Anti-MAL antibody, compared to CD200, is more effective at distinguishing PMBCL from DLBCL-NOS

This month, Michael Gentry, MD, from the Cleveland Clinic, Cleveland, OH, and colleagues published data in the American Journal of Surgical Pathology on a Myelin And Lymphocyte (MAL) protein specific monoclonal antibody they identified and its sensitivity and specificity in distinguishing PMBCL from DLBCL-NOS compared to CD23, CD30, and the polyclonal CD200 antibody.

Cases of DLBCL-NOS without mediastinal mass and PMBCL were gathered from the Cleveland Clinic’s Institute of Pathology and Laboratory Medicine archives. Exclusion criteria consisted of a history of immunosuppression or previous low-grade lymphomas.

A 3-tier scale based on intensity was used to grade MAL and CD200 antibody immunohistochemical staining: weak scored 1+, moderate scored 2+, and strong scored 3+. Multiplication of this intensity score by the percentage of positively stained tumor cells resulted in a H-score. A cut-off of ≥10% tumor cells was used to determine if MAL and CD200 antibody staining was positive or not.

Key Highlights:

• Western Blots:
  • Strong expression reported at the appropriate size of 17kD in hyperplastic tonsil and PMBCL cell lines; no expression reported in non-PMBCL cell lines
• MAL expression:
  • Expressed in 72% (31/43) PMBCL cases (median H score = 160; range, 10–300)
  • Expressed in 0% (0/57) DLBCL-NOS cases
  • MAL expression significantly associated with PMBCL rather than DLBCL-NOS (P < 0.0001)
  • MAL staining sensitivity = 72% & specificity = 100% in identifying PMBCL over DLBCL-NOS
• CD200 expression:
  • Expressed in 81% (35/43) PMBCL cases (median H score = 180; range, 10–300)
  • Expressed in 13% (8/61) DLBCL-NOS cases (median H score = 125; range, 10–300)
  • CD200 expression was significantly different between PMBCL and DLBCL-NOS (P < 0.0001)
  • CD200 staining sensitivity = 81% & specificity = 87% for identifying PMBCL over DLBCL-NOS
• CD23 and CD30:
  • CD23 expression sensitivity = 62% and specificity = 97% for identifying PMBCL over DLBCL-NOS
  • CD30 expression sensitivity = 47% and specificity = 79% for identifying PMBCL over DLBCL-NOS
• Combined scoring:
  • Either CD200 or MAL staining, sensitivity and specificity for PMBCL = 86% and 87%
  • CD200 and MAL staining, sensitivity and specificity for PMBCL = 67% and 100%

The authors stated that they have identified a MAL specific monoclonal antibody, which can be made available commercially. Western Blotting confirmed that the antibody recognizes

MAL with apparent high affinity. The authors also found that the MAL antibody, compared to CD200, was slightly more effective at distinguishing PMBCL from DLBCL-NOS due to its higher specificity in spite of a lower sensitivity. As the authors placed a premium on specificity rather than sensitivity, no advantage was found when combining MAL and CD200 immunohistochemistry data compared to MAL alone in differentiating PMBCL from DLBCL-NOS. Because of this, and CD200’s polyclonal nature, the authors recommend using the MAL antibody alone to aid the diagnosis of PMBCL. Lastly, MAL exceeded both the sensitivity and specificity of CD23 and CD30 expression in identifying PMBCL over DLBCL-NOS. The authors concluded by stating that adding their MAL antibody to diagnostic panels could be useful in identifying patients with PMBCL in clinical practice.

Abstract:

Myelin and lymphocyte (MAL) protein has been previously reported as a highly specific marker for distinguishing primary mediastinal large B-cell lymphoma (PMBL) from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). However, there has not been a commercially available MAL antibody for immunohistochemistry. We identified a commercially available MAL monoclonal antibody and evaluated it by immunohistochemistry on 43 cases of PMBL and 63 cases of DLBCL, NOS. We also compared this with a CD200 antibody that was previously reported useful in distinguishing PMBL and DLBCL, NOS. A threshold of 10% positive tumor cells was used to determine positive protein expression. MAL was expressed in 72% cases of PMBL and 0% of cases of DLBCL, NOS (sensitivity=72%, specificity=100%). CD200 was expressed in 81% of PMBL cases and 13% of DLBCL, NOS cases (sensitivity=81%, specificity=87%). To our knowledge, this is the first report on the utility of a commercially available MAL monoclonal antibody in the diagnosis of PMBL. There is a high specificity with good sensitivity in distinguishing PMBL from DLBCL, NOS, similar to previous studies with a noncommercial source. This antibody will likely prove useful in identifying cases of PMBL in routine practice.