Ki-1 Anaplastic Large Cell Lymphoma Research Articles

Primary hepatic anaplastic large cell ki-1 lymphoma and celiac disease: a casual association?

Although liver is one of the extranodal organs commonly involved in both Hodgkin and non-Hodgkin lymphoma, Primary Hepatic Lymphoma (PHL) is rare. In non-immunocompromised patients, primary hepatic malignant non-hodgkin’s lymphoma is a rare disease, with less than 100 cases reported (1). Anaplastic large-cell lymphomas (ALCL) were first described by Stein et al. in 1985 (2) as large-cell neoplasms with a pleomorphic appearance, subtotal effacement of the lymph node structure and expression of the lymphoid activation antigen CD-30 (ki-1). ALCL frequently involves both lymph nodes and extranodal sites (3). The most common extra-nodal sites affected by ALCL include skin, bone, soft tissue, lung, and liver. However, is extremely rare for ALCL to present as a liver primary lymphoma, and only eight cases have been reported. ALCL accounts for approximately 3% of adult non-Hodgkin lymphomas. The neoplastic cells consistently express CD30 molecule in all variants. Most cases of ALCL are associated with the characteristic chromosomal translocation t[2;5], which results in up regulation of anaplastic lymphoma kinase (ALK) protein. We report a case of a primary hepatic anaplastic large T-cell ki-1 non-Hodgkin lymphoma in a 55-year-old patient with celiac disease.

Primary Pancreatic Lymphoma in Korea-A Single Center Experience

The aim of this study was to report a single center experience of primary pancreatic lymphoma (PPL) in Korea. We analyzed the clinicopathological data from four PPL patients (three male, median age 36 yr) diagnosed from 1997 to 2007 at Seoul National University Hospital. The diagnoses were: diffuse large B cell lymphoma (n=2), Ki-1 (+) anaplastic large cell lymphoma (n=1), and Burkitt lymphoma (n=1). Presenting symptoms and signs were: abdominal pain (n=4), pancreatitis (n=2), weight loss (n=2) and abdominal mass (n=1). No patient underwent surgery. The Ann Arbor stages of the patients were: IEA (n=1), IIEA (n=1), and IVEB (n=2). Two patients underwent treatment. The stage IEA patient underwent chemotherapy and radiation therapy that resulted in a complete remission. The stage IVEB patient who underwent chemotherapy relapsed. This patient underwent subsequent peripheral blood stem cell transplantation and is alive at 30 months. Two patients (stages IVEB and IIEA) without treatment died at 0.8 and 7.0 months, respectively. For PPL patients, chemotherapy-based treatment, and addition of radiation therapy, if possible, may offer good prognosis.

Asynchronous burst-suppression in a child with callosal Ki-1 anaplastic large cell lymphoma

A 13-year-old girl with Ki-1 anaplastic large cell lymphoma (Ki-1ALCL) bulky deposits in the brain developed raised intracranial pressure and coma associated with asynchronous burst-suppression following standard dose cranial irradiation. Supportive care, steroids, and chemotherapy resulted in clinical improvement. Burst-suppression coma may be reversible when secondary to tumor, decrease in steroids, or radiation effects; the asynchrony localizes the lesion to cortical interconnections such as the corpus callosum.

Primary ???Cutaneous??? T-Cell Anaplastic Large Cell Lymphoma, CD30+, Neutrophil-Rich Variant with Subcutaneous Panniculitic Lesions, in a Post-Renal Transplant Patient

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

Prevalence and characterization of anaplastic large cell lymphoma and its association with Epstein-Barr virus in Pakistani patients

Anaplastic large cell lymphoma (ALCL), CD30+, is a subtype of T-non-Hodgkin's lymphoma (NHL). Its most common form is a classical systemic type that involves multiple nodal and extranodal sites. In this study, morphologic, immunohistologic, and genetic studies were performed on ALCL cases in Pakistani patients. The median age of the patients in this study was 45 years (age range: 5–70 years), with a male to female ratio of 3.4:1. Thirty-seven (37) patients were diagnosed to have Ki-1 (CD30+) ALCL, which constituted 2% of all NHLs and 12.6% of all T-NHLs, over a period of 11 years (January 01, 1992–December 31, 2002). The tumors were of either T- or null-cell type with constant (100%) expression of CD30 (Ki-1). The majority of the cases (89.2%) expressed EMA, whereas 40.5% of the cases expressed either CD45 (LCA), CD45RO (UCHL1), or ALK. The mean age of ALCL patients with null-cell phenotype was 33.8 years as compared to those with T-cell phenotype having a mean age of 36.3 years. Out of the 37 cases diagnosed as ALCL, amplifiable DNA was isolated from 28 cases, which were further assessed for T-cell clonality for T-cell receptor (TCR)-β, γ, and immunoglobulin heavy chain (IgH) for the FR2 and FR3 regions. The polymerase chain reaction (PCR) technique demonstrated clonal rearrangement of the TCR β, γ, and IgH regions in 15 (53.6%), 11 (39.3%), and 2 (7.1%) ALCL cases, respectively, out of 28 cases. Association of Epstein-Barr virus (EBV) was noted in seven out of 28 cases (25%) of ALCL by PCR, whereas ISH for EBV-encoded nuclear RNA-1 (EBER-1) detected the presence of EBV in two (16.7%) out of 12 cases, where one was T-cell ALCL and the other null-cell ALCL. Immunostaining for LMP-1 could not be performed, because tissue material was not available. In conclusion, our study demonstrated that the prevalence of ALCL in Pakistan is comparable to that reported for some of the Asian communities and by the International Lymphoma Study Group and that EBV could be partly responsible for the pathogenesis of ALCL.

Posttransplant CD30+ (Ki-1) anaplastic large cell lymphoma: a case report and review of the literature.

Posttransplant CD30(+) (Ki-1) anaplastic large cell lymphoma (ALCL) is rare. A review of the literature revealed only 3 such cases. All 3 cases were developed after single-organ transplantation. We describe CD30(+) (Ki-1) ALCL in a dual-organ (liver and heart) transplantation recipient. The patient was a 68-year-old white female who underwent an orthotopic heart transplantation in 1999 and a liver transplantation in 2000. She presented with nausea and was found to have CD30(+) (Ki-1) ALCL by pathologic examination of the gastric antrum biopsy specimen. To our knowledge, this patient represents the first reported case of posttransplant CD30(+) ALCL following a dual-organ transplantation.

Combination of 13-cis Retinoic Acid and Interferon-α in the Treatment of Recurrent or Refractory Peripheral T-cell Lymphoma

We previously reported the therapeutic efficacy of 13-cis retinoic acid (13-cRA) in some subtypes of peripheral T-cell lymphoma (PTCL). This study sought to clarify if the addition of interferon- α 2a (IFN- α 2a), an agent with synergistic cytotoxicity with 13-cRA in many types of malignant cells, may be more effective in the treatment of PTCL. Eligible patients has histologically proven PTCL, which was recurrent after or refractory to anthracycline-containing systemic chemotherapy. The treatment included oral administration of 13-cRA 1 mg/kg/day, divided into three doses, and intramuscular injection of IFN- α 2a 4.5 MU/m 2, three times per week. From March 1995 to July 2000, a total of 17 patients, 10 men and 7 women, with a median age of 47 years (range, 18-77 years), were recruited. The histologic diagnosis included 7 cases of unspecified PTCL, 6 cases of Ki-1 anaplastic large cell lymphoma (ALCL), 1 case of angioimmunoblastic T-cell lymphoma, and 3 cases of angiocentric nasal NK/T cell lymphoma. They received a median of 1.7 months of treatment (range, 0.4-13.3 months). One patient refused further treatment due to toxicity. The doses of 13-cRA and IFN- α 2a had to be decreased in 7 and 7 patients, respectively. Grade III/IV hematologic and non-hematologic toxicity developed in 2 and 5 patients, respectively. There were 5 partial responses (Ki-1, 4; unspecified PTCL, 1), with a total response rate of 31.3% (95% Cl, 5.7-56.8%). The median duration of response for the responders was 2.5 months (range, 0.8-7.2 months). The median overall survival for the entire group of patients was 3.6 months. In conclusion, a combination of 13-cRA and IFN- α 2a is a useful salvage treatment for selected patients with recurrent or refractory PTCL, particularly those with the Ki-1 subtype. However, the data does not support that addition of IFN- α 2a is superior to 13-cRA alone.

Ki-1 anaplastic large cell lymphoma diagnosed on pleural fluid cytology

Ki-1 anaplastic large cell lymphoma diagnosed on pleural fluid cytology

Mature B-cell lymphoma/leukemia in children and adolescents: Intergroup pathologist consensus with the Revised European—American Lymphoma Classification

The Revised European-American Lymphoma (R.E.A.L.) Classification criteria were evaluated in the international protocol FAB LMB 96 Treatment of Mature B-cell Lymphoma/Leukemia: A SFOP LMB 96/CCG-5961/UKCCSG NHL 9600 Cooperative Study. This includes B-lineage lymphomas: Burkitt's lymphoma (including ALL-L3); high-grade B-cell lymphoma, Burkitt-like; diffuse large B-cell lymphoma (excluding anaplastic large cell Ki-1 lymphoma). Cases were independently reviewed by eight hematopathologists from the three cooperative national groups (two SFOP, two CCG, four UKCCSG), without prior discussion of classification criteria or guidelines for case rejection. Consensus diagnosis was determined by each national cooperative group, and final consensus diagnosis established when at least two national consensus diagnoses were in agreement, or following group agreement at a multiheaded microscope. Two hundred eight cases were reviewed, with final consensus diagnosis established in two hundred three. The percent agreement of each group's national consensus diagnosis with final consensus diagnosis was 86%, 86% and 71%. The percent agreement of the group's national consensus diagnosis with final consensus diagnosis for Burkitt's and diffuse large B-cell lymphoma were 88% and 80%, respectively, but only 42% for Burkitt-like lymphoma. International panel review of mature B-cell lymphoma/leukemia in children and adolescents highlighted difficulties in subclassification, particularly with Burkitt-like, which is a 'provisional entity' in the R.E.A.L. Classification. The absence of previous discussion of classification and guidelines for case rejection may in part explain the discrepancy between pathologists. These results underline that morphology may need to be complemented by other studies, such as molecular genetic and cytogenetics, to discriminate between the mature B-cell lymphomas.

COULD CISPLATIN AS A FRONT-LINE TREATMENT IN CHILDHOOD NON-HODGKIN'S LYMPHOMA BE A PROMISING THERAPY?

Non-Hodgkin's lymphomas (NHL) were often erroneously diagnosed as other malignancies and treated accordingly. In this study cisplatin combined with vincristine, cyclophosphamide, and Adriamycin was used incidentally as a front-line treatment in seven children with NHL, because the initial histologic diagnosis was that of a sarcoma. After reevaluation three patients had Ki-1 anaplastic large cell lymphoma of T-cell origin, two abdominal B-cell diffuse high-grade NHL, one mediastinal diffuse large B-cell lymphoma, and one B-cell lymphoma in the stomach. They received at least two courses of cisplatin combined regimen and continued with other protocols for NHL. All patients showed an extremely good response from the first course of therapy and the masses vanished completely. They were followed up for a mean time of 29.5 months and are all in complete remission. The data indicate that cisplatin is active against NHL and might be a promising alternative front-line therapy.

CD30 differential staining is useful in classifying lymphomas intermediate between Hodgkin's disease and anaplastic large cell (Ki1) lymphoma.

The authors analyzed the BerH2 reactivity patterns of the tumor cells in 23 Hodgkin's lymphomas (HD), in 13 CD30+ anaplastic large cell (Ki1) lymphomas (ALCL), in two HD with transition to secondary CD30+ ALCL, and in six additional lymphomas intermediate between HD and ALCL. Paraffin blocks of formalin-fixed biopsies were immunostained. Immunostaining was modified by pronase digestion and by microwave assistance. Hodgkin-Reed-Sternberg (HRS) cells of all 23 Hodgkin's lymphomas were reactive for BerH2, but the reactivity patterns differed: after pronase digestion, HRS cells of 17/23 Hodgkin's lymphomas showed exclusively or at least predominantly cytoplasmic BerH2 reactivity, whereas only four Hodgkin's lymphomas presented with prominent membrane-bound positivity. Microwave processing in 16/23 Hodgkin's lymphomas induced membrane-bound BerH2 positivity in the HRS cells; a minority of five cases retained the distinct cytoplasmic pattern. In contrast, 10/13 ALCLs were characterized by membranous reactions, independent of whether pronase or microwave pretreatment had been applied. The CD30+ ALCLs secondary to HD also showed a tendency towards membranous positivity more than did the antecedent Hodgkin's lymphomas. In the HD/ALCL borderline group, 3/6 cases revealed cytoplasmic BerH2 patterns after pronase digestion and thus were more closely related to HD, whereas 2/6 cases reacted with membranous positivity as did the genuine ALCLs of our series. We conclude from these findings that the above modifications in CD30 immunostaining can be helpful in the characterization of lymphomas that constitute a continuous histomorphological as well as phenotypical spectrum between HD and ALCL.

Primary CD30-positive anaplastic large cell lymphoma of the lip

We report a case of primary CD30-positive anaplastic large cell lymphoma of the lip. While extranodal involvement is not uncommon in Ki-1(CD30) anaplastic large cell lymphoma, this is the first reported case of primary lip involvement. The clinical features and clinical outcome in Ki-1 anaplastic large cell lymphoma are discussed.

Multiple Giant Cell Tumors in a Patient with Gulf War Syndrome

"Persian Gulf syndrome" refers to a group of clinical findings found in military personnel who served in the Persian Gulf War. The most commonly reported symptoms include chronic fatigue, headache, and neurologic disorders. Recently, new information has linked Whipple's disease and Ki-1 anaplastic large cell lymphoma to this syndrome. Presented here is an unusual case of multiple giant cell tumors of the hand in a patient with documented Persian Gulf syndrome. The epidemiologic significance between these two entities is unclear, because this is a single reported case. However, the practical message is clear. Physicians must meticulously evaluate patients who are veterans of the Persian Gulf conflict to further our understanding and confirm the existence of this syndrome.

Ki-1 Anaplastic Large-Cell Lymphoma in the Differential Diagnosis of Unknown Primary Cancer

The importance of immunohistochemical analysis of anaplastic or undifferentiated carcinoma, especially in the setting of an unusual clinical presentation, is illustrated by two cases of metastatic undifferentiated carcinoma. Re-evaluation of pathological material resulted in a diagnosis of Ki-1 lymphoma and led to substantial alteration in therapeutic strategy and long-term outlook. The response to therapy was unusually favorable in both cases, and survival was prolonged in both. Archival pathological material was retrieved in order to perform special studies that were not originally available at the time of diagnosis, consisting of immunoperoxidase detection of hematological markers that are preserved in formalin-fixed, paraffin-embedded tissues. Both tumors were found in retrospect to actually represent anaplastic, Ki-1-positive, large-cell lymphoma. This neoplastic entity has been introduced to the oncologic literature only within the past decade. Because this neoplasm shows chemosensitivity and responsiveness similar to that of other large-cell lymphomas, we alert paractitioners to consider this diagnosis in any patient who presents with an apparently metastatic undifferentiated tumor.

Clinicopathologic, cytogenetic, and molecular studies of 13 Chinese patients with Ki-1 anaplastic large cell lymphoma: Special emphasis on the tumor response to 13-Cis retinoic acid

The clinicopathologic and molecular features of the newly characterized Ki-1 lymphoma, although well studied in Western countries, are less well described in Asia. Pathology material of lymphoma cases, consecutively diagnosed at our institution between 1986 and 1994, was reviewed. The cases fulfilling the diagnostic criteria of Ki-1 lymphoma were selected, and their clinicopathologic features were studied. Immunohistochemistry and cytogenetic studies of the lymphoma tissues, and molecular analysis for nucleophosmin (NPM) gene translocation were performed. A total of 13 cases (2.3%) of Ki-1 large cell lymphoma were identified from a total of 572 cases of non-Hodgkin's lymphoma diagnosed during this period of time. There were 10 men and 3 women with a median age of 43 years (range, 18 to 61 years). The initial presenting sites included the skin alone in five cases, lymph node alone in one case, both skin and lymph node in five cases, and the stomach in one case. All cases had large cell morphology, with the majority of the neoplastic cells expressing Ki-1 antigen (CD30). Except for the case with gastric involvement, all other cases were T-cell lymphomas. One of seven cases examined had chromosomal abnormality of t (2;5). Rearrangement of the NPM gene at chromosome 5 was detected by Southern blot analysis in three of nine cases. Two of seven cases tested by reverse-transcriptase polymerase chain reaction showed fusion of the NPM gene and anaplastic lymphoma kinase gene. Seven (78%) of 9 patients who had received systemic chemotherapy with a standard cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen obtained a complete remission (CR). The median duration of remission was 33 months. Three (60%) of 5 patients, of whom 4 recurred from previous intensive chemotherapy, achieved a prolonged CR with treatment with 13-cis retinoic acid (RA). The median survival of the whole group has not yet been reached at a median follow-up of 40 months. The clinicopathologic and molecular features of Ki-1 lymphoma of Chinese patients are comparable to those reported from Western countries. 13-cis RA appears to be an effective treatment of Ki-1 lymphoma.

Ki-1 anaplastic large cell lymphoma with a prominent leukemic phase

Patients with Ki-1 (CD30)-positive anaplastic large cell lymphoma (ALCL) occasionally have rare circulating lymphoma cells. We report a case of ALCL with a prominent leukemic phase. A 36-year-old man presented with widespread ALCL involving lymph nodes, spleen, pleural fluid, cerebrospinal fluid, and bone marrow. His white blood cell count was 106,000/mm 3 with 20% lymphoma cells. The circulating neoplastic cells were large, and had irregular nuclei with multiple small nucleoli, ample cytoplasm, and multiple clear cytoplasmic vacuoles. This case illustrates that ALCL may have a marked leukemic phase composed of large anaplastic cells.

AIDS lymphoma.

Most AIDS-related non-Hodgkin's lymphomas can be categorized into one of three histologic subtypes: large-cell immunoblastic, small non-cleaved cell (Burkitt's or Burkitt's-like) and diffuse large cell. Rare histologies include Ki-1 anaplastic large cell lymphoma, angiotropic large cell lymphoma, mucosa-associated lymphoid tissue, primary pulmonary T-cell lymphoma, and Sézary syndrome. Although the role of Epstein-Barr virus remains uncertain, a new herpes virus, human herpes virus 8, has been identified in the rare subset of effusion-based lymphomas. Overexpression of the cytokines interleukin-6 and interleukin-10 may have a role in pathogenesis, and they may serve as potential therapeutic targets. In addition, chronic antigenic stimulation may correlate with elevated serum CD22 levels and may serve as a tool for early detection. Novel investigational therapies in clinical development include new chemotherapy-based regimens, immune modulators, antibody therapy, as well as cellular therapy.

Cytology of extranodal Ki‐1 anaplastic large cell lymphoma

Ki-1-positive anaplastic large-cell lymphoma (ALCL) is an uncommon neoplasm which may present with extranodal as well as nodal disease. By definition, the tumor cells are immunoreactive for Ki-1 or Ber-H2 antigen (CD30). There have been few published cytologic descriptions of this lymphoma, or of its detection in extranodal sites. We describe the cytologic findings in five cases of extranodal Ki-1 lymphoma. Cytologic findings in all five cases were similar and consisted of a heterogeneous population of lymphocytes and bizarre, pleomorphic tumor cells. These cells were characterized by generous amounts of vacuolated, basophilic cytoplasm, eccentric, multilobulated nuclei with some showing “wreath-like” configurations. Some nuclei contained huge nucleoli simulating Reed-Sternberg cells. All cases showed the characteristic surface membrane and cytoplasmic paranuclear dot-like staining for CD30. Our findings indicate that fine-needle aspiration and exfoliative cytology have a useful role in the diagnosis of Ki-1 ALCL in extranodal sites. Furthermore, effusions containing anaplastic cells suspicious for lymphoma, particularly in AIDS patients, should be immunostained with antibodies to CD30. Diagn Cytopathol 1996;14:155–161. © 1996 Wiley-Liss, Inc.

Extracorporeal photochemotherapy in a patient with Ki-1-positive anaplastic large-ceil lymphoma

A 57-year-old man with Ki-1 anaplastic large-cell lymphoma treated with extracorporeal photochemotherapy is described.

Aggressive primary hepatic lymphoma in Chinese patients. Presentation, pathologic features, and outcome.

Primary non-Hodgkin's lymphoma of the liver is rare. In this study, the presentation, pathologic features, and outcome of seven Chinese patients with primary hepatic lymphoma are described. From 1984 to 1994, the clinical records of 14 Chinese patients with non-Hodgkin's lymphoma and histologically proven liver involvement were reviewed. Seven (four males, three females; median age, 54 years) were considered to have primary hepatic lymphoma. Histologic and immunohistochemical studies were performed on paraffin embedded liver tissue. "B" symptoms including fever (86%) and weight loss (57%) were the most striking presenting features. Hepatomegaly was present in all patients, splenomegaly in three (43%), and thrombocytopenia in six (86%). Only one patient was hepatitis B surface antigen-seropositive. None had preexisting liver disease. Histologic subtypes, though heterogeneous, were mostly unfavorable and consisted of diffuse large cell lymphoma (two patients), small lymphocytic lymphoma (one patient), lymphoblastic lymphoma (one case), mantle cell lymphoma (one patient), anaplastic large cell Ki-1 lymphoma (one patient), and hepatosplenic T-cell lymphoma (one patient). Three patients expressed B-cell and 2 expressed T-cell phenotypes. Six patients received cytotoxic chemotherapy. One had resection and one had splenectomy, but none achieved complete remission, and only one remained alive as of this writing. The median survival was 3.7 months (range, 8 days to 47.7 months). Chinese patients with primary non-Hodgkin's lymphoma of the liver have prominent "B" symptoms, disease with a highly aggressive course, a poor response to local and systemic treatment, and short survival. Hepatitis B virus infection is not a major etiologic factor for these patients.