[Successful bridging therapy with alectinib prior to allogeneic stem cell transplantation for refractory ALK-positive anaplastic large cell lymphoma].

Although alectinib is effective for relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) and has a favorable safety profile, its role as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the role of allo-HSCT itself in this setting are unknown. A 35-year-old man with ALK-positive ALCL experienced relapse after first-line therapy with CHOP. Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed. However, disease progressed 15 months after transplantation, and alectinib was initiated. Complete response (CR) was achieved after three months of treatment, and alectinib was continued for 5 months. After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate. The post-transplant course was unremarkable except for grade I acute GVHD. The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.

Financial Toxicity in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

BACKGROUND: Financial toxicity is a growing concern due to its considerable effects on medical adherence, quality of life, and mortality. The cost associated with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is substantial from diagnosis to treatment, including adjuvant therapy and surgery. This study aims to assess the prevalence of financial toxicity in BIA-ALCL patients. METHODS: We performed a cross-sectional, survey-based study on women with confirmed cases of BIA-ALCL from December 2019 to March 2023. The primary study outcomes were financial toxicity measured by Comprehensive Score for Financial Toxicity (COST) score and patient-reported financial burden measured by the responses to the Evaluation of the Financial Impact of BIA-ALCL survey. Lower COST scores signify higher financial toxicity. Responses were linked to patient data extracted from the medical records. RESULTS: Thirty-two women treated for confirmed BIA-ALCL were included. Patients were all White and were diagnosed at a median age of 51 years (range, 41-65 years). The mean COST score was 27.9 ± 2.23. Lower COST scores were associated with receipt of radiotherapy ( P = 0.033), exceeding credit card limits ( P = 0.036), living paycheck to paycheck ( P = 0.00027), requiring financial support from friends and family ( P = 0.00044), and instability in household finances ( P = 0.034). CONCLUSIONS: Financial toxicity is prevalent in BIA-ALCL patients and has a substantial impact on patient reported burden. Insurance denial is frequent for patients with a prior history of cosmetic augmentation. Risk assessments and cost discussions should occur throughout the care continuum to minimize financial burden.

Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial.

ABSTRACT: New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 chimeric antigen receptor (CAR), designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-Ts) were evaluated in a phase 1 dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3, followed by infusion of 5F11-Ts on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had classical Hodgkin lymphoma, and 1 had anaplastic large-cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume of 66.1 mL (range, 6.4-486.7 mL). The overall response rate was 43%; 1 patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4/5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new-onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3/4 cytopenias, with recovery time of ≥30 days, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early because of toxicity. Median peak blood CAR+ cells per µL was 26 (range, 1-513 cells per µL), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-Ts had low efficacy and substantial toxicities, which limit further development of 5F11-Ts. This trial was registered at www.clinicaltrials.gov as #NCT03049449.

Case report: Differential diagnosis of highly amplified anti-CD5 CAR T cells and relapsed lymphoma cells in a patient with refractory ALK positive anaplastic large cell lymphoma.

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. Trial registration number: NCT04767308.

Oncological Outcomes After Multidisciplinary Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon type of non-Hodgkin lymphoma, associated with breast implant capsules. Despite improvements in our understanding of BIA-ALCL, communicating the prognosis to patients remains challenging due to limited long-term follow-up data. This has important implications for decision-making, including recommendations for subsequent reconstructive procedures. The aim of this study was to assess the longer-term oncological outcomes of patients receiving multidisciplinary treatment for BIA-ALCL. METHODS: This was a retrospective cohort study of BIA-ALCL patients treated at a tertiary referral unit. The data are presented using simple descriptive statistics. RESULTS: Between 2015 and 2022, 18 BIA-ALCL patients were treated at our institution. The median age at diagnosis was 48.5 (IQR 41-55) years. Ten patients developed BIA-ALCL after cosmetic breast augmentation, and 8 after breast reconstruction following mastectomy for cancer. All patients had a history of textured implant insertion. The median time from first implant surgery to diagnosis was 8.5 (IQR 7-12) years. All patients underwent en-bloc total capsulectomy with implant removal, and 2 received systemic therapy. Fifteen patients had Stage I (IA-IC) disease, 2 had Stage IIA and 1 Stage III BIA-ALCL, based on the TNM classification system. At a median follow-up of 45 (IQR 15-71) months, there were no episodes of local or systemic relapse or death. CONCLUSIONS: Surgical management for BIA-ALCL is sufficient in early-stage disease, and associated with excellent oncological outcomes. This information is reassuring for patients when discussing recurrence risk.

Clinical Implications and Management of Non-BIA-ALCL Breast Implant Capsular Pathology.

SUMMARY: The breast implant capsule is a dynamic structure that forms following the implantation of a device. Although normally benign, increased awareness of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) highlights that disease may arise from the capsule. BIA-ALCL presents as a late seroma or mass but explains few of the late seromas found in breast implant patients. To date, many of these seromas lack a clear cause and are often described as "idiopathic." Several benign and malignant breast implant capsular diseases can cause a late seroma or mass, including breast implant-associated squamous cell carcinoma. Similar to early reports of BIA-ALCL, these conditions are rare and largely limited to case reports or series. The purpose of this special topic is to present a narrative review highlighting capsular abnormalities that contribute to the formation of late seroma or mass in an attempt to broaden the differential diagnosis and help plastic surgeons identify the cause. Specifically, we review the presentation and management of BIA-ALCL, synovial metaplasia, capsular epithelialization, late hematoma, double capsule, breast cancer, squamous cell carcinoma, mesenchymal tumor, and B-cell lymphoma. Although rare, plastic surgeons should consider these capsular conditions as causes of late seromas and masses. Usually, these conditions may be diagnosed by following the National Comprehensive Cancer Network screening guidelines for BIA-ALCL. Thorough evaluation and workup of late seromas and masses may lead to improved characterization of these rare breast implant capsular conditions and improve our understanding of their pathophysiology and management.

Allogeneic haematopoietic cell transplant in patients with relapsed/refractory anaplastic large cell lymphoma.

The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.8; p < 0.001) and refractory disease at allo-HCT (HR 3.2, 95% CI 1.6-6.2; p < 0.001) were predictive of inferior OS. Similarly, African-American race (HR 2.1, 95% CI 1.3-3.4; p = 0.003), other minority race (HR 2.5, 95% CI 1.2-5.3; p = 0.02) and refractory disease (HR 2.2, 95% CI 1.2-4.3; p = 0.01) were predictive of inferior PFS. These data, demonstrate that allo-HCT can result in durable disease control in a sizable proportion of patients with R/R ALCL. Refractory disease and racial minority status predicted inferior allo-HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL after allo-HCT are driven by differences in disease biology or disparities in post allo-HCT care, or both, requires further investigation.

Clinical recommendations for diagnosis and treatment according to current updated knowledge on BIA-ALCL.

Shared strategies and correct information are essential to guide physicians in the management of such an uncommon disease as Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). A systematic review of the literature was performed to collect the most relevant evidence on BIA-ALCL reported cases. A panel of multidisciplinary experts discussed the scientific evidence on BIA-ALCL, and updated consensus recommendations were developed through the Delphi process. The lastest reported Italian incidence of BIA-ALCL is 3.5 per 100.000 implanted patients (95% CI, 1.36 to 5.78), and the disease counts over 1216 cases worldwide as of June 2022. The most common presentation symptom is a late onset seroma followed by a palpable breast mass. In the event of a suspicious case, ultrasound-guided fine-needle aspiration should be the first step in evaluation, followed by cytologic and immunohistochemical examination. In patients with confirmed diagnosis of BIA-ALCL confined to the capsule, the en-bloc capsulectomy should be performed, followed by immediate autologous reconstruction, while delayed reconstruction applies for disseminate disease or radically unresectable tumor. Nevertheless, a multidisciplinary team approach is essential for the correct management of this pathology.

Breast Implant-Associated Anaplastic Large-Cell Lymphoma: Updated Systematic Review and Analysis of Treatment Strategies.

BACKGROUND: Although guidelines have been published on treatment of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL), there has been no comprehensive analysis of BIA-ALCL treatment variation based on the available literature. The authors sought to assess current treatment strategies of BIA-ALCL relative to current guidelines. METHODS: Database searches were conducted in June of 2020. Included articles were case reports and case series with patient-level data. Collected variables included clinicopathologic features, implant characteristics, diagnostic tests, ALCL characteristics, treatment, and details of follow-up and outcome. Treatment data from before and after 2017 were compared with National Cancer Center Network guidelines. RESULTS: A total of 89 publications were included and 178 cases of BIA-ALCL were identified. Most patients presented with seroma ( n = 114, 70.4 percent), followed by a mass ( n = 14, 8.6 percent), or both ( n = 23, 14.2 percent). Treatment included en bloc capsulectomy of the affected implant in 122 out of 126 cases with treatment details provided (96.8 percent). Radiation therapy was given in 38 cases (30.2 percent) and chemotherapy was given in 71 cases (56.3 percent). Practitioners used less chemotherapy for local disease after treatment guideline publication in 2017 ( p < 0.001), whereas treatment for advanced disease remained unchanged ( p = 0.3). There were 10 recurrences and eight fatalities attributable to BIA-ALCL, which were associated with advanced presentation (29 versus 2.1 percent; OR, 19.4; 95 percent CI, 3.9 to 96.3; p < 0.001). CONCLUSIONS: BIA-ALCL remains a morbid but treatable condition. Current guidelines focus treatment for local disease and reduce nonsurgical interventions with radiation or chemotherapy. Patients presenting with advanced BIA-ALCL experience higher rates of recurrence and mortality.

Long-term remission of primary refractory ALK-positive anaplastic large cell lymphoma after allogeneic hematopoietic stem cell transplantation.

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) has a favorable prognosis in general; however, some cases are resistant to chemotherapy, which leads to a poor clinical outcome. We herein report the case of a 32-year-old male with aggressive ALK+ ALCL who presented with hemorrhage from a large tumor in the duodenum and multiple tumors in the lungs, mediastinum, and peritoneal cavity. Although induction chemotherapy resulted in a marked reduction of the tumor lesions, premature progression with massive pulmonary infiltration and central nervous system invasion occurred immediately after the completion of chemotherapy. The patient was then promptly treated with brentuximab vedotin (BV) and high-dose methotrexate, which resulted in complete remission. Subsequently, he successfully underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor and has been healthy and did not relapse for more than 3 years after transplantation without any additional therapy. Allo-HSCT may be a promising treatment option for ALK+ ALCL due to its graft-versus-lymphoma effect. In addition, molecular targeting agents, such as BV, may be promising as a bridging therapy before allo-HSCT to achieve disease remission.

Clinical Manifestations and Surgical Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma: Beyond the NCCN Guidelines.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T cell lymphoma arising in response to textured-surface breast implants. Frequently, BIA-ALCL is indolent and typically presents with peri-implant swelling after breast reconstruction or cosmetic augmentation. However, patients can present with an invasive breast or chest wall mass, palpable lymphadenopathy, or metastatic disease. The current literature is limited regarding surgical recommendations for patients with a more aggressive presentation of BIA-ALCL. This report aims to review the various clinical manifestations of BIA-ALCL, including the more advanced and less frequently encountered presentations, with an emphasis on a multidisciplinary approach, with early involvement of a surgical oncologist.

Role of stem cell transplant in CD30+ PTCL following frontline brentuximab vedotin plus CHP or CHOP in ECHELON-2.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas, the majority of which have high relapse rates following standard therapy. Despite use of consolidative stem cell transplant (SCT) following frontline therapy, there remains no consensus on its utility. The double-blind randomized phase 3 ECHELON-2 study (#NCT01777152; clinicaltrials.gov) demonstrated improved progression-free survival (PFS) and overall survival with frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP). Herein, we conducted an exploratory subgroups analysis of the impact of consolidative SCT on PFS in patients with previously untreated CD30+ PTCL (ALK- anaplastic large cell lymphoma [ALCL] and non-ALCL) who were in complete response (CR) after frontline treatment with A+CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone. Median PFS follow-up was 47.57 months. The PFS hazard ratio was 0.36, equating to a 64% reduction in the risk of a PFS event in patients who underwent SCT. The median PFS in patients who underwent SCT was not reached, vs 55.66 months in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK- ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30+PTCL who achieve CR following treatment with A+CHP.

Invasive stage III breast implant-associated anaplastic large cell lymphoma successfully treated with incomplete resection.

A woman with history of bilateral breast augmentation 15 years prior presented with right breast swelling, peri-implant effusion and a palpable inferomedial mass. Effusion aspiration demonstrated pleiomorphic cells consistent with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Further diagnostic studies confirmed stage III disease with a 4.7 cm right breast mass and fluorodeoxyglucose uptake in an internal mammary chain lymph node. The patient underwent surgery with incomplete resection due to invasion of the chest wall followed by chemotherapy and radiation therapy. BIA-ALCL typically presents as an indolent effusion, however advanced disease carries a worse prognosis. This case highlights successful treatment without recurrence past the one-year mark as well as the need for multidisciplinary management when dealing with advanced disease.

Breast-implant-associated anaplastic large-cell lymphoma.

Breast-implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is an uncommon, recently recognized disease that seems to occur only in relation with implants with textured surfaces. Most cases present with late-onset peri-implant effusion or fluid collections that develop more than 12 months after insertion of the implant. The diagnosis is reached by cytological analysis of fluid samples obtained by ultrasound-guided fine-needle aspiration. These patients usually have a good prognosis after surgical removal of the implant. A small percentage of patients present with a nodule or mass adjacent to the implant that usually develops late. In these cases, the diagnosis is reached by the histological analysis of core-needle biopsy specimens. These patients have a worse prognosis and require a combination of surgery and systemic chemotherapy. The main immunophenotypic characteristics of this lymphoma are intense expression of CD30 and a lack of expression of anaplastic lymphoma kinase (ALK). Here we present a case of BIA-ALCL in a patient with implants with a textured surface that presented with peri-implant effusion and incipient formation of a millimetric nodule and was treated with removal of the implant and bilateral capsulectomy. It is important to point out that the disease requires multidisciplinary management and that the Spanish Agency of Medicines and Medical Devices (AEMPS) should be notified when the diagnosis is confirmed.

An Updated Approach and Understanding of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare subtype of T-cell non-Hodgkin lymphoma that is usually localized to the fluid and capsule surrounding a breast implant. There have only been <1,000 cases and 36 deaths reported to date and the average patient presents 7 to 10 years following initial breast implant placement. Most patients present with delayed seromas, a breast mass, capsular abnormalities, lymphadenopathy, or cutaneous masses. Unlike other forms of non-Hodgkin lymphoma, most cases are cured with surgery alone. The challenge of BIA-ALCL surrounds its rarity-in regard to both its diagnosis as well as the limited available data to guide therapy for more advanced cases. Careful pathology evaluation to analyze both the fluid surrounding the capsule and the capsule itself is critical. Studies to identify which patients are at greater risk of development of this rare entity are ongoing.

Cost and clinical benefit of imaging surveillance after treatment for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

Recent UK guidelines recommend that surveillance imaging should not be offered to patients who have undergone treatment for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) unless clinically indicated. The aim of this study was to explore the evolving practice at a tertiary referral unit and quantify the direct economic costs (DEC) associated with post-treatment BIA-ALCL routine radiological surveillance prior to adoption of the guidelines. Eleven patients were treated for BIA-ALCL between 2015 and 2020. At a median follow-up of 38 months (IQR 12-47) there were no local or distant relapses. Two patients did not have any radiological surveillance and 1 had follow-up elsewhere. The remaining 8 patients had a combination of positron emission tomography/computed tomography (PET/CT) (n = 10), CT (n = 2), breast ultrasound (n = 6), mammogram (n = 4) and breast magnetic resonance imaging (MRI) (n = 1) as routine imaging follow-up not guided by clinical concerns. Total cost of imaging was £10,396 (€12,257) with a median cost of £1953 (€2304) per patient [IQR £526-2029 (€621-2394)]. This cost could have been saved based on current guidelines recommending no routine surveillance for asymptomatic patients.

Coexpression of MCT1 and MCT4 in ALK-positive Anaplastic Large Cell Lymphoma: Diagnostic and Therapeutic Implications.

In solid tumors, glycolytic cancer or stromal cells export lactates through monocarboxylate transporter (MCT) 4, while oxidative cancer or stromal cells take up lactates as metabolic fuels or signaling molecules through MCT1. CD147 acts as a chaperone of MCT1 or MCT4. Unlike solid tumors, malignant lymphomas have a peculiar tumor microenvironment. To investigate the metabolic phenotype of malignant lymphoma associated with lactate transport, we analyzed immunohistochemical expressions of MCT1, MCT4, and CD147 in 247 cases of various malignant lymphomas. Surprisingly, both MCT1 and MCT4 were diffusely expressed on tumor cell membranes in all cases (11/11, 100%) of anaplastic lymphoma kinase (ALK) (+) anaplastic large cell lymphoma (ALCL). In contrast, only MCT1 was diffusely expressed in tumor cells of ALK(-) ALCL, as well as in B-cell, natural killer/T-cell, T-cell, and classic Hodgkin lymphomas. In these lymphomas, MCT4 expression was mostly localized to adjacent stromal cells. The pattern of diffuse membranous MCT1 and partial MCT4 expressions in tumor cells was observed in 1 case each of peripheral T-cell lymphoma (1/15, 6.7%) and multiple myeloma (1/34, 2.9%). CD147 was diffusely expressed in all types of lymphoma tumor and/or stromal cells. In conclusion, ALK(+) ALCL has a unique metabolism showing high coexpression of MCT1 and MCT4 in tumor cells. Because only ALK(+) ALCL overexpresses MCT4, immunostaining for MCT4 together with ALK is very useful for differential diagnosis from ALK(-) ALCL or peripheral T-cell lymphoma. Moreover, dual targeting against MCT1 and MCT4 would be an appropriate therapeutic approach for ALK(+) ALCL.

[Breast implant-associated anaplastic large cell lymphoma].

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a serious complication in patients with breast implants. In this case report, a 38-year-old woman who was diagnosed with BIA-ALCL presented with seroma in her left breast eight years after her breast implantation surgery. The purpose of this case report is to draw attention to the fact that "late-onset" seroma in patients with breast implants can be a sign of malignancy. A multidisciplinary approach in the diagnosis and treatment of these patients is important. Manifestations, investigation and management of the disease are reviewed.

Breast implant-associated anaplastic large cell lymphoma: clinical follow-up and analysis of sequential pathologic specimens of untreated patients shows persistent or progressive disease.

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can involve surrounding tissues, spread to regional lymph nodes, and rarely metastasize to distant sites. The aim of this study was to assess sequential pathologic specimens from patients with breast implant-associated ALCL to better understand the natural history of early-stage disease. To achieve this goal, we searched our files for patients who had breast implant-associated ALCL and who had undergone earlier surgical intervention with assessment of biopsy or cytologic specimens. We then focused on the patient subset in whom a definitive diagnosis was not established, and patients did not receive current standard-of-care therapy at that time. We identified a study group of ten patients with breast implant-associated ALCL in whom pathologic specimens were collected 0.5 to 4 years before a definitive diagnosis was established. A comparison of these serial biopsy specimens showed persistent disease without change in pathologic stage in three patients, progression in five patients, and persistence versus progression in two patients. Eventually, six patients underwent implant removal with complete capsulectomy and four underwent partial capsulectomy. Seven patients also received chemotherapy because of invasive disease, three of whom also received radiation therapy, two brentuximab vedotin after chemotherapy failure, and one allogeneic stem cell transplant. Eight patients achieved complete remission and two had partial remission after definitive therapy. At time of last follow-up, six patients were alive without disease, one had evidence of disease, one died of disease, and two patients died of unrelated cancers. In summary, this analysis of sequential specimens from patients with breast implant-associated ALCL suggests these neoplasms persist or progress over time if not treated with standard-of-care therapy.