Clinical presentation mostly depends on the subtype of Non-Hodgkin lymphoma and the area which it involves. It can either follow an indolent path or may progress in a very aggressive pace.

Most of the aggressive lymphomas present with a rapidly growing tumor mass, fever, night sweats, weight loss, and increased levels of serum lactate dehydrogenase and uric acid. Burkitt’s lymphoma and diffuse large B cell lymphoma are the common examples of aggressive tumors.

Slow growing or indolent lymphomas usually present with lymphadenopathy, hepatomegaly, splenomegaly or different types of cytopenias [6]. Common examples are follicular lymphoma and marginal zone lymphoma.
Few subtypes of Non-Hodgkin lymphoma may also present with rash, pruritus, generalized aches and pains.

• Splenomegaly

  Computed tomography scan of the chest and abdomen showed paratracheal and subcarinal lymphadenopathy and splenomegaly, with the findings being compatible with lymphoma. [ncbi.nlm.nih.gov]

  Splenomegaly. Hepatomegaly. Intermediate- and high-grade lymphomas: Most patients present with rapidly growing and bulky lymphadenopathy. [patient.info]

  Leukemia is usually associated with anemia, fever, hemorrhagic episodes, and splenomegaly. [icd9data.com]

  Slow growing or indolent lymphomas usually present with lymphadenopathy, hepatomegaly, splenomegaly or different types of cytopenias. [symptoma.com]

  Splenomegaly is observed in approximately 40% of patients; the spleen is rarely the only involved site at presentation. [emedicine.medscape.com]

• Massive Splenomegaly

  splenomegaly and peripheral blood and bone marrow involvement, usually without adenopathy.[ 98 - 100 ] This type of lymphoma is otherwise known as splenic lymphoma with villous lymphocytes. [web.archive.org]

  splenomegaly and peripheral blood and bone marrow involvement, usually without adenopathy.[ 109, 110 ] This type of lymphoma is otherwise known as splenic lymphoma with villous lymphocytes. [cancer.gov]

• Generalized Lymphadenopathy

  Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 1984 ; 311 : 565 –70. ↵ Beral V, Peterman T, Berkelman R, et al. AIDS-associated non-Hodgkin lymphoma. [sti.bmj.com]

• Hodgkin Lymphoma

  Non-Hodgkin lymphoma Other names Non-Hodgkin disease Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. H&E stain. [en.wikipedia.org]

  The main differentiating feature between Non-Hodgkin and Hodgkin lymphoma is the absence of Reed Sternberg cells in non-Hodgkin’s lymphoma. [symptoma.com]

  For non-Hodgkin lymphoma, 27.8% are diagnosed at the local stage. The 5-year survival for localized non-Hodgkin lymphoma is 81.6%. [web.archive.org]

  Diffuse large B cell lymphoma Diffuse large B cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma (NHL). NHL is a cancer of the lymphatic system. Burkitt lymphoma Burkitt lymphoma is a type of non-Hodgkin lymphoma (NHL). [cancerresearchuk.org]

  Additional Information Learn more about non-Hodgkin lymphoma More Information Here are some resources for learning more about non-Hodgkin lymphoma. [seer.cancer.gov]

• Fever

  […] intermediate Q fever endemicity. [ncbi.nlm.nih.gov]

  If you have NHL, call your provider if you experience persistent fever or other signs of infection. [nlm.nih.gov]

  Most of the aggressive lymphomas present with a rapidly growing tumor mass, fever, night sweats, weight loss, and increased levels of serum lactate dehydrogenase and uric acid. [symptoma.com]

  Three patients presented with symptoms—acute right lower quadrant pain and a fever—that were diagnosed clinically as acute appendicitis. [ajronline.org]

• Weight Loss

  Symptoms may include: a cough, difficulty swallowing or breathlessness (if the lymphoma is in the chest area) indigestion, tummy pain or weight loss (if the lymphoma is in the stomach or bowel). [christie.nhs.uk]

  Most of the aggressive lymphomas present with a rapidly growing tumor mass, fever, night sweats, weight loss, and increased levels of serum lactate dehydrogenase and uric acid. [symptoma.com]

  Loss Wound Care Patients & Visitors Admission Information Billing & Payments Visiting Hours Directions Classes & Events Weight Loss Seminar News Contact Search form Search Future of Healthcare Future of Healthcare Honoring Our Past Honoring Our Past [stfrancistopeka.org]

  […] moderate to severe weight loss, and most others have some weight loss.[54] Greater weight loss is associated with poorer prognosis.[54] Theories about contributing factors include appetite loss related to reduced activity, additional energy required [en.wikipedia.org]

  Treatment depends on: The specific type of NHL The stage when you are first diagnosed Your age and overall health Symptoms, including weight loss, fever, and night sweats You may receive chemotherapy, radiation therapy, or both. [nlm.nih.gov]

• Swelling

  cheek swelling and paraspinal mass present in one (1%) each. [ncbi.nlm.nih.gov]

  Sometimes the lymph nodes involved are in the stomach or intestines so there may be swelling of the abdomen, abdominal pain or constipation. [curesearch.org]

  Hodgkin disease usually begins with a painless swelling of a lymph node, and it may involve lymph nodes anywhere in the body. Non-Hodgkin lymphoma arises from either B lymphocytes or T lymphocytes. It may have an indolent course, as in… Read More [britannica.com]

  Symptoms The most common symptom of non-Hodgkin's lymphoma is a mass or swelling of the lymph nodes of the neck, collarbone, groin, and armpit. If you find swelling in one of these areas, you must be examined by a physician. [verywell.com]

• Fatigue

  The patient was a 77-year-old man with history of symptoms of partial bowel obstruction, intermittent right iliac fossa pain, loss of weight, vomiting and fatigue. [ncbi.nlm.nih.gov]

  […] malignant lymphomas (such as Burkitt's lymphoma) that are not classified as Hodgkin's disease, have malignant cells derived from B cells, T cells, or natural killer cells, and are characterized especially by enlarged lymph nodes, fever, night sweats, fatigue [merriam-webster.com]

  Other symptoms may include the following: Unexplained fever Night sweats Constant fatigue Unexplained weight loss Itchy skin Reddened patches on the skin However, these symptoms are not sure signs of non-Hodgkin's lymphoma. [ucsfhealth.org]

• Pleural Effusion

  Four years after the diagnosis of lymphoma, she presented with a left pleural effusion. Large biopsies of the pleura showed a malignant mesothelioma, biphasic type, and pleural plaques. [ncbi.nlm.nih.gov]

  Large pericardial effusion or arrhythmias secondary to cardiac metastases. Respiratory problems secondary to pleural effusion and/or parenchymal lesions. Superior vena cava obstruction secondary to a large mediastinal tumour. [patient.info]

  Massive left pleural effusion as a complication of an upper anterior mediastinal T-lymphoblastic lymphoma. Note the atelectatic left lung. The diagnosis was established by means of thoracentesis. [emedicine.medscape.com]

• Nausea

  The most frequently reported (>20%) adverse events of any grade in the population in which safety was studied were hyperglycemia, fatigue, and nausea (36.1% each), depression (29.2%), diarrhea (27.8%), and anxiety (25.0%). [ncbi.nlm.nih.gov]

  […] other areas Weight loss Coughing or shortness of breath if the cancer affects the thymus gland or lymph nodes in the chest, putting pressure on the windpipe (trachea) or its branches Abdominal pain or swelling, leading to loss of appetite, constipation, nausea [nlm.nih.gov]

• Abdominal Pain

  The second case also describes an 8-year-old boy admitted for abdominal pain and vomiting. [ncbi.nlm.nih.gov]

  View larger version (171K) Fig. 2A. —42-year-old man with AIDS who presented with fever, leukocytosis, and acute right lower quadrant abdominal pain. [ajronline.org]

  Sometimes the lymph nodes involved are in the stomach or intestines so there may be swelling of the abdomen, abdominal pain or constipation. [curesearch.org]

  These types of malignancies affecting the gastrointestinal tract can manifest with different symptoms, such as abdominal pain, anorexia, weight loss, diarrhea, and ileus.[16] All of our 4 cases presented abdominal pain, 2 also presented diarrhea, anorexia [journals.lww.com]

• Loss of Appetite

  Our first case describes an 8-year-old boy with a history of iron deficiency anemia, admitted in our clinic for recurrent abdominal pain, weight loss, loss of appetite, diarrheic stools, and fever. [ncbi.nlm.nih.gov]

  In addition to swollen lymph nodes, other signs include night sweats; chills or fevers; unexpected weight loss; loss of appetite; lack of energy or tiredness; itching or rash; coughing; difficulties in breathing; enlarged tonsils; or headaches. [lymphomanewstoday.com]

  […] in the chest, putting pressure on the windpipe (trachea) or its branches Abdominal pain or swelling, leading to loss of appetite, constipation, nausea, and vomiting Headache, concentration problems, personality changes, or seizures if the cancer affects [nlm.nih.gov]

  B-cell lymphoma also causes symptoms like these: Night sweats Fever Unexplained weight loss Fatigue Appetite loss Trouble breathing Pain or swelling in your belly Severe itching [webmd.com]

• Abdominal Mass

  The abdominal ultrasound and the CT scan revealed an abdominal mass which, according to the histopathological exam, was a Burkitt lymphoma. [ncbi.nlm.nih.gov]

  We performed an abdominal CT scan which suggested that the aspect of the abdominal mass could plead for an intestinal lymphoma with spleen and renal secondary determinations. [journals.lww.com]

  Burkitt's lymphoma: often presents with a large abdominal mass and symptoms of bowel obstruction. Differential diagnosis See also separate Generalised Lymphadenopathy and Splenomegaly and Hypersplenism articles. Hodgkin's lymphoma. [patient.info]

  Patients with Burkitt lymphoma (occurring in the United States) often present with a large abdominal mass and symptoms of bowel obstruction. [emedicine.medscape.com]

• Diarrhea

  The most frequently reported (>20%) adverse events of any grade in the population in which safety was studied were hyperglycemia, fatigue, and nausea (36.1% each), depression (29.2%), diarrhea (27.8%), and anxiety (25.0%). [ncbi.nlm.nih.gov]

  Home treatment for diarrhea includes resting your stomach and being alert for signs of dehydration. Check with your doctor before you use any nonprescription medicines for your diarrhea. [uofmhealth.org]

  These types of malignancies affecting the gastrointestinal tract can manifest with different symptoms, such as abdominal pain, anorexia, weight loss, diarrhea, and ileus.[16] All of our 4 cases presented abdominal pain, 2 also presented diarrhea, anorexia [journals.lww.com]

  Excess nutrient losses Losses from the gastrointestinal can occur because of symptoms such as vomiting or diarrhea, as well as fistulae and stomas. There can also be losses from drains, including nasogastric tubes. [en.wikipedia.org]

• Hepatomegaly

  Hepatomegaly. Intermediate- and high-grade lymphomas: Most patients present with rapidly growing and bulky lymphadenopathy. [patient.info]

  The abdominal ultrasound showed a retroperitoneal mass of approximately 134/61.4 mm that crossed the median line, a hypoechoic mass in the liver, hepatomegaly, splenomegaly, and extrinsic compression of the urinary bladder. [journals.lww.com]

  Slow growing or indolent lymphomas usually present with lymphadenopathy, hepatomegaly, splenomegaly or different types of cytopenias. [symptoma.com]

  Intermediate- and high-grade lymphomas may produce the following physical examination findings: Rapidly growing and bulky lymphadenopathy Splenomegaly Hepatomegaly Large abdominal mass : this usually occurs in Burkitt lymphoma Testicular mass Complications [emedicine.medscape.com]

  Splenomegaly and hepatomegaly may be present. [clinicaladvisor.com]

• Back Pain

  The patient began suffering from low back pain radiating to the groin and to the anterior regions of the right thigh and leg, A nuclear magnetic resonance (NMR) of the lumbar spine showed disc protrusions at the L3-L4 and L5-S1 levels with impingement [ncbi.nlm.nih.gov]

  They may become painful if the enlarged glands press on organs, bones, and other structures. Some people confuse lymphoma with back pain. Lymph nodes can also swell during common infections, such as a cold. [medicalnewstoday.com]

  They also may reduce chronic low back pain, joint pain, headaches, and pain from treatments. Before you try a complementary therapy, talk to your doctor about the possible value and potential side effects. [uofmhealth.org]

  Abdominal lymphoma may cause abdominal pain & fullness, GI obstruction or bleeding, ascites, back pain & leg swelling. Lymph node enlargement in the chest can lead to compression of the trachea or bronchus, causing shortness of breath & coughing. [physio-pedia.com]

• Night Sweats

  Most of the aggressive lymphomas present with a rapidly growing tumor mass, fever, night sweats, weight loss, and increased levels of serum lactate dehydrogenase and uric acid. [symptoma.com]

  For the television series, see Night Sweats. Night sweats Other names Sleep sweats, nocturnal hyperhidrosis Specialty Infectious disease, oncology Night sweats is the occurrence of excessive sweating during sleep. [en.wikipedia.org]

  Treatment depends on: The specific type of NHL The stage when you are first diagnosed Your age and overall health Symptoms, including weight loss, fever, and night sweats You may receive chemotherapy, radiation therapy, or both. [nlm.nih.gov]

  sweats, fatigue, and weight loss First Known Use of non-Hodgkin's lymphoma 1972, in the meaning defined above Learn More about non-Hodgkin's lymphoma Statistics for non-Hodgkin's lymphoma Cite this Entry “Non-Hodgkin's lymphoma.” [merriam-webster.com]

  Non-Hodgkin lymphoma stages can be further classified by A to indicate the absence or B to indicate the presence of systemic symptoms (weight loss, fever, or night sweats). [msdmanuals.com]

• Pruritus

  Common examples are follicular lymphoma and marginal zone lymphoma.Few subtypes of Non-Hodgkin lymphoma may also present with rash, pruritus, generalized aches and pains. [symptoma.com]

  […] hypergammaglobulinemia.[ 56 ] (Refer to the information on night sweats in the PDQ summary on Hot Flashes and Night Sweats, information on weight loss in the in the PDQ summary on Nutrition in Cancer Care, and information on skin rash in the PDQ summary on Pruritus [web.archive.org]

  […] hypergammaglobulinemia.[ 70 ] (Refer to the information on night sweats in the PDQ summary on Hot Flashes and Night Sweats, information on weight loss in the in the PDQ summary on Nutrition in Cancer Care, and information on skin rash in the PDQ summary on Pruritus [cancer.gov]

• Neck Swelling

  She presented with chronic left ear pain, a mass in the left EAC, and rapid growth of an anterior neck swelling that had led to left vocal fold palsy. [ncbi.nlm.nih.gov]

• Numb Chin Syndrome

  KEYWORDS: Extranodal lymphoma; non-Hodgkin lymphoma; numb chin syndrome; periapical lesion [ncbi.nlm.nih.gov]

• Headache

  This syndrome causes symptoms such as fever, nausea, chills, tachycardia, and headache. Other potential side effects include serious infections and a weakened immune system. [cnn.com]

  Symptoms of infection include: fever headache aching muscles diarrhoea tiredness a painful blistering rash Many of the treatments for lymphoma can cause infertility, which is often temporary, but in some cases it may be a permanent side effect. [healthdirect.gov.au]

  In addition to swollen lymph nodes, other signs include night sweats; chills or fevers; unexpected weight loss; loss of appetite; lack of energy or tiredness; itching or rash; coughing; difficulties in breathing; enlarged tonsils; or headaches. [lymphomanewstoday.com]

  Coughing or shortness of breath if the cancer affects the thymus gland or lymph nodes in the chest, putting pressure on the windpipe (trachea) or its branches Abdominal pain or swelling, leading to loss of appetite, constipation, nausea, and vomiting Headache [nlm.nih.gov]

  The most common treatment-emergent adverse events in the GP arm were back pain (56.3%), platelet count decreased (25.0%), headache, diarrhoea, and nausea (18.8% each). [ncbi.nlm.nih.gov]

• Seizure

  […] thymus gland or lymph nodes in the chest, putting pressure on the windpipe (trachea) or its branches Abdominal pain or swelling, leading to loss of appetite, constipation, nausea, and vomiting Headache, concentration problems, personality changes, or seizures [nlm.nih.gov]

  […] used to treat psoriatic and rheumatoid arthritis and inflammatory bowel disease Prior exposure to chemotherapy and/or radiation used to treat a prior diagnosis of cancer Treatment with a medication called Dilantin (phenytoin), commonly used to treat seizure [webmd.com]

  These may include: Breathing problems Chest pain Enlarged or swollen lymph nodes in the groin, armpits or neck Fatigue Fever Lumps and itchiness Night sweats Seizures, weakness, personality changes, and problems with thinking, if cancer develops in the [docdoc.com.sg]

  Diagnose Multiple Systems Atrophy based on the 2008 criteria Arteriovenous Malformation Coma/Level of Consciousness Demyelinating Disease Dermatome Map Functional Outcome Head & Neck Trauma Headache Intracerebral Hemorrhage Ischemic Stroke Neurophysiology Seizure [qxmd.com]

• Guillain-Barré Syndrome

  Fitting the Pieces of the POEMS Syndrome Jigsaw Puzzle - Guillain-Barré Syndrome in a Patient with Refractory Ascites: Case Report. [hastane.hacettepe.edu.tr]

Evaluation or workup of the patients with Non-Hodgkin lymphoma is quite similar to those suffering from Hodgkin's disease. The following investigations are mandatory to be carried out in the individuals suspected for Non-Hodgkin lymphoma [7] [8]:

• Complete blood count
• Erythrocyte sedimentation rate
• Chemistry studies reflecting major organ function
• Serum levels of lactate dehydrogenase (LDH) and β2 microglobulin and serum protein electrophoresis.
• Computed tomography (CT) scan of the chest, abdomen and pelvis
• Bone marrow biopsy
• PET and gallium scan – although not required for primary staging of the tumor but if performed at the end of therapy, helps evaluating the persisting mediastinal radiographic abnormalities.

Staging of any type of tumor is a very critical issue and is addressed according. Staging for Non-Hodgkin lymphoma is done using the Ann Arbor Staging System which was first devised for Hodgkin’s disease.

I: Single lymph node region or lymphoid structure like (thymus, spleen or Waldeyer’s ring) is involved

II: Two or more lymph node regions on the same side of the diaphragm are involved

III: Lymph node regions or lymphoid structures on the both sides of diaphragm are involved

III 1: Subdiaphragmatic involvement limited to spleen, splenic hilar nodes, celiac nodes, or portal nodes

III 2: Subdiaphragmatic involvement of paraaortic, iliac and mesenteric nodes in addition to the structures involved in III1

IV: Extranodal sites beyond liver and bone marrow are involved.
More than one extranodal deposit at any location
Involvement of liver or bone marrow of any type

IV A: Symptomless

IV B: Unexplained weight loss more than 10% body weight during 6 months before initiating investigation, Unexplained, persistent and recurrent fever with tem more than 38 degree celcius in the last month, Drenching and recurrent night sweats in the last month

E: If extralymphatic tissue other than liver and bone marrow is involved, but the lesion is localized and solitary

• Mediastinal Mass

  The patient presented initially with persistent cough and an anterior mediastinal mass and had no bone marrow or CNS involvement at diagnosis. During re-induction treatment, a routine lumbar puncture revealed blasts in the cerebrospinal fluid (CSF). [ncbi.nlm.nih.gov]

  Lymphoblastic lymphoma: high-grade lymphoma, which often manifests with a mediastinal mass, superior vena cava syndrome and meningeal disease with cranial nerve palsies. [patient.info]

  On the other hand, DLBCL rarely metastasizes to the bone marrow or central nervous system, but it can manifest as both abdominal or mediastinal mass. [journals.lww.com]

  Lymphoblastic lymphoma, a high-grade lymphoma, often manifests with an anterior superior mediastinal mass, superior vena cava (SVC) syndrome, and leptomeningeal disease with cranial nerve palsies. [emedicine.medscape.com]

  Lymphoblastic lymphoma is commonly associated with large mediastinal masses and has a high predilection for disseminating to bone marrow and the central nervous system (CNS). [web.archive.org]

• Nephrolithiasis

  Depression Eating Disorder Obsessive Compulsive Disorder Pediatrics Psychosis Psychosomatic Acute Kidney Injury Chronic Kidney Disease Fluids & Electrolytes Glomerulonephritis Hemodialysis Hypertension REFERENCE BOOK Screening for Hypertension | CTFPHC Nephrolithiasis [qxmd.com]

• Superior Mediastinal Mass

  Lymphoblastic lymphoma, a high-grade lymphoma, often manifests with an anterior superior mediastinal mass, superior vena cava (SVC) syndrome, and leptomeningeal disease with cranial nerve palsies. [emedicine.medscape.com]

• Thrombocytosis

  In the first case, the laboratory tests showed anemia, thrombocytosis, elevated inflammatory biomarkers, a low level of iron, and hypoproteinemia. [ncbi.nlm.nih.gov]

  Thrombocytosis and lymphocytosis may also occur. Renal function and electrolytes: obstructive nephropathy, hypercalcaemia. LFTs. Serology: HIV, HTLV-1, hepatitis C. [patient.info]

  […] palpable in the inferior left iliac fossa), weight (W): 20 kg, hight (H): 125 cm. 2.1.3 Diagnostic focus and assessment The complete cellular blood count revealed anemia (hemoglobin [Hb] 8.7 g/dL, hematocrit 30.5%, medium cellular volume 64.5 fL), and thrombocytosis [journals.lww.com]

  […] lymphoma [2] Testing Laboratory studies in a patient with suspected NHL should include the following: CBC count: May be normal in early-stage disease; in more advanced stages, may demonstrate anemia, thrombocytopenia/leukopenia/pancytopenia, lymphocytosis, thrombocytosis [emedicine.medscape.com]

• Lymphocytes Increased

  In NHL, lymphocytes keep dividing and grow out of the body’s control. Over time, the number of abnormal lymphocytes increases and abnormal lymphocytes collect in your lymph nodes, or elsewhere in the body. There are many different types of NHL. [aidsmap.com]

  In NHL, lymphocytes grow indefinitely, so the number of circulating lymphocytes increases, filling up the lymph nodes and causing them to swell. [medicinenet.com]

• Hyperglobulinemia

  It is characterized by hyperglobulinemia, excess bence-jones proteins (free monoclonal immunoglobulin light chains) in the urine, skeletal destruction, bone pain, and fractures. Other features include anemia; hypercalcemia; and renal insufficiency. [icd9data.com]

• Pleural Effusion

  Four years after the diagnosis of lymphoma, she presented with a left pleural effusion. Large biopsies of the pleura showed a malignant mesothelioma, biphasic type, and pleural plaques. [ncbi.nlm.nih.gov]

  Large pericardial effusion or arrhythmias secondary to cardiac metastases. Respiratory problems secondary to pleural effusion and/or parenchymal lesions. Superior vena cava obstruction secondary to a large mediastinal tumour. [patient.info]

  Massive left pleural effusion as a complication of an upper anterior mediastinal T-lymphoblastic lymphoma. Note the atelectatic left lung. The diagnosis was established by means of thoracentesis. [emedicine.medscape.com]

The treatment options depend on the type of lymphoma, its stage and other prognostic factors and include chemotherapy (most common), radiation therapy, Rituximab administration, bone marrow transplantation, radioimmunotherapy, antibiotics and surgery.

Although prognosis of Non-Hodgkin lymphoma varies from type to type of the tumor, however a central and well defined system has been devised to determine the prognosis of Non-Hodgkin lymphoma. It is known as International Prognostic Index for NHL. This one index is referred to as a very strong indicator to the outcome of all subtypes of Non-Hodgkin lymphoma.
According to this system patients are assigned a score based on the absence or presence of mainly five adverse prognostic factors. Some patients have none while others may have all the five adverse factors.

International prognostic index for NHL [7]
Five clinical risk factors

• Age > 60 years

• Serum lactate dehydrogenase levels elevated
• Performance status > 2 (ECOG) or < 70 (Karnofsky)
• Ann Arbor stage III or IV
• >1 site of extranodal involvement

Patients are assigned a number for each risk factor they have
Patients are grouped differently based upon the type of lymphoma. (ECOG – Eastern Cooperative Oncology Group)

The etiology of Non-Hodgkin lymphoma is very complex as numerous factors are responsible for its cause. Immunodeficiency states, both primary and secondary are thought to be the most important cause of Non-Hodgkin lymphoma. Patients with HIV infection, organ transplant, and with inherited immunodeficiency states like sicca syndrome and rheumatoid arthritis are more likely to have Non-Hodgkin lymphoma [2] [3] [4].

Common diseases or exposures increasing the risk of Non-Hodgkin lymphoma are listed below:

• Inherited immunodeficiency disease: Klinefelter’s syndrome, Chediak-Higashi syndrome, Ataxia-telangiectasia syndrome, Wiskott-Aldrich syndrome, Common variable immunodeficiency disease

• Acquired immunodeficiency diseases: Iatrogenic immunosuppression, HIV-1 infection, Acquired hypogammaglobulinemia

• Autoimmune disease: Sjogren’s syndrome, Celiac sprue, Rheumatoid arthritis, Systemic lupus erythematosus
• Chemical or drug exposures: Phenytoin, Digoxin, Phenoxy herbicides, Radiation, Prior Chemo- or Radiotherapy

Environment plays a vital role in the causation of this disease with certain infectious agents, chemicals (specifically agricultural chemicals) and medical treatments being common examples [5].

Few specific infectious agents associated with certain subtypes of Non-Hodgkin lymphoma are:

• Epstein-Barr virus: Burkitt’s lymphoma, Post organ transplant lymphoma, Primary CNS diffuse large B cell lymphoma, Hodgkin’s disease, Extranodal NK/T cell lymphoma, nasal type

• HTLV-1 (human T cell lymphotropic virus): Adult T cell leukemia or lymphoma
• HIV (human immunodeficiency virus): Diffuse large B cell lymphoma, Burkitt’s lymphoma
• Hepatitis C virus: Lymphoplasmacytic lymphoma
• Helicobacter pylori: Gastric MALT (mucosa associated lymphoid tissue) lymphoma
• Human herpesvirus 8: Primary effusion lymphoma, Multicentric castleman’s disease

Patients who suffered from Hodgkin’s disease and were treated for that may develop Non-Hodgkin lymphoma. It is not sure whether the cause of Non-Hodgkin lymphoma in such cases is either the radiation exposure or the Hodgkin’s disease itself.

The following list shows the relative frequency of the various types of Non-Hodgkin lymphoma:

Diffuse large B cell lymphoma: 31%
Follicular lymphoma: 22%
MALT lymphoma: 7.6%
Mature T cell lymphoma: 7.6%
Small lymphocytic lymphoma: 6.7%
Mantle cell lymphoma: 6%
Mediastinal large B cell lymphoma: 2.4%
Anaplastic large cell lymphoma: 2.4%
Burkitt’s lymphoma: 2.4%
Nodular marginal zone lymphoma: 1.8%
Precursor T lymphoblastic lymphoma: 1.7%
Lymphoplasmacytic lymphoma: 1.2%
Others: 7.4%

The most prevalent form of lymphoid neoplasm in Western world in chronic lymphoid leukemia (CLL). It occurs in older adults. According to a data in 2010, almost 15.000 new cases of chronic lymphoid leukemia were diagnosed in the United States. It is more common in men than in women. Moreover, whites are affected more than the blacks.

Acute lymphoid leukemias (ALLs) most commonly affect children and young adults. Burkitt’s lymphoma, one of the types of ALL occur due to infection with Epstein - Barr virus (EBV) in infancy. Trisomy 21 (Down syndrome) increases the chance of acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) in children. Radiation exposure increases the risk of T-cell acute lymphoid leukemia manifold.

A 4 % increase was observed in the United States in cases of Non Hodgkin lymphoma between 1950 and late 1990s. Globally this increases was 2 to 8%. In 2010, the number of new cases all over the world was 360,000 whereas in United States it was 65,000. These lymphomas are more common in men and in elderly. Elderly men are more frequently affected by the Non-Hodgkin lymphoma.

Lymphoid cells are derived from a common progenitor known as hematopoietic stem cell. It gives rise to all the lineages including the lymphoid, myeloid, erythroid, monocyte and megakaryocyte. B cells are notorious for having almost 75% of all lymphoid leukemias and 90% of all lymphomas.

Phenotype of the cell surface of the lymphoid cells in malignancy are not much yielding in defining the nature of the tumor because there are certain examples in which the clinical outcome is contradictory to what is the phenotype. For example, clinically Burkitt’s lymphoma is the most aggressive lymphoid leukemia, yet it has a phenotype of mature B-cell. Leukemias having very primitive cells phenotypically are much less aggressive and respond to curative measures.

Lymphoid cell malignancies are very closely related to repeating genetic abnormalities. Certain types of genetic abnormalities leading to Non-Hodgkin lymphoma are gross chromosomal changes like additions, deletions, or translocations, rearrangement of specific genes, under expression, overexpression or mutation of some specific oncogenes.

Common chromosomes affected in lymphoid malignancies especially NHL are 2, 14 and 22 in B cells, and 7 and 14 in T cells. Cytogenetic abnormality leading to certain lymphoid disease are given in the table. Cytogenetic translocations for some common subtypes of Non-Hodgkin’s lymphoma are t(14;18) (follicular lymphoma), t(2;5) (anaplastic large T cell lymphoma), t(8;14) (Burkitt’s lymphoma) and t(11;14) (mantle cell lymphoma).

There are no guidelines for prevention of Non-Hodgkin lymphoma.

Non-Hodgkin lymphomas are a group of lymphoid malignancies that includes all the cancerous conditions of the lymphoid cells except Hodgkin’s disease. The main differentiating feature between Non-Hodgkin and Hodgkin lymphoma is the absence of Reed Sternberg cells in non-Hodgkin’s lymphoma [1]. This separation between Hodgkin’s disease and non-Hodgkin’s lymphomas was done early in the twentieth century.

Lymphoid cell malignancies can range from benign to the most aggressive ones. Tumor cells arise from the immune system cells at different stages of differentiation and thus may give rise to wide variety immunologic, morphologic and clinical findings.
Non-Hodgkin cell lymphomas may present as leukemia (involvement of bone marrow and blood), lymphomas (solid tumors of the immune system) and both leukemia and lymphomas.

Non-Hodgkin lymphoma includes a wide array of lymphoid malignancies and the most common subtype is diffuse large B cell lymphoma.

Infections with Epstein Barr virus (EBV) and human T cell leukemia virus (HTLV-1) are the two most common and well recognized causes. Other possible causes are exposure to radiations, nitrates in drinking water, pesticides, hair dye use, alcohol and tobacco. Certain drugs like amphotericin B and vancomycin also increase its susceptibility.
It presents with lymphadenopathy and systemic symptoms like fever, rigors, night sweats and weight loss.

If the above mentioned symptoms appear, patient must visit the physician as soon as possible. Important investigations that must be carried out in this setting are complete blood count, erythrocyte sedimentation rate, chemistry studies reflecting major organ function, serum levels of lactate dehydrogenase (LDH) and β2 microglobulin and serum protein electrophoresis, computed tomography (CT) scan of the chest, abdomen and pelvis and bone marrow biopsy. Once developed appropriate chemotherapy and radiotherapy must be carried out to get rid of it.

1. Greiner TC, Medeiros LJ, Elaine S. Jaffe ES., Non-Hodgkin's lymphoma; International Journal of the American Cancer Society Volume 75 2006, Issue Supplement S1, p 370–380.
2. Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst 2006; 98:51.
3. Ramos-Casals M, la Civita L, de Vita S, et al. Characterization of B cell lymphoma in patients with Sjögren's syndrome and hepatitis C virus infection. Arthritis Rheum 2007; 57:161.
4. Martí-Carvajal AJ, Cardona AF, Lawrence A. Interventions for previously untreated patients with AIDS-associated non-Hodgkin's lymphoma. Cochrane Database Syst Rev. Jul 8 2009;CD005419.
5. Chiu BC, Dave BJ, Blair A, et al. Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma. Blood 2006; 108:1363.
6. Zhang QY, Foucar K. Bone marrow involvement by Hodgkin and non-Hodgkin lymphomas. Hematol Oncol Clin North Am. Aug 2009;23(4):873-902.
7. Conlan MG, Armitage JO, Bast M, Weisenburger DD. Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at diagnosis. Cancer 1991; 67:1389.
8. McKenna RW, Bloomfield CD, Brunning RD. Nodular lymphoma: bone marrow and blood manifestations. Cancer 1975; 36:428.