Pathology
Thyroid cancer is a malignant tumor that originates from the cells of the thyroid gland, an endocrine organ located in the anterior neck, just below the thyroid cartilage. The thyroid has a characteristic butterfly shape: the two lateral lobes lie on either side of the larynx, while the central portion connecting them is known as the isthmus.
The thyroid gland produces hormones essential for regulating metabolism, heart rate, body temperature, and, in children, normal physical and cognitive development.
Thyroid cancer most commonly affects women between the ages of 40 and 60 and represents the second most frequent malignancy in women under 50.
The Numbers in Italy
According to data from the AIRTUM registry, approximately 11,378 new cases of thyroid cancer were diagnosed in Italy in 2024, including 8,322 women and 3,056 men.
The incidence of thyroid cancer has increased in recent decades, largely due to the more widespread use of diagnostic ultrasound. This has led to the detection of very small thyroid nodules, some of which may be clinically indolent and not clinically significant.
Types
Thyroid cancer includes several histological subtypes:
- Well-differentiated forms (papillary and follicular): approximately 85–90% of cases
- Poorly differentiated carcinoma: approximately 5–7% of cases
- Medullary carcinoma: approximately 5–7% of cases
- Undifferentiated (anaplastic) carcinoma: approximately 2–3% of cases; the most aggressive form
In addition to traditional histological classification, current clinical practice increasingly considers the molecular characteristics of tumors, which can help guide more personalized treatment strategies. Prognosis depends on both tumor type and the presence of specific molecular alterations. Well-differentiated forms generally have an excellent prognosis, whereas poorly differentiated, medullary, and anaplastic forms require more complex and individualized therapeutic approaches.
Symptoms
Thyroid nodules typically do not affect thyroid function, and many patients remain asymptomatic.
The most common clinical finding is the presence of a palpable nodule in the thyroid gland, detected in the anterior neck region. It is important to emphasize that the majority of thyroid nodules are benign; only about 5–10% correspond to malignant tumors.
In rarer cases, particularly in more aggressive forms, the disease may present as a rapidly enlarging neck mass involving the thyroid gland and laterocervical lymph nodes. Even in less aggressive tumors, lymph node involvement may occur; therefore, careful ultrasound evaluation is essential, especially in younger patients.
Risk Factors
Thyroid cancer is more common in women, with a female-to-male ratio of approximately 4:1.
Known risk factors include:
- Iodine deficiency, which may lead to goiter (enlargement of the thyroid gland) and the development of multiple nodules, some of which may undergo malignant transformation
- Exposure to ionizing radiation, particularly during childhood or adolescence, including prior radiotherapy to the neck or exposure to radioactive fallout. For this reason, unnecessary medical radiation exposure (e.g., CT scans or X-rays involving the neck region) should be carefully evaluated in younger patients
- Family history, especially in hereditary forms of medullary thyroid carcinoma, which may occur as part of multiple endocrine neoplasia (MEN) syndromes. These are often associated with mutations in the RET oncogene, which can be inherited
Family members of patients with medullary thyroid carcinoma are advised to undergo specialist evaluation and genetic testing to assess the presence of RET mutations associated with hereditary disease.
Diagnosis and Evaluation
At the Candiolo Cancer Institute, the diagnostic pathway for suspected thyroid cancer begins with a specialist clinical evaluation involving ENT surgeons, general surgeons, and endocrinologists.
During the initial assessment, thyroid function tests are reviewed if already available, or prescribed if necessary. All patients undergo neck ultrasound as a first-line imaging examination. When indicated, further diagnostic investigations are performed, including advanced imaging studies and interventional procedures such as ultrasound-guided fine-needle aspiration biopsy (FNAB) to obtain cytological confirmation.
Neck Ultrasound
Neck ultrasound is a noninvasive, readily available imaging examination that provides high-resolution visualization of the thyroid gland.
It allows clinicians to:
- Detect even very small thyroid nodules that cannot be identified on physical examination
- Assess nodule size and morphological characteristics
- Evaluate the surrounding thyroid tissue
- Examine cervical lymph nodes for possible pathological involvement
Because of its accuracy and safety, neck ultrasound is a fundamental first-line tool in the diagnostic evaluation of thyroid disease.
Fibrolaryngoscopy
Fibrolaryngoscopy is an endoscopic examination that may be performed by the ENT specialist to assess vocal cord mobility and identify any structural or surface abnormalities.
The procedure is carried out using a flexible fiber-optic endoscope. This thin, flexible tube is gently inserted through the patient’s nasal cavity, allowing the physician to obtain a direct and detailed view of the larynx and surrounding structures.
Fibrolaryngoscopy is performed in an outpatient ENT setting and is generally well tolerated. It can be conducted without anesthesia or, when necessary, with the application of local anesthesia to improve patient comfort.
Thyroid Scintigraphy
Thyroid scintigraphy is a nuclear medicine imaging technique used to evaluate the functional activity of one or more thyroid nodules and to help differentiate between hyperfunctioning (often benign) and non-functioning lesions.
The examination involves the intravenous administration of a small amount of radioactive tracer, typically technetium-99m (99mTc) pertechnetate, which is taken up by thyroid tissue. The radiation emitted is detected by a gamma camera, which generates an image of the thyroid gland showing the distribution and functional activity of the tracer within the tissue.
This allows clinicians to distinguish different types of nodules based on their uptake patterns and functional behavior.
The procedure is simple, noninvasive, and painless. The administered radiopharmaceutical is generally well tolerated and does not cause allergic reactions.
CT and MRI of the Neck and Thorax
Computed tomography (CT) and magnetic resonance imaging (MRI) of the neck and thorax are advanced radiological examinations that may be required to obtain a more detailed assessment of the extent of thyroid disease.
These imaging techniques provide high-resolution information on the primary tumor, its relationship with adjacent anatomical structures, and any possible involvement of regional lymph nodes or mediastinal structures. They are particularly useful in cases where a more comprehensive evaluation is needed for accurate staging and treatment planning.
Parathyroid Scintigraphy and PET Scan
Parathyroid scintigraphy using 99mTc-sestaMIBI and PET imaging with 18F-Choline are advanced diagnostic examinations that may be indicated when ultrasound findings or laboratory tests suggest morphological or functional abnormalities of the parathyroid glands.
The parathyroid glands are small, oval-shaped endocrine structures located near the thyroid gland, and in some cases may be found within the thyroid tissue or in the mediastinum.
These imaging techniques are used to localize abnormal parathyroid tissue and to support the diagnosis and preoperative planning in patients with suspected parathyroid disease.
Fine-Needle Aspiration (FNA)
If ultrasound examination identifies suspicious thyroid nodules, it may be necessary to obtain a cellular sample to determine whether the lesion is benign or malignant. This procedure, known as fine-needle aspiration (FNA), is typically performed within a few days of the specialist consultation.
FNA is an outpatient procedure that does not require anesthesia. Under ultrasound guidance, a thin needle is inserted into the suspicious nodule to collect a small number of cells. These samples are then analyzed by a pathologist through cytological examination to assess their characteristics and establish a definitive diagnosis.
Cytological Examination
Cytological examination refers to the analysis of cellular material obtained from thyroid nodules, usually through fine-needle aspiration. Its primary purpose is to determine whether a nodule is benign, which is the most common finding, or malignant. When malignancy is confirmed or suspected, the pathologist further characterizes the tumor type and its specific features.
Thyroid cancers are broadly classified into three main categories:
- Differentiated carcinoma, which includes papillary and follicular subtypes
- Medullary carcinoma
- Undifferentiated (anaplastic) carcinoma
Papillary and follicular differentiated carcinomas are the most frequent, accounting for approximately 75% and 15% of thyroid cancer cases respectively, and are associated with a very favorable prognosis, with long-term survival rates reaching around 90% at 20 years after diagnosis.
Medullary carcinoma represents approximately 5–10% of thyroid cancers. In about 25% of cases, it is associated with a hereditary mutation of the RET gene. This tumor has a tendency to spread to other organs, although outcomes can still be favorable depending on the stage at diagnosis.
Anaplastic carcinoma is rare (approximately 1–3% of cases) but represents the most aggressive and difficult-to-treat form of thyroid cancer.
The cytology report also provides an assessment of the risk of malignancy using the TIR classification system, which ranges from 1 to 5:
- TIR 1: Inadequate sample; insufficient cellular material for diagnosis. Repeat fine-needle aspiration is usually recommended, except in cystic lesions (TIR 1C).
- TIR 2: Benign nodule.
- TIR 3 (A and B): Indeterminate or non-diagnostic findings; histological examination of tissue is required for further evaluation.
- TIR 4: Suspicious for malignancy.
- TIR 5: Malignant nodule.
Therapies
Once cytology results are available, each case is systematically reviewed within the GIC (Interdisciplinary Care Group), which includes surgeons, endocrinologists, nuclear medicine physicians, and radiologists. This multidisciplinary evaluation is essential for defining an individualized treatment strategy for each patient.
Therapeutic decisions are based on multiple factors, including tumor type and extent, potential treatment-related side effects, and the patient’s overall clinical condition and comorbidities. After the most appropriate care pathway has been established, the treating physician discusses the available options with the patient in detail, ensuring a clear and shared understanding of the proposed plan.
For selected patients with particularly aggressive disease who have not responded adequately to standard treatments, participation in clinical trials may be considered. These studies, conducted by the institute’s research teams, offer access to experimental therapies under strict scientific and ethical oversight. When appropriate, this option is presented by the multidisciplinary team and discussed with the patient to support a fully informed and shared decision-making process.
Surgical Treatment
Surgery is typically the first planned therapeutic approach and may be followed by adjuvant treatments aimed at reducing the risk of metastasis or disease recurrence after the operation.
In most cases, a total thyroidectomy is preferred, involving complete removal of the thyroid gland. However, when the malignant nodule is small and well localized, a more conservative approach such as lobectomy may be performed, consisting of removal of only the affected lobe of the gland.
Thyroidectomy is carried out through a transverse incision in the anterior neck region. During the procedure, the surgeon may perform intraoperative assessment of suspicious nodules or adjacent lymph nodes to optimize surgical completeness and reduce the need for further intervention.
To minimize complications, recurrent laryngeal nerve monitoring is routinely used during surgery. These nerves are responsible for vocal cord movement, and their preservation is essential to avoid postoperative complications. Injury to these structures may result in voice alterations and, in some cases, breathing difficulties.
Complementary (Adjuvant) Therapies
Complementary, or adjuvant, therapies are administered after surgery in cases of more aggressive thyroid cancers that carry a higher risk of recurrence or have a tendency to spread to other organs.
The main adjuvant treatments for thyroid cancer include radioiodine therapy and biological (targeted) therapies.
These treatments are selected based on the pathological characteristics of the tumor and the patient’s overall clinical profile, with the aim of reducing the risk of disease recurrence and improving long-term outcomes.
Radioiodine Radiometabolic Therapy
Radioiodine radiometabolic therapy is indicated in cases of papillary or follicular thyroid carcinoma that have extended to surrounding tissues, cervical lymph nodes, or distant organs, as well as in tumors with aggressive histological features.
The aim of this treatment is to eliminate any residual thyroid tissue or microscopic cancer cells that may remain after surgery. It consists of the oral administration of radioactive iodine (I-131), which is selectively taken up by thyroid cells, both benign and malignant. The emitted radiation leads to the destruction of these cells through local energy release.
Treatment generally requires a short hospital stay in a Nuclear Medicine Unit, during which patients are isolated to allow for the safe decay and elimination of the radiopharmaceutical, primarily through natural bodily excretion.
Biological (Molecularly Targeted) Therapies
Biological therapies, also known as targeted or molecularly targeted therapies, are drugs designed to act on specific molecular alterations involved in tumor growth and progression. These agents selectively interfere with key signaling pathways present in cancer cells, inhibiting one or more mechanisms that drive tumor development.
They are typically indicated in rare cases where radioiodine therapy is no longer effective, as well as in advanced or metastatic thyroid cancer.
The selection of the most appropriate targeted therapy is based on the histological characteristics of the tumor and, in particular, on its molecular profile, including the presence of specific genetic mutations. This approach allows for a more personalized and precise treatment strategy.
Ongoing Support
At the Candiolo Cancer Institute, patients receive continuous support before, during, and after treatment, ensuring comprehensive assistance throughout the entire care pathway.
This ongoing support is designed to accompany each patient through diagnosis, therapy, and recovery, with close coordination among all members of the GIC (Interdisciplinary Care Group). The goal is to provide continuity of care, timely clinical responses, and individualized guidance at every stage of the treatment journey.
Psychological Support
A cancer diagnosis has a profound impact not only on physical health but also on psychological well-being. It is a life-changing event that can affect all aspects of a person’s experience and may lead to anxiety, fear, anger, sadness, or depression.
At the Candiolo Cancer Institute, alongside advanced medical treatments, the care pathway includes dedicated psycho-oncological support. This service is designed to help patients cope constructively with both treatment and the often complex emotional and psychological phases of recovery.
Patients also have the opportunity to take part in psychological support groups, where they can share experiences with others facing similar challenges. These groups provide a space for mutual support, helping to reduce feelings of isolation and fostering emotional resilience throughout the treatment journey.
Direct Line to Specialists
To ensure timely and direct support and provide prompt answers to patients’ concerns and questions, the Candiolo Cancer Institute offers a dedicated helpline service.
From Monday to Friday, between 8:00 a.m. and 5:00 p.m., patients can contact the Oncology Day Hospital Secretariat at +39 011 993 3775 to request an urgent consultation.
Patients are then rapidly connected with their treating specialist, ensuring clear communication, immediate support, and continuity of care whenever needed.
Supportive and Palliative Care
The cancer patient presents complex needs that require multidisciplinary support extending beyond the treatment of the disease itself, encompassing all related physical and psychological aspects.
At the Candiolo Cancer Institute, patients who require or request it have access to a wide range of specialist services, including nutritional support, physical therapy, pain management, and the treatment of other associated conditions.
This integrated approach ensures comprehensive and continuous care aimed at improving quality of life and supporting patients throughout all stages of their disease and treatment journey.
Social Work Support
The Social Service Department of the Candiolo Cancer Institute provides information and guidance for patients and their families on how to access local services and available welfare and social security benefits предусмотрed by law, including disability support, assistance for aids and prostheses, and work-related leave.
The service offers orientation interviews to help patients navigate administrative and social support systems and is available on Wednesdays and Fridays from 9:00 a.m. to 1:00 p.m. (Tel. +39 011 993 3059).
Follow-up
Following completion of the treatment course, patients enter a structured follow-up phase consisting of a long-term monitoring program tailored to the individual. The schedule is based on the type of thyroid cancer, patient age, and the estimated risk of recurrence.
Although most thyroid tumors have a low risk of recurrence, follow-up is essential because disease relapse may occur even many years after initial diagnosis. For this reason, periodic check-ups are recommended throughout the patient’s lifetime.
During follow-up visits, the patient’s clinical condition is assessed and the results of any required tests are reviewed. These typically include blood tests and neck ultrasound. In selected cases, additional investigations such as radioiodine scintigraphy or second-level imaging exams (CT, PET, or MRI) may be indicated.
Patients who have undergone total thyroidectomy require lifelong hormone replacement therapy. This treatment replaces the hormones normally produced by the thyroid gland, which are essential for regulating multiple vital bodily functions. Hormone therapy is administered orally on a daily basis.
Multi Disciplinary Team
Every cancer requires a multidisciplinary approach at all stages of disease management. At the Candiolo Cancer Institute, this is provided by a team of specialists from various clinical and surgical departments, known as the GIC, Interdisciplinary Care Group (or MDT). The GIC ensures that each patient is supported throughout the diagnostic and therapeutic process, including arranging and coordinating examinations and maintaining communication with the patient and their family.
For each patient, the GIC (MDT) defines and shares a personalized care pathway based not only on the type and stage of the tumor but also on the patient’s individual characteristics. The goal is to achieve the best possible outcomes both oncologically and functionally, while maintaining a high quality of life.
The Group also collaborates closely with the Institute’s researchers to provide patients with rapid access to the latest innovations in screening, diagnosis, and treatment.
Clinical Divisions
The diagnostic and therapeutic pathway for thyroid and endocrine gland cancers at the Candiolo Cancer Institute is managed through a multidisciplinary approach involving several clinical divisions, including:
- Oncologic Surgery
- Otolaryngology
- Anesthesia and Resuscitation
- Medical Oncology
- Nuclear Medicine
- Radiotherapy
- Radiodiagnostics
- Anatomical Pathology
Research and Innovation
At the Candiolo Cancer Institute, key areas of research in thyroid cancer include the development and application of advanced diagnostic and molecular techniques.
These include the use of state-of-the-art technologies that enable detailed analysis of tumor DNA and RNA. In more complex cases, molecular investigations are performed to support the identification and classification of previously uncharacterized or difficult-to-classify tumor subtypes.
Another important area of research is the identification of novel molecular markers, biological indicators detectable in blood or tissue that are associated with the development and progression of thyroid malignancies. These markers can improve the preoperative assessment of thyroid nodules and help refine the evaluation of malignancy risk.
In addition, researchers analyze specific genetic mutations linked to more aggressive forms of thyroid cancer. By studying samples from indeterminate or complex nodules, it is possible to better characterize tumor behavior, assess its potential aggressiveness, and support more personalized treatment strategies tailored to the biological features of the disease.
Why Choose Us
At the Candiolo Cancer Institute, each patient with head and neck cancer is managed according to highly specialized clinical standards, supported by the coordinated work of a dedicated Interdisciplinary Care Group (GIC).
Clinical Experience and Tailored Approach
Due to the high number of cases treated each year, the Candiolo Cancer Institute is a national reference center for the management of esophageal cancer. This extensive clinical experience enables the institute to address even the most complex cases, consistently applying a personalized approach tailored to each patient’s clinical condition and individual profile.
Imaging Technologies and Advanced Diagnostics
Establishing the treatment plan always begins with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that enable a precise assessment of the extent of the disease.
In addition, the Candiolo Cancer Institute provides advanced laboratory investigations, including molecular and genomic analyses, which are essential for identifying the biological characteristics of cancer and guiding therapeutic decision-making.
Minimally Invasive Surgical Techniques and Multidisciplinarity
When indicated, surgery is performed using minimally invasive techniques, such as laparoscopic or thoracoscopic approaches. These methods reduce operative trauma, promote faster recovery, and improve postoperative quality of life.
Every treatment decision is defined within the GIC (Interdisciplinary Care Group), ensuring a consistent, coordinated, and fully integrated approach to patient management at the Candiolo Cancer Institute.
Clinical Research and Access to Trials
As an IRCCS, the Candiolo Cancer Institute integrates clinical practice with a strong commitment to scientific research. Patients may be evaluated for inclusion in active clinical trials, which provide access to innovative therapies not yet available in standard clinical practice.
This close collaboration between clinical care and research represents a distinctive strength of the institute and translates into concrete opportunities for eligible patients.
Care and Support Every Step of the Way
The Interdisciplinary Care Group (GIC) of the Candiolo Cancer Institute supports patients at every stage of the care pathway, from diagnosis through treatment to follow-up, ensuring a fully integrated and continuous approach.
Particular attention is given to nutritional support, psychological well-being, and reintegration into daily life. The organization of examinations, clinical visits, and treatments is structured to ensure continuity of care and a smooth, well-coordinated experience.
Throughout the entire process, emphasis is placed on the human dimension of care, with the aim of providing reassurance, consistency, and comprehensive support for patients and their families.