Research

Cancer diagnosis

It is now well known that early diagnosis of cancer is a key to have early therapies, that in turn increases the survival rate. There are several diagnostic techniques available that can diagnose cancer, the popular one being the ultrasound based sonography. Sonography sends sound waves and acquires the reflction of the sound thereby forming images of the tissues through some signal processing.

Through these diagnostic techniques, if cancer is detected, then the clinican will decide to do a surgery or some other therapy depending upon the intensity and the grade / stage of the diagnosis. Once the surgery is done, the removed tissue will be sent to a hostopathology lab which performs a biopsy on the tissue. The biopsy confirms cancer and that is the gold standard for cancer diagnosis. However, this process starts after surgery and removal of the tissue from the patient. Hence there is a strong need to provide accurate pre-operative diagnosis to decide to go for surgery.

Thyroid cancer: Perspective from an Indian context

Thyroid nodule, a discrete palpable swelling within an otherwise apparently normal thyroid gland, is a common occurrence with a prevalence of 8% in adult population. The important concern with respect to these nodules is the differentiation between the normal ones and the cancerous ones.  Although a very small percentage of these nodules may be malignant (cancer), there is no easy way of differentiating the benign from the malignant except through excision biopsy. Performing an excision biopsy on all the detected nodules is not an efficient technique due to two reasons: The technique is invasive and also leaves a scar on the patient. Secondly, performing biopsy for all the patients becomes labor-intensive besides increasing the cost, given the fact that only a very small percentage of these nodules may be malignant.

Non-invasive diagnostics for thyroid nodule: Photoacoustic (PA) sensing as a possibility

Current commonly used diagnostic techniques available are ultrasound based (e.g., sonography, elastography etc.) and Fine Needle Aspiration Cytology (FNAC). Ultrasound is a completely non-invasive technique that identifies cysts efficiently, but it lacks specificity in differentiating benign from malignant solid nodules.  While FNAC enables direct visualization of cellular architecture, it is an invasive technique and expertise in sampling and interpretation are not widely available resulting in sampling errors and reduced specificity for the average clinician. The addition of elastography to ultrasound and use of isotope studies of thyroid nodules has not improved diagnostic accuracy. The use of genetic studies has not lived out to the early promises and costs remain prohibitive in most countries. Hence there is still a need for the development of a non-invasive diagnostic screening test for thyroid nodules that can be efficient in determining the type of tumor that requires surgery.

The conventional clinical practice for evaluating thyroid nodules is to perform ultrasound and FNAC for diagnosis. The ultrasound report would contain a Thyroid Imaging Report and Data System (TIRADS) and the FNAC is reported according to a standardized Bethesda system. Based on these reports and clinical evaluation, the surgeon takes a decision on the need for surgery. After performing the surgery, the excised tissue sample would be sent for definitive histopathology. Table 1 provides the different TIRADS categories and the risk of malignancy in the nodule that would be used to determine the necessity of surgery.

Table 1: Different TIRADS categories and their risk of malignancy

  TIRADS      Category      Malignancy risk (%)

TIRADS-1:   negative 0

TIRADS-2:   benign 0

TIRADS-3:   probably benign 1.7

TIRADS-4a: low suspicion 3.3

TIRADS-4b : intermediate suspicion 9.2

TIRADS-4c : moderate concern 44.4-72.4

TIRADS-5 :   highly suggestive 87.5

In one study patient with three thyroid nodules on ultrasound evaluation, two nodules were reported TIRAD-4A and one TIRAD-4B as shown in Fig.1a. Subsequently, surgery was performed and the histopathological results inversely show the nodule with higher ultrasound suspicion to be benign and two with lower suspicion to be follicular variant of papillary thyroid carcinoma (FV-PTC), as shown in Fig.1b. This is a typical clinical situation, where it becomes difficult to non invasively differentiate a benign nodule from FV-PTC .  In the case of FV-PTC the density of malignant cells change, which in-turn affects the tissue properties such as elasticity and density.