History

Fact Explanation
Enlarged lymph nodes Lymphoma is a disorder of abnormal proliferation of lymphoid tissue. It is a hematological malignancy. It presents as lymphadenopathy in most. Usually they are not painful. [1],[2],[3],[4],[5],[6],[11]
Fever 25% of patients experience fever. The patho physiology of tumor-induced fever may be due to several mechanisms of which include release of cytokines from malignant cells or infiltrating mononuclear cells (e.g., tumor necrosis factor and interleukin-1). Pel-Epstein fever is the prototype fever associated with Hodgkin’s lymphoma and consists of several days of fever separated by afebrile episodes of similar duration, typically 7 to 14 days. [1],[2],[3],[4],[5],[6]
Excessive night sweats Patient may wake up at night drenched in sweat. This is called as "Drenching night sweats". When body detects a rise in temperature and attempts to cool itself down by sweating. [1],[2],[3],[4],[5],[6]
Weight loss Weight loss more than 10% of body weight loss occurs rapidly over a couple of months. Anorexia also contributes for this. [1],[2],[3],[4],[5],[6]
Pruritis Pruritis is related to the secretion of cytokines from the lymphoma cells. It can also occur because of lymphoma in the skin itself. [1],[2],[3],[4],[5],[6]
Fatigue The malignant infiltration of bone marrow results in anemia due to reduced red cell production. Also hypercalcemia causes fatigue. [1],[2],[3],[4],[5],[6]
Anorexia Many individuals feel a considerable loss in their appetite due to cytokines secreted by malignant cells. [1],[2],[3],[4],[5],[6]
Alcohol induced pain There is a well-known phenomenon of alcohol-related lymph node enlargement in people with Hodgkin’s lymphoma. This swelling likely caused pressure on a nerve, resulting in the arm pain. The physiological basis for this is unknown, but probably has to do with irritation of the malignant cells by alcohol directly, causing the release of inflammatory cytokines that then attract normal reactive cells to the lymph node. [1],[2],[3],[4],[5],[6],[9]
Swelling of face. When a lymphoma involves the neck or mediastinum, it may block the flow of some vessels and lead to a swelling of the face and neck. [1],[2],[3],[4],[5],[6],[8]
Cough Enlarged lymph nodes in the mediastinum may press on lung tissue, on the breathing passages nearby causing cough. [8]
Breathlessness Due to he pressure of enlarged chest lymph nodes on lungs and airways they have to work harder to get enough oxygen into the body. Lymphoma in the chest can damage the lymph nodes or the tissues around them resulting plural effusion. Both above reasons and anemia it self can cause breathlessness. [1],[2],[3],[4],[5],[6],[8]
Abdominal pain Abdomen is the most common site of extra nodal lymphoma. Patient might have a feeling of fullness after eating even small amounts of food. A lymphoma in stomach lining can cause burning pain and bleeding. Lymphoma in bowel cause abdominal pain change in bowel habits. [1],[2],[3],[4],[5],[6],[7]
Headache and leg weakness. When lymphoma involving brain it results in headache, seizures, memory problems and leg weakness. [1],[2],[3],[4],[5],[6],[10]
References
  1. SANKARANARAYANAN SREEDHARANP, KRISHNAN YAMINI, AL SHEMMARI SALEM. Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era. Lung India [online] 2014 December [viewed 18 September 2014] Available from: doi:10.4103/0970-2113.135760
  2. LAW MF, NG TY, CHAN HN, LAI HK, HA CY, LEUNG C, NG C, YEUNG YM, YIP SF. Clinical features and treatment outcomes of Hodgkin's lymphoma in Hong Kong Chinese Arch Med Sci [online] 2014 Jun 29, 10(3):498-504 [viewed 18 September 2014] Available from: doi:10.5114/aoms.2014.43744
  3. KIESEWETTER B, LUKAS J, KUCHAR A, MAYERHOEFER ME, STREUBEL B, LAGLER H, MüLLAUER L, WöHRER S, FISCHBACH J, RADERER M. Clinical features, treatment and outcome of mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa: single center experience of 60 patients. PLoS One [online] 2014, 9(7):e104004 [viewed 18 September 2014] Available from: doi:10.1371/journal.pone.0104004
  4. BOLUKBAS F, KUTLUTURKAN S. Symptoms and Symptom Clusters in Non Hodgkin's Lymphoma Patients in Turkey. Asian Pac J Cancer Prev [online] 2014, 15(17):7153-8 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/252278
  5. LEE SJ, SUH CW, LEE SI, KIM WS, LEE WS, KIM HJ, CHOI CW, KIM JS, SHIN HJ, CONSORTIUM FOR IMPROVING SURVIVAL OF LYMPHOMA. Clinical characteristics, pathological distribution, and prognostic factors in non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study. Korean J Intern Med [online] 2014 May, 29(3):352-60 [viewed 18 September 2014] Available from: doi:10.3904/kjim.2014.29.3.352
  6. STANCA O, CIOBANU AM, LUPU AR, GHIMICI C, TRIANTAFYLLIDIS I, COLITA A, MUT ID. Onset risk factors and treatment response features of refractory hodgkin lymphoma. Maedica (Buchar) [online] 2013 Sep, 8(4):343-6 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24790665
  7. CHEN JH, HO CL, CHEN YC, CHAO TY, KAO WY. Clinicopathological analysis and prognostic factors of 11 patients with primary non-Hodgkin lymphoma of the small intestine in a single institute. Oncol Lett [online] 2014 Aug, 8(2):876-880 [viewed 18 September 2014] Available from: doi:10.3892/ol.2014.2209
  8. WANG J, HU C, ZHAO Y, YI P, HUANG M, ZHANG G. [Clinical analysis of 82 cases of primary mediastinal large B cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi [online] 2014 Jun, 35(6):491-4 [viewed 18 September 2014] Available from: doi:10.3760/cma.j.issn.0253-2727.2014.06.003
  9. DE WINTER JG. Alcohol-induced Pain in Hodgkin's Disease Br Med J [online] 1953 Sep 12, 2(4836):604-605 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2029621
  10. FOO SH, SOBAH SA. Burkitt's lymphoma presenting with hypopituitarism: a case report and review of literature. Endocrinol Diabetes Metab Case Rep [online] 2014:140029 [viewed 18 September 2014] Available from: doi:10.1530/EDM-14-0029
  11. AGOSTINELLI C, PILERI S. Pathobiology of hodgkin lymphoma. Mediterr J Hematol Infect Dis [online] 2014, 6(1):e2014040 [viewed 18 September 2014] Available from: doi:10.4084/MJHID.2014.040

Examination

Fact Explanation
Lymphadenopathy Lymph node enlargement, most often of cervical nodes can be seen. Usually these are painless and rubbery in consistency. The pattern of spread is usually contagious. [1],[2],[3],[4],[5],[6]
Hepatosplenomegaly Lymphoma is a disorder of abnormal proliferation of lymphoid tissue. Therefore hepatomegaly and splenomegaly are common clinical signs. [1],[2],[3],[4],[5],[6],[7],[10]
Cachexia. Due to significant rapid weight loss low BMI value can be seen. [1],[2],[3],[4],[5],[6]
Scratch marks Due to pruritis scratch marks can be noted in these patients. [1],[2],[3],[4],[5],[6]
Skin lesions Lymphoma in the skin can produce flat red patches,raised plaques with scaly surface or some times lumps. [1],[2],[3],[4],[5],[6]
Pallor Pallor is a important sign to identify anemia in these patients. [1],[2],[3],[4],[5],[6]
Facial swelling When a lymphoma involves the neck or mediastinum, it may block the flow of some vessels and lead to a swelling of the face and neck. [1],[2],[3],[4],[5],[6],[8]
Breathlessness Due to he pressure of enlarged chest lymph nodes on lungs and airways they have to work harder to get enough oxygen into the body. Lymphoma in the chest can damage the lymph nodes or the tissues around them resulting plural effusion. Both above reasons and anemia it self can cause breathlessness. [1],[2],[3],[4],[5],[6],[8]
Abdominal distension This occurs with hepato splenomegaly and with ascites. [1],[2],[3],[4],[5],[6],[7]
Leg weakness When lymphoma involving brain it results in leg weakness. [1],[2],[3],[4],[5],[6],[9]
References
  1. SANKARANARAYANAN SREEDHARANP, KRISHNAN YAMINI, AL SHEMMARI SALEM. Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era. Lung India [online] 2014 December [viewed 18 September 2014] Available from: doi:10.4103/0970-2113.135760
  2. LAW MF, NG TY, CHAN HN, LAI HK, HA CY, LEUNG C, NG C, YEUNG YM, YIP SF. Clinical features and treatment outcomes of Hodgkin's lymphoma in Hong Kong Chinese Arch Med Sci [online] 2014 Jun 29, 10(3):498-504 [viewed 18 September 2014] Available from: doi:10.5114/aoms.2014.43744
  3. KIESEWETTER B, LUKAS J, KUCHAR A, MAYERHOEFER ME, STREUBEL B, LAGLER H, MüLLAUER L, WöHRER S, FISCHBACH J, RADERER M. Clinical features, treatment and outcome of mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa: single center experience of 60 patients. PLoS One [online] 2014, 9(7):e104004 [viewed 18 September 2014] Available from: doi:10.1371/journal.pone.0104004
  4. BOLUKBAS F, KUTLUTURKAN S. Symptoms and Symptom Clusters in Non Hodgkin's Lymphoma Patients in Turkey. Asian Pac J Cancer Prev [online] 2014, 15(17):7153-8 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/252278
  5. LEE SJ, SUH CW, LEE SI, KIM WS, LEE WS, KIM HJ, CHOI CW, KIM JS, SHIN HJ, CONSORTIUM FOR IMPROVING SURVIVAL OF LYMPHOMA. Clinical characteristics, pathological distribution, and prognostic factors in non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study. Korean J Intern Med [online] 2014 May, 29(3):352-60 [viewed 18 September 2014] Available from: doi:10.3904/kjim.2014.29.3.352
  6. STANCA O, CIOBANU AM, LUPU AR, GHIMICI C, TRIANTAFYLLIDIS I, COLITA A, MUT ID. Onset risk factors and treatment response features of refractory hodgkin lymphoma. Maedica (Buchar) [online] 2013 Sep, 8(4):343-6 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24790665
  7. CHEN JH, HO CL, CHEN YC, CHAO TY, KAO WY. Clinicopathological analysis and prognostic factors of 11 patients with primary non-Hodgkin lymphoma of the small intestine in a single institute. Oncol Lett [online] 2014 Aug, 8(2):876-880 [viewed 18 September 2014] Available from: doi:10.3892/ol.2014.2209
  8. WANG J, HU C, ZHAO Y, YI P, HUANG M, ZHANG G. [Clinical analysis of 82 cases of primary mediastinal large B cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi [online] 2014 Jun, 35(6):491-4 [viewed 18 September 2014] Available from: doi:10.3760/cma.j.issn.0253-2727.2014.06.003
  9. FOO SH, SOBAH SA. Burkitt's lymphoma presenting with hypopituitarism: a case report and review of literature. Endocrinol Diabetes Metab Case Rep [online] 2014:140029 [viewed 18 September 2014] Available from: doi:10.1530/EDM-14-0029
  10. AGOSTINELLI C, PILERI S. Pathobiology of hodgkin lymphoma. Mediterr J Hematol Infect Dis [online] 2014, 6(1):e2014040 [viewed 18 September 2014] Available from: doi:10.4084/MJHID.2014.040

Differential Diagnoses

Fact Explanation
Acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is an acute form of leukemia, characterized by the overproduction of lymphoblasts. Common symptoms are generalized weakness and fatigue, anemia, frequent or unexplained fever, weight loss with loss of appetite, bone pain, joint pain, breathlessness. On examination enlarged lymph nodes, liver and/or spleen can be seen. [1],[2]
Cytomegalo virus infection Cytomegalo virus (CMV) usually causes an asymptomatic infection or produces flu like symptoms. This is a cause for pyrexia of unknown origin. The lymph nodes and spleen may be enlarged during examination. [1],[2]
Infectious Mononucleosis This is caused by Epstein-Barr virus (EBV) infection. Most patients with infectious mononucleosis are asymptomatic. Mild fever, fatigue and prolonged malaise are common symptoms. [1],[2]
Lung Cancer (Small Cell) Common presenting symptoms of the small cell lung cancer are shortness of breath, cough, weight loss, fatigue and neurologic dysfunction. [1],[2]
Systemic Lupus Erythematosus (SLE) SLE is an inflammatory connective tissue disease. It is a cause for pyrexia of unknown origin. Many organ systems will be affected in SLE with immune complexes and autoantibodies, (ANAs). It is a disease characterized by relapses, flares, and remissions. [1],[2]
Tuberculosis (TB) Clinical features associated with pulmonary TB are cough, weight loss, anorexia, evening pyrexia, night sweat, chest pain and hemoptysis. Cervical lymph node enlargement is a common clinical sign. [1],[2]
Syphilis Syphilis is an infectious venereal disease caused by Treponema pallidum. Many other infections and immune-mediated processes in advanced stage will be mimicked by the presentations of the disease. Cervical lymph node enlargement, fever and malaise are common clinical features to both syphilis and lymphoma. [1],[2]
Toxoplasmosis Toxoplasmosis is caused by infection with Toxoplasma gondii. .It produces a wide range of clinical symptoms. It is a cause for pyrexia of unknown origin with cervical lymph node enlargement. [1],[2]
Sarcoidosis Sarcoidosis is a multisystem inflammatory disease of unknown etiology. Fever, anorexia are common symptoms. It is a cause for pyrexia of unknown origin with cervical lymph node enlargement. [1],[2]
References
  1. FERRY JA. Burkitt's lymphoma: clinicopathologic features and differential diagnosis. Oncologist [online] 2006 Apr, 11(4):375-83 [viewed 19 September 2014] Available from: doi:10.1634/theoncologist.11-4-375
  2. BOLUKBAS F, KUTLUTURKAN S. Symptoms and Symptom Clusters in Non Hodgkin's Lymphoma Patients in Turkey. Asian Pac J Cancer Prev [online] 2014, 15(17):7153-8 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/252278

Investigations - for Diagnosis

Fact Explanation
Full Blood count This can be normal, or there can be a normochromic, normocytic anaemia. Lymphopenia and occassionaly eosinophilia present. [1],[2],[3],[4]
Erythrocyte sedimentation rate (ESR) ESR is usually raised and it is an indicator of disease activity. [1],[2],[3],[4]
Serum lactate dehydrogenase (LDH) Raised level is a adverse prognostic factor. [1],[2],[3],[4]
Liver boichemistry Is often abnormal with or without liver involvement. [1],[2],[3],[4]
Lymph node biopsy Lymph node biopsy is required for histological confirmation. [1],[2],[3],[4]
Uric acid Is normal or raised. [1],[2],[3],[4]
Chest X-ray Chest X-ray may show mediastinal widening withor without lung involvement. [1],[2],[3],[4]
Ultrasound scan abdomen To identify involved organs and nodal involvement. [1],[2],[3],[4]
Bone marrow biopsy Bone marrow aspirate and trephine biopsy are rarely done but show involvement in patients with advanced disease. This is unusual in initial presentation. [1],[2],[3],[4]
References
  1. KOCJAN G. BEST PRACTICE No 185 Cytological and molecular diagnosis of lymphoma J Clin Pathol [online] 2005 Jun, 58(6):561-567 [viewed 19 September 2014] Available from: doi:10.1136/jcp.2004.019133
  2. AGOSTINELLI C, PILERI S. Pathobiology of hodgkin lymphoma. Mediterr J Hematol Infect Dis [online] 2014, 6(1):e2014040 [viewed 18 September 2014] Available from: doi:10.4084/MJHID.2014.040
  3. SPRIGGS AI, VANHEGAN RI. Cytological diagnosis of lymphoma in serous effusions. J Clin Pathol [online] 1981 Dec, 34(12):1311-1325 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494587
  4. KITAMURA Y, NANBA E, INUI S, TANIGAWA T, ICHIHARA K. Diagnosis of lymphoma in paraffin wax sections by nested PCR and immunohistochemistry. J Clin Pathol [online] 1996 Apr, 49(4):333-337 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC500462

Investigations - Screening/Staging

Fact Explanation
CT scan This is the investigation of choice for staging. CT Scans show involvement of intrathorasic node in 70% cases. abdominal or pelvic lymph nodes are also found. [1],[2],[3]
Positron emission tomography (PET) PET is increasingly being used for staging, assessment or response and direction of therapy. [1],[2],[3]
References
  1. AGOSTINELLI C, PILERI S. Pathobiology of hodgkin lymphoma. Mediterr J Hematol Infect Dis [online] 2014, 6(1):e2014040 [viewed 18 September 2014] Available from: doi:10.4084/MJHID.2014.040
  2. D'SOUZA MM, JAIMINI A, BANSAL A, TRIPATHI M, SHARMA R, MONDAL A, TRIPATHI RP. FDG-PET/CT in lymphoma Indian J Radiol Imaging [online] 2013, 23(4):354-365 [viewed 19 September 2014] Available from: doi:10.4103/0971-3026.125626
  3. ANSELL SM, ARMITAGE JO. Positron Emission Tomographic Scans in Lymphoma: Convention and Controversy Mayo Clin Proc [online] 2012 Jun, 87(6):571-580 [viewed 19 September 2014] Available from: doi:10.1016/j.mayocp.2012.03.006

Management - General Measures

Fact Explanation
Breaking Bad news Lymphoma is a hematological malignancy. Therefore breaking bad news to the patient is a very important part of management. The effective communication with patient and family members provides a supportive environment for management. [1],[2],[3]
Educate the patient about disease. Educate the patient about lymphoma, types of lymphoma, prognosis, available treatment options, duration of treatments, possible side effects, importance of continuation of treatments are important points need to be discuused. [1],[2],[3]
Advise patient. Because of lymphopenia these patient are immuno compromised. Chemotherapy also causes neutropenia. Therefore these patients are vulnarable for infections. These patient must be advised to increase attention to their hygiene. Advise them to avoid crowded places and infected individuals. [1],[2],[3],[4]
Antibiotic prophylaxis Infections represent a well-known complication of antineoplastic chemotherapy. Bacterial infections are major causes of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Therefore a program of antibiotic prophylaxis for febrile neutropenia may be considered in the management strategy for lymphoma patients. [1],[2],[3],[4]
References
  1. FLOWERS CR, KARTEN C. Communicating safe outpatient management of fever and neutropenia. J Oncol Pract [online] 2013 Jul, 9(4):207-10 [viewed 19 September 2014] Available from: doi:10.1200/JOP.2012.000815
  2. STIENEN JJ, OTTEVANGER PB, WENNEKES L, VAN DE SCHANS SA, DEKKER HM, BLIJLEVENS NM, VAN DER MAAZEN RW, VAN KRIEKEN JH, HERMENS RP. Delivering high-quality care to patients with a non-Hodgkin's lymphoma: barriers perceived by patients and physicians. Neth J Med [online] 2014 Jan, 72(1):41-8 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24457441
  3. STANCA O, CIOBANU AM, LUPU AR, GHIMICI C, TRIANTAFYLLIDIS I, COLITA A, MUT ID. Onset risk factors and treatment response features of refractory hodgkin lymphoma. Maedica (Buchar) [online] 2013 Sep, 8(4):343-6 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24790665
  4. CASTAGNOLA E. The role of prophylaxis of bacterial infections in children with acute leukemia/non-hodgkin lymphoma. Pediatr Rep [online] 2014 May 6, 6(2):5332 [viewed 19 September 2014] Available from: doi:10.4081/pr.2014.5332

Management - Specific Treatments

Fact Explanation
Planning of treatment These are important factors need to be considered when taking management decisions. The type of lymphoma, stage of lymphoma, presence of B symptoms, investigation results, patient's age, general health and fitness need to be evaluated. [1],[2],[3],[4],[5]
Radiation therapy Radiation therapy uses high-energy rays (20-30 Gy) to kill Malignant cells. It is a local therapy. For Hodgkin lymphoma early stages ( IA, IIA) involved field irradiation is used. For advanced disease irradiation at sites of bulk disease has been standard at many centers. Depending on site and type of radiation is administered, it may cause certain side effects such as fatigue, anorexia, nausea, diarrhea, and skin problems. The radiation is usually administered in five days a week over the course of several weeks. It increase benefit and reduces side effects. [1],[2],[3],[4],[5]
Chemotherapy Chemotherapy is a systemic therapy. It may administered intravenously or orally. Chemotherapy is given in cycles. The most common side effects of chemotherapy are anemia, leucopenia,and clotting problems due to throbocytopenia. One chemotherapy cycle includes the period of actual treatment, usually several days, followed by a period of rest for several weeks. That rest period allow recovery from side effects. Cyclical combination chemotherapy is usen in many centers. Adriamycin, Bleomycin, Vinblastine and Dacarbazine combination used for Hodgkin lymphoma. [1],[2],[3],[4],[5]
Immunotherapy Immunotherapy is a method of helping natural immunity of body. These therapies are beneficial because they cause anticancer effects without undesirable side effects. Monoclonal antibodies and cytokines are commonly used for immunotherapy. [1],[2],[3],[4],[5]
References
  1. FANALE M. Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment? Hematology Am Soc Hematol Educ Program [online] 2013:406-13 [viewed 19 September 2014] Available from: doi:10.1182/asheducation-2013.1.406
  2. JOHNSON PW. Management of early-stage Hodgkin lymphoma: is there still a role for radiation? Hematology Am Soc Hematol Educ Program [online] 2013:400-5 [viewed 19 September 2014] Available from: doi:10.1182/asheducation-2013.1.400
  3. STANCA O, CIOBANU AM, LUPU AR, GHIMICI C, TRIANTAFYLLIDIS I, COLITA A, MUT ID. Onset risk factors and treatment response features of refractory hodgkin lymphoma. Maedica (Buchar) [online] 2013 Sep, 8(4):343-6 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24790665
  4. ING VW. Hodgkin's Disease: Treatment and Prognosis Can Fam Physician [online] 1982 Mar:487-491 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2306384
  5. MOUNTER P, LENNARD A. Management of non-Hodgkin's lymphomas Postgrad Med J [online] 1999 Jan, 75(879):2-6 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1741115