Context.—

Immunophenotypic variations in mantle cell lymphoma (MCL) from the classic CD5+/CD10/CD23/FMC-7+ immunophenotype have been reported in the literature, but correlation with clinical behavior and outcome has not been fully studied.

Objective.—

To investigate clinicopathologic and prognostic differences between immunophenotypically aberrant MCL and immunophenotypically typical MCL.

Design.—

We evaluated differences in clinical presentation, laboratory parameters, prognostic indices, response to initial treatment, and progression-free and overall survival between patients with aberrant MCL and patients with immunophenotypically typical MCL.

Results.—

There were 158 patients with newly diagnosed cyclin D1 or t(11;14)(q13;q32)+ MCL identified in the original search, of which, 29 patients (18%) showed immunophenotypic aberrancies, with CD23 coexpression being the most common. When compared with 33 randomly selected patients with immunophenotypically typical MCL, statistically significant differences were seen in white blood cell counts (P = .02), in the presence of absolute lymphocytosis (P = .03), in the MCL International Prognostic Index score (P = .02), and in response to initial treatment (P = .04). The “immunophenotypic status” of the MCL was the only independent factor associated with response to treatment (P = .05), but not with the MCL International Prognostic Index score, absolute lymphocytosis, or white blood cell count. No significant differences were seen for progression-free or overall survival.

Conclusions.—

Immunophenotypic variations in MCL are associated with differences in clinical presentation and response to therapy when compared with immunophenotypically typical MCL. However, with current intensive frontline immunochemotherapy, immunophenotypic aberrations do not appear to affect progression-free or overall survival.

Mantle cell lymphoma (MCL) is a well characterized B-cell lymphoma defined by a proliferation of small- to medium-sized lymphoid cells, with nodular, diffuse, or mantle zone growth patterns. It accounts for approximately 5% to 10% of non-Hodgkin lymphomas and predominantly occurs in elderly men.1  The genetic hallmark of this lymphoma, considered to be the primary genetic event, is the t(11;14)(q13;q32) translocation between the immunoglobulin H (IgH) gene and the cyclin D1 gene (CCND1), leading to overexpression of the cyclin D1 protein, which is easily detected by immunohistochemistry.1 

Flow cytometry has become an integral part in the subclassification of B-cell lymphomas, with CD5, CD10, CD23, and FMC-7 representing the most frequently used antigens. Routine use of these markers has revealed immunophenotypic aberrancies in MCL, potentially causing diagnostic confusion with other B-cell lymphomas, specifically chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The classic immunophenotype of MCL is that of CD19+/CD20+/CD5+/CD10/FMC-7+/CD23, with bright expression of surface immunoglobulins. Aberrancies in CD23 expression appear to be the most widely investigated, with most studies focusing on correlating morphologic features and disease extent.25  Likewise, the few published articles on CD10 and CD5 aberrancies in MCL compare the immunophenotype to histopathologic findings and clinical stage of disease.69  Correlation of immunophenotypic variations with outcome has, thus far, been comprehensively reported only by Kelemen et al2 , comparing CD5+/CD23+ MCL to immunophenotypically classic MCL. Our study is the first, to our knowledge, and largest that correlates multiple variant immunophenotypes in MCL with prognostic factors, such as the Mantle Cell Lymphoma International Prognostic Index (MIPI) score and clinical outcome, such as response to initial treatment, progression-free survival (PFS), and overall survival (OS).

Case Selection

This study was reviewed and approved by the institutional review board of the Washington University School of Medicine (St Louis, Missouri). For this retrospective study, a search of the Lauren V. Ackerman Division of Anatomic and Molecular Pathology database at the Washington University School of Medicine was conducted, for the period from 2010 to 2015, for newly diagnosed cyclin D1 or t(11;14)(q13;q32)+ cases of MCL.

Immunophenotypic workup of MCL by flow cytometry included a monoclonal antibody combination of sλ/sκ/sCD3/CD19/CD20/CD5/CD10/CD23/FMC-7/CD45. Positivity for an antibody marker was defined as staining of at least 20% of the lymphoma cells based on the negative control. Dim/weak staining was present when 20% to 39% of lymphoma cells stained positively. Staining at 40% to 59% for an antibody was regarded as moderate expression, and staining of 60% or more was regarded as strong staining. Any MCL case that deviated from the typical immunophenotype of CD5+/CD23/CD10/FMC-7+ was placed into the immunophenotypically aberrant MCL (aMCL) group. The control group was composed of sequential MCL cases with the classic CD5+/CD23/CD10/FMC7+ immunophenotype, selected from a random date forward.

Electronic medical records were subsequently reviewed to investigate patient demographics as well as laboratory and clinical characteristics at presentation, including white blood cell (WBC) count; hemoglobin; platelets; lactate dehydrogenase (LDH); Eastern Cooperative Oncology Group (ECOG) performance status, which assesses the functional status of the patient; and the MIPI score.10  The MIPI score was originally derived from clinical trial data of 455 patients with advanced-stage MCL, who were classified into 3 risk groups based on age, LDH level, ECOG performance status, and WBC count.11  The score is calculated with the following formula:

\(\def\upalpha{\unicode[Times]{x3B1}}\)\(\def\upbeta{\unicode[Times]{x3B2}}\)\(\def\upgamma{\unicode[Times]{x3B3}}\)\(\def\updelta{\unicode[Times]{x3B4}}\)\(\def\upvarepsilon{\unicode[Times]{x3B5}}\)\(\def\upzeta{\unicode[Times]{x3B6}}\)\(\def\upeta{\unicode[Times]{x3B7}}\)\(\def\uptheta{\unicode[Times]{x3B8}}\)\(\def\upiota{\unicode[Times]{x3B9}}\)\(\def\upkappa{\unicode[Times]{x3BA}}\)\(\def\uplambda{\unicode[Times]{x3BB}}\)\(\def\upmu{\unicode[Times]{x3BC}}\)\(\def\upnu{\unicode[Times]{x3BD}}\)\(\def\upxi{\unicode[Times]{x3BE}}\)\(\def\upomicron{\unicode[Times]{x3BF}}\)\(\def\uppi{\unicode[Times]{x3C0}}\)\(\def\uprho{\unicode[Times]{x3C1}}\)\(\def\upsigma{\unicode[Times]{x3C3}}\)\(\def\uptau{\unicode[Times]{x3C4}}\)\(\def\upupsilon{\unicode[Times]{x3C5}}\)\(\def\upphi{\unicode[Times]{x3C6}}\)\(\def\upchi{\unicode[Times]{x3C7}}\)\(\def\uppsy{\unicode[Times]{x3C8}}\)\(\def\upomega{\unicode[Times]{x3C9}}\)\(\def\bialpha{\boldsymbol{\alpha}}\)\(\def\bibeta{\boldsymbol{\beta}}\)\(\def\bigamma{\boldsymbol{\gamma}}\)\(\def\bidelta{\boldsymbol{\delta}}\)\(\def\bivarepsilon{\boldsymbol{\varepsilon}}\)\(\def\bizeta{\boldsymbol{\zeta}}\)\(\def\bieta{\boldsymbol{\eta}}\)\(\def\bitheta{\boldsymbol{\theta}}\)\(\def\biiota{\boldsymbol{\iota}}\)\(\def\bikappa{\boldsymbol{\kappa}}\)\(\def\bilambda{\boldsymbol{\lambda}}\)\(\def\bimu{\boldsymbol{\mu}}\)\(\def\binu{\boldsymbol{\nu}}\)\(\def\bixi{\boldsymbol{\xi}}\)\(\def\biomicron{\boldsymbol{\micron}}\)\(\def\bipi{\boldsymbol{\pi}}\)\(\def\birho{\boldsymbol{\rho}}\)\(\def\bisigma{\boldsymbol{\sigma}}\)\(\def\bitau{\boldsymbol{\tau}}\)\(\def\biupsilon{\boldsymbol{\upsilon}}\)\(\def\biphi{\boldsymbol{\phi}}\)\(\def\bichi{\boldsymbol{\chi}}\)\(\def\bipsy{\boldsymbol{\psy}}\)\(\def\biomega{\boldsymbol{\omega}}\)\(\def\bupalpha{\bf{\alpha}}\)\(\def\bupbeta{\bf{\beta}}\)\(\def\bupgamma{\bf{\gamma}}\)\(\def\bupdelta{\bf{\delta}}\)\(\def\bupvarepsilon{\bf{\varepsilon}}\)\(\def\bupzeta{\bf{\zeta}}\)\(\def\bupeta{\bf{\eta}}\)\(\def\buptheta{\bf{\theta}}\)\(\def\bupiota{\bf{\iota}}\)\(\def\bupkappa{\bf{\kappa}}\)\(\def\buplambda{\bf{\lambda}}\)\(\def\bupmu{\bf{\mu}}\)\(\def\bupnu{\bf{\nu}}\)\(\def\bupxi{\bf{\xi}}\)\(\def\bupomicron{\bf{\micron}}\)\(\def\buppi{\bf{\pi}}\)\(\def\buprho{\bf{\rho}}\)\(\def\bupsigma{\bf{\sigma}}\)\(\def\buptau{\bf{\tau}}\)\(\def\bupupsilon{\bf{\upsilon}}\)\(\def\bupphi{\bf{\phi}}\)\(\def\bupchi{\bf{\chi}}\)\(\def\buppsy{\bf{\psy}}\)\(\def\bupomega{\bf{\omega}}\)\(\def\bGamma{\bf{\Gamma}}\)\(\def\bDelta{\bf{\Delta}}\)\(\def\bTheta{\bf{\Theta}}\)\(\def\bLambda{\bf{\Lambda}}\)\(\def\bXi{\bf{\Xi}}\)\(\def\bPi{\bf{\Pi}}\)\(\def\bSigma{\bf{\Sigma}}\)\(\def\bPhi{\bf{\Phi}}\)\(\def\bPsi{\bf{\Psi}}\)\(\def\bOmega{\bf{\Omega}}\)\begin{equation}\left[ {0.03535 \times {\rm{age}}\left( {\rm{y}} \right)} \right] + 0.6978{\rm{}}\left( {{\rm{if\ ECOG\ 2}}-4} \right) + \left[ {1.367 \times \log 10\left( {{\rm{LDH/ULN}}} \right)} \right] + 0.9393 \times \log 10\left( {{\rm{WBC}}} \right),\end{equation}

where ULN is the upper limit of the LDH reference range, and WBC is the WBC count per microliter (×106). A MIPI score of less than 5.7 represents a low disease risk, a score of 5.7 to less than 6.2 is an intermediate disease risk, and a score of 6.2 or greater is a high disease risk.11  We also assessed patients for response to initial treatment, PFS, and OS.

The variables above were compared between the aMCL group and the immunophenotypically typical MCL (tMCL) group. From the pool of 129 classic MCL cases, 33 sequential tMCL, selected from a random date forward were used as the comparator group.

Statistical Analysis

The differences in demographic and clinical characteristics between the 2 MCL groups were compared with the Fisher exact test, Wilcoxon rank-sum test, or 2-sample t test, as appropriate. The OS was defined as the time from diagnosis to death from any cause, and survivors were censored at the date of last contact. The PFS was defined as the time from diagnosis to disease progression. Those patients alive and progression free were censored at their date of last contact. The between-group differences in OS and PFS were described by the Kaplan-Meier product-limit method and compared by log-rank tests. All analyses were 2-sided, and significance was set at a P value of .05. Statistical analyses were performed using SAS software (version 9.4, SAS Institutes, Cary, North Carolina).

Immunophenotypic Aberrancies in aMCL

We retrospectively identified 29 newly diagnosed patients with cyclin D1 or t(11;14)(q13;q32)+ MCL and immunophenotypic aberrancies, representing approximately 18.4% of all 158 MCLs diagnosed between 2010 and 2015 at our institution. Of the 158 MCL cases, 19 (12.0%) revealed coexpression of CD5 and CD23, the most common immunophenotypic aberrancy, followed by 7 cases (4.4%) with expression of CD10; 2 cases (1.3%) lacking CD5, CD23, or CD10 coexpression; and 1 case (0.6%) lacking expression of CD5 and CD10 but expressing CD23. The various aberrant immunophenotypes and their frequencies within the aMCL group are listed in Table 1, and representative scattergrams are displayed in Figure 1.

Table 1

Immunophenotypic Aberrancies in Mantle Cell Lymphoma Detected by Flow Cytometry

Immunophenotypic Aberrancies in Mantle Cell Lymphoma Detected by Flow Cytometry
Immunophenotypic Aberrancies in Mantle Cell Lymphoma Detected by Flow Cytometry
Figure 1

Patterns of immunophenotypic aberrancies in mantle cell lymphoma. All cases showed cyclin D1 expression or t(11;14)(q13;q32) by fluorescence in situ hybridization. Mantle cell lymphoma showing dim CD5 and dim CD23 expression (A through D); CD5 and CD10 coexpression (E through H); CD5 negativity, but CD23 expression (I through K); and negativity for CD5, CD10, and CD23 (L through N).

Figure 1

Patterns of immunophenotypic aberrancies in mantle cell lymphoma. All cases showed cyclin D1 expression or t(11;14)(q13;q32) by fluorescence in situ hybridization. Mantle cell lymphoma showing dim CD5 and dim CD23 expression (A through D); CD5 and CD10 coexpression (E through H); CD5 negativity, but CD23 expression (I through K); and negativity for CD5, CD10, and CD23 (L through N).

Close modal

The CD5+/CD23+/CD10 MCL group was further subdivided into a CD5+ group with moderate or strong CD23 coexpression (8 of 19 cases; 42.1%), a CD5+ group with CD23 dim expression (6 of 19 cases; 31.6%), and a CD5+ (dim) and CD23+ (dim) group (5 of 19 cases; 26.3%) (Figure 1; Table 1). FMC-7 expression patterns were available for 13 of those cases. Ten cases showed at least moderate coexpression for this marker, with most cases showing strong coexpression, whereas 3 cases revealed absent or dim coexpression. The latter cases all belonged to the CD5+ (strong) and CD23+ (dim) MCL group (data not shown).

Of the 7 CD10-expressing MCLs, 5 (71.4%) coexpressed CD5 and lacked expression of CD23, and 2 (28.6%) were negative or dim for CD5, with 1 case coexpressing CD23 (Figure 1, E through H; Table 1).

Patient Characteristics, Laboratory Parameters, Morphologic Subtype, and Performance Status

No statistically significant differences were observed between the 2 groups for age and gender distribution (tMCL age mean [SD], 58.8 [11.4]; aMCL, 61.9 [10.0]; P = .26; tMCL male to female ratio, 7.25; aMCL, 3.8; P = .36). When comparing the 2 groups for laboratory parameters, statistical significance was found only for the WBC count and for absolute lymphocytosis. The aMCL group presented with a significantly higher WBC counts and significantly greater absolute lymphocytosis frequencies (aMCL WBC mean, 22.4 × 103/μl; tMCL, 9.35 × 103/μl ; P = .02; number of patients with aMCL and absolute lymphocytosis, 13; tMCL, 6; P = .03) (Table 2). There was no statistically significant difference between the 2 groups regarding frequency of “leukemic” phase presentation of MCL, a distinct clinical subtype, which is characterized by involvement of peripheral blood, bone marrow, and often, spleen but not lymph nodes (aMCL, approximately 10%; tMCL, approximately 3%; P = .33) (Table 2). No statistically significant differences between the 2 groups were noted for hemoglobin levels, platelet counts, LDH levels, or morphologic subtypes (Table 2).

Table 2

Clinical Characteristics Based on Disease Group

Clinical Characteristics Based on Disease Group
Clinical Characteristics Based on Disease Group

The ECOG performance status did not differ statistically between the 2 groups. Most patients presented with an ECOG status of 0 or 1 (tMCL ECOG status of 0 or 1, 83%; aMCL, 91%; P = .41). However, of the 22 patients within the aMCL group for whom MIPI data were available, more patients, namely 10 (45.5%), scored in the high disease risk group, whereas only 6 patients (27.3%) scored in the low disease risk group, compared with the 23 patients in the tMCL group with data available, in which 3 patients (13.0%) scored in the high disease risk group, and 15 patients (65.2%) scored in the low disease risk group. That finding was statistically significant (P = .02) (Table 2).

Response to Treatment, PFS, and OS

Clinical follow-up data were available for 28 of 29 patients (96.6%) in the aMCL group and 32 of 33 patients (97.0%) in the tMCL group, which ranged from 2 to 73 months (median, 28 months) for the aMCL group, and 2 to 77 months (median, 44 months) for the tMCL group. Response to initial treatment was significantly better for patients in the tMCL group with 23 patients achieving complete remission, compared with only 14 patients in the aMCL group (complete remission, tMCL, 77%; aMCL, 52%; P = .04) (Table 2). Using initial response to treatment as an outcome, the “immunophenotypic status” of the MCL was the only independent factor associated with response to treatment (P = .05) but not with MIPI (P = .10), absolute lymphocytosis (P = .63), or WBC counts (P = .55) (Table 3). The most commonly administered immunotherapy/chemotherapy regimens in both groups were methotrexate with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; or rituximab-bendamustine, and rituximab-hypercyclophosphamide, vincristine, doxorubicin, and dexamethasone. When the 2 groups were compared regarding PFS and OS, no statistical significance was observed (P = .82 and P = .56, respectively) (Figure 2, A and B).

Table 3

Correlation of Immunophenotype, Mantle Cell Lymphoma International Prognostic Index (MIPI), Absolute Lymphocytosis, and White Blood Cell (WBC) Counts With Remission Rates After Initial Treatment

Correlation of Immunophenotype, Mantle Cell Lymphoma International Prognostic Index (MIPI), Absolute Lymphocytosis, and White Blood Cell (WBC) Counts With Remission Rates After Initial Treatment
Correlation of Immunophenotype, Mantle Cell Lymphoma International Prognostic Index (MIPI), Absolute Lymphocytosis, and White Blood Cell (WBC) Counts With Remission Rates After Initial Treatment
Figure 2

Progression-free survival (A) and overall survival (B) curves comparing the immunophenotypically aberrant mantle cell lymphoma and immunophenotypically typical mantle cell lymphoma groups.

Figure 2

Progression-free survival (A) and overall survival (B) curves comparing the immunophenotypically aberrant mantle cell lymphoma and immunophenotypically typical mantle cell lymphoma groups.

Close modal

Although MCL is a well-characterized B-cell lymphoma defined by the t(11;14)(q13;q32) translocation associated with overexpression of cyclin D1, which is readily detectable by immunohistochemistry, variations from the typical immunophenotype of CD5+/CD10/CD23/FMC-7+ may cause diagnostic confusion with other B-cell lymphomas, particularly CLL/SLL. Immunophenotypic aberrancies in MCL have been described in the literature.2,49  Our study is the first, to our knowledge, and largest report that correlates multiple antigen-expression aberrancies, including CD10 expression, with prognostic factors, such as MIPI score and clinical outcome, such as response to initial treatment, PFS, and OS. The only other, smaller series that incorporated outcome data, to our knowledge, were published by Kelemen et al2  in 2008 and Gong et al3  in 2011, focusing on the CD5+/CD23+ MCL.

The spectrum of immunophenotypic aberrancies observed in our case cohort involved all the diagnostically relevant antigens CD5, CD10, CD23, and FMC-7. CD23 expression, ranging from dim to strong, was the most common finding and in keeping with other published observations.3,5  The frequency of CD23+ coexpression by flow cytometry in MCL varies in the literature with the highest, 45%, reported by Gong et al.3  In our cohort of 158 cases, 19 (approximately 12%) showed CD23 coexpression, a rate similar to a literature review of 9 case series summarized by Schlette et al,4  where 21 of 146 MCL cases (14.4%) were reported to aberrantly coexpress CD23. The variability in frequency of this antigen aberrancy may be explained, in part, by the lack of a standardized cutoff for “positivity” and the relatively few MCL cases investigated per study reviewed. Interestingly, the frequency of CD23 coexpression within the distinct clinical subtype of leukemic MCL has been reported by Schlette et al12  to be at 13%.

In our series, in addition to CD23 positivity, 3 of the 13 cases (23%) with available FMC-7 data had negative or dim FMC-7 staining. FMC-7 is another marker useful in distinguishing MCL from CLL/SLL because this antigen usually stains positively for MCL and usually does not stain for CLL/SLL.13  The FMC-7 negativity/dimness was only noted in the CD5+ (strong) and CD23+ (dim) cases, which caused diagnostic confusion with CLL/SLL. Our frequency of CD23+/FMC7/dim MCL is in accordance with the reported 22% by Schlette et al4  and 29% by Kelemen et al2  but is higher than the approximately 11% observed in the study by Gao et al.5 

CD10 coexpression in MCL was not infrequent in our case series. It occurred in approximately 7 (4.5%) of all MCLs diagnosed between 2010 and 2015 and represented 7 (24%) of the aMCL cohort. Five co-expressed CD5 and lacked expression of CD23, and 2 were negative or dim for CD5 with 1 case partially coexpressing CD23. Zanetto et al7  reported the largest series of CD10+ MCL, comprising 13 patients. Nine patients (69%) had a CD5+/CD10+ immunophenotype at diagnosis, whereas 2 (15%) were CD5/CD10+. The 2 remaining patients (15%), initially negative for CD10 on lymphoma cells, gained CD10 expression in subsequent lymphoma specimens.7  Clinical features of these patients did not differ from a larger series of unselected MCL patients, with most patients presenting with disseminated disease, with or without peripheral blood involvement. Likewise, frequency of pleomorphic or blastoid morphology (8% at diagnosis; 31% at relapse) was not significantly different compared with the larger unselected series of MCL.7  In our cohort, only 1 case (14%) of CD10+ MCL showed blastoid morphology, but combining all immunophenotypic aberrancies, blastoid morphology was present in approximately 17% of cases, an incidence rate not different from the published 17% to 38% of unselected MCL case series.14,15 

CD5/CD10 MCL comprised only 3 (2%) of all MCL in our study, less frequent than the roughly 6% reported by Yatabe et al16  or 11% by Liu et al9 , both representing the largest published series on this immunophenotypic aberrancy in MCL. Although the overall number of cyclin D1 or t(11;14)(q13;q32)-proven CD5/CD10 MCL in those 2 reported studies is low, it appears that the extent of disease involvement or morphology did not differ from the classic counterpart.9 

Most literature on immunophenotypically aberrant MCL showed no differences in age, sex predilection, morphology, disease extent, or peripheral blood involvement when compared with immunophenotypical counterparts.2,4,7,9,17  Our study agreed with findings regarding age and sex predilection but disagreed on peripheral blood involvement. The WBC count and the presence of absolute lymphocytosis differed significantly between our 2 groups, with the aMCL group showing a mean WBC count of 22.4 × 103/μl versus 9.35 × 103/μl for the tMCL (P = .02), and the aMCL group comprised 13 patients (48%) with absolute lymphocytosis versus only 6 (21%) for the tMCL group (P = .03). The frequency of absolute lymphocytosis in our aMCL group approached the percentage of 56% seen by Schlette et al,4  who investigated 18 cases of CD23+ MCLs, but was much higher than the 20% observed for the CD23+ MCL group comprising 14 patients by Kelemen et al.2  Furthermore, the incidence of absolute lymphocytosis was not statistically significant between CD23 MCL and CD23+ MCL in the Kelemen et al2  study or in the WBC counts between these 2 groups. The statistically increased WBC count and absolute lymphocytosis observed in our aMCL group was not associated with a greater frequency of leukemic phase MCL when compared with the tMCL group.

For LDH levels and ECOG performance status, our observations are in concordance with those from Kelemen et al,2  where no statistically significant differences were found.

An important focus of our study was to compare aMCL and tMCL in disease risk stratification and outcome. Using the MIPI scoring system, low scores for disease risk were more commonly seen in the tMCL group (15 of 23 versus 6 of 22; 65% versus 27%), whereas high scores for disease risk were found more commonly in the aMCL group (10 of 22 versus 3 of 23; 45% vs 13%; P = .02). Looking at response rate to initial treatment, the aMCL group achieved a lower rate of complete remission than the tMCL group (14 of 27 versus 23 of 30; 52% versus 77%; P = .04). The immunophenotypic status of MCL appeared to be the only independent variable significantly associated with initial response. However, no statistical difference was noted in PFS or OS between the 2 groups, which differs from observations published by Kelemen et al,2  who reported a superior survival outcome for CD23+ MCL compared with CD23 MCL. Furthermore, we did not find statistical significance for PFS or OS when the CD23+ MCL group (19 cases) was compared separately to the tMCL group (data not shown). In the study by Kelemen et al,2  the 4-year event-free survival for CD23+ MCL was 45% compared with 19% for the CD23 cases. Likewise, the 4-year overall survival for CD23+ MCL was 75% compared with 53% for CD23 cases. Gong et al3  did not find a significant association between CD23 intensity in MCL and clinical stage or survival. However, the authors cautioned that all 10 CD23+ MCL cases, which were compared with 12 CD23 cases were dim for CD23, the overall case numbers were few, and the clinical follow-up time was short, limiting more meaningful interpretation.3  Furthermore, treatment of MCL has changed substantially in recent years, with the use of intensive cytarabine-containing induction therapy with autologous stem cell transplant and the introduction of novel therapies, such as bendamustine and biologic agents. The predictive value of MCL immunophenotype on PFS and OS may have been surpassed by intensified frontline immunochemotherapy.

In summary, our study demonstrates that immunophenotypic variations in MCL are broad and involve all diagnostically relevant antigens CD5, CD10, CD23, and FMC-7. Although the immunophenotypically aberrant MCL group presented with more-pronounced peripheral blood involvement, greater disease risk by MIPI score, and worse response to initial treatment, survival data were similar to the immunophenotypical control group. Our outcome results differ from previously published work, which may, to some extent, be explained by the heterogeneity of aberrancies included in this analysis, the lack of standardization of “positivity” among studies, the few cases, and the differences in MCL treatment over time.

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.

Presented in part at the 2016 United States and Canadian Academy of Pathology Meeting; March 15, 2016; Seattle, Washington.