Primary effusion lymphoma in Taiwan shows two distinctive clinicopathological subtypes with rare human immunodeficiency virus association.

AIMS: To investigate the clinicopathological and molecular features of primary effusion lymphoma (PEL) in Taiwan and the association with human immunodeficiency virus (HIV), human herpesvirus 8 (HHV8) and Epstein-Barr virus (EBV). METHODS AND RESULTS: We investigated retrospectively 26 cases with a median age of 76.5. Only one (4%) patient was infected with HIV. Cytologically, all lymphoma cells revealed typical immunoblastic to plasmablastic morphology. Immunohistochemically, HHV8 was positive in eight (32%) tumours and negative in 17 (68%) cases. All 23 tested cases examined were of the non-germinal-centre B cell phenotype. MYC proto-oncogene (MYC) and Epstein-Barr encoding mRNA (EBER) were positive in 43% (nine of 21) and 17% (four of 23) cases, respectively. Immunoglobulin heavy chain (IGH), B cell lymphoma (BCL)2, BCL6 and MYC were rearranged in 71%, 11%, 12% and 18% cases, respectively. By univariate analysis, the overall survival (OS) was associated statistically with MYC expression (P = 0.012) and BCL2 rearrangement (P = 0.035), but not with the others. By multivariate analysis, no factor was statistically significant. Compared to the HHV8-negative cases, the HHV8-positive cases were mainly of the plasmablastic immunophenotype expressing CD30 and CD138, and with a less frequent expression of pan-B cell markers. CONCLUSIONS: Apart from the phenotypical difference, our HHV8-positive neoplasms were not distinct from the HHV8-negative group. Literature review of 256 cases, including our cases, revealed that HHV8-positive cases were associated more frequently with HIV and EBV infection, with rare MYC rearrangement, and a poorer prognosis than HHV8-negative cases. We propose to name the HHV8-positive cases as 'classical' or 'type I PEL' and the HHV8-negative cases as 'type II PEL', stressing the similarities and the distinctive features between these two groups.

Ciliated muconodular papillary tumor of the lung: a newly defined peripheral pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: a case report and review of literature.

We report the case of a 68-year-old man with a newly defined rare entity of a peripheral pulmonary tumor, consisting of a nodular papillary lesion with papillary structures containing ciliated columnar and goblet cells, as well as floating tumor cells in the mucin pool. The conspicuous mucin pool was observed to be mimicking colloid adenocarcinoma in a low-power view, particularly in a frozen section slide. We originally reported it as an adenocarcinoma during intraoperative consultation. Immunohistochemically, the tumor cells exhibited a similar immunophenotype to pulmonary adenocarcinoma, except for the presence of focal ciliated and basaloid cells, which we found using CK5/6 and P63 immunostaining. No KRAS or EGFR mutation was found. We revised the diagnosis to that of a ciliated muconodular papillary tumor (CMPT). Four years after a wedge resection, the patient remained free of tumors. Although the malignant potential of CMPT cannot be ignored, a wedge resection with a safe margin might be a treatment option for CMPT patients.

Cutaneous EBV-positive γδ T-cell lymphoma vs. extranodal NK/T-cell lymphoma: a case report and literature review.

Primary cutaneous γδ T-cell lymphoma and extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type are two distinct lymphoma entities in the World Health Organization (WHO) classification. We report the case of an aggressive cutaneous lymphoma of γδ T-cell origin showing overlapping features of both lymphomas. A 78-year-old female presented with confluent erythematous plaques with ulcerations over her right thigh. Microscopically, section of the skin showed a diffuse dermal and subcutaneous lymphocytic infiltration with tumor necrosis and angioinvasion. The medium- to large-sized tumor cells expressed CD3, CD8, cytotoxic molecules and T-cell receptor (TCR)-γ but not CD4, CD20, CD30, CD56 or ßF1. In situ hybridization for Epstein-Barr virus-encoded mRNA (EBER) was diffusely positive. Polymerase chain reaction-based clonality assay showed a clonal TCR-γ chain gene rearrangement. The features compatible with γδ T-cell lymphoma include dermal and subcutaneous involvements, cytotoxic phenotype, expression of TCR-γ, as well as an aggressive course. On the other hand, the diffuse EBER positivity, angioinvasion, tumor necrosis and cytotoxic phenotype may also fit in the diagnosis of an ENKTL of T-cell lineage. We review the literature on EBER-positive γδ T-cell lymphoma and discuss the diagnostic dilemma using the current WHO classification system.

Uterine lipoleiomyosarcoma: report of 2 cases and review of the literature.

Uterine lipoleiomyosarcoma is a rare entity with only 6 case reports in the Pubmed database at the time of writing this article. We report 2 additional cases of uterine lipoleiomyosarcoma, characterized on microscopy by coexistence of leiomyosarcomatous and liposarcomatous components, with focal intermingling, without an intervening lipoleiomyomatous area. The liposarcomatous component in both of our cases had the morphology of myxoid liposarcoma. Both cases underwent postoperative chemotherapy. One of our cases had recurrence in the pelvis with microscopic features of myxoid liposarcoma. This patient died with multiple metastases 4.5 yr after hysterectomy, with the metastatic lesions being liposarcomas, without an evident leiomyosarcomatous component. Although lacking a treatment protocol because of the rarity of such cases, postoperative adjuvant therapy is mandatory.

Mast Cell Sarcoma of the Retroperitoneum With Concurrent Systemic Mastocytosis and an Undisclosed Associated Hematologic Neoplasm: A Case Report.

Mastocytosis is a rare disorder affecting both children and adults by gathering of functionally defective mast cells in the body's tissues. The World Health Organization (WHO) classified mastocytosis into cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma (MCS). We hereby present a case of retroperitoneal MCS with concurrent systemic mastocytosis and an undisclosed associated hematological neoplasm (SM-undisclosed AHN). The diagnosis of MCS and SM was made after the second biopsy over retroperitoneal mass, lymph node, and ovary for rapidly progressive disease with the presentation of unexplained recurrent flushing, palpitation, and shock, in addition to abdominal pain. A clonal myeloid neoplasm was also suspected by the karyotype and hemogram data. Unfortunately, the patient succumbed to the disease quickly. Apart from this unique case, the previously reported cases of SM with MCS in the literature were also reviewed.

MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Targeted Next-generation Sequencing Reveals a Wide Morphologic and Immunophenotypic Spectrum of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma.

Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.

Primary appendiceal precursor B lymphoblastic lymphoma with peculiar morphology mimicking diffuse large B cell lymphoma.

Precursor B lymphoblastic neoplasm usually presented as childhood leukemia. Most precursor lymphoblastic lymphoma are T-cell lineage and precursor B lymphoblastic lymphoma constitutes only about 10% of cases according to the WHO Classification of Tumours of Haematologic and Lymphoid Tissues. The most frequent sites of involvement in precursor B lymphoblastic lymphoma are the skin, soft tissue, bone and lymph nodes. Primary appendiceal involvement is an uncommon condition. We present an unusual case of primary appendiceal precursor B lymphoblastic lymphoma in an 11-year-old boy with peculiar histological morphology mimicking diffuse large B cell lymphoma. Histologically, the tumor was composed of diffusely infiltrated large cells from mucosa and extended to the subserosal area. The tumor cells were positive to CD79a, CD20, PAX5, BCL2, CD10, TdT, p53 but not to CD3, BCL6 and CD34 by immunohistochemical studies. The response to conventional treatment regimen for lymphoblastic lymphoma was not good, with early relapse within three months. Partial remission was achieved by adding rituximab. Unfortunately, the patient died in ten months due to uncontrolled relapsed disease with generalized lymphadenopathy and massive pleural effusion. The special morphologic changes and poor response to chemotherapy may be related to the overexpression of p53.

Aberrant expression of CD19 and CD43 in a patient with therapy-related acute myeloid leukemia and a history of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with frequent involvement of the gastrointestinal tract and peripheral blood (PB). In addition to the B cell markers, the neoplastic cells express CD5 and CD43. In patients with a prior history of MCL with PB involvement, the appearance of leukemic cells after chemotherapy usually heralds a relapse, particularly if the leukemic cells express B cell markers and CD43. We report a patient with MCL who presented with multiple lymphomatous polyposis of the intestine. The staging procedures revealed the involvement of lymph nodes, bone marrow and PB. Three years after chemotherapy, thrombocytopenia with the appearance of rare leukemic cells in the PB was noted. Leukemic cells obtained from bone marrow aspirate expressed CD19 and CD43, suggesting a relapse. Detailed cytomorphological and immunophenotypic studies unveiled the myeloid nature of these leukemic cells, and a diagnosis of therapy-related acute myeloid leukemia was made. This case illustrates the importance of morphologic examination and performing a complete antibody panel in the diagnosis of a suspected relapse in patients with a prior history of lymphoma.

Pituitary spindle cell oncocytoma presented as pituitary apoplexy.

Spindle cell oncocytoma is a rare nonfunctioning neoplasm of the adenohypophysis, and was first described in 2002 by Roncaroli et al. In 2007, spindle cell oncocytoma has been categorized as a separate entity by the World Health Organization (WHO) and is classified as a Grade 1 tumor of the central nervous system. Spindle cell oncocytoma of pituitary gland usually occurs in adults and accounts for 0.1-0.4% of all sellar region tumors. Clinically and radiologically, they are indistinguishable from nonfunctioning pituitary adenomas. From 2002 to 2018, approximately 46 cases of spindle cell oncocytoma of pituitary gland had been reported in the English literature and we would like to report a case of 28-year-old woman presented with pituitary apoplexy proved to be a case of spindle cell oncocytoma of pituitary gland which probably will be the 47th reported case.

Adenomyoma of the jejunum --- a rare cause of gastrointestinal bleeding.

Adenomyoma of the small intestine is rare. It occurs mostly in the periampullary region or ileum. The common presentations are intussusception and intestinal or biliary obstruction, depending on the location. To our knowledge, gastrointestinal (GI) bleeding from a jejunal adenomyoma has not been reported previously. We present a 74-year-old female patient who suffered intermittent tarry stool passage for 1 month. Initial upper GI endoscopy, colonoscopy and computed tomography failed to find the bleeder. A papilla-like tumor with central depression and active bleeding in the proximal jejunum was found by push enteroscopy. Exploratory laparotomy showed a submucosal nodule about 1.5 cm in size located about 20 cm distal to the Treitz ligament. Wedge resection was carried out. Pathologic examination revealed that the tumor was composed of some cystic exocrine-type ducts and bundles of smooth muscle, indicating adenomyoma. The patient was symptom-free following operation.

Mycosis fungoides in Taiwan shows a relatively high frequency of large cell transformation and CD56 expression.

Mycosis fungoides (MF) is an indolent cutaneous T-cell lymphoma and may transform into large cell lymphoma in the disease course. The incidence of MF in Taiwan is lower as compared to that in the West. In this study we aimed to characterise the clinicopathological, immunohistochemical, and genetic features of transformed MF (t-MF) in Taiwan. We retrospectively collected MF cases from April 2004 to April 2015 from four medical centres in Taiwan, reviewed the clinical history and histopathology, and performed immunohistochemistry, in situ hybridisation for EBV (EBER), and fluorescence in situ hybridisation (FISH) for DUSP22/MUM1 gene translocation. Fifty-one specimens from 32 patients with MF were identified with a male to female ratio of 1.5:1 and a median age of 50.5 (range 16-82). Tumours from 11 patients (34%) underwent large cell transformation, with the median age at 61 (range 26-82). The tumour cells of t-MF expressed CD30 and MUM1 in 82% and 100% cases, respectively. CD56 was expressed in two (10%) of 21 MF cases and two (18%) of 11 t-MF cases, respectively; and all four CD56-positive cases were of a helper T-cell phenotype. All CD56 expressing MF and t-MF tumours tested for EBER were negative. FISH study showed rearranged DUSP22/IRF4 in one (9%) of 11 t-MF cases, but not in any of the 19 non-transformed MF specimens. Four patients with t-MF died of disease and six were alive with disease in a median follow-up time of 25 months (mean 44.7 months). Large cell transformation and aberrant CD56 expression were more frequent in patients with MF in Taiwan compared to those in the West. Larger case series and/or national studies are needed to clarify the significance and impact of large cell transformation on the prognosis of patients with MF.

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis.

Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n=8), polycythemia vera (n=3), and chronic myelomonocytic leukemia (n=4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.

Histopathology and immunohistochemistry in distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma with very high proliferation index and with or without a starry-sky pattern: a comparative study with EBER and FISH.

Burkitt lymphoma (BL) is characterized by c-myc translocation and CD10+/bc-2-/bcl-6+ with a very high Ki-67 proliferation index (PI). Occasional diffuse large B-cell lymphomas may exhibit a very high PI with or without a starry-sky pattern (DLBCL-HPSS). We compared 28 consecutive BL and 16 DLBCL-HPSS cases in immunocompetent Taiwanese diagnosed by histopathologic examination and immunophenotyping and compared the results with results for Epstein-Barr virus-encoded messenger RNA (EBER) and fluorescence in situ hybridization (FISH). There were statistically significant differences in the expression of CD10 (28/28 vs 1/16), bcl-2 (3/28 vs 11/16), MUM1 (5/28 vs 15/16), a PI of 95.0% or more (27/28 vs 2/16), and combined CD10+/bcl-2-/bcl-6+ (24/28 vs 1/16) between BLs and DLBCL-HPSSs. Of the BLs, 7 (25%) of 28 and 26 (96%) of 27 were positive for EBER and c-myc rearrangement as compared with 0 of 16 and 1 (7%) of 15 DLBCL-HPSSs, respectively. We can confidently distinguish BL from DLBCL-HPSS by using histopathologic and immunohistochemical (CD10, bcl-2, bcl-6, Ki-67) methods without the aid of EBER and FISH in the great majority of cases.

EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma.

We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (>/=1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.

Primary cardiac lymphoma with unusual presentation: A report of two cases.

Primary cardiac tumors are rare, with an incidence of 0.056% according to autopsy reports. The most common type is myxoma, while other types, including sarcoma, lipoma, papillary fibroelastoma, rhabdomyoma, fibroma, hemangioma, teratoma, lymphoma and mesothelioma also occur. Primary cardiac tumors usually cause embolization, pericardial effusion and arrhythmia, leading to heart failure. Only 10% of primary cardiac tumors are malignant, approximately 95% of which are sarcomas, while the remaining 5% are cardiac lymphomas and mesotheliomas. The present study reported a case of primary cardiac lymphoma (PCL) with bilateral renal involvement and a case of PCL with bilateral adrenal gland involvement. The prognosis of PCL is poor due to the low rate of early detection and treatment. The definitive diagnosis is dependent on pathology, and timely treatment with chemotherapy can be effective. The two cases developed life-threatening arrhythmia and responded to the initial chemotherapy. In the first case, complete remission was achieved after finalization of therapy. However, the second case refused further chemotherapy and succumbed to his condition after two months.

Primary non-Hodgkin's lymphoma of bone: a rare disorder with high frequency of T-cell phenotype in southern Taiwan.

Primary non-Hodgkin's lymphoma of bone (PLB) is a rare disorder representing less than 1% of all non-Hodgkin's lymphomas and has rarely been reported in Taiwan. A retrospective clinicopathological study was performed according to the 2002 World Health Organization criteria and identified 14 cases during a 13-year period in 2 medical centers in southern Taiwan. There was male predominance (M:F = 6:1) with a median age of 42 and bone pain (6 patients, 43%) as the most common symptom. Half of the patients had monostotic and the other half polyostotic lesions. Axial skeletons (10 cases, 71%) were the most frequent sites of involvement. The staging results were stage I (9 patients, 64%), stage II (2, 14%) and stage IV (3, 21%). Eight cases (57%) were of B-cell phenotype and the remaining 6 (43%), T-cell. Histologically, 7 (50%) were diffuse large B-cell lymphomas (DLBCLs) and 5 (36%) anaplastic large cell lymphomas. Seven patients received chemotherapy and radiotherapy; 4 chemotherapy and 3 radiotherapy alone. Of the 11 patients with follow-up information, 6 (55%) died of disease within 1 year including 5 with T-cell lymphomas, while all the 5 patients surviving over 1 year were of B-cell phenotype. The overall 1-year survival rate was 45%. The survival of B-cell lymphomas was significantly better than T-cell tumors (p = 0.016, log-rank test). In summary, this study reported the largest series of PBL in Taiwan and confirmed that the majority was DLBCL and B-cell tumors had more favorable prognosis. As compared to the Western series, the cases showed a striking male predominance, higher percentage of axial skeleton involvement, higher relative frequency of T-lineage tumors and poorer prognosis.

A clinicopathologic and molecular study of follicular lymphoma in Taiwan.

BACKGROUND: The clinicopathologic and molecular features of follicular lymphoma (FL) in Taiwan have not been well defined. We conducted a retrospective study including history review, immunohistochemistry, and molecular study for the major breakpoint region (MBR) of t(14;18) and correlated these findings with survival. PATIENTS AND METHODS: Sixty-five FLs were identified, with a male to female ratio of 1.9:1 and a median age of 63 years (mean, 60 years). Sixty cases (92%) were nodal, 4 (6%) were extranodal, and 1 (2%) was indeterminate. The median ages of the nodal and extranodal cases were 63 years and 44 years, respectively. Disease staging in 59 patients included 15 patients (25%) with stage I disease, 14 (24%) with stage II, 20 (34%) with stage III, and 10 (17%) with stage IV. Forty-four patients received chemotherapy, 2 patients received chemotherapy with palliative radiation therapy, and 13 patients received supportive treatment/observation. RESULTS: The 5-year survival rate was 52.6%. The cases were classified as grades 1 (n = 27; 42%), 2 (n = 22; 34%), 3A (n = 13; 20%), and 3B (n = 3; 5%). Twenty cases (31%) were positive for MBR, including 19 of 57 (33%) nodal cases and 1 of 4 (25%) primary extanodal FLs. Patients with low-stage disease (stages I/II) had a better survival rate than patients with high-stage disease (III/IV; log-rank test, P = 0.012). CONCLUSION: This is the largest series of Taiwanese FLs with immunophenotypes and MBR detection rates similar to those of the West. Disease stage was statistically significant with regard to survival. Although the number of extranodal FLs cases was small, the patients were younger, their tumors had lower CD10 expression, and they had more favorable survival rates than patients with nodal disease.

Primary extranodal natural killer/T-cell lymphoma of bronchus and lung: A case report and review of literature.

Primary pulmonary non-Hodgkin's lymphoma (NHL) is very rare. It represents less than 1% of all NHL, and 0.5-1% of all primary pulmonary malignancies. Almost all cases of primary pulmonary NHL originate from B-cell lineage. We present a case of a 53-year-old man with primary extranodal NK/T-cell lymphoma of the bronchus and lung, presented progressive dyspnea caused by right lower lung consolidation, and pleural effusion. Initial chest computed tomography suggested advanced lung cancer. Bronchofiberscopy showed a polypoid tumor on which a biopsy was performed. Histologically, the diffusely infiltrative atypical cells were positive for cytoplasmic CD3, CD56, granzyme B, and negative for cytokeratin, CD20 immunostains, suggesting NK/T cell lineages. In situ hybridization for Epstein-Barr virus encoded ribonucleic acid (EBER) was positive. Herein, we discuss the clinicopathological features of this case and review the literature on primary extranodal NK/T-cell lymphoma of the lung. Compared with other patients, who died after the first cycle of chemotherapy and/or within three months, our patient had longer survival under aggressive chemotherapy and auto-peripheral blood stem cell transplantation.