic or supranumerary glands, parathyroid carcinoma, MEN 1 and also by parathyromatosis, a rare recently described entity. This latest lesion consists of hyperfunctioning parathyroid tissue disposed as micronodules or cellular aggregates capriciously scattered in the cervical loge and mediastinum but also on/in the thyroid gland, thymic rests, adipose and muscular surrounding soft structures [1-4].

Sporadic case reports and small surgical series of parahyromatosis distinguished two pathogenic varieties: - the first of them is due to the hyperplasia of glandular nests from embryological descent of parathyroids; - the second and more frequent one is determined by the inadvertent intraoperative fracture of glandular capsule or parenchyma which can become implanted in the surgical area [5,6].

The diagnosis of parathyromatosis seldom confounded with parathyroid carcinoma is difficult, the lesion often escaping to imaging studies, being identified only intraoperatively or by microscopic examination [7]. The mainstay treatment of this bizarre lesion is surgery however a coherent operative strategy is missing due to the small number of cases. Administration of calcimimetics have controversial effects. Both methods seems to be unable to assure an optimistic percentage of definitive cure [8]. Like another parathyroid lesions parathyromatosis can be associated with different thyroid pathological changes. The present case described the fortuitous coexistence of parathyromatosis with papillary thyroid carcinoma, an entity which have not yet be reported in the literature.

Case description

A 56 year old woman is admitted in our clinic with recurrent primary hyperparathyroidism six years after a right inferior adenoma removal done elsewere. The diagnosis is sustained by the relapse in the last year of pyelic lithiasis with frequent renal colics, osteoarticular pains, anorexia and dyspeptic symptoms, myasthenia, emotional irritability and depression. The laboratory tests showed raised levels of iPTH – 348 ng/l and alkaline phosphatase – 195 iu/l but normal values of seric calcium and phosphorus. Ultrasonography noticed an unhomogeneous hypoechoic zone of about 5 mm in diameter situated at the inferior right pole of the thyroid gland, image unsustained by Tc- 99m tetrophosmin scan which only indicates diminished tracer uptake. (Figure 1)

Figure 1: Ultrasonography : hipoechoic area in the lower pole of the right pole of the thyroid.

The reintervention going on in a “hostile” surgical field determined by fibrosis and adherences identified an irregular, not bounded, whiteyellowish, 5 mm mass, situated laterally and under the inferior pole of the thyroid to which it is adhering and extended in the thyrothymic ligament. Moreover about 15-20 similar micronodules until 2 mm are scattered on the surface or even inlaided in the thyroid tissue or in the fibrofatty atmosphere of the tracheoesophageal groove. Excision and frozen section of the main mass and two of the satellite lesions showed the presence of hypercellular parathyroid tissue without stigma of malignancy.

However the impossibility to exclude the presence of a carcinoma conduced to an extended thyroid lobectomy involving the isthmus and 3-4 cm from thyrothymic ligament retrosternally together with parathyroid fibrofatty tissues.

The definitive paraffin examination confirmed the existence of many fold microgrowths and cellular agregates composed of benign parathyroid chief cells with uniform nuclei and clear cytoplasma without atypia but also a limited foci of papillary thyroid microcarcinoma measuring about 2 mm, without tissular, vascular or lymphatic extension. Figure 2, 3 considering the characters of both lesions, especially of those of incidentally discovered thyroid microcarcinoma, periodical recurring at regular intervals of the patient was decided. At 6, 12 and 24 months postoperatively she is symptom free without any local recurrence and normocalcemic. Levels of iPTH and TSH are 76, 46 and 29 ng/l respectively 1,5, 2 and 2,5 ml/l. However the effects of the adopted surgical solution, beneficial for each of diseases, are unfortunately no definitive imposing a long-period supervision.

Figure 2: Parathyroid nodular hyperplasia (HE x 200).

Figure 3: Foci of papillary thyroid microcarcinoma (HE x 100).

Parathyromatosis was initially mentioned by Palmer [9] which described the lesion in a patient with tertiary hyperparathyroidism and by Reddick [10] which proposed the actual denomination.“De novo” observations without any preceding operations and primitive (onthogenic) cases are very rare appearing preferentially in patients with refractory renal hyperparathyroidism on chronic hemodialysis while the more common second type occurs after spillage and seeding of glandular tissue indifferently of pathologic substratum [11,12]. However in primary hyperparathyroidism the risk of fracture of the capsule and glandular tissue seeding is minimal in the exeresis (even minimally invasive) of adenomas and also rare notified in operations for parathyroid hyperplasia.

The majority of cases are recorded after parathyroidectomies for renal hyperparathyroidism where the dissection and handling of the little glands recommended to be done at the minuscule pedicle’s level and also the eventually sections can produce solutions of continuity of the capsule or parenchyma.

It must be remembered that chronic kidney failure consitued a permanent stimulating factor concerning the both embryonary and postoperative glandular rests. Otherwise even the hypertrophy and hyperplasia of the transplanted fragment of the “most normal” gland in the arm or another locations is considered a variety of parathyromatosis. Rarely evoked or affirmed before operation the diagnosis of this condition is however suggested by the context of previous parathyroid operation and by persistence or recurrence of the clinical and bioumoral syndrome. Imaging explorations included ultrasonography which identified multiple hypoechoic areas scattered deeply and superficially in the anterior cervical and retromanubrial territories sometimes in atypical locations and often hypervascularised at Doppler examination and related uptake at single-proton emission computer tomography better observed with a parallel collimator than with a pinhole one. Fine needle aspiration biopsy appeared utile in some observations [7,11,14]. For all these conditions intraoperative exploration confirmed by definitive paraffin examinations constituted the main elements of diagnosis.

Macroscopically the lesions appeared as multiple (until 80) irregular white-yellowish nodules, with 1-30 mm O aleatory distributed in the perithyroid atmosphere, usually in the side previously operated in the tracheoesophageal groove, on or in the thyroid gland, in the superior mediastinum, in all of these suggering initially the presence of secondary carcinomatous deposits. Cicatriceal modifications and fibrosis render more difficult the evaluation. Microscopic characters attests the lesion’s benignity: trabecular disposition, presence of mitoses and nuclear pleomorfism without vascular or lymphatic invasion. However the examination can surprisingly discover malignant aspects or the coexistence of another cancerous pathology as in our observation [15]. The treatment of parathyromatosis cannot be standardized owing to small number of cases. Surgery represents the necessary resource both for the diagnosis and the therapeutics, operative strategy being ad-hoc established in the majority of cases depending of the absence of preoperative diagnosis and lesional surprises with their chaotic distribution and (un)recognition or confusion with a carcinoma [5,7,9,16,17]. The main objective of the operation is as complete as possible excision of the hyperfunctionally glandular tissue which is practically impossible to do because beyond the identificable microlesions there are microscopic foci which once cannot be visualized. Therefore a semblable attitude with that for carcinomas is adopted as is were en block exeresis of all the visible lesions together with the ipsilateral thyroid lobe and the surrounding fibrofatty atmosphere from the thyroid cartilage to the thymic lodge [18]. A radical surgical act become more difficult because of the unequally degree of development of the parathyroid lesions at the time of intervention, the eventually residual foci influenced by their stimulating factors continuing their own evolution and imposing repeated more and more difficult operations. The high parathyromatosis potential for recurrences engendered skepticism regarding both the eficacity of its surgical treatment and prognosis, some authors assigning an irreversible course of this entity. Percutaneous ethanol injection with subsequent ischemic necrosis together with administration of biphosphonates, vitamine D analogues and especially calcimimetics was also proposed in the therapy of parathyromatosis. The last ones completes and prolongs the clinical effects of surgery and stabilized for notable intervals the levels of iPTH, calcium and phosphates [19-21].

Even if the prevalence of nonmedullary thyroid microcarcinoma in the parathyroid gland surgery is notable, the coexistence of this neoplasia with parathyromatosis was not yet been reported and our case seems to be the first related one in medical literature.

Inspite of possible pathogenic speculations for a causative relationships this immediate association remains a simple coincidence. Every endocrine surgeon needs to be aware of the possible synchronous presence of thyroid and parathyroid lesions, careful exploration of both glands is mandatory in surgery for hyperparathyroidism in order to exclude the presence of a thyroid carcinoma. Incidentally discovered (micro) nodulary thyroid lesions should be prompt submitted to a frozen section diagnosis and no less than a total lobectomy must be done.

Consent: The patient has given her consent for the case report to be published

Competing interest: The authors mentioned that they have not competing interest

Author’s contribution: MRD was the major contributor in writing the manuscript.MG and SD performed the clinical assessement and the literature review. MG confirmed the diagnosis by histopathological findings. All authors read and approved the final manuscript.

The authors thanks dr E Popescu for its friendly support in the manuscript typewriting