Immunohistochemical assessment of the diagnostic utility of <scp>PD</scp>‐L1: a preliminary analysis of anti‐<scp>PD</scp>‐L1 antibody (<scp>SP</scp>142) for lymphoproliferative diseases with tumour and non‐malignant Hodgkin–Reed‐Sternberg (<scp>HRS</scp>)‐like cells

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Although several reports have highlighted neoplastic PD‐L1 (nPD‐L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV‐CHL), with and without Epstein–Barr virus (EBV) association, and highlight the diagnostic utility of PD‐L1 (clone SP142) immunohistochemistry. The patients were a 61‐year‐old male, 45‐year‐old male, 85‐year‐old female, and 89‐year‐old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV‐CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed–Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD‐L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD‐L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing ‘confluent’ sheets in the diagnostic workup for SV‐CHL.

Section: Discussionsupporting

confidence: 71%

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry

Kohno

Sakakibara

Iwakoshi

et al. 2020

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“…The PD1/PD‐L1 pathway is important for immune evasion of tumor cells that contribute to lymphomagenesis through T‐cell exhaustion . In previous reports, PD‐L1 expression of tumor cells was detected in the majority of EBV‐positive (EBV + ) HL and 16 to 100% of EBV‐positive DLBCL‐NOS . It is speculated that immune evasion of tumor cells through the PD1/PD‐L1 pathway is key for the pathogenesis of these EBV + lymphomas.…”

Section: Discussionmentioning

confidence: 98%

EBV‐positive mucocutaneous ulcer arising in rheumatoid arthritis patients treated with methotrexate: Single center series of nine cases

Satou

Banno

Hanamura

et al. 2019

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Methotrexate (MTX) is currently used as first‐line anchor drug for rheumatoid arthritis (RA). Therefore, the number of MTX‐associated lymphoproliferative disorders, including Epstein–Barr virus‐positive mucocutaneous ulcer (EBVMCU), has increased. Some aspects of MTX‐associated EBVMCU (MTX‐EBVMCU), particularly clinical behavior and treatment for RA after MTX cessation, have not been well described. Herein, we report nine cases of MTX‐EBVMCU with clinical information regarding RA. Seven of nine patients showed spontaneous regression (SR) after immunosuppressive (IS) cessation. The other two required cytotoxic chemotherapy. Eventually, all achieved complete remission. No patients experienced EBVMCU relapse. Eight patients had RA flare after IS cessation. To control the RA activity, rituximab was administered to three patients. The remaining patients were treated by other agents. Regarding the RA activity, all were in the status of low disease activity or clinical remission. In conclusion, MTX‐associated EBVMCU has an indolent clinical course and SR after IS cessation can be expected. After the withdrawal of MTX, the majority of patients experience RA flare and required treatment. In our series, RA was well controlled without reinitiating MTX. Therefore, to prevent the EBVMCU relapse, it might be advisable to avoid MTX reintroduction, and rituximab might be the more preferable agent for RA treatment.

“…The morphological features and immunohistochemical findings were consistent with a diagnosis of mixed cellularity CHL according to the WHO 2016 classification and the recent literatures. 1,5,6 However, EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), formerly EBV-positive DLBCL of the elderly, and EBV-positive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL, also known as gray zone lymphoma with features intermediate between DLBCL and CHL, were considered as differential diagnoses because both tumors are also EBV-positive large B-cell neoplasms with reactive inflammatory cells and sometimes contain HRS-like cells. 6,7 In addition, these two neoplasms are aggressive diseases and the current case was fulminant disease.…”

Section: Discussionmentioning

confidence: 99%

“…PCR analysis using DNA extracted from formalin‐fixed paraffin‐embedded specimens showed monoclonal rearrangement of immunoglobulin heavy chain, whereas monoclonal T cell receptor gene rearrangement was not detected. From these findings, we diagnosed mixed cellularity CHL according to the latest WHO 2016 classification and recent literatures …”

Section: Pathological Findingsmentioning

confidence: 99%

“…From these findings, we diagnosed mixed cellularity CHL according to the latest WHO 2016 classification and recent literatures. 1,5,6 In addition, marked angiodestructive lesions from infiltrating HRS-like cells were observed in extranodal organs such as the liver, spleen, and adrenal glands. The portal veins of the liver and veins in the spleen and adrenal glands were affected.…”

Section: Pathological Findingsmentioning

confidence: 99%

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A fulminant case of classical Hodgkin lymphoma: A diagnostic dilemma of Epstein‐Barr virus‐positive large B‐cell neoplasms

Ichimata

Kobayashi

Ohya

et al. 2019

We report a fulminant case of classical Hodgkin lymphoma (CHL). The patient died only approximately 2 months after the onset of subjective symptoms. Autopsy specimens revealed atypical cells resembling Hodgkin and Reed‐Sternberg (HRS) cells in a rich inflammatory background in various organs. There were marked, characteristic angiodestructive lesions from infiltrating HRS‐like cells and numerous macrophages. The HRS‐like cells were infected with Epstein‐Barr virus (EBV), immunohistochemically positive for PAX5 and CD30, and negative for CD3, CD20, and ALK. Most B‐cell markers other than PAX5 were negative, and the HRS‐like cells also expressed cytotoxic molecules. Monoclonal rearrangement of immunoglobulin heavy chain was detected by PCR analysis. According to the 2016 WHO classification, we diagnosed mixed cellularity CHL. However, EBV‐positive diffuse large B‐cell lymphoma (DLBCL), not otherwise specified and EBV‐positive B‐cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL were considered as differential diagnoses because both tumors are aggressive EBV‐positive large B‐cell neoplasms with reactive inflammatory cells and sometimes contains HRS‐like cells. The clinical condition of the current case was closer to these two entities than to CHL. A diagnosis of EBV‐positive large B‐cell neoplasms was difficult because of overlapping morphological and immunohistochemical characteristics, but should be considered for prognosis.