Unusual presentation of Mönckeberg’s sclerosis in the thyroid vessels of three female patients

Abstract

Histopathological findings of Mönckeberg’s sclerosis in the thyroid vessels of three female patients are described. Two of the patients presented with papillary carcinoma and the third presented with two cystic adenomatous nodules. Lesions of chronic lymphocytic thyroiditis were observed in two of the cases. The presence of Mönckeberg’s sclerosis is an indication for further examination of patients’ vascular systems because of the high risk for cardiovascular events.

Mönckeberg’s sclerosis (MS) is a noninflammatory vascular disease of obscure etiology. It is characterized by calcification of the media of muscular arteries, although there is evidence to support an MS definition of calcification of both the media and the internal elastic lamina (IEL) (1). It is usually observed in the lower limb arteries of elderly men and very rarely appears as massive areas of soft tissue calcifications (2). It is strongly associated with diabetes mellitus and end-stage renal disease (3,4).

Calcification of the arteries surrounding the thyroid was observed in three of 76 thyroidectomy specimens submitted to the Areteion Hospital pathology laboratory (University of Athens, Athens, Greece) over a period of 12 months. All three specimens belonged to female patients. After a literature search, we learned that the presence of MS has been observed in the region of the neck and in the vessels surrounding the thyroid (1,2); however, to our knowledge, there has not been a case report solely devoted to the calcification of the thyroid vessels.

We present the clinicopathological features of these three cases.

CASE PRESENTATIONS

Case 1

A 58-year-old woman was diagnosed with thyroid nodular disease for which she received thyroid hormone replacement. After one year of treatment, she was admitted to Areteion Hospital, Athens, and surgical removal of the gland was performed. The fine-needle aspiration (FNA) biopsy that was performed before the surgery did not show signs of malignancy. The patient did not receive any other drugs and had no contributing factors in her family history. Her physical examination revealed no abnormal physical findings in the cardiovascular, respiratory, gastrointestinal and other systems. Serum levels of calcium, phosphorus, alkaline phosphatase and calcium regulatory hormones were within normal limits. The patient did not have diabetes mellitus or renal disease. Chest and neck x-rays did not show any pathological findings, while a neck ultrasound confirmed nodular disease of the right lobe of the thyroid gland. A thyroidectomy was performed and the specimen was sent for pathological examination. The tissue was fixed in 10% neutral buffered formaldehyde at 4°C for 24 h and processed for routine paraffin embedding. Tissue sections 3 μm thick were stained with hematoxylin and eosin, which is the routine staining procedure. Histological examination showed multiple lesions of nodular disease and revealed a papillary carcinoma 0.5 cm in maximal diameter in the left lobe of the thyroid. The carcinoma did not extend beyond the thyroid capsule, did not include psammoma bodies and was characterized as an incidental finding. The examination also revealed substantial ring-like basophilic calcification of the medial layer of some vessels surrounding the right lobe in hematoxylin and eosin-stained slides (Figure 1A), indicative of MS. A few vessels in the IEL were also involved in the calcification (Figure 1B). von Kossa’s stain confirmed the nature of the deposits by staining the calcium black.

Figure 1).

A Histological section of the thyroid gland showing a medium-sized vessel with Mönckeberg’s sclerosis (arrow) (hematoxylin and eosin stain, original magnification ×25). B Histological section of a large vessel with Mönckeberg’s sclerosis involving both the media and internal elastic lamina (arrows) (hematoxylin and eosin stain, original magnification ×100)

Case 2

A 68-year-old woman presented with a node of 2.5 cm in maximal diameter in the left lobe of her thyroid gland. The FNA biopsy of the node was negative for malignancy. The patient did not receive any pharmaceutical treatment other than that for her thyroid condition. Her physical examination revealed no abnormal findings in any system. Renal function was normal and no laboratory results exceeded the highest normal levels. A neck ultrasound confirmed the presence of a node and revealed diffuse, small, hypoechoic areas. The left lobe and the isthmus were surgically removed. Tissue processing and application of von Kossa’s stain for demonstrating calcification was performed as described in case 1. According to the histopathological examination, the left lobe showed a cystic adenomatous node 2.5 cm in maximal diameter, as well as focal lesions of chronic lymphocytic thyroiditis. A smaller cystic adenomatous nodule of 0.4 cm in maximal diameter was found in the isthmus. The media of most arteries around the left lobe was calcified (Figure 2A). In some cases, the calcium deposits were causing an inward displacement of the intima, and the lumen appeared narrowed (Figure 2B).

Figure 2).

A Histological section of the thyroid gland with chronic lymphocytic thyroiditis and a medium-sized vessel with Mönckeberg’s sclerosis (arrow) (hematoxylin and eosin stain, original magnification ×25). B Histological section of the thyroid gland showing Mönckeberg’s sclerosis with concomitant luminal stenosis (arrow) (hematoxylin and eosin stain, original magnification ×250)

Case 3

A 60-year-old woman was admitted to Areteion Hospital for surgical removal of her thyroid gland. The clinical diagnosis was “nodular disease and chronic lymphocytic thyroiditis”. An FNA biopsy was negative for malignancy. The patient was also receiving pharmaceutical treatment for atrial fibrillation that had been diagnosed six months previously. From her physical examination, there were no pathological findings from the respiratory, gastrointestinal and neurological systems. Routine laboratory data were normal. The tests performed for renal disease and diabetes mellitus were negative.

Thyroid scintigraphy confirmed nodular disease, whereas a neck ultrasound revealed diffuse, hypoechoic areas in both lobes. The histological examination with hematoxylin and eosin stain, and the immunohistochemical study with von Kossa’s stain, showed multiple lesions of chronic lymphocytic thyroiditis and nodular disease. It also revealed three areas 0.1 cm to 0.3 cm in maximal diameter of papillary carcinoma (one in the right lobe and two in the left). The carcinoma did not extend beyond the thyroid capsule and showed no signs of calcification. In the vessels surrounding the right lobe, significant calcification of the media and IEL was observed, as well as luminal stenosis (Figure 3).

Figure 3).

Histological section of thyroid vessels with extensive Mönckeberg’s sclerosis (arrows) displacing the intima and causing narrowing of the lumen (hematoxylin and eosin stain, original magnification ×100)

DISCUSSION

MS, or medial arterial calcification, is one of two types of vascular calcification. It appears as ring-like calcific deposits within the media of small- and medium-sized vascular arteries. The other type, intimal arterial calcification, occurs in atherosclerotic plaques. Discontinuous calcific deposits are observed solely in the IEL of large- and medium-sized arteries, obstructing the arterial lumen. Although intimal arterial calcification affects older patients, and medial arterial calcification affects younger and middle-aged patients, the main criterion that differentiates them is their localization. In a recent review, Michelleti et al (1) reported that “none of the 14 cases reviewed here, which we believe are typical of those called MS, had calcification limited to the media; IEL involvement was a universal finding”. In all three cases of MS presented above, IEL involvement was observed to a different extent. Furthermore, in a few vessels, the calcium deposits were causing an inward displacement of the intima and narrowing of the lumen.

MS was originally observed in the arteries of the lower limbs of elderly men, although it has also been frequently described in women – in the arteries of the uterus, the breasts and the thyroid. In fact, the calcification of the arcuate arteries of the uterus as a manifestation of MS is not an uncommon finding in surgical specimens and is considered to be insignificant by pathologists (5). A recent study showed that its prevalence in the population was 13.3% for men and 6.9% for women (6). Prevalence of MS was calculated with the use of ankle-brachial index cut-off values; thus, the cases involving MS in the smaller arteries were not included. Given the fact that it can occur in the arteries of the female breasts and uterus, it is possible that it affects women as much as men, or even more.

The etiology of MS is unknown. Sato et al (7) performed a study using rats to establish the relationship between the physiological concentration of thyroid hormones and vascular calcification. A decrease in thyroid hormone proved to increase the vascular calcification in vivo, clearly demonstrating that the physiological concentration of thyroid hormone has a direct protective role against vascular smooth muscle calcification (7). The decrease of thyroid hormone in hypothyroidism could be responsible for the calcification of the arteries in humans, a lesion that cannot be reversed when hypothyroidism is diagnosed and the patient receives thyroid hormone replacement.

Until recently, MS was believed to be a rather harmless condition. Radiologists who saw the distinct tramline patterns of MS on plain radiographs of the lower limbs considered them to be merely incidental findings. However, this is not the case. Medial calcification is responsible for the loss of elasticity of the arteries and is now thought to lead to isolated systolic hypertension, left ventricular hypertrophy (and failure) and reduced myocardial perfusion (8). Different studies have shown that cardiovascular morbidity and mortality are substantially higher in patients with chronic kidney disease, compared with the nonrenal disease population, and arterial calcifications are responsible (4). In the same way, the artery stiffness caused by MS leads to increased cardiovascular mortality and morbidity in patients with noninsulin-dependent diabetes mellitus (3). MS has also been linked with autonomic neuropathy and lower limb critical ischemia, which can lead to limb amputation (9).

In two of the three cases that we presented, areas of papillary carcinoma were observed, but no psammoma bodies were found. There is no evidence that their concurrent presence with the calcifications of the vessels surrounding the thyroid is connected.

Although the presence of MS in thyroid muscular arteries has been reported before (1), it is not known whether MS is restricted to the thyroid in these patients or whether it is a sign of more generalized arterial calcification. Micheletti et al (1) reported that two of the 12 patients in their review had MS in more than one tissue. One of them was a woman, in whom arteries of the thyroid and uterus were involved (1). However, it is not mentioned whether these 12 patients were further examined to establish the presence of MS in other arteries. It is possible that MS was not restricted to one tissue.

The association of MS with cardiovascular morbidity and mortality in patients with chronic kidney disease (4,8) and patients with noninsulin-dependent diabetes mellitus (3) has been confirmed by many studies.

CONCLUSION

When MS is diagnosed in small or medium-sized arteries, further examinations should be performed to establish whether other larger arteries are also affected, especially if the patient is diabetic or has renal disease, in which case, the risk for cardiovascular events is even higher.