A Rare Case of Leukemia Cutis as the First Presentation of a Myelodysplastic Syndrome to Acute Myeloid Leukemia Transformation.

Leukemia cutis (LC) is a rare presentation of leukemia. It is characterized by the infiltration of leukemic cells into the different layers of the skin causing varying skin manifestations. It can occur before the hematological presentation of leukemia or during the disease course and carries a poor prognosis. Here, we report a patient with therapy-related myelodysplastic syndrome (t-MDS) whose transformation to acute leukemia was heralded by the development of LC. Worrisome cutaneous lesions should not be overlooked, and a skin biopsy should be pursued to confirm the diagnosis. A high index of suspicion is the key to early recognition of sometimes nonspecific skin findings of widespread systemic disease.

The Potential Clinical Benefit of Tocilizumab Therapy for Patients with HHV-8-infected AIDS-related Multicentric Castleman Disease: A Case Report and Literature Review.

Castleman disease (CD), also known as angiofollicular hyperplasia, is a rare disorder characterized by nonmalignant mediastinal lymph node enlargement provoked by excess interleukin-6 (IL-6) secretion. It could be unicentric or multicentric (MCD). Here, we describe a 27-year-old man with a prior history of AIDS, Kaposi sarcoma (KS), and latent syphilis who presented to the ED for persistent fatigue, fever, chills, night sweats, and productive cough. Infectious workup was negative, and the patient continued to have a high fever despite empiric antibiotic therapy. Bone marrow biopsy was performed and was negative for malignancy. The patient eventually underwent a left clavicular lymph node biopsy, which showed a plasma cell variant CD with positive immunostaining for human herpesvirus 8 (HHV-8), and high HHV-8 viral load. We started the patient on rituximab and liposomal doxorubicin, but unfortunately, the patient had a severe anaphylactic reaction to the rituximab, so we could not proceed with this treatment. We, therefore, started tocilizumab treatment, which improved the patient's general condition, and he was eventually discharged from our hospital. Upon follow-up 11-months later, a repeat CT scan of the chest and abdomen showed a near-complete treatment response with decreased lymphadenopathy throughout and hepatosplenomegaly. IL-6 overproduction in patients with CD is linked to the production of inflammatory cytokines and has a role in tumor angiogenesis, which makes it potential for IL-6 targeted therapy. The diagnosis of CD, especially MCD, requires a high index of suspicion, and a lymph node biopsy is essential in the diagnosis. Tocilizumab, an IL-6 receptor antibody, could potentially be considered as a practical therapeutic approach in managing HHV-8 positive MCD patients who do not tolerate or respond to initial rituximab therapy.

A Unique Case of Testicular Plasmablastic Lymphoma in a Patient with Human Immunodeficiency Virus.

Plasmablastic lymphoma (PBL) is a rare, aggressive, diffuse large B-cell lymphoma usually arising in the oral cavity of human immunodeficiency virus (HIV) patients. Here we describe a patient with HIV who presented with cutaneous nodules that were biopsied and found to be positive for PBL, but whose primary source was found to be testicular. This is the first reported case of a patient with HIV who presented with cutaneous nodules that tested positive for PBL, but whose primary source of neoplasm was found to be testicular.

Thrombocytosis as an Initial Presentation of Plasma Cell Neoplasm: A Case Report.

Plasma cell neoplasms are usually associated with normal or decreased platelet count. The association of thrombocytosis and multiple myeloma is exceedingly rare, with only six such cases reported in the literature until now. Differentiating clonal from secondary causes of thrombocytosis can be extremely difficult, yet the distinction has important therapeutic implications. We report the case of a woman presenting with thrombocytosis that led to the diagnosis of multiple myeloma. The possible etiological link between both these entities is also discussed.

Choriocarcinoma Syndrome: A Potentially Fatal Complication of Testicular Cancer.

Choriocarcinoma syndrome is a rare clinical entity with advanced, high volume choriocarcinomatous tumors and markedly elevated B-hCG (>50,000 IU/L). Recognition is important because the diagnosis of this syndrome identifies poor prognosis without mortality-proven management options. We present a case of a male in his twenties with metastatic choriocarcinoma who developed choriocarcinoma syndrome acutely after chemotherapy commencement. The patient deceased after hypoxic respiratory failure due to diffuse alveolar hemorrhage as a result of death of vascular tumors. While the prognosis for early diagnosis and treatment is excellent, the prognosis for late diagnosis is grim. Unfortunately, despite surgical or chemotherapeutic intervention, this syndrome has poor outcome.

Paraneoplastic Inflammatory Arthritis.

The immunodeficiency virus infection is known to increase the risk of malignancies, including lymphomas. We report a case of a 51-year-old male with a history of human immunodeficiency virus (HIV) infection, well-controlled on antiretroviral treatment, who presented with polyarthritis and hypercalcemia due to an elevated parathyroid-hormone-related peptide. Computer tomography (CT) revealed diffuse lymphadenopathy and a lymph node biopsy revealed large B-cell lymphoma. He was treated and responded well to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy regimen. Our case highlights the importance of recognizing inflammatory arthritis as an initial manifestation of occult malignancy like large B-cell lymphoma, as the arthritis preceded his eventual diagnosis of lymphoma by several months.

Burkitt Lymphoma Presenting as an Intracardiac Mass: Case Report and Review of Literature.

BACKGROUND Non-neoplastic causes such as infections and thrombi account for most intracardiac masses. Primary tumors such as myxomas and metastasis from breast cancer, lung cancer, or melanomas account for many of the remaining cases. Burkitt lymphoma manifesting as an intracardiac mass is a rare entity, with 21 cases reported in the English literature. CASE REPORT We report the case of a man infected with human immunodeficiency virus (HIV) who presented with non-specific cardiac symptoms and was later found to have intracardiac mass caused by Burkitt lymphoma. His rapid decline with unexpected complications was reversed with prompt management. Subsequent to induction, the patient achieved a near complete response with considerable improvement in his condition. CONCLUSIONS Lymphoma should be considered in the differential diagnosis of intracardiac masses. Associated cardiac symptoms are frequently non-specific and can often be overlooked or underappreciated. Burkitt lymphoma has a short doubling time and an intracardiac lesion can become life-threatening in a matter of days. Early recognition and prompt treatment are crucial to achieving optimal outcomes.

Plasmoblastic lymphoma as cause of perianal fistula: a case report and literature review.

We report the case of a 33-year-old HIV-infected man who presented with a recurrent, nonhealing perianal fistula. After multiple benign biopsies, the diagnosis of plasmablastic lymphoma (PBL) eventually was made. The patient underwent chemotherapy and radiation with a complete response. Perianal fistulas are frequent in HIV-positive patients, but PBL as a cause is extremely rare. This often delays the diagnosis and treatment of this highly aggressive disease. We review the literature and discuss the pitfalls in the diagnosis and management of the disease.

Successful large-volume cerebrospinal fluid aspiration for an accidental overdose of intrathecal cytarabine.

Intrathecal therapy with cytarabine is widely used in the treatment of acute lymphocytic leukemia. We report the first case of accidental intrathecal cytarabine overdose in an adult patient. Overdose of intrathecal chemotherapy has been reported to cause severe neurological damage including seizures, coma and death. Methotrexate levels can help guide intrathecal dosing of methotrexate, but no such test is commercially available for cytarabine. There are no standardized treatment recommendations for the management of this medical emergency. Intrathecal methotrexate overdose has been variously treated with cerebrospinal fluid drainage or exchange. Ventriculo-lumbar perfusion, steroids and leucovorin have also been used. It seems crucial to quickly remove as much drug as possible from the cerebrospinal fluid. Our patient was successfully treated with large-volume cerebrospinal fluid aspiration through an Ommaya reservoir. She did not suffer any significant immediate or late complications at 4 months of follow-up.

Prognosis and outcome of small (<=1 cm), node-negative breast cancer on the basis of hormonal and HER-2 status.

Long-term outcomes and hence the role of adjuvant therapy in patients with small (≤1 cm), node-negative breast cancer remain unclear. This study's objective was to evaluate whether human epidermal growth factor receptor (HER)-2 status is an independent, poor prognostic marker in patients with these tumors and to identify a subgroup of patients with these small tumors who might benefit from adjuvant systemic therapy. All patients with a diagnosis of a node-negative breast tumor measuring ≤1 cm and available HER-2 test results between January 1, 2001, and December 31, 2005, at the three Mayo Clinic sites were identified. Clinicopathologic data were compared in three groups: HER-2(-), HER-2(+), and triple-negative (TN) tumors. Of the 421 tumors identified, 364 (86.5%) were HER-2(-), 28 (6.7%) were HER-2(+), and 29 (6.9%) were TN. The median follow-up time was 1,015 days (range, 1-2,549 days). Groups were balanced in terms of patient age and tumor histology. Eleven patients with HER-2(-) tumors (3.0%), seven with HER-2(+) tumors (25.0%), and eight with TN tumors (27.6%) received adjuvant chemotherapy. Follow-up data were available for 357, 28, and 28 patients in the three groups, respectively. Death rates in the three groups were 6.4% (23 of 357) (one recurrence-related death), 0% (0 of 28), and 7.1% (2 of 28) (one recurrence-related death), respectively. During follow-up, the tumor recurred in nine patients: four were HER-2(-) tumors (1.1%), two were HER-2(+) tumors (7.1%), and three were TN tumors (10.7%). Patients with small, node-negative breast tumors have an excellent prognosis, but HER-2(+) and TN tumors appear to have a higher recurrence rate, warranting consideration for broad use and optimization of systemic adjuvant treatments.

In newly diagnosed breast cancer, screening MRI of the contralateral breast detects mammographically occult cancer, even in elderly women: the mayo clinic in Florida experience.

The role of magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer is somewhat controversial. The purpose of this study was to evaluate the prevalence of synchronous, occult contralateral breast cancer detected by MRI but not by mammography or clinical breast examination in women with newly diagnosed breast cancer, including those aged 70 years or older at our institution. MRI results for women with newly diagnosed breast cancer who underwent bilateral breast MRI after negative mammography and clinical examination between February 2003 and November 2007 at Mayo Clinic in Florida were reviewed. The prevalence of pathologically confirmed contralateral carcinoma diagnosed solely by MRI was determined and analyzed in the context of age, family history, menopausal status, breast density, and primary-tumor characteristics. Logistic regression was used to explore the association between contralateral carcinoma and potential patient risk factors. A total of 425 women were evaluated, of whom 129 (30%) were aged 70 years or older. A contralateral biopsy was recommended and performed solely on the basis of MRI in 72 of the 425 women (17%). Sixteen of these 72 women (22%) had pathologically confirmed carcinoma, including seven in the older subgroup. The prevalence of clinically and mammographically occult contralateral carcinoma detected by MRI was 3.8% (16/425) overall and 5.4% (7/129) in the group of older women. When potential risk factors for contralateral breast cancer were evaluated, postmenopausal status was the only significant predictor of contralateral cancer detected by MRI (p = 0.016). We concluded that contralateral breast screening with MRI should be considered in postmenopausal women with newly diagnosed breast cancer, even those aged 70 years or older at diagnosis.

Treatment of metastatic breast cancer: looking towards the future.

The armamentarium for the treatment of metastatic breast cancer is increasing with the introduction of newer chemotherapeutic agents and the development of molecular targeted therapies. The clinical utility of anthracyclines in advanced breast cancer has been limited by significant adverse events; therefore the taxanes are increasingly used in the metastatic setting. Trastuzumab with a taxane as first-line therapy is now standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Other targeted therapies, including the antiangiogenesis agents such as bevacizumab, are being investigated both as monotherapy and in combination regimens. While the number of available agents is growing rapidly, challenges remain concerning appropriate dose, schedule, treatment duration and management of drug resistance. This paper reviews recent data regarding the established and investigational medical treatments for endocrine-refractory metastatic breast cancer, and presents treatment recommendations.

Issues and controversies in the treatment of HER2 positive metastatic breast cancer.

Targeted therapies against the human epidermal growth factor receptor HER2, have led to revolutionary strides in breast cancer research and treatment. Clinical therapeutic decisions in the treatment of patients with HER2 positive metastatic breast cancer are based on appropriate patient selection, the clinical situation, and data related to the available therapeutic agents trastuzumab and lapatinib. Trastuzumab was the first agent tested and approved in 1996 as single agent for patients with chemotherapy-refractory disease, and in combination with paclitaxel as first-line treatment. This intravenous humanized monoclonal antibody is directed against the extracellular domain of the HER2 protein. Lapatinib, an oral small molecule tyrosine kinase inhibitor has more recently become available (in 2007), approved for used in combination with capecitabine for patients with HER2 positive metastatic disease that has progressed on trastuzumab. Important questions and controversies still remain and are reviewed, including patient selection for anti-HER2 treatment of metastatic disease based on HER2 testing, dose scheduling of trastuzumab, duration of therapy, tolerability, role of lapatinib and clinical significance of trastuzumab resistance and efficacy. Ongoing trials designed to maximize the therapeutic ratio of these agents, are also discussed.

Letrozole: present and future role in the treatment of breast cancer.

State of the art hormonal therapy for women with breast cancer has evolved over the last few years. Tamoxifen used to be the gold standard for adjuvant treatment of postmenopausal women with hormone-sensitive early breast cancer and also for patients with metastatic disease in whom hormonal manipulation was considered, but the introduction of third generation aromatase inhibitors has changed this concept. This article discusses the clinical implications of recent trials with one of the aromatase inhibitors letrozole, including pharmacokinetic and pharmacodynamic data as well as recent data on relative benefits and side effects compared with other available hormonal agents. Relevant ongoing clinical-translational trials evaluating this agent are also discussed.