Ki-1-positive anaplastic large cell lymphoma initially diagnosed as Hodgkin's disease by fine needle aspiration (FNA) cytology

A 45-year-old male presented with a large mass in the left axilla. FNA cytology was interpreted as Hodgkin's disease (HD), lymphocyte depletion (LD) type, but histopathologic and immunohistochemical examination showed features of Ki-1-positive anaplastic large cell lymphoma. Unrepresentative sampling by the FNA from the tumour periphery resulted in a false impression of dual reactive and neoplastic cell populations. which together with the frequent Reed-Sternberg-like cells led to the initial erroneous impression of HD. Therefore, the cytologic diagnosis of HD, LD should be approached with caution.     

Spontaneous anaplastic large cell lymphoma in a chimpanzee: A clinicopathological and immunohistochemical study

Abstract: An anaplastic large cell lymphoma with disseminated abdominal metastases was diagnosed in a 35-year-old male chimpanzee. Clinically, the animal displayed lethargy, weight loss, ascites, and abdominal distention. Imaging studies showed several large abdominal masses. At necropsy, variably sized masses of neoplastic mesenteric lymph nodes that encompassed several intestinal loops were present throughout the abdomen. The largest mass measured 9 × 5 cm and had cauliflower-like protrusions into the jejunal lumen. The entire abdominal cavity was covered by a sheet of neoplastic tissue. Histopathologically, the tumor consisted of solid sheets of proliferating lymphoid cells forming a cohesive growth that filled the lymph node sinuses. The tumor had invaded the intestinal wall. Anaplastic large cell lymphoma was diagnosed from immunohistochemistry findings on the basis of positive reaction to the CD3 and CD30 markers and negative reaction to the CD20 marker. Serologic analysis revealed positive titers for Epstein-Barr, cytomegalo-, and varicella-zoster viruses. Both serologic and virologic studies showed no evidence of detectable retroviral infection. This type of tumor has not been reported before in the chimpanzee.     

RNASET2--an autoantigen in anaplastic large cell lymphoma identified by protein array analysis

Characterising tumour-associated antigens (TAAs) not only represents an important approach to the identification of new diagnostic/prognostic markers, but can also provide information on disease processes and additional potential therapeutic targets. Preliminary screening of a protein macroarray, containing more than 12,000 different proteins, with sera from anaplastic lymphoma kinase (ALK)-negative and ALK-positive anaplastic large cell lymphoma (ALCL) patients identified ribonuclease and tumour suppressor protein Ribonuclease T2 (RNASET2), phosphatase lipid phosphate phosphatase-related protein type 3 (LPPR3) and apoptotic adaptor molecule Fas-associating protein (FADD) as ALK-negative ALCL-associated TAAs. Further validation of these observations was confirmed using the ALCL sera in reverse ELISAs. The circulating anti-RNASET2 autoantibodies present in ALCL patients' sera also recognised eukaryotically expressed RNASET2 protein. RNASET2 expression was then investigated in normal tissues and in lymphomas to explore its clinical potential. RNASET2 protein and mRNA levels showed highest expression in the spleen, leucocytes and pancreas. RNASET2 protein expression was not restricted to ALK-negative ALCL (81%), being expressed in ALK-positive ALCL (65%) as well as in a number of other lymphomas. The immunological recognition of RNASET2, its expression in ALCL and other lymphomas together with its known tumourigenic properties suggest that further studies on this autoantigen are warranted.     

Cytomorphologic differentiation of Hodgkin's lymphoma and Ki-1+ anaplastic large cell lymphoma in fine needle aspirates

OBJECTIVE: To cytomorphologically differentiate Hodgkin's lymphoma (HL) from Ki-1+ anaplastic large cell lymphoma (ALCL) in fine needle aspirates. STUDY DESIGN: We blindly reviewed 63 fine needle aspiration (FNA) smears from histologically and immunophenotypically proven cases of ALCL (n = 15) and HL (n = 48). The smears were reviewed for the following criteria: (1) estimated percentages of abnormal cells, (2) pattern of the smears (polymorphous vs. dimorphous), and (3) presence or absence of multilobated cells. RESULTS: All cases were phenotyped by immunohistochemistry for CD3, CD15, CD20, CD30 and CD45, with flow cytometric immunophenotpyping in 41 cases. Flow cytometric phenotyping was not successful in any of the cases. The smears were polymorphous in all 15 cases of ALCL and in 1 case of HL (2%). The percentage of abnormal cells ranged from 10% to 90% in cases of ALCL (median, 30%) whereas it ranged from 1% to 25% in HL (median 3%; P = .0003). Three cases of HL showed abnormal cells constituting > or = 20% of the smears. They were all grade 2 disease. Multilobated cells were identified in 14 of the 15 cases of ALCL (93%) and in 3 of the 48 cases of HL (6.25%; P = .0008). CONCLUSION: Our findings indicate that the differentiation of ALCL from HL can be achieved in FNA smears through identification of abnormal cells representing > 30% of the population, a spectrum of abnormal cells and the presence of multilobated nuclei. Rare cases of grade 2 HL may be difficult to differentiate from ALCL.     

Mass spectrometry-based proteomic studies of human anaplastic large cell lymphoma

Malignant lymphomas are a diverse group of malignant neoplasms that arise as a result of a complex interplay of multiple factors including genetic aberrations, immunosuppression, and exposure to noxious agents such as ionizing radiation and chemical agents. Anaplastic large cell lymphoma (ALCL) is an aggressive T-lineage lymphoma harboring chromosomal translocations involving the anaplastic lymphoma kinase (ALK) tyrosine kinase. The most common translocation in ALCL is the t(2;5)(p23;q35). This results in the formation of a chimeric fusion kinase, nucleophosmin/ALK. Nucleophosmin/ALK activates numerous downstream signaling pathways resulting in enhanced survival and proliferation. Using a variety of mass spectrometry-driven proteomic strategies, we have studied several aspects of the ALCL proteome. In this review, we provide a summary of mass spectrometry-based proteomic studies that expands the current understanding of the molecular pathogenesis of ALCL and provides the basis for the identification of biomarkers and targets for novel therapeutic agents.     

Hodgkin's disease: diagnostic accuracy of fine needle aspiration; a report based on 62 consecutive cases

We report on our series of 62 cases occurring between January 1977 and December 1990, which were diagnosed as Hodgkin's disease by fine needle aspiration (FNA) samples. the overall accuracy of the cytological diagnosis was high, with only four incorrect diagnoses and a positive predictive value of 93.5%. the value of FNA as a first level diagnostic technique in the screening of lymphadenopathies is discussed, as well as the limitations and pitfalls of the cytological diagnosis.     

Impairment in proliferation,lymphokine production and frequency distribution of mitogen-responsive and interleukin-2-producing cells in Hodgkin's disease

Summary In this paper, we have correlated the ability of peripheral blood lymphocytes (PBL) from Hodgkin's Disease patients to proliferate in response to a mitogen, phytohaemagglutinin (PHA), with production of lymphokines interleukin-2 (IL-2) and interferon (IFN), accumulating in the activated lymphocyte culture supernatants. We have also studied the frequency distribution of PHA-responsive and IL-2-producing T cells from PBL using limiting-dilution analysis. We observed that the levels of IL-2 and IFN in the supernatants of activated lymphocytes from patients with Hodgkin's disease were significantly reduced compared to those of healthy donors. Substage-B patients showed marked reduction in the ability to produce IFN. Levels of IL-2 and IFN in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regressison (r = 0.79 andr = 0.60 respectively). However, production of the two lymphokines by activated lymphocytes from the same patients did not correlate (r = +0.04). Further, the frequencies of PHA-responsive cells and IL-2-producing cells in the PBL of patients with Hodgkin's disease (ranges 1/111–1/554 and 1/3009–1/6709 respectively) were also less than those of the healthy donors (ranges 1/80–1/181 and 1/761–1/1828 respectively). Proliferation, IL-2 production in bulk cultures and frequencies of PHA-responsive and IL-2-producing cells correlated well in individual healthy donors. Whereas, one patient (BC 11 214) with a frequency of PHA-responsive cells within normal limits had a very low frequency of IL-2-producing cells. Taken together, the results indicate abnormalities in cytokine production and frequency distribution of cells required for amplification of immune response in patients with Hodgkin's disease.     

The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma

Progress has been made recently in developing antibody-drug conjugates (ADCs) that can selectively deliver cancer drugs to tumor cells. In principle, the idea is simple: by attaching drugs to tumor-seeking antibodies, target cells will be killed and nontarget cells will be spared. In practice, many parameters needed to be addressed to develop safe and effective ADCs, including the expression profiles of tumor versus normal tissues, the potency of the drug, the linker attaching the drug and placement of the drug on the antibody, and the pharmacokinetic and stability profiles of the resulting ADC. All these issues had been taken into account in developing brentuximab vedotin (Adcetris), an ADC that recently received accelerated approval by the US Food and Drug Administration for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Research is under way to extend the applications of brentuximab vedotin and to advance the field by developing other ADCs with new linker and conjugation strategies.     

A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma

Background  

Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy.     

A patient death attributable to implant-related primary anaplastic large cell lymphoma of the breast

Implant-related primary anaplastic large cell lymphoma (ALCL) of the breast is a rare clinical entity. With increasing attention being paid to this disease, most cases reported to date in the literature have demonstrated indolent clinical courses responsive to explantation, capsulectomy, chemotherapy, and/or radiotherapy. The authors describe a case of bilateral implant-related primary ALCL of the breast that proved refractory to both standard and aggressive interventions, ultimately resulting in patient death secondary to disease progression. The authors situate this case in the context of the current state of knowledge regarding implant-related primary ALCL of the breast and suggest that this entity is generally, but not universally, indolent in nature. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.     

Hyaluronan synthesis by anaplastic large cell lymphoma with massive lymphomatous effusion. A case report

BACKGROUND: Hyaluronan (HA) synthesis is frequently observed in malignant mesothelioma cells, whereas it is rarely found in lymphoma cells. Previous studies have reported that a high HA concentration in the serum was related to poor prognosis in lymphomas, although the mechanism was not elucidated. We recently encountered a case of anaplastic large cell lymphoma with an HA-rich, massive, lymphomatous effusion. Several studies were performed to clarify the character of this unusual lymphoma and to observe whether the lymphoma cells synthesized HA. CASE: A 59-year-old female was admitted with abdominal pain. Radiologic studies revealed a pleural effusion and paraaortic lymph node swelling. A biopsied specimen was compatible with anaplastic large cell lymphoma. Detailed cytologic observations revealed that the lymphoma cells in the pleural effusion had alcian blue-positive, productive material in the prominent Golgi area and microvillous structures on the surface. Further studies found that most of the lymphoma cells had HA-binding protein and expressed CD44 antigen, a receptor for HA. In addition, the HA concentration in the supernatant of the primary culture cells was extremely high and increased time dependently. CONCLUSION: These observations suggest that the lymphoma cells synthesized and released HA. Interactions of the released HA and CD44 on the surface might play an important role in the peculiar serosal growth of lymphoma cells.