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.

Traditional and emerging therapies for anaplastic large cell lymphoma (Review).

Anaplastic large cell lymphoma (ALCL) is a rare and highly invasive non­Hodgkin's lymphoma. In the past few decades, traditional chemotherapy regimens, such as as the cyclophosphamide, vincristine, doxorubicin and prednisone regimen, have been recommended for first­line treatment. In order to improve the survival of patients, dose­intensive chemotherapy and hematopoietic stem cell transplantation have been deeply studied and some progress has been made. Recently, with the accumulation of clinical cases and the development of clinical trials, as well improvements to our in­depth understanding of the biological behavior of ALCL, the signaling pathways and the immunotherapy involved, research on this topic is in full swing. The emergence of several targeted drugs and immunotherapies, including anaplastic lymphoma kinase inhibitors, brentuximab vedotin, mTOR inhibitors, programmed cell death protein 1/programmed death ligand 1 inhibitors and chimeric antigen receptor­T cell therapy, seems to provide new opportunities for certain patients with ALCL. The present review focuses on the current use of traditional therapy and the treatment prospects of these new drugs in ALCL.

Breast Implant-associated Anaplastic Large Cell Lymphoma: An Evidence-based Systematic Review.

OBJECTIVE: This evidence-based systematic review synthesizes and critically appraises current clinical recommendations and advances in the diagnosis and treatment of BIA-ALCL. This review also aims to broaden physician awareness across diverse specialties, particularly among general practitioners, breast surgeons, surgical oncologists, and other clinicians who may encounter patients with breast implants in their practice. BACKGROUND: BIA-ALCL is an emerging and treatable immune cell cancer definitively linked to textured-surface breast implants. Although the National Comprehensive Cancer Network (NCCN) consensus guidelines and other clinical recommendations have been established, the evidence supporting these guidelines has not been systematically studied. The purpose of this evidence-based systematic review is to synthesize and critically appraise current clinical guidelines and recommendations while highlighting advances in diagnosis and treatment and raising awareness for this emerging disease. METHODS: This evidence-based systematic review evaluated primary research studies focusing on the diagnosis and treatment of BIA-ALCL that were published in PubMed, Google Scholar, and other scientific databases through March 2020. RESULTS AND CONCLUSIONS: The clinical knowledge of BIA-ALCL has evolved rapidly over the last several years with major advances in diagnosis and treatment, including en bloc resection as the standard of care. Despite a limited number of high-quality clinical studies comprised mainly of Level III and Level V evidence, current evidence aligns with established NCCN consensus guidelines. When diagnosed and treated in accordance with NCCN guidelines, BIA-ALCL carries an excellent prognosis.

A Rare Case of a Transgender Female With Breast Implant-Associated Anaplastic Large Cell Lymphoma Treated With Radiotherapy and a Review of the Literature.

We are reporting a case of a 54-year-old transgender female with a history of breast augmentation with bilateral silicone implants. Seventeen years later, she presented with an enlarging right breast mass. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (Ann Arbor Stage IIE, TNM Stage III BIA-ALCL). The patient underwent bilateral capsulectomy, sentinel lymph node biopsy with adjuvant CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, and radiotherapy to the right chest, axilla, and supraclavicular lymph nodes. BIA-ALCL is a rare entity, especially in transgender females. We report this case and a review of the literature in this report.

Challenges of driving CD30-directed CAR-T cells to the clinic.

Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas. Preclinical studies with CD30-directed CAR-T cells support the feasibility of this approach. Recently, two clinical trials of CD30-directed CAR-T cells in relapsed/refractory CD30+ lymphomas, including Hodgkin lymphoma, have been reported with minimal toxicities noted and preliminary efficacy seen in a proportion of patients. However, improving the persistence and expansion of CAR-T cells is key to further enhancing the efficacy of this treatment approach. Future directions include optimizing the lymphodepletion regimen, enhancing migration to the tumor site, and combination with other immune regulators. Several ongoing and upcoming clinical trials of CD30-directed CAR-T cells are expected to further enhance this approach to treat patients with relapsed and refractory CD30+ lymphomas.

2019 NCCN Consensus Guidelines on the Diagnosis and Treatment of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

National Comprehensive Cancer Network (NCCN) guidelines represent the consensus standard of care for diagnosis and management of the majority of known cancers. NCCN guidelines on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) have been recognized by the US Food and Drug Administration and widely advocated by national specialty societies. Consensus guidelines have helped create a treatment standardization for BIA-ALCL at all stages of disease. NCCN guidelines are evidence-based where possible and utilize expert consensus opinion to fill in gaps that may exist. NCCN undergoes annual panel review by multidisciplinary faculty members, and this article represents the most up-to-date 2019 guidelines. Recommendations focus on parameters for achieving reliable diagnosis and disease management and emphasize the critical role for complete surgical ablation. Suggestions for adjunct treatments and chemotherapy regimens are included for advanced BIA-ALCL with lymph node involvement. BIA-ALCL recurrence and management of unresectable disease, and organ metastasis are addressed. Adherence to recognized BIA-ALCL guidelines ensures patients receive the most current efficacious treatment available.

How I treat breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently described form of T-cell non-Hodgkin lymphoma now formally recognized by the World Health Organization classification of lymphoid neoplasms. The disease most often presents with a delayed seroma around the breast implant, almost exclusively with a textured surface, and manifests with breast pain, swelling or asymmetry, capsular contracture, but can also present with a breast mass, and lymph node involvement. The prognosis of BIA-ALCL is favorable compared with many other subtypes of systemic T-cell lymphoma; however, unlike other non-Hodgkin lymphomas, complete surgical excision for localized disease is an important part of the management of these patients. In this paper, we share our recommendations for a multidisciplinary team approach to the diagnosis, workup, and treatment of BIA-ALCL in line with consensus guidelines by the National Comprehensive Cancer Network.

[Breast implant-associated anaplastic large-cell lymphoma: A case report and a review of literature]. / Assotsiirovannaia s implantatom anaplasticheskaia krupnokletochnaia limfoma molochnoi zhelezy: opisanie klinicheskogo sluchaia i obzor literatury.

Breast implant-associated anaplastic large-cell lymphoma will be identified as a separate nosological entity in the 2017 adapted WHO classification due to differences in its clinical presentations, pathogenesis, and prognosis with those of nodal and cutaneous anaplastic large-cell lymphomas. The paper gives a review of the literature and describes the authors' own clinical case of common breast implant-associated anaplastic large-cell lymphoma involving breast tissue, axillary lymph nodes, anterior chest muscles, and bone marrow. The treatment policy chosen by the authors could achieve complete remission.

Breast implant-associated anaplastic large cell lymphoma - From diagnosis to treatment.

Breast lymphomas comprise a rare group of malignant breast tumors. Among these, a new entity has emerged as a potentially under-diagnosed disease. Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) most often manifests as a late periprosthetic effusion between 1 and 10 years after the implantation of silicone or saline-filled breast prostheses. BI-ALCL is an anaplastic lymphoma kinase-negative T-cell lymphoma that has a distinctively different clinical course than other breast lymphomas or ALCLs. Diagnosis is based on aspiration of the effusion around the implant and CD30 positivity of the sample. Every periprosthetic effusion after breast augmentation or reconstruction using implants should be considered as potential BI-ALCL until proven otherwise. The majority of cases at diagnosis are in the in situ stage, i.e., confined to the lumen around the prosthesis. Most patients have an excellent prognosis when complete removal of the capsule and prosthesis with negative margins is achieved surgically. Some patients, however, develop infiltrative disease with a potentially life-threatening clinical course. Treatment planning regarding the extent of surgery and role of adjuvant therapy, especially in advanced cases, requires further investigation.

NCCN Consensus Guidelines for the Diagnosis and Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Published case series demonstrate a lack of treatment standardization for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) with a wide variety of therapeutic strategies being employed at all stages of disease. The National Comprehensive Cancer Network (NCCN) annually publishes Clinical Practice Guidelines for Non-Hodgkin Lymphomas. For the first time, BIA-ALCL management will be included which signifies an important and needed guideline addition. The new BIA-ALCL guideline was achieved by a consensus of lymphoma oncologists, plastic surgeons, radiation oncologists, and surgical oncologists. NCCN guidelines focus on the diagnosis and management throughout the stages of many lymphoma subtypes based upon the most current data available. This article summarizes the essential recommendations and optimal therapeutic strategies of the NCCN guidelines critical to the plastic surgery community. We encourage international adoption of these BIA-ALCL treatment standards by our specialty societies across the oncology and surgery disciplines.

Lymphomatoid papulosis: Treatment response and associated lymphomas in a study of 180 patients.

BACKGROUND: Lymphomatoid papulosis (LyP) is a CD30(+) lymphoproliferative disorder, with a self-regressing clinical course and malignant histopathology. OBJECTIVE: The aim of this study was to evaluate characteristics, risk factors, associated malignancies, long-term outcome, and treatment of LyP in a large cohort representing the experience of the MD Anderson Cancer Center. METHODS: Patient charts and clinical and histopathologic data of 180 patients with LyP were retrospectively assessed. RESULTS: A total of 56.7% of patients was men. Histologic subtype A was found in 47.2%, type B in 17.2%, type C in 22.8%, type D in 7.8%, type E in 0.6%, and mixed subtype in 4.4% of the patients. One hundred fourteen lymphomas were observed in 93 patients, with mycosis fungoides (61.4%) and anaplastic large cell lymphoma (26.3%) being the most common forms. Risk factors for development of lymphoma included sex and histologic subtype. Number of lesions and symptom severity were not associated with lymphoma development. Patients with type D were less likely to have lymphomas. Treatment provided symptomatic relief but did not prevent progression to lymphoma. LIMITATIONS: The limitation of this study is the retrospective study design. CONCLUSION: Patients with LyP are at increased risk of associated lymphomas. Thorough patient counseling is needed and long follow-up periods are required to detect and treat secondary lymphomas.

[Treatment of primary thyroid lymphomas]. / Traitement des lymphomes thyroïdiens primitifs de stade localisé

Primary lymphomas of the thyroid (LPT) are a rare entity. LPT represent between 5 and 15% of all thyroid neoplasms. Cytology has limited value; biopsy should be recommended. The differential diagnosis of thyroid carcinoma is differentiated forms indolent or aggressive forms for anaplastic and high grade that may occur by a mass rapidly progressive and compressive. LPT represent a histologically and clinically heterogeneous disease. The most common forms are high-grade LPT (DBLCL) of diffuse large cell type or mucosa-associated lymphoid tissue (MALT). DBLCL receive chemotherapy. The benefit of irradiation is highly debated in view of the data from randomized lymphoma studies (nodal with a minority of extranodal forms) versus those of retrospective studies specifically addressing the case of LPT. Localized MALT lymphomas can be treated with radiation alone. The treatment of other LPT is presented.

Anaplastic large cell lymphoma, ALK-positive.

Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive (ALK+ ALCL) is an aggressive CD30-positive T-cell lymphoma that exhibits a chromosomal translocation involving the ALK gene and the expression of ALK protein. No particular risk factor has been clearly identified for ALCL. ALK+ ALCL shows a broad morphologic spectrum, but all cases contain a variable proportion of cells with eccentric, horseshoe- or kidney-shaped nuclei often with an eosinophilic region near the nucleus (hallmark cells). Five morphologic patterns can be recognized. ALK+ ALCL occurs in young subjects (median age ∼35 years), with male predominance, and frequently presents at an advanced stage, with systemic symptoms and extranodal involvement. Near 40% of patients are low risk according to the International Prognostic Index (IPI). Overall, the prognosis of ALK+ ALCL is remarkably better than other T-cell lymphomas. The IPI and the PIT scores in general predict survival in patients with ALK+ ALCL. Standard first-line treatment for ALK+ ALCL consists of doxorubicin-containing polychemotherapy, which is associated with an overall response rate of ∼90%, a 5-year relapse-free survival of ∼60%, and a 5-year overall survival of 70%. Excellent results have been reported with a variety of anthracycline-based chemotherapy regimens including CHOP, CHOEP or MACOP-B. Consolidative high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) has also been evaluated in patients in first remission with favourable results, however, superiority to standard chemotherapy is unproven and this approach remains investigational. Following universally accepted guidelines for the treatment of failed aggressive lymphomas, HDC/ASCT can effectively salvage a proportion of patients with relapsed or refractory ALK+ ALCL. Recently, the development of novel therapies targeting CD30 and ALK appear promising.

Primary cutaneous anaplastic large cell lymphoma successfully treated with local thermotherapy using pocket hand warmers.

Apart from for cutaneous deep fungal or mycobacterial infections, thermotherapy has been used for various malignant tumors. We report a case of primary cutaneous anaplastic large cell lymphoma, which responded quite well to topical thermotherapy using chemical pocket hand warmers. The treatment resulted in an immediate tumor regression without recurrence. This method is simple and might be a useful tool against solitary cutaneous lymphoma, especially of elderly patients with poor performance status or with various systemic complications.

Novel use of 308-nm excimer laser to treat a primary cutaneous CD30+ lymphoproliferative nodule.

CD30+ cutaneous lymphoproliferative disorders, the second most common cutaneous T cell lymphoma after mycosis fungoides, represent a spectrum of conditions ranging from lymphomatoid papulosis to borderline CD30+ lesions to anaplastic large-cell lymphoma. We report the case of a solitary cutaneous CD30+ lymphoproliferative nodule that was successfully treated with a 308-nm excimer laser. Our findings suggest that the 308-nm excimer laser may be a safe, effective, and well-tolerated therapy for primary localized CD30+ cutaneous lymphoproliferative lesions.

The therapy of primary adult systemic CD30-positive anaplastic large cell lymphoma: results of 40 cases treated in a single center.

The outcome of a series of adult patients, affected by primary systemic CD30-positive anaplastic large cell lymphoma (ALCL), treated with a sequential intensive therapeutic program, has been analyzed and all data available in the literature have been reviewed. Forty consecutive, unselected patients with ALCL were treated with the F-MACHOP regimen, followed by radiotherapy (RT) for residual mediastinal disease (15 cases) and by autologous stem cell transplantation (ASCT) conditioned with BAVC (29 cases). Eighty-nine percent (32/36) of the patients younger than 60 years were eligible for completing the sequential treatment. Since then, 3 patients in CR refused ASCT, 1 was excluded for cardiac toxicity and 3 progressed and died of disease. Thus, 29 have been so far submitted to the transplant procedure. CR and PR rates were 40% and 45% respectively after CHT; 52.5% and 35% after RT; 80% and 5% after ASCT, with 78% of patients transplanted in PR convertin to a CR. Actuarial overall survival is 85% at 48.5 months (93% at 66 months for the 29 transplanted patients) and disease free survival is 100% at 54 and 64 months respectively, with no relapses observed among patients who reached a CR. Considering our data and those of the literature, it can be concluded that although the role of ASCT in the therapy of ALCL must not be considered as definitive, its efficacy in converting PR into CR and in preventing relapses, suggests that a randomized trial comparing CHT alone vs CHT+ASCT should be undertaken.