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Journal of Clinical Oncology logoLink to Journal of Clinical Oncology
. 2020 Jun 17;38(24):2819–2820. doi: 10.1200/JCO.20.00931

Reply to M. Romero et al

Elaine S Jaffe 1,, Andrew L Feldman 1, Philippe Gaulard 1, Roberto N Miranda 1, Aliyah R Sohani 1
PMCID: PMC7430216  PMID: 32552469

Romero et al1 have described their comprehensive data analysis of 39 periprosthetic fluid samples. Of these, a diagnosis of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) was made in 11.11% (n = 4 patients) on the basis of Wright-Giemsa staining, flow cytometry (FC), and immunohistochemistry. In their letter, Romero et al1 emphasize the value of FC and question our designation of FC as a second-line technique. In our guideline, we acknowledged the value of FC, illustrating both positive and negative results. We contrasted the flow cytometric features of CD30-positive cells in reactive effusions with the CD30-positive cells of BIA-ALCL, emphasizing the absence of CD3 demonstrable by FC. However, we also opined that, with a limited sample volume insufficient for all methodologies, we would give priority to the creation of a cell block over FC.

Our article2 was created to provide guidance for the handling of periprosthetic fluid samples in a variety of practice settings. In a tertiary care center, such as that of Fundacion Santa Fe de Bogota, their experienced laboratory has validated FC for the detection of CD30 and many T-cell– and B-cell–associated antigens. However, even in their own series, they acknowledge that they analyzed anaplastic lymphoma kinase (ALK) by immunohistochemistry performed on cell blocks, while noting that they now have a working FC assay. Our informal survey of reference and hospital laboratories indicated that FC for detection of CD30 was not always available and that practice patterns, including availability of FC, differed considerably among different geographic regions. A key consideration for our panel was that specimens with a diagnostic question of benign seroma versus BIA-ALCL come from a variety of clinical settings, many of which may be remote from a sophisticated pathology laboratory.

Our goal was to provide diverse health care providers with practical guidelines that could most easily and accurately answer a critical diagnostic question for patient care. We advocated for generous sampling of the effusion fluid to permit cytologic evaluation, FC, and preparation of a cell block for immunohistochemistry and molecular diagnostics. All of these methodologies are complementary, and, in an individual case, one or more may provide the key diagnostic answer.3

Additionally, a cell block can be used for a variety of diagnostic questions, beyond those answerable by FC. The differential diagnosis of BIA-ALCL includes Epstein-Barr virus–positive diffuse large B-cell lymphoma with chronic inflammation4 and the related condition, fibrin-associated large B-cell lymphoma.5 Only in a cell block can Epstein-Barr virus-encoded small RNAs (EBER) in situ hybridization, necessary to make this diagnosis, be performed. Also, a cell block provides a permanent resource that can be used in the future by ancillary techniques. Recent studies are beginning to explore the molecular pathogenesis of BIA-ALCL, and access to formalin-fixed paraffin-embedded blocks has been critical in allowing this research to go forward.6-8 Future studies may better define the risk factors for the development of BIA-ALCL and delineate genomic variables that might alter disease management.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Reply to M. Romero et al

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Elaine S. Jaffe

Stock and Other Ownership Interests: Gilead Sciences, Merck, Teva

Andrew L. Feldman

Research Funding: Seattle Genetics (Inst)

Patents, Royalties, Other Intellectual Property: Inventor of technology for which Mayo Clinic holds an unlicensed patent or has submitted a patent application (Inst)

Philippe Gaulard

Honoraria: Takeda, Gilead

Consulting or Advisory Role: Takeda

Research Funding: Takeda (Inst), Innate Pharma (Inst)

Travel, Accommodations, Expenses: Roche

Roberto N. Miranda

Honoraria: Seattle Genetics

Patents, Royalties, Other Intellectual Property: Author of book edited by Elsevier

Aliyah R. Sohani

No other potential conflicts of interest were reported.

REFERENCES

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