Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma

BACKGROUND: A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings. METHODS: Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined. RESULTS: Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11-20% in 14 patients, 21-30% in 3 patients, 31-40% in 4 patients, 41-50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033). CONCLUSION: The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.

A t(8;9)(p22;p24)/PCM1-JAK2 Translocation in a Patient With Myeloproliferative Neoplasm and Myeloid Sarcoma: First Report in Korea

No abstract available.

Langerhans Cell Histiocytosis Followed by Hodgkin's Lymphoma

A 22-year-old man was referred to our institution due to lower back pain and was diagnosed with Langerhans cell histiocytosis of the thoracic and lumbar spine. The patient achieved complete remission with radiotherapy and chemotherapy. One year later, right cervical lymphadenopathy was observed and Hodgkin's lymphoma was confirmed on biopsy. The patient was treated with chemotherapy and autologous stem cell transplantation, and experienced no further symptoms. Further, no evidence of recurrence was observed on follow-up imaging. This report discusses the association between Langerhans cell histiocytosis and Hodgkin's lymphoma.

Clinico-hematologic Findings of Leukemic Bone Marrow Involvement in Korean Patients with Non-Hodgkin Lymphoma

BACKGROUND: The purpose of the present study was to investigate the clinico-hematological findings of bone marrow (BM) involvement and leukemic phase in Korean patients with non-Hodgkin lymphoma (NHL). METHODS: We included 791 patients with NHL that were classified with the WHO (2008) criteria. Laboratory data, bone marrow histomorphologic features and medical records were reviewed. Leukemic phase was defined as when the proportion of neoplastic lymphoid cells comprised more than 10% of leukocytes in the peripheral blood or more than 25% of nucleated cells in the BM. RESULTS: We found that 21.7% (172/791) of the patients had BM involvement, and 6.2% (49/791) developed leukemic phase of the disease. NHL subtypes showing high frequencies of leukemic phase development were mantle cell lymphoma (40%), angioimmunoblastic T cell lymphoma (40%), lymphoblastic lymphoma (36.4%), and Burkitt lymphoma (26.1%). Compared to B-cell type, T-cell type of NHL showed significantly higher frequencies of BM involvement (18.6% vs 30.9%; P=0.0004) and leukemic phase development (4.8% vs 10.3%, P=0.008). Complete remission rate was significantly lower in leukemic (55.6%) than in non-leukemic (85.9%) group of patients (P=0.0002), whereas relapse rate was not different between the two groups. Death rate was higher in leukemic (46.9%) than in non-leukemic (30.1%) group of patients, and the 5-yr overall survival probability was significantly lower in leukemic group (P=0.02). CONCLUSIONS: The incidence of leukemic phase development in NHL was lower in Korean patients than that reported for Western populations and higher in T-cell lymphoma. We confirmed that the presence of leukemic phase in NHL patients is associated with a poor prognosis.

Langerhans Cell Sarcoma Arising in a Lymph Node: A Case Report and Review of the Literature

We report a case of Langerhans cell sarcoma presented as a solitary mass in the left supraclavicular area in a 31-year-old woman. Computed tomography revealed a relatively well-defined and lightly enhancing mass in the left supraclavicular area, measuring 5.5x4.5x3.2 cm. Excision was subsequently performed. Microscopically, the specimen consisted of an enlarged and partially effaced lymph node. Nests of different size composed of atypical tumor cells were located in the paracortex and the medulla of the lymph node. The tumor cells exhibited abundant eosinophilic or clear cytoplasm and displayed marked nuclear atypia and increased mitotic figures. Infiltration of many eosinophils was identified in the periphery and between the tumor cells. The tumor cells were reactive for CD1a and S100 protein. Ultrastructually, they were found to have Birbeck granules in the cytoplasm.

Role of CD4(+)CD25(high+)FOXP3(+) Regulatory T Cells in Psoriasis

BACKGROUND: CD4(+)CD25(high+)regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis. OBJECTIVE: To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis. METHODS: Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients. RESULTS: An increase in the FOXP3(+) cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3(+) cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3(+) Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls. CONCLUSION: The deficiency of FOXP3(+) Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.

Splenic Littoral Cell Angioma with Hepatitis C Associated Liver Cirrhosis

Littoral cell angioma (LCA) of spleen is an uncommon vascular neoplasm of littoral cell origin. It is well established that LCA may be associated with other malignancy or autoimmune disorders. We describe a 34-year-old woman with viral hepatitis C associated liver cirrhosis who presented with the incidental finding of LCA. She showed ascites, esophageal varix and drowsy mentality. Abdominal computed tomography (CT) showed multiple benign looking nodules in both hepatic lobes, but no abnormality in spleen. Liver transplantation and splenectomy were performed. Microscopic findings revealed narrow anastomosing vascular channels lined with plump cells that exfoliated into the lumen. Immunohistochemically the lining cells were positive for CD31, CD68 and negative for CD34, consistent with LCA. Herein, a second case of an incidentally detected LCA with cirrhosis, viral hepatitis C associated in Korea is reported.

Prognostic Impact of Helicobacter pylori Infection and Eradication Therapy in Gastric Mucosa-associated Lymphoid Tissue Lymphoma / 대한진단검사의학회지

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection and H. pylori eradication is used as its first-line therapy. However, controversies exist about the prognostic value of H. pylori infection in these patients. We evaluated the prognostic impact of H. pylori infection and eradication therapy in gastric MALT lymphoma. METHODS: A total of 292 patients diagnosed with MALT lymphoma since 2000 were analysed. MALT lymphoma was diagnosed with tissue biopsy and H. pylori infection was diagnosed with hematoxylin-eosin and additional Warthin-Starry stains on tissue sections. Clinical variables such as bone marrow (BM) involvement, multiorgan involvement, tumor stage at diagnosis, and remission were obtained with retrospective review of electronic medical records. RESULTS: Non-gastric MALT lymphoma patients showed higher multiorgan involvement rates (26.6% vs. 9.6%, P or =3 (27.7% vs. 16.7%, P=0.029) than gastric cases. Regarding gastric MALT lymphoma, patients with H. pylori infection at diagnosis showed significantly less BM (2.1% vs. 21.8%, P<0.001) and multiorgan involvement rates (6.3% vs. 18.2%, P=0.011) than those without infection. But there was no significant difference in remission rates between them. In contrast, those with successful H. pylori eradication therapy showed significantly higher remission rates (81.0% vs. 30.8%, P<0.001) than those with failure. CONCLUSIONS: Non-gastric MALT lymphoma patients showed worse prognosis compared to gastric cases. As for remission rates in patients with gastric MALT lymphoma, successful H. pylori eradication therapy could be a good prognostic factor even if H. pylori infection was present at diagnosis.

A Case of CD5 Negative Chronic Lymphocytic Leukemia / 대한혈액학회지

Neoplastic lymphoid cells of chronic lymphocytic leukemia (CLL) typically co-express CD5 and CD23. CD5-negative CLL is a rare variant of CLL; only 1 case of it has been reported in Korea. We describe a case of CD5-negative CLL. A 48-year-old female complained of a palpable neck mass that had been present for over 1 year. The initial WBC count was 7,300/microliter, with 69% lymphocytes. A CT scan revealed multiple enlarged lymph nodes, both of each in the neck, axilla, and common iliac areas. The athologic results of the cervical lymph node was consistent with small lymphocytic lymphoma, of which tumor cells do not express CD5. In a bone marrow study, neoplastic lymphoid cells comprise 34.8% of all nucleated cells, which showed small size, round nuclei with clumped chromatin, and sparse cytoplasm. Immunophenotyping of small lymphoid cells displayed phenotypes that were CD45-, CD23-, CD20-, and CD19-positive, but CD5-negative. The patient was diagnosed with CD5-negative CLL, and has been followed up for 2.5 years after chemotherapy.

Omental Histiocytic Sarcoma: A Case Report

We report a case of perigastric histiocytic sarcoma (HS) involving the lesser omental sac in a 30-year-old man. HS is an exceedingly rare malignancy of mature tissue histiocyte. The tumor was a multi-lobulated, bulging enhancing mass in the lesser omentum with metastasis to lymph nodes and liver. The tumor consisted of diffuse non-cohesive proliferation of pleomorphic large oval to round neoplastic cells with giant cells showing vesicular chromatin and ample eosinophilic cytoplasm. In some areas, the tumor cells showed spindling with elongation of the nuclei and cellular shapes. Many of the tumor cells, especially giant forms contained phagocytosed lymphocytes. Immunohistochemical analysis of the tumor cells showed expression of leukocyte common antigen, CD68, lysozyme, vimentin, CD4, and CD163. Ki-67 index was 50-60%. After the operation, he was treated with chemotherapy, but the response was poor.

Expression Pattern of the Cortical Immature Thymocyte Specific Antigen JL1 in Thymomas; a New Adjunctive Diagnostic Marker

BACKGROUND: JL1 is a novel antigen that has been reported to be expressed exclusively in immature CD4 CD8 double positive T-cells in the thymic cortex. Thymomas are often infiltrated with lymphocytes that are mostly immature T-cells. METHODS: We evaluated 67 cases of surgically resected thymomas and reviewed their histological, surgical, and clinical findings. Representative sections were immunostained using anti-JL1 monoclonal antibody and the immunostaining score was evaluated in each case. RESULTS: JL1 was strongly positive in immature T cells infiltrated in various subtypes of thymomas. The mean value of the immunostaining score was 0 for type A, 0.24 for the A areas of type AB, 2.71 for the B areas of type AB, 3 for type B1, 1.87 for type B2, 0.67 for type B3, and 0.13 for type C. The immunostaining score correlated with the histological subtypes according to the WHO classification, and stages according to the modified Masaoka system. CONCLUSION: JL1 was specifically detected in immature thymocytes in thymomas. Therefore, JL1 immunostaining can be useful for subtyping thymomas. JL1 can also serve as an adjunctive marker to diagnose thymomas in small biopsy specimens.

A Case of Diffuse Large B-cell Lymphoma in a Kidney Transplant Recipient / 대한신장학회잡지

Posttransplant lymphoproliferative disorders (PTLD) is an infrequent but serious complication of transplantation. Previous studies have suggested the terms of reference, "early PTLD" (referring to PTLD that occurs within 1 year of transplantation) and "late PTLD" (PTLD that occurs after 1 year). Early PTLD generally involves a single organ or nodal region and often responds favorably to a decrease in immunosuppression. Late PTLD tends to be disseminated, responds less frequently to a decrease in immunosuppression, and has a dismal prognosis. We encountered a diffuse large B-cell lymphoma in a 44-year-old man who underwent kidney transplantation over 10 years ago, in 1995. In situ hybridization for Epstein-Barr virus showed positive results in tumor cell. With decreased immunosuppressants and chemotheraphy, he is currently in complete remission.

A Case of Systemic Castleman's Disease in a Child and Successful Treatment with Oral Prednisolone / 소아과

Castleman's disease is a rare non-neoplastic lymphoproliferative disorder of unknown etiology. It is divided into three histologic subtypes; hyaline-vascular(HV), plasma cell(PC) type and mixed type (HV-PC). It has two clinical expressions. The localized form, which presents as a slow growing mass, has a relatively benign clinical course. The multicentric form is multilocated and holds significant morbidity. The mainstay of treatment of the localized form is surgical resection. The multicentric form requires medical treatment comprising prednisolone and other immunosuppressor drugs. The disease in children seems to have a more favorable course than in adults. We report a 13-year- old boy with Castleman's disease of multicentric form who was successfully treated with prednisolone and intravenous immunoglobulin.

A Case of Duodenal Relapse of Epstein-Barr Virus-positive, CD56-negative Extranodal NK/T-cell Lymphoma, Nasal Type / 대한소화기내시경학회지

Mature T-cell and natural killer-cell neoplasms account for 10 to 15% of all non-Hodgkin's lymphomas. Of the various subtypes of mature T-cell and NK-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type (nasal type NK/T-L) is relatively more common among Asians including Koreans. Nasal type NK/T-L is an aggressive, Epstein-Barr virus-associated lymphoma with characteristic expression of NK-cell antigen CD56. In this report, we present an unusual case of EBV(+), CD56(-) NK/T-L of oropharynx which recurred in duodenum after the period of complete remission lasting for 10 years. A 58-year-old woman presented with 3 months history of abdominal pain. Gastroduodenoscopy showed the diffuse wall thickening with multiple ulcerations in bulb and proximal second portion of the duodenum. Pathological examination revealed the infiltration of atypical lymphocytes, which was positive for CD3, CD4, CD5, TIA-1, and EBV and was negative for CD15, CD20, and CD56, consistent with NK/T-L of mature T-cell origin. The past medical history included the presence of oropharyngeal mass 10 years earlier, which was diagnosed as polymorphic reticulosis. The mass resolved completely after the radiation therapy, and she remained free of the disease for 10 years. Upon review, the oropharyngeal biopsy showed an identical morphology and immunophenotype with duodenal lesion. In conclusion, we experienced an unusal case of NK/T-cell lymphoma, nasal type recured in the duodenum.

Lymphocytic Gastritis in Helicobacter pylori-positive Gastric MALT Lymphoma: Report of Two Cases / 대한소화기학회지

Both lymphocytic gastritis and gastric mucosa associated lymphoid tissue (MALT) lymphoma are associated with Helicobacter pylori (H. pylori) infection. However, this association has not been fully elucidated. We report two cases of lymphocytic gastritis in 57-year-old male and 47-year-old female patients which were diagnosed after the H. pylori eradication to treat gastric MALT lymphoma. MALT lymphoma was successfully treated in case 1, but residual MALT lymphoma remained in case 2. During the follow-up endoscopic examinations, several elevated erosions in case 1 and irregular mucosal atrophy in case 2 were newly detected. Biopsy specimens showed marked infiltration of lymphocytes in the surface epithelium (56.6+/-15.9 intraepithelial lymphocytes (IELs)/100 epithelial cells in case 1 and 40.5+/-9.3 IELs/100 epithelial cells in case 2), which were exclusively CD8-positive T lymphocytes. These findings suggest that H. pylori infection may cause a monoclonal proliferation of B lymphocytes, leading to MALT lymphoma as well as polyclonal proliferation of T lymphocytes which subsequently infiltrated into the surface epithelium as a host immune reaction, resulting in lymphocytic gastritis.

Complete remission of high grade gastric MALT lymphoma after Helicobacter pylori eradication: a case report / 대한내과학회지

Low grade MALT lymphoma of stomach is associated with H. pylori infection in more than 90% of cases, and eradication of H. pylori leads to regression of the low grade MALT lymphoma in 60~90% of cases. On the contrary, high grade MALT lymphoma is thought to be independent from H. pylori for growth and usually is thought to require antitumor chemotherapy. However, there have been recent reports of high grade MALT lymphoma regressing after H. pylori eradication. We experienced and are reporting a case of high grade MALT lymphoma arising in the background of low grade MALT lymphoma that showed complete regression after H. pylori eradication.

Three Cases of Primary Effusion Lymphoma / 대한혈액학회지

Primary effusion lymphoma (PEL) is a recently described rare type of non-Hodgkin's lymphoma which develops in serous body cavity without clinically identifiable tumor masses. Human herpesvirus (HHV)-8 was recognized to play a pathogenic role in the development of PEL in immunocompromised patients such as human immunodeficiency virus (HIV) positive patients or elderly. However, several cases of HHV-8 negative PEL have been reported. Here we describe a case of HHV-8 positive PEL with both of hepatocellular carcinoma and liver cirrhosis and two cases of HHV-8 negative PEL with liver cirrhosis and fatty liver each. Considering the reported and current HHV-8 negative PEL cases, we need to expand the concept of PEL.

Bfl-1 Gene Expression in Breast Cancer: Its Relationship with other Prognostic Factors

The Bfl-1 gene, which was isolated from human fetal liver and only recently described, is a member of the Bcl-2 gene family. Reverse transcriptase-polymerase chain reaction was performed on RNA drawn from 30 breast cancer tissues to compare the expression of the Bfl-1 gene with other prognostic factors. The median relative ratio was 3.0 (range, 0.12-26.83) and the Bfl-1 gene expression rate was 36.7% (11/30). There was no statistically significant relationship between the clinicopathologic parameters of patients and the expression value of Bfl-1 gene. The level of Bfl-1 gene expression was higher in more advanced breast cancers than in early cancers. There was no significant relationship between the expression values and currently acknowledged prognostic factors, but a higher expression pattern was noticed in the groups of positive hormone receptors and negative p53 and negative c-erbB2, albeit statistically not significant. It seems that the increased expression of the Bfl-1 gene serves as a contributory factor in breast cancer, in the same way that another group of genes, the Bcl-2 family, contributes to apoptosis.

Primary Intestinal Lymphoma

PURPOSE: Primary gastrointestinal lymphoma is the most common form of extranodal lymphoma. The clinical features, histological distributions, treatment results and prognosis of the primary intestinal lymphoma were evaluated. METHODS: A retrospective study was performed on 62 patients with primary intestinal lymphoma, as defined by Lewin's criteria, from May 1990 to February 2002. The WHO classification and Ann Arbor staging system were used for histological classification and staging, respectively. RESULTS: The sex ratio of the patients was 43: 19 (male: female), and the median age was 54 years. Abdominal pain, a palpable mass, and bleeding were the most frequent symptoms on presentation. The ileocecal area was the most frequent pathological site. Fifty-three cases were non- Hodgkin's lymphoma of B-cell origination; all of the remaining were T-cell originated. The mean survival period of B-cell and T-cell originated were 59.3 and 14.3 months, respectively (P<0.05). The 5 year survival rates of the patients in stage IE and IIE, and stage IIIE and IVE, were 52.4 and 32.6%, respectively (P=0.03). Six patients received surgery, 17 chemotherapy, and 39 surgery with adjuvant chemotherapy. Among the patients confined to stage IE and IIE, the 3 year survival rates of the surgery and surgery with adjuvant chemotherapy groups were 34 and 84%, respectively (P=0.0049). CONCLUSION: Primary gastrointestinal lymphoma of B-cell origination was predominant in relation to the WHO classification and revealed a better prognosis when compared to the T-cell originated lymphoma. For the patients with localized intestinal lymphoma, multimodality treatment (surgery with adjuvant chemotherapy) is preferred to the sole administration of chemotherapy.

Mucosa-Associated Lymphoid Tissue Lymphoma Following Kidney Transplantation / 대한혈액학회지

Posttransplant lymphoproliferative disorder (PTLD) is one of the most serious complication occuring after solid organ transplantation. In general, mucosa-associated lymphoid tissue (MALT) lymphoma of stomach has not been considered to be part of this spectrum, because most of the MALT lymphoma are associated with not EBV but H.pylori. Until now, there have been only a few cases of MALT lymphoma after transplantation. We report case of gastric MALT lymphoma following renal transplantation and review the reported cases in the literatures.