Background

A 54-year old male, presented with a history of anterior neck swelling, gradually increasing since 1.5 years. CT neck revealed right lobe of thyroid replaced by a heterogeneously hyper-enhancing mass 12.5 x 7.5 x 4cm with multiple right sided cervical lymphadenopathy. S. calcitonin levels were 9.36 pg/ml. FNAC was done from right thyroid lobe. Patient underwent total thyroidectomy with removal of neck nodes.

FNAC Smears

Fig.13a; Giemsa; 4x

Fig.13b; Giemsa; 40x

Gross specimen

Fig.13c. Gross 1

Fig.13d. Gross 2

Fig. 13c-d: Gross examination shows a solid grey white to yellowish mass in right thyroid lobe.

Microscopy

Fig.13e; H&E; 4x

Fig.13f; H&E; 4x

Fig.13g; H&E; 15x

Fig.13h; H&E; 4x

Fig.13i; H&E; 7x

Fig.13j; H&E; 4x

Fig.13k; H&E; 30x

Fig.13l; H&E; 4x

Fig.13m; ? stain

Questions & Answers:

1. What is your diagnosis?
   • Anaplastic Thyroid Carcinoma
   • Papillary Thyroid Carcinoma
   • Medullary Thyroid Carcinoma
   • Poorly Differentiated Thyroid Carcinoma (with coexistent Papillary Thyroid Carcinoma)
2. Which of the following Immunohistochemical (IHC) marker is shown in Fig. 13m?
   • PAX8
   • TTF1
   • Thyroglobulin
   • Cytokeratin
3. What is the name of the diagnostic algorithm for this tumor, which is now accepted and integrated in the WHO classification?
   • MSKCC criteria
   • Turin Consensus Proposal
   • ATA guidelines
   • AMES criteria

POINTS TO REMEMBER

• The term “poorly differentiated thyroid carcinoma” (PDTC) was first introduced by Granner and Buckwalter in the early 1960.
• However, World Health Organization (WHO) series of malignant human neoplasms, first accepted and introduced this entity in 2004.
• Morphologically and biologically, this tumor is placed between well differentiated thyroid carcinoma (PTC, follicular thyroid carcinoma (FTC)) and anaplastic thyroid carcinoma.
• Clinical Features:
  • Mean patient age at diagnosis: 55-63 years
  • Clinical presentation: Usually large solitary thyroid mass. Distant metastasis at presentation is reported in 15% of cases.
  • Tumor spread and staging: Widely invasive into perithyroidal soft tissue, regional lymph nodes and distant metastasis (most commonly, lung followed by bones and other sites). Higher pTNM than well-differentiated thyroid carcinomas.
• Fine-needle Aspiration:
  • Challenging owing to their rareness, overlapping morphology with follicular neoplasms and sampling error of the poorly differentiated component.
  • Most of the cases are reported as suggestive of follicular neoplasm.
  • Cytological features most predictive of PDTC are: severe crowding, clusters with solid/insular architecture, single cells, high N:C ratio and mitotic activity.
• Diagnostic Algorithm for the diagnosis of PDTC using Turin consensus criteria:

Diagnostic Algorithm for diagnosis of PDTC using Turin consensus criteria

• How much poorly differentiated component is needed to call it PDTC?
  • Even PDTC component as little as 10% of an otherwise well differentiated tumor, may be associated with aggressive features or have unfavourable prognosis.
• Immunophenotype:
  • General features intermediate between well differentiated and anaplastic thyroid carcinomas. No specific marker is diagnostic of PDTC.
• Genetic Profile:
  • Early driver events in thyroid carcinogenesis: RAS family, BRAF mutations & ALK fusions
  • Late events associated with tumor dedifferentiation: TP53, TERT, CTNN1, AKT1 mutations
  • However, there is a vast overlap of mutations in the different subtypes and the lack of specific mutations.
  • miR-221 and miR-222 are increasingly deregulated in PDTC as compared with PTC
• Prognosis:
  • Overall 5-year survival 60-70%
  • The relapse-free survival is less than 12 months
• Treatment:
  • No standardized treatment for PDTC to date.
  • More aggressive approach is needed to treat these tumors as compared with standard low-risk thyroid carcinomas.
  • Response to radioiodine treatment is generally poor.
  • Tyrosine kinase inhibitors offer new treatment options in these very difficult to treat tumors.
  • Sorafenib and Lenvatinib were approved by the U.S. Food and Drug Administration (FDA) for patients with radioiodine-resistant progressive, recurrent, or metastatic disease.

Contributed & Compiled by: Dr Divya Bansal

In case of queries, email us at: divya.bansal@rgcirc.org

Head & Neck Neoplasms Poorly differentiated thyroid carcinoma Thyroid Turin Consensus Proposal

Last modified: 11/07/2021