Thyroid Cancer

 

About Thyroid Cancer

According to an article published in JCO (Journal of Clinical Oncology) in 2018, Thyroid Cancer has risen in India particularly among the younger population (age group < 45). According to the article, "Over a decade, the incidence rate of thyroid cancer in India in women increased from 2.4 (95% confidence interval (CI) 2.2-2.7) to 3.9 (95%CI 3.6-4.2) and in men from 0.9 (95%CI 0.8-1.1) to 1.3 (95%CI 1.2-1.5) per 100,000 population respectively, a relative increase of 62% and 48% respectively."

Features

-More commonly affects women; M:F = 1:3
-Age is generally > 30 years
-Papillary Cancer is the most common variety
-Ionizing Radiations cause the Papillary variety; Follicular variety can develop in long standing goitre and Medullary variety can run in families harboring RET gene mutation
-Anaplastic or Undifferentiated variety is very aggressive with average survival being less than 6 months

Presentation

-Most common is lump in lower anterior neck, which moves with swallowing, sometimes associated with pain
-In advanced stages, the lump or swelling is associated with hoarseness of voice; difficulty in swallowing or breathing and the lump becomes fixed
-The Papillary and Medullary variety can also present with swellings in lateral neck, which are Lymph nodal metastases
-Rarely, thyroid cancer can present as bony swellings, which are metastases from thyroid cancer with small or occult primary in the gland

Evaluation

1. Thyroid Function Test: Thyroid cancers are generally Euthyroid they do not secrete thyroid hormones. In advanced stages or in cases with background of Goitre, some element of hypothyroidism sets in.

2. Serum Thyroglobulin (TG)/ Anti Tg anti-body: Thyroglobulin is secreted by differentiated Thyroid Cancers like Papillary or Follicular, so its assessment is good for prognostication. Diagnosis cannot be made on it. Also assessment of Anti Tg antibodies has to be made along with to make sure that lower levels of TG are not due to raised antibodies against it.

3. Se Calcitonin/Se CEA: Serum Calcitonin helps in diagnosis of Medullary Cancer Thyroid (MTC) along with prognostication and staging. Se CEA is also used for prognostication of MTC.

4. Ultrasound (USG): This is the first investigation to evaluate a thyroid swelling. Majority of thyroid nodules are benign, but certain features like irregular margins, solid character, increased echogenicity, increased vascularity, micro-calcification, loss of elasticity, etc. suggest towards malignancy. Also, metastases to lymph nodes are evaluated.

5. FNAC (Fine Needle Aspiration Cytology): The USG findings are confirmed by FNAC. It is usually performed under the USG guidance so that appropriate area can be sampled. Cystic lesions with benign features, FNAC can be therapeutic. The presence of lymph nodal disease is also sometimes confirmed by it.

6. Cross-Sectional Imaging: It is used in Locally Advanced stages to assess the involvement of adjacent organs like Trachea (Wind Pipe) and Esophagus (Food Pipe). Also, encasement of vessels like carotid artery and IJV can be studied along with lymph nodal metastases. Both MRI and CT scan give more or less similar information.

Note: CT scan does not hinder the adjuvant (post surgery) Radio iodine therapy, the iodine given during the CT scan study as contrast is eliminated from the body by 6 weeks, which is the time taken for post surgery recovery and achieving hypothyroidism for the administration of Radio iodine

7. FOL (Fiber Optic Laryngoscopy) is mandatory before planning any thyroid surgery to make sure the optimum functioning of vocal cords.

8. Distant disease: It is usually evaluated with CT scan. PET scan can also be used, though the affiidity of Thyroid Cancer for Radiolabelled de-oxy glucose is low. PET is more useful in recurrent disease. For differentiated Thyroid cancer s like Papillary and Follicular cancers, post Thyroidectomy Radio iodine scan is the most definitive modality for evaluation of distant disease. For Medullary variety Dotanoc PET CT is very useful for complete evaluation

Types of Thyroid Cancer

1. Differentiated Thyroid Cancer (DTC)

1.A. PAPILLARY CANCER THYROID (PTC)

-Most common of all thyroid cancer subtypes: 80%
-Good prognosis, 10 yr survival around 90%
-Ionizing radiation is an important causative agent. I have seen patients developing 2nd primary PTC thyroid after receiving radiation for Squamous cell Head Neck Cancer
-Most Common age group 30 to 50 years and Male: Female ratio is 1:3
-It frequently spreads to lymph nodes. The presence of lymph nodal disease depends on the size of tumor. The bigger the size of tumor, the more chances of lymph nodal disease. The presence of lymph nodal metastases increases the chances of recurrence
-Locally Advanced disease has worse prognosis. Early disease, younger age and female sex have better prognosis
-Most common sites for distant metastases – lungs, liver, bone

>

1.B. FOLLICULAR THYROID CANCER (FTC)

-It forms around 12 to 15% of the total thyroid cancers
-Females have higher propensity similar to papillary Carcinoma, age is a decade or two older i.e. between 40 to 60 years
-The prognosis of Follicular ca is good but slightly less than the Papillary variety
-It spreads via vascular invasion with tendency for spread to lung, bone, liver, brain and skin.
-Long standing goitre or Multi-nodular goitre can harbor Follicular cancer.
-FNAC cannot differentiate between Follicular Adenoma vs. Follicular Cancer i.e. benign vs. cancerous as the morphology of cells of Follicular cancer and Follicular adenoma is similar under microscope. The report is generally given as follicular neoplasm; it is after surgical excision the diagnosis is confirmed

Note: There is a newer diagnostic tool, which is available. The cytology sample is being subjected to genetic analysis in form of Next Gen Sequencing (NGS). If the high-risk genes are detected, then it is inferred that the chances of malignancy is high. Therefore, patient can be directly taken for total thyroidectomy instead of doing a hemi-thyroidectomy first followed by completion thyroidectomy.

Treatment

The standard treatment is surgery as the first step. The extent of surgery is decided on the stage of disease.

1. Early Stage Disease: Hemi-thyroidectomy i.e. removal of the affected lobe only can be considered if following conditions are met.

a. Papillary Cancer: Tumor size < 2.5cm, age < 50 yrs, female patient with no history of radiation
b. Follicular Cancer: Diagnosis is not conclusive, Tumor size < 1cm, age < 40 years and female patient
2. Advanced Stage Disease: Adequate surgery plays a significant role in achieving cancer control. Complete removal of the tumor, even in conditions with partial involvement of adjacent organs like trachea and esophagus. Morbidity of adjacent organ resections can be managed by reconstructive surgery.
3. Metastatic Disease: In Differentiated Thyroid Cancer, even in cases of metastases to lung, bone etc. surgery for removal of thyroid primary along with rest of thyroid is essential. The Radio Iodine ablation of the metastatic tumor deposits in lung, bone etc. is treatment modality of choice. For the RAI to reach the metastatic sites thyroidectomy is essential otherwise all the Iodine gets concentrated in the thyroid gland itself.

Hemi Thyroidectomy vs. Total Thyroidectomy:

Hemi Thyroidectomy is removal of the thyroid lobe harboring the neoplastic lesion along with isthmus and Total Thyroidectomy is removal of all the thyroid tissue in the neck. During the present times there is no place for surgeries like subtotal or near total thyroidectomies.

When to go for Hemi Thyroidectomy:

1. Diagnosis is not conclusive, especially in situation where the FNAC report of Thyroid nodule suggests Follicular Neoplasm. I will recommend doing a Hemi Thyroidectomy first, and proceed to completion Thyroidectomy only if carcinoma is confirmed. More than 50% times Follicular neoplasm turns out to be benign in nature, thus saving patients from unnecessary permanent hypothyroidism

2. Early Stage Differentiated Thyroid Cancer as suggested previously

Hemi Thyroidectomy saves the patient from risks of:

1. Permanent Hypocalcaemia: During Total Thyroidectomy if unfortunately all the four parathyroid glands get removed or get de-vascularized, then patient lands up in permanent hypocalcaemia, needing to take large doses calcium supplements for a substantial time period. In case of HT, only the involved side parathyroid glands will be at risk, the other side parathyroid will not be exposed at all. The patient of HT usually doesn’t require calcium monitoring or supplementation.

2. Debilitating Hypothyroidism: Post Total thyroidectomy patient requires complete thyroid hormone supplementation amounting to more than 150 ug/day to maintain Euthyroid state, whereas after HT, the minimal supplementation of around 25 ug is needed.

3. Permanent Hoarseness: HT just puts the nerve of the ipsilateral (affected) side at risk. Although it is very rare and unfortunate that the nerves of both the sides get damaged permanently, still such incidents have been reported.

As a practice principle, I do Total Thyroidectomy only when it is absolutely necessary. It is preferable to advise patient a possibility of completion surgery as majority if times it will not be needed and risk benefit ratio favors Hemi Thyroidectomy.

Radio Iodine Ablation:

Thyroid tissue and metastases from differentiated Thyroid cancer concentrate Iodine. Radioactive isotope of iodine i.e. I 131 is administered which gets concentrated in the metastatic site and ablates the adjacent tissue. Surgical removal of Thyroid gland is necessary so that the iodine can reach the metastatic site otherwise, major portion of it will get concentrated in thyroid gland itself.

It usually takes 6 weeks for TSH to raise post thyroidectomy for iodine to concentrate in effective doses in the metastatic sites, which is the normal time taken for recovery after Thyroid surgery. Recombinant TSH (Thyrogen) can also be used if the patient doesn’t want to experience hypothyroid symptoms. Iodine also gets concentrated in saliva, tears, bone marrow, etc.

In metastatic differentiated thyroid cancer RAI is the best modality for controlling the metastases. In early stage cancers the histopathology features like Extra thyroidal spread, Lymph node involvement, Lymphovascular emboli and size of primary tumor especially the follicular variety warrant a post operative RAI scan and ablation if needed

2. Medullary Thyroid Cancer (MTC)

1. It constitutes 3 % of the total Thyroid cancer load. It arises from Para Follicular C cells mostly in upper central part of thyroid lobe

2. Its lump can be painful at presentation. It has a very high propensity for lymph nodal metastases.

3. Advanced MTC might present with Diarrhoea, Breathlessness due to increase release of Catecholamines and Prostaglandins.

4. More common in females; 30% of it is Hereditary and radiation exposure is not a causative factor.

5. Hereditary cancers occur due to mutation in RET proto-oncogene. The pathogenesis is initial occurrence of C cell hyperplasia, which progresses into carcinoma.

6. Liver, bone, brain, adrenal medulla are common sites for distant metastases.

7. Prognosis depends on the stage and presence of lymph node and distant metastases.
10 year survival for:
i.) Early stage disease is 90%
ii.) Presence of lymph node metastases 70%
iii.) With distant disease is 20%

8. During evaluation of MTC, I make it a point to rule out pheochromocytoma.

9. Treatment is surgery for early and locally advanced stages. Surgery is more extensive than DTC
a. Not much role of Hemi Thyroidectomy; Total Thyroidectomy is the surgery of choice
b. I routinely do Elective ipsilateral (affected) side central compartment clearance even if clinico-radiological evaluation suggests no lymph nodal due to higher chances of lymph node metastases

10. Locally Advanced Cancers: Surgery for Locally advanced MTC differs from DTC. In DTC, if the disease involves adjacent structures like Trachea (wind pipe) and/or esophagus (food pipe), extensive resections are avoided as adjuvant RAI can ablate the tumor, which is left behind. In MTC as there is no back up of RAI, it is preferable to do a multi-organ resection for complete removal and accept some morbidity

11. MTC entails extensive Lymph node dissection especially in presence of lymph node disease

12. The hereditary variety of MTC is generally associated with pheochromocytoma. The syndrome having MTC + Pheochromocytoma+ Parathyroid hyperplasia constitutes MEN IIa syndrome & without parathyroid hyperplasia constitutes MEN IIb syndrome. Patients with MEN IIb have marfanoid habitus and presence of ganglioneuromas

13. Prophylactic thyroidectomy is recommended in Hereditary MTC with confirmed RET gene mutation.

3. Anaplastic Thyroid Carcinoma (ATC)

1. It comprises 1% of the Thyroid Cancer. Mostly patients do not survive for more than 6 months to a year

2. It has a male preponderance with M:F=2:1 and patients tend to fall in in 6th or 7th decade of life

3. It normally arises in background of long standing goitre or DTC. It is sometimes associated with radiation exposure

4. It is associated with lymph nodal disease and local organ involvement and it is associated with progressive increase in mass. Adjacent organ like tracheal involvement is found in 25 % cases and almost 50% patients will have lung mets

5. Treatment is generally palliative. Cure lies with surgical resection. If complete removal is possible, then surgical resection should be considered

Follow-up

DTC: Thyroglobulin and USG neck are the main parameters utilized for follow up

MTC: Serum levels of Calcitonin; CEA; USG neck and X-ray Chest are used for following up MTC

Prognosis

DTC especially if the patient is less than 50 yr the survival is around 98%

MTC prognosis depends upon the surgical clearance

Anaplastic variety has very poor prognosis, the only chance of disease control lies with if complete surgical resection is possible

Breast Cancer

Breast cancer occurs when some breast cells begin to grow abnormally.lifestyle and environmental factors that may increase your risk of breast cancer.

About Breast Cancer

Breast Cancer is the most common cancer among women in India. Every year around 1.5 to 2 lakh new women are being diagnosed with Breast Cancer.

According to GLOBOCAN 2012,” India is facing challenging situation due to 11.54% increases in incidence and 13.82% increase in mortality due to breast cancer.”

In Urban areas 1 in 22 women are likely to be affected by breast cancer. Upto 50% of these don’t survive within 5 years of the diagnosis, More than half of the cases are detected at advanced stage i.e. Stage III and above i.e. majority of women in India when they are diagnosed with Breast cancer, the cancer has already progressed to arm pit or it has involved the Breast skin or nipple. Out of the two women who are diagnosed with Breast cancer only one survives due to advanced stage of disease presentation. In western population more than 80 % women are being detected when the disease is limited to breast, not spread to armpit or any other site in the body and having a small volume i.e. < 2cm tumor size i.e. Stage I/ II with a survival rate of more than 80%.

Figure

Causes Of Breast Cancer

While research is still evolving to ascertain the causes for Breast Cancer, it is generally caused due to the following factors:

1. Lifetsyle Issues: A female’s body is governed by the interplay of estrogen and progesterone hormones. Estrogen promotes cell growth whereas Progesterone causes cell maturation and stabilization. In a woman’s life if estrogen exposure is more, it means more cell growth and cell multiplication, therefore more chances of mutation(changes which cause cancer) to occurleading to Breast cancer. Such situations occur with :
a. Early Puberty
b. Late or no Pregnancy
c. Limited or No Breast Feeding
d. Hormonal exposure in form of Hormonal replacement therapy or Hormones in any form; assisted reproduction methods
e. Even increased stress and alcohol causes estrogen to rise in a woman’s body
f. Obesity and lack of exercise also cause increased levels of estrogen

2. Environmental Factors : Increased exposure to pollutants also contribute to rising Breast cancer in India.
a. The carbon in the air pollution or when a woman smokes bind to the estrogen receptors in the body and breast. Today air pollution is on the rise and lot of women have started to smoke.
b. The Pesticides and chemicals in our food and water also bind to these estrogen receptors and contribute to rise in Breast Cancer.

3. Hereditary factors : There are certain genes like BRCA 1 and BRCA 2 which cause mainly Breast and Ovarian cancers run in the family. It means that if a woman harbour’s BRCA gene there is 80% chance that she will get Breast cancer in her lifetime and 40 % chance that she will get Ovarian cancer. There is a 50 % probability that the gene will be transferred to the next generation and can cause cancer. The exact prevalence of these genes in Indian population is not yet known. In US, around 15% of Breast cancer is Hereditary. A lot more needs to be written about the Hereditary component of Breast Cancer which shall be followed in subsequent articles.

Screening & Early Detection

The only possible solution for the rising problem of Breast Cancer is early detection i.e. catching it at an early stage. At early stage with proper treatment we can expect 80 to 90% survival, 100% Breast preservation and high chances of de-escalation of adjuvant chemotherapy and radiation.

Breast Cancer screening in India is at very early stage, also we attribute it to Mammography whereas it forms just one small portion of Breast screening. According to American Cancer Society Guidelines, the standard screening process of mammography should start at the age of 45 followed by yearly intervals till the age of 55 and thereafter 2 yearly interval. In India as we know now, Breast Cancer women is a decade younger in comparison to western women, the disease peaks at 45 – 50 years. The Indian women have inherently higher breast density as compared to west. Both the facts suggest limited application of screening mammography in Indian settings. . For screening process to be effective it should start atleast 10 yrs. before the peak age of incidence. Advising Mammogram at the age of 35 is not at all effective

The manual breast screening methods in form of Self Breast Examination and Clinical Breast Examination are effective but sparingly used also sparingly used. Every woman should do a self Breast Examination. SBE is nothing but to be aware and conscious of the changes happening in one’s breast. If done regularly the woman can definitely detect Breast cancer if unfortunately it has to happen at a much early stage

How does Breast Cancer Present?

The Cancer presents as
• Lump in Breast
• Change in Nipple position in form of retraction or tethering
• Discharge from Nipple especially Bloody discharge
• Depression or scaring of Breast skin
• Redness or changes of Breast skin especially the Peu d orange
form (skin looks and feel like orange peel)
• Fungating mass through the skin
• Mass or swelling in the armpit

Breast Lump Evaluation:
Clinical history and examination, which includes examination of Breast,
axilla and neck to evaluate the primary tumor and nodal metastatic
spread along with suspicion of distant sites. A clinical staging is also put forth.
The cause of the cancer is and need for genetic evaluation is ascertained.

• Routine blood and other standard evaluation
• Ultrasound and Mammogram (SONOMAMMOGRAM)
• According to the results further steps are planned. The report comes in BIRADS category.
• BI-RADS stands for Breast Imaging Reporting and Data System.
The following can be the result post Sonomammogram
◦ 0- incomplete
◦ 1-negative
◦ 2-benign findings
◦ 3-probably benign
◦ 4-suspicious abnormality
◦ 5-highly suspicious of malignancy
◦ 6-known biopsy with proven malignancy

Accordingly the following evaluation and treatment is done.

BIRADS 1 & 2 are evaluated and treated as benign breast lumps

BIRADS 4 and above are evaluated as malignant by doing a core needle biopsy/FNAB to confirm the malignancy

BIRADS 3 the preference is to get a breast MRI

Breast MRI has basically three main uses

1. Further evaluation of BIRADS 3 lesion, which suggests further whether to recommend a histological evaluation or keep the patient in follow up

2. Evaluating Centricity or Focality of Breast Tumor: The MRI is a better investigation to make sure that their is no other focus of malignancy in the same breast both in the same quadrant as well as other quadrants and also in the other breast. This evaluation is very important to select the suitable patient for Breast Conservation surgical procedure

3. Mammogram shows ACR C/D i.e. when the Breasts are dense which make them unsuitable for mammographic evaluation, Breast lumps or other pathologies occurring in these women will be evaluated by MRI

Followed by Clinical and radiological examination:

Histopathological evaluation is needed which is preferentially done by Core needle (Trucut) Biopsy to proof whether the lump is cancerous (Malignant) or not.

Core needle Biopsy is preferable or FNAC due
• Its better accuracy in terms of specificity i.e. false positivity
• It Provides tissue for IHC or Molecular analysis and categorization

Following histological confirmation, further diagnostic tests are prescribed according to clinical staging.

1. If Clinically its an early stage disease i.e. lump size less than 5 cm with no palpable lymph nodes in axilla then tests for systemic evaluation shall be just Ultrasound abdomen and X ray of the chest.

2. If clinically its an advanced stage disease i.e. a large size lump with or without changes in nipple and/or breast skin with palpable Lymph nodes in axilla and/or neck then systemic evaluation in form of CECT scan of chest and abdomen with bone scan with or without MRI Brain OR a whole body PET CT scan is required.

MRI brain is more relevant in triple Negative Breast cancers.