Edit concept Question Editor Create issue ticket

Mantle Cell Lymphoma

Centrocytic Small Cell Lymphoma

Mantle cell lymphoma is a rare subtype of non-Hodgkin B cell lymphoma that is most frequently diagnosed in older males. Fatigue, generalized lymphadenopathy and splenomegaly are its typical features. The bone marrow, peripheral blood and the gastrointestinal tract are notable extranodal sites. Biopsy and subsequent immunophenotyping is necessary to make the diagnosis. Despite aggressive treatment that consists of chemotherapy and bone marrow transplant, overall survival rates are rarely over 5 years.

Mantle Cell Lymphoma - Symptom Checker

Ad Check possible symptoms of Mantle Cell Lymphoma now!

Presentation

The often aggressive nature of the tumor may be one of the factors why almost 70% of patients present in late stage of the disease, which is characterized by fatigue, systemic symptoms and the appearance of generalized lymphadenopathy and splenomegaly [2] [9]. Splenomegaly is often massive [2], while aberrant WBC count may be seen, either as markedly high leukocytosis or pancytopenia [10]. An indolent type of MCL is seen in approximately 10-15% of cases, with minimal lymphadenopathy and splenomegaly [4].

Splenomegaly
  • Splenomegaly is often massive, while aberrant WBC count may be seen, either as markedly high leukocytosis or pancytopenia. An indolent type of MCL is seen in approximately 10-15% of cases, with minimal lymphadenopathy and splenomegaly.[symptoma.com]
  • Abstract A baseline F-FDG PET/CT scan in a patient with mantle cell lymphoma showed diffuse minimally FDG-avid lymphadenopathy and splenomegaly. There was also a focus of uptake in the left subscapularis muscle without a CT correlate.[ncbi.nlm.nih.gov]
  • Case report: A 64-year-old male initially presented with fatigue, splenomegaly, and bicytopenia. The bone marrow biopsy specimen revealed extensive infiltration with MCL.[ncbi.nlm.nih.gov]
  • MCL can present with prominent splenomegaly with circulating atypical lymphocytes, mimicking the clinical presentation of chronic lymphocytic leukemia.[cancertherapyadvisor.com]
  • Characteristics at diagnosis involved lymphadenopathy (82%), splenomegaly (44%), B-symptoms (39%), and hepatomegaly (10%). Bone marrow invasion was present at diagnosis in 77%. Stage at diagnosis was advanced in the majority of cases.[ncbi.nlm.nih.gov]
Generalized Lymphadenopathy
  • Extreme fatigue, an enlarged spleen and diffuse swelling of lymph nodes (known as generalized lymphadenopathy) are typical findings.[symptoma.com]
  • lymphadenopathies in 90%, bone marrow involvement (70%), frequent splenomegaly (50%), hepatomegaly (30%), and gastro-intestinal involvement (20%), and lymphocytosis (30%); elevated LDH in 50% Leukemic phase of mantle cell lymphoma.[atlasgeneticsoncology.org]
  • Patients with MCL typically present with generalized lymphadenopathy and extranodal involvement, particularly in the bone marrow, spleen, and gastrointestinal tract.[hematology.org]
Fever
  • He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma.[ncbi.nlm.nih.gov]
  • Fever and impaired general condition (fatigue, loss of appetite and weight loss) may occur.[orpha.net]
  • IIA), where B means presence of B symptoms (see below) while A means abscence of the following symptoms: Unexplained a href ”/fever/” fever 38 Centigrade Unexplained weight loss (defined as 10% of body weight in 6 months) Night sweats Prognosis of Mantle[myvmc.com]
  • Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA Decrease in blood cell counts.[imbruvica.com]
  • Other symptoms may include abdominal bloating, nausea, tiredness, loss of appetite, fevers, unexplained weight loss and night sweats. Who does mantle cell lymphoma commonly affect? The average age at diagnosis of MCL is 60-65 years.[leukaemia.org.au]
Fatigue
  • Case report: A 64-year-old male initially presented with fatigue, splenomegaly, and bicytopenia. The bone marrow biopsy specimen revealed extensive infiltration with MCL.[ncbi.nlm.nih.gov]
  • The regimen's toxicity profile was acceptable; only 25% of the cycles resulted in grade 3 or 4 neutropenia or thrombocytopenia, and only 3% of cycles produced grade 3-4 fatigue. There were no episodes of grade 3-4 neuropathy.[ncbi.nlm.nih.gov]
  • The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n 58) were fatigue (38%) and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each).[ncbi.nlm.nih.gov]
  • The most common adverse events were primarily grade 1 or 2 and were headache (47 [38%]), diarrhoea (38 [31%]), fatigue (34 [27%]), and myalgia (26 [21%]).[ncbi.nlm.nih.gov]
  • Extreme fatigue, an enlarged spleen and diffuse swelling of lymph nodes (known as generalized lymphadenopathy) are typical findings.[symptoma.com]
Weight Loss
  • He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma.[ncbi.nlm.nih.gov]
  • Abstract We present a middle-aged woman complaining of weakness, lethargy and weight loss for 6 months. Positron emission tomography (PET)/CT scan revealed huge bilateral adrenal masses with intense 18F-fluorodeoxyglucose avidity.[ncbi.nlm.nih.gov]
  • Fever and impaired general condition (fatigue, loss of appetite and weight loss) may occur.[orpha.net]
  • Other symptoms may include abdominal bloating, nausea, tiredness, loss of appetite, fevers, unexplained weight loss and night sweats. Who does mantle cell lymphoma commonly affect? The average age at diagnosis of MCL is 60-65 years.[leukaemia.org.au]
  • Signs and symptoms of MCL may include fever, night sweats, enlarged lymph nodes, fatigue, splenomegaly ( enlarged spleen ), hepatomegaly ( enlarged liver ), and weight loss.[rxlist.com]
Anemia
  • CASE REPORT: A 79-year-old woman with a 3-month history of bruising and heavy menorrhagia presented with ongoing vaginal bleeding, symptomatic anemia, and a right thigh hematoma.[ncbi.nlm.nih.gov]
  • The 3 patients were all men, ranging from 51 to 74 years in age, and they all presented with systemic lymphadenopathy with anemia, hypoalbuminemia, elevated serum levels of C-reactive protein, and polyclonal hypergammaglobulinemia.[ncbi.nlm.nih.gov]
  • Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%).[ncbi.nlm.nih.gov]
  • Grade 3 or higher effects included low white cell blood counts, anemia and diarrhea. One case of pneumonia was thought to be treatment-related. This was consistent with safety data previously reported, Wang said.[sciencedaily.com]
  • The most common side effects reported in participants receiving Imbruvica are low levels of platelets in the blood (thrombocytopenia), diarrhea, a decrease in infection-fighting white blood cells (neutropenia), anemia, fatigue, musculoskeletal pain, swelling[web.archive.org]
Rapidly Progressive Glomerulonephritis
  • We describe a patient with rapidly progressive glomerulonephritis whose renal biopsy showed effacement of the renal parenchyma by MCL and a membranoproliferative pattern of glomerular injury.[ncbi.nlm.nih.gov]
Diarrhea
  • Two weeks after the start of ibrutinib, he developed grade 3 diarrhea that required interruption of ibrutinib.[ncbi.nlm.nih.gov]
  • Tiredness Bruising Diarrhea Mouth sores (stomatitis) Muscle spasms Nausea Tiredness Mouth sores (stomatitis) Pneumonia Bruising Muscle spasms Diarrhea Nausea Diarrhea is a common side effect in people who take IMBRUVICA .[imbruvica.com]
  • Most side effects were minor and included diarrhea, fatigue, upper respiratory tract infections, nausea and rash. Grade 3 or higher effects included low white cell blood counts, anemia and diarrhea.[sciencedaily.com]
  • Complications of treatment Complications from chemotherapy may include the following: Infection, neutropenia, anemia, and thrombocytopenia Fatigue Neuropathy Dehydration after diarrhea or vomiting Cardiac toxicity from doxorubicin[emedicine.com]
Abdominal Distension
  • PATIENT CONCERNS: A 58-year-old man was admitted to our hospital with epigastric pain, abdominal distension, nausea, and melena. Endoscopy identified submucosal neoplasms and diffuse gastrointestinal tract involvement including the esophagus.[ncbi.nlm.nih.gov]
Hepatomegaly
  • Characteristics at diagnosis involved lymphadenopathy (82%), splenomegaly (44%), B-symptoms (39%), and hepatomegaly (10%). Bone marrow invasion was present at diagnosis in 77%. Stage at diagnosis was advanced in the majority of cases.[ncbi.nlm.nih.gov]
  • Signs and symptoms of MCL may include fever, night sweats, enlarged lymph nodes, fatigue, splenomegaly ( enlarged spleen ), hepatomegaly ( enlarged liver ), and weight loss.[rxlist.com]
  • cell stem origin B-cell lineage Epidemiology 5% of NHL; sex ratio: 3M/1F; median age: 65 yrs Clinics advanced disease (Ann Harbor stage III-IV) with generalized lymphadenopathies in 90%, bone marrow involvement (70%), frequent splenomegaly (50%), hepatomegaly[atlasgeneticsoncology.org]
Hepatosplenomegaly
  • Most patients present with advanced stage disease with lymphadenopathy, hepatosplenomegaly, and bone marrow involvement. The gastrointestinal tract is the most commonly affected extranodal site by this type of non-hodgkin lymphoma.[icd9data.com]
  • MCL manisfests preferentially in middle-aged to older male patients with advanced stage disease with lymphadenopathy, hepatosplenomegaly, and bone marrow involvement.[codes.iarc.fr]
  • […] follicles, mostly of naïve pre-GC type. 7, 12 MCL is generally regarded as an aggressive, incurable disease with the median survival of affected patients being 3–4 years. 12 Clinical features MCL more often presents in stage III–IV with lymphadenopathy, hepatosplenomegaly[haematologica.org]
Diplopia
  • He experienced resolution of his diplopia and ptosis after one cycle of chemotherapy and achieved complete remission of the orbital masses and myasthenia symptoms after 6 cycles.[ncbi.nlm.nih.gov]
Night Sweats
  • He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma.[ncbi.nlm.nih.gov]
  • The disease is grade “A” if there are no common symptoms, such as night sweats. It is grade “B” if those symptoms are present.[lymphomainfo.net]
  • Other symptoms may include abdominal bloating, nausea, tiredness, loss of appetite, fevers, unexplained weight loss and night sweats. Who does mantle cell lymphoma commonly affect? The average age at diagnosis of MCL is 60-65 years.[leukaemia.org.au]
  • Signs and symptoms of MCL may include fever, night sweats, enlarged lymph nodes, fatigue, splenomegaly ( enlarged spleen ), hepatomegaly ( enlarged liver ), and weight loss.[rxlist.com]
Vaginal Bleeding
  • CASE REPORT: A 79-year-old woman with a 3-month history of bruising and heavy menorrhagia presented with ongoing vaginal bleeding, symptomatic anemia, and a right thigh hematoma.[ncbi.nlm.nih.gov]
Papilledema
  • Ophthalmoscopic examination and magnetic resonance angiography found the presence of papilledema due to thrombosis in superior sagittal sinus. The examination findings revealed a mantle cell lymphoma.[ncbi.nlm.nih.gov]

Workup

Initial laboratory studies should encompass a complete blood count (CBC), levels of LDH and basic biochemical parameters (renal function tests, alkaline phosphatase, hepatic enzymes, serum electrolyte levels and serum protein electrophoresis) [3], while imaging studies such as computed tomography (CT) of the chest, pelvis and abdomen are equally important in the diagnostic workup [2]. If possible, fluorodeoxyglucose positron emission tomography (FDG/PET) should be performed [2]. To make the diagnosis, biopsy of the tissue that is suspected to be infiltrated with malignant cells (most commonly the lymph node, but also bone marrow or peripheral blood) is necessary [2]. Immunophenotyping is used to determine presence of CD5+ and CD20+ and absence of CD10 and Bcl6 [2]. Moreover, to confirm the characteristic t(11;14) translocation that causes overexpression of cyclin D1 seen in virtually all mantle cell lymphomas, fluorescent in situ hybridization (FISH) is the recommended diagnostic procedure [4]. The increased expression of the transcription factor SOX11 is also mentioned as a diagnostic marker for MCL, but also as a distinguishing feature from diffuse large B-cell lymphoma, in which SOX11 expression is normal [10], whereas high Ki-67 proliferation index, mutations of p53 and p16 deletions are important markers of more aggressive forms of the disease [2].

Cytopenia
  • Persistent cytopenia in 29 patients who had received R-FC precluded participation in the second randomization, because maintenance therapy with interferon alfa required adequate hematopoietic function.[nejm.org]
  • Diarrhea, fatigue, cytopenias, hypertension, and nausea were observed in some patients.[tandfonline.com]

Treatment

Some studies suggest that asymptomatic elderly patients should not receive immediate therapy [10] but treatment should be initiated as soon as the diagnosis is confirmed. Various strategies exist depending on the overall condition of the patient, presence of comorbidities and age [4]. The standard therapeutic approach consists of the R-CHOP regimen (rituximab + cyclophosphamide, doxorubicin, vincristine and prednisone), which is effective in 80% of patients, but approximately 25% of patients relapse within a few years [4]. In patients who are able to tolerate an aggressive approach, R-CHOP together with cytarabine is recommended. A progression-free survival (PFS) was shown to be > 5 years under such circumstances [4]. If patients respond to therapy, evaluation for possible ASCT (allogenic stem cell transplant) is performed [11]. In fact, nonmyeloablative allogeneic HCT has been shown to be of significant benefit, especially in those who experience relapses or those who are refractory to therapy [6]. Additionally, various second-line and third-line agents have been recommended for use [4]. Bortezomib, temsirolimus, lenalidomide, ibrutinib, and bendamustine are all potential agents that are currently in various phases of clinical trials, but their long-term effects and efficacy compared to standard regimens is yet to be confirmed [10] [12].

Prognosis

In the past decades, median overall survival rarely exceeded more than 2.5 years, but the introduction of novel therapeutic strategies has somewhat improved patient outcomes, increasing the overall survival to > 5 years [4]. Other studies report that median survival of MCL patients ranges between 1 year in those with aggressive disease to > 10 years in those who develop an indolent form of the disease [8]. In recent years, the mantle cell lymphoma international prognostic index (MIPI) has been developed and consists of four factors: age, Eastern Cooperative Oncology Group (ECOG) performance status, levels of LDH and white blood cell (WBC) count [1]. On the basis of this prognostic index, patients can be classified into low, intermediate and high-risk groups [1], which is now being used to determine the therapeutic approach. Unfortunately, many patients are diagnosed in advanced stages of the disease, leading to a significantly reduced overall survival [2].

Etiology

Mantle cell lymphoma originates from antigen-naive B cells in the mantle zone around germinal centers of the lymph nodes [7]. On the basis of its morphologic (diffuse, nodular, mantle zone) and cytologic (pleomorphic, blastoid or small cells) features, the tumor may be subsequently divided into various forms [4]. The cause of malignant transformation stems from a translocation t(11;14) that subsequently leads to overexpression of cyclin D1 protein, which is involved in regulation of the cell cycle [8]. So far, genetic studies have established mutations of various genes, including p53, BIRC3,WHSC1, ATM and NOTCH1 [4], as well as various defects in the cell cycle and DNA signaling pathways [5].

Epidemiology

Although exact incidence and prevalence rates of MCL are not known, it comprises approximately 3-6% of all non-Hodgkin lymphomas [1]. This tumor is most frequently diagnosed in the sixth and seventh decade of life and a significant predilection toward males has been observed (3:1 male-to-female ratio) [4]. Apart from typical nodal location of the tumor, various extranodal sites have been described in literature, including the stomach, liver, colon, the skin, lacrimal glands and the central nervous system [2].

Sex distribution
Age distribution

Pathophysiology

The pathogenesis starts with overexpression of cyclin D1, one of the most important regulatory proteins in the cell cycle, specifically during the G1/S phase transition. This genetic aberration occurs as a result of t(11;14)(q13;q32) translocation, which is the hallmark of MCL, while various secondary mutations have been detected, including those involved in cell survival signals, cell cycle defects (specifically BMI1, ARF, CDK4, RB1 and several other) and pathways that involve DNA damage (p53, p16) [5]. These mutations create favorable conditions for malignant proliferation and differentiation, but the exact model of disease is yet to be established. A small subset of patients were diagnosed with cyclin D1-negative MCL that expressed cyclins D2 and D3, showing that other mechanisms are potentially used by malignant cells to continue proliferating [8].

Prevention

At this moment, preventive strategies against MCL do not exist, despite the fact that the underlying genetic mechanism of disease is established.

Summary

Mantle cell lymphoma (MCL) is a rare but insidious and aggressive tumor that belongs to the group of non-Hodgkin lymphomas (NHLs) and constitutes approximately 3-6% of all tumors in this group [1]. MCL stems from naive B cells in the mantle zone, around the germinal centers of the lymph nodes, but various extranodal sites have been described, including the gastrointestinal tract, the central nervous system, skin and lacrimal glands [2]. The main oncogenic event in MCL is translocation t(11;14)(q13;q32) that fuses cyclin D1 gene and IgH locus [3], leading to overexpression of cyclin D1, a protein involved in regulation of the cell cycle during the G1/S phase transition. In addition, several other genetic mutations have been discovered, involving p53, p16, RB1, ARF, CDK4, NOTCH and several other [4] [5]. This tumor is most commonly diagnosed in patients during their sixth and seventh decade of life and a marked predilection toward male gender, with a 3:1 male-to-female ratio, was determined across numerous reports [4]. The clinical presentation involves generalized lymphadenopathy, splenomegaly that is often massive and systemic symptoms, primarily because the vast majority of patients are diagnosed in advanced stages of the disease [2] [3]. In a small subset of patients, an indolent form that is characterized by minimal or absent lymphadenopathy and a milder clinical course may be seen [4]. Laboratory workup must include evaluation of all blood lineages, and either pancytopenia or marked leukocytosis may be observed. Levels of lactate dehydrogenase (LDH), and also hepatic and kidney parameters should be assessed. In addition, imaging studies such as computed tomography and plain radiography of the chest, pelvis and abdomen are recommended, so that the status of the internal organs and lymphoid tissue may be determined [2] [4]. To confirm MCL, however, a biopsy with subsequent immunophenotyping is vital in order to distinguish between various types of lymphomas and to determine optimal therapy [2]. Treatment principles rest on aggressive chemotherapy in younger patients who are able to tolerate the effects of chemotherapeutic drugs. Rituximab, cyclophosphamide, vincristine, prednisone, and doxorubicin, (known as the R-CHOP regimen) together with cytarabine are recommended for MCL treatment [4], whereas autologous stem cell transplantation (ASCT) is recommended as an adjunctive therapeutic measure [6]. Although several drugs are currently being tested in patients, the prognosis is still very poor. Recently, the mantle cell lymphoma international prognostic index (MIPI) was designed to assess patients based on their clinical and laboratory findings and median overall survival rates of little over 5 years have been determined [4]. For this reason, early recognition of the disease is essential in achieving better patient outcomes, but this may not be easy due to the nature of the tumor and its silent clinical progression.

Patient Information

Mantle cell lymphoma (MCL) is a rare but very dangerous tumor of white blood cells and belongs to a large group of non-Hodgkin lymphomas (NHLs), comprising approximately 3-6% of all tumors in this group. Various genetic mutations have been identified, but it is thought that overexpression of one of the proteins involved in regulation of the normal cell cycle occurs due to a specific chromosomal aberration, thus leading to an increased susceptibility for malignant transformation of cells. In most cases, MCL develops in lymph nodes (it was named Mantle cell due to the fact that it develops in mantle zones of the lymph nodes), but other sites have also been reported, such as the gastrointestinal tract, the central nervous system and the skin. This tumor is most frequently diagnosed in elderly individuals in their 60s, with a strong predilection toward male gender for unknown reasons. Many patients present when the disease is already in advanced stages. Extreme fatigue, an enlarged spleen and diffuse swelling of lymph nodes (known as generalized lymphadenopathy) are typical findings. In a small number of cases, however, an indolent form of MCL may be recognized that is distinguished by the absence of lymph node enlargement, which may present a diagnostic challenge for the physician. Nevertheless, a complete laboratory panel should be obtained that will include a complete blood count, liver and kidney function tests, as well as serum electrolytes. Additionally, imaging procedures such as computed tomography (CT scan) of the abdomen, pelvis and chest are equally important in assessing the general status of the patient, but also to determine the stage of the disease. To confirm MCL, a biopsy of the tissue in which the tumor grows (lymph node, bone marrow, gastrointestinal tract) and subsequent microscopic examination is necessary. Treatment is initiated as soon as the diagnosis is confirmed, except in asymptomatic patients and consists of an aggressive chemotherapy regimen known as R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine and prednisone), while cytarabine is added in younger patients and those who do not have additional comorbidities. In addition to chemotherapy, stem cell transplantation is performed as a follow-up measure whenever possible. Despite the fact that many drugs are currently tested to improve patient outcomes in the case of MCL, the prognosis is still very poor, as overall survival rates rarely exceed > 5 years. For this reason, it is imperative to find strategies that will recognize this condition early on.

References

Article

  1. Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008;111(2):558–65.
  2. Vose JM. Mantle cell lymphoma: 2015 update on diagnosis, risk-stratification, and clinical management. Am J Hematol. 2015;90(8):739-745.
  3. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
  4. Avivi I, Goy A. Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice. Clin Cancer Res. 2015;21(17):3853-3861.
  5. Jares P, Campo E. Advances in the understanding of mantle cell lymphoma. Br J Haematol. 2008;142(2):149-165.
  6. Vaughn JE, Sorror ML, Storer BE, Chauncey TR, Pulsipher MA, Maziarz RT, et al. Long-term sustained disease control in patients with mantle cell lymphoma with or without active disease after treatment with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Cancer. 2015;121(20):3709-3716.
  7. Sander B. Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers. Semin Diagn Pathol. 2011;28(3):245-255.
  8. Rosenwald A, Wright G, Wiestner A, Chan WC et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma.Cancer Cell. 2003;3(2):185-197.
  9. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
  10. Rajabi B, Sweetenham JW. Mantle cell lymphoma: observation to transplantation. Ther Adv Hematol. 2015;1:37-48.
  11. Maddocks K, Blum KA. Treatment strategies in mantle cell lymphoma. Cancer Treat Res. 2015;165:251-270.
  12. Hambley B, Caimi PF, William BM. Bortezomib for the treatment of mantle cell lymphoma: an update. Ther Adv Hematol. 2016;7(4):196-208.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-22 03:06