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Follicular Lymphoma

Brill Symmers Disease

Follicular lymphoma is a common type of non-Hodgkin lymphoma.

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Presentation

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]
  • Computed tomography (CT) revealed systemic lymphadenopathy, splenomegaly, and thickening of the sigmoid colon and rectum walls. 18F-fluorodeoxy-glucose positron emission tomography (18F-FDG-PET/CT) revealed intense tubular 18F-FDG accumulation extending[ncbi.nlm.nih.gov]
  • Abstract A 73-year-old man, in clinical remission 17 years after radiation therapy for a localized low-grade follicular lymphoma (FL), developed extensive lymphadenopathy, ascites, and splenomegaly with splenic masses.[ncbi.nlm.nih.gov]
  • Computed tomography scan 11 months later showed decreased adenopathy and splenomegaly, which has been sustained for 4 years.[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]
  • Abstract Follicular lymphoma (FL) is a low-grade lymphoma that is usually characterized by generalized lymphadenopathy.[ncbi.nlm.nih.gov]
  • 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]
  • INTRODUCTION 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 disseminated[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]
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]
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]
  • We report the case of a 70 year-old patient with arthralgia, weight loss and chronic fever over two months.[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]
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]
  • In our report, a 62-year-old female was initially diagnosed with a low-grade follicular lymphoma, and 2 years later she presented with bilateral lung masses and lymphadenopathy.[ncbi.nlm.nih.gov]
  • This patient was a 58 years old with generalized lymphadenopathy and Ann Arbor Stage III disease.[ncbi.nlm.nih.gov]
  • The close association between the tumor cells and extramedullary hematopoietic tissue in the absence of lymphadenopathies or other tissue involvement suggests a relationship of this tumor with the recently described primary FL of the bone marrow.[ncbi.nlm.nih.gov]
  • Computed tomography and positron emission tomography showed multiple lymphadenopathies. He was diagnosed with follicular lymphoma (Ann Arbor stage IVA) and PNP-related BO.[ncbi.nlm.nih.gov]
Weight Loss
  • A 59-year-old Japanese man with diarrhea and body weight loss was referred to our hospital.[ncbi.nlm.nih.gov]
  • We report the case of a 70 year-old patient with arthralgia, weight loss and chronic fever over two months.[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]
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]
  • 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]
  • : 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]
  • Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal.[gazyva.com]
  • Night sweats, fever, unexplained weight loss, fatigue, and other symptoms can also occur, mostly in advanced stages.[lymphomanewstoday.com]
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]
  • We report a 65-year old patient with autoimmune hemolytic anemia (AIHA) complicated by a follicular lymphoma (FL) in situ and other B-cell clones in the spleen.[ncbi.nlm.nih.gov]
  • In addition, poor performance status and increasing areas of diffuse histology predicted for a worse survival, while anemia and male sex predicted for a worse FFP.[ncbi.nlm.nih.gov]
  • […] 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]
  • Indications for prednisone given with chlorambucil are autoimmune hemolytic anemia and autoimmune thrombocytopenia.[oncolex.org]
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]
Loss of Appetite
  • Other symptoms may include loss of appetite and tiredness, shortness of breath and generalised unexplained aches and pains.[leukaemia.org.au]
  • No chills, no fever, no fatigue, no loss of appetite, no loss of weight and no general ill feeling. So the doctor has recommended the "watch and wait" approach. As hockeypuck stated earlier, if you are not "sick", you may not need chemo.[cancercompass.com]
  • Symptoms include: Loss of appetite Loss of weight, nausea, vomiting, indigestion or pain in the abdomen A feeling of bloating Itching, bone pain, headaches, constant coughing and abnormal pressure and congestion in the face, neck and upper chest Fatigue[cedars-sinai.edu]
  • 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]
Abdominal Pain
  • We present the case of a 26-year-old female with no significant past medical history who presented to the ER with abdominal pain.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
  • Patient 2 presented in November 2003 at age 69 with transient abdominal pain, which led to ultrasound examination. Imaging showed splenomegaly and retroperitoneal adenopathy. There were no constitutional symptoms.[ncbi.nlm.nih.gov]
Peritoneal Disease
  • We present the unusual case of a patient, clinically deteriorating, whose malignant peritoneal disease was due to an underlying follicular lymphoma.[ncbi.nlm.nih.gov]
Hepatosplenomegaly
  • Splenomegaly is present in approximately 50% of patients at presentation, and hepatosplenomegaly may occur.[emedicine.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]
  • 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]
  • In general, cytopenias can occur but constitutional symptoms of fever, night sweats, and weight loss are uncommon. DIAGNOSIS: Diagnosis is based on histology of preferably a biopsy of a lymph node.[ncbi.nlm.nih.gov]
  • 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.[symptoma.com]
  • Symptoms include night sweats, swollen lymph nodes, and weight loss. Treatment To date, there is no definitive cure for follicular lymphoma and it is considered a terminal illness.[livestrong.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]
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.com]

Workup

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 

Treatment

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:

Prognosis

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%.

Etiology

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.

Epidemiology

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.

Sex distribution
Age distribution

Pathophysiology

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.

Prevention

There is no prevention for this condition.

Summary

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

Patient Information

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.

References

Article

  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

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Last updated: 2019-07-11 21:19