The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells

Abstract

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

A lymphohistiocytic variant of anaplastic large cell lymphoma with demonstration of the t(2;5)(p23;q35) chromosome translocation

“…Ki-1 (CD30) positive anaplastic large cell lymphoma (ALCL), first described as a distinct morphological entity by Stein et al (1985), was found to be associated with the translocation t(2;5)(p23;q35) in 30-40% of cases (Le Beau et al, 1989;Mason et al, 1990). By classic cytogenetics, it was also possible to detect the t(2;5) in the small-cell predominant variant of ALCL (Kinney et al, 1993).…”

Toxin-Based Therapeutic Approaches

“…In addition to their classical ribosome-inactivating glycosidase activity, other activities and enzymatic properties were associated with RIPs: antiviral activity [265], depurination of (non-ribosomal) RNA and adenine DNA glycosylase activity [266][267][268][269][270], deoxyribonuclease activity [271][272][273][274][275][276][277][278], ribonuclease activity [279,280], removal of adenine from poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase (an enzyme involved in DNA repair) [281,282], depurination of the capped RNA template [283,284], superoxide dismutase (SOD) activity [285][286][287] and phospholipase activities [288]. The involvement of these non-classical RIP activities in cytotoxicity is debatable, though accumulating evidence suggests that ribosome inactivation is not the sole means by which RIPs execute their toxic effects [264,[289][290][291][292][293][294][295] CD25 and CD30 are lymphoid activation markers which are highly expressed on the surface of Hodgkin's lymphoma cells and only present on a minority of normal human cells [135,[296][297][298]. In order to target these cells, two immunotoxins, RFT5-dgA (IMTOX25) and ki-4.dgA, were constructed.…”

Adverse drug reactions in the mouth

“…Primary cutaneous anaplastic large cell lymphoma in an elderly patient with cryoglobulinaemic hepatitis C virus infection DOI: 10.1111/j. 1365-2133.2004.06232.x SIR, CD30+ or Ki-1+ anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin's lymphoma (NHL) first described by Stein et al 1 It has a distinctive pleomorphic appearance, sinusoidal growth pattern, and reactivity with the CD30 antibody. ALCL may be classified according to the location of the original tumour: primary nodal, primary cutaneous or secondary cutaneous.…”

“…ALCL was defined by a frequent cohesive proliferation of large pleomorphic blasts and constant expression of the CD30 molecule in all neoplastic cells. 1 These proliferations first arise in lymph nodes in most cases but may involve other parts of the body, especially the skin, as a primary site. 8 Recently recognized cytogenetic and immunophenotypic differences confirm the clinical evidence that primary nodal and primary cutaneous ALCL are distinct entities.…”

“…They are generally small, and giant epidermal cysts with a diameter of 5 cm or more are rare. 1,2 An epidermal cyst is usually a unilocular lesion. [1][2][3] To our knowledge, all of the giant subcutaneous epidermal cysts reported in the English language literature have been unilocular, except for one lesion reported by Shibata et al 4 (a lobulated mass).…”