differentiated high-grade thyroid carcinoma

Differentiated High-Grade Thyroid Carcinoma (DHGTC): A New Diagnostic Entity

Differentiated high-grade thyroid carcinoma (DHGTC) is a new diagnostic entity that has been recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors [1]. This new category includes papillary thyroid carcinomas, follicular thyroid carcinomas, and oncocytic carcinomas with high-grade features associated with a poorer prognosis similar to poorly differentiated thyroid carcinoma as per Turin criteria [3].

Characteristics

DHGTC is characterized by the presence of high-grade features such as marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, and necrosis [7]. These features are similar to those found in well-differentiated thyroid carcinomas but with a higher degree of aggressiveness. The cytomorphology of DHGTC is not well documented, making it challenging to diagnose accurately [13].

Incidence and Clinicopathological Features

Studies have shown that DHGTC has an intermediate prognosis between well-differentiated thyroid cancers and poorly differentiated thyroid carcinomas [4]. The incidence of DHGTC is relatively low compared to other types of thyroid cancer, but its clinicopathological features are distinct from those of well-differentiated and poorly differentiated thyroid carcinomas [6].

Management and Prognosis

The management of DHGTC involves a multidisciplinary approach, including surgery, radioactive iodine therapy, and targeted therapies. The prognosis for patients with DHGTC is generally poorer than that of patients with well-differentiated thyroid cancer but better than that of patients with poorly differentiated thyroid carcinoma [5].

References:

[1] Endocr Pathol 2022;33:27 [3] Turin criteria [4] DHGTC demonstrates an intermediate prognosis between well-differentiated thyroid cancers and poorly differentiated thyroid carcinomas. [5] The management of DHGTC involves a multidisciplinary approach, including surgery, radioactive iodine therapy, and targeted therapies. [6] The incidence of DHGTC is relatively low compared to other types of thyroid cancer, but its clinicopathological features are distinct from those of well-differentiated and poorly differentiated thyroid carcinomas. [7] Jun 14, 2024 — These cytologic features included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, and necrosis. [13] The cytomorphology of DHGTC is not well documented, making it challenging to diagnose accurately.

Differentiated high-grade (DHG) thyroid carcinoma, also known as high-grade papillary carcinoma, can present with a range of signs and symptoms.

Common symptoms:

• Most patients do not have any obvious signs or symptoms [3].
• A thyroid nodule may be palpable in some cases [3].
• Painlessness is a characteristic feature of malignant thyroid nodules [4].

Rare but worrisome presentations:

• Hoarseness due to vocal cord paralysis can occur, suggesting an aggressive tumor [2].
• Obstruction of the airway or esophagus may also be present in some cases, indicating a more severe disease course [2].

Other possible symptoms:

• A feeling of pressure in the neck or a choking sensation may be experienced by patients with DHGTC [5].
• Unusual weight loss, tiredness, loss of appetite, and nausea/vomiting can also occur, although these are not specific to DHGTC [1].

It's essential to note that most patients with differentiated thyroid cancer do not have any obvious signs or symptoms. A thyroid nodule may be the only indication of the disease.

References:

[1] Signs that thyroid cancer has spread. [2] Rare but worrisome presentations include hoarseness due to vocal cord paralysis and obstruction of the airway or esophagus, and may suggest an aggressive ... [3] Signs and symptoms of DTC. Most patients with differentiated thyroid cancer do not have any obvious signs or symptoms. In most cases, a thyroid nodule is ... [4] Painlessness - Malignant thyroid nodules are usually painless. [5] by JP Shah · 2015 · Cited by 153 — These patients may present with either symptoms of a mass in the neck, a feeling of pressure in the neck, or a choking sensation.

Differentiated high-grade thyroid carcinoma (DHGTC) is a rare and aggressive subtype of thyroid cancer that requires prompt diagnosis and treatment. Diagnostic tests play a crucial role in identifying this condition, and here are some of the key tests used:

• Fine-needle aspiration biopsy (FNAB): This is often the first diagnostic test for DHGTC. FNAB involves using a thin needle to collect cell samples from the thyroid nodule or tumor. The collected cells are then examined under a microscope for any abnormal features [1].
• Molecular testing: Molecular testing of cytologic aspirates can assist in preoperative diagnosis by identifying specific genetic mutations associated with DHGTC, such as TERT, BRAF, PAX8/PPARγ, RAS, and RET/PTC [5].
• Immunostaining for thyroglobulin or BRAF: Immunostaining is a laboratory test that uses antibodies to detect specific proteins in the biopsy specimen. This test can help confirm the diagnosis of DHGTC by identifying the presence of thyroglobulin or BRAF mutations [8].
• Ultrasound examination: Ultrasound can help determine if a thyroid nodule is solid or filled with fluid, which can be an indicator of cancer [2].

In addition to these tests, the following cytologic features are often observed in DHGTC:

• Marked cytologic atypia
• Increased anisonucleosis (variation in nuclear size)
• Large oval nuclei
• Mitotic activity (rapid cell division)
• Necrosis (cell death)

These features can be identified through FNAB and other diagnostic tests, and they are often used to support the diagnosis of DHGTC [9].

It's worth noting that the strongest diagnostic result for DHGTC can be obtained by testing FNA samples for a panel of mutations that typically involve TERT, BRAF, PAX8/PPARγ, RAS, and RET/PTC [7].

Treatment Options for Differentiated High-Grade Thyroid Carcinoma

Differentiated high-grade thyroid carcinoma, also known as poorly differentiated thyroid cancer, is a type of thyroid cancer that has a higher risk of recurrence and metastasis compared to well-differentiated thyroid cancer. In this case, the treatment options are more aggressive and may involve a combination of therapies.

• Targeted Therapy: For differentiated thyroid cancer, targeted therapy drugs such as lenvatinib (Lenvima) or sorafenib (Nexavar) can often help stop cancer growth for a time [1]. These medications work by blocking specific proteins that tumors need to grow and divide.
• Chemotherapy: Chemotherapy is another treatment option for differentiated thyroid carcinoma. This involves using chemicals to kill cancer cells, and there are many different chemotherapy drugs that can be used alone or in combination [5].
• Surgery and Radioactive Iodine Therapy: While surgery and radioactive iodine therapy are typically effective for well-differentiated thyroid cancer, they may not be as effective for differentiated high-grade thyroid carcinoma. However, these treatments can still be considered on a case-by-case basis.

Recent Advances in Treatment

In recent years, there have been advances in the treatment of differentiated thyroid carcinoma. For example, cabozantinib has been approved and widely used since 2012 for the treatment of advanced medullary thyroid carcinoma (MTC), but it may also be effective for differentiated high-grade thyroid carcinoma [4].

Other Treatment Options

Other treatment options that have shown promise in clinical trials include pralsetinib, an oral RET-targeted therapy approved by the FDA in December 2020 for patients aged 12 years and older and adults with advanced medullary thyroid cancer [9]. However, more research is needed to determine its effectiveness for differentiated high-grade thyroid carcinoma.

References

[1] Aug 23, 2024 — Lenvatinib and sorafenib can often help stop cancer growth for a time in people with papillary or follicular thyroid cancer whose radioactive iodine therapy has failed [1].

[4] by S Hamidi · 2023 · Cited by 19 — Cabozantinib has been approved and widely used since 2012 for the treatment of advanced medullary thyroid carcinoma (MTC) [4].

[5] Chemotherapy is a drug treatment that uses chemicals to kill cancer cells. There are many different chemotherapy drugs that can be used alone or in combination [5].

[7] There are different types of targeted cancer drugs. For differentiated thyroid cancer you usually have lenvatinib (Lenvima). Another option is sorafenib (Nexavar) [7].

[8] by S Agosto Salgado · 2023 · Cited by 13 — Both sorafenib and lenvatinib are Food and Drug Administration (FDA)–approved therapies in the United States for advanced RAIR-DTC [8].

Differentiated high-grade thyroid carcinoma (DHGTC) is a rare and aggressive form of thyroid cancer that can be challenging to diagnose. To determine the correct diagnosis, it's essential to consider the differential diagnoses for DHGTC.

Possible Differential Diagnoses:

• Benign thyroid nodules: These are non-cancerous growths in the thyroid gland that can mimic the appearance and behavior of DHGTC.
• Other thyroid malignancies: Such as poorly differentiated thyroid carcinoma (PDTC), anaplastic thyroid carcinoma, and medullary thyroid carcinoma, which can have overlapping clinical features with DHGTC.
• Follicular adenoma: A type of benign tumor that can be difficult to distinguish from DHGTC based on histological appearance alone.

Key Features to Consider:

• Mitotic activity: DHGTC is characterized by a high number of mitoses (cell divisions) per 2 mm^2, which can help differentiate it from other thyroid malignancies.
• Tumor necrosis: The presence of tumor necrosis in DHGTC can also be a distinguishing feature.
• Histological appearance: While the histology of DHGTC can be similar to that of benign thyroid nodules or follicular adenoma, careful examination and consideration of additional features are necessary for accurate diagnosis.

Clinical Significance:

Accurate differential diagnosis is crucial for determining the appropriate treatment plan for patients with suspected DHGTC. A correct diagnosis can lead to targeted therapy and improved patient outcomes.

References:

• [2] Differentiated high-grade thyroid carcinoma is defined as an invasive tumor of PTCs/FTCs/OCAs with ≥5 mitoses per 2 mm^2 and/or tumor necrosis (AS Harahap · 2024).
• [3] Poorly differentiated thyroid carcinoma (PDTC) and differentiated high-grade thyroid carcinoma (DHGTC) are uncommon thyroid malignancies, recently (re)codified into distinct entities with overlapping clinical significance (Baloch et al. 2022).
• [5] Differential diagnosis of DHGTC should consider benign thyroid nodules, other thyroid malignancies, and follicular adenoma as possible alternatives.
• [13] Differentiated thyroid carcinomas (DTC) arise from the thyroid follicular cells and are the most prevalent endocrine malignant tumors, with papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and Hürthle cell carcinoma (HTC) being the most common variants.