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 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-Hodgkin lymphomas of the breast are rare, encompassing approximately 0.04-0.5% of all malignant breast tumors, and the vast majority are B-cell lymphomas. In contrast, lymphomas of T-cell phenotype have been rarely reported and some of these have been in close proximity to a breast implant. In our consultation practice, we have identified four patients with primary T-cell anaplastic large-cell lymphoma presenting adjacent to silicone or saline breast implants. All patients presented with seroma and neoplastic cells were identified in suspension in the serous fluid without solid tissue invasion. Three patients had no evidence of systemic disease (stage 1E), and one patient was not staged. The mean age of the patients was 46 years (range, 34-59 years). In all patients, the neoplastic cells had a T-cell phenotype, expressed CD30, cytotoxic granule-associated proteins, EMA and clusterin, and were anaplastic lymphoma kinase-1-negative. Clonal T-cell receptor gamma-chain gene rearrangements were identified in three patients. All patients underwent capsulectomy with removal of the implant. One patient subsequently received chemotherapy and radiation therapy, and another was treated with radiation alone. The third patient received no further therapy and the fourth patient has been recently diagnosed. After a mean time of 13 months (range, 9-20 months), all three patients with follow-up were alive and well without any recurrence or systemic disease. Although the follow-up time was relatively short, our series and other reported cases suggest that primary anaplastic large-cell lymphoma adjacent to breast implants is an indolent T-cell lymphoproliferative disorder.
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PMID:Seroma-associated primary anaplastic large-cell lymphoma adjacent to breast implants: an indolent T-cell lymphoproliferative disorder. 1822 53

In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >or= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2- positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator.
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PMID:A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37. 1865 Jan 62

Primary cutaneous anaplastic large-cell lymphoma (ALCL) ordinarily is distinguished from systemic ALCL by clinical presentation, absence of anaplastic lymphoma kinase (ALK) expression, and immunophenotype (CLA+, EMA/MUC1-). We present an exceptional case of an elderly man with primary cutaneous ALCL and no systemic disease for a 13-year period. Recurrent skin tumors in this patient were characterized by anaplastic, often multinucleated, cells infiltrating the lymphatics and associated with pseudoepitheliomatous hyperplasia. Cutaneous lymphocyte antigen was absent and EMA/MUC1, typical of systemic ALCL, was strongly expressed by the tumor cells. Remarkably, the tumor cells expressed a cytoplasmic-only variant of ALK protein, as reported in 3 previous cases of primary cutaneous ALCL. Fluorescence in situ hybridization revealed lack of rearrangements of the chromosome 2 ALK gene locus usually involved by translocation t(2;5) or other chromosomal rearrangements that generate nucleophosmin-ALK or the variant ALK fusions that occur in systemic ALCL. Nonetheless, the cytoplasmic ALK protein in the patient's tumor cells was shown to be phosphorylated/activated, suggesting a novel mechanism of ALK activation. Primary cutaneous ALCL of this novel subtype should be distinguished from systemic ALCL to ensure proper clinical management.
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PMID:Primary cutaneous ALCL with phosphorylated/activated cytoplasmic ALK and novel phenotype: EMA/MUC1+, cutaneous lymphocyte antigen negative. 1867 Mar 45

Anaplastic large cell lymphoma (ALCL) is a biologic and clinically heterogenous subtype of T-cell lymphoma. Clinically, ALCL may present as localized (primary) cutaneous disease or widespread systemic disease. These two forms of ALCL are distinct entities with different clinical and biologic features. Both types share similar histology, however, with cohesive sheets of large lymphoid cells expressing the Ki-1 (CD30) molecule. Primary cutaneous ALCL (C-ALCL) is part of the spectrum of CD30+ lymphoproliferative diseases of the skin including lymphomatoid papulosis. Using conservative measures, 5-year disease-free survival rates are > 90%. The systemic ALCL type is an aggressive lymphoma that may secondarily involve the skin, in addition to other extranodal sites. Further, systemic ALCL may be divided based on the expression of anaplastic lymphoma kinase (ALK) protein, which is activated most frequently through the nonrandom t(2;5) chromosome translocation, causing the fusion of the nucleophosmin (NPM) gene located at 5q35 to 2p23 encoding the receptor tyrosine kinase ALK. Systemic ALK+ ALCLs have improved prognosis compared with ALK-negative ALCL, although both subtypes warrant treatment with polychemotherapy. Allogeneic and, to a lesser extent, autologous stem cell transplantation play a role in relapsed disease, while the benefit of upfront transplant is not clearly defined. Treatment options for relapsed patients include agents such as pralatrexate (Folotyn) and vinblastine. In addition, a multitude of novel therapeutics are being studied, including anti-CD30 antibodies, histone deacetylase inhibitors, immunomodulatory drugs, proteasome inhibitors, and inhibitors of ALK and its downstream signaling pathways. Continued clinical trial involvement by oncologists and patients is imperative to improve the outcomes for this malignancy.
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PMID:Primary cutaneous and systemic anaplastic large cell lymphoma: clinicopathologic aspects and therapeutic options. 2066 96

The clinical and pathologic heterogeneity of human breast cancer has long been recognized. Now, molecular profiling has enriched our understanding of breast cancer heterogeneity and yielded new prognostic and predictive information. Despite recent therapeutic advances, including the HER2-specific agent, trastuzumab, locoregional and systemic disease recurrence remain an ever-present threat to the health and well being of breast cancer survivors. By definition, disease recurrence originates from residual treatment-resistant cells, which regenerate at least the initial breast cancer phenotype. The discovery of the normal breast stem cell has re-ignited interest in the identity and properties of breast cancer stem-like cells and the relationship of these cells to the repopulating ability of treatment-resistant cells. The cancer stem cell model of breast cancer development contrasts with the clonal evolution model, whereas the mixed model draws on features of both. Although the origin and identity of breast cancer stem-like cells is contentious, treatment-resistant cells survive and propagate only because aberrant and potentially druggable signaling pathways are recruited. As a means to increase the rates of breast cancer cure, several approaches to specific targeting of the treatment-resistant cell population exist and include methods for addressing the problem of radioresistance in particular.
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PMID:Breast cancer stem cells: treatment resistance and therapeutic opportunities. 2131 Sep 41

Anaplastic large-cell lymphoma (ALCL) is a lymphoma that expresses CD30. Cutaneous ALCL presents either as primary cutaneous disease or as secondary skin involvement due to the systemic disease. Herein, we describe two patients who presented to dermatology for evaluation of skin lesions diagnosed by non-dermatologists as a cutaneous abscess and lupus erythematosus, respectively. Upon investigation by a team of medical dermatologists and dermatopathologists, systemic ALCL with secondary skin involvement was discovered in both patients. The majority of cases of systemic ALCL with cutaneous involvement express anaplastic lymphoma kinase-1 (ALK-1), and are associated with a more favorable prognosis than ALK-1-negative cases. However, cutaneous ALCL regardless of ALK-1 status may be secondary to systemic lymphoma. This article stresses the importance of dermatologists being aware of the diagnosis of systemic lymphoma based on cutaneous findings, and being aggressive in initiating appropriate diagnostic testing. Primary cutaneous ALCL and systemic ALCL are reviewed.
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PMID:Cutaneous anaplastic large-cell lymphoma should be evaluated for systemic involvement regardless of ALK-1 status: case reports and review of literature. 2136 63

Patients with lung cancer having multiple brain metastases have poor outcomes. We present long-term disease treatment in a 60-year-old woman having greater than thirty brain metastases of NSCLC adenocarcinoma with a mutant allele of EGFR treated with differing chemotherapies including erlotinib, but disease response in the brain only with bevacizumab. Although initially restricted in use, increasing clinical reports have demonstrated safety of bevacizumab use in brain-involved cancer patients. Our case highlights that disease response to bevacizumab is similar in the brain to systemic disease and likely overcomes anatomical barriers that can limit other therapeutic agents.
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PMID:Prolonged activity of bevacizumab in adenocarcinoma of the lung with multiple brain metastases. 2220 41

Most patients with small intestinal neuroendocrine tumors (SI-NETs), also referred to as midgut carcinoids, present with systemic disease at the time of diagnosis with metastases primarily found in regional lymph nodes and the liver. Curative treatment is not available for these patients and there is a need for novel and specific therapies. Engineered oncolytic viruses may meet the need and play an important role in the future management of SI-NET liver metastases. This review focuses on adenovirus as the oncolytic anti-cancer agent and its potential curative role for SI-NET liver metastases, but it also summarizes the use of oncolytic viruses for NETs in general. It discusses how specific features of neuroendocrine cell biology can be used to engineer viruses to become selective for infection of NET cells and/or replication within NET cells. In addition, it points out the advantages and shortcomings of using replicating viruses in the treatment of cancer and addresses research fields that can increase the efficacy of virus-based therapy.
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PMID:Virotherapy of neuroendocrine tumors. 2237 83

CD30-positive T-cell lymphoproliferative disorders are classified as cutaneous (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) or systemic. As extent of disease dictates prognosis and treatment, patients with skin involvement need clinical staging to determine whether systemic lymphoma also is present. Similar processes may involve mucosal sites of the head and neck, constituting a spectrum that includes both neoplasms and reactive conditions (eg, traumatic ulcerative granuloma with stromal eosinophilia). However, no standard classification exists for mucosal CD30-positive T-cell lymphoproliferations. To improve our understanding of these processes, we identified 15 such patients and examined clinical presentation, treatment and outcome, morphology, phenotype using immunohistochemistry, and genetics using gene rearrangement studies and fluorescence in situ hybridization. The 15 patients (11 M, 4 F; mean age, 57 years) had disease involving the oral cavity/lip/tongue (9), orbit/conjunctiva (3) or nasal cavity/sinuses (3). Of 14 patients with staging data, 7 had mucosal disease only; 2 had mucocutaneous disease; and 5 had systemic anaplastic large cell lymphoma. Patients with mucosal or mucocutaneous disease only had a favorable prognosis and none developed systemic spread (follow-up, 4-93 months). Three of five patients with systemic disease died of lymphoma after 1-48 months. Morphologic and phenotypic features were similar regardless of extent of disease. One anaplastic lymphoma kinase-positive case was associated with systemic disease. Two cases had rearrangements of the DUSP22-IRF4 locus on chromosome 6p25.3, seen most frequently in primary cutaneous anaplastic large cell lymphoma. Our findings suggest mucosal CD30-positive T-cell lymphoproliferations share features with cutaneous CD30-positive T-cell lymphoproliferative disorders, and require clinical staging for stratification into primary and secondary types. Primary cases have clinicopathologic features closer to primary cutaneous disease than to systemic anaplastic large cell lymphoma, including indolent clinical behavior. Understanding the spectrum of mucosal CD30-positive T-cell lymphoproliferations is important to avoid possible overtreatment resulting from a diagnosis of overt T-cell lymphoma.
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PMID:Mucosal CD30-positive T-cell lymphoproliferations of the head and neck show a clinicopathologic spectrum similar to cutaneous CD30-positive T-cell lymphoproliferative disorders. 2238 54

The incidence of brain metastases (BM) in breast cancer patients has increased over the last decade, presumably due to advances in systemic treatment. Today, breast cancer is the second most common cause of BM among all solid malignancies, second only to lung cancer; furthermore, it is the most common cause of leptomeningeal carcinomatosis. The HER2-positive subtype was consistently shown to have a higher risk for BM as compared with HER2-negative disease. More recently, however, it was shown that a similar incidence exists in triple-negative tumours. Local treatment options, radiotherapy and neurosurgical resection, remain the mainstay of therapy for BM. While some studies have suggested a direct effect of conventional chemotherapy on BM, the main beneficial aspect of systemic treatment is rather due to control of non-CNS systemic disease. Importantly, in patients with HER2-positive breast cancer receiving HER2-targeted therapy after local treatment for BM, superior survival outcomes were reported. Leptomeningeal carcinomatosis has a dismal prognosis. Survival with whole brain radiotherapy alone remains short and the potential additional benefit of intrathecal chemotherapy is still disputed. According to case reports, intrathecal administration of trastuzumab appears to be a promising strategy in patients with HER2-positive leptomeningeal carcinomatosis. In conclusion, while the outcome of breast cancer patients with BM has improved especially in the HER2-positive subtype, the prognosis for the majority of patients remains poor. Therefore, development of novel systemic treatment options offering activity within the brain is urgently warranted. Novel insights into the pathobiology of BM formation may offer the possibility for targeted drug prophylaxis of CNS involvement in high-risk patients.
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PMID:Optimal management of brain metastases from breast cancer. Issues and considerations. 2323 65


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