The histological features and the biological behavior differ grossly among the spectrum of thyroid cancers. One end of the spectrum is a slow-growing differenti­ated thyroid cancer of follicular cell origin with favorable outcome and the other end is fast-growing undifferentiated thyroid cancer with a very dismal outcome. It also encompasses cancers of follicular cell origin, parafollicular cell origin, and stromal cell origin.

1.7% of all thyroid cancers, respectively.

PTC is the commonest of DTC and includes 14 variants in addition to the con­ventional type and also has a new additional accepted entry; the Hobnail variant. Tall cell variant, columnar cell variant, Hobnail variant, and solid variant have higher chances of adverse outcome. The newer classication has recognized Encapsulated Conventional PTC (completely covered by the capsule) as a separate variant with a favorable outcome even when regional node metastases are present. Encapsulated follicular variant of papillary thyroid neoplasm was brought to lime­light in 2016 [4] and the 4th edition of WHO classication downgraded it to the benign category and renamed it as non-invasive follicular thyroid neoplasm with papillary nuclear features (NIFTP) [3].

RET proto-oncogene rearrangement was the earliest known genetic background of PTC.Mutations of RAS genes that are involved in the regulation of MAPK and P13K/AKT pathways are generally found in follicular variants of PTC.BRAF gene is also signaling through MAPK pathways which control the proliferation of cells. A point mutation in BRAF accounts for the genetic basis of about 45% of PTC and the phenotype expressions show aggressive pathological features. Telomerase Reverse Transcriptase (TERT) promoter mutations are found in approximately 11.3% PTC and when coexisting with BRAF V600E exert a synergistic effect and induce aggres­sive histological features and adverse outcomes [4]. Follicular variants include two different histologic expressions; the encapsulated neoplasm and the inltrative tumor and reveal RAS mutations or PAX8/PPAR gamma rearrangements.

1. The minimally invasive FTC (shows capsular invasion only).

2. Encapsulated angioinvasive FTC.This category includes a subtype of limited

3. Widely invasive FTC.

Hürthle cell tumors are composed of >75% oncocytic cells without character­istic nuclear features of PTC and are characterized by capsular and vascular inva­sions [7]. Like the other forms of DTC, HCC is more common in females and is frequently found to harbor concurrent regional and distant metastases at the time of diagnosis [8].

Histologically Hürthle cell cancers are classied as: (1) The minimally invasive HCC (capsular invasion only); (2) Encapsulated angioinvasive HCC.This category includes two subtypes: (a) limited vascular invasion (invasion <4 vessels) and (b) extensive vascular invasion (>4 vessels invasion); (3) Widely invasive HCC.

A preoperative conrmed diagnosis is not usual since the ultrasound has no characteristic features or cytology does not detect vascular or capsular invasion which are hallmark features in arriving at the diagnosis of HCC.Hürthle cells are seen in inammatory diseases like Hashimoto’s thyroiditis and are frequently encountered in aspiration cytology. Bethesda category III and IV cytology with predominant Hürthle cells are usually reported as Hürthle cell lesions and neoplasms.

85.1% and 71.1%, respectively [11].

non- insular forms with trabecular or solid patterns were also recognized as histo­logical features of PDTC. Rarely, both histological features coexist in the same tumor [3].

The rst major suggestion regarding a consensus in the correct histological de­nition of PDTC was from Memorial Sloan Kettering Cancer Center (MSKCC). The key features to predict PDTC were high mitotic rate and/or tumor necrosis [12]. The present-day consensus about diagnostic criterion (Turin-PDTC) included “solid/tra­becular/insular pattern of growth, absence of conventional nuclear features of papil­lary carcinoma, and with at least one of the following features: convoluted nuclei, mitotic activity ≥3/10 high power microscopic elds (HPF), and tumor necrosis” [13]. But, the coexistence of a poorly differentiated area within PDTC will signi­cantly affect patient prognosis [14] and so thorough scrutiny of all areas is necessary.

Clinical features: PDTC is generally found in the 6th and 7th decades of life and is more frequently seen in females (sex ratio of 1:2). The majority of patients are diagnosed with advanced disease and the tumors usually have transgressed beyond the thyroid capsule with metastases in regional lymph nodes. There is a high chance of concurrent distant metastases at the time of initial diagnosis of PDTC [16]. Elderly patients with extensive locoregional disease disproportional to the duration of disease are clinically suspicious PDTC.

UTC is generally considered stage 4 disease considering the unfavorable outcome, but the median survival was longer in thyroidectomized patients (6.6 months) compared to that for non-surgical patients (2.1 months) [20]. Diagnosis of UTC is arrived in more than 50% by routine cytology and immunohistochemistry studies on cell blocks. Core biopsy should be undertaken with extreme caution since resultant bleeding could be fatal. Genetic studies are recommended since targeted therapy is an option at a later stage. Concurrent occurrence of distant metastasis at the time of initial diagnosis is over 50% and so advanced imaging like FDG-PET CT is advisable before operation. Locoregional spread is better assessed by regional CT [1]. In view of relative gloomy outcome, patients and their relatives are counseled for treatment explaining the details.

The commonest form of thyroid cancers are DTCs which show slow progression and a high rate of overall survival. The treatment modications are aimed to prevent recurrences and to increase disease-free survival. AJCC staging essentially esti­mates the overall survival and not the disease-free survival.