Differentials

Common

Thoracic aortic aneurysm

History

often asymptomatic; may present with chest or back pain; sudden-onset chest or back pain with associated hypotension and shock may be caused by aneurysm dissection or rupture; compression of adjacent structures may cause dysphagia or dyspnoea; vascular compromise may lead to anginal symptoms, orthopnoea, and peripheral oedema; may have associated history of Marfan's syndrome

Exam

signs of heart failure (elevated venous pressure, peripheral oedema, respiratory distress); signs of aortic insufficiency (diastolic murmur, collapsing pulse); signs of aneurysm dissection or rupture (hypotension and shock, weak or unequal peripheral extremity pulses); associated signs of Marfan's syndrome (arm span exceeding height, arachnodactyly, joint hypermobility)

1st investigation
  • CT angiogram of chest:

    detects thoracic aortic aneurysm, and determines its size, indicates if evidence of dissection or contained rupture

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Other investigations
  • CXR:

    widened mediastinum silhouette, enlarged aortic knob

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  • trans-oesophageal echocardiography:

    assess size, location of aneurysm, and the presence of a dissection; assess coexisting aortic valvular abnormalities

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  • MRI:

    detects thoracic aortic aneurysm and determines its size; not used in the acute setting

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Non-Hodgkin's lymphoma

History

persistently enlarged lymph nodes, constitutional or B symptoms (fever, rash, night sweats, and/or weight loss)

Exam

lymphadenopathy in one or more regions, hepatosplenomegaly may be present, fever, bulky mass in prevascular (anterior) mediastinum with signs consistent with superior vena cava syndrome indicates primary mediastinal B-cell lymphoma

1st investigation
  • peripheral lymph node excision biopsy:

    type and grade of non-Hodgkin's lymphoma

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Other investigations
  • FBC:

    anaemia, pancytopenia

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  • lactate dehydrogenase (LDH):

    elevated; is a sign for disease activity and a prognostic marker

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  • bone marrow biopsy:

    lymphoma cells may be present in bone marrow

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  • CT scan of neck, chest, abdomen, and pelvis:

    evaluation of the extent of lymphadenopathy and staging

    More
  • 18F-FDG PET-CT scan of neck, chest, abdomen, and pelvis:

    evaluation of the extent of lymphadenopathy and staging

  • HIV serology:

    may be positive

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  • hepatitis B and C serology:

    may be positive

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Metastatic cancer

History

prior cancer history in the presence of new lymphadenopathy should raise suspicion for recurrent or metastatic disease; patients may complain of fatigue, weight loss, and other constitutional symptoms

Exam

weight loss, occasionally fever, pallor; other physical examination findings vary according to the cancer type

1st investigation
  • biopsy:

    identification of malignant cells in lymph node

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Other investigations
  • FBC:

    anaemia may be present in any malignancy; pancytopenia may indicate bone marrow infiltration

  • CT scan:

    staging; identify primary tumour or other sites of metastasis; lymph nodes may have central necrosis

  • PET scan:

    staging; identify primary tumour or other sites of metastasis

  • Gallium 68 PET scan:

    staging; identify metastatic neuroendocrine tumour

Thymoma

History

presenting symptoms depend on tumour location, size, growth rate, and paraneoplastic syndromes; half of patients with thymomas are asymptomatic; in symptomatic patients, 40% have myasthenic symptoms; paraneoplastic syndromes include myasthenia gravis, limbic encephalitis, pure red cell aplasia; symptoms include chest pressure, hoarseness, chest wall pain, dysphagia, and dyspnoea related to tumour compression or invasion; myasthenic manifestations include easy fatigability, ptosis, diplopia, dysarthria; limbic encephalitis manifestation includes mood or behavioural changes, cognitive dysfunction

Exam

often asymptomatic; airway compression (stridor, prolonged inspiration/expiration); recurrent laryngeal nerve compression (hoarseness); superior vena cava obstruction (facial swelling, collateral veins, plethora); myasthenic manifestations (easy fatigability, ptosis, diplopia, dysarthria); limbic encephalitis (cognitive dysfunction, complex partial seizures, hyperthermia)

1st investigation
  • CT scan of chest:

    enlarged thymus often with well-defined borders and preservation of fat planes; local invasion may be present

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  • MRI:

    distinguishes between cysts, thymic neoplasm, and thymic hyperplasia

Other investigations
  • acetylcholine receptor antibody:

    elevated titre (range varies with assay used)

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  • FBC:

    anaemia may be a result of paraneoplastic pure red cell aplasia

  • biopsy:

    only necessary when prevascular (anterior) mediastinal mass appears infiltrative or invasive, which often requires neo-adjuvant therapy; if mass is characteristic of a resectable thymoma, pre-operative biopsy is generally avoided

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Lung cancer

History

may present with cough, dyspnoea, haemoptysis, chest pain, weight loss; fatigue, hoarseness, dysphagia; bone metastases suspected if bone pain and/or fractures; brain metastases suspected if confusion, personality changes, nausea and vomiting, headache, seizures present

Exam

wheeze, rales, decreased breath sounds, and dullness to percussion; cervical or supraclavicular adenopathy, finger clubbing, hypertrophic osteoarthropathy; in superior vena cava (SVC) syndrome: facial swelling, dilated neck or chest/abdominal wall veins

1st investigation
  • CXR:

    non-small cell lung cancer (NSCLC): variable; may detect single or multiple pulmonary nodule(s), mass, pleural effusion, lung collapse, or mediastinal or hilar fullness; small cell lung cancer (SCLC): central or peripheral mass, hilar lymphadenopathy, superior mediastinal lymphadenopathy, pleural effusion

  • CT chest:

    NSCLC: shows size, location, and extent of primary tumour; evaluates for hilar and/or mediastinal lymphadenopathy and distant metastases; SCLC: massive lymphadenopathy and direct mediastinal invasion are common features of SCLC; determines extent of disease

Other investigations
  • bronchoscopy:

    endobronchial lesions

  • biopsy:

    malignant cells, high nuclear to cytoplasmic ratio, nuclear fragmentation often present

  • 18F-FDG PET-CT:

    NSCLC: evaluates location and extent of primary tumour; evaluates for hilar and/or mediastinal lymphadenopathy and distant metastases

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Uncommon

Aortic dissection

History

sudden-onset chest pain, usually described as ripping or tearing; pain is often maximal at onset and changes as the dissection evolves; pain radiating into the neck or jaw may indicate that the dissection involves the aortic arch and extends into the great vessels of the arch; pain that is felt in the intrascapular area may indicate that the dissection involves the descending aorta; aortic dissection can be painless in about 10% of patients and especially in patients with collagen vascular disorder

Exam

hypertension may result from a catecholamine surge or underlying essential hypertension; hypotension may be the result of excessive vagal tone, cardiac tamponade, or hypovolaemia from rupture of the dissection; neurological deficits occur in 20% of cases; most common neurological findings are syncope and altered mental status; dyspnoea may be caused by congestive heart failure or tracheal or bronchial compression; new diastolic murmur from aortic insufficiency; asymmetrical pulses and blood pressure measurements

1st investigation
  • CT scan of chest with contrast enhancement:

    detects aortic dissection and determines its size

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  • trans-oesophageal echocardiography:

    diagnostic of aortic dissection and assesses aortic valvular abnormalities

    More
Other investigations
  • CXR:

    widened mediastinum silhouette, enlarged aortic knob, displacement of aortic intimal calcification

    More
  • angiography:

    aortic dissection and associated vascular abnormalities

    More
  • MRI:

    detects size and location of thoracic aortic aneurysm

    More

Hodgkin's lymphoma

History

persistently enlarged lymph nodes, constitutional or B symptoms (fevers, night sweats, and/or weight loss)

Exam

lymphadenopathy in one or more regions, hepatosplenomegaly may be present, fever

1st investigation
  • peripheral lymph node excisional biopsy:

    type of Hodgkin's lymphoma

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Other investigations
  • FBC:

    anaemia or pancytopenia may be present

    More
  • lactate dehydrogenase (LDH):

    elevated; is a sign for disease activity and a prognostic marker

  • CT scan of neck, chest, abdomen, and pelvis:

    evaluation of the extent of lymphadenopathy and staging

    More
  • PET-CT scan of neck, chest, abdomen, and pelvis:

    evaluation of the extent of lymphadenopathy and staging

  • bone marrow biopsy:

    lymphoma cells may be present in bone marrow

    More

Mediastinal germ cell tumour: seminoma

History

presenting symptoms depend on tumour location, growth rate, and size; seminomas tend to grow slowly and metastasise later than non-seminomas, and may reach a larger size at presentation; symptoms include chest pressure, hoarseness, chest wall pain, dysphagia, and dyspnoea; occurs in people aged 20 to 40 years, with male predominance

Exam

often asymptomatic; airway compression may present with stridor and prolonged inspiration/expiration; recurrent laryngeal nerve compression may present with hoarseness; superior vena cava obstruction may present with facial swelling, collateral veins, plethora; testicle examination may reveal testicle mass

1st investigation
  • CT scan of chest, abdomen, and pelvis:

    bulky, locally invasive mass; irregular borders; pulmonary and intrathoracic metastases may be seen

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Other investigations
  • biopsy:

    type and grade of seminoma

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  • serum beta-HCG:

    may be elevated

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  • serum alpha-fetoprotein:

    negative; if elevated, non-seminomatous components are present

  • testicular ultrasound:

    testicular neoplasm may appear as well-defined hypoechoic lesions or inhomogeneous lesions with calcifications, cystic areas, and indistinct margins

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Mediastinal germ cell tumour: non-seminoma

History

patients often have symptoms at presentation; symptoms include chest pressure, hoarseness, chest wall pain, dysphagia, and dyspnoea; constitutional symptoms include fever, chills, and weight loss

Exam

signs of airway compression (stridor, prolonged inspiration/expiration); signs of recurrent laryngeal nerve compression (hoarseness); signs of superior vena cava obstruction (facial swelling, collateral veins, plethora); testicle examination may reveal testicle mass; gynaecomastia

1st investigation
  • CT scan of chest, abdomen, and pelvis:

    large lobulated inhomogeneous mass with thin capsule, may contain areas of haemorrhage and necrosis; mediastinal fat invasion commonly seen; pulmonary and intrathoracic metastases may be seen

Other investigations
  • biopsy:

    depends on type and grade of seminoma

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  • beta-HCG:

    may be elevated

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  • alpha-fetoprotein:

    elevated

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  • testicular ultrasound:

    testicular neoplasm may appear as well-defined hypoechoic lesions or inhomogeneous lesions with calcifications, cystic areas, and indistinct margins

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Thymic carcinoma

History

majority of patients are symptomatic at presentation; symptoms may include chest pressure, hoarseness, chest wall pain, dysphagia, and dyspnoea; symptoms from tumour metastases may be present, such as bone pain or lymphadenopathy; may have constitutional symptoms of fever, weight loss, or sweats; paraneoplastic symptoms uncommon

Exam

signs of airway compression (stridor, prolonged inspiration/expiration); sign of recurrent laryngeal nerve compression (hoarseness); signs of superior vena cava obstruction (facial swelling, collateral veins, plethora)

1st investigation
  • CT scan of chest, abdomen, and pelvis:

    invasive, poorly defined mediastinal mass with obliteration on mediastinal fat plane; vascular invasion, lymphadenopathy, and extrathymic metastases are common; may also contain calcification and necrosis

    More
Other investigations
  • biopsy:

    depends on type and grade of thymoma

    More
  • FBC:

    anaemia may be a result of paraneoplastic pure red cell aplasia

Primary tracheal tumours

History

tracheal obstruction results in dyspnoea, cough, and stridor (may be misdiagnosed as asthma in children); acute respiratory distress may not be present until the trachea is almost completely occluded; haemoptysis may occur

Exam

tracheal obstruction results in respiratory distress, cough, wheezing, and stridor

1st investigation
  • CT scan of chest with contrast enhancement:

    tumours are often small, solid, and located within the tracheal lumen; extra-tracheal invasion may be present

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Other investigations
  • bronchoscopy:

    assesses location and extent of tumour, provides access for tumour biopsy

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  • pulmonary function test:

    flattening of inspiratory and expiratory curve on flow-volume loop

  • biopsy:

    results depend on type and grade of tumour

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Neurogenic tumour

History

no gender predilection; commonly occurs in young adults; asymptomatic in majority of adults but only 20% of children; children commonly present with respiratory symptoms such as dyspnoea and cough; if associated with neurofibromatosis, multiple skin neuromas are present; depending on size and location, tumours may result in spinal cord compression, pain, numbness, weakness, and muscle atrophy

Exam

hypertension and/or tachycardia, may be a sign of a catecholamine-secreting tumour; classic triad of phaeochromocytoma may present with headache, sweats, and tachycardia; airway compression may present with stridor, prolonged inspiration/expiration; recurrent laryngeal nerve compression may present with hoarseness; superior vena cava obstruction may present with facial swelling, collateral veins, plethora

1st investigation
  • CT scan of chest with contrast enhancement:

    almost always located in paravertebral (posterior) mediastinum along costovertebral sulcus; rounded or spindle- or dumbbell-shaped mass; spinal invasion or spinal canal extension; intratumoral calcification may be present

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Other investigations
  • metaiodobenzylguanidine (MIBG) scan:

    defines extent and identifies other areas of involvement of a catecholamine-secreting tumour

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  • plasma free metanephrines (also known as metadrenalines) or 24-hour urine fractionated metanephrines (also known as metadrenalines) and normetanephrines (also known as normetadrenalines):

    elevated levels support diagnosis of catecholamine-secreting tumour

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  • biopsy:

    results depend on type and grade of neurogenic tumour

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Thyroid neoplasm

History

patients often have a known goitre; substernal extension may present with exertional dyspnoea, positional dyspnoea, stridor, wheezing, or cough

Exam

often painless solitary nodules; presence of goitre (80% to 90% of patients with substernal goitres have a visible goitre); hypertension and tachycardia may be a sign of thyrotoxicosis or phaeochromocytoma; substernal extension suggested by inability to identify the lower pole of thyroid gland; airway compression may present with stridor, prolonged inspiration/expiration; tracheal deviation if goitre is asymmetrical; presence of Pemberton's sign (neck vein distension and facial flushing when arms are held vertically above head - Pemberton's manoeuvre)

1st investigation
  • CT scan of neck and chest without contrast enhancement:

    determines extent and size of thyroid mass

    More
Other investigations
  • thyroid-stimulating hormone:

    usually elevated if hypothyroidal, normal if euthyroidal, or suppressed if hyperthyroidal

  • thyroglobulin and anti-thyroglobulin antibody levels:

    may be elevated in thyroid cancer but not in medullary thyroid cancer

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  • calcitonin level:

    may be elevated in medullary thyroid cancer

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  • radioactive iodine thyroid scan:

    'cold' nodule may be indicative of a thyroid neoplasm

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  • MRI neck and chest:

    assesses relationship of mass to vascular structures

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  • biopsy:

    result depends on type and grade of thyroid tumour

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Substernal goitre

History

history of known goitre; exertional or positional dyspnoea; stridor or wheezing; cough; hyperthyroidism symptoms (heat intolerance, weight loss, insomnia)

Exam

80% to 90% of patients with substernal goitres have a visible goitre; substernal extension suggested by inability to identify lower pole of thyroid gland; airway compression may present with stridor, prolonged inspiration/expiration; signs of thyrotoxicosis (weight loss, hypertension, and tachycardia); tracheal deviation if goitre is asymmetrical, presence of Pemberton's sign (neck vein distension and facial flushing when arms held vertically above head - Pemberton's manoeuvre)

1st investigation
  • CT scan of neck and chest without contrast enhancement:

    determines extent and size of thyroid

    More
Other investigations
  • thyroid-stimulating hormone:

    usually elevated if hypothyroidal, normal if euthyroidal, or suppressed if hyperthyroidal

  • MRI neck and chest:

    assesses relationship of mass to vascular structures

    More

Acute lymphocytic leukaemia (ALL)

History

fatigue, dyspnoea, dizziness, bleeding, easy bruising, and recurrent infections

Exam

pallor and ecchymoses, and rarely lymphadenopathy and hepatosplenomegaly

1st investigation
  • FBC:

    anaemia, leukocytosis, leukopenia, and/or thrombocytopenia

Other investigations
  • bone marrow biopsy:

    bone marrow hypercellularity and infiltration by leukaemic lymphoblasts

  • molecular studies:

    to detect genetic abnormalities associated with ALL

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  • mediastinoscopy and biopsy:

    performed if marrow or peripheral blood testing is non-diagnostic

Chronic lymphocytic leukaemia

History

age >60 years; frequently asymptomatic and detected as an incidental finding on blood tests for another reason; B symptoms: fever, chills, night sweats, weight loss, and fatigue

Exam

painless peripheral lymphadenopathy, splenomegaly

1st investigation
  • FBC:

    elevated WBC count with absolute lymphocytosis >5000/microlitre; anaemia and thrombocytopenia may be present

  • blood film:

    smudge cells present

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Other investigations
  • flow cytometry on peripheral blood:

    CD5, CD19, and CD23 positive

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  • bone marrow biopsy:

    more than 30% of the cells are lymphocytes

  • mediastinoscopy and biopsy:

    performed if marrow or peripheral blood testing is non-diagnostic or if there is suspicion that mediastinal lymphadenopathy is a different process

Pericardial cyst

History

thin-walled cysts that arise from the pericardium; almost always asymptomatic and identified incidentally; signs of congestive heart failure (dyspnoea, oedema, fatigue, and palpitations)

Exam

haemodynamic compromise may occur depending on size and location of lesion; signs of congestive heart failure (oedema, elevated jugular venous pressure); arrhythmia (atrial fibrillation) may also be present

1st investigation
  • CT scan of chest with contrast enhancement:

    non-enhancing, thin-walled, well-defined, homogeneous masses; attenuation is close to water density

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Other investigations
  • MRI:

    cysts have low signal intensity on T1 weighted images and high signal intensity on T2 weighted images

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Bronchogenic cyst

History

occurs in both adults and children without gender predilection; may be asymptomatic and identified incidentally; chest pain and dysphagia are most common presenting symptom; consider bronchogenic cyst in patients with recurrent lung infections

Exam

signs of airway compromise (cough, wheezing, dyspnoea, and respiratory distress); signs of infection (fever, purulent sputum, cough)

1st investigation
  • CXR:

    well-defined round mass often located in the vicinity of the carina; air-fluid level may be present

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Other investigations
  • CT scan of chest with contrast enhancement:

    non-enhancing, thin-walled, well-defined, homogeneous masses; cyst may contain blood, pus, or secretions; calcifications may be present

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Oesophageal cyst (includes oesophageal duplication cyst)

History

almost always asymptomatic and identified incidentally; often present during childhood; chest tightness or fullness and dysphagia may be present

Exam

almost always asymptomatic

1st investigation
  • CT scan of chest with contrast enhancement:

    non-enhancing, well-defined, homogeneous masses

    More
Other investigations
  • barium swallow:

    demonstrates the presence of communication between cyst and oesophagus lumen

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  • endoscopy and endoscopic ultrasound (EUS):

    identifies an oesophageal duplication cyst to be a protruding, submucosal mass that is covered by normal epithelium; EUS differentiates between an intramural or extramural mass and delineates the relation of the cyst to surrounding structures

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Mediastinal germ cell tumour: mature teratoma

History

often asymptomatic and is an incidental finding; presenting symptoms depend on tumour location and size; symptoms include chest pressure, hoarseness, chest wall pain, dysphagia, and dyspnoea; can occur in any age group but more common in children or young adults, with no gender predilection

Exam

often asymptomatic; airway compression (stridor, prolonged inspiration/expiration); recurrent laryngeal nerve compression (hoarseness); superior vena cava obstruction (facial swelling, collateral veins, plethora)

1st investigation
  • CT scan of chest, abdomen, and pelvis:

    mass may be solid or cystic; well delineated from surrounding tissue; fat-fluid level or fatty mass with globular calcification may be seen; tumour may have a calcified capsule and occasionally contain teeth

    More
Other investigations
  • biopsy:

    depends on type and grade of teratoma

    More
  • serum beta-HCG:

    negative

    More
  • serum alpha-fetoprotein:

    negative

    More

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