Tuesday, February 27, 2024

Poorly Differentiated Thyroid Cancer Prognosis

Analysis Of Clinical Outcome Of Patients With Poorly Differentiated Thyroid Carcinoma

Poorly Differentiated Carcinoma of the Thyroid with Dr. Margaret Brandwein

Katsuhiro TanakaAcademic Editor: Received


Background. We retrospectively analyzed whether poor differentiation is the independent prognostic factor for thyroid carcinoma or not. Methods. The subjects were 29 patients with PDTC who were treated between April 1996 and March 2006 to compare with those of well-differentiated papillary carcinoma patients . Results. The relapse free , distant relapse-free survival and cause-specific survival, rates were significantly lower in patients with PDTC . After classification into focal and diffuse type of PDTC, there were no significant differences in RFS and cause-specific survival due to component type or proportion of poorly differentiated component. On multivariate analysis, poor differentiation and extrathyroidal infiltration showed a significant impact on DFS, and poor differentiation and age significantly impacted cause-specific survival. . Poor differentiation was an independent factor for survival. Distant relapse was significantly more common among PDTC patients, and systemic therapy might be warranted.

1. Introduction

We retrospectively analyzed the outcome of patients with poorly differentiated thyroid carcinoma who were initially treated in our hospital between April 1996 and March 2006. Furthermore, we compared findings with those of well-differentiated papillary carcinoma patients who underwent surgery during the same period in order to evaluate the characteristics of the subjects.

2. Patients and Methods

Standard Treatment Options For Papillary And Follicular Thyroid Cancer

Localized/regional papillary and follicular thyroid cancer

Surgery is the therapy of choice for all primary lesions. Surgical optionsinclude total thyroidectomy or lobectomy. The choice of procedure isinfluenced mainly by the age of the patient and the size of the nodule. Survival results with the two procedures are similar for early-stage disease, with differences in the ratesof surgical complications and local recurrences.

Standard treatment options for localized/regional papillary and follicular thyroid cancer

Standard treatment options for localized/regional papillary and follicular thyroid cancer include the following:

  • External-beam radiation therapy .
  • Surgery

    The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with RAI. The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning. For patients undergoing RAI, removal of all normal thyroid tissue is an important surgical objective. Additionally, for accurate long-term surveillance, RAI whole-body scanning and measurement of serum thyroglobulin are affected by residual, normal thyroid tissue, and in these situations, near total or total thyroidectomy is required. This approach facilitates follow-up thyroid scanning.

    Total thyroidectomy

    Evidence :

    Radioactive iodine therapy

    Evidence :

    What Is A 5

    A relative survival rate compares people with the same type and stage of thyroid cancer to people in the overall population. For example, if the 5-year relative survival rate for a specific stage of thyroid cancer is 90%, it means that people who have that cancer are, on average, about 90% as likely as people who dont have that cancer to live for at least 5 years after being diagnosed.

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    Cellular Classification Of Thyroid Cancer

    In thyroid cancer, cell type is an important determinant of prognosis and treatment. The thyroid has two cell types: follicular cells and parafollicular C cells. The management of thyroid cancer depends on the cell of origin and how well the integrity of the cell type is maintained. The four main types of thyroid cancer are divided into the following two categories for clinical management:

    Differentiated thyroid cancers.

  • Well-differentiated.
  • Hürthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis.
  • Poorly differentiated.
  • Parafollicular C cell thyroid cancers.

  • Medullary thyroid carcinoma.
  • Other types .

  • Carcinosarcoma.
  • References
  • LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Lippincott-Raven, 1997, pp 127-175.
  • Kushchayeva Y, Duh QY, Kebebew E, et al.: Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195 : 457-62, 2008.
  • Mills SC, Haq M, Smellie WJ, et al.: Hürthle cell carcinoma of the thyroid: Retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003. Eur J Surg Oncol 35 : 230-4, 2009.
  • Specificity Of Diagnosis In Pdtc


    Ultimately, the recent reclassification of PDTC is intended to improve patient care, with more uniform, accurate reporting. Importantly, the criteria exist to link objective findings with clinical outcomes, biological potential, and hopefully, following additional study, molecular mechanisms with targeted treatment modalities and improved outcomes. For instance, oncocytic neoplasms were excluded in the Turin proposal. However, in a recent validation by the Mayo group in collaboration with the Turin group, about 1/3 of tumors had oncocytic features . Also, a very recent study reviewing a large cohort of aggressive thyroid carcinomas identified 18 oncocytic PDTC . However, this group does not distinguish the 18 oncocytic PDTC from other oncocytic carcinomas present among the 129 cases, and the majority of these cases were included due to necrosis, in addition to STI growth pattern. What constitutes convoluted nuclei in this group , with oncocytic nuclei generally thought of as round with prominent, centrally located nucleoli, is unclear.

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    Outcome Of Pdtc Patients Stratified By Tg Group

    In our cohort of 38 PDTC patients, 14 died , with 9 deaths being specifically related to the disease . The number of disease-related deaths was significantly higher in the group with detectable Tg . In the first year of follow-up, deaths were observed in 13% of the patients in the group with detectable Tg levels compared with no deaths in the group with undetectable Tg .

    There were 14 cases of recurrence : 7 locoregional and 7 metastatic. Patients with detectable Tg levels had a significant increase in recurrent disease . Both locoregional and distant recurrence were significantly increased in the group with detectable Tg levels . In the first year of follow-up, recurrence was observed in 50% of the group with detectable Tg levels and in 12.5% of the group with undetectable Tg levels . These 2 patients with early recurrence despite negative Tg levels both had a status of pT4, with the largest tumor diameters of 52 and 60 mm with tracheal invasion in one case and positive N1a status in the other.

    After a median follow-up of 7.35 years , a trend towards a lower 5-year OS was observed in patients with detectable Tg . As shown in Figure 1, patients with detectable Tg had a significant decrease in 5-year DSS , a significant decrease in 5-year RFS , a significant decrease in 5-year regional control , as well as a decrease in 5-year distant control .

    Fig. 1.

    For additional information:

    Variable Response To Radioactive Iodine Treatment In Poorly Differentiated Thyroid Carcinoma

    Hunter J. Underwood1, Ashok R. Shaha2, Kepal N. Patel1

    1Division of Endocrine Surgery, NYU Langone Health, New York, NY , USA

    Correspondence to:

    Provenance: This is an invited article commissioned by the Section Editor De-tao Yin .

    Submitted Oct 16, 2019. Accepted for publication Oct 21, 2019.

    doi: 10.21037/gs.2019.10.14

    The global incidence of thyroid cancer has steadily increased, however mortality has remained unchanged as most thyroid malignancies are well-differentiated with indolent behavior. The incidence, however, of poorly differentiated and anaplastic thyroid cancer have also increased proportionally and these are aggressive tumors associated with significant morbidity and mortality . PDTC has been recognized as a distinct entity that represents an intermediate position in the sequence of de-differentiation from WDTC to ATC with unique histopathology, molecular abnormalities, and diagnostic criteria .

    Thyroid carcinoma is a continuum of diseases, where at one end there is papillary thyroid cancer, the human cancer with one of the best prognoses, a long term survival > 98%. On the other end of the spectrum is ATC, the deadliest human cancer, with almost 99% mortality. It is an amazing and biological enigma that in the same human organ we see this huge variation. The molecular biology of this disease may help us to understand this spectrum and help in providing targets for therapy.

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    Overview And Diagnosis Of Differentiated Thyroid Cancer

    Lori Wirth, MD: Im Lori Wirth, and Im a medical oncologist at Massachusetts General Hospital in Boston, Massachusetts.

    For a brief overview of differentiated thyroid cancer: It is a spectrum of various thyroid cancers that derive from the follicular cells in the thyroid gland. There are several subtypes the most common subtype, a papillary thyroid cancer, follicular thyroid cancer, Hürthle cell carcinoma, and poorly differentiated thyroid cancers. All these subtypes are referred to as differentiated thyroid cancer to distinguish them from anaplastic thyroid cancer or medullary thyroid cancer.

    Overall, in the United States, we see approximately 45,000 patients every year who are newly diagnosed with differentiated thyroid cancer. In terms of the prognosis, most patients with differentiated thyroid cancer will do quite well. Most patients will be cured with treatment involving surgery plus or minus radioactive iodine. There is, however, a subset of patients who do not do well. In the United States we see approximately 2200 deaths per year from thyroid cancer.

    Transcript edited for clarity.

    Histopathology And Immunohistochemistry As Prognostic Factors For Poorly Differentiated Thyroid Cancer In A Series Of Polish Patients

    Management of Differentiated Thyroid Carcinoma in the Era of Targeted Therapy
    • Roles Data curation, Investigation, Methodology, Writing original draft

      Affiliation Department of Surgical Pathology, Holycross Cancer Center, Kielce, Poland

    • Affiliations Endocrinology Clinic, Holycross Cancer Center, Kielce, Poland, Collegium Medicum, Jan Kochanowski University, Kielce, Poland

    • Roles Data curation, Formal analysis, Methodology

      Affiliation Faculty of Natural Sciences, Jan Kochanowski University, Kielce, Poland

    • Affiliation Department of Surgical Pathology, Holycross Cancer Center, Kielce, Poland

    • Roles Project administration, Supervision, Writing review & editing

      Affiliations Collegium Medicum, Jan Kochanowski University, Kielce, Poland, Clinical Oncology Clinic, Holycross Cancer Center, Kielce, Poland

    • Roles Conceptualization, Project administration, Resources, Supervision, Writing review & editing

      Affiliations Endocrinology Clinic, Holycross Cancer Center, Kielce, Poland, Collegium Medicum, Jan Kochanowski University, Kielce, Poland

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    Stage Information For Papillary And Follicular Thyroid Cancer

    Table 4. Definitions of Differentiated TNM Stage III for Papillary and Follicular Thyroid Carcinomaa

    Stage Illustration
    T = primary tumor N = regional lymph node M = distant metastasis.
    aReprinted with permission from AJCC: Thyroid–Differentiated and Anaplastic Carcinoma. In: Amin, MB, Edge Sb, Greene FL et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 87390.
    bAll categories may be subdivided: solitary tumor and multifocal tumor .
    Age at diagnosis is 55 years:
    III T4a, Any N, M0 T4a = Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size.
    Any N = See descriptions in Table 2.
    M0 = No distant metastasis.

    How Is The Stage Determined

    The staging system most often used for thyroid cancer is the AJCC TNM system, which is based on 3 key pieces of information:

    • The extent of the tumor : How large is the cancer? Has it grown into nearby structures?
    • The spread to nearby lymph nodes : Has the cancer spread to nearby lymph nodes?
    • The spread to distant sites : Has the cancer spread to the distant organs such as the lungs or liver?

    The systems described below are the most recent AJCC systems effective January 2018 and applies to differentiated, anaplastic and medullary thyroid cancers.

    Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a persons T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage. For more information see Cancer Staging.

    The staging system in the table below uses the pathologic stage . It is determined by examining tissue removed during an operation. Sometimes, if surgery is not possible right away or at all, the cancer will be given a clinical stage instead. This is based on the results of a physical exam, biopsy, and imaging tests. The clinical stage will be used to help plan treatment. Sometimes, though, the cancer has spread further than the clinical stage estimates, and might not predict the patients outlook as accurately as a pathologic stage.

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    Rai And Histological Phenotype In Patients With Detectable And Undetectable Tg

    The study included 38 cases from 1986 to 2011 .

    After total thyroidectomy and RAI, 15 patients had detectable and 23 had undetectable Tg levels. Patients received a median cumulative activity of 8.362 GBq . Patients with detectable Tg and undetectable Tg levels received a median cumulative activity of RAI of 8.362 GBq and 6.771 GBq, respectively . Only 1 patient received an activity < 3.7 GBq.

    The pathological subtypes in the 15 patients with detectable Tg were insular , solid , trabecular , and mixed phenotype . In the 23 patients with undetectable Tg, these were insular , solid , trabecular , and mixed phenotype .

    Poorly Differentiated Thyroid Carcinomas

    Pathology Outlines

    Clinical Features and Pathogenesis

    Poorly differentiated thyroid carcinomas include a heterogeneous group of neoplasms whose behavioral and histologic features are intermediate between well-differentiated and anaplastic thyroid carcinomas.341343 Synonyms include insular carcinoma. The frequency of this tumor type appears to differ in different geographic regions. In central Italy, the tumors account for approximately 4% of all thyroid carcinomas. It is much less common in the United States and most other countries.

    There is a slight female predominance, and the median age at diagnosis is 55 years. Most patients present with a thyroid mass of variable duration. Analysis of several series of cases revealed regional metastases in 36% and distant metastases in 26% at presentation.283

    Pathologic Features and Differential Diagnosis

    Papillary thyroid carcinomas may also show high-grade features or act like a poorly differentiated thyroid carcinoma however, there is lack of a consensus for utilizing these additive terms in papillary thyroid carcinoma specifically. The pathology group at Memorial Sloan Kettering Cancer Center proposed a definition for poorly differentiated thyroid carcinoma that includes any follicular cell-derived tumors, including papillary morphology as tumors with > 5 mitoses/10 HPF and/or tumor necrosis.347

    Treatment and Prognosis

    Edmund S. Cibas, in, 2014

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    Case Report: Poorly Differentiated Thyroid Carcinoma In A Young Female Patient

    Shane Kaysen1^, Peter Anderson2, Jeffrey Mohlman3

    1 Rocky Vista University College of Osteopathic Medicine, Parker , South Valley ENT and Steward Healthcare , Professional Diagnostics Inc. and Steward Healthcare , USA

    ^ORCID: 0000-0003-4418-8589.

    Correspondence to:

    Background: Poorly differentiated thyroid carcinoma is a rare subtype of thyroid cancer that is often overlooked on differentials for thyroid neoplasms, and its etiology is poorly understood. This report provides an additional clinical and genetic profile to the literature of this rare and often complex entity as well as discusses a multitude of genetic findings seen in PDTC.

    This tumor type is rare in this age group and has few studies explaining its etiology. The genetic analysis in this case had a unique genetic profile showing MYC amplification and mutations of undetermined significance without the previously reported finding of a DICER1 mutation.

    Keywords: Case report poorly differentiated thyroid carcinoma DICER syndrome Turin criteria MYC amplification

    Received: 09 February 2022 Accepted: 07 April 2022 Published: 10 May 2022.

    doi: 10.21037/aot-21-20

    Prognostic Factors For Well

    Age appears to be thesingle most important prognostic factor. The prognosis for differentiatedcarcinoma withoutextracapsular extension or vascular invasion is better for patients younger than 40 years.

    Patients considered at low risk according to age, metastases, extent, and size risk criteria include women younger than 50 years and men youngerthan 40 years without evidence of distant metastases. The low-risk group also includes older patients with primary papillary tumors smaller than 5cm without evidence of gross extrathyroidalinvasion, and older patients with follicular cancer without major capsular invasion or bloodvessel invasion. Using these criteria, a retrospective study of 1,019patients showed that the 20-year survival rate was 98% for low-risk patients and50% for high-risk patients.

    Aretrospective surgical series of 931 previously untreated patients withdifferentiated thyroid cancer found that age older than 45 years, follicular histology, primary tumor larger than 4cm , extrathyroidal extension , and distant metastases were adverse prognostic factors. Favorable prognostic factors included female gender, multifocality, andregional lymph node involvement. Other studies, however, have shown that regional lymph node involvement had noeffect or had an adverse effect on survival.

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    Thyroid Cancer Survival Rates By Type And Stage

    Survival rates can give you an idea of what percentage of people with the same type and stage of cancer are still alive a certain amount of time after they were diagnosed. They can’t tell you how long you will live, but they may help give you a better understanding of how likely it is that your treatment will be successful.

    Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Your doctor is familiar with yoursituation ask how these numbers may apply to you.

    Patient And Tumor Factors Predictive Of Dss

    67-Year-Old Woman With Differentiated Thyroid Cancer

    Age 45 years, pT size 4 cm, higher pT, ETE, positive margins, and distant metastasis at presentation were predictive of worse outcome on univariate analysis . Multivariate analysis of age, pT stage, and M1 showed that pT4a stage and M1 remained independent predictors of worse DSS. Patients with pT4a disease were seven times more likely to die of disease compared to those with pT1/2 disease . Patients with M1 disease were three times more likely to die of disease compared to those without M1 disease . pT size and ETE were not used in the multivariate analysis because they were incorporated in the pT stage variable.

    A, Five-year DSS stratified by pathological T stage. B, Five-year DSS stratified by M status.

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