Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL

Monika Pilichowska, Stefania Pittaluga, Judith A. Ferry, Jessica Hemminger, Hong Chang, Jennifer A. Kanakry, Laurie H. Sehn, Tatyana Feldman, Jeremy S. Abramson, Athena Kritharis, Francisco J. Hernandez-Ilizaliturri, Izidore S. Lossos, Oliver W. Press, Timothy S. Fenske, Jonathan W. Friedberg, Julie M. Vose, Kristie A. Blum, Deepa Jagadeesh, Bruce Woda, Gaurav K. GuptaRandy D. Gascoyne, Elaine S. Jaffe, Andrew M. Evens

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Gray zone lymphoma (GZL) is described as sharing featureswith classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 NorthAmerican academic centerswere evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universalB-cellderivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV1 DLBCL, n=3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n=1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P=.038) and less likely more than 1 extranodal site (0%vs 25%; P5.019).With a 44-monthmedian follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P=.19 and P=.15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P=.01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP6R) was associated with improved 3-year PFS (70% vs 20%; P=.03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

Original languageEnglish (US)
Pages (from-to)2600-2609
Number of pages10
JournalBlood Advances
Volume1
Issue number26
DOIs
StatePublished - Dec 12 2017
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Lymphoma
Disease-Free Survival
Sclerosis
Hodgkin Disease
Human Herpesvirus 4
Mediastinal Diseases
Hypoalbuminemia
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Multivariate Analysis
Immunohistochemistry
Lymphocytes
Pathology
Survival
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Pilichowska, M., Pittaluga, S., Ferry, J. A., Hemminger, J., Chang, H., Kanakry, J. A., ... Evens, A. M. (2017). Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL. Blood Advances, 1(26), 2600-2609. https://doi.org/10.1182/bloodadvances.2017009472

Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL. / Pilichowska, Monika; Pittaluga, Stefania; Ferry, Judith A.; Hemminger, Jessica; Chang, Hong; Kanakry, Jennifer A.; Sehn, Laurie H.; Feldman, Tatyana; Abramson, Jeremy S.; Kritharis, Athena; Hernandez-Ilizaliturri, Francisco J.; Lossos, Izidore S.; Press, Oliver W.; Fenske, Timothy S.; Friedberg, Jonathan W.; Vose, Julie M.; Blum, Kristie A.; Jagadeesh, Deepa; Woda, Bruce; Gupta, Gaurav K.; Gascoyne, Randy D.; Jaffe, Elaine S.; Evens, Andrew M.

In: Blood Advances, Vol. 1, No. 26, 12.12.2017, p. 2600-2609.

Research output: Contribution to journalArticle

Pilichowska, M, Pittaluga, S, Ferry, JA, Hemminger, J, Chang, H, Kanakry, JA, Sehn, LH, Feldman, T, Abramson, JS, Kritharis, A, Hernandez-Ilizaliturri, FJ, Lossos, IS, Press, OW, Fenske, TS, Friedberg, JW, Vose, JM, Blum, KA, Jagadeesh, D, Woda, B, Gupta, GK, Gascoyne, RD, Jaffe, ES & Evens, AM 2017, 'Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL', Blood Advances, vol. 1, no. 26, pp. 2600-2609. https://doi.org/10.1182/bloodadvances.2017009472
Pilichowska, Monika ; Pittaluga, Stefania ; Ferry, Judith A. ; Hemminger, Jessica ; Chang, Hong ; Kanakry, Jennifer A. ; Sehn, Laurie H. ; Feldman, Tatyana ; Abramson, Jeremy S. ; Kritharis, Athena ; Hernandez-Ilizaliturri, Francisco J. ; Lossos, Izidore S. ; Press, Oliver W. ; Fenske, Timothy S. ; Friedberg, Jonathan W. ; Vose, Julie M. ; Blum, Kristie A. ; Jagadeesh, Deepa ; Woda, Bruce ; Gupta, Gaurav K. ; Gascoyne, Randy D. ; Jaffe, Elaine S. ; Evens, Andrew M. / Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL. In: Blood Advances. 2017 ; Vol. 1, No. 26. pp. 2600-2609.
@article{67e206c1515c47ec94a08629e9bea62f,
title = "Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL",
abstract = "Gray zone lymphoma (GZL) is described as sharing featureswith classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 NorthAmerican academic centerswere evaluated by central pathology review to achieve consensus. Of these, only 26 (38{\%}) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universalB-cellderivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83{\%}; PAX5+, 100{\%}; BCL6+, 20{\%}; MUM1+, 100{\%}; CD30+, 92{\%}; EBV+, 4{\%}). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV1 DLBCL, n=3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n=1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69{\%} vs 41{\%}; P=.038) and less likely more than 1 extranodal site (0{\%}vs 25{\%}; P5.019).With a 44-monthmedian follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39{\%} and 95{\%}, respectively, vs 58{\%} and 85{\%}, respectively, for reclassified cases (P=.19 and P=.15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12{\%} vs 64{\%}; P=.01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP6R) was associated with improved 3-year PFS (70{\%} vs 20{\%}; P=.03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.",
author = "Monika Pilichowska and Stefania Pittaluga and Ferry, {Judith A.} and Jessica Hemminger and Hong Chang and Kanakry, {Jennifer A.} and Sehn, {Laurie H.} and Tatyana Feldman and Abramson, {Jeremy S.} and Athena Kritharis and Hernandez-Ilizaliturri, {Francisco J.} and Lossos, {Izidore S.} and Press, {Oliver W.} and Fenske, {Timothy S.} and Friedberg, {Jonathan W.} and Vose, {Julie M.} and Blum, {Kristie A.} and Deepa Jagadeesh and Bruce Woda and Gupta, {Gaurav K.} and Gascoyne, {Randy D.} and Jaffe, {Elaine S.} and Evens, {Andrew M.}",
year = "2017",
month = "12",
day = "12",
doi = "10.1182/bloodadvances.2017009472",
language = "English (US)",
volume = "1",
pages = "2600--2609",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "26",

}

TY - JOUR

T1 - Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL

AU - Pilichowska, Monika

AU - Pittaluga, Stefania

AU - Ferry, Judith A.

AU - Hemminger, Jessica

AU - Chang, Hong

AU - Kanakry, Jennifer A.

AU - Sehn, Laurie H.

AU - Feldman, Tatyana

AU - Abramson, Jeremy S.

AU - Kritharis, Athena

AU - Hernandez-Ilizaliturri, Francisco J.

AU - Lossos, Izidore S.

AU - Press, Oliver W.

AU - Fenske, Timothy S.

AU - Friedberg, Jonathan W.

AU - Vose, Julie M.

AU - Blum, Kristie A.

AU - Jagadeesh, Deepa

AU - Woda, Bruce

AU - Gupta, Gaurav K.

AU - Gascoyne, Randy D.

AU - Jaffe, Elaine S.

AU - Evens, Andrew M.

PY - 2017/12/12

Y1 - 2017/12/12

N2 - Gray zone lymphoma (GZL) is described as sharing featureswith classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 NorthAmerican academic centerswere evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universalB-cellderivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV1 DLBCL, n=3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n=1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P=.038) and less likely more than 1 extranodal site (0%vs 25%; P5.019).With a 44-monthmedian follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P=.19 and P=.15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P=.01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP6R) was associated with improved 3-year PFS (70% vs 20%; P=.03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

AB - Gray zone lymphoma (GZL) is described as sharing featureswith classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 NorthAmerican academic centerswere evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universalB-cellderivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV1 DLBCL, n=3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n=1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P=.038) and less likely more than 1 extranodal site (0%vs 25%; P5.019).With a 44-monthmedian follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P=.19 and P=.15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P=.01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP6R) was associated with improved 3-year PFS (70% vs 20%; P=.03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

UR - http://www.scopus.com/inward/record.url?scp=85056156966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056156966&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2017009472

DO - 10.1182/bloodadvances.2017009472

M3 - Article

AN - SCOPUS:85056156966

VL - 1

SP - 2600

EP - 2609

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 26

ER -