Fig (a) Peripheral Blood Smear

In this issue we present the case of a 72-year-old man who was previously well. On a visit to his family physician for treatment of an upper respiratory tract infection, he is found to be pale. His haemoglobin is10.8 g/dl (14.0 – 18.0), MCV 72 fl (78 – 98), MCHC 31.8 g/dl (32 – 36). RBC distribution width (RDW) is 21.9 (normal range 10.9-15.7). Figure (a) shows the peripheral blood smear. During an executive physical examination 5 years ago his haemoglobin was 14.0 g/dl, MCV 88fl, and RDW 12.4. He also admits to having mild rectal bleeding for the past month. What is the diagnosis? (Hint: Refer to table 1 for differential diagnosis of microcytic, hypochromic anaemia as shown in the blood smear). What would be the next best step?

A) Barium enema
B) Upper oesophagogastroendoscopy
C) Colonoscopy
D) Haemoglobin electrophoresis
E) Start iron supplements and repeat haemoglobin in 3 months.

Table 1: Differential diagnosis of microcytic hypochromic anaemia
1.	Inherited haemoglobinopathy a. Alpha or beta thalassaemia b. Thalassaemia trait c. Haemoglobin E
2.	Iron deficiency a. Blood loss from gastrointestinal tract --- peptic ulcers, malignancies, parasites b. Inadequate intake, food faddism c. Decreased absorption secondary to achlorhydria, gastrectomy d. Increased requirement from pregnancy and lactation
3.	Sideroblastic anaemia
4.	Severe anaemia of chronic disease

Fig (b) A tumour in the Sigmoid Colon

He is then referred to a colorectal surgeon for colonoscopy. It reveals a tumour in the sigmoid colon (fig.b). A biopsy reveals an adenocarcinoma.

He is referred to a medical oncologist, who orders some staging investigations. However, before the investigations can be done the patient has acute-onset haematochezia (passage of bloody stools) followed by severe central chest pain associated with profuse sweating and nausea. Figure (c) shows the ECG done at the accident and emergency department. What is the diagnosis?
A) Pulmonary embolism
B) ECG changes due to electrolyte imbalances related to his tumour
C) ECG changes related to hyperventilation due to anxiety from diagnosis of cancer
D) Acute anteroseptal myocardial infarction
E) Intestinal obstruction due to his tumour.

Fig (c ) ST elevation in anterior leads

He is admitted and given appropriate care. Staging investigations done after recovery from the acute event reveals that, apart from the primary tumour in the sigmoid colon, there is a 1.8 cm nodule in the right adrenal gland suspicious of a metastasis. His CEA level is 1.8 ng/dl. Which of the following statements is correct?
A) He has metastatic stage IV disease, hence best supportive care is in order
B) He should undergo an open colectomy and adrenal biopsy
C) His CEA is normal hence metastatic disease is ruled out and CT findings should be ignored.
D) Because of the recent myocardial infarction, a non-invasive test should be considered for evaluation of the adrenal mass.

His PET /CT scans are shown in figure (d)

Fig d: PET/CT scan shows avid FDG uptake in the sigmoid tumour but low uptake in the adrenal nodule. This means that the right adrenal nodule is likely to be a benign “incidentaloma”.

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DISCUSSION

This elderly patient had a normocytic blood picture and a normal haemoglobin a few years ago, hence inherited haemoglobinopathies are ruled out. Furthermore, in inherited disorders with fixed heme iron and globin-chain imbalance the red blood cells are of uniform size, hence the microcytosis and hypochromia is accompanied by a normal RDW. By contrast, in iron-deficiency anaemia the RDW is wide, and there is a high degree of anisocoria (different shapes of red blood cells) and anisocytosis (different sizes red cells). The patient’s peripheral blood smear shows these three features. With his gastrointestinal bleeding, his anaemia is most likely due to iron deficiency resulting from a gastrointestinal abnormality. Since his symptoms are from the lower gastrointestinal tract, commencing with investigations of the area is sensible. If melaena were the main complaint, a lesion above the ligament of Trietz may be more likely and upper endoscopy would be favoured. Though a barium enema will demonstrate an abnormality, direct visualisation and biopsy would be required for confirmation. Hence a colonoscopy is the most prudent test.

The patient’s sudden passage of blood in the stools, followed by chest pain and nausea and vomiting is due to anteroseptal myocardial infarction. The infarction is likely to have been triggered by the anaemia from acute gastrointestinal blood loss on a background of iron-deficiency anaemia. Though cancers are related to hypercoagulability and some colorectal cancers are associated with diarrhoea, which can lead to electrolyte imbalances, the ECG picture of ST elevation in the anterior lead, and ST depression in the inferior lead is pathognomonic of myocardial ischaemia. His ECG done 2 hours after emergency percutaneous transluminal coronary angioplasty (PTCA) is shown in figure (e).

Antiplatelet therapy (with aspirin), anticoagulation, and even fibrinolysis with streptokinase or urokinase are common therapies for acute MI. However, when skills for PTCA exist, an early attempt at revascularisation with this procedure is effective and will minimise the need for fibrinolysis, which is important in this case with gastrointestinal bleeding. If complications or stenting are not required, need for anticoagulation would also be less.

A normal CEA does not rule out metastatic disease. Nevertheless, since chemotherapy offers survival advantage over no treatment even in patients with metastatic disease, best supportive care alone is not appropriate. The adrenal lesion might be a metastatic tumour, or a benign tumour, or a second primary. This differential diagnosis can be sorted out by CT-guided needle biopsy, or by a PET scan, which is emerging as a new non-invasive adjunct. In the overall management of this patient with symptomatic lower gastrointestinal bleeding, surgical resection may still be required. However, if a non-invasive option were available, it will be wise to avoid retroperitoneal sampling of the adrenals by a lengthy open procedure, with its risk of bleeding and need for salvage surgery, which would not be tolerated well by a patient so soon after a myocardial infarction. CT-guided needle biopsy is one such option.

In summary, this patient has non-metastatic colon cancer with lower gastrointestinal bleeding. Definitive treatment of this patient would be surgical resection after careful evaluation of his cardiac risk, and chemotherapy would be needed only if the tumour is of high-risk histological type or if there is node invasion.

Dr Donald Poon Registrar Medical Oncology

Dr Sandeep Rajan Senior Consultant Medical Oncology