Large Granular Lymphocytic Leukemia: A Report of Response to Rituximab.

Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration. A CBC showed that pancytopenia with an absolute neutrophil count (ANC) was 0. Peripheral blood flow cytometry detected increased number of T cell large granular lymphocytes and T cell receptor rearrangement study detected a clonal T cell population. Bone marrow biopsy showed peripheral T cell lymphoma, most consistent with T-large granulocytic leukemia. The patient was treated with prednisone and oral cyclophosphamide for four months with no response. Thereafter, she received four weekly infusions of rituximab with improvement in her blood counts. A response to rituximab in refractory cases such as ours has been reported and may guide us towards exploring other immune-based therapeutics in this rare disease.

Antiphospholipid Syndrome: Multiple Manifestations in a Single Patient-A High Suspicion Is Still Needed.

Antiphospholipid Syndrome (APS) is an autoimmune disorder with clinical and laboratory features of vascular thrombosis, pregnancy loss, and persistent antiphospholipid antibodies (aPLs). The pathophysiology is thought to involve the activation of endothelial cells, monocytes, platelets, and complement by aPLs. Disease can range from asymptomatic to rapidly fatal catastrophic APS. We present a case of a 34-year-old male referred for pancytopenia and splenomegaly. On examination, he had decreased sensation and 4/5 power in the left upper extremity. A lacy, purplish rash was noted on the trunk and upper extremity. MRI of brain showed acute/subacute lacunar infarctions. Laboratory studies revealed an elevated lactate dehydrogenase level, bilirubin and ferritin, decreased haptoglobin, and positive Coombs test. Antinuclear antibody test was negative and antiphospholipid antibody panel revealed positivity for anti-cardiolipin IgG and IgM, antiphosphatidylserine IgG, and anti-ß2-glycoprotein IgG. The patient was diagnosed with primary APS. Pancytopenia is relatively rare in primary APS and is more often seen in secondary APS. Our patient demonstrated involvement of multiple organ systems as well as livedo reticularis and autoimmune-related findings such as Raynaud phenomenon and Coombs positive hemolytic anemia. We discuss the various clinical and laboratory findings in patients with APS that aid in diagnosis, as well as important management considerations.

Composite Diffuse Large B-cell and Mantle Cell Lymphoma: A Case Report.

Composite lymphoma is an extremely rare clinical entity and is characterized by the presence of two different subtypes of lymphoma in the same lymph node. We report a case of composite lymphoma in a 57-year-old male presenting with leg and groin pain. The right inguinal lymph node biopsy showed large and small cells. Immunohistochemistry was consistent with large cells staining for diffuse large B-cell lymphoma (DLBCL) and small cells positive for mantle cell lymphoma (MCL). Polymerase chain reaction (PCR) analysis of immunoglobulin heavy (IGH) chain and immunoglobulin kappa (IGK) light chain gene rearrangements confirmed that the two were clonally unrelated neoplasms. There are only two reported cases of composite lymphoma with this combination in the published English literature. We report the third such case and discuss the pathology, diagnostic challenges and management of composite lymphoma.

Soft Tissue Myoepithelial Carcinoma of the Neck with Spinal Invasion.

Soft tissue myoepithelial neoplasms are a rare yet diverse group of tumors, ranging from benign to malignant lesions. Their presentation in the head and neck region is uncommon and represents a challenging diagnosis. Early identification of myoepithelial carcinoma is crucial given its more aggressive course compared to its benign counterpart, although the histopathological distinction between the two can be difficult. EWSR1 gene rearrangement is found in half the cases and has a speculative role in pathogenesis. Complete excision remains the treatment of choice. The roles of chemotherapy and radiation are unclear. We report the hospital course of a 33-year-old female who presented to our institution with a posterior neck mass with spinal invasion, diagnosed as myoepithelial cancer. A literature review of these rare tumors is discussed here.

Long-term Survival in a Patient with Recurrent Pulmonary Metastases from Uterine Leiomyosarcoma.

Chemotherapy is the standard of care for disseminated uterine leiomyosarcoma; however, long-term survival is rarely achieved with this aggressive disease. We report a patient with recurrent pulmonary metastatic disease from uterine leiomyosarcoma who is doing well without significant disease nine years after her initial diagnosis. We discuss her clinical course, the treatment modalities she received, and the clinical evidence supporting these.

Stage IV EGFR Mutation-Negative and ALK Mutation-Negative Lung Adenocarcinoma: Long-Term Survival is Possible.

Lung cancer is the leading cause of cancer death in the United States with a five-year survival of 16.8% for all stages and median survival of four months for Stage IV disease. We report a case of a 54-year-old male with a seven-year survival after being diagnosed with Stage IV epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK) mutation-negative adenocarcinoma of the lung, demonstrating an exceptional response to treatment.

The value of the pretreatment neutrophil lymphocyte ratio vs. platelet lymphocyte ratio in predicting the long-term survival in colorectal cancer.

BACKGROUND: The neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) have been well studied as inflammatory markers and predictors for outcomes in colorectal cancer patients. Our aim was to determine the predictive value of both above ratios in colorectal cancer patients. METHODS: This is a longitudinal retrospective study of a prospectively maintained database, included 580 patients, who had a complete blood count recorded before treatment (surgery or chemotherapy). We excluded patients presented with obstruction, infection, active hematological disease or those receiving steroid. The primary outcome (4-year cancer-related mortality) was obtained from our cancer registry. RESULTS: The 4-year cancer-related mortality rate in the 3rd tertile of NLR was 37% in comparison with 13% and 19% in lower tertiles, P value < 0.001. Similarly the 3rd tertile of PLR was 32% with 18% and 19% in lower tertiles, P value < 0.0005. In the multivariate survival analyses, elevated NLR was associated with higher mortality (a hazard ratio of 2.31(1.4-3.8) for the highest tertile and 5% increase in mortality for each unit increase in NLR, p < 0.001). Similarly, elevated NLR was a significant predictor for a worse disease-free survival. However, PLR was not significant predictor of mortality when adjusted for other confounding variables. CONCLUSION: Elevated pretreatment NLR is an independent predictor of both worse overall and disease free survival in colorectal cancer, whereas PLR was not after adjusting for confounding variables.

Acute mesenteric ischemia: a sequela of abdominal aortography.

The use of abdominal angiography and transcatheter embolization has increased rapidly in the last few decades. Although improvement in angiographic techniques has made the procedure safe, ischemic colitis is a rare but potentially dreadful complication. We report a case of a 51-year-old woman who developed ischemic colitis following aortography, demonstrating that such angiographic studies may produce substantial morbidity.

Benign and Malignant Hematological Manifestations of Chronic Hepatitis C Virus Infection.

Chronic hepatitis C virus (HCV) infection, that affects 3% of world's population, is associated with several hematological manifestations mainly benign cytopenias, coagulopathy and lymphoproliferative diseases. Immune or non-immune-mediated thrombocytopenia is a major challenge in chronic HCV infected patients especially in the setting of an advanced liver disease, with average prevalence of nearly 24%. Although several treatment modalities such as steroids, intravenous immunoglobulin, splenectomy and immunosuppresants have been tried with some success, their efficacy is not impressive and can result in an increase in viral load or other thrombotic complications. Even though a recent phase 2 study has shown promising role of a platelet growth factor, eltrombopag, in boosting platelets counts prior to antiviral treatment, its use in pre-operative setting had unexpected complications. Unlike thrombocytopenia, anemia and neutropenia are more frequently seen in treated patients and are often the result of antiviral therapy. HCV infection also pre-disposes to lymphoproliferative diseases, mainly non-Hodkings lymphomas, likely as a result of chronic antigenic stimulation and mutation of several genes involved in carcinogenesis. Understanding of the role of HCV infection in these conditions has therapeutic implications. Whereas antiviral therapy has shown therapeutic role in HCV-associated indolent lymphomas, monitoring of hepatic function and viral load is important in the management of diffuse large B-cell lymphoma in HCV-infected patients. Although our knowledge about the HCV infection and hematological manifestations has substantially grown in last few decades, further studies are important to advance our therapeutic approach.

Reversible bone marrow aplasia induced by pegylated interferon-α-2a therapy in a patient with primary myelofibrosis.

Interferon has been widely used in the management of patients with hematological malignancies such as polycythemia vera, myelofibrosis, chronic myeloid leukemia and viral infections such as chronic hepatitis C. Hematological adverse effects such as cytopenias have been observed, particularly in patients who receive a combination of interferon-α-2a and ribavirin for hepatitis C. Mild myelosuppression can be seen with pegylated interferon; however, bone marrow aplasia in patients with myelofibrosis has not been reported. It is important to be aware of such a serious complication since persistent bone marrow aplasia can be fatal. We describe a case of pegylated interferon-induced reversible bone marrow aplasia in a patient with primary myelofibrosis.

IgM Myeloma or Waldenstrom's Macroglobulinemia Is the Big Question?

ABSTRACT: Although critical from therapeutic and prognostic perspectives, differentiating IgM Myeloma (MM) from Waldenstrom's macroglobulinemia (WM) is fraught with failure. WM can usually be distinguished from IgM MM by the lymphoplasmacytic versus pure plasmacytic morphology, absent versus present lytic bone lesions, and immunophenotypic findings. However, all these features have their own limitations; hence, it requires constant vigilance and periodic re-evaluation. Here we describe a case of a 70-year-old woman initially diagnosed as smoldering IgM MM, who eventually turned out to have WM.

Concurrent Acute Monoblastic Leukemia and Multiple Myeloma in a 66-Year-Old Chemotherapy-Naive Woman.

Concurrent acute myeloid leukemia (AML) and multiple myeloma (MM) is rare, more so in chemotherapy-naive patients. Concurrent occurrence of these two malignancies portends poor prognosis. Although anthracycline-based AML regimen, allogeneic hematopoietic stem cell transplantation, tipifarnib and bortezomib have shown promising results in small number of patients, there is a lack of established therapy. We describe a case of concurrent AML and MM in a 66-year-old woman and review previously published literature.

The value of the pretreatment albumin/globulin ratio in predicting the long-term survival in colorectal cancer.

BACKGROUND: Low serum albumin was found as a predictor of long-term mortality in colorectal cancer (CRC) patients. Our aim was to evaluate the value of the pretreatment albumin/globulin ratio (AGR) to predict the long-term mortality in CRC patients. METHODS: Patients were included if they had comprehensive metabolic panel (CMP) before treatment (surgery or chemotherapy). The albumin/globulin ratio, routinely reported in CMP, is calculated [AGR = Albumin/(Total protein - Albumin)]. Patients were divided into three equal tertiles according to their pretreatment AGR. The primary outcome was cancer-related mortality, which was obtained from our cancer registry database. RESULTS: A total of 534 consecutive CRC patients had pretreatment CMP. The 1st AGR tertile had a significant higher 4-year mortality compared to the second and third AGR tertiles (42 vs. 19 and 7 %, p < 0.0001 according to Fisher's exact two-tailed test). In the multivariate model, AGR remained an independent predictor of survival with 75 % decrease in mortality among the highest AGR tertile in comparison to the lowest AGR tertile, p < 0.0001. In the subset of 234 patients with normal serum albumin (albumin of >3.5 g/dl), serum AGR continues to be an independent predictor of cancer-related mortality with an adjusted hazard ratio of the third tertile compared to the first tertile equal to 0.05 (95 % confidence interval 0.01-0.33, p = 0.002). CONCLUSION: Low AGR was a strong independent predictor of long-term cancer-specific survival among colorectal cancer patients. Additionally, among the patients with normal albumin (>3.5 g/dl), patients with lower globulins but higher albumin and AGR levels had better survival.

Acclimatisation in trekkers with and without recent exposure to high altitude.

In mountaineers, recent altitude exposure has been shown to improve climbing performance and clinical outcomes during re-exposure to high altitude. However, the timing of previous altitude exposure has not been clearly reported and previous findings might be driven by individuals who were still acclimatised at the time of re-exposure. Our goal was to determine whether recent altitude exposure would confer an advantage even in individuals who had de-acclimatised for ≥ 1 week before being re-exposure. Low-altitude natives kept a daily trekking log throughout 7- to 8-day trek from Lukla (2,840 m) to Gokyo Ri (5,360 m). Trekkers with recent altitude exposure (re-acclimatisers, RA; n = 20) walked 20% faster (p < 0.01), reported lower acute mountain sickness scores (9 ± 8 vs. 15 ± 13; p = 0.02), and used less medication to treat headache (p < 0.05) compared to trekkers with no recent altitude exposure (initial acclimatisers, IA; n = 30). On Gokyo Ri, S(p)O(2) was significantly higher in RA than IA trekkers (85 ± 6 vs. 78 ± 6; p = 0.01). These data indicate improved functional outcomes and physiological compensation for hypoxia in RA. However, even after de-acclimatisation for 7-30 days, it is possible that RA trekkers began the trek in a more acclimatised state than IA trekkers. RA trekkers might represent a self-selected group that has previously tolerated altitude well and has therefore opted to return. Some findings might also reflect improved psychological altitude tolerance in RA. A direct comparison of the functional and physiological responses to hypoxia throughout an initial and re-acclimatisation to high altitude is needed.

Cardiac tamponade in acute pancreatitis.

A 47-year-old man presented with severe acute pancreatitis. On hospitalisation day 8, the patient became hypotensive and developed new-onset atrial fibrillation. Echocardiography showed significant pericardial effusion with right ventricular collapse. A pericardial window was made and the effusion drained. There was rapid clinical improvement following the procedure.