Chiung-Tang Huang

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, With Unusual Clinical Presentation of Bluish-Reddish Multicolored Rainbow Pattern

Case Report To our knowledge, we report, for the first time, the clinical findings of a 40-year-old woman with a large tumor approximately 20 15 cm in size that appeared as a bluish-reddish multicolored rainbow pattern over the back area. Biopsy revealed primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT). She first came to our hospital because of the large tumor and also due to a fever occurring off and on for 2 weeks. Other associated symptoms and signs were general malaise and body weight loss of 5 kg in 1 month. She denied any underlying disease. The characteristics of the huge tumor were purple-black patch with erythematous papules and central erosion with bluish-reddish multicolored rainbow pattern approximately 20 15 cm (Fig 1). She described the tumor as being approximately 5 cm for about 3 years, but noted rapid growth of up to 20 cm over a 3-month period. Initial laboratory findings revealed a WBC count of 3,600/ L, hemoglobin of 8.1 g/dL, and platelets of 321,000/ L. The renal and liver functions were normal. The tumor biopsy revealed diffuse lymphoid of a mediumto large-sized nature infiltrated from papillary dermis to deep reticular dermis and pleomorphic nuclei with coarse chromatin and scant to moderate cytoplasm (original magnification, 400; Fig 2, arrow). Immunohistochemical analysis revealed that the neoplastic cells were positive for CD20 (original magnification, 400; Fig 3, arrow), Bcl-2, and Ki-67 (data not shown), but negative for CD3, CD56, CD15, and ALK-1. The diagnosis was primary cutaneous diffuse large B-cell lymphoma, leg type. Positron emission tomography revealed increased fluorodeoxyglucose avidity over the back area (Fig 4; arrows). Bone marrow biopsy revealed primary cutaneous B-cell lymphoma with bone marrow invasion (data not shown), and immunohistochemical findings were positive for CD20. There was no other systemic organ involvement. The patient began receiving systemic chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. After two cycles of treatment, the large tumor showed gradual improvement.

Higher lipocalin 2 expression may represent an independent favorable prognostic factor in cytogenetically normal acute myeloid leukemia

Abstract Several molecular markers, such as NPM1, FLT3 and CEBPA, have been incorporated into both the World Health Organization and European LeukemiaNet classifications as routine assessments for the diagnosis and evaluation of prognostic significance in acute myeloid leukemia (AML). Lipocalin 2 (LCN2) is related to cancer development and is believed to be associated with the outcome of cytogenetically normal (CN)-AML. In the present study, we analyzed the prognostic effects and interactions of LCN2 expression (by molecular analysis, quantitative real-time polymerase chain reaction [qRT-PCR]) with neucleophosmin 1, fms-related tyrosine kinase 3 (FLT3) and CCAAT/enhancer-binding protein alpha mutations in 85 patients with CN-AML receiving intensive induction chemotherapy. Our results indicate that patients with higher LCN2 mRNA expression in the bone marrow (LCN2high), especially in combination with wild type FLT3-ITD, had better prognoses. FLT3-ITD compensated LCN2-overexpression-enhanced oxidative stress-induced apoptosis in cell line studies. In conclusion, LCN2high was associated with better prognosis, and FLT3 status had an adjuvant effect on overall survival.

Utilization of 18F-FDG PET/CT as a staging tool in patients with newly diagnosed lymphoma

The aim of this study was to investigate the role of 2‐fluorine‐18‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) in the initial staging and prediction of bone marrow involvement in patients with newly diagnosed lymphoma. A total of 185 patients with newly diagnosed lymphoma were enrolled. All patients received PET/CT and bone marrow biopsy as part of a staging work‐up. At the initial staging, 17 patients (9.2%) with occult nodal or extranodal lesions were upstaged after a review of the PET/CT studies. PET/CT was found to be useful in the differentiation of aggressive lymphoma subtypes from the indolent subtype based on higher standardized uptake value (SUV) (16.67 vs. 7.98, p < 0.001). The results of bone marrow biopsy and PET/CT in the detection of bone marrow involvement were concordant in 152 patients (82.1%); positive concordance was observed in 21 patients, and negative concordance was observed in 131 patients. A high concordance rate was found between aggressive B cell lymphoma and Hodgkins lymphoma (88.1% and 93.8%, respectively). High negative predictive values (NPVs) for excluding bone marrow involvement were observed in aggressive B‐cell lymphoma (93.2%) and Hodgkins lymphoma (100%). Diffuse bone marrow FDG uptake accurately predicted bone marrow in aggressive B‐cell lymphoma with a positive predictive value (PPV) of 100%. The concordance rate was lower in indolent B‐cell lymphoma (66.0%). In conclusion, PET/CT resulted in the upstaging of patients with occult extranodal or nodal lesions. A high SUV level can predict aggressive subtype of lymphoma and detect aggressive components in indolent lymphoma. PET/CT had a high PPV for aggressive B‐cell lymphoma with diffuse bone marrow FDG uptake and high NPVs for excluding bone marrow involvement in aggressive B‐cell lymphoma and Hodgkins lymphoma. Bone marrow biopsy may be omitted for the above subgroups of patients with medical conditions not suitable for this procedure. For patients with indolent B‐cell lymphoma, bone marrow biopsy is still an indispensable procedure for staging.

Positron-emission tomography findings indicating the involvement of the whole body skin in subcutaneous panniculitis-like T cell lymphoma

Dear Editor, We report, for the first time, the imaging findings of a 31year-old man who was diagnosed with massive subcutaneous panniculitis-like T cell lymphoma based on positron-emission tomography (PET) scan findings of multiple area involvement, including the subcutaneous layer of the whole body and the bone marrow. He visited our hospital with complaints of fever occurring off and on for 1 month. Other associated symptoms and signs were general malaise and skin nodules over the abdomen and bilateral hands. He denied any underlying disease. We noted nodular lesions with brownish-like plaques over the skin of the face, neck, bilateral hands, and abdomen. Further, ulcerative lesions were observed over the left upper arm. Initial laboratory findings revealed a white blood cell (WBC) count of 3,400/μl, hemoglobin of 15 g/dl, and platelets of 193,000/μl. The renal and liver functions were normal. After 10 days,WBC count of 2,000/μl, hemoglobin of 11.2 g/dl, and platelets of 68,000/μl indicated pancytopenia. The results of liver function test revealed aspartate aminotransferase/alanine aminotransferase, 589/428 IU/l; bilirubin (T/D), 7.72/4.82 mg/dl; gammaglutamyl transpeptidase, 1,756 IU/l; and alkaline phosphatase, 198 IU/l. Other lab data revealed that serum ferritin level was 66,430 ng/ml; fibrinogen, 73 mg/dl; and triglyceride, 401 mg/ dl. Bone marrow examination was performed to determine the cause of unexpected pancytopenia, and it revealed fulminant hemophagocytosis (Fig. 1). Neck nodular biopsy revealed lymphoid infiltration involving the fat lobules with the sparing of septa. The neoplastic lymphoid cells showed irregular and hyperchromatic nuclei with rimming of palestaining cytoplasm (Fig. 1). Immunohistochemical analysis revealed that the neoplastic cells were positive for CD3 (Fig. 1) and Ki67 (data not shown), but negative for CD20, CD30, and CD56. The diagnosis put on subcutaneous panniculitis-like T cell lymphoma, and αβ phenotype of T cell receptor was favorable. Bone marrow biopsy revealed subcutaneous panniculitis-like T cell lymphoma (SPTCL) with bone marrow invasion (data not shown), and immunohistochemical findings were positive for CD3 but negative for CD20 and CD30. PET revealed diffuse subcutaneous infiltration with increased fluorodeoxyglucose (FDG) avidity over the subcutaneous area of the whole body (Fig. 1) and the bone marrow of bilateral lower limbs. This patient started to receive systemic chemotherapy with EPOCH (Etoposide, Epirubicin, Vincristine, Cyclophosphamide, and Prednisolone) after detecting SPTCL, stage IV with hemophagocytic syndrome. After two cycles of treatment, the skin lesions, hemogram, liver function test, and hemophagocytosis showed gradual improvement. SPTCL is a primary T cell lymphoma that specifically involves the subcutaneous tissue. The skin presentation can mimic that of benign panniculitis. SPTCLs constitute less than 1% of the non-Hodgkin lymphomas [1]. In 1991, Gonzalez et al. first described eight cases of T cell lymphoma localized primarily in the subcutaneous area [2]. In 2005, the World Health Organization-European Organization for Research and Treatment of Cancer C.-T. Huang :W.-C. Yang : S.-F. Lin Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

HIV-negative disseminated Kaposi's sarcoma in a Taiwanese patient.

Kaposis sarcoma is a common malignancy associated with HIV/AIDS. Herein, we describe the case of a 26‐year‐old man who presented with bilateral neck and inguinal lymphadenopathy, a massive tumor on the gum, and a nodule over the left eye. A series of tests, including tumor biopsies, were performed, and disseminated Kaposis sarcoma with human herpesvirus 8 infection was diagnosed. To test for HIV, we used enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction, but the results were negative. The patient was treated by biweekly intravenous infusion of pegylated liposomal doxorubicin (25 mg/m2), and this treatment resulted in a partial response.

Previous Exposure to Statin May Reduce the Risk of Subsequent Non-Hodgkin Lymphoma: A Nationwide Population-Based Case-Control Study

Background The purpose of this study was to investigate the association between previous exposure to statins and the risk of non-Hodgkin lymphoma (NHL). Methods This nationwide population-based case–control study was conducted using the National Health Insurance Research Database of Taiwan. The NHL group consisted of the patients with a first-time diagnosis of NHL between 2005 and 2008. The cases of the control group were pair-matched to the NHL group according to sex, year of birth and date of NHL diagnosis (index date). The statin administration data from both groups were retrospectively collected from the index date to January 1, 1996. The cumulative defined daily dose (cDDD) was estimated to evaluate the statin exposure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression. Results The study population was composed of 1715 NHL patients and 16942 control subjects. The analysis revealed that previous statin administration was associated with a reduced risk of subsequent NHL with an adjusted OR of 0.52 (95% CI, 0.43–0.62). Additionally, there was a dose-response relationship between statin administration and the risk of NHL. The adjusted ORs were 0.63 (95% CI, 0.46–0.86), 0.58 (95% CI, 0.42–0.79), 0.51 (95% CI, 0.38–0.67), and 0.36 (95% CI, 0.24–0.53) for the subjects with statin administrations of fewer than 28, 28 to 90, 91 to 365, and more than 365 cDDDs, respectively, relative to the subjects without any statin administration. Conclusions The results of this study suggest that previous statin administration is associated with a lower risk of subsequent NHL. As statins are widely used medications, the magnitude of the risk reduction may have a substantial influence on public health. Further studies to confirm our findings are warranted.

Investigation on treatment strategy, prognostic factors, and risk factors for early death in elderly Taiwanese patients with diffuse large B-cell lymphoma

This study aimed to investigate the treatment strategy, prognostic factors, and risk factors of early death in elderly patients (age ≥ 65 years) with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Data from elderly patients diagnosed with DLBCL between 2008 and 2014 were collected for analysis. Patients who were younger and had a better performance status were more likely to receive intensive frontline treatment. The median progression-free survival (PFS) and overall survival were 15 and 21 months, respectively. Anthracycline-containing chemotherapy achieved a higher remission rate and showed a trend towards better overall survival but a higher risk of severe neutropenia. Multivariate analysis revealed that very old age (≥81 years), a high-risk age-adjusted international prognostic index (aaIPI) score, and bone marrow involvement were associated with poorer PFS and overall survival. Progression of lymphoma was the major cause of death in the study population. In addition, approximately 25% of patients died within 120 days of being diagnosed. The risk factors for early mortality included very old age, a high-risk aaIPI score, and bone marrow involvement. The appearance of symptoms or signs of tumour lysis syndrome at diagnosis was associated with a trend towards early death.

Pyoderma gangrenosum: Intractable leg ulcers in Sjogren's syndrome

I am writing with regard to a patient with pyoderma gangrenosum; a rare skin disease. This 52-year-old woman had multiple wounds with poor healing over her right lower leg and ankle for 3 years after a traffic accident. The wounds were initially small, abrasive, and shallow, and subsequently progressed to become a deep ulcer with some necrotic tissue (Fig. 1A and B). She did not have diabetes, hypertension, or hyperlipidemia. A blood test revealed a platelet count of 40,000/mL, white blood cell count of 4300/mL, hemoglobin level of 10.5 g/dL, and Creactive protein level of 1.06 mg/L. A bone marrow study showed reactive marrow to peripheral destruction, and an immunological study revealed that she was negative for rheumatoid factor, positive for Ro, La, and doublestranded DNA antibodies, and had an antinuclear antibody ratio of 1:1280. The levels of C3 and C4 were modestly lower at 70 mg/dL and 14 mg/dL, respectively. She also complained of dry eyes and mouth. A subsequent Schirmer’s test was positive, and salivary scintigraphy showed delayed uptake, suggesting moderate sialoadenitis over both parotid glands and the right submandibular gland. Based on the above findings, Sjogren’s syndrome was diagnosed. A skin biopsy revealed inflammatory cells with neutrophilic and lymphoplasmacytic infiltration, however, there was no evidence of thrombosis or vasculitis (Fig. 1C and D). These features were compatible with pyoderma gangrenosum. Pyoderma gangrenosum is often associated with underlying diseases and is a rare ulcerative skin disease [1e3]. It is defined as an inflammatory, reactive, noninfective, nonneoplastic skin disease, and is associated with antiphospholipid syndrome, systemic lupus erythematous,

Chronic mucocutaneous herpes simplex virus.

A 19-year-old male underwent allogeneic peripheral blood hematopoietic stem cell transplantation with human leukocyte antigen matched from an unrelated donor after complete remission of his myelodysplastic syndrome/ myeloproliferative neoplasm with acute leukemic change. The condition regimen was total body irradiation, cyclophosphamide, and Thymoglobulin; and methotrexate, leucovorin, and cyclosporine were used for prophylactic graftversus-host disease. On post-transplantation Day 120, the patient complained of papillomatous and verrucous plaques (lesions) over the orolabial and nasal areas (Fig. 1A) that developed within the past month. Virologic test result was positive for immunoglobulin G of herpes simplex virus. Results of skin biopsy revealed epidermal necrosis, ballooning degeneration of keratinocytes, and virus inclusion body (Fig. 1C). The clinical and laboratory picture was consistent with

Diffuse large B-cell lymphoma presenting with type B lactic acidosis and hemophagocytic syndrome.

We report the case of a 51-year-old woman who was diagnosed with diffuse large B cell lymphoma presenting with hemophagocytic syndrome complicated by type B lactic acidosis. The patient came to our hospital because of an intermittent fever for 1 week. The initial laboratory findings revealed the following: white blood cell count, 3600/mL; hemoglobin, 10.1 g/dL; platelet, 28,000/mL. Her serum Creactive protein level was 47.7 mg/L, and arterial blood gas analysis showed pH 7.28, PCO2 38.1 mmHg, and HCO3 17.6 m mol/L. Her lactate level was 11.8mEq/L, sodium 135mg/dL, and chloride 104 mg/dL. A high anion gap metabolic acidosis related to lactic acidosis was noted. She had a pulse rate of 95 beats/minute, and her blood pressure was 130/75 mmHg. The bone marrow examination revealed hemophagocytosis (Fig. 1A). The patient’s computed tomography scan revealed a right adrenal gland tumor of about 6.8 cm and a liver nodule of about 4.7 cm in S6eS7 (Fig. 1B). A liver nodular biopsy revealed diffuse, large lymphoid cells containing coarse chromatin and scant-to-moderate cytoplasm (Fig. 1C), and the immunohistochemical analysis revealed that the neoplastic cells were positive for CD20 (Fig. 1D), Bcl-2, and Ki-67 (data not shown), but negative for CD3. The final diagnosis was diffuse large B-cell lymphoma complicated by type B lactic acidosis and hemophagocytic syndrome. Positron emission tomography revealed increased fluorodeoxyglucose avidity over the pelvic, liver, bilateral adrenal gland, shoulder, and right neck areas (data not shown). The patient was then treated with a systemic chemotherapy consisting of EPOCH (etoposide, epirubicin, vincristine, cyclophosphamide, and prednisolone). Because