Introduction

With every component of its pathogenicity further having variables it becomes difficult to point in one direction when talking about the clinical picture of a patient suffering from Cancer. Each case of cancer can vary considerably from another case of the same type of cancer but certain features of this disease have been found to be consistent in most cases. These clinical markers can be helpful in early diagnosis of the disease in unsuspected cases, especially cases with a strong predilection for the disease due to any factor that is placing them at a higher risk than the others. If you work in a factory or industry which is involved with regular handling of potent carcinogens, if you have a habit of smoking tobacco, chewing tobacco or practicing any adverse habit involving tobacco, if you not only smoke but also consume alcohol, if you have a previous history of chronic infections with viral agents like EBV etc or a poor dietary intake of essential vitamins and minerals then you must keep a close eye on every reaction your body is giving you as it may be signalling to alert you of a developing cancer. The strongest factor that puts you on a pedestal in this situation is a positive family history. If anyone in your close family has suffered from cancer it may indicate a hereditary pattern, making you a high-risk candidate.

W.H.O performance status of a cancer patient

This is helpful in judging the status of the patient and for determining the overall prognosis.

• A person is able to carry out normal activity without restrictions.
• Restricted in physically strenuous activity but walking about and able to carry out light work.
• Walking about and capable of self- care but unable to carry out any work, up and about >50% of waking hours.
• Capable of self- care; confined to bed or chair for more than 50% of the waking hours.
• Completely disabled; not carrying out self-care; totally confined to bed or chair.

Signs and symptoms - is your body flashing you a red flag!

Knowing how your body will react towards a developing cancer can help you decrease any paranoia that you may have about cancer. Besides this knowledge may be used for early diagnosis just based on the clinical features and hence bypass unnecessary screening and tests that may be misleading.

Pain

The most common complaint encountered in cancer patients would be pain. Pain that is unexplained and persistent indicates strongly the presence of a malignancy. Pain can be the result of the tumour compressing a nerve or infiltrating it. Pain can also be associated with the malignant spread of the cancer to involve multiple systems and hence a dangerous stage of the disease. Pain can be frequently seen during treatment phase too.

Managing pain

• Pain caused by nerve infiltration and damage via local pressure may respond to amitriptyline.
• Bone pain may respond to Nonsteroidal Anti Inflammatory Drugs (NSAIDs) e.g. ibuprofen or a nerve block.
• Changing the causative treatment procedure where possible e.g. radiotherapy, hormones, chemotherapy, surgery.
• Adjuvant analgesics may be given like: Non steroidal anti inflammatory drugs (NSAIDs), steroids, muscle relaxants, anxiolytic agents, antidepressants.
• Opioids are the first choice of treatment for severe acute pain. The route of administration can be changed if effect is not achieved after repeating the dose. Morphine is used by most specialists and has a reliable lasting duration of up to 4 hrs. As soon as pain decreases the patient should be moved to ibuprofen and paracetamol.

Unexplained weight loss

Sudden unexplained Weight loss occurs due to multiple reasons and along with pain it is a commonly observed feature of cancer. It may be due to involvement of the gastrointestinal tract where the tract has either been obstructed by the tumour mass making digestion and further nutrition an unachievable goal. Weight loss can also be due to metastatic liver involvement by the tumour or it may be a poorly understood general cachexia syndrome with anorexia and malaise produced by certain factors released by the tumour. Weight loss is also frequently seen exaggerated during treatment. The best way to counteract the effect of weight loss during treatment phase is by keeping a healthy and nutritionally balanced diet to give the body a fair chance at recovery.

Localised swelling of tumour mass

Any swelling that is chronic and not subsiding within a few days indicates a need for biopsy or fine needle aspiration and immediate attention by the doctors. As the tumour mass grows, it invades nearby spaces and may be clearly visible as a swollen mass of a firmer nature than normal swellings. This not only presents as an aesthetic issue but also may be severely handicapping in most cases. Such tumour masses may be reported by the patient or may even go unsuspected when occurring in deeper organs and may be only evident on palpation or on special examination.

Sudden onset of chronic numbness

If a tumour mass is impinging over a nerve then it may induce a sudden feeling of numbness over the areas that are under the sensory coverage of the nerve. If a region in your body has gone numb and the numbness is not subsiding by itself within a limited time then it may be a clear indication of nerve blockage by a tumour mass e.g. in carcinoma of tongue patient may experience a sudden numbness of the tongue, numbness of lower lip is a common feature in cancer of mandible.

Fever

Fever is the body’s way of showing that a foreign substance has invaded its security. It is a normal immune response and although it is mostly seen only when a superimposed infection is present in a cancer case, fever may be observed in certain cancers as a particular feature. These may be cancers of kidney, liver or lymphomas. Fever in such cases is seen as drenching night sweats without rigors.

Anaemia

Due to bleeding or due to malabsorption as a result of gastrointestinal tract involvement by any of the reasons described above NORMOCHROMIC (sometimes HYPOCHROMIC), NORMOCYTIC anaemia is frequently seen. Bone marrow suppression during chemical or radiotherapy in the treatment phase may produce anaemia along with leukaemia and hence presenting as an immunologically debilitated patient.

Hypercalcemia

An increased blood and serum level of calcium signifies involvement of skeleton by widespread metastasis or it may indicate paraneoplastic syndrome. Unlike parathyroid disease the onset of hypocalcaemia in a cancer patient is rapid and there are none of the classic symptoms (stones, bones, groans). Instead the clinical features include - polyuria, thirst, confusion, fatigue and coma. An immediate treatment of hypocalcaemia when established improves the patient’s health considerably.

Clinical features specific to head & neck cancer

Head and neck cancers are a wide range of cancers ranging from cancers of the head and neck skin to lesions involving the salivary glands, the jaws, the lymph nodes and the oral cavity. Certain features are clinically specific to this region of the human body.

Hoarseness of voice

A sudden change in voice texture to a hoarser one indicates that the larynx is diseases. Commonly hoarseness in voice is noticed in carcinoma of larynx occurring in any site of the larynx (Supraglottis, Glottis or Subglottis).

Long-standing multinodular lumps

If goitre appears to be long standing or it is rapidly growing, hard or present with restricted mobility, follicular carcinoma of thyroid gland should be considered. Lumps in neck region may indicate a metastatic head and neck cancer that has progressed to involve the lymph nodes.

Salivary gland tumours

Generally tumours involving salivary gland present as a swelling in the region, which is hard and relatively fixed, xerostomia may be present as a feature.

Trismus

Trismus or difficulty in opening mouth completely is a common finding in many head and neck cancers. Some cancers might grow large in size and hence interfere with the normal jaw movements. E.g. Oral Submucous Fibrosis, bone tumours.

Oral lesions

Oral complaints are frequently of a “sore mouth”. Common clinical findings are - ulcerations, redness of the mucosa indicating inflammation, thinness of the epithelium, fixation, failure of ulceration to heal, burning sensation of the mouth, inability to tolerate spicy food, regional lymphadenopathy or white patches (leukoplakia) indicating an increased keratosis. Oral premalignant conditions and premalignant lesions are seen prior to development of the cancer proper. These are areas that are associated with a high risk of cancer than the normal regions. Many red and white lesions are seen in the oral cavity some of which are associated with cancer formation. These include oral submucous fibrosis (white bands), leukoplakia (white patches), erythroplakia (red patches) etc.

Skin lesions

Never healing ulcers on skin may indicate basal cell carcinoma or squamous cell carcinoma, melanomas may present as the classic ABCD - asymmetric lesion, border irregularity, colour changes and diameter(> or <6mm).

Facial nerve paralysis

Tumours occurring in the head and neck region have a strong tendency to impinge on the facial nerve causing facial nerve paralysis characterized by drooping of the eyelid/ same side of face/ corner of mouth/ inability to blow out cheek of the same side/ inability to close the eye of the same side etc e.g. Pleomorphic adenoma.

Screening for cancer to help in early diagnosis

Screening is used for early diagnosis in otherwise asymptomatic cases, which can be achieved by observation (skin/mouth/external genitalia/cervix), palpation (breast/ mouth/ thyroid/ rectum/ anus/ prostate/ testes/ lymph nodes) and laboratory tests and procedures (papanicolaou smear, sigmoidoscopy/ mammography etc). Cancers of breast, colon, cervix, oral cavity and skin are some of the cancers in which an early diagnosis has led to excellent results after treatment.

Lung cancer

Lung cancer is by far the most common cancer occurring in the United States with an overall increase in its incidence ever since cigarette smoking became endemic. Lung cancer occurs as Adenocarcinoma, Small cell, squamous Cell and Large Cell carcinoma. With the exception of adenocarcinomas which occur in peripheral lung zones, most lung cancers arise in proximal bronchi. A simpler classification divides lung cancer into SMALL CELL and NON-SMALL CELL TYPE.

What causes lung cancer?

1. Cigarette smoking contributes as the major cause of lung cancer.
2. Cigar and pipe smoking are also potent causes for lung cancer.
3. Certain occupational agents which can contribute to lung cancer are asbestos exposure, uranium mining or exposure to arsenic and nickel.
4. Suspected cofactors are exposure to radon, beryllium and various hydrocarbons.
5. Passive smoking also increases the risk for lung cancer.

Clinical picture of lung cancer

• Asymptomatic pulmonary nodules are only discovered on screening X-ray and are important because of their high potential to be cured.
• Primary symptoms include - cough, dyspnea, hemoptysis and wheezing.
• Regional effects -
  • Hoarseness and esophageal compression
  • Superior vena cava syndrome
  • Horner’s syndrome
  • Pleural and pericardial effusions
  • Phrenic nerve paralysis.
• Metastasis may progress to involve brain, bone, liver, adrenal glands.
• Hypercalcemia may occur.

Diagnosis

• Physical signs - physical examination may detect supraclavicular lymphadenopathy , pleural effusion, localized wheeze of bronchial obstruction, weight loss, clubbing of fingers or the signs of gross metastatic disease.
• Laboratory tests may uncover anaemia, hepatic dysfunction, hypercalcemia and hyponatremia.
• Cytologic examination of sputum may be performed for a non-invasive clue.
• Cytologic and histologic specimens are obtained from peripheral lesions through transthoracic fine needle aspiration or core biopsy, under computed tomography or ultrasound guidance.
• Centrally located tumours are usually accessed by bronchoscopy.
• CT scans of chest, pelvis and abdomen, radionuclide bone scans, CT or magnetic resonance imaging of brain and positron emission tomography scan can also be used for staging of the cancer once diagnosis has been established.

Treatment

Small cell cancer

• There is a systemic effect associated with this type of cancer and hence it requires systemic chemotherapy.
• Untreated cancers of this type are usually deadly with a median survival rate of only a few months.
• Patients with the disease limited to only side of the thorax respond to chemotherapy in 90% cases.
• Patients with extensive stage disease also respond to chemotherapy.

Non small cell cancer

• This type of lung cancer is treated surgically if possible.
• Most patients only report when the tumour mass has reached an unresectable condition
• Chemotherapy and radiotherapy can be given but are of significantly less advantage when considering long term survival.

Breast cancer

Breast cancer is the most common cancer occurring in women and also the second leading cause of deaths occurring in women due to cancer. A greater risk of developing breast cancer occurs at around the 6th decade of life. Most breast cancers are adenocarcinomas. Invasive breast carcinoma comprises 75 to 85% of all breast cancers. Carcinoma in situ comprises almost 15-20% of all breast cancer.

What can cause breast cancer?

1. Hereditary has been noted in about 5-20% of cases with specific germline mutations in genes like the breast cancer gene -1(BRCA1) and 2(BRCA2).
2. Hormonal factors play a significant role, the effect of early menarche, late pregnancy and late menopause acts to prolong the cyclic stimulation.
3. Diet and obesity may be related to increased amounts of estrogens.
4. Alcohol intake also increases estrogens metabolism which acts as a promoter to more fundamental molecular perturbations.

Clinical features

• The usual clinical presentation is a painless lump or a localized thickened mass in the breast, but not all breast masses are cancer. Most breast masses in premenopausal women are due to fibrocystic disease or fibroadenoma. Non-malignant masses in postmenopausal age group are sclerosing adenosis, fibrocystic disease, fibroadenoma or fat necrosis due to unappreciated trauma.
• Pain or discomfort while more common in non malignant breast masses, may be an important feature in cancer.
• In more advanced cases there will be dimpling or puckering of the overlying skin, distortion in shape of the breast or nipple.
• Palpable axillary or supraclavicular lymph nodes.
• Skin fixation, ulceration and adjacent skin nodules may be seen in locally advanced cases.
• By screening using mammographic examination, it may present as a mammographic abnormality before it is detectable by physical examination.

Diagnosis

• Mammography is done before biopsy to evaluate the appearance of the mass.
• Ultrasonography is useful for distinguishing solid masses from cystic masses.
• Breast Magnetic Resonance Imaging (MRI) is highly sensitive and used for screening of high risk patients.
• Positron emission Tomography scan (PET) is used to evaluate distant metastatic disease.
• Tissue examination can be done by fine needle aspiration cytology (FNAC) or core-needle biopsy.
• Sentinel node biopsy is performed at the time of resection of breast mass to judge which nodes are draining the tumour mass.
• Additional staging tests may include radionuclide bone scan or brain magnetic resonance imaging.

Tumour-Node-Metastasis classification for breast cancer

Staging of breast cancer

Treatment

Treatment can be given as:

• Surgery (Patey's Mastectomy, conservative techniques like lumpectomy, segmental mastectomy) total mastectomy with ipsilateral axillary node dissection is the most acceptable surgical procedure with no need for adjuvant radiotherapy.
• Radiotherapy E.g. Interstitial iridium - 192 implants
• Systemic adjuvant therapy (cyclophosphamide, methotrexate, 5 - fluorouracil, adriamycin, tamoxifen)
• Neoadjuvant chemotherapy with subsequent radiotherapy or surgery.
• Hormonal therapy

Follow-up after treatment

• Long term follow up following the treatment is essential.
• New cancers occur in contralateral breast at the rate of 1% annually, which can be reduced by the administration of tamoxifen.
• Chances of relapse of the same cancer or new cancer is 5-20% in patients undergoing breast-sparing procedure and hence require regular screening and mammographic examinations.

Cervical cancer

There has been a marked decrease in the rates of occurrence and the mortality rates of cervical cancer in the last 50 years due to the availability of screening programs and due to better knowledge about the prevention of cancer. But in developing nations where such methods and knowledge is not readily available the mortality rates are extremely high at 50% with an average of 4 lac new cases diagnosed each year. Cervix cancer is age related in its occurrence. With majority of cases occurring in the age groups of 45-50 years. It is extremely rare to find cases of cervix cancer below 20 years of age as well as in women above 75 years of age. Cervical intraepithelial neoplasia is the premalignant precursor of cervical cancer. Majority of cervical cancers are squamous cell.

What can cause cervical cancer?

1. The major risk factor is heredity.
2. Another important risk factor is the early onset of sexual activity and multiple sexual partners.
3. Other risk factors are a history of a sexually transmitted disease, multiple pregnancies, low socioeconomic status and immune suppression.
4. Cervical cancer is almost always associated with human papilloma virus (HPV) infection which is transmitted during sexual activity. Most commonly associated are HPV-16 and HPV-18
5. Tobacco habits, cigarette smoking or any environmental exposure to smoke is extremely dangerous to already HPV infected women.

Clinical features

• Cervical intraepithelial neoplasia and carcinoma in situ are asymptomatic and usually discovered during routine examinations.
• The most common symptoms are abnormal vaginal bleeding, postcoital bleeding and vaginal discharge that are watery, mucoid or purulent. Vaginal discharge may be mistaken for severe cervicitis.
• Locally advanced disease causes pelvic or lower back pains.
• Urinary symptoms include:
  • Haematuria
  • Ureteral obstruction
• Edema of one or both extremities.

Screening and diagnosing

• Vaccination is now available against HPV infection and these can prevent cervical cancer as 80% of cervical cancers are caused by HPV transmitted sexually, e.g. Gardasil and Cervarix. These vaccines can prevent cervical cancer if given to a girl or women before exposure to the virus. Standard regimen for vaccination is by 11-12 yrs but can be given as early as 9 years. If not received by then the Centre for disease control and prevention recommends the vaccination by the age of 26. It is given in three doses, the 2nd injection is given 1-2 months after the first one and the third is given 6 months after the second injection
• Annual pelvic exams with a pap smear from the cervix should begin at the age of onset of sexual activity.
• Testing for HPV DNA in high risk population may improve early detection and management.
• Self collected vaginal swabs for DNA testing may improve screening in areas where cytologic studies are not readily available or in women who are hesitant to undergo regular examinations.
• After 2 to 3 negative annual examinations or after negative results for dysplasia and HPV the frequency for screening can be shifted to every 2 to 3 years.
• Examination of most cases have a visible cervical lesion ranging from a superficial ulceration to exophytic tumours.
• Punch biopsy taken from the edge of the tumour can confirm the diagnosis.
• If the cervix appears normal colposcopy and direct biopsy is of value.

Tumour- Node- Metastasis classification for cervical cancer

Staging and survival in cervical cancer

Management

• Cervical intraepithelial neoplasia, carcinoma in situ and very early cases of cervical cancer are readily treated by Conization (removal of the outer portion of the cervix for the diagnosis and treatment of cases with abnormal vaginal bleeding or cases of cervical carcinoma)
• Women with stage I and stage IIA can be treated by radical hysterectomy with lymphadenectomy or definitive radiation therapy (combined external beam and intracavitary brachytherapy)
• In women who wish to preserve their fertility radical Trachelectomy (removal of the cervix and parametria with preservation of the uterus and the ovaries) is a valuable alternative to radical hysterectomy.
• Adjuvant chemotherapy can be given in cases with stage I and stage IIIA with bulky tumours or positive resection margins.
• For locally advanced stages IIB, III and IVA, chemoradiation is the preferred approach.
• Patients with stage IVB should be given palliative treatment by radiation or chemotherapy to reduce the pain and the uterine bleeding.

Prostate cancer

Prostate cancer is one of the most frequently diagnosed cancers in men. About 30% of men above the age of 50 years are estimated to have prostate cancer. Prostate cancer below the age of 40 years is rare and only 1 % cases of such an occurrence have been reported. Death from prostate cancer is most common in 75 year old men. Racial variances occur when considering the chances of developing prostate cancer, with the highest risk being in the African-American races followed by the American men and then Asian men. Histological most prostate cancers are acinar adenocarcinomas. Small cell tumours, squamous cell carcinoma and lymphomas are rare. Prostate cancer develops from the peripheries of the gland (posterior lobe is the most common initial site), as it advances it invades the prostate capsule and if not treated it invades the pelvic wall and the seminal vesicle.

What can cause prostate cancer?

1. Prostate cancer is not seen in castrated men thereby indicating that androgens play an important role in its development.
2. A family history of prostate cancer increases your chances of prostate cancer by two folds.
3. Occupational predilection makes rubber factory workers at high risk.

Clinical features

• Low grade, low- stage prostate cancer may remain asymptomatic throughout the patient’s life such cases are diagnosed only during routine rectal examination.
• Indurations or non painful irregular nodules may be a common finding.
• Symptoms if present indicate that the disease has advanced.
• Urinary symptoms include:
  • Suddenly noticing urinary tract obstruction
  • Poor urine flow
  • Urgency to urinate
  • Haematuria
• Bone pains can occur from metastatic disease.
• Haematospermia is caused by seminal vesicle invasion.
• Leukoerythroblastic anemia is typical for bone marrow invasion.
• Ureteral obstruction may result in post-renal kidney failure
• Other symptoms: Back aches, Paraplegia

Diagnosis

• Prostate Specific Antigen (PSA) when elevated indicates prostate cancer. It is a proteolytic enzyme that is secreted by the prostate acinar cells under normal conditions to liquefy the seminal plasma coagulum. Cancer cells secrete this enzyme at three times the rate of normal cells.
  • Normal PSA level- <4 ng/ml
    • Values higher than 10 ng/ml should raise a suspicion for prostate cancer as it indicates a 60% chance of prostate cancer. Values higher than 20 ng/ml of PSA indicate a 95% chance of prostate cancer.
  • Once Prostate cancer is suspected a Trans-rectal Ultrasound (TRUS) should be performed.
  • Histological diagnosis is established by transperitoneal needle biopsy or by trans-rectal fine needle aspiration cytology (FNAC).
  • Routine examinations like urine analysis, complete blood picture, renal and liver profile, serum alkaline phosphatase , serum calcium and phosphorus levels, chest X-ray and X-ray of bony secondary sites is carried out.

Gleason scoring of prostate cancer

According to the gleason grading scale, prostate cancer can be divided into-

1. Well differentiated - score 2 to 4
2. Moderately differentiated - score 5 to 7
3. Poorly differentiated - score 8 to 10

Tumour-Node-Metastasis classification for prostate cancer

Stagin

Management

• Patients with stage 2 prostate cancer may be treated by curative beam radiation or radical prostatectomy (single nodule of less than 2 cm).
• Radical surgery is limited in its use due to factors like an increased risk of impotency, lymphoedema, pulmonary embolism.
• In advanced stages transurethral resection of the prostate is done to relieve the bladder obstruction purely as a palliative measure.
• Radiation therapy may be employed either alone or as an adjunct to radical surgery but Local recurrence may be higher after radiation. Stage 3 patients should be treated with radiation therapy.
• Patients with bone metastasis should receive hormonal therapy e.g. Luteinizing Hormone Releasing Hormone (LHRH) therapy.
• Short course of antiandrogen should accompany LHRH therapy
• Patients whose metastatic prostate cancer is not responding to anti-androgen therapy may benefit from chemotherapeutic drug docetaxel.

References

1. SILVERMAN’S ORAL CANCER- 4th Edition, Chapter 4: Diagnosis
2. BURKET’s ORAL MEDICINE,DIAGNOSIS AND TREATMENT- 10th edition, Chapter: 8 oral cancer: presenting signs and symptoms
3. PETERSON's PRINCIPLES OF ORAL AND MAXILLOFACIAL SURGERY- 2nd edition Part 5- Maxillofacial Pathology, chapter 32: Oral Cancer : classification, staging and diagnosis, chapter 37:Head and Neck Skin Cancer.
4. CURRENT MEDICAL DIAGNOSIS AND TREATMENT- 2006, Tierney, Lawrence M. ,McPhee, Stephen J, Papadakis, Maxine A., 45th edition, Chapter 40: Cancer
5. CURRENT SURGICAL DIAGNOSIS AND TREATMENT, 12th Edition- McGraw Hill, Chapter 15: head and neck tumors, chapter 46: oncology.
6. KOCHAR’s CLINICAL MEDICINE FOR STUDENTS- 5th Edition, Chapter 102: Breast Cancer, Chapter 104: Lung cancer Chapter 106: Prostate Cancer
7. OXFORD HANDBOOK OF CLINICAL MEDICINE - 6th edition, Chapter 12: Oncology
8. OXFORD HANDBOOK OF TROPICAL MEDICINE - 2nd Edition, PART 3- Multi system disease and infections - Chapter 5: Cancer
9. API TEXTBOOK OF MEDICINE- GS SAINANI- 6th edition, section 14- oncology.