1. ANOTHER LUMP IN THE NECK
Amanda Brown, is a 35 year old primary school teacher. She has a history of pancreatitis, and no medication except the oral contraceptive pill. She smokes 10 cigarettes/day.
The G.P, Dr Black records for this problem are as follows:
3rd October: Dry cough and (?) slight breathlessness
Chest and throat clear on examination, PEFR = 420 l/min
Advised symptomatic treatment (fluids, paracetamol, aspirin gargles) Told to stop smoking
11th Nov: Returns to GP - cough worse, keeping her awake at night. No sputum. She has now developed chest pain.
She is complaining of feeling hot at night and has lost 6kg in weight
O/E: Temperature 38.20C
Rubbery non-tender 2cm lymph node in left anterior triangle of neck
How would the GP have examined the neck?
Consider the differential diagnosis for an enlarged lymph node in the neck.
What is the procedure for urgent assessment in this situation?

2. Things to consider Differential diagnosis in relation to
Her age
Her symptoms
Characteristics of the neck lump
Causes of lumps in the neck
Which investigations ?

4. Causes of enlarged lymph nodes
Age: node biopsies showing malignancy
20%<20y
80%>50y
Characteristics of the lump
Size
Location eg supraclavicular v post cervical
Tender nodes less likely to be malignant
Matted/fixed adherent more malignant
BIOPSY TO BE SURE

5. Differential diagnosis of lumps in neck
Acute infection
bacterial, viral
Chronic infection
mycobacterial, toxoplasmosis
Inflammatory process
granulomatous disease
Malignant process
primary or secondary?
Other causes
Developmental cysts
Lipoma
Nodular goitre

6. Investigations at this stage
GP might consider:
Serological testing: HIV, EBV (monospot)
Full blood count
Biochemical testing: LFT, LDH
Chest X-ray
Referral to rapid access neck lump clinic

7. Neck lump clinic Recommendation of cancer network
Rapid access: ENT assessment +FNA/Biopsy
FNA: may help to distinguish if infective or malignant
Biopsy: best for establishing diagnosis of lymphoma/other malignancy

8. Dr Black refers her urgently to the local neck lump clinic
Dr Black refers her urgently to the local neck lump clinic. She is given an appointment for the following week. However, before then her chest pain becomes more severe and she attends the A&E Department. She is more breathless and finds it difficult to lie flat. She is admitted to hospital. A chest X-Ray is reported as showing a mediastinal mass with left paratracheal nodes
What differential diagnosis should be considered by the doctor in A&E?
Which urgent investigations should be requested?

9. Causes of chest pain and breathlessness in this context
Infection
Pulmonary embolism
Pleural effusion
Malignant infiltration of lungs/heart
Pericarditis
Pulmonary oedema
Mass effect
History and clinical findings will help differentiate cause
Investigations: Chest X ray, FBC

10. Causes of a Mediastinal Mass on CXR
Anterior mediastinum
Thymus
Lymphoma
Pericardial cyst
Thyroid, parathryroid
Middle mediastinum
Bronchial carcinoma
Infectious process
Metastatic node
Posterior mediastinum
Vascular lesion
Neurogenic tumour

11. Chest X-Ray in Lymphoma

12. What other investigations are required?
An opinion is sought from Dr White, the Haematologist. She recommends a lymph node biopsy. Amanda is worried about scarring to the neck and asks if there is an alternative method of getting a result. Dr White tells her that a complete lymph node biopsy will be necessary to obtain the diagnosis and that other investigations are also necessary
What methods are used to get tissue from lymph nodes? Which is the most suitable in this case?
What other investigations are required?

13. Best practice in lymphoma diagnosis and reporting (BCSH 2007)
Recommendations
Fine needle aspiration samples should not normally be used as the sole tissue for diagnosis (Grade B; evidence level III)
“Lymph node biopsies should be taken whenever possible. Core biopsies may be necessary from inaccessible sites but it is recognised that diagnoses where architecture is important e.g indolent lymphomas may be difficult”
Each MDT should have at least one identified Pathologist who will review material from all new diagnoses (Grade C; evidence level IV)

14. Investigations CT Thorax Lymph node biopsy FBC
consider Thoracoscopy and mediastinal biopsy if no peripheral nodes
FBC
Renal, Liver function, Lactate Dehydrogenase (LDH)
Echocardiogram
HIV serology

15. The biopsy is reported as showing Diffuse Large Cell Non-Hodgkin’s Lymphoma (DLBCL). Dr White sees Amanda with the Joanne Green the haematology Specialist Nurse to explain the diagnosis and treatment. Dr White informs her that her case will be discussed at the Lymphoma MDT where a complete treatment plan will be made and she will discuss the results with her. She also outlines the benefits and risks associated with treatment and possible long term side effects. Joanne Green stays behind to talk further to Amanda and gives her a information booklets on NHL, chemotherapy and consent to treatment. The nurse reports that Amanda’s main concern are the possible effects on fertility as she would like to have children, although does not have a partner at the present time.

16. Questions: Why/how to we stage Non – Hodgkin’s Lymphoma?
What are the implications of being diagnosed with this condition?
What are the side effects of chemotherapy?
What is the role of the multidisciplinary team in managing cancer?
What sources of patient information are available?

17. Lymphoma Malignancy of cells of lymphoid origin
The major subdivision is Hodgkin's Lymphoma (HL) and
Non Hodgkin's Lymphoma (NHL) – histologically distinct
The incidence of lymphomas compared to leukaemias
~ 500 cases of CML in UK annually
~2,500 cases of AML in UK annually
7,500 cases of NHL in UK annually
1,200 adult cases of HL UK annually
Hodgkin’s Lymphoma
Differs clinically from NHL
Characteristic Reed-Sternberg cells found which are not usually present in NHL

18. Classification of Lymphoma
WHO classification of lymphoma (2001)
Cell lineage i.e. B, T /NK
Morphology
Immunophenotype
Clinical behaviour
Genetic features
Defines specific disease entities allowing tailored treatments and indications of prognosis

20. WHO/REAL Classification of Lymphoid Neoplasms
B-Cell Neoplasms
Precursor B-cell neoplasm
Precursor B-lymphoblastic leukemia/lymphoma
(precursor B-acute lymphoblastic leukemia)
Mature (peripheral) B-neoplasms
B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma‡
Splenic marginal zone B-cell lymphoma
(+ villous lymphocytes)*
Hairy cell leukemia
Plasma cell myeloma/plasmacytoma
Extranodal marginal zone B-cell lymphoma of MALT type
Nodal marginal zone B-cell lymphoma
(+ monocytoid B cells)*
Follicular lymphoma
Mantle cell lymphoma
Diffuse large B-cell lymphoma
Mediastinal large B-cell lymphoma
Primary effusion lymphoma†
Burkitt’s lymphoma/Burkitt cell leukemia§
T and NK-Cell Neoplasms
Precursor T-cell neoplasm
Precursor T-lymphoblastic leukemia/lymphoma
(precursor T-acute lymphoblastic leukemia
‡ Formerly known as lymphoplasmacytoid lymphoma or immunocytoma
II Entities formally grouped under the heading large granular lymphocyte
leukemia of T- and NK-cell types
* Provisional entities in the REAL classification
Mature (peripheral) T neoplasms
T-cell chronic lymphocytic leukemia / small
lymphocytic lymphoma
T-cell prolymphocytic leukemia
T-cell granular lymphocytic leukemiaII
Aggressive NK leukemia
Adult T-cell lymphoma/leukemia (HTLV-1+)
Extranodal NK/T-cell lymphoma, nasal type#
Enteropathy-like T-cell lymphoma**
Hepatosplenic γδ T-cell lymphoma*
Subcutaneous panniculitis-like T-cell lymphoma*
Mycosis fungoides/Sézary syndrome
Anaplastic large cell lymphoma, T/null cell,
primary cutaneous type
Peripheral T-cell lymphoma, not otherwise characterized
Angioimmunoblastic T-cell lymphoma
primary systemic type
Hodgkin’s Lymphoma (Hodgkin’s Disease)
Nodular lymphocyte predominance Hodgkin’s lymphoma
Classic Hodgkin’s lymphoma
Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)
Lymphocyte-rich classic Hodgkin’s lymphoma
Mixed cellularity Hodgkin’s lymphoma
Lymphocyte depletion Hodgkin’s lymphoma
† Not described in REAL classification
§ Includes the so-called Burkitt-like lymphomas
** Formerly known as intestinal T-cell lymphoma
# Formerly know as angiocentric lymphoma

21. NHL v HD ?
HD spreads in contiguous fashion from one nodal area to next geographical area
NHL more widespread at presentation
NHL more likely to have disease on both sides of diaphragm
Waldeyers ring involvement suggests NHL
HL predominantly in young people
Biopsy with immunohistochemistry is definitive

22. Histology
CD20 expression in DLBCL

23. Diffuse Large B-cell Lymphoma (high grade lymphoma)
Most common NHL (~35%)
Typically de novo but can arise following transformation
Affects both sexes equally
Median age at diagnosis is 50 years
Can arise in nodal sites and extranodal sites
Highly aggressive
Highly responsive to combination chemotherapy ~ 40%
of patients with advanced stage achieving a cure

24. Staging Lymphoma
Assessment of extent of disease before and after treatment
Indication of prognosis
May dictate nature and intensity of treatment
Investigations:
CT scans
Bone marrow biopsy

25. Cotswold Classification (modifiedAnn Arbor) staging
Stage I - Involvement of only one lymph node region
Stage II - Two or more lymph node areas involved confined to one side of the diaphragm
Stage III - Involvement of lymph nodes above and below the diaphragm
Stage IV – Multi-focal involvement of an extranodal site
A = No constitutional symptoms
B = Constitutional symptoms present ( 10% weight loss; night sweats; unexplained fever – but not pruritis)
E = Extra-nodal disease at a single site with or without adjacent adenopathy (IE or IIE; by convention IIIE is stage IV)
X = Bulk disease. > 10cm max dimension or >1/3rd widening of mediastinum

26. Involved areas Each rectangle corresponds to one nodal area
Count 2 sites if bilateral
Spleen is considered extra nodal site

27. Staging scans Pre treatment: neck, thorax, abdo, pelvis
Interim - if clinical response uncertain or not assessable
Post treatment
(Follow up)
PET scanning now routine pre and post treatment for DLBCL (and hodgkin)

28. International Prognostic Index ( For DLBCL treated with R-CHOP)
Age > 60
Elevated LDH
Ann Arbor Stage III or IV
ECOG PS ≥ 2
Number of Extranodal sites > 1
SCORE
RISK GROUP
4 YR PFS
4 YR OS
Very Good 94
1,2
Good 80 79
3,4,5
Poor 53 55
Blood 2006

29. Management of NHL Indolent Aggressive Watch and wait
Chemo for symptomatic disease
Rituximab based regimes (R-CVP)
Aggressive
Localised (stage 1A) or medically unfit
Radiotherapy
Advanced
Chemo with Rituximab based regimes (R-CHOP) for B cell neoplasms

30. Coiffier et al. NEJM 2002

31. Side effects of treatment
Acute
Hair loss
Myelosupression (sepsis)
Emesis
Neuropathy
Pulmonary fibrosis
Longer term
Infertility
Hypothyroidism
Secondary malignancy
Myelodysplasia/leukaemia
Breast cancer (esp if radiotherapy before mid 20s)
Lung cancer
Cardiac disease

32. Late effects of treatment
Risks are increased by combined modality therapy (chemo plus RT)
Risks increased with larger radiation field and with mustine type drugs (MOPP)
Can we reduce treatment further for those with early favourable disease?
Prognostic scores
Imaging
How do we identify those that need additional treatment to maximise effectiveness?
GOALS OF TREATMENT
so there has ben a great deal of focus on trying to reduce these late effects.
Effective treatment
Minimise complications v

33. Individualising treatment
More aggressive regimes for poor prognosis disease
eg testicular lymphoma, Burkitts, T cell lymphomas
Reducing chemo based on predicted good outcome
Modification for co morbidities eg to encompass more elderly patients

34. Cancer standards: the MDT
MDT brings together all the professionals who are involved in diagnosis and care
Aims to improve quality of diagnosis and ensure equitable access to best possible care either at local hospital of cancer centre
Members should include cancer experts from specialist centres
Access to trials and research discussed
Holistic issues important
Discussions recorded with plans and outcomes documented: patient offered copy
MDT arrangements subject to peer review

35. The central purpose of the MDT meeting is to review every new case on a prospective, multi-disciplinary basis, identify missing data and those
investigations requiring further analysis, assign clinical stage, prognostic
scores (IPI, Hasenclever, EORTC) and determine appropriate
management/eligibility for trial entry according to network guidelines.

36. Amanda starts chemotherapy the following week
Amanda starts chemotherapy the following week. Dr White gets a phone call from Dr Black as the school have written to him requesting details of her treatment and when she might be fit to return to work. Dr White understands from Amanda that there will be pressure on her to return as soon as possible and she is worried about paying her mortgage if her sick pay runs out.

37. Consider the patient’s perspective
Issues affecting cancer patients
Telling family and friends
Work
Childcare
Sexual relationships
Financial
Psychological
Respect individuals privacy and wishes

38. Sources of support for cancer patients
Nurse and other trained counsellors
Social workers
Written information: BACUP, LRF, Lymphoma association, (internet)
Complimentary therapies