Treatment And Overview Of Hodgkins Lymphoma Biology Essay

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This case study will focus on a hypothetical scenario of a 19 year old male patient who is diagnosed with Hodgkin's Lymphoma. The case study will cover a description of the condition, clinical presentation, patient presentation, imaging and appearance, treatment options and outcomes and a summary. Hodgkin's Lymphoma is a very rare, specific type of cancer arising from the white blood cells in the body, known as Lymphocytes. It causes uncontrolled cell production of the lymphatic system, in particular the lymph nodes, liver, spleen and bone marrow (Merck, 2008). Hodgkin's can be confined to one particular area of the body or it can be diffuse or disseminated, involving a number of extranodal organs or tissues (Diehl, et al. 2008). Hodgkin's lymphoma affects the lymph system and is typified by the systemic invasion of the condition from one lymph node grouping to the next group. Hodgkin's disease can be confirmed by biopsy and the presence of multinucleated Reed-Sternberg cells when looked at microscopically. The disease has an incidence of around 2.4 per 100, 000 per year (Yung & Linch, 2003). Hodgkin's is more common in men than women and occurs predominantly between the ages of 15 and 40 years, it is a bimodal disease and there is a second peak of the condition in the age range of 50 to 60 years (Merck, 2008). The incidence of the disease for women peaks in their 30's, however the risk of developing Hodgkin's remains constant for men even after this time (Yung & Linch, 2003). The cause of the condition is still not known however there are possible contributing factors such as genetic predisposition and environmental factors. Exposure to certain drugs such as Phenytoin, previous radiation or chemotherapy, infection with HIV, herpes virus type 6 or tuberculosis may also be causative factors to developing Hodgkin's (Merck, 2008). Patients who are immunosuppresed are also at higher risk of developing Hodgkin's, this can cover a range of conditions from post organ-transplantation/bone marrow transplant patients to those with congenital immunodeficiency (Yung & Linch, 2003). Hodgkin's is divided into two categories: Nodular lymphocyte-predominant Hodgkin's and Classical Hodgkin's lymphoma. Nodular lymphocyte-predominant is the least common variant and comprises only 3% of all Hodgkin's cases. It occurs usually asymptomatically in the neck and arises in males more commonly. Classical Hodgkin's is further divided into four subgroups. These subgroups are determined by the cell morphology of the biopsy (Table 1. Merck, 2008). Nodular Sclerosing Hodgkin's accounts for two thirds of all cases, followed by the Mixed Cellularity subtype with around a quarter of cases (Merck, 2008). While the cell morphology of the subtypes may differ, the treatment options do not (Yung & Linch, 2003). Hodgkin's lymphoma can be treated using a variety of techniques including, Chemotherapy, Radiation therapy, Surgery to excise the lymphoma or in some advanced cases Haematopoietic stem cell transplantation. The choice of treatment modality is dependant on the stage of the disease. Survival rates are high for this type of disease, dependant on staging. 10 year survival rates for stage I-III (based on the Ann Arbor staging classification (Table 2, Diehl, et al. 2008)) indicate a 90% survival rating (Armitage, 2010). Staging is carried out using various methods and imaging modalities. Staging will take into account the patient's physical examination, blood tests, histological results of biopsy and also through imaging modalities such as x-ray chest plain film radiographs, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and through the use of Positron Emission Spectroscopy - Computed Tomography (PET-CT). Prior to these imaging techniques, laparoscopy and lymphangiography were used to stage Hodgkin's but these were supplanted in favour of CT and PET and PET-CT due to their non-invasive nature and advances in image resolution (Yung & Linch, 2003).

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Hodgkin's lymphoma may present in patients in a variety of symptoms. Many will present with painless, swollen lymph nodes in the cervical or supraclavicular region (Yung & Linch, 2003). The majority of cases which present with lymphadenopathy can have a rubbery nodal texture and are usually freely moveable, while those cases which have a fibrotic or sclerotic nature tend to exhibit a hard and firm adenopathy (Nursinglink, 2010). Around 25% of patients with Hodgkin's disease will present with systemic symptoms such as low-grade fever, drenching night sweats, unexplained itching all over the body, known as pruritus and general tiredness/fatigue (Yung & Linch, 2003). Pruritus is estimated to be found in around 30% of all Hodgkin's cases and is one of the primary symptoms. It can precede the clinical presentation of the condition by up to 5 years and tends to be associated with the Nodular Sclerosing form of Hodgkin's disease, along with mediastinal mass. The intense itching also tends to concentrate in the areas drained by and the immediate area around the affected nodes (Krajnik & Zylicz, 2001). Other symptoms which patients present with include unexplained and unintentional weight loss. More than 10% of initial body weight within a period of 6 months is an indicator to the condition and may allude to involvement of internal lymph nodes such as the mediastinal or retroperitoneal. It may also indicate bone marrow or liver involvement. Further symptoms which commonly present can be splenomegaly, enlargement of the spleen which affects around 30% of patients, and hepatomegaly, enlargement of the liver (Grainger & Allison, 2008). Fever which lasts for a number of days which then subsides over a period of days or weeks and then returns is also a sign of Hodgkin's. This relapsing/remitting fever cycle is known as Pel-Ebstein fever (Nursinglink, 2010). Pain upon ingestion of alcohol in the affected areas has also been noted as a symptom at presentation (Merck, 2008). Due to impingement on structures by tumour masses, other symptoms may present such as jaundice if there is obstruction of bile ducts, limb oedema may also be present due to lymphatic drainage blockage (Merck, 2008). Mediastinal adenopathy is among the most common of clinical presentations and 67-74% of patients which present have abnormal findings with 90% of those having bilateral, asymmetric, lymph node disease (Gupta & Bomanji, 2009). These findings are made due to the presentation of patients with coughing, chest pains and dyspnoea as a result of tracheobrachial compression (Merck, 2008). Another indicator for Hodgkin's is through bloodwork as Hodgkin's causes a variety of haematologic abnormalities such as eosinophilia, present in around 20% of cases as is thrombocytosis which is an abnormal number of platelets in the blood, which may lead to clotting (Nursinglink, 2010).

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The patient in this hypothetical scenario is a 19 year old male with no previous medical conditions or disorders. The patient was admitted to the Accident and Emergency department one evening following an injury sustained a few days earlier. He had been struck in the chest with an ice-hockey puck while at training and over the course of a few days bruising at the site of impact had developed. The patient found themselves with difficulty breathing and chest pain and was subsequently taken to A&E. Once in the department a posteroanterior chest radiograph was requested to query a possible pneumothorax and rule out any rib fractures. The chest radiograph revealed the presence of an opaque dense mass in the lung field with apparent mediastinal involvement. (Fig. 1. xray2000, 2009) At this point the suspected diagnosis was Hodgkin's Lymphoma, based on the patient's age and that there was no history of smoking to indicate lung cancer. However the patient reported no other associated symptoms such as fever, unexplained weight loss, pruritus or night sweats. Blood was drawn for testing and Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), alkaline phosphatase, lactate dehydrogenase levels and renal and liver function tests were carried out (Merck, 2008). The patient was admitted onto the ward and referred for further imaging using CT to confirm findings and to detect any additional masses in the body (Nursinglink, 2010). The patient was scheduled for a CT chest-abdo-pelvis volume scan with oral and IV contrast using Gastrografin and Omnipaque 300 iodine based IV contrast. Contraindications to contrast were assessed and renal function tests were conducted prior to scanning to ensure a suitable glomerular filtration rate (GFR). The patient was given 15ml Gastrografin in 500ml water, 2 hours prior and again 30 minutes prior to the scan. The patient positioned supine on the CT bed and a topogram to plan the scan was carried out to localise. IV contrast was connected via cannula and a volume CT scan from lung apices to pubis symphisis was planned. A 1 breath-hold, volume scan was used, in place of the normal 2-phase scan, with a 40-second delay and 100ml IV contrast at a flow rate of 4ml/s to visualise any malignant nodes through contrast uptake. The CT scan was carried out using a 64-slice scanner, collimating to 0.6mm slices and reconstructed to 1.0mm, using a "care" dose to minimise radiation exposure to the patient due to their age (Pattison, 2010). On CT the enlarged mediastinal lymph nodes were visualised and seen as rounded, soft tissue masses with enhancement due to contrast uptake (Fig. 2. AAFP, 2000), there were no additional enlarged lymph nodes seen outside of the localised area of the mediastinum. Lymph nodes are considered enlarged when measured to be 10mm or larger on their short axis (Grainger & Allison, 2008). Diagnosis of Hodgkin's was confirmed by histologic examination after an excisional biopsy under general anaesthetic was performed (Diehl, et al. 2008). The procedure known as mediastinoscopy, allows the sampling of the affected nodes from an incision point above the suprasternal notch to allow insertion of the mediastinoscope and dissect the nodes of interest (Scott-Conner & Dawson, 2009). From the biopsy the subtype of Hodgkin's was identified histologically, as the most common form of Classical Hodgkin's - Nodular Sclerosing. Prior to commencing treatment the patient was sent for further imaging, one week post biopsy, this time for a 18Fluorodeoxyglucose-Positron Emission Tomography - Computed Tomography (FDG-PET-CT) scan at nuclear medicine to provide a baseline scan to assess the metabolic activity of the affected node(s) (Gupta & Bomanji, 2009). This was to provide additional information for the purposes of staging the disease as FDG-PET is more sensitive in the detection of affected areas as it has a sensitivity of 90% and a specificity of 91% (Isasi & Lu, 2005; Papathanassiou et al, 2008). After the patient had fasted so that their glucose level was ~10mmol/l they were given a radiopharmaceutical tracer, an analogue of 18F and glucose, of ~400MBq activity. The patient was instructed to rest for 60 minutes, to allow metabolic uptake of the glucose analogue to the sites of malignancy. They were positioned head-first, supine on the bed and a whole body scan, using the PET-CT, was conducted to identify the lymph nodes with increased uptake and metabolic activity. The scan field was from the skull base to the mid-thigh to include all lymph nodes with appropriate PET-CT scan settings (Table 3. Poon, 2010). The resultant images from the FDG scan showed increased uptake in the area of the mediastinal lymph nodes which appeared as discrete black areas on the images (Fig. 3. Gupta & Bomanji, 2009). Once reconstructed and combined with the CT scan, metabolically active lymph nodes were visualised (Fig. 4. Poon, 2010). After the initial FDG-PET scan the patient would return at set periods to monitor their progress during the course of their treatment (Poon, 2010).

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Hodgkin's is treated using a variety of methods depending on the type and subtype and also the staging of the condition. Stages IA and IIA of Hodgkin's are considered early stage favourable; stages IB, IIB are considered early stage unfavourable and stages IIIA/B and IVA and IVB are termed "Advanced disease", according to the European Organisation for Research and Treatment of Cancer (EORTC) (Eghbali, H. 2005). The patient in this case study was staged at IIA as the CT scan, PET-CT scan and nodal biopsy found enlargement in the prevascular and paratracheal lymph node groups in the anterior mediastinum (Fig. 5. Gupta & Bomanji, 2009), but without any accompanying B symptoms or bulky disease and with no other involved nodes below the diaphragm (Table 2. Diehl, et al. 2008). The patient was given treatment according to the staging of his condition, which was a combination of short duration chemotherapy and involved field radiotherapy. Chemotherapy was given prior to radiotherapy to shrink the size of the masses in order to avoid unnecessarily irradiating lung tissue and causing radiation fibrosis (Grainger & Allison, 2008). Chemotherapy consisted of four cycles of Adriamycin (doxorubicin), Bleomycin, Vinblastine and Dacarbazine (ABVD) therapy over several months and involved field radiotherapy of the affected nodes, of 20-30Gy. This particular type of treatment for this stage of Hodgkin's has been shown to be effective with a 10 year survival rate of 95% of patients (Diehl, et al. 2008). Patients with early stage unfavourable Hodgkin's are given an additional 2 cycles of ABVD therapy as well as involved-field radiotherapy. Patients with advanced stage are given a more aggressive, multi-agent chemotherapy regimen which may include standard ABVD or BEACOPP (Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Oncovin (Vincristine), Procarbazine and Prednisone); which is given with or without combination radiotherapy. However the aggressive nature of the chemotherapy involved with BEACOPP chemotherapy regimen, while producing 10-20% more cure rates than ABVD in advanced stage, comes with risks. The BEACOPP therapy increases risk of secondary neoplasms such as leukaemia (Diehl, et al, 2008). The patient responded well to the ABVD chemotherapy and radiotherapy and on subsequent follow-up CT and PET-CT scans, taken after completing 2 cycles of chemotherapy, the nodes were found to have reduced metabolic activity, indicative of remission. As stated by Nusinglink (2008), the patient experienced some common side-affects due to the chemotherapy, including nausea, fatigue and some minor hair loss. The patient was advised that regular check ups were necessary to ensure complete remission. Prior to completing treatment the patient was brought back every month to conduct blood tests and physical observations. Follow-up visits for the patient will continue over a number of years at intervals of around 2-4 months over the first 1-2 years and then 3-6 months over the next 3-5 years. To monitor the patients remission various imaging will also be undertaken over this time period including additional chest radiographs, CT scanning and PET-CT scanning (Dessain & Spears, 2010).

As a result of continued research and better understanding of Hodgkin's and the advancement in detection and treatment of the disease, cure rates and survival rates have increased (Diehl, et al. 2008). In this case study the patient received the international gold standard in early stage Hodgkin's lymphoma detection and treatment, consistent with the recommendations as described by the EORTC.