By the numbers, and what they mean
By Mark Clemens, MD
On February 6, 2019, the U.S. Food and Drug Administration (FDA) released an annual safety communication updating the current understanding of BIA-ALCL. Many members have expressed confusion over much of the data surrounding BIA-ALCL. The purpose of this document is to discuss and bring clarity to some of the figures surrounding this rare disease.
The recent BIA-ALCL update reported that the FDA has been made aware of 660 medical device reports (MDRs) related to breast implants and ALCL as of September 2018. This is in comparison to 414 MDRs in March 2018, 359 MDRs in March 2017, 258 MDRs in January 2016 and 64 MDRs in January 2011. For the first time, the FDA has systematically reviewed the MDRs, removed duplicates, and reports that 457 MDRs are unique and meet the pathologic criteria of BIA-ALCL. MDRs may be reported by patients, physicians or manufacturers. It's important to note the MDRs are not individual cases, as there are duplicate reports as well as unconfirmed cases suspicious for ALCL within the MDRs. The FDA describes the adverse event reports in its MAUDE database as "unconfirmed, inaccurate and biased" and, therefore, this data should not be taken as the definitive number of cases in the US or worldwide.
The recent FDA update of 457 reports included 24 (5 percent) smooth implant reports. This is similar to last year's update of 414 reports in 2018 including 30 (7 percent) smooth implants and 359 reports in 2017 including 28 (8 percent) smooth cases, and 258 patients which included 11 (4 percent) smooth implant reports in 2016. Previously, the FDA noted that all smooth reports were either mixed textured implant case histories or no clinical history available for review. For the first time, the FDA reports smooth only cases made available to them. The FDA reports that they are aware of smooth only cases however they warn that this information is "unverified” and potentially "inaccurate." To date, no purely smooth-implant case of BIA-ALCL has ever been reported in any series, registry, or case report with a detailed history. The FDA confirmed that BIA-ALCL is predominantly associated with textured surface implants.
The FDA reports 9 deaths reported in the MDRs. These are part of the 21 known deaths worldwide from BIA-ALCL. Two patients died from stem cell transplants, one died from development of a second unrelated lymphoma, and 14 patients died from direct extension of the cancer into their chest wall, ultimately expiring from respiratory failure. Of these deaths, none received complete surgical excision at any point in the patient's clinical history, none received targeted therapy, and most were significantly delayed in diagnosis or receiving any treatment (on average 1-2 years from onset of symptoms).
285 suspected/confirmed United States cases have been reported to the PROFILE registry. The PROFILE registry is a joint collaboration between the FDA and ASPS/PSF to prospectively track BIA-ALCL patients. Based upon a global network of international plastic surgery societies sharing tracking of cases, ASPS is now aware of 732 unique cases worldwide with 21 disease-related deaths over 30 countries.
The current lifetime risk of BIA-ALCL is estimated to be 1:3817 - 1:30,000 women with textured implants based upon current confirmed cases and textured implant sales data over the past two decades. Certain geographic locations have demonstrated variable risks. For instance, a December 2016 update from the Therapeutic Goods Administration of Australia and New Zealand reported a risk of 1:1,000 to 1:10,000 for textured implants. Researchers in Netherlands recently found a risk of 1:6900 women with textured implants, and a report by Health Canada has found a risk of 1:24000 women with textured implants based upon 5 cases reported to government authorities. These discrepancies may represent variable reporting or may represent geographic and genetic predisposition which is under investigation.
There are 1,400 patients per year diagnosed with ALCL. ALCL is a family of diseases from the very aggressive systemic ALCL to the indolent lymphoproliferative disorder primary cutaneous ALCL. For the first time in 2016, the World Health Organization added BIA-ALCL as a provisionally recognized lymphoma to the family of existing ALCL. It is important to differentiate BIA-ALCL from primary lymphoma of the breast which is predominantly a B-cell lymphoma with an incidence of approximately 1:4 million. ALK+ disease and B cell pathology should be concerning for primary lymphoma of the breast rather than BIA-ALCL.
Approximately 550,000 total breast implants are placed per year in the U.S. Of these, approximately 70,000 textured breast implants are placed, representing 12.7 percent of the market. This market share has remained relatively stable over the past 6 years.
93 percent of patients are disease free at 3 years follow-up, which is an excellent prognosis when treated appropriately. The National Comprehensive Cancer Network defines optimal treatment which is total capsulectomy and implant removal for the majority of patients with disease confined to the capsule (35 percent of patients) or a resectable mass (40 percent of patients). Advanced disease with lymph node metastasis (14 percent of patients) or organ metastasis (1 percent of patients) may require further treatment with chemotherapy using either CHOP anthracycline based-protocol or targeted therapy with brentuximab vedotin. Radiation therapy is only reserved for local unresectable disease such as into the chest wall and mediastinum.
For a suspected patient with a delayed seroma (>1 year), fluid should be aspirated and sent for CD30 immunohistochemistry, cytology, and flow cytometry. CD30 is the main diagnostic test that must be performed on the seroma fluid as routine pathology or H&E staining can frequently miss the diagnosis.
*Page last updated on June 14, 2019