In 1985, dominantly inherited multitumor syndrome of myxomas, spotty skin pigmentation, and endocrine over activity, now referred to as Carney complex. Later, psammomatous melanotic schwannoma, epithelioid blue nevus, and osteochondromyxoma of bone were added to the syndrome. In 1997, Stratakis reported tumors of the thyroid gland in 3 of 53 patients (6%) with CNC. In 2009, Bertherat et al found a thyroid disorder in 88 of 353 patients with CNC (25%); papillary or follicular carcinoma or both occurred in 9 of the 353 patients (2.5%). The present investigation was undertaken to study the pathologic findings in the thyroid gland in CNC.
This study was approved by the Mayo Clinic Institutional Review Board. The clinical and pathology records of Mayo Clinic and records of the National Institutes of Health (NIH) from January 1999 through June 2016 were searched for patients with CNC who had thyroid gland surgery or who likely had thyroid gland pathology because of thyroid symptoms (thyrotoxicosis). Patient CNC-associated findings and thyroid-related clinical, surgical, and pathologic findings and follow-up information were abstracted from the records. A second search of those records was conducted for patients with CNC and normal thyroid clinical findings who had died of nonthyroid-related causes and whose thyroid gland was available at autopsy for histologic study. The world medical literature from January 1999 through June 2016 was searched for reports of patients with CNC and mention of the thyroid gland.
The first search identified 10 patients with CNC who had or likely had thyroid gland pathology (8 women and 2 men; 3 were in Mayo Clinic records, 5 were in J.A.C.'s files, and 2 were in the NIH files). Two patients who had Graves disease and a third who had a nodule that caused thyrotoxicosis were presumed to have thyroid pathology. Patient sex, age at diagnosis of CNC, age at diagnosis of a thyroid disorder, CNC components, and PRKAR1A mutational status are discussed further in full article. Patients 5 and 8 were mother and daughter.
Gross and microscopic findings of lesions and follow-up for patients 1, 4, and 9 are presented in full article. along with findings from another 4 patients with follicular carcinoma reported in the literature. Histologic findings in patient 4 are presented in full article. Immunostaining of the carcinomas in patients 1, 4, and 9 showed cytoplasmic positivity for thyroglobulin (3 of 3 tumors), nuclear positivity for PAX8 (3 of 3), nuclear positivity (50% of cells) for HBME-1 (2 of 3 tumors), scattered cells positive for galectin-3 (3 of 3), and no staining with cytokeratin 19 and calcitonin (3 of 3 tumors).
Mutational findings and pathologic diagnoses in the 16 reported patients are shown in full article Microscopic findings in patient 22 were unusual. The patient, a 13-year-old girl, had a total thyroidectomy for an asymptomatic multinodular goiter. The pathology report mentioned a 1.5×1×1-cm tumor. The diagnosis was “multifocal papillary and follicular hyperplasia, atypical.” Review of the histologic findings revealed a multinodular goiter, follicular adenoma, and microscopic follicular adenomatosis.
The components of CNC have emerged over time. Thyroid involvement in the syndrome was reported in 1997,12 years after the first description of CNC and confirmed more than a decade later. Herein, we have described the clinical, pathologic, and follow-up findings for 26 patients with CNC who had thyroid gland surgery. Of the 10 patients identified from the records of Mayo Clinic, J.A.C., and the NIH, 6 had thyroid-related symptoms and 4 had thyrotoxicosis Of the 16 patients identified from the literature search, 15 were asymptomatic.
Summary of Clinical and Histopathologic Findings in the Thyroid Gland of Patients With Carney Complex
The results of the combined study and literature findings showed that a thyroid disorder was an uncommon and late-developing feature of CNC. Most of the patients were asymptomatic women; the female to male ratio was approximately 2:1. The patients ranged in age from the second through the sixth decades. The youngest and oldest at operation were 13 and 57 years, respectively; the mean age was 34 years. Follicular carcinoma accounts for about 20% of all thyroid carcinomas Lymph node metastasis is found in less than 10% of cases.
Four patients had thyrotoxicosis caused by diffuse follicular hyperplasia and follicular adenoma. Transient thyrotoxicosis occurred in a patient with CNC not included in the study. Interestingly, ablation of thyroid-specific PRKAR1A in mice resulted in follicular carcinoma and hyperthyroidism.
As has been described, several benign and malignant follicular lesions occurred among the 26 patients. This is the multilesional pattern found in the adrenal and testis in CNC; primary pigmented nodular adrenocortical disease, cortical adenoma, and cortical carcinoma occur in the adrenal, and Leydig cell hyperplasia, Leydig cell tumor and Leydig cell carcinoma occur in the testis.
Early detection and surgical resection of follicular and papillary carcinomas offers the best hope of cure. Long-term surveillance of CNC patients is required to detect thyroid carcinomas at an early and curable stage. Clinical or sonographic examination of the gland at annual or biennial cardiac echocardiographic evaluations should improve detection of the lesions.
In summary, we report the clinical and pathologic findings in the thyroid gland of 26 patients with CNC. The findings showed that follicular carcinoma was the most serious lesion.
In summary, we report the clinical and pathologic findings in the thyroid gland of 26 patients with CNC. The findings 1) showed that follicular carcinoma was the most serious lesion affecting the gland in the syndrome; 2) described unusual features of the carcinomas; 3) added follicular hyperplasia (Graves disease) to the pathologic lesions; 4) mentioned a possibly unique type of microscopic multifocal follicular hyperplasia; and 5) added thyrotoxicosis to the clinical findings in the syndrome. Long-term surveillance of patients with CNC is necessary to detect and treat the thyroid lesions, particularly the carcinomas.