Oncology: overview
Cancer is one of the leading causes of death worldwide, accounting for >8 million deaths in 2012.1 Age is a fundamental risk factor for the development of cancer. In the UK, cancer rates have risen by 23% in males and 43% in females since the mid 1970s with more than a third of new cancer diagnoses made in those aged ≥75. The burden of this disease will inevitably increase in ageing Western populations. Oncology is the medical specialty that deals with the diagnosis and management of solid cancers. Most management decisions take place in the outpatient setting and clinics will therefore form the basis of your attachment. However, you will see very little acute oncology here and it is vital that you also spend significant time on the specialist oncology wards and on-call to gain this experience.
Cases to see
The ‘big four’ tumour groups: breast, lung, prostate, and bowel cancer
You should have a basic understanding of the diagnosis and management of these four main tumour groups. This will best be done in outpatients. Follow-up clinics will not be useful to you so ask your consultant specifically about ‘new patient’ clinics. MDT meetings will also be beneficial as it is here that major treatment decisions are made.
Neutropenic sepsis
It is crucial you know how to manage this oncological emergency. Spend a couple of days shadowing the oncology SHO on-call and you should get good exposure to the cases that frequently present in the ED.
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The Sepsis Six bundle
The ‘Surviving Sepsis campaign’ (
www.survivingsepsis.org) was launched in 2002 with the aim of reducing mortality from severe sepsis and septic shock worldwide. The campaign saw the introduction of ‘sepsis bundles’, a selected set of evidence-based care elements which, when implemented, are designed to ensure the most effective management of the septic patient. ‘The Sepsis Six’ is a set of six interventions that can be delivered by any junior doctor in the acute setting to improve their patient’s chance of sepsis survival:
• Administer high-flow oxygen.
• Administer broad-spectrum antibiotics.
• Start IV fluid resuscitation.
• Take blood cultures.
• Measure serum lactate and FBC.
• Measure hourly urine output.
Malignant spinal cord compression (MSCC)
Find out who the oncology registrar on-call is and ask them to call you when a case is referred. Suspected cases are relatively common so you should see a reasonable number.
Superior vena cava obstruction
Cases are rarer than MSCC but again, make the on-call registrar aware and you should be able to see at least one during your attachment.
Hypercalcaemia
A very common metabolic emergency in oncology patients. You will undoubtedly see numerous cases on the wards.
Tumour lysis syndrome (TLS)
Although more common in haematological malignancies, TLS is also seen in solid tumours. Ask the ward registrar to direct you to high-risk patients and pay close attention to their pre-chemotherapy protocols and blood results.
Procedures to see
External beam radiotherapy
Radiotherapy lists take place all day, every day. Find the department and liaise with the radiographers who will be able to take you through the set-up and the different aspects of treatment.
Places to visit
Chemotherapy day unit
It is worth spending some time on the day unit. Extravasation and anaphylactoid reactions are undesirable but inevitable consequences of chemotherapy and you will gain good experience here in their acute management. Chemotherapy nurses are arguably the best around when it comes to venous cannulation and there will be ample opportunity to practise. It is a great place to hone your practical skills away from the pressure of the wards.
The hospice
Palliative care forms a major part of oncology with symptom control and the emotional and psychological support of cancer patients being crucial to the holistic approach to their care. All specialist oncology units will have a palliative care team. Shadowing them and visiting a hospice should be easily negotiable and will give you a unique insight into the vital work they do.
Things to see
The oncology ward is perhaps one of the best places to see a number of things that will be useful to you both in exams and as a junior doctor. Signs include radiotherapy tattoos, radiation-induced skin changes, and clubbing (it does exist!). Devices include colostomies, pleural drains, ascitic drains, syringe drivers, Hickman/PICC lines, and portacaths. Patients with such devices in situ are a favourite for OSCE examiners as they provide an excellent discriminator in identifying those candidates who have actually spent time on the wards.
Reference
1. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Lyon: International Agency for Research on Cancer. www.globocan.iarc.fr/Default.aspx
Oncology: on the ward
Malignant spinal cord compression
Most commonly caused by direct pressure on the spinal cord/cauda equina from vertebral bone metastases. Prostate, lung, and breast cancers account for the majority of solid tumour cases. Any delay in diagnosis and treatment can have catastrophic neurological consequences thus a high index of suspicion is required. Presentation: the earliest manifestation is back pain. This may be followed by muscle weakness, loss of sensation, and bladder/bowel dysfunction. Management: high-dose dexamethasone should be commenced immediately and an urgent MRI scan of the whole spine arranged to occur within 24 hours. Patients with a good performance status and prognosis >3 months should be considered for decompressive surgery. All others can be treated with palliative radiotherapy. Treatment should commence within 24 hours of a positive MRI diagnosis.
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Indications for surgical decompression
Decompressive surgery plus radiotherapy has been shown to have significantly improved outcomes in terms of regaining ambulation and pain control when compared to radiotherapy alone.1 Common indications include:
• unstable spine
• cervical cord lesion
• solitary vertebral metastasis
• radioresistant tumour (e.g. melanoma, sarcoma)
• unknown primary (to obtain tissue diagnosis)
• previous radiotherapy
• neurological deterioration while having radiotherapy.
Superior vena cava obstruction
Due to compression or invasion of the SVC by tumour, thrombus, or mediastinal lymph nodes. Bronchial carcinoma and lymphoma account for the vast majority of cases. Presentation: onset is usually insidious over weeks with gradual development of shortness of breath, headache, facial swelling, and visual disturbance. Signs: distended thoracic veins and a raised JVP. Pemberton’s sign: marked by facial congestion, dyspnoea, and cyanosis upon elevation of both arms. Management: supportive measures such as oxygen, analgesia, and high-dose dexamethasone for short-term symptomatic relief. Stenting is effective in >95% as a holding measure, providing relief within 48 hours. Chemotherapy is indicated in chemosensitive tumours (small cell lung cancer, germ cell tumours) and radiotherapy in all other solid tumours. Both may take up to 2 weeks to have their effect.
Hypercalcaemia
Defined by a corrected plasma calcium concentration of 2.6 mmol/L. Occurs as a result of direct destruction of the bone by metastases or consequent to circulating factors such as PTH-related peptide secreted by tumour cells. Incidence: highest in lung, breast, head, and neck and renal carcinomas. Symptoms: confusion, vomiting, constipation, abdominal pain, polyuria, and polydipsia. Left untreated, hypercalcaemia can progress to coma and death. Management: aggressive IV fluid administration forms the mainstay of treatment, ideally 3 L of crystalloid over 12 hours. Once adequately hydrated, IV bisphosphonates can be given and continued on a regular basis for maintenance.
Tumour lysis syndrome
Occurs due to excessive lysis of dying tumour cells, usually following chemotherapy, resulting in a huge release of intracellular contents into the systemic circulation. A series of metabolic derangements occur including hyperkalaemia, hyperuricaemia, hyperphosphataemia, and hypocalcaemia which can precipitate renal failure, arrhythmias, and seizures. Prevention is key to managing TLS. High-risk patients should be aggressively hydrated prior to chemotherapy and receive IV allopurinol—a xanthine oxidase inhibitor to reduce uric acid accumulation. Haemodialysis may be required if AKI still ensues.
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Risk factors for tumour lysis syndrome
Identifying patients at risk is critical in preventing TLS. The following parameters are associated with a higher incidence of TLS:
• Highly proliferating tumour (leukaemia, lymphoma).
• Tumour highly sensitive to chemotherapy (small cell lung cancer, germ cell tumours).
• Bulky disease.
• Elevated LDH.
• Pre-existing renal impairment.
• Dehydration.
• High-intensity chemotherapy.
Reference
1. Patchell RA, Tibbs PA, Regine WF, et al. (2005). Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 366(9486):643–8.
Oncology: in the emergency department
Neutropenic sepsis
Defined as a fever > 38°C and neutrophil count <500 cells/μL. Neutropenia means patients may not present with routine manifestations of sepsis such as tachycardia, sweating, and localized signs, so it may be easily missed. Have a high index of suspicion in all patients receiving chemotherapy. Broad-spectrum IV antibiotics must be commenced within 60 min of pyrexia, together with IV fluids. There is high potential for sudden deterioration into septic shock requiring aggressive resuscitation and rapid escalation of care. A full ‘septic screen’ should be performed including cultures (blood, sputum, etc.), blood tests, urinalysis, and CXR, but antibiotics are the priority—do not delay their administration while obtaining investigations! Ideally antibiotics, fluids, and paracetamol should be administered within <1 hour of presentation.
Symptom control
This is fundamental in the management of oncology patients. Patients may present to the ED with symptoms related to their disease, or side effects from either chemotherapy or radiotherapy.
Pain
This can be notoriously difficult to control, and cancer patients may require strong opioid analgesia at doses which you may not be experienced in prescribing. Patients attending the ED with intractable pain should be admitted and advice sought from the on-call palliative care team as soon as possible.
Nausea and vomiting
These are common side effects of both chemotherapy and radiotherapy. However, this is a diagnosis of exclusion and a full assessment of the patient is required to rule out all other possible causes first. Common underlying pathologies include sepsis, bowel obstruction, hypercalcaemia, and raised ICP secondary to brain metastases. Patients with severe N&V will most likely be dehydrated. Having excluded other organic causes, they should be admitted for symptom control in the form of IV fluid resuscitation and IV antiemetics. 5HT antagonists (e.g. ondansetron) are the preferred choice in chemotherapy-induced N&V.
Diarrhoea
As with N&V, diarrhoea is a common side effect of both chemotherapy and radiotherapy. Radiation colitis is the most severe form of the latter. Patients may again present significantly dehydrated. Infective causes should be excluded and patients should then be admitted and managed with aggressive IV fluid resuscitation and antidiarrhoeal agents such as loperamide.
Oncology: in clinic
While it is all too easy to sit and observe consultations from the safety of the corner of the clinic room, you will learn far more and gain invaluable points with your consultant if you see a patient first and present the case. No one will expect you to come up with a definitive treatment plan but taking an adequate history of both the patient and the tumour will allow for a sensible discussion as to how best to manage the case. When assessing the patient, take into consideration their presenting symptoms, risk factors, and importantly, their comorbidities. Surgery, chemotherapy, and radiotherapy can be intense treatments and not all patients will be fit enough to tolerate them.
Performance status
An impressive way for you to quantify a patient’s fitness would be by quoting their ‘performance status’ (Table 24.1).
Table 24.1 The European Cooperative Oncology Group (ECOG) Performance Status scale
| Grade |
ECOG Performance Status |
| 0 |
Fully active, able to carry on all pre-disease performance without restriction |
| 1 |
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work |
| 2 |
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours |
| 3 |
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours |
| 4 |
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair |
| 5 |
Dead |
Oken MM, Creech RH, Tormey DC, et al. (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649–55
Staging and grading
When assessing the tumour, you should record both the histological diagnosis and the stage of the cancer. Histology will usually include the tumour type (e.g. adenocarcinoma, squamous cell carcinoma), the tumour grade, and the degree of differentiation. High-grade, poorly differentiated tumours tend to be associated with poorer prognoses. Staging describes the anatomical extent of the disease and is best defined using TNM staging. Each tumour group will have its own criteria for TNM staging, the minutiae of which you will not be expected to remember. A broad understanding of the principles of the system as described below should suffice (Table 24.2 and Table 24.3).
Table 24.2 The TNM classification of malignant tumours
| Parameter |
Description |
| T |
The size of the primary tumour and its invasion into local tissue (T1–T4) |
| N |
The extent of regional lymph node spread (N0–N3) |
| M |
The presence of metastases to distant organs (M0–M1) |
Table 24.3 Generic grading system for many types of cancer
| Grade |
Description |
| Grade X |
Grade cannot be assessed |
| Grade 1 |
Low grade |
Well differentiated |
| Grade 2 |
Intermediate grade |
Moderately differentiated |
| Grade 3 |
High grade |
Poorly differentiated |
| Grade 4 |
High grade |
Undifferentiated |
Tumour markers
Circulating tumour markers produced by cancers may serve as a useful adjunct to the histological diagnosis and staging of tumours and should be noted. However, tumour markers should be solely relied on since there is a high risk of giving false positives and hence causing anxiety to patients. There has to be a strong reason to request these and in some hospital, permission from consultants must be sought before ordering these investigations. They may be helpful in predicting prognosis and in monitoring response to treatment (e.g. cancer surveillancing). You may find yourself quizzed on the most clinically relevant tumour markers (Table 24.4).
Table 24.4 Common tumour markers and their associated cancers
| Tumour marker |
Cancer |
| PSA (prostate-specific antigen) |
Prostate |
| CEA (carcinoembryonic antigen) |
Colon |
| CA15-3 |
Breast |
| CA19-9 |
Pancreas |
| CA125 |
Ovarian |
| AFP (alpha-fetoprotein) |
Hepatocellular, testicular |
| β-HCG (beta-human chorionic gonadotrophin) |
Testicular, ovarian germ cell |
| LDH (lactate dehydrogenase) |
Testicular, lymphoma |
National cancer screening
Programmes
Breast, lung, prostate, and bowel cancer together account for over half of all new cancer diagnoses per year. Cancers diagnosed at the earliest stage are those most amenable to cure. Cancer screening programmes are designed to try and identify disease in individuals in a population prior to the development of signs and symptoms, enabling earlier intervention and reducing the risk of mortality. There are currently three NHS cancer screening programmes in the UK: those for breast cancer, bowel cancer, and cervical cancer. There are currently no screening programmes for lung or prostate cancer. A successful screening programme must be robust, viable, cost-effective, and appropriate. WHO guidelines known as Wilson’s criteria1 were introduced in 1968 and these form the basis of the criteria used to justify the introduction of new screening programmes today.
Wilson’s criteria for screening
1. The condition should be an important health problem.
2. The natural history of the condition should be understood.
3. There should be a recognizable latent or early symptomatic stage.
4. There should be a test that is easy to perform and interpret, acceptable, accurate, reliable, sensitive, and specific.
5. There should be an accepted treatment recognized for the disease.
6. Treatment should be more effective if started early.
7. There should be a policy on who should be treated.
8. Diagnosis and treatment should be cost-effective.
9. Case-finding should be a continuous process.
Prostate cancer
This accounts for ~30% of all cancers in men and is second only to lung cancer as the commonest cause of male cancer deaths. There is no national screening programme. Presentation: early-stage disease is often asymptomatic, but symptoms of ‘prostatism’ consequent to obstruction of urinary flow through an enlarged prostate may be present. Obstructive symptoms include hesitancy, terminal dribbling, poor or double stream, nocturia, and frequency. Examination/diagnosis: after taking a focused micturition history and performing a digital rectal examination, diagnostic investigations should include a PSA and transrectal ultrasound-guided prostate biopsy. Bear in mind that the PSA may be elevated in patient after performing a digital rectal examination so PSA can be tested beforehand. Staging investigations should include an MRI of the pelvis to assess local spread and a radionuclide bone scan to look for metastasis. Management: early stage, prostate-confined disease is managed with curative intent either with surgical prostatectomy or radical radiotherapy. Metastatic disease is treated with anti-androgen therapy and chemotherapy.
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Gleason grading system
Prostate cancer is histologically graded using the Gleason system. This is based on the degree of glandular differentiation with grade 1 being well differentiated and grade 5 being the most poorly differentiated. The Gleason grades of the two most common histological patterns found within the tumour are summated to form the overall Gleason score, giving a range from 2 to 10. The higher the Gleason score, the more aggressive the cancer and the higher the risk of recurrence and mortality:
• Gleason < 7: low risk and favourable prognosis.
• Gleason = 7: moderate risk and intermediate prognosis.
• Gleason > 7: high risk and poor prognosis.
Breast cancer
Accounts for 20% of all cancer diagnoses and there is a 1 in 9 lifetime risk for women. There is a National Screening Programme for breast cancer in the form of a 3-yearly mammogram offered to all women aged 50–70. Risk factors: age >60, early menarche and late menopause, nulliparity, hormone replacement therapy, the oral contraceptive pill, and family history. Genetics: ~5–10% of cases are thought to be hereditary arising from germline mutations in BRCA1 or BRCA2 genes. Diagnostic investigations: mammogram (or US) and fine-needle aspiration (FNA) for histology. Tissue is always tested for the presence of oestrogen (ER), progesterone (PR) and HER-2 receptors. Management: surgery, either wide local excision (WLE) or mastectomy forms the mainstay of treatment for early breast cancer and surgical staging of axillary nodes takes place during primary surgery. Preoperative staging investigations are not routinely performed in low-risk patients. Following WLE and in high-risk mastectomy patients, locoregional radiotherapy is indicated to reduce the risk of local relapse. ER/PR-positive tumours are treated with hormone therapy such as antioestrogens such as tamoxifen and HER-2-positive tumours with trastuzumab®. Both treatments have been shown to improve survival. Chemotherapy is considered for high-risk early-stage patients (high grade, nodal involvement, HER-2 positive) and in metastatic disease.
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Sentinel lymph node biopsy
Surgical staging of the axilla is carried out in all patients with invasive disease. Previously, this was done by axillary clearance but sentinel lymph node (SLN) biopsy is now the gold standard:
• The SLN is the first draining lymph node from the breast, thus it is the first to receive tumour cells from the primary tumour.
• Methylene blue dye and a radioisotope are injected preoperatively to identify the SLN.
• SLN is removed and examined histologically for tumour cells.
• If SLN is –ve, no further surgery is required. Axillary clearance and its associated morbidity (lymphoedema, pain) is avoided.
• If SLN is +ve, axillary clearance or radiation may be required
Lung cancer
Accounts for ~15% of all cancer diagnoses. It is the commonest cause of cancer death in men and equals the breast cancer mortality rate in women. Aetiology: smoking is the primary cause and is responsible for 80% of cases. Smoking is the commonest carcinogenic factor and risk of cancer is correlated with the number of pack-years. One pack-year is equivalent to smoking 20 cigarettes per day, every day for 1 year. Symptoms: cough, haemoptysis, shortness of breath, chest pain, hoarseness, and dysphagia on a background of fatigue, weight loss, and recurrent chest infections. Investigations: diagnostic investigations include pleural fluid aspiration and cytology, bronchoscopic biopsy, or CT-guided biopsy, depending on the location of the tumour. Staging investigations will include bronchoscopy and CT of the chest and abdomen. Types: lung cancer is divided histologically into two distinct clinical entities: small cell and non-small cell lung cancer (NSCLC). NSCLC: staged using the TNM system and early-stage disease is treated with curative intent with either surgical resection or radical radiotherapy. Small cell disease: tends to be advanced at presentation and surgery is not usually an option. It is staged as either limited or extensive depending on whether the disease extends beyond one hemithorax. Chemotherapy is the standard treatment together with concurrent thoracic radiotherapy in limited-stage disease.
To ask the boss
Stereotactic ablative radiotherapy (SABR)
SABR is a specialized form of radiotherapy that can be used to treat small, early-stage NSCLC in patients whose comorbidities or preferences preclude surgery. Compared to conventional radiotherapy which involves giving daily low doses of radiation over numerous weeks, SABR uses thin, focused beams to deliver higher doses to the tumour in far fewer treatments, usually between three and eight.
Bowel cancer
Accounts for ~13% of all cancer diagnoses and is the third most common cause of cancer deaths in both men and women.
Genetics
710–15% of cases can be attributed to underlying inherited genetic conditions such as HNPCC and familial adenomatous polyposis.
Symptoms
Depend on the location of the tumour but may include changes in bowel habit (alternating diarrhoea and constipation), PR bleeding, tenesmus, weight loss, and fatigue.
Investigations
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Bowel cancer screening
The NHS Bowel Cancer Screening Programme was introduced in England in 2006:
• Screening is offered every 2 years to all men and women aged between 60 and 74.
• Those eligible are sent out a letter and a faecal occult blood (FOB) test kit with instructions for use.
• Once samples are received in the lab, the test is processed and results sent out within 2 weeks.
• Those with a positive result are offered a colonoscopy.
• Those with a negative result return to routine screening.
A systematic review of bowel cancer screening using the FOB test has shown to reduce the risk of mortality from the disease by 16%.
Colonoscopy plus biopsy is the gold standard diagnostic investigation. Those intolerant to endoscopy can be referred for CT pneumocolon. Staging is with CT of the chest, abdomen, and pelvis.
Management
Surgical resection is the mainstay of treatment for all except extensive metastatic disease where palliative chemotherapy can be considered. Palliative stomas can also be an option for pain resulting from distal tumour obstruction.
Reference
1. Wilson JMG, Jugner G (1968). Principles and Practice of Screening for Disease. Geneva: World Health Organization.
Oncology: in exams
History station
Being able to take an appropriate history from a patient with suspected malignancy is an absolute must for medical students and is therefore one of the most commonly examined scenarios in the history station.
History of presenting complaint
Know your red flags! If a patient presents with one, establish its details (duration, timing, exacerbating/relieving factors, etc.) and then ask about the rest associated with that tumour (Table 24.5). Follow this up immediately by enquiring about the systemic features of malignancy. So-called constitutional symptoms consist of weight loss (to cachexia), fatigue, and anorexia ± night sweats. Recurrent infections may also occur.
Table 24.5 ‘Red flag’ symptoms for specific tumour groups
| Cancer |
‘Red flag’ symptoms |
| Colorectal |
Change in bowel habit (diarrhoea/constipation), painless PR bleed, tenesmus, abdominal mass, mucoid discharge |
| Upper GI (stomach, oesophagus) |
Dysphagia, dyspepsia, melaena, haematemesis, epigastric mass |
| Lung |
Haemoptysis, chronic cough, recurrent pneumonia, chest pain, hoarseness, shortness of breath |
| Urogenitary (prostate, bladder, renal) |
Painless haematuria, frequency, nocturia, urinary retention, poor stream, hesitancy |
Past medical history
Ask generally and then about any previous history of malignancy. Certain medical conditions predispose to individual cancers, particularly those of the GI tract and the best candidates will enquire about them specifically where relevant (see Table 24.6).
Table 24.6 Medical conditions predisposing to GI cancers
| Cancer |
Predisposing medical condition |
| Colorectal |
Ulcerative colitis, Crohn’s disease |
| Oesophageal |
Barrett’s oesophagus, coeliac disease, GORD |
| Stomach |
Pernicious anaemia |
Family history
Again, ask generally and then specifically enquire about any family history of malignancy. 5–10% of breast cancers and 10–15% of bowel cancers are hereditary.
Social history
Smoking and alcohol are risk factors for numerous cancers so accurately quantify previous and current habits. Occupation is also important to establish any prior exposure to carcinogens.
Examination
Malignancy will form part of the differential diagnosis for a number of cases that may arise in the clinical exam. It should be considered in the patient with jaundice, ascites, pleural effusion, hepatomegaly, splenomegaly, and lymphadenopathy.
Lung cancer
The one tumour group that may present as the primary diagnosis in the clinical exam. Look for the thoracotomy scar! So often missed as it may be subtle and well-hidden posterolaterally, its presence suggests a previous pneumonectomy or lobectomy and puts lung cancer right at the top of your differential. With the deal pretty much in the bag, you can then go on to confidently elicit any associated signs such as clubbing, cachexia, nicotine staining, Horner’s syndrome, radiotherapy tattoos, and cervical lymphadenopathy. Ask about lifestyle factors that 
the risk of cancer (alcohol and smoking). More information is available for breast examination and prostate examination.
Final quick tips
Bear in mind that patients with cancer, a chronic process, can present late and may result in exudative effusions which can be massive before symptoms present, since there has been time to compensate (e.g. pleural effusion, ascites, etc.). Don’t let this throw you. Finally, just remember, ‘cancer’ can be a highly emotive word and you should always take care to maintain sensitivity when presenting in front of patients in the clinical exam. ‘Mitotic lesion’ or ‘neoplasm’ are acceptable alternatives.