Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities

Charles Van Slambrouck, Jooryung Huh, Cheolwon Suh, Joo Y. Song, Madhu P. Menon, Aliyah R. Sohani, Amy S. Duffield, Reva C. Goldberg, Paola Dama, Kazuma Kiyotani, James Godfrey, Carrie Fitzpatrick, Justin Kline, Sonali M. Smith, Elaine S. Jaffe, Sylvia Hartmann, Girish Venkataraman

Research output: Contribution to journalArticle

Abstract

Although the distinction of classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin lymphoma and diagnostically challenging B- and T-cell non-Hodgkin lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 classical Hodgkin lymphomas (31% EBV+), 34 nodular lymphocyte predominant Hodgkin lymphomas, 34 mimicking B- and T-cell non-Hodgkin lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 (PD-L1) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most classical Hodgkin lymphomas showed nuclear staining for STAT6YE361 [46/57 cases (80%)] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26%)], while dual nuclear and cytoplasmic localization was more common [34/46 (74%)]. In contrast, all nodular lymphocyte predominant Hodgkin lymphomas [0/34 (0%)] were negative for nuclear STAT6YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin lymphomas, nuclear STAT6YE361 was seen in: B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, and in primary mediastinal large B-cell lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, although STAT6YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one classical Hodgkin lymphoma patient positive for nuclear STAT6YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6YE361 nuclear staining has 100% positive predictive value and 85.7% negative predictive value in confirming or excluding classical Hodgkin lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin lymphoma and other benign and malignant entities.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StateAccepted/In press - Jan 1 2019

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Hodgkin Disease
T-Cell Lymphoma
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Staining and Labeling
Exome
Lymphoma, Large B-Cell, Diffuse
Mutation
Ligands
Biopsy
Recurrence
Gene Amplification
Human Herpesvirus 4
Histology
Monoclonal Antibodies
Lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Van Slambrouck, C., Huh, J., Suh, C., Song, J. Y., Menon, M. P., Sohani, A. R., ... Venkataraman, G. (Accepted/In press). Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities. Modern Pathology. https://doi.org/10.1038/s41379-019-0428-0

Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities. / Van Slambrouck, Charles; Huh, Jooryung; Suh, Cheolwon; Song, Joo Y.; Menon, Madhu P.; Sohani, Aliyah R.; Duffield, Amy S.; Goldberg, Reva C.; Dama, Paola; Kiyotani, Kazuma; Godfrey, James; Fitzpatrick, Carrie; Kline, Justin; Smith, Sonali M.; Jaffe, Elaine S.; Hartmann, Sylvia; Venkataraman, Girish.

In: Modern Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Van Slambrouck, C, Huh, J, Suh, C, Song, JY, Menon, MP, Sohani, AR, Duffield, AS, Goldberg, RC, Dama, P, Kiyotani, K, Godfrey, J, Fitzpatrick, C, Kline, J, Smith, SM, Jaffe, ES, Hartmann, S & Venkataraman, G 2019, 'Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities', Modern Pathology. https://doi.org/10.1038/s41379-019-0428-0
Van Slambrouck, Charles ; Huh, Jooryung ; Suh, Cheolwon ; Song, Joo Y. ; Menon, Madhu P. ; Sohani, Aliyah R. ; Duffield, Amy S. ; Goldberg, Reva C. ; Dama, Paola ; Kiyotani, Kazuma ; Godfrey, James ; Fitzpatrick, Carrie ; Kline, Justin ; Smith, Sonali M. ; Jaffe, Elaine S. ; Hartmann, Sylvia ; Venkataraman, Girish. / Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities. In: Modern Pathology. 2019.
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abstract = "Although the distinction of classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin lymphoma and diagnostically challenging B- and T-cell non-Hodgkin lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 classical Hodgkin lymphomas (31{\%} EBV+), 34 nodular lymphocyte predominant Hodgkin lymphomas, 34 mimicking B- and T-cell non-Hodgkin lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 (PD-L1) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most classical Hodgkin lymphomas showed nuclear staining for STAT6YE361 [46/57 cases (80{\%})] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26{\%})], while dual nuclear and cytoplasmic localization was more common [34/46 (74{\%})]. In contrast, all nodular lymphocyte predominant Hodgkin lymphomas [0/34 (0{\%})] were negative for nuclear STAT6YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin lymphomas, nuclear STAT6YE361 was seen in: B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, and in primary mediastinal large B-cell lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, although STAT6YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one classical Hodgkin lymphoma patient positive for nuclear STAT6YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6YE361 nuclear staining has 100{\%} positive predictive value and 85.7{\%} negative predictive value in confirming or excluding classical Hodgkin lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin lymphoma and other benign and malignant entities.",
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AU - Van Slambrouck, Charles

AU - Huh, Jooryung

AU - Suh, Cheolwon

AU - Song, Joo Y.

AU - Menon, Madhu P.

AU - Sohani, Aliyah R.

AU - Duffield, Amy S.

AU - Goldberg, Reva C.

AU - Dama, Paola

AU - Kiyotani, Kazuma

AU - Godfrey, James

AU - Fitzpatrick, Carrie

AU - Kline, Justin

AU - Smith, Sonali M.

AU - Jaffe, Elaine S.

AU - Hartmann, Sylvia

AU - Venkataraman, Girish

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N2 - Although the distinction of classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin lymphoma and diagnostically challenging B- and T-cell non-Hodgkin lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 classical Hodgkin lymphomas (31% EBV+), 34 nodular lymphocyte predominant Hodgkin lymphomas, 34 mimicking B- and T-cell non-Hodgkin lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 (PD-L1) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most classical Hodgkin lymphomas showed nuclear staining for STAT6YE361 [46/57 cases (80%)] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26%)], while dual nuclear and cytoplasmic localization was more common [34/46 (74%)]. In contrast, all nodular lymphocyte predominant Hodgkin lymphomas [0/34 (0%)] were negative for nuclear STAT6YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin lymphomas, nuclear STAT6YE361 was seen in: B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, and in primary mediastinal large B-cell lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, although STAT6YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one classical Hodgkin lymphoma patient positive for nuclear STAT6YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6YE361 nuclear staining has 100% positive predictive value and 85.7% negative predictive value in confirming or excluding classical Hodgkin lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin lymphoma and other benign and malignant entities.

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