Case Report
Jorge Gabriel Ruiz-Sánchez*, Paola Parra Ramírez and Arturo Lisbona Catalán
A rare association of two endocrine tumours: non- functional oncocytic adrenocortical carcinoma and Papillary thyroid carcinoma
https://doi.org/10.1515/hmbci-2020-0080 Received November 13, 2020; accepted February 16, 2021; published online March 8, 2021
Abstract
Objectives: To describe a rare association of two endocrine tumours in a clinical case.
Case presentation: A 54-year-old woman with a classic Papillary thyroid cancer (PTC) assessed by the Endocrinology Department of a tertiary hospital from May-2015 to May-2020. PTC was treated with a total thyroidectomy and lymphade- nectomy in May-2015. Initial staging (AJCC/TNM 7th edition): T3N1bMx. Additionally, two ablative doses of 150 mCi of 131-I (RAI) were administered until September-2016. No patho- logical uptake was found on the post-RAI whole-body scan at any level. Due to a persistent incomplete biochemical response in February-2017, a 18Fluor-dexosiglucose positron emission computed tomography (FDG-PET) was performed. FDG-PET showed an intense pathological deposit in the right adrenal, suggestive of malignancy. Right adrenalectomy was carried out, and pathology revealed an Adrenocortical car- cinoma (ACC). Genetic syndromes associated to ACC are: Li- Fraumeni syndrome (caused by an autosomal mutation in the TP53 gene), the Multiple Endocrine Neoplasia (MEN) type 1 (caused by Menin gene mutations), and MEN type 4 (caused by heterozygous mutations in the CDNK1B gene). However, none of them are associated to PTC.
Conclusions: To our knowledge this is the sixth published case reporting an ACC in presence of a PTC. The pathological factors behind the relation between these malignancies
have not been elucidated. We do not discard the possibility of a genetic relationship between PTC and ACC.
Keywords: adrenal metastasis; adrenocortical carcinoma; differentiated thyroid cancer; Papillary thyroid cancer; Papillary thyroid cancer metastasis.
When two or more endocrine malignancies are detected in a same person, a genetic or hereditary disorder should be ruled out. However, in some endocrine cancer associations a known genetic cause has not been elucidated. We present a unique case of a woman, with a malignant incidental adrenal lesion detected during the follow-up of a Papillary thyroid cancer (PTC).
A 54-year-old woman was in follow-up by the Endocri- nology Department due to a classic PTC. She had a medical history of hypertension treated with enalapril daily, with no familiar history of malignancy or hyper-functional endocrine diseases. Her PTC was treated with a total thyroidectomy and a functional and recurrent cervical lymphadenectomy, with an initial T3N1bMx staging (AJCC/TNM 7th edition) in May- 2015. Three months after surgery, the post-surgical TSH-stimulated serum thyroglobulin was 96.6 ng/ml, and a first ablative dose of 150 mCi of 131-I was administered. The whole-body scan performed after radioiodine-therapy (RAI) showed only a low local uptake corresponding to functioning thyroid remains (Figure 1A). During the follow-up, a sup- pressive dose of oral levothyroxine was established. Basal serum thyroglobulin at this period was between 4.4 and 6.3 ng/mL. A second ablative dose of 150 mCi of 131-I was indicated in September-2016 due to a persistent incomplete biochemical response, characterized by a TSH-stimulated thyroglobulin of 91.6 ng/ml and positive anti-thyroid anti- bodies, with non-structural lesions. The second post-RAI whole-body scan showed no pathological uptake on any levels (Figure 1B), however basal thyroglobulin remained between 4 and 6.9 ng/ml. Finally, in Febreuary-2017, a 18Fluor-dexosiglucose positron emission computed tomog- raphy (FDG-PET) revealed a highly pathological increase of the glycidic index in the supraclavicular, paratracheal and
*Corresponding author: Jorge Gabriel Ruiz-Sánchez, MD, Servicio de Endocrinología y Nutrición, Hospital Clínico San Carlos, Calle del Prof. Martín Lagos, s/n, 28040 Madrid, Spain,
E-mail: gajo_saru@hotmail.com. https://orcid.org/0000-0003-1305- 9354
Paola Parra Ramírez and Arturo Lisbona Catalán, Servicio de Endocrinología y Nutrición, Hospital Universitario La Paz, Madrid, Spain. https://orcid.org/0000-0002-0310-7095 (P. Parra Ramírez)
mediastinal lymph-nodes, all of them below 1 cm. An intense pathological deposit adjacent to the medial border of segment VII of the liver, suggesting a right adrenal lesion (Figure 1C), was also found. Contrast- enhanced MRI confirmed a hyperenhancing right adre- nal lesion measuring 15 mm. In context of known ma- lignancy in this patient, the possibility of PTC metastasis was raised. In the hyper-functionality workup, only a slightly increased serum aldosterone/renin ratio was observed, and the other adrenal hormones were within normal limits. With these findings, the multidisciplinary committee on endocrine tumours of our hospital dis- cussed the management alternatives depending on whether the adrenal lesion was a PTC metastasis or a primary adrenal malignancy. After that, a laparoscopic right adrenalectomy was chosen. Pathology revealed a non-functional adrenocortical oncocytic neoplasm with histological criteria of aggressiveness, compatible with localised Adrenocortical carcinoma (ACC), with no affected surgical borders (R0 resection). After surgery, the FDG-PET scan showed no evidence of adrenal tumour recurrence. After a multidisciplinary discussion, no adjuvant therapy with mitotane for ACC was performed, and the suppressive dose of levothyroxine for PTC was maintained. Within the three years of follow-up, the patient did not present any evidence of structural pro- gression of either ACC or PTC.
Thyroid cancer is the most common endocrine malig- nancy. PTC is the most prevalent histological type and generally has a good prognosis, expressed by ~95% of overall survival rate [1]. Distant metastatic disease of PTC is not common, and is seen in 1-2% of cases [1], leading to worse prognosis, with close to 50% of long-term survival.
On the other hand, ACC is a very rare malignancy, representing 1.2-12% of adrenal tumours [2]. ACC has a high rate of progression, with a five year survival below 50% if locally advanced [2, 3].
Secondary metastatic involvement is the most frequent cause of a malignant adrenal mass. This can be bilateral in 50% of the cases and caused by adenocarcinoma tumours in over 90% of the cases [3]. Therefore, the likelihood of a malignant adrenal mass being metastatic is much higher in the setting of an extra-adrenal malignancy. However, there are some types of malignancies with a low rate of adrenal involvement, such as PTC. Adrenal PTC metastases are rare, with fewer than 10 reported cases to our knowledge.
There is no consensus about how the physicians should act when a malignant adrenal mass is detected in the follow- up of a PTC. In the presence of an adrenal mass with an extra-adrenal primary malignancy, clinical guidelines recommend ruling out hyperfunction of the adrenal lesion
A.
B.
C.
and performing a biopsy, except when an ACC is suspected [2]. Thus, since some cancers rarely metastasize to adrenal glands, an individualized analysis based on the clinical and epidemiological characteristics of the primary tumour should be developed in order to decide the management of these lesions.
Some genetic syndromes have been clearly associated with ACC, they are the Li-Fraumeni syndrome (which is caused by an autosomal mutation in the TP53 gene) [4], and the Multiple Endocrine Neoplasia (MEN) type 1 (caused by Menin gene mutations) [5]. Furthermore, there are some reports of adrenal tumours related to MEN type 4 (caused by heterozygous mutations in the CDNK1B gene) [5]. However, none of these syndromes have been associated with PTC.
To our knowledge this is the sixth published case reporting an ACC in the presence of a PTC. At present, the pathological factors behind the likely association between these malignancies have not yet been elucidated, and
whether there is some mutation contributing with the pathogenesis of both tumours is unknown. Although in our patient, a genetic study was not developed due to the absence of familiar history, we do not discard the possi- bility of a genetic relationship between PTC and ACC. Therefore, more studies reporting this association will be necessary to direct a research about this clinical situation.
Research funding: JGR-S has a contract as a researcher with the Foundation for Biomedical Research at the Hospital Clínico San Carlos (Reference number. INV-15- 2019). But no funding was received to assist with the preparation of this manuscript.
Author contributions: Conceptualization: Jorge Gabriel Ruiz Sánchez and Arturo Lisbona Catalán; Methodology: Jorge Gabriel Ruiz Sánchez and Paola Parra Ramírez; Formal analysis and investigation: Jorge Gabriel Ruiz Sánchez; Writing - original draft preparation: Jorge Gabriel Ruiz Sánchez; Writing - review and editing: Jorge Gabriel Ruiz Sánchez, Paola Parra Ramírez and Arturo Lisbona Catalán; Resources: Arturo Lisbona Catalán; Supervision: Arturo Lisbona Catalán. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent is not applicable given the retrospective nature of the study.
Ethical approval: The conducted research is not related to either human or animals use. All procedures performed in this study were in accordance with the ethical standards of the local institutional committee, Spanish regulation and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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