Biomedical subjects
Publications and source records attributed to J K Chan.
A male infant was diagnosed as having diabetes mellitus 1 d after birth and died on the third day. Histological examination of the pancreas showed small and inconspicuous islets of Langerhans that were completely devoid of insulin-secreting cells. There was no evidence of insulitis.
Most follicular lymphomas can be readily diagnosed on morphological grounds by finding closely packed pale-staining follicles partitioned by scanty dark-staining interfollicular tissue. We describe two cases of an unusual 'reverse' variant of follicular lymphoma in which the nodules have dark-staining centres and pale-staining cuffs due to concentration of centroblasts at the periphery of the neoplastic follicles. Recognition of this unusual pattern of follicular lymphoma is important, to avoid confusion with progressive transformation of germinal centres or nodular lymphocyte predominance Hodgkin's disease.
Penicillium marneffei is a rare human pathogen that often causes problems in clinical and histological diagnosis. A patient who presented with autoimmune haemolytic anaemia and hepatosplenomegaly, and was subsequently found to be suffering from disseminated Penicillium marneffei infection, is reported. The liver biopsy showed epithelioid cell granulomas only, and tuberculosis was initially considered the most likely diagnosis. The correct diagnosis became evident in a subsequent colonic biopsy, which showed extensive infiltration by penicillium-laden macrophages.
A case of T-prolymphocytic leukemia leading to rapid demise of a 67-year-old man is reported. He presented with multiple skin lesions and splenomegaly. A unique feature was that a proportion of circulating leukemic cells assumed bizarre shapes, resembling carrots. The leukemic cells expressed the T-cell markers T11, T8 and Dako-T2, and the natural killer cell markers NKH1, Leu7 and Leu 11b.
One hundred sixty-five non-Hodgkin's lymphomas (101 B, 63 T, one histiocytic) were immunostained with an antibody (beta F1) reactive with a common framework determinant on the beta-subunit of the T cell receptor (TCR). beta F1 stained T lymphomas exclusively, including 53% of peripheral T cell lymphomas but only 33% of T lymphoblastic lymphomas. When expression of beta F1 and CD3 were considered together, 4 types of T lymphoma were delineated: 1) beta F1+CD3+; 2) beta F1+CD3-; 3) beta F1-CD3+, and 4) beta F1-CD3-. The first represented lymphomas with classical T immunophenotype. The second might represent T lymphomas with aberrant loss of CD3 expression. The third might represent T lymphomas with a putative second TCR or cases with an immature phenotype expressing cytoplasmic CD3 only. The fourth type included cases that may be derived from natural killer cells instead of T cells, cases of T lymphoma with aberrant loss of both beta F1 and CD3, and some cases of immature T cell (lymphoblastic) lymphoma. beta F1-CD3- lymphomas exhibited a remarkable predilection for the nasal region. beta F1 is useful in studying T cell lymphomas and distinguishing a novel immunophenotype frequently expressed by nasal lymphomas.
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A 44 year-old Chinese male presented with lymphoid blast crisis of chronic myeloid leukemia, in which the blast cells exhibited a pre-pre-B cell phenotype (B4+B1-J5+12+smIg-). There was a phenotypic transition during the course of the disease to a more mature B cell phenotype (B4+B1+J5+12+smIgG lambda+). The maturation of blast crisis cells may be related to the chemotherapeutic agents used in the treatment of the disease.
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A case of malignant lymphoma probably representing the neoplastic counterpart of "monocytoid B cells" is described. The lymphoma cells had medium-sized, oval to indented nuclei and moderate amounts of pale cytoplasm. Immunohistochemical studies on cryostat sections revealed positive staining for pan-B, B1, B4, BA2, 12 (HLA-DR), and IgM lambda, but not T-cell or monocytic markers.
A subset of T lymphocytes has recently been reported to express S-100 protein. We report a case of S-100-positive peripheral T-cell lymphoma with a sinusoidal pattern of lymph node involvement. The immunophenotypic profile was T1+, T3+, T4+, T6-, T8-, T11+. The 12-year-old boy presented with thrombocytopenia and splenomegaly and was found to have malignant lymphoma involving the para-aortic lymph nodes, spleen, and bone marrow. The disease ran a rapidly fatal course.
One hundred forty-nine cases of non-Hodgkin's lymphoma were studied with a panel of monoclonal antibodies, including antibodies to natural killer (NK) cells--anti-NKH1, anti-Leu 7, and anti-Leu 11b. There were 95 B-cell, 51 T-cell, and three null cell lymphomas. Seventeen T-cell lymphomas (33 per cent) expressed NKH1, Leu 7, and/or Leu 11b. None of the B- or null cell lymphomas expressed the NK markers. In comparison with the NK-negative T-cell lymphomas, the NK-positive cases showed a predilection for the nasal and paranasal region. There was a more significant loss of the T-cell markers T3 (peripheral T cell) and T4 (T-helper cell) in NK-positive lymphomas. The difference was due to a high proportion of nasal/paranasal lymphomas, which were associated with a frequent loss of T-cell markers, among the NK-positive cases. However, a similar degree of loss of T-cell markers was observed among NK-positive and NK-negative nasal/paranasal lymphomas. We conclude that expression of NK markers occurs exclusively in a proportion of T-cell lymphomas, but not B-cell or null cell lymphomas. The reason this occurs predominantly in nasal and paranasal lymphomas is unknown.
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Eleven consecutive cases of nasal/nasopharyngeal lymphoma were studied histologically and with a panel of monoclonal antibodies. The disease showed a male predominance and occurred over a wide age range, with a median of 52 years. Five patients had midfacial destructive disease, and six had gross tumor masses involving the nose/nasopharynx. Three cases were classified as small cleaved cell, two cases as mixed cell, five cases as large cell, and one case as immunoblastic lymphoma. Those belonging to the first two categories also satisfied the diagnostic criteria of so-called polymorphic reticulosis. Epithelial invasion, angioinvasion, and coagulative necrosis were demonstrated in seven, eight, and nine cases respectively. Immunohistochemical studies confirmed that the atypical cells of all 11 cases exhibited T-cell markers. All but one case had lost one or more T-cell markers associated with peripheral T cells, particularly T1 and T3. Loss of T-cell markers in the five cases histologically consistent with polymorphic reticulosis provided further support to indicate that the lesion was neoplastic. A significant proportion of cases also expressed the activated T-cell markers 12 (HLA-DR) and interleukin-2 receptor (IL-2R1).
Four commercially available monoclonal antibodies, MB1, MB2, LN1 and LN2, were studied to determine their sensitivity and specificity for the diagnosis of B-cell lymphomas when used on formalin-fixed paraffin-embedded tissues. In addition to 125 cases of immunologically characterized non-Hodgkin's lymphoma, a range of normal tissues, reactive lymphoid proliferations, Hodgkin's disease and granulocytic sarcomas were also studied. MB1 was found to give positive results in 53.6% of B-cell lymphomas, but the staining was sometimes weak and patchy; there was also cross-reaction with 1.8% of T-cell lymphomas. MB2 reacted with 88.4% of B-cell lymphomas and the reaction was often strong and diffuse, but it showed cross-reaction with 18.2% of T-cell lymphomas. LN1 and LN2 gave positive staining of 44.9 and 46.4% of B-cell lymphomas respectively, and the results appeared to be inferior to that obtained in B5-fixed tissues; staining was sometimes weak and focal, and they also gave false-positive results in a few cases of T-cell lymphoma. This study shows that MB1, LN1 and LN2 are fairly but not entirely specific for B-cells in the non-Hodgkin's lymphomas, but are not very sensitive when applied to formalin-fixed tissues. MB2 shows a high sensitivity but only moderate specificity. Therefore, when these antibodies are used to determine the immunophenotype of malignant lymphomas, the B-cell nature can be predicted with great confidence only when two, preferably three or more, of the antibodies give positive results. The potential applications of these antibodies are discussed.
Seventeen prostatic-type polyps of the lower urinary tract are reported. All occurred in males, and the mean ages of the patients with ureteric orifice, bladder and urethral polyps were 20.5, 60.2 and 36.6 years, respectively. The commonest presentation for the bladder and ureteric orifice polyps was haematuria, whereas that for the urethral polyps was either dysuria or haematuria. The polyps consisted of acini and papillae lined by prostatic-type epithelium, as confirmed by immunostaining for prostatic-specific antigen. Most had interspersed islands or complete covering of transitional epithelium on the surface. We believe that the histogenesis of prostatic-type polyps may differ in the different sites. For the ureteric orifice polyp, the early age of presentation and the simple occurrence of prostatic acini beneath an intact urothelium suggest a developmental abnormality. For the bladder polyp, the late onset of disease and the commonly observed transition with cystitis cystica-glandularis suggest that it may be a metaplastic variant of cystitis cystica-glandularis. On the other hand, the urethral polyp probably represents a hyperplastic lesion, since the prostatic urethra is normally lined partly by prostatic-type epithelium.
Among extranodal lymphomas, the Waldeyer's ring is the second most frequently involved site after the gastrointestinal tract. Fresh tissue from 23 consecutive cases of malignant lymphoma of the faucial tonsil, palate and base of tongue were studied histologically and with a panel of 25 monoclonal antibodies. Twenty cases were primary Waldeyer's ring lymphoma, and all were found to express B-cell phenotype. Most cases were classified as diffuse centroblastic lymphoma, polymorphic subtype, in which there were immunoblast-like, centrocyte-like and/or multilobated centroblasts. All except one case expressed all three B-cell lineage antigens CD19, CD20 and CD22, but they showed inconsistent expression of the B-cell antigens CD9 and CD24. Four cases lacked surface immunoglobulin. Six cases expressed interleukin-2 receptor, suggesting that they were composed of highly activated B-cells. Three cases represented relapse in the tonsil or tongue in patients with known malignant lymphoma in other sites; one case expressed T-cell and two cases B-cell phenotype (both of which also expressed interleukin-2 receptor). The clinical features and immunohistological findings suggest that Waldeyer's ring lymphomas, other than those of the nasopharynx, share some of the characteristics of 'mucosa-associated lymphoid tissue' lymphomas. In contrast, nasopharyngeal lymphomas are more related to nasal lymphomas, and are almost exclusively peripheral T-cell neoplasms.
Three cases of an unusual diffuse sclerosing variant of papillary carcinoma of the thyroid occurring in young adults are reported. The tumour is characterized by diffuse involvement of one or both lobes of the thyroid, marked squamous metaplasia, numerous psammoma bodies, extensive interstitial fibrosis and heavy lymphocytic infiltration with formation of germinal centres. Lymphatic and vascular permeation was found in all three cases. An interesting finding was the presence of irregularly disposed thin bundles of smooth muscle within the fibrous stroma, presumably a result of splaying of the smooth muscle of vessel walls by the sclerotic process. The papillary areas of the tumour stained for thyroglobulin and cytokeratin, while the squamous areas stained strongly for cytokeratin but not for thyroglobulin. The tumours were negative for calcitonin and carcinoembryonic antigen, but showed weak staining for S-100 protein. Numerous S-100 positive Langerhans/interdigitating reticulum cells were scattered within the tumour islands and the lymphoid infiltrate, suggesting an immunological reaction mediated by these antigen-presenting cells.