The CD15 antigen, also known as Lewis (hapten)X, serves as an immuno-phenotypic marker for Reed-Sternberg cells and its expression has diagnostic, but also prognostic significance in Hodgkin Lymphoma.

Mycoplasma infection causes cold autoimmune haemolytic anaemia (AIHA). The rest of the aforementioned options cause warm AIHA.

AIHA may be divided into ‘warm’ and ‘cold’ types, according to the temperature at which the antibodies best cause haemolysis. It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection, or drugs.

1. Warm AIHA:
In warm AIHA, the antibody (usually IgG) causes haemolysis best at body temperature and tends to occur in extravascular sites, for example, spleen. Management options include steroids, immunosuppression, and splenectomy. It is caused by autoimmune diseases such as SLE (rarely causes mixed-type AIHA), cancers such as lymphomas and CLL, and drugs such as methyldopa.

2. Cold AIHA:
The antibody in cold AIHA is usually IgM and causes haemolysis best at 4°C and occurs more commonly intravascularly. Features may include symptoms of Raynaud’s disease and acrocyanosis. Patients do not respond well to steroids. Cold AIHA is caused by cancers such as lymphomas, and infections such as mycoplasma and EBV.

This patient is a case of chronic myeloid leukaemia (CML) and should be started on imatinib as the first-line drug of choice.

The direct Coombs test will specifically confirm immune-mediated haemolysis occurring post-transfusion in the aforementioned case.

There are two types of Coombs test used in immunohematology and immunology:

1. Direct Coombs test – It confirms autoimmune haemolytic anaemia by detecting antibodies or complement proteins attached to the surface of red blood cells.

2. Indirect Coombs test – It is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. It detects antibodies floating freely in the blood, against foreign red blood cells.

Tumour marker CA 125 is mostly associated with primary peritoneal cancer and ovarian cancer. It can be used to monitor response to chemotherapy, alongside regular CT scans.

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)

Deletion of part of chromosome 5 or 7 is a poor prognostic feature for 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.

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.

Gamma delta T cells are of low abundance in the body, are found in the gut mucosa, skin, lungs and uterus, and are involved in the initiation and propagation of immune responses. Their ligands are not known in detail, but the gamma delta T cell receptors recognise intact proteins rather than MHC-presented peptides. Like alpha beta T cells, they develop in the thymus.

Urinary porphobilinogen is increased between attacks of acute intermittent porphyria (AIP) and even more so, between acute attacks.

AIP is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. This results in the toxic accumulation of delta-aminolaevulinic acid and porphobilinogen.

Abdominal and neuropsychiatric symptoms are characteristic of AIP especially in people between the ages of 20-40 years. The disease is more common in females than in males (5:1). Major signs and symptoms of AIP include abdominal pain, vomiting, motor neuropathy, hypertension, tachycardia, and depression.

Diagnosis:
1. Urine turns deep red on standing (classical picture of AIP)
2. Raised urinary porphobilinogen (elevated between attacks and to a greater extent, between acute attacks)
3. Raised serum levels of delta-aminolaevulinic acid and porphobilinogen
4. Assay of red blood cells for porphobilinogen deaminase

Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion characterised by the acute onset of non-cardiogenic pulmonary oedema following transfusion of blood products.

TRALI is a more severe manifestation of the febrile non-haemolytic group of transfusion reactions and usually occur in patients who have had multiple previous transfusions. TRALI is related to leucocyte antibodies which are present in the plasma of the blood donor. Multiparous women are the highest-risk donors for TRALI.

For management, leucocyte-depleted blood is now used for transfusion and this is associated with a reduced risk of this type of transfusion reaction.

Immune thrombocytopenic purpura (ITP) refers to thrombocytopaenia occurring in the absence of toxic exposure or other diseases associated with low platelets and involves IgG-type antibodies. It is characterised by normal or increased marrow megakaryocytes, shortened platelet survival, and the absence of splenomegaly. Autoimmune haemolytic anaemia (AIHA) occurs commonly in association with ITP. Leukemic transformation, however, does not occur in ITP.

In neonatal ITP, IgG antibodies are passively transferred across the placenta. The infant platelet count may be normal at birth but decreases within 12-24 hours. It is rarely severe enough to induce bleeding diathesis in the infant.

Burkitt lymphoma is a germinal centre B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer.

The patient has spinal cord compression until proven otherwise. Urgent assessment is required.

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

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include weight loss and lethargy; monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

A Coomb’s test should be performed to test for autoimmune haemolytic anaemia. Spherocytes and reticulocytes in the blood film are indications for haemolytic anaemia.

NICE guidelines on hypercalcemia recommend that maintaining good hydration equals drinking 3-4 L of fluid/day, provided there are no contraindications. A low calcium diet is not necessary because intestinal absorption of calcium is reduced. The patient should avoid any other drugs or vitamins that could worsen the hypercalcemia. Mobilization is encouraged and any symptoms of hypercalcemia should be reported.

Patients with a VTE within the previous three months, patients with AF and previous stroke or TIA or multiple other risk factors, and patients with a mitral valve replacement should be considered for bridging therapy.

The most appropriate bridging therapy in this case would be low-molecular-weight heparin (LMWH), with the last dose given not less than 24 hours prior to the procedure. Warfarin should be discontinued 5 days prior to the procedure. If the INR is still above 3 on the day prior to the procedure, vitamin K should be administered.

In hereditary non-polyposis colonic carcinoma (HNPCC), mutations in MSH2, MSH6, PMS2 or MLH1 genes are found.
Ataxia telangiectasia – ATM gene is affected.
Familial adenomatous polyposis – APC gene is affected.
Li-Fraumeni syndrome – mutation of the TP53 tumour suppressor gene. Neurofibromatosis – mutation in or a deletion of the NF1 gene

Bulbar palsy and pseudobulbar palsy are rare types of a motor neuron disease that affect the cranial motor nerves. Bulbar palsy is a lower motor neuron palsy that affects the nuclei of the 9th to 12th cranial nerves. Pseudobulbar palsy is an upper motor neuron palsy that affects the corticobulbar tracts of the 5th, 7th and 9th to 12th cranial nerves. Any condition which disrupts or damages the cranial nerve nuclei or corticobulbar tracts can cause bulbar or pseudobulbar palsy (e.g., stroke, multiple sclerosis, infections, brain stem tumours). Both bulbar and pseudobulbar palsy are seen mainly in men over 75 years old and present with progressive dysarthria and dysphagia. In addition, patients with pseudobulbar palsy present with a lack of facial expression, difficulty chewing, and emotional lability. Lower motor neuron signs (atrophy and fasciculations of the tongue, absent gag reflex) differentiate bulbar palsy from pseudobulbar palsy, which presents with upper motor neuron signs (spastic tongue, exaggerated gag, and jaw jerk reflexes). Diagnosis is mainly clinical and treatment mostly supportive with a poor prognosis. Life expectancy is around 1-3 years following diagnosis.

Leukemoid reaction has a high LAP score.

Leukemoid reaction refers to leucocytosis occurring as a physiological response to stress or infection which may be mistaken for leukaemia, especially chronic myeloid leukaemia (CML). Leucocytosis occurs, initially, because of accelerated release of cells from the bone marrow and is associated with increased count of more immature neutrophils in the blood (left-shift). In order to differentiate, LAP score is used. Leukocytic alkaline phosphatase (ALP) activity is high in a leukemoid reaction but low in CML.

LAP score is high in:
1. Leukemoid reaction
2. Infections
3. Myelofibrosis
4. Polycythaemia rubra vera
5. Steroids, Cushing’s syndrome
6. Pregnancy, oral contraceptive pill

LAP score is low in:
1. CML
2. Pernicious anaemia
3. Paroxysmal nocturnal haemoglobinuria (PNH)
4. Infectious mononucleosis

Normal pO2 but decreased oxygen saturation is characteristic of methemoglobinemia.

Methemoglobinemia is a rare condition in which the haemoglobin iron is in oxidized or ferric state (Fe3+) and cannot reversibly bind oxygen. Normally, the conversion of ferrous form of iron (Fe2+) to its ferric form (Fe3+) is regulated by NADH methaemoglobin reductase, which results in the reduction of methaemoglobin to haemoglobin. Disruption in the enzyme leads to increased methaemoglobin in the blood. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxygen-haemoglobin dissociation curve is shifted to the left.

Methemoglobinemia can occur due to congenital or acquired causes. Congenital causes include haemoglobin variants such as HbM and HbH, and deficiency of NADH methaemoglobin reductase. Acquired causes are drugs (e.g. sulphonamides, nitrates, dapsone, sodium nitroprusside, and primaquine) and chemicals (such as aniline dyes).

The features of methemoglobinemia are cyanosis, dyspnoea, anxiety, headache, severe acidosis, arrhythmias, seizures, and loss of consciousness. Patients have normal pO2 but oxygen saturation is decreased. Moreover, presence of chocolate-brown coloured arterial blood (colour does not change with addition of O2) and brown urine also point towards the diagnosis of methemoglobinemia.

Extra-nodal presentation is more common in non-Hodgkin lymphoma (NHL) than in Hodgkin lymphoma (HL). Bone marrow infiltration is more common in low-grade than in high-grade NHLs.

Low-grade NHL is predominantly a disease of older people. Most present with advanced disease, bone marrow infiltration being almost invariable. Anaemia, leucocytosis, and/or thrombocytopaenia in a patient are suggestive of bone marrow involvement. For definitive diagnosis, lymph node biopsy is sufficient.

The other aforementioned statements are ruled out because:
1. Renal impairment in NHL usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement.

2. Burkitt lymphoma is a high-grade NHL, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement, and ovarian tumours. It develops most often in children or young adults and is uncommon in older people.

3. High-grade lymphomas are potentially curable. They have a better prognosis and are responsive to chemotherapy unlike low-grade lymphomas, which are incurable with conventional therapy.

Neutrophilia is also commonly associated with polycythaemia vera.

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5-15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli. The laboratory results will usually include fragmented RBCs, decreased serum haptoglobin, reduced platelet count, nonspecific WBC changes, and normal coagulation tests (PTT included).

Haemochromatosis is an abnormally high rate of the production of haemoglobin. It is an autosomal recessive disease copied on chromosome 6. It is associated with hepatic disorders, cardiac diseases and skin pigmentation. It is treated by regular venesection.

Red cell aplasia is commonly associated with thymomas.

Thymoma is the most common tumour of the anterior mediastinum and is usually detected between the sixth and seventh decades of life. It is associated with myasthenia gravis (30-40% of patients), red cell aplasia, and dermatomyositis. Compression of airway and cardiac tamponade are the common causes of death in thymoma.

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.

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).