Ki-67 Labeling Indices in 'Classic' versus 'Blastoid' Mantle Cell Lymphomas - Proposed Cutoff Values for Routine Diagnostic Workup

  • Pervez, Shahid (Department of Pathology and Laboratory Medicine, Aga Khan University Hospital) ;
  • Haroon, Saroona (Department of Pathology and Laboratory Medicine, Aga Khan University Hospital) ;
  • Awan, Dreema (Department of Pathology and Laboratory Medicine, Aga Khan University Hospital)
  • Published : 2015.10.06


Background: Mantle-cell lymphoma (MCL) is a unique entity of peripheral B-cell lymphoma that has a discrete morphologic, immunologic, and genetic phenotype, with more common 'classic' and less frequent 'blastoid' and 'pleomorphic' variants, associated with an aggressive clinical course. The aim of this study was to analyze proliferation (Ki-67) indices of 'classic' (c-MCL) and 'blastoid' (b-MCL) variants of a cohort of MCL and to suggest cut off values for the Ki-67 proliferation index in these two subsets. Materials and Methods: MCL cases diagnosed over $4{\frac{1}{2}}$ years at Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi were retrieved and reviewed. Ki-67 labelling was scored and analysed. Results: A total of 90 of cases of MCL were scrutinized. Mean age ${\pm}SD$ was $60.2{\pm}12.5$ years and the male to female ratio was 4:1, with 67 (75%) cases of c-MCL and 23 (25%) cases of b-MCL. Most samples were lymph node biopsies (n=68), whereas the remainder were from various extranodal sites The mean Ki-67 proliferation index was $29.5%{\pm}14.4%$ in classic variants and $64.4{\pm}15.2%$ for the blastoid variant, the difference being statistically significant (p = 0.029). Conclusions: It was concluded that differential cut-off values of Ki-67 labeling may be used in more objective way to reliably classify MCL into classic or blastoid variants by diagnostic pathologists. We propose a < 40 proliferative index to be suggestive of c-MCL and one of > 50 for the blastoid variant.


Mantle cell lymphoma;classic;blastoid;Ki-67 labelling index


  1. Blaker YN, Brodtkorb M, Maddison J, et al (2015). Computerized image analysis of the KI-67 proliferation index in mantle cell lymphoma. Histopathol, 67, 62-9.
  2. Determann O, Hoster E, Ott G, et al (2008). Ki-67 predicts outcome in advanced stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the european MCL network and the german low grade lymphoma study group. Blood, 111, 2385-387.
  3. Dreyling M, Ferrero S, Vogt N, Klapper W, European Mantle Cell Lymphoma Network (2014). New paradigms in mantle cell lymphoma: is it time to risk-stratify treatment based on the proliferative signature? Clin Cancer Res, 15, 5194-206.
  4. Ek S, Bjorck E, Porwit-MacDonald A, Nordenskjold M, Borrebaeck CA (2004). Increased expression of Ki-67 in mantle cell lymphoma is associated with deregulation of several cell cycle regulatory components, as identified by global gene expression analysis. Haematologica, 89, 686-95.
  5. Haroon S, Memon A, Pervez S (2014). Multiple lymphomatous polyposis form of blastoid variant of mantle cell lymphoma in colon: a case report and review of literature. J Gastrointest Cancer, 45, 48-50.
  6. He X, Chen Z, Fu T, et al (2014). Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis. BMC Cancer, 14.
  7. Hoster E, Dreyling M, Klapper W, et al (2008). A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood, 111, 558-65.
  8. Katzenberger T, Petzoldt C, Holler S, et al (2006). The Ki67 proliferation index is a quantitative indicator of clinical risk in mantle cell lymphoma [letter]. Blood, 107, 3407.
  9. Klapper W, Hoster E, Determann O, et al (2009). Ki-67 as a prognostic marker in mantle cell lymphoma- Consensus guidelines of the pathology panel of the European MCL Network. J Hematop, 2, 103-11.
  10. Mushtaq S, Akhtar N, Jamal S, et al (2008). Malignant lymphomas in pakistan according to WHO classification of lymphoid neoplasms. Asian Pac J Cancer Prev, 9, 229-32.
  11. Raty R, Franssila K, Jansson SE, et al (2003). Predictive factors for blastoid transformation in the common variant of mantle cell lymphoma. Eur J Cancer, 39, 321-29.
  12. Raty R, Franssila K, Joensuu H, Teerenhovi L, Elonen E. (2002). Ki-67 expression level, histological subtype, and the international prognostic Index as outcome predictors in mantle cell lymphoma. Eur J Haematol, 69,11-20.
  13. Sader-Ghorra C, Rassy M, Naderi S, Kourie HR, Kattan J (2014). Type distribution of lymphomas in Lebanon: Fiveyear single institution experience. Asian Pac J Cancer Prev, 15, 5825-28.
  14. Salek D, Vesela P, Boudova L, et al (2014). Retrospective analysis of 235 unselected patients with mantle cell lymphoma confirms prognostic relevance of mantle cell lymphomainternational prognostic index and Ki-67 in the era of rituzimeb: long-term data from Czech Lymphoma Project Database. Leuk Lymphoma, 55, 802-10.
  15. Swerdlow SH, Campo E, Seto M, Muller-Hermelink HK (2008). Mantle cell lymphoma. In: Swerdlow SH, Campo E, Harris NL et al, 4th eds. WHO Classification of Tumours of Haematopoeitic and Lymphoid Tissues, IARC Press, Lyon, France: 229-32.
  16. Tiemann M, Schrader C, Klapper W, et al (2005) Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol, 13, 29-38.
  17. Todorovic M, Balint B, Andjelic B, et al (2012). Outcome prediction of advanced mantle cell lymphoma by international prognostic index versus different mantle cell lymphoma indexes: one institution study. Med Oncol, 29, 2212-9
  18. Vose JM (2013) Mantle cell lymphoma: 2013 update on diagnosis, risk-stratification, and clinical management. Am J Hematol, 88, 1082-8
  19. Yngvild N Blaker, Marianne Brodtkorb, John Maddison, et al (2015). Computerized image analysis of the Ki-67 proliferation index in mantle cell lymphoma. Histopathol, 67, 62-9.

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