Poorly differentiated thyroid carcinoma: a case report

¹Ear, Nose and Throat Department, Avicenna Military Hospital, Marrakech, Morocco

^&Corresponding author
Mossab Tayane, Ear, Nose and Throat Department, Avicenna Military Hospital, Marrakech, Morocco

Introduction    

The poorly differentiated thyroid carcinoma (PDTC) was described in 1983, and since then, those tumors was a subject of discussion, on their morphological diagnosis features, molecular profile, and their clinical evolution. First of all, it was described as an intermediate tumor between Anaplastic Thyroid Carcinoma (ATC) and Differentiated Thyroid Carcinoma (DTC), introduced in the WHO classification of endocrine tumors as a new entity [1]. Then more features and diagnosis criteria were proposed by Memorial Sloan Kettering Cancer Center (MSKCC) in 2006 and adopted in the Turin proposal to set universal diagnosis criteria [2].

There is no specific stratification of tumor for the PDTC, the system of staging commonly used is the 8^th version of the AJCC/UICC staging system, which consider the PDTC and ATC those ones as stage IV [3]. The American Thyroid Association (ATA) has established some guidelines to treat thyroid tumors, based on the staging system and the molecular profile of those tumors. We report a case of PDTC with aggressive features clinically, pulmonary and cerebral metastasis. and discussing the pathology with some review of the literature.

Patient and observation     

Patient information and timeline: our case is about a 54-year-old male patient, with no background of pathology, neither therapeutic intervention nor familial history of cancers, consulting for a neck tumor, progressing for about 6 months, situated cervical anterior, moving up and down with the swallowing, with a firm consistency. It was about a swelling of the thyroid gland, without any clinical signs of hyperthyroidism or hypothyroidism. Moreover, the patient reported a notion of chronic cough for 4 months.

Clinical findings: the examination of the cervical lymphatic nodes found a 2cm node situated in the left IIa territory, with a hard consistency. The pulmonary and neurological examinations were normal.

Diagnostic assessment: the cervical ultrasound check found a multinodular goiter with some EUTIRADS 3 and 5 nodes. The thyroid gland was considerably enlarged responsible for compression of the trachea and esophagus. Fine needle aspiration was done among the most scored thyroid node, and its cytological diagnosis was in favor of a Bethesda 3. However, in order to establish a diagnosis, we were in the obligation to make a biopsy, which was done surgically. Its histological features were in favor of a poorly differentiated thyroid carcinoma. In order to make a lesion assessment, a TAP CT found a voluminous goiter among the left lobe, with microcalcifications, compressing the aerodigestive axis (Figure 1). Moreover, it found some metastatic pulmonary localizations, and mediastinal nodes (Figure 2, Figure 3); also, a cerebral MRI was done in the profit of our patient, which localized some supra and subtentorial lesions with a secondary appearance compressive at the level of the posterior cerebral fossa (Figure 4), with the onset of an engagement.

Therapeutic intervention: we consulted the neurosurgical team about the cerebral localization, they decided to prescribe an anticomitial medication with full abstention from any kind of surgical intervention. The case was presented in a multidisciplinary meeting, gathering the neurosurgical, oncology, and endocrinology teams, who decided to indicate exclusive radiotherapy with anti-comitial medication as the primary prevention of epileptic seizures. However, the patient underwent a tracheostomy premiere.

Outcomes: the treatment proposed to our patient aimed to improve the quality of life and extend the survival of the patient. For this purpose, he was addressed to an oncology-radiotherapy center.

Informed consent: as a medical team, we communicated with the patient and informed him about our intention to publish his case. He was consentient and aware of the fact that his identity will be respected and preserved, also that there may be no benefits from this publication.

Discussion     

The PDTC was first described in 1983 as a carcinoma whose behavior was intermediate between well-differentiated thyroid carcinomas (WDTC) and anaplastic thyroid carcinoma (ATC) in terms of its clinical evolution and pathological features defined as a thyroid-globulin-producing non-follicular non-papillary carcinoma. It is considered a histological entity since 2004 according to the WHO classification of endocrine organ tumors [1]. This classification situated the PDTC between the WDTC and the ATC as an intermediate histological type. However, this classification was based on both architectural and high-grade features, which means a non-follicular and non-papillary growth pattern on the first hand, and a high mitotic index, invasive growth, and necrosis on the other hand [4]. Since then, the diagnostic criteria were debated as the old criteria were overlapped by other tumors with the same features or pattern of growth. A proposal was established by the Memorial Sloan Kettering Cancer Center (MSKCC) in 2006, which excluded the growth pattern from the criteria, and defined the PDTC based on the mitotic index and the presence of necrosis in a tumor with pathological or immunohistochemical evidence of follicular differentiation; this definition was adopted by the Turin proposal to set universal diagnosis criteria [2,5]. Since then, the diagnosis criteria are: 1) solid or trabecular or insular growth pattern; 2) lack of nuclear features of papillary thyroid carcinoma required; 3) at least one of the following three features: mitotic index ≥3/10 HPFs, tumor necrosis, convoluted nuclei. Also, those criteria were adopted by the WHO in their classification of tumors of endocrine organs in 2017 [6].

As the diagnosis is established, adequate staging is required to decide about the treatment. The latest staging system commonly used is the American Joint Committee on Cancer and UICC staging system, it replaced the 7^th edition of the AJCC/UICC staging system, and it had proven efficiency in terms of survival. Some variables were adjusted in the 8^th edition to improve the discrimination between patients and was based on the epidemiological observations and the clinical evidence. However, the current stratifications and studies concern Differentiated Thyroid carcinoma (DTC), but still it could be used on ATC and PDTC. These are staged as IV straight away [3].

The American Thyroid Association has defined an algorithm as recommendations to treat thyroid carcinomas based on the stages of the tumor. As the PDTC was staged VI, the first option was surgery as far as it was resectable, however, if not, the new guidelines preconize genetic testing to look for a genetic mutation on the BRAFV600E gene [7]. Tumors with a BRAFV600E mutation showed an excellent response to Dabrafenib/Trametinib - which was a kinase inhibitor for BRAF mutation - with an overall response rate of 65% in multiple results reported [8,9]. The surgery after treatment was always indicated if possible. This aggressive multimodal treatment based on kinase inhibitors combined with surgery is now recommended by the ATA and showed a decent outcome of ATC and PDTC in terms of survival, in front of the refractoriness of those carcinomas to radio-Iodine. An experimental study conducted on ATC and PDTC patient-derived cells by Sabine Wächter et al. consists of examining the efficacy of two different tyrosine kinase inhibitors and histone deacetylase inhibitor (HDACI) panobinostat. It showed a reduction of cell-viability after prolonged treatment with sorafenib-selumetinib and panobinostat by nearly 100%, also regulated the radio-iodine retention in comparison with dabrafenib-trametinib [10].

Poorly differentiated thyroid carcinoma should also be a subject of a systematized algorithm, to help teams take charge and care the patients with this type of tumor, which is not available in the literature as it is a new entity of thyroid cancers. However, as with all cancers, the treatment remains multidisciplinary between laryngologists, oncologists, neurosurgeons, and endocrinologists.

Conclusion     

Our case was introduced in an interdisciplinary consultation meeting, which opted to a radiotherapy for the cerebral metastasis since the patient was not operable anymore. Our patient presented a quick evolution of the disease, with asymptomatic secondary locations, all those factors give evidence of the aggressiveness of the PDTC, less than the ATC but widely more than the DTC. We also put the light on the efficiency of the tyrosine kinase inhibitors combined with surgery as an aggressive approach, which is recommended by the ATA. Also, this topic is still a subject of experimental studies, studying the histone deacetylase inhibitor as a potential therapy of PDTC.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All the authors have read and agreed to the final manuscript.

Figures     

Figure 1: voluminous goiter with tracheal deviation

Figure 2: mediastinal and pulmonary metastasis 1

Figure 3: mediastinal and pulmonary metastasis 2

Figure 4: posterior cerebral fossa secondary location

References