In most cases, follicular lymphoma shows a painless, slow and progressive adenopathy [9]. Systemic symptoms like fever, night sweats and weight loss is not seen at presentation most of the time but it can be seen in later stages of the disease.

Progression to an intermediate-grade or high-grade lymphoma is considered as soon as a patient develops any systemic symptoms.
Another set of symptoms which may occur in the later stages of the condition are those depicting dysfunction of the bone marrow such as anemia, leukopenia and thrombocytopenia.

• Splenomegaly

  Splenic infiltration of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is caused not only by tumor involvement but also by non-tumorous disorders. [ncbi.nlm.nih.gov]

  At diagnosis, patients usually present with adenopathy and, in 50% of cases, splenomegaly. [orpha.net]

• Generalized Lymphadenopathy

  This patient was a 58 years old with generalized lymphadenopathy and Ann Arbor Stage III disease. [ncbi.nlm.nih.gov]

  It presents with painless generalized lymphadenopathy. Extranodal sites are less commonly involved. Morphology: Grossly, the involved lymph nodes show nodularity which disappears in advanced cases due to diffuse growth pattern. [webpathology.com]

  Nodal FL will often present with generalized lymphadenopathy and bone marrow involvement. Occasionally, it can also involve the GI system. [archivesofpathology.org]

  INTRODUCTION Section: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and is characterized by an indolent clinical course presenting with generalized lymphadenopathy and marrow involvement. 1 Eighty-five percent of patients have [doi.org]

• Axillary Lymphadenopathy

  Physical examination revealed right axillary lymphadenopathy without splenohepatomegaly. The lymph node was sent for flow cytometry and histomorphologic evaluation. Flow cytometric analysis revealed the presence of CD45+ and CD45- cell populations. [ncbi.nlm.nih.gov]

• Cervical Lymphadenopathy

  Magnetic resonance imaging revealed a dural-based tumoral lesion and cervical lymphadenopathies. The lesion was diagnosed radiologically as a meningioma, and tumor resection was planned. [ncbi.nlm.nih.gov]

• Fever

  A 55-year-old abattoir worker presented with a fever. He had had splenectomy for follicular lymphoma and rituximab maintenance therapy by four months before the presentation. [ncbi.nlm.nih.gov]

  If you have symptoms such as fever, chills, weight loss, low blood count or enlarged lymph nodes in various sites, your doctor may start you on therapy. [cancercare.org]

  Symptoms appear at an advanced stage of the disease and can include fever, night sweats and weight loss. At diagnosis, patients usually present with adenopathy and, in 50% of cases, splenomegaly. [orpha.net]

• Weight Loss

  Common symptoms of FL include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, as well as fatigue, shortness of breath, night sweats, and weight loss. [lymphoma.org]

  Symptoms appear at an advanced stage of the disease and can include fever, night sweats and weight loss. At diagnosis, patients usually present with adenopathy and, in 50% of cases, splenomegaly. [orpha.net]

• Lymphadenopathy

  The patient did not have any significant peripheral or axial lymphadenopathy, which made the diagnosis difficult in absence of histopathology. [ncbi.nlm.nih.gov]

• Fatigue

  A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. [ncbi.nlm.nih.gov]

  Common symptoms of FL include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, as well as fatigue, shortness of breath, night sweats, and weight loss. [lymphoma.org]

  The most common grades 3 and 4 toxicities included lymphopenia (45%), neutropenia (55%), fatigue (23%), and hyponatremia (9%). [current-oncology.com]

  Supplementation and sun exposure Muskuloskeletal health Heart health Cancer Autoimmune conditions Mental health Developmental disorders Pregnancy and fertility Aging Fitness and exercise Gastrointestinal health Asthma Infections Everyday aliments: fatigue [vitamindcouncil.org]

• Anemia

  Abstract A 46-year-old woman underwent upper endoscopy for evaluation of anemia, which revealed whitish granules at the duodenal papilla, diagnosed as duodenal follicular lymphoma (DFL) by biopsy. [ncbi.nlm.nih.gov]

  Myelosuppression, opportunistic infections, and autoimmune hemolytic anemia are the most common side effects of fludarabine. [lsmuni.lt]

  […] to an intermediate-grade or high-grade lymphoma is considered as soon as a patient develops any systemic symptoms.Another set of symptoms which may occur in the later stages of the condition are those depicting dysfunction of the bone marrow such as anemia [symptoma.com]

• Pneumonia

  The patient presented respiratory insufficiency secondary to severe pneumonia; he was admitted to the ICU and thoracic and abdominal CT scans were ordered. [elsevier.es]

  […] must agree to discontinue nursing Willing and able to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions including mandatory prophylaxis for Pneumocystis jirovecii pneumonia [clinicaltrials.gov]

  The most frequent grades 3 and 4 adverse events included diarrhea (15%), pneumonia (19%), rash (9%), fatigue (4%), and febrile neutropenia (3%). [current-oncology.com]

  Grade 3 or higher toxicities included neutropenia (27%), transaminase elevations (13%), diarrhea (13%), and pneumonia (7%). Based upon this data, idelalisib received accelerated approval by the FDA in 2014. [bloodjournal.org]

  Several studies with idelalisib were halted due to toxicities related to development of Pneumocystis jiroveci pneumonia (PJP) and reactivation of cytomegalovirus (CMV) infection. Therefore, PJP prophylaxis is strongly recommended. [emedicine.medscape.com]

• Dyspnea

  A 60-year-old male patient suffered from mild exertional dyspnea, wheezing, and systemic blisters. He was diagnosed with paraneoplastic pemphigus (PNP) with follicular lymphoma in the pancreas head and pelvic cavity. [ncbi.nlm.nih.gov]

  Herein we report a 55-year-old female that presented with fever and dyspnea after completing her third cycle of FMD (fludarabine, mitoxantrone, and dexamethasone) chemotherapy for stage IV non-Hodgkin follicular lymphoma. [lsmuni.lt]

  They may present dyspnea of varying magnitudes and jaundice in some cases.5 The diagnosis is complemented with radiography and computed tomography (CT) studies. [elsevier.es]

• Diarrhea

  A 59-year-old Japanese man with diarrhea and body weight loss was referred to our hospital. [ncbi.nlm.nih.gov]

  Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness Infections: While you’re taking GAZYVA, you may develop infections. [gazyva.com]

  Both regimens had similar safety profiles, with the most common toxicities being fatigue (55%), diarrhea (43%), and nausea (37%). [current-oncology.com]

  Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness Infections: While a patient is taking Gazyva, the patient may develop infections. Some of these infections may be severe. [gene.com]

  Fistula between the small and large intestine Diarrhea Passage of undigested food Fistula between the intestine and the bladder Urinary tract infection Burning with urination Cloudy urine or blood in the urine Fistula between the intestine and the vagina [crohnscolitisfoundation.org]

• Loss of Appetite

  Other symptoms include fatigue, unexplained weight loss, loss of appetite, fever and night sweats. [news-medical.net]

  Other symptoms may include loss of appetite and tiredness, shortness of breath and generalised unexplained aches and pains. [leukaemia.org.au]

  This can cause symptoms such as: loss of appetite anaemia - due to low number of red blood cells in your blood bruising or bleeding easily - due to low number of blood-clotting cells (platelets) in your blood. [macmillan.org.uk]

  […] of appetite or weight Fever of unknown reason Tiredness and ongoing fatigue Excessive sweating If follicular lymphoma occurs outside of the lymphatic system, symptoms are more likely to include shortness of breath and/or stomach pain Diagnosis and Staging [conquer-magazine.com]

• Abdominal Pain

  A 71-year-old woman had epigastric and left upper quadrant abdominal pain. Computed tomography (CT) revealed features of acute pancreatitis. [ncbi.nlm.nih.gov]

  Non-Hodgkin's lymphoma care at Mayo Clinic Types Symptoms Signs and symptoms of non-Hodgkin's lymphoma may include: Painless, swollen lymph nodes in your neck, armpits or groin Abdominal pain or swelling Chest pain, coughing or trouble breathing Persistent [mayoclinic.org]

  If the gastrointestinal tract is affected, then the lymphoma may cause changes in the bowels and abdominal pain. Risk Factors of Follicular lymphoma There are no known risk factors for the development of follicular lymphoma. [tuftsmedicalcenter.org]

  HBF usually appear in the context of a florid infection, with fever and leukocytosis, abdominal pain in the right hypochondrium and occasionally pleuritic pain and cough. [elsevier.es]

• Hypertension

  Aortic Stenosis/Outflow Aortic disease Atrial Fibrillation Bleeding Risk Coronary Artery Disease ECG Echocardiography Heart Failure Hypertension Invasive Hemodynamics Miscellaneous Mitral Regurgitation Mitral Stenosis PCI and Cardiac Surgery Pre-operative [qxmd.com]

  No other causes were found for the pulmonary hypertension that was considered to be associated with lymphoproliferative disease – pulmonary hypertension type 5. Hypoparathyroidism was considered secondary to parathyroid infiltration. [sponcologia.pt]

  One of the most prevalent non-neoplastic causes is portal hypertension mostly due to liver cirrhosis. On the other hand, liver cirrhosis may underlie various extrahepatic manifestations including development of B-cell non-Hodgkin lymphomas. [ncbi.nlm.nih.gov]

  Beyond genetic or congenital conditions, your risk of developing an arteriovenous fistula may increase due to certain factors, including: Cardiac catheterization, especially if the procedure involves blood vessels in your groin High blood pressure (hypertension [mayoclinic.org]

• Hepatosplenomegaly

  Splenomegaly is present in approximately 50% of patients at presentation, and hepatosplenomegaly may occur. [emedicine.medscape.com]

  Clinical examination revealed significant axillary and inguinal adenopathy (node size, >1.0 cm), and radiological examination (computed tomography scan and ultrasonography) showed hepatosplenomegaly. [nature.com]

• Hepatomegaly

  An abdominal ultrasound showed inferior vena cava suprahepatic veins dilation without hepatomegaly. She had normal thyroid function and serum immunology, and HIV testing was negative. [sponcologia.pt]

• Night Sweats

  CASE REPORT: A 64-y old man was presented with fatigue and night sweat in July 2013. Physical examination revealed right axillary lymphadenopathy without splenohepatomegaly. The lymph node was sent for flow cytometry and histomorphologic evaluation. [ncbi.nlm.nih.gov]

  Common symptoms of FL include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, as well as fatigue, shortness of breath, night sweats, and weight loss. [lymphoma.org]

  Symptoms appear at an advanced stage of the disease and can include fever, night sweats and weight loss. At diagnosis, patients usually present with adenopathy and, in 50% of cases, splenomegaly. [orpha.net]

  Night sweats: Night sweats differ from hot flashes and sweating in that many times they are literally drenching and people need to change their bedclothes and bedding, sometimes several times during the night. [verywellhealth.com]

• Pruritus

  The patient had exertion dyspnoea, loss of appetite, nausea, and circum-oral and extremities paresthesias for 1 year, and generalized pruritus for the last 2 months. She had no weight-loss, fever, orthopnoea or paroxysmal nocturnal dyspnoea. [sponcologia.pt]

  Bland fistulae may excrete pus, sometimes serous fluid and rarely feces, leading to pruritus ani, itching and skin maceration. Severe symptoms occur only occasionally, when spontaneous closure of the fistula leads to recurrent abscess formation. [ncbi.nlm.nih.gov]

  elevated levels of serum lactose dehydrogenase or beta-2 microglobulin;[4] presence of localized bone lesions; kidney involvement; reduced levels of cicurlating blood platelets or any of the various types of white blood cells; onset of significant pruritus [en.wikipedia.org]

• Aggressive Behavior

  Conversely follicular lymphomas that grow predominantly diffusely have lost a key characteristic of follicle cells, which is a sign of dedifferentiation and a harbinger of more aggressive behavior. [pleiad.umdnj.edu]

• Asthenia

  Systemic symptoms, such as fever, drenching night sweats, or weight loss in excess of 10% of ideal body weight, or asthenia, are infrequent at presentation but can be observed in later stages of the disease. [emedicine.medscape.com]

Tests and procedures used to diagnose follicular lymphoma include [9]:

• Physical examination 
• Blood and urine tests (to rule out other infections) 
• Imaging tests 
• Lymph node biopsy 
• Bone marrow biopsy 

Indolent lymphomas that don't cause signs and symptoms may not require treatment for years [10].

When signs and symptoms are fully developed, treatment may include any of the following:

• Chemotherapy (may be a single agent such as bendamustine or chlorambucil in combination with rituximab, or combination chemotherapy such as cyclophosphamide, doxorubicin, vincristine and prednisolone known collectively as CHOP)
• Radiation therapy
• Stem cell transplant (using either the stem cells of patient (autologous) or stem cells from a donor (allogeneic))
• Targeted radioimmunotherapy

The median survival is placed at 10 years with a wide range which could be as little as one year in some and more than 20 years in others [8]. The overall 5 year survival rate for the condition is 72 to 77%.

There is a definite cause for follicular lymphoma but several etiologic factors have been indicated [3].

• Viruses have been implicated as etiologic factors for the condition and include Epstein-Barr virus (EBV), human T-cell lymphotropic virus (HTLV) type I as well as the human herpes virus HHV-8 commonly associated with Kaposi sarcoma [4 ]. However, these viruses have been implicated as etiologic factors in mostly diffuse or high-grade lymphomas.
• Chemical such as pesticides and hair dyes have been associated with this condition [5].
• Congenital immunodeficiencies are other etiologic factors for lymphoma. Acquired immunodeficiencies involve HIV. Most lymphomas which are linked to HIV, are intermediate grade, or high grade lymphomas. 
• Immunosuppressant drugs may bring about diffuse or high grade lymphomas in some individuals.

In the United States, the fifth most frequently diagnosed malignancy is non-Hodgkin lymphoma. Over 50,000 cases are diagnosed each year and out of these, 15 to 20% are follicular lymphomas. No sex preponderance is seen in the US [6].

Internationally, the age rates of non-Hodgkin lymphoma are higher in more developed countries. The incidence of follicular lymphomas increases with age and so it is rarely seen in children.

The median age at diagnosis is 60 to 65 years. Variations in racial incidence have been noted around the world. The incidence of follicular lymphoma is low in China and Japan but higher in people of Jewish descent. In the United States, the condition is seen more in blacks than in whites.

In patients with follicular lymphoma, the most common acquired non-random chromosomal translocation is t(14;18) [7]. It is seen in more than 80% of all cases.

With this chromosomal translocation, the bcl2 protooncogen is brought under the transcriptional influence of the immunoglobulin heavy-chain gene and this leads to overexpression of a functionally normal bcl-2 protein.

Overexpression of bcl-2 confers a survival advantage to the cancer cells by preventing apoptosis. Although the exact mechanism and course of action of bcl-2 is not quite clear, its interaction with other homologues is believed to have an influence on the possibility of a cell undergoing apoptosis.

The t(14;18) product is detected by polymerase chain reaction (PCR) and is used frequently in the diagnosis and follow-up of patients who have follicular lymphomas.

There is no prevention for this condition.

Follicular lymphoma is a type of B-cell lymphoma [1]. It is one of the most common forms of non-Hodgkin lymphoma. The disorder is characterized by tumor cells which look circular or clump-like when viewed under the microscope. The irregular shaped follicles distort the usual appearance and structure of a lymph node. In people with follicular lymphoma, the CD20 protein is visible on the surface of the cancerous cells. Some treatment models target proteins synthesis.

Most patients with follicular lymphoma are diagnosed at its advanced stage and the bone marrow is involved most of the time at diagnosis.

Follicular lymphoma has four stages [2]:

• Stage I: One lymph node or lymph node area is involved.
• Stage II: Two or more lymph nodes or lymph node areas on the same side of diaphragm are involved.
• Stage III: Lymph node or lymph node areas on both sides of diaphragm are involved.
• Stage IV: The disease is disseminated involving the bone marrow, liver, or central nervous system.

Follicular lymphoma is categorized into grades further depending on the number of centroblasts per high-power field (hpf), as follows:

• Grade 1: 0-5 centroblasts per hpf 
• Grade 2: 6-15 centroblasts per hpf 
• Grade 3: > 15 centroblasts per hpf

In follicular lymphoma, tumors develop from lymphocytes which are of basically white blood cell. It is mostly seen in people aged 50 and above are did and the average age at diagnosis is 60 years. Most people with follicular lymphoma are aged over 65 and the condition is seen more in men than in women.

The causes of follicular lymphoma are unclear but it does not arise as a result of to infection. The condition is therefore not contagious.

Treatment for follicular lymphoma depends on the individual situation. If it is confined to one area, local radiotherapy is the treatment given. When follicular lymphoma is at an early stage and/or the person is symptom-free, the waiting approach is usually adoptedD. This involves close monitoring by the specialist, with active treatments such as chemotherapy being postponed till symptoms become visible.

1. Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology Am Soc Hematol Educ Program. 2,007; 216-25.
2. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, et al. CVP chemotherapy plus rituximab Compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. February 15 2005, 105 (4): 1417 -23.
3. Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmit R, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) Significantly Improves the outcome for patients with advanced- stage follicular lymphoma Compared with therapy with CHOP alone:. results of a prospective randomized study of the German Low Grade Lymphoma Study Group . Blood Dec 1 2005, 106 (12): 3725-32. 
4. Vitolo U, Ferreri AJ, Montoto S. Follicular lymphomas. Crit Rev Oncol Hematol. June 2008, 66 (3): 248-61.
5. Rosenberg SA . Follicular lymphoma revisited . J Clin Oncol February 1, 2008; 26 (4): 515-6. 
6. Morton LM, Wang SS, Devesa SS, et al Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 2006; 107: 265th 
7. Sant M Allemani C Tereanu C., et al . Incidence of hematologic malignancies in Europe by morphologic subtype: results of the project HAEMACARE Blood 2010; 116: 3724th 
8. Biagi JJ, Seymour JF . Insights into the molecular pathogenesis of follicular lymphoma Arising from analysis of geographic variation Blood 2002; 99: 4265th 
9. Shirley MH, Sayeed S, Barnes I, et al. Incidence of Haematological Malignancies by ethnic group in England, 2001-7. Br J Haematol 2013; 163: 465th 
10. Laurini YES, Perry AM, Boilesen E, et al . Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases Blood 2012; 120: 4795th