Out of the aforementioned markers, low corrected calcium is the only biochemistry result consistent with the diagnosis. All of the other markers are elevated in TLS.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. As phosphate precipitates calcium, the serum concentration of calcium becomes low. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Patients at high risk of TLS should be given IV rasburicase or IV allopurinol immediately prior to and during the first few days of chemotherapy. Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower-risk groups
should be given oral allopurinol during cycles of chemotherapy in an attempt to avoid the condition.

TLS is graded according to the Cairo-Bishop scoring system as:
1. Laboratory tumour lysis syndrome
2. Clinical tumour lysis syndrome

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

Thalassaemias are a group of genetic disorders characterised by decreased production of either alpha or beta chains of haemoglobin (Hb). Beta thalassaemia trait is an autosomal recessive condition in which a disproportionate hypochromic, microcytic anaemia occurs—microcytosis is disproportionate to the Hb level. It is usually asymptomatic.

Microcytic anaemia in a female should raise the possibility of either gastrointestinal blood loss or menorrhagia. However, there is no history to suggest this in the aforementioned patient. This, combined with characteristic disproportionate microcytosis and raised HbA2 levels ( >3.5%), point towards beta thalassaemia trait.

Basophilic stippling is also seen in lead poisoning but the raised HbA2 levels cannot be explained in such a case.

Rasburicase should be given prior to chemotherapy in order to reduce the risk of tumour lysis syndrome (TLS). Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is 5–10 times more soluble than uric acid, hence, renal excretion is more effective.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Burkitt lymphoma is a high-grade B-cell neoplasm. There are two major forms:
1. Endemic (African) form: typically involves maxilla or mandible.
2. Sporadic form: abdominal (e.g. ileocaecal) tumours are the most common form. More common in patients with HIV.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14). The Epstein-Barr virus (EBV) is strongly implicated in development of the African form of Burkitt lymphoma and to a lesser extent, the sporadic form.

Management of the lymphoma is with chemotherapy. This tends to produce a rapid response which may cause TLS.

An MRI whole spine should be performed in a patient suspected of spinal metastasis which can occur before developing metastatic spinal cord compression. This patient has renal cell carcinoma, which readily metastasises to the bones and also has progressive back pain. He, therefore, needs urgent imaging of his spine before any neurological compromise develops. MRI whole spine is preferable because patients with spinal metastasis often have metastases at multiple levels within the spine. Plain radiographs and CT scans should not be performed as they have a lower sensitivity for revealing lesions and cannot exclude cord compression.

In general, imaging should be performed within one week if symptoms suspicious of spinal metastasis without neurological symptoms are present. If there are symptoms suggestive of malignant spinal cord compression, then imaging should be done within 24 hours.

The signs and symptoms of spinal metastases include:
1. Unrelenting lumbar back pain
2. Thoracic or cervical back pain
3. Pain associated with tenderness and worsens with sneezing, coughing, or straining
4. Nocturnal pain

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect nearly any organ system: the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin. The histopathological features are similar across organs, regardless of the site. IgG4-RD is analogous to sarcoidosis, in which diverse organ manifestations are linked by similar histopathological characteristics. Raised concentrations of IgG4 in tissue and serum can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.

Some IgG4-RDs are:
1. Autoimmune pancreatitis
2. Riedel’s Thyroiditis
3. Mediastinal and Retroperitoneal Fibrosis
4. Periaortitis/periarteritis/Inflammatory aortic aneurysm
5. Kuttner Tumour (submandibular glands)
6. IgG4-related Mikulicz disease (lacrimal, parotid, and submandibular glands)

Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Patients at high risk of TLS should be given IV rasburicase or IV allopurinol immediately prior to and during the first few days of chemotherapy. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower-risk groups should be given oral allopurinol during cycles of chemotherapy in an attempt to avoid the condition.

TLS is graded according to the Cairo-Bishop scoring system as:
1. Laboratory tumour lysis syndrome
2. Clinical tumour lysis syndrome

Vitamin B12 is mostly used in the body for the development of red blood cells and maintenance of the nervous system. It is actively absorbed in the terminal ileum after binding to the intrinsic factor (IF) which is secreted from the parietal cells of stomach. Moreover, a small amount is also passively absorbed without being bound to IF.

Vitamin B12 deficiency is characterised by sore tongue and mouth, mood disturbances, ataxia, and macrocytic anaemia. Its causes include poor diet, impaired absorption (due to disorders of terminal ileum), pernicious anaemia, and post-gastrectomy. While managing this condition, if the person is also deficient in folic acid, then it is important to treat the B12 deficiency first in order to avoid precipitating subacute combined degeneration of the cord.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

Patients with active cancer are at a continuous risk of having venous thromboembolism (VTE), such as DVT. Therefore, a six-month course of an anticoagulant such as LMWH is recommended. LMWH is the drug of choice since its side effects can be reversed and it can be stopped easily in case of a cancer-related bleed, for example, massive haemoptysis in a patient with lung cancer.

Elevated haemoglobin A2 level is seen in beta thalassaemia trait, whereas, it is typically low in iron deficiency anaemia unless the patient has received a recent blood transfusion.

Low mean corpuscular volume (MCV) and reduced haematocrit (Ht) are encountered in both conditions. Peripheral blood smear is grossly abnormal in both beta thalassaemia and severe iron deficiency anaemia, showing bizarre morphology, target cells, and a small number of nucleated red blood cells.

Nausea and vomiting are the common side effects of chemotherapy. Risk factors for the development of these symptoms include age<50 years, anxiety, concurrent use of opioids, and the type of chemotherapy administered. For patients at low risk of these symptoms, drugs such as metoclopramide may be used. For high-risk patients, however, 5-HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone.

A translocation between chromosome 15 and 17 is seen in acute promyelocytic leukaemia (APL), which is known to carry a good prognosis.

Acute myeloid leukaemia (AML) is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly. The disease has poor prognosis if:

The disease has poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

APL is an aggressive form of AML. It is associated with t(15;17) and has a good prognosis. The general age of presentation is less than that in other types of AML (average age is 25 years old). On blood film, abundant Auer rods are seen with myeloperoxidase staining. Thrombocytopaenia or DIC is seen in patients presenting with this disease.

Group AB donors are the universal donors of FFP. This is because they produce neither anti-A nor anti-B antigens in their plasma and are, therefore, compatible with all ABO groups.

The aforementioned patient’s blood group is B meaning, thereby, she naturally produces anti-A antigens in her plasma and would need to receive plasma that does not have anti-B antigens in it. Hence, she can only receive FFP from donors of group B or AB. Moreover, as she is of childbearing age, she must receive RhD negative blood in order to avoid problems with future pregnancies if her foetus would be RhD positive.

The patient has Meigs syndrome. Meigs syndrome is defined as a triad of benign ovarian tumour with ascites and pleural effusion that resolves after resection of the tumour. Ovarian fibromas constitute the majority of the benign tumours seen in Meigs syndrome.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

The diagnosis of Hodgkin disease requires the identification of Reed-Sternberg cells in a characteristic cellular background. The normal cell of origin for the Reed-Sternberg cells remains unclear, with the predominance of evidence indicating a B or T lymphocyte.

Bombesin is a tumour marker elevated in small cell lung carcinomas, as well as in gastric carcinomas and retinoblastomas.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

The prognosis of breast cancer depends chiefly on the extent of nodal metastases.

The breast cancer TNM staging system is the most common way that doctors use to stage breast cancer. TNM stands for Tumour, Node, Metastasis. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero), which is non-invasive ductal carcinoma in situ (DCIS), and stages I through IV (1 through 4), which are used for invasive breast cancer.

Staging can be clinical or pathological. Clinical staging is based on the results of tests done before surgery, which may include physical examinations, mammogram, ultrasound, and MRI scans. Pathologic staging is based on what is found during surgery to remove breast tissue and lymph nodes. In general, pathological staging provides the most information to determine a patient’s prognosis.

There are two main reasons for using combinations of chemotherapeutic agents rather than single agents. First, different drugs exert their effects through different mechanisms, therefore, carefully combining them will increase the number of tumour cells killed in each cycle as well as decrease their chances of developing drug resistance. Second, there may be an even greater effect with drugs that are synergistic.

The upper motor neurone signs in this patient point towards a diagnosis of spinal cord compression above the level of L1 and rules out cauda equina syndrome.

Spinal cord compression is an oncological emergency and affects up to 5% of cancer patients. Extradural compression accounts for the majority of cases, usually due to vertebral body metastases. One of the most common causes of spinal cord compression is osteoarthritis. It is also more commonly seen in patients with lung, breast, or prostate cancer.

Clinical features include:
1. Back pain: the earliest and most common symptom, may worsen on lying down or coughing
2. Lower limb weakness
3. Sensory changes: sensory loss and numbness
4. Neurological signs: depending on the level of the lesion.
Lesions above L1 usually result in upper motor neurone signs in the legs. Lesions below L1 usually cause lower motor neurone signs in the legs and perianal numbness. Tendon reflexes are increased below the level of the lesion and absent at the level of the lesion.

Management options are:
1. High-dose oral dexamethasone
2. Urgent MRI for consideration of radiotherapy or surgery

B2-microglobulin is a useful marker of prognosis in multiple myeloma (MM). Raised levels imply a poorer prognosis. Low levels of albumin are also associated with a poor prognosis.

The principal mechanism of action of taxanes (e.g. docetaxel) is the prevention of microtubule disassembly.

Other aforementioned options are ruled out because:

1. Doxorubicin: stabilizes DNA topoisomerase II complex and inhibits DNA and RNA synthesis.

2. Vincristine, vinblastine: inhibits formation of microtubules.

3. Cisplatin: causes cross-linking in DNA.

Of all the listed options, gastric cancer is least likely to be inherited.

The above mentioned tumours are ruled out as explained below:
1. Breast and Ovarian cancers: Between 5%–10% of all breast cancers are thought to be hereditary. Mutation in the BRCA1 and BRCA2 genes also increase the risk of ovarian cancer.

2. Colorectal and Endometrial cancers: About 5% of cases of colorectal cancer are caused by hereditary non-polyposis colorectal carcinoma (HNPCC) and 1% are due to familial adenomatous polyposis. Women who have HNPCC also have a markedly increased risk of developing endometrial cancer—around 5% of endometrial cancers occur in women with this risk factor.

Cyclophosphamide is a cytotoxic alkylating agent that acts by causing cross-linking of DNA strands. Its major adverse effects include haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma.

Cardiomyopathy is caused by doxorubicin and ototoxicity is caused by cisplatin. Alopecia and weight gain are associated with a variety of chemotherapeutic agents especially those that treat breast cancers (e.g. paclitaxel).

This is a picture of bone marrow failure secondary to acute myeloid leukaemia (AML). AML is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly.

The disease has poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

Acute promyelocytic leukaemia (APL) is an aggressive form of AML.

Other listed options are ruled out because:
1. Von Willebrand disease: may present with epistaxis and bleeding gums in severe cases but rarely with abnormalities on blood results.

2. Acute lymphoblastic leukaemia: mostly seen in children.

3. Lymphoma: usually presents with rubbery enlargement of lymph nodes.

4. Warfarin overdose: no bilobed large mononuclear cells seen on blood film.

Subcutaneous (S/C) low-molecular-weight heparin (LMWH) is a preferred anticoagulant in pregnancy. Warfarin is contraindicated due to its teratogenic effects, especially in the first trimester and at term.

Pregnancy is a hypercoagulable state with the majority of VTE incidents occurring in the last trimester.

Hypercoagulability in pregnancy is caused by:
1. Increase in factors VII, VIII, X, and fibrinogen
2. Decrease in protein S
3. Uterus pressing on IVC causing venous stasis in legs

Management options include:
1. S/C LMWH preferred to IV heparin (less bleeding and thrombocytopaenia)
2. Warfarin contraindicated

Exposure to aniline dyes is a risk factor for transitional cell carcinoma. Aniline dyes are used in dyestuffs and pigment manufacturing.

The other aforementioned options are ruled out because:
1. Feed production may expose to aflatoxin (hepatocellular carcinoma).

2. Being a military personnel may expose to mustard gas (lung cancer).

3. Rubber industry may expose to nitrosamines (oesophageal and gastric cancer).

4. Refrigerant production before 1974 may expose to vinyl chloride (hepatic angiosarcoma).

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

The most common type of Hodgkin’s lymphoma (HL) is nodular sclerosing.

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

According to the histological classification, there are four types of HL:

1. Nodular sclerosing: most common (around 70%), more common in women, associated with lacunar cells, good prognosis

2. Mixed cellularity: Around 20%, associated with a large number of Reed-Sternberg cells, good prognosis

3. Lymphocyte-predominant: Around 5%, Reed-Sternberg cells with nuclei surrounded by a clear space found, best prognosis

4. Lymphocyte-depleted: rare, worst prognosis

Prostate cancer is the most common primary tumour that metastasises to the bone.

Most common tumours causing bone metastasis (in descending order):
1. Prostate (32%)
2. Breast (22%)
3. Kidneys (16%)
4. Lungs
5. Thyroid

Most common sites of bone metastasis (in descending order):
1. Spine
2. Pelvis
3. Ribs
4. Skull
5. Long bones