LymphomaBMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g3736 (Published 16 June 2014) Cite this as: BMJ 2014;348:g3736
- Michael Frank Harris, general practitioner and patient1,
- Christopher Knechtli, consultant haematologist2
- 1Gore Cottage, Old Gore Lane, Emborough, Radstock BA3 4SJ
- 2Royal United Hospital Bath NHS Trust, Combe Park, Bath BA1 3NG
- Correspondence to: M F Harris
- Accepted 16 April 2014
Two years ago, standing in front of the bathroom mirror, I noticed that I had a right inguinal swelling. Palpation showed it to be a rubbery, mobile mass, 2.5 cm in diameter. Examining more generally, I found that I had bilateral inguinal adenopathy, the contralateral glands being only 1 cm in diameter. I was unable to palpate any cervical or axillary glands.
I was a fit 55 year old general practitioner. I was aware that the pattern was unusual, but any malignant glands that I have felt in my career have been hard and fixed. Also, like most competitive road cyclists, I shave my legs, so I hoped that the adenopathy was due to razor rash.
After a month my wife made an appointment for me to see my general practitioner, but I cancelled it as I was convinced that the swellings were getting smaller. Another month later, I realised that there had been no significant change, so I saw my general practitioner. She examined me carefully, and, even though I had felt something catch her fingers when she was palpating my left upper quadrant, it was still a surprise when she said “I think you’ve got a spleen.” It was just palpable, halfway through deep inspiration.
Spending an hour googling “splenomegaly” and “regional adenopathy” made me realise that I had a diagnosis of lymphoma until proved otherwise. My general practitioner and consultant colleagues kindly let me organise an urgent inguinal node biopsy. Histology showed follicular lymphoma. I became anorexic and lost weight, so I assumed that I had the B type symptoms.
By the time I saw Dr Knechtli, the consultant haematologist, my appetite was returning, making me realise that my “B type” symptoms had actually been due to anxiety. However, the presence of splenomegaly on top of adenopathy in two areas suggested that I had widespread, stage IV lymphoma. The recommended management was “watchful waiting,” with no advantage in beginning chemotherapy until it started to cause problems. I read that recent improvements in treatment mean that life expectancy has lengthened considerably, but, as one of the papers coyly put it, there is as yet “no levelling off of the survival curve.”
My blood count was normal apart from showing lymphopenia, and the haematologist seemed pleasantly surprised that the bone marrow aspirate and trephine results showed no sign of involvement by lymphoma. However, staging computed tomography showed some mild mediastinal and abdominal lymphadenopathy. It also showed extensive nodular shadowing in my lungs, reported as being “likely to be related to lymphoma.” I was inclined to accept that diagnosis and, in view of my lack of any relevant symptoms, wait until it caused problems. The haematologist, however, told me that lung infiltration was not typical of lymphoma and persuaded me to accept a respiratory referral.
The chest consultant explained that there were four possible causes of the computed tomography findings: lymphoma, infection, sarcoidosis, and “a surprise,” which I took to be a euphemism for carcinoma. Bronchoscopy was normal, so I was listed for a lung biopsy. As a medical student in the late 1970s, I had spent time on a chest surgery ward and had vivid memories of patients with uncontrolled postoperative pain. To my relief, modern video-assisted thoracic surgery with excellent general and local anaesthesia, as well as nurses who ensured that I had sufficient analgesia, meant that my postoperative progress was not nearly as unpleasant as I had feared.
I was on holiday in France when the chest physician phoned with the histology: sarcoidosis. This was a huge relief. My knowledge of sarcoidosis was minimal, as I had never encountered a patient with it, so I spent a lot of time reading it up. I found that many cases, like mine, are asymptomatic, coincidental findings that may resolve spontaneously.
An interesting finding was that sarcoidosis can cause splenomegaly and inguinal adenopathy, as well as lymphopenia. I felt so well that it was difficult to believe that I had widespread lymphoma, so the overlap between the clinical findings in the two conditions made me start to question my lymphoma staging. When I saw Dr Knechtli for a follow-up appointment, I asked him whether all my clinical findings, apart from the single larger, biopsied inguinal gland, could actually be due to sarcoidosis. Unlike the haematologist, I had had two weeks to think and read up about that as a possible alternative explanation for my clinical signs. As a general practitioner, I know just how difficult it is when patients come up with a completely different way of interpreting their symptoms, and I could see in the haematologist’s face his struggle to analyse the alternative diagnosis and lymphoma staging that I had sprung on him.
He agreed that my lymphoma staging was now uncertain but said that the only way to confirm it absolutely would be to have an excision biopsy of my spleen, a mediastinoscopic lymph node biopsy, and a computed tomography guided biopsy of my abdominal glands. Given the risks and morbidity attached, these were not attractive options.
After discussion, I requested a biopsy of my mildly enlarged contralateral inguinal nodes. To my delight, they were reported as being reactive rather than due to lymphoma or sarcoidosis. That led me to hypothesise that all my clinical findings could be due to sarcoidosis or be reactive, apart from a single gland on the right side that had undergone lymphomatous change. If true, it would mean that I had stage I follicular lymphoma with an 80% chance of cure by radiotherapy.
Discussions with Dr Knechtli and a clinical oncologist confirmed that radiotherapy was a reasonable option. They ensured that I was aware that I may indeed have stage IV lymphoma, making a course of radiotherapy futile. However, given the “sporting chance” that I had only stage I disease, the risks and morbidity associated with the relatively low dose of treatment seemed acceptable, so I had a course of radical radiotherapy to my right hemi-pelvis.
A haematologist’s perspective
Staging a patient’s lymphoma is the most important part of the pre-treatment evaluation. In the Ann Arbor staging system, early stage lymphoma is defined by the involvement of only one group of affected lymph nodes (stage I) or of two or more affected lymph node groups on the same side of the diaphragm (stage II) in the absence of any constitutional “B” symptoms, such as unexplained weight loss, severe night sweats, or fevers. For the small minority of patients with follicular lymphoma presenting with stage I or II disease involving contiguous nodal groups and no B symptoms, the recommended management is radiotherapy to the affected areas.
However, more than 90% of patients present with more advanced stage (IIB to IVB) disease. Here, combination chemotherapy is indicated if the patient has significant symptoms, bulky disease (especially if it is compromising organ function), or impaired marrow function due to lymphomatous involvement. Such treatment is highly effective in inducing remission but is not considered to be curative.
Early chemotherapy confers no survival advantage for asymptomatic advanced stage patients, so for that group a “watch and wait” approach is usually adopted. However, evidence from a recent trial shows that such patients can benefit from the provision of weekly rituximab infusions for four weeks followed by two monthly rituximab maintenance for two years.1
I will confess that I initially suspected that my patient had advanced stage lymphoma with splenic involvement and lymphadenopathy on both sides of his diaphragm. However, the nodular pulmonary involvement did not fit with the usual behaviour of low grade lymphoma. I knew that establishing the cause of the pulmonary findings would require an invasive procedure. In these circumstances, it is tempting to ignore the problem, perhaps citing Occam’s razor: when evaluating two hypotheses, the simpler explanation should be given preference. This can be expressed more colloquially as: “When you hear the sound of hooves, think horses not zebras.” On the other hand, this runs a risk of missing dual pathology. So further investigation is merited if a feature of a patient’s presentation does not fit with the working diagnosis.
Once Dr Harris’s concurrent diagnosis of sarcoidosis was made, the challenge was how to establish the stage of his lymphoma. At its most thorough, and in order to avoid sampling error, this would require excision biopsies of all suspicious lymph nodes and a diagnostic splenectomy. My patient and I agreed that the potential morbidity from this approach was prohibitive. However, we agreed that if his enlarged contralateral inguinal nodes showed no involvement, this would provide some support to the hypothesis of localised lymphoma. The biopsy yielded reactive tissue, and we took a “leap of faith” with radiotherapy to his right hemi-pelvis.
We will know if we made the correct decision only after many years of follow-up. However, my confidence in Dr Harris’s understanding of the complexity of the situation helped me to support the final treatment decision. Less well informed patients sometimes struggle to put all the pieces of the puzzle together without getting lost in the process.
Christopher J C Knechtli
I have been in the unusual position of having moved from an early diagnosis of stage IV (and probably incurable) follicular lymphoma to the possibility that I may have a much earlier, potentially curable stage. Because of my dual diagnoses, each of which can mimic the other, there have been 19 rate limiting steps from my initial working diagnosis to starting definitive treatment. Whereas the mean waiting time for each of them was two weeks, I needed to arrange private treatment three times to avoid considerably longer waits, and the overall nine month delay felt never ending. My observation of other European health systems suggests that the process would have been much faster in them, and I suspect that is one of the many reasons for their better cancer survival rates.
Modern evidence based treatment and superb clinical skills meant that I experienced far fewer side effects from investigations and radiotherapy than I would have experienced when I qualified in 1980. One surprise has been that, of all the clinicians who have examined me, by far the most skilled and thorough clinical examinations have been done by my general practitioner and the haematologist. That may be because they are less reliant on imaging to tell them what is going on. I would urge all my colleagues to follow their example: although in many cases clinical examination does not tell us anything unexpected, sometimes it does. My own general practitioner’s knowledge that she needed to look for my spleen, and her competence in finding it, were key in accelerating my initial investigations.
A year has passed since my radiotherapy. My blood markers are back to normal; a recent scan showed a normal sized spleen and no adenopathy. Although this is encouraging, follicular lymphoma is a very slow growing malignancy. It will be some years before I know with any degree of confidence whether my “stage I” hypothesis is correct and whether the treatment was successful.
Useful resources for patients and clinicians
Lymphoma Association (www.lymphomas.org.uk)—A UK charity dedicated exclusively to providing specialist information and support to help lymphoma patients and their relatives, friends, and carers
British Committee for Standards in Haematology (www.bcshguidelines.com)—Provides up to date evidence based guidelines for both clinical and laboratory haematologists on the diagnosis and treatment of haematological disease
American Society of Hematology (www.hematology.org)—The world’s largest professional society concerned with the causes and treatments of blood disorders
British Lung Foundation (www.blf.org.uk)—Supports people affected by lung conditions including sarcoidosis, funds research, and promotes greater understanding of lung disease
Sarcoidosis Association (www.sa-uk.org)—A British voluntary organisation dedicated to promoting and providing support to patients with sarcoidosis and their carers
Foundation for Sarcoidosis Research (www.stopsarcoidosis.org)—A non-profit US organisation that aims to find a cure for sarcoidosis and improve the care of patients with the condition
Cite this as: BMJ 2014;348:g3736
This is one of a series of occasional articles by patients about their experiences that offer lessons to doctors.
Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.
Provenance and peer review: Not commissioned; not externally peer reviewed.