A Unique Case of Mantle Cell Lymphoma Masquerading as a Cecal Mass

Mantle cell lymphoma (MCL), a type of B-cell non-Hodgkin’s lymphoma, is a rare and aggressive disease with a poor prognosis due to its advanced presentation at diagnosis. It is characterized by a translocation in the Bcl-1 gene, which results in overexpression of cyclin D1. MCL is frequently seen in the form of multiple lymphomatous polyposis (MLP) in which innumerable polyps are observed in the gastrointestinal (GI) tract. In rare instances, MCL presents a single mass. The most common presentation involves male patients in their sixties, with generalized lymphadenopathy, extranodal involvement, and B symptoms (night sweats, fever, and weight loss). Endoscopic findings of MLP include cerebroid folding of the gastric mucosa and innumerable polyps extending from the duodenum to the large intestine and are reported in approximately 9% of all GI lymphomas. Less commonly, only 2–4% of GI malignancies present as a primary GI MCL as a single mass, usually in the stomach and ileocecal region in the intestine. Radiologic findings include lymphadenopathy, splenomegaly, multiple polyposis, or wall thickening with ulceration or mass formation. In most instances, advanced disease is found at diagnosis, for which 5-year survival ranges only from 26 to 46%, even when appropriate treatment is initiated. High mitotic rate, or Ki-67 index, is of prognostic value and is associated with poor prognosis. Treatment involves conventional chemo-immunotherapy consisting of R CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or RB (rituximab and bendamustine), with the latter being better tolerated and associated with longer progression-free survival. Surgical resection is usually limited to patients in which complications are seen such as bleeding, perforation, or bowel obstruction. We present a unique case of a 70-year-old male with nonbilious, nonbloody emesis, and symptomatic anemia who was found to have a cecal mass consistent with MCL.

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Prognostic significance of p53, Sox11, and Pax5 co-expression in mantle cell lymphoma

Scientific Reports ◽

10.1038/s41598-021-91433-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Caixia Jing ◽

Yuhuan Zheng ◽

Yu Feng ◽

Xia Cao ◽

Caigang Xu

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Significance ◽

Prognostic Index ◽

Progression Free Survival ◽

Tissue Array ◽

Ki 67 ◽

Mutation Status ◽

Mantle Cell

AbstractMantle cell lymphoma (MCL) is a relatively rare subtype of non-Hodgkin’s lymphoma. To identify molecular biomarkers in MCL, we performed immunohistochemistry tissue arrays using biopsies from 64 MCL patients diagnosed in West China Hospital from 2012 to 2016. TP53 mutation status in those patients was also examined by sequencing. The sequencing results showed TP53 mutations were highly heterogeneous in MCL. We identified four novel TP53 mutations in MCL: P151R, G199R, V218E, and G325R. The MCL patients with TP53 mutations had inferior progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.011). Tissue array results showed the expression of p53, Sox11, or Pax5 alone did not correlate with the patient PFS and OS. However, the MCL patients with triple-positive expression of p53/Sox11/Pax5 had inferior PFS (p = 0.008) and OS (p = 0.002). Such risk stratification was independent to the mantle cell lymphoma international prognostic index (MIPI), Ki-67 value, and TP53 mutation status of the patients. The triple-positive patients might represent a subtype of high-risk MCL. Our findings might indicate a novel way to stratify MCL and predict patients’ prognosis.

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Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma

Blood ◽

10.1182/blood-2011-10-388298 ◽

2012 ◽

Vol 119 (20) ◽

pp. 4597-4607 ◽

Cited By ~ 204

Author(s):

John P. Leonard ◽

Ann S. LaCasce ◽

Mitchell R. Smith ◽

Ariela Noy ◽

Lucian R. Chirieac ◽

...

Keyword(s):

Cyclin D1 ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Objective Response ◽

Treatment Strategies ◽

Progression Free Survival ◽

Ki 67 ◽

Flt Pet ◽

Mantle Cell ◽

Rb Phosphorylation

Abstract Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1–dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3-deoxy-3[18F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUVmax), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUVmax and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.

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Faculty Opinions recommendation of Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726183219.793548359 ◽

2018 ◽

Author(s):

Leo Gordon

Keyword(s):

Mantle Cell Lymphoma ◽

Growth Pattern ◽

Prognostic Value ◽

Randomized Trials ◽

Cell Lymphoma ◽

Ki 67 ◽

Mantle Cell

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Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma

Blood Cancer Journal ◽

10.1038/s41408-020-00394-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alessia Castellino ◽

Aung M. Tun ◽

Yucai Wang ◽

Thomas M. Habermann ◽

Rebecca L. King ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

Local Therapy ◽

Progression Free Survival ◽

Cell Transplant ◽

Multiple Lesions ◽

Mantle Cell

AbstractPrimary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes.

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High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma

Blood ◽

10.1182/blood-2015-02-628792 ◽

2015 ◽

Vol 126 (5) ◽

pp. 604-611 ◽

Cited By ~ 66

Author(s):

Marie-Hélène Delfau-Larue ◽

Wolfram Klapper ◽

Françoise Berger ◽

Fabrice Jardin ◽

Josette Briere ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Prognostic Value ◽

Cell Lymphoma ◽

Standard Of Care ◽

High Dose ◽

Current Standard ◽

Ki 67 ◽

Key Points ◽

Mantle Cell ◽

High Dose Cytarabine

Key Points CDKN2A and TP53 deletions remain of bad prognostic value in younger MCL patients treated according to the current standard of care. CDKN2A and TP53 deletions have independent deleterious effects and should be considered for treatment decisions in addition to MIPI and Ki-67 index.

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Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma

Blood ◽

10.1182/blood.v95.2.619 ◽

2000 ◽

Vol 95 (2) ◽

pp. 619-626 ◽

Cited By ~ 156

Author(s):

Roberto Chiarle ◽

Leo M. Budel ◽

Jeffrey Skolnik ◽

Glauco Frizzera ◽

Marco Chilosi ◽

...

Keyword(s):

Overall Survival ◽

Protein Degradation ◽

Mantle Cell Lymphoma ◽

Molecular Mechanisms ◽

Kinase Inhibitor ◽

Cell Lymphoma ◽

Low Grade ◽

High Grade ◽

Ki 67 ◽

Mantle Cell

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)

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Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma

Blood Advances ◽

10.1182/bloodadvances.2020002068 ◽

2020 ◽

Vol 4 (15) ◽

pp. 3486-3494

Author(s):

Diego Villa ◽

Laurie H. Sehn ◽

Kerry J. Savage ◽

Cynthia L. Toze ◽

Kevin Song ◽

...

Keyword(s):

High Risk ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

First Line ◽

Ki 67 ◽

Historical Cohort ◽

Entire Cohort ◽

Mantle Cell

Abstract Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those >65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.

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p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis

Blood ◽

10.1182/blood.v87.10.4302.bloodjournal87104302 ◽

1996 ◽

Vol 87 (10) ◽

pp. 4302-4310 ◽

Cited By ~ 206

Author(s):

TC Greiner ◽

MJ Moynihan ◽

WC Chan ◽

DM Lytle ◽

A Pedersen ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Median Survival ◽

Poor Prognosis ◽

Denaturing Gradient Gel Electrophoresis ◽

Cell Lymphoma ◽

P53 Protein ◽

Prognostic Significance ◽

Missense Mutations ◽

P53 Mutations ◽

Mantle Cell

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5–8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.

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