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Purpose@#Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model. @*Materials and Methods@#A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88). @*Results@#The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. @*Conclusion@#Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.
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Background@#Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases. @*Methods@#We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes. @*Results@#The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066). @*Conclusions@#We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.
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Purpose@#We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system. @*Materials and Methods@#A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60). @*Results@#The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes. @*Conclusion@#Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.
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Background@#Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases. @*Methods@#We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes. @*Results@#The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066). @*Conclusions@#We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.
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Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a followup period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.
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Purpose@#In contrast to the Western diffuse large B-cell lymphoma (DLBCL), prognostic impact of age in a Korean population with DLBCL has not been fully evaluated. @*Materials and Methods@#Six hundred and eight DLBCL patients treated with rituximab-containing chemotherapeutic regimens from January 2002 to March 2012 in Asan Medical Center were enrolled. Survival models using the restricted cubic spine−transformed age variable were constructed to evaluate non-linear relationships between age and survival outcome. Finally, age was categorized according to the conventional international prognostic index (IPI), National Comprehensive Cancer Network (NCCN)-IPI, and Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI schemes and the prognostic implications were evaluated. @*Results@#The relative hazard did not change significantly during the first to fifth decades, but began to increase exponentially in patients aged over 62 years. This pattern or relationship was also retained in a multivariate model fitted to the age-adjusted IPI and relative dose intensity. Multivariate survival analysis revealed that age > 75 years, but not age > 60 years, was associated independently with poor overall and progression-free survival when the relative dose intensity and age-adjusted IPI were taken into account. @*Conclusion@#The outcome of DLBCL in Korean populations may deteriorate rapidly as age exceeds 62 years. Therefore, a consensus cutoff value for age in Korean DLBCL patients should be determined to better predict prognosis.
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Purpose@#We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system. @*Materials and Methods@#A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60). @*Results@#The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes. @*Conclusion@#Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.
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BACKGROUND: JL1, a CD43 epitope and mucin family cell surface glycoprotein, is expressed on leukemic cells. An anti-JL1 antibody combined with a toxic substance can have targeted therapeutic effects against JL1-positive leukemia; however, JL1 expression on bone marrow (BM) lymphoma cells has not been assessed using flow cytometry. We investigated JL1 expression on BM lymphoma cells from patients with non-Hodgkin lymphoma (NHL) to assess the potential of JL1 as a therapeutic target. METHODS: Patients with BM involvement of mature B-cell (N=44) or T- and natural killer (NK)-cell (N=4) lymphomas were enrolled from May 2015 to September 2016. JL1 expression on BM lymphoma cells was investigated using flow cytometry. Clinical, pathological, and cytogenetic characteristics, and treatment responses were compared according to JL1 expression status. RESULTS: Of the patients with NHL and BM involvement, 37.5% (18/48) were JL1-positive. Among mature B-cell lymphomas, 100%, 38.9%, 33.3%, 100%, and 25.0% of Burkitt lymphomas, diffuse large B-cell leukemias, mantle cell leukemias, Waldenstrom macroglobulinemia, and other B-cell lymphomas, respectively, were JL1-positive. Three mature T- and NK-cell NHLs were JL1-positive. JL1 expression was associated with age (P=0.045), complete response (P=0.004), and BM involvement at follow-up (P=0.017), but not with sex, performance status, the B symptoms, packed marrow pattern, cytogenetic abnormalities, or survival. CONCLUSIONS: JL1 positivity was associated with superior complete response and less BM involvement in NHL following chemotherapy.
Subject(s)
Humans , B-Lymphocytes , Bone Marrow , Burkitt Lymphoma , Chromosome Aberrations , Cytogenetics , Drug Therapy , Flow Cytometry , Follow-Up Studies , Leukemia , Leukemia, B-Cell , Lymphoma , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Membrane Glycoproteins , Mucins , Therapeutic Uses , Waldenstrom MacroglobulinemiaABSTRACT
BACKGROUND: While cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is the most commonly used chemotherapeutic regimen for patients with peripheral T-cell lymphomas (PTCLs), elderly patients are more vulnerable to associated toxicities. We evaluated the efficacy and safety of dose-attenuated CHOP in elderly patients with PTCL. METHODS: Patients with PTCL aged >70 years or 65–70-years with comorbidities were treated with dose-attenuated CHOP (cyclophosphamide: 562.5 mg/m2, doxorubicin: 37.5 mg/m2, vincristine: 1.4 mg/m2, and prednisolone: 100 mg for five days; 25% reduced dose of cyclophosphamide and doxorubicin vs. full-dose CHOP) as first-line therapy were included. RESULTS: Forty-four patients (median age, 74 yr) were analyzed. The majority (N=42, 95.5%) had advanced stage disease and 36 (81.8%) were classified as high/high-intermediate risk by the international prognostic index. The overall response rate was 61.4%, and 21 patients achieved complete response (47.7%). With median follow-up period of 28.8 months, the estimated two-year progression-free and overall survival rates were 36.7% and 46.6%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 26.9% and 7.4% of 204 total cycles, which affected 76.7% and 25.6% of the patients, respectively. Nineteen patients (44.2%) experienced febrile neutropenia, and six died due to treatment-related toxicities. High lactate dehydrogenase levels and an involvement of >1 extranodal sites were prognostic indicators of poor survival. CONCLUSION: Dose-attenuated CHOP does not compromise treatment efficacy but retains significant toxicity. Our results suggest that some patients can be effectively treated with dose-attenuated CHOP, however a novel therapy for elderly patients with PTCL is required.
Subject(s)
Aged , Humans , Comorbidity , Cyclophosphamide , Doxorubicin , Drug Therapy , Febrile Neutropenia , Follow-Up Studies , L-Lactate Dehydrogenase , Lymphoma, T-Cell, Peripheral , Neutropenia , Prednisolone , Survival Rate , Thrombocytopenia , Treatment Outcome , VincristineABSTRACT
Immunohistochemistry (IHC) is an important auxiliary method for pathologists in routine diagnostic work as well as in basic and clinical research including exploration of biomarkers, as IHC allows confirmation of target molecule expressions in the context of microenvironment. Although there has been a considerable progress in automation and standardization of IHC, there are still many things to be considered in proper optimization and appropriate interpretation. In this review, we aim to provide possible pitfalls and useful tips for practicing pathologists and residents in pathology training. First, general procedure of IHC is summarized, followed by pitfalls and tips in each step and a summary of troubleshooting. Second, ways to an accurate interpretation of IHC are discussed, with introduction to general quantification and analysis methods. This review is not intended to provide complete information on IHC, but to be used as a basic reference for practice and publication.
Subject(s)
Antigen-Antibody Reactions , Automation , Biomarkers , Immunohistochemistry , Methods , Pathology , PublicationsABSTRACT
BACKGROUND: CD99 is a cell surface transmembrane glycoprotein expressed in various tissues. CD99 is differentially expressed between subpopulations of each tissue and is highly expressed in certain hematopoietic and precursor cells. However, there has been no comprehensive study of CD99 expression in normal skin. We evaluated CD99 expression in normal human skin and developing fetal skin. METHODS: Seventy-five adult skin samples containing normal skin and eight fetal skin samples of different gestational ages were collected. CD99 immunohistochemical staining was performed to evaluate expression pattern in adult and fetal skin samples. CD99 and CD34 expression were compared by double immunofluorescence. RESULTS: In normal adult skin, CD99 was strongly expressed in the membrane of epidermal basal keratinocytes, hair follicle bulges and outer root sheaths, and inner secretory cells of eccrine sweat glands. In fetal skin, CD99 was not expressed on the periderm at 16 weeks of gestation but was expressed in basal cells of fetal skin at around 19 weeks of gestation. CD99 expression became comparable to that of the adult skin after 20 weeks of gestation. CD99 and CD34 were co-expressed in hair follicle outer root sheaths, as seen by double immunofluorescence study. CONCLUSIONS: This is the first study examining CD99 expression pattern in normal adult and fetal skin. CD99 tends to be expressed in the basal/precursor cells of epidermis and in hair follicles. These results provide a basis for future investigation on functions of CD99 in the skin and provide a novel potential target for the treatment of dermatologic lesions.
Subject(s)
Adult , Humans , Pregnancy , Epidermis , Fluorescent Antibody Technique , Gestational Age , Glycoproteins , Hair Follicle , Immunohistochemistry , Keratinocytes , Membranes , Skin , Sweat GlandsABSTRACT
No abstract available.
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BACKGROUND: The survival and growth of melanocytes are controlled by the binding of stem cell factor to its cell surface receptor c-kit+ (CD117). We have observed that c-kit+ melanocytes existed in some lesions of vitiligo, while Melan A+ cells were absent. OBJECTIVE: To verify possible relation between c-kit+ expression and treatment response in non-segmental vitiligo lesions. METHODS: Skin biopsies were done from the center of the 47 lesions from the 47 patients with non-segmental vitiligo. Expression of c-kit+ and Melan A, and amounts of melanin in the epidermis were assessed in each lesion, and treatment responses to excimer laser were evaluated. RESULTS: Thirty-five of the 47 lesions (74.5%) had c-kit+ phenotypes. There was significant difference of c-kit staining value between good responders in 3 months of excimer laser treatment (average of 24 sessions) and the others. CONCLUSION: c-Kit expression in vitiliginous epidermis may be related to better treatment responses to excimer laser.
Subject(s)
Humans , Biopsy , Epidermis , Lasers, Excimer , MART-1 Antigen , Melanins , Melanocytes , Phenotype , Proto-Oncogene Proteins c-kit , Skin , Stem Cell Factor , VitiligoABSTRACT
CD99 signaling is crucial to a diverse range of biological functions including survival and proliferation. CD99 engagement is reported to augment activator protein-1 (AP-1) activity through mitogen-activated protein (MAP) kinase pathways in a T-lymphoblastic lymphoma cell line Jurkat and in breast cancer cell lines. In this study, we report that CD99 differentially regulated AP-1 activity in the human myeloma cell line RPMI8226. CD99 was highly expressed and the CD99 engagement led to activation of the MAP kinases, but suppressed AP-1 activity by inducing the expression of basic leucine zipper transcription factor, ATF-like (BATF), a negative regulator of AP-1 in RPMI8226 cells. By contrast, engagement of CD99 enhanced AP-1 activity and did not change the BATF expression in Jurkat cells. CD99 engagement reduced the proliferation of RPMI8226 cells and expression of cyclin 1 and 3. Overall, these results suggest novel CD99 functions in RPMI8226 cells.
Subject(s)
Humans , Breast Neoplasms , Cell Line , Cyclins , Jurkat Cells , Leucine Zippers , Lymphoma , Multiple Myeloma , Phosphotransferases , Transcription Factor AP-1 , Transcription FactorsABSTRACT
Here we report a case of a 76-year-old man with diffuse large B-cell lymphoma (DLBCL) with simultaneous involvement of the right breast and left testicle. The patient underwent complete resection of the involved testis, followed by immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and prophylactic radiotherapy to the contralateral testis. Following this multimodal therapy, he achieved a complete response. This is a rare case of DLBCL involving both the breast and the testis in a male patient.
Subject(s)
Aged , Humans , Male , Breast , Cyclophosphamide , Doxorubicin , Lymphoma, B-Cell , Prednisolone , Radiotherapy , Testis , VincristineABSTRACT
No abstract available.
Subject(s)
Female , Humans , Middle Aged , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , PAX5 Transcription Factor/metabolism , Bone Marrow/metabolism , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Endoscopy, Digestive System , Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor , Genetic Loci , Liver/metabolism , Lymphocytes/cytology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, T-Cell, Peripheral/complications , Prednisone/therapeutic use , Receptors, Antigen, T-Cell, gamma-delta/genetics , Tomography, X-Ray Computed , Vincristine/therapeutic useABSTRACT
BACKGROUND: Abbreviated chemotherapy followed by radiotherapy or full cycles of chemotherapy is recommended as a standard treatment for limited-stage (LS) diffuse large B-cell lymphoma (DLBCL). After complete resection of tumors, however, Burkitt and childhood B-cell Non-Hodgkin lymphoma show favorable outcomes, even after abbreviated chemotherapy of only 2 or 3 cycles. We investigated the effectiveness of abbreviated chemotherapy in patients with LS DLBCL after complete tumor resection. METHODS: We retrospectively reviewed 18 patients with LS DLBCL who underwent complete tumor resection followed by either 3 or 4 cycles of chemotherapy between March 2002 and May 2010. RESULTS: With a median follow-up period of 57.9 months (range, 31.8-130.2 months), no patients experienced disease relapse or progression; however, 1 patient experienced secondary acute myeloid leukemia during follow-up. The 5-year progression-free survival rate and overall survival rate were 93.3% and 94.1%, respectively. CONCLUSION: These results warrant further investigation into abbreviated chemotherapy as an alternative treatment for patients who have undergone complete resection of LS DLBCL.
Subject(s)
Humans , B-Lymphocytes , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Leukemia, Myeloid, Acute , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Radiotherapy , Recurrence , Retrospective Studies , Survival RateABSTRACT
No abstract available.