Cancer is a heterogeneous group of conditions characterized by the abnormal proliferation of cells. While the etiology is often multifactorial, there is growing evidence that cancer is related to upregulation of oncogenes, downregulation of tumor suppressor genes or epigenetic phenomena which lead to unregulated cell growth and division.

Cancer can present in a variety of ways depending on the cell type affected, which could be either solid tumors (primarily affecting solid organs such as breast, lung, colon) or liquid tumors (which are primarily the hematogenous malignancies such as lymphoma and leukemia).

Given that cancer falls into the differential diagnosis of many presenting complaints, the differential diagnosis is large and depends on the signs and symptoms with which the patient presents. For example, a lump in the breast may well be a sign of breast cancer, but may also be of benign etiology, such as a cyst, fibroadenoma, or fat necrosis.

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Shortness of breath and hemoptysis may be signs of lung cancer, but tuberculosis and other infectious etiologies should also be considered.

Patients presenting with weight loss and fatigue may well have lymphoma, but depression may also be on the differential diagnosis. Because of the aggressive nature of cancer, however, clinicians should have a high index of suspicion for this diagnosis so as not to misdiagnose patients with cancer with other non-malignant conditions.

As with most problems, the initial approach is with a thorough history and physical examination. Nearly any symptom may signal a malignant etiology. Be sure to consider systemic symptoms such as fevers, chills, weight loss, and fatigue along with more specific ones like shortness of breath, abdominal pain, hemoptysis, melena, hematochezia, hematuria, and early satiety.

Physical examination should be head to toe: be sure to evaluate lymph node basins. In addition, a number of signs may trigger a higher index of suspicion for various cancers: an asymmetric mole, a breast mass, a Sister Mary Joseph’s nodule, Virchow’s node, or mass/blood on rectal exam.


  • Have you had any fevers, chills or weight loss?

  • Are there any new masses that are growing?

  • Have there been any changes in moles?

  • Is there any abnormal bleeding – hemoptysis, hematochezia, hematuria, melena?

  • Is there any shortness of breath, abdominal pain or bone pain?


In general, a thorough physical examination will allow one to have insight into a potential malignancy. Be sure to do a complete skin, breast and rectal exam. Examine the neck for both thyroid masses as well as lymph nodes. Examine all lymph node basins – note that a Virchow’s node may be reflective of an intra-abdominal malignancy. Examine the umbilicus for a Sister Mary Joseph’s nodule. In women, a pelvic exam may reveal pelvic malignancies.


Tests are directed to the type of malignancy suspected. A routine complete blood count (CBC) may provide a clue to leukemias and lymphomas. Liver function tests may allow for some clue into liver involvement, although disruption of liver function is often a late finding.

Chest x-ray or computed tomography (CT) scan of the chest may reveal lung cancers; mammograms are needed for evaluation for breast cancer; thyroid ultrasound may be useful for thyroid cancer; colonoscopy is helpful for colon cancer; upper gastrointestinal (GI) endoscopy may be useful for esophageal and/or gastric cancers; CT scan of the abdomen and pelvis may reveal malignancies in these cavities; bone scan will lead to some sense of bony involvement; prostate-specific antigen (PSA) may be useful for prostate cancer; etc.

While some clinicians may favor a positron emission tomography (PET) scan, it should be noted that PET has a lower limit of detection of around 1cm.


The diagnosis of cancer most often rests on biopsy – in general, radiographic and laboratory findings are insufficient to make a diagnosis of cancer, particularly of solid organs.


A targeted approach should be utilized in making a specific cancer diagnosis. This starts with a history and physical, and then tests aimed at explaining signs and symptoms – targeting specific cancers. A “gunshot approach” such as head-to-toe CT or PET should be avoided without a primary diagnosis.

The “Choosing Wisely” guidelines adopted by a number of professional organizations may be useful in avoiding wasted tests.


Most cancers are not “emergencies” – i.e. while life threatening, it is often best to carefully make a diagnosis, stage the patient and plan for multidisciplinary treatment rather than rushed management. However, there are some symptoms that may require urgent treatment.

These urgent or even emergent situations may include paraneoplastic crises, acute shortness of breath from malignant pleural effusion, malignant pericardial effusion that can cause tamponade, superior vena cava syndrome, impending spinal cord compression from malignant disease, and impending fractures or those that occurred from bony metastases.

Patients should be medically stabilized in these circumstances, and referral to medical, surgical or radiation oncology may be warranted. Also, be aware that patients with cancer who are on active treatment may also present with acute issues warranting immediate attention – in particular, neutropenia may put patients at risk of sepsis. A heightened index of suspicion is warranted.

Management of cancer really depends on the type of cancer. Often a disease-specific multidisciplinary team is involved, as treatment includes surgery, radiation and systemic therapy for many cancers. Communication between these disciplines is critical, and often occurs at tumor boards where imaging and pathology are also reviewed.

Consideration of clinical trials is important, as patients who participate in clinical trials tend to have better outcomes. The side effects of various types of surgery, radiation and systemic therapy varies with the procedure, drug and disease site involved.

Schnipper, LE, Smith, TJ, Raghavan, D. “American Society of Clinical Oncology Identifies Five Key Opportunities to Improve Care and Reduce Costs: The Top Five List for Oncology”. J Clin Oncol. April 3, 2012.

Samphao, S, Eremin, JM, Eremin, O. “Oncological emergencies: clinical importance and principles of management”. Eur J Cancer Care (Engl). vol. 19. 2010. pp. 707-713.