Classification of natural killer cell neoplasms.
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Biomedical subjects
Publications and source records attributed to J K Chan.
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Granulomatous slack skin is an extremely uncommon form of cutaneous T-cell lymphoma. We report a case occurring in a 29-year-old man, who had generalized, progressive skin lesions evolving to nodular swellings and folds in the flexural regions, and peripheral blood and marrow involvement. The biopsies were initially misinterpreted as xanthogranuloma or granulomatous inflammation. Histologically, the entire dermis and subcutis was infiltrated by non-necrotizing granulomas comprising mononuclear histiocytes, multinucleated giant cells and small lymphoid cells with irregularly folded nuclei, associated with loss of elastic fibres. The small lymphoid cells showed focal epidermotropism. Immunohistochemical studies showed that they were of T-lineage (CD3+, CD43+, CD45RO+). The multinucleated giant cells, which showed reactivity with the histiocytic markers CD68 and Mac387, were highlighted by intense, thick membrane staining with CD45, CD43 and CD45RO. Ultrastructurally, they exhibited features of macrophages with numerous surface villous processes and lysosomes. Greater awareness of this entity may facilitate more prompt and accurate diagnosis, obviating a futile search for a non-existent infective aetiology.
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A new classification of lymphoid neoplasms, mostly based on existing terminology, is proposed by the International Lymphoma Study Group. The proposed classification was reached through a consensus of the members, despite their diverse backgrounds, and consists of a listing of currently recognized clinicopathological entities. These tumours are divided into three major categories: B-cell neoplasms, T-cell and postulated natural killer cell neoplasms, and Hodgkin's disease. The characterization of each entity is based on a synthesis of all available information. This concept departs from a purely morphological approach to lymphoma classification, which is considered to be inadequate, because many biologically distinctive lymphoma types can exhibit a broad and overlapping morphological spectrum. Some entities are provisional, pending further data to confirm that their recognition is reproducible. The salient clinicopathological features of each entity are summarized in this review.
CD56, a natural killer cell marker reactive with the neuronal-cell adhesion molecule (NCAM), identifies a group of lymphomas with distinctive clinicopathologic features. The disease affects mostly middle-aged adults who often present with fever, skin rash and hepatosplenomegaly in the absence of peripheral lymphadenopathy. Extranodal involvement is common, particularly the skin, aerodigestive tract and central nervous system. Histologically, an angiocentric and angiodestructive pattern of infiltrate is often seen, but the cytological spectrum of the lymphoma cells is very broad. Cytoplasmic granules, however, are frequently found when Giemsa-stained cytologic preparations are examined. Immunologically, CD56-positive lymphomas can be sub-classified into CD3-positive (T-cell) and CD3-negative (probably true natural killer cell) subtypes. T-cell receptor gene rearrangement can be demonstrated in the former cases, but not in the latter. Clinically, CD56-positive lymphomas are aggressive neoplasms.
The Epstein-Barr virus (EBV)-encoded RNAs in situ localization procedure is a convenient, highly sensitive, and highly specific technique that is applicable to routinely fixed, paraffin-embedded tissue sections; this technique can be used for the study of the association and, hence, the possible causal role of EBV in tumors. This study was performed to elucidate whether EBV plays a role in the pathogenesis of tumors that arise in the salivary glands, since the salivary gland is known to be a reservoir for EBV replication. Cases that were selected included 61 examples of various benign and malignant neoplasms, as well as tumorlike conditions of the major and minor salivary glands. Only the five cases of lymphoepithelial carcinoma (so-called malignant lymphoepithelial lesion) and the single case of metastatic nasopharyngeal undifferentiated carcinoma showed staining with EBV-encoded RNAs, whereas negative findings were found in all of the other cases. In the cases with positive results, all of the neoplastic epithelial cells showed strong nuclear signals, but the lymphoid cells were negative. The consistent association of EBV with lymphoepithelial carcinoma of the salivary gland suggests that the virus probably plays a causal role in this tumor, at least in the Asian population, whereas there is no evidence for a causal role of EBV in other primary tumors of the salivary gland.
Seventy-five cases of Kikuchi's lymphadenitis, a self-limiting pseudomalignant condition, were reviewed to determine the spectrum of histologic findings. There were 55 females and 20 males; ages ranged from 9 to 57 years (mean, 25.5). Most patients presented with cervical lymphadenopathy (68 cases). Associated clinical findings were fever (20/52) and leukopenia (15/33). Serum antinuclear antibodies were negative in 15 patients among 16 tested. Among 32 patients with follow-up information, 31 remained well, including one who developed recurrence after 2 years. One patient died of fatal myocardial disease during the active disease. Histologically, the lymph nodes showed paracortical hyperplasia, often associated with a starry-sky appearance resulting from interspersed histiocytes and immunoblasts. The consistent finding was the presence of variable-sized discrete or confluent nodules in the paracortex composed of the following: (a) karyorrhectic and eosinophilic granular debris; (b) histiocytes, many of which were phagocytic and possessed distinctive peripherally placed crescentic nuclei and voluminous cytoplasm containing eosinophilic or karyorrhectic debris (for which we propose the designation crescentic histiocytes), mixed with nonphagocytic histiocytes having twisted or reniform nuclei which were often centrally placed; (c) plasmacytoid monocytes, which were medium-sized cells with eccentrically placed round nuclei and amphophilic cytoplasm; and (d) variable numbers of immunoblasts, which sometimes showed atypia such as irregular nuclear foldings and coarse chromatin. Neutrophils were absent or very sparse. In some nodules, coagulative necrosis was present in the center (45 cases). Foamy histiocytes were found in 23 cases, and they predominated in 11. Small clusters of plasmacytoid monocytes were noted in the paracortex in 40 cases. Perinodal inflammation was a common finding, and perinodal involvement by the karyorrhectic process occurred in 15 cases. In addition, we found a number of previously unreported features. Signet-ring histiocytes with clear or homogeneous lightly amphophilic cytoplasm and nuclei compressed into thin crescents, found in seven cases, could mimic signet-ring cell adenocarcinoma. In three cases, some germinal centers were involved by the karyorrhectic process. Foci of lymphocyte-depleted fibrovascular organization were present in eight cases, probably representing the resolving phase of the karyorrhectic process. Despite the broad morphologic spectrum, the intermingling of the distinctive crescentic histiocytes, karyorrhectic debris, and plasmacytoid monocytes in the form of nodules, together with the paucity of neutrophils, are the consistent findings that should permit a confident histologic diagnosis of Kikuchi's lymphadenitis.
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In this study tetraethylammonium (TEA) was used as a model compound to determine the effect of the lysine selective modifying reagent, phenylisothiocyanate (PITC), on organic cation transport across the brush-border membrane of opossum kidney (OK) cells. TEA uptake in OK cell monolayers treated with PITC was reduced in a time- and concentration- dependent manner (IC50, 200 microM). Two lines of evidence suggested that amine rather than sulfhydryl residues were being modified by PITC. First, treatment of the cells with PITC at pH 8.5 was significantly more effective in reducing TEA uptake than PITC treatment at pH 7.4. Secondly, dithiothreitol (10 mM) could not reverse the effect of PITC on TEA uptake. Preincubation of OK cell monolayers with PITC (50 microM) resulted in a significant increase in the Km of TEA (control cells: 81 +/- 10 microM; treated cells: 165 +/- 54 microM), whereas the Vmax was unaffected. Incubation of the cells with quinine or unlabeled TEA significantly altered the inhibitory effects of PITC on TEA uptake. At low concentrations, quinine protected the transporter from the inhibitory effects of PITC, whereas at higher concentrations (> 2.5 microM) quinine enhanced PITC inhibition of TEA uptake. Other organic cations that are substrates for the transporter including cimetidine and N1-methylnicotinamide did not alter the effects of PITC on TEA transport. Collectively, these data suggest that covalent modification of amine groups reduces the transport of TEA in OK cells by decreasing the affinity of TEA to the transporter.(ABSTRACT TRUNCATED AT 250 WORDS)
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Disseminated cryptococcal infection is an uncommon initial manifestation in patients with the acquired immunodeficiency syndrome. The most common sites of involvement by cryptococci are the central nervous system and the lungs, and involvement of the marrow is rare. There are few descriptions in the literature on the cytologic findings of marrow cryptococcosis. We report a patient with disseminated cryptococcosis in which cytologic examination of the marrow provides the first clue to the diagnosis.
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Leukemic transformation is not uncommon in polycythemia vera, particularly after treatment with chemotherapeutic agents. The leukemias that supervene are mostly of myeloid type but megakaryoblastic transformation is distinctly uncommon. We report a case of polycythemia vera terminating in megakaryoblastic leukemia with associated hypercalcemia.
The effect of dietary alpha-linolenic acid (18:3n-3) and its ratio to linoleic acid (18:2n-6) on platelet and plasma phospholipid (PL) fatty acid patterns and prostanoid production were studied in normolipidemic men. The study consisted of two 42-d phases. Each was divided into a 6-d pre-experimental period, during which a mixed fat diet was fed, and two-18 d experimental periods, during which a mixture of sunflower and olive oil [low 18:3n-3 content, high 18:2/18:3 ratio (LO-HI diet)], soybean oil (intermediate 18:3n-3 content, intermediate 18:2/18:3 ratio), canola oil (intermediate 18:3n-3 content, low 18:2/18:3 ratio) and a mixture of sunflower, olive and flax oil [high 18:3n-3 content, low 18:2/18:3 ratio (HI-LO diet)] provided 77% of the fat (26% of the energy) in the diet. The 18:3n-3 content and the 18:2/18:3 ratio of the experimental diets were: 0.8%, 27.4; 6.5%, 6.9; 6.6%, 3.0; and 13.4%, 2.7, respectively. There were appreciable differences in the fatty acid composition of platelet and plasma PLs. Nevertheless, 18:1n-9, 18:2n-6 and 18:3n-3 levels in PL reflected the fatty acid composition of the diets, although very little 18:3n-3 was incorporated into PL. Both the level of 18:3n-3 in the diet and the 18:2/18:3 ratio were important in influencing the levels of longer chain n-3 fatty acid, especially 20:5n-3, in platelet and plasma PL. Production of 6-keto-PGF1 alpha was significantly (P < 0.05) higher following the HI-LO diet than the LO-HI diet although dietary fat source had no effect on bleeding time or thromboxane B2 production.(ABSTRACT TRUNCATED AT 250 WORDS)
In biopsy specimens of B-cell chronic lymphocytic leukemia, large cells with cytologic features of Reed-Sternberg cells and mononuclear Hodgkin's cells are an uncommon occurrence. The nature of these large cells has not been fully elucidated, and the relationship of these cases with Hodgkin's disease is unclear. Immunophenotypic analysis of a case of chronic lymphocytic leukemia with interspersed Reed-Sternberg cells showed that the large cells were positive for CD45 (LCA), various B-cell markers (CD19, CD20, CD22), and CD30 (Ki-1), but were negative for CD15 (Leu-M1), suggesting that they represented activated neoplastic B cells. These results were compared with those reported in the literature.