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Biomedical subjects

D M Knowles

Publications and source records attributed to D M Knowles.

At least 217 records · Page 12Linked to original sources

Extracardiac rhabdomyoma: a clinicopathologic study and review of the literature.

Extracardiac rhabdomyomas are rare benign neoplasms that in the past have been divided by histologic criteria into adult and fetal types. In this series, 15 previously unpublished cases are presented and analyzed in combination with 51 acceptable cases from the literature. The adult type of rhabdomyoma occurs almost exclusively in the head and neck region (93% of all cases), particularly in the larynx and pharynx of adult males. The fetal type of rhabdomyoma may be subdivided on histologic grounds into myxoid and cellular variants. The fetal myxoid type usually occurs in the vulvovaginal region of middle aged women or in the postauricular region of male infants. The fetal cellular type has not been previously emphasized. This type tends to occur in the head and neck region of adult males. It may be mistaken for a sarcoma because of its high degree of cellularity. Local recurrence of a rhabdomyoma is rare and has only been occasionally reported in the adult type of rhabdomyoma. In no instance has a rhabdomyoma been shown to possess aggressive local growth or metastatic potential. Therefore, it is essential that these neoplasms be recognized histologically and that they be treated conservatively by local excision.

Adult↗

Orbital lymphoid neoplasms: a clinicopathologic study of 60 patients.

Sixty cases of orbital lymphoid neoplasms originally accessioned as malignant lymphomas were analyzed histopathologically and the follow-up data evaluated separately for each category as follows: inflammatory pseudo-tumor, 5; reactive lymphoid hyperplasia, 8; atypical lymphoid hyperplasia, 7; and malignant lymphocytic lymphoma (classified according to Rappaport), 40. Significant clinical differences were not observed among these patients, suggesting that the lesions must be distinguished by histologic rather than clinical criteria. Systematic application of the histologic criteria discussed here improved diagnostic accuracy and our ability to predict clinical outcome as substantiated by follow-up data. Two of 13 patients (15%) with benign pseudo-lymphomas, 2 of 7 patients (29%) with atypical lymphoid hyperplasia, 2 of 8 patients (25%) with well differentiated lymphocytic lymphomas, and 22 of 32 patients (68%) with less differentiated lymphocytic lymphomas either had or later developed systemic lymphomas. Thus, the degree of cytologic differentiation appears to be the single most important factor for determining the prognosis of patients with orbital lymphoid neoplasms.

Adolescent↗

Ocular pathology for clinicians. 6. Lymphoid tumor of the lid.

A 56-year-old white man presented with bilateral inferior lid tumors with a rubbery consistency suggesting lymphoid lesions. An excisional biopsy specimen of the larger lesion in the left lower lid led to routine pathologic, immunologic, histochemical, and electron microscopic investigations. The tumor displayed a diffuse pattern microscopically and was composed of atypical lymphocytes with intermediate differentiation. The immunologic and histochemical marker studies revealed that 90% of the constituent lymphocytes were B-lymphocytes bearing IgM-IgD immunoglobulins on their surface membranes; the remaining 10% of the cells being reactive T-lymphocytes. A diagnosis of a monoclonal proliferation was established and a systemic workup revealed disseminated lymphoma. The use of immunoglobulin and histochemical analyses of ocular adnexal lymphoid tumors is outlined.

B-Lymphocytes↗

Cytochemically demonstrable B-glucuronidase activity in normal and neoplastic human lymphoid cells.

Mononuclear cell suspensions were prepared from 40 normal peripheral blood and lymphoid tissue specimens and 42 neoplastic specimens obtained from patients with malignant lymphoma and lymphocytic leukemia. These suspensions were analyzed for la antigens, surface immunoglobulin (Slg), sheep erythrocyte (E) rosette formation and, in some instances, acid alpha-naphthyl acetate esterase (ANAE) activity. The results of these studies were correlated with the expression of cytochemically demonstrable BG activity. The percentage of BG+ lymphocytes was found to be comparable, within 10%, to the percentage of E+ (T) cells in the majority of normal, non-neoplastic peripheral blood, tonsil, spleen, and lymph node specimens examined. Occasionally, the percentage of E+ cells exceeded the percentage of BG+ cells by 20% or more, suggesting the presence of an E+BG- T cell subpopulation. BG+ B lymphocytes were only demonstrated in 1 of 40 non-neoplastic lymphoid specimens. The neoplastic B cells in each of 14 B cell (la+Slg+E-) lymphomas were BG-. However, a variable proportion of the neoplastic cells isolated from 6 cases of B cell chronic lymphocytic leukemia and neoplastic plasma cells isolated from 7 cases of multiple myeloma expressed BG activity. Thus, it appears that both normal and neoplastic BG- and BG+ B lymphocyte populations exist; the latter may be related to a state of activation or a stage of B cell differentiation. The neoplastic cells isolated from 4 T cell (la-Slg-E+) malignancies were BG+ while those isolated from 3 T cell malignancies were BG-. The variable expression of BG activity by T cell malignancies may be related to T cell differentiation. Investigation of BG expression by T cell derived malignancies may prove useful in sorting out T cell phenotypes.

Cell Transformation, Neoplastic↗

Nodular lymphocytic lymphoma eventuating into diffuse histiocytic lymphoma: immunoperoxidase demonstration of monoclonality.

The patient described here had a nodular, poorly differentiated lymphocytic lymphoma associated with a serum monoclonal protein, IgG lambda. Following a three year period of radiation-induced clinical remission she developed generalized diffuse histiocytic lymphoma. Direct immunoperoxidase staining of the tissue sections demonstrated that the neoplastic cells of each biopsy only contained IgG lambda immunoglobulin, identical to the serum monoclonal protein. This is presumptive evidence that these two histopathologically distinctive malignant lymphomas, occurring consecutively in the same patient, were responsible for the synthesis and secretion of the same serum M component. This strongly suggests that both lymphoid neoplasms arose from the same malignant clone. The results 1) confirm the light microscopic observation that nodular lymphocytic lymphoma may progress to diffuse histiocytic lymphoma and 2) offer further evidence that histiocytic lymphomas arising in patients with previous B cell malignancies are most probably related to the original B cell proliferation and do not represent the emergence of a second, separate malignant clone.

Female↗

Immunologic characterization of ocular adnexal lymphoid neoplasms.

We correlated the light microscopic features of ten ocular adnexal lymphoid neoplasms with the results of selected immunologic and histochemical lymphocyte marker studies. The lesions were divided into three histomorphologic patterns: inflammatory pseudotumor, reactive follicular hyperplasia, and malignant lymphoma. The six inflammatory pseudotumors, and reactive follicular hyperplasia, despite diverse histomorphology, were immunologically polyclonal and consisted of from 45 to 73% T cells and 27 to 60% B cells, the B cells being polyclonal with respect to light chain determinants. The four malignant lymphomas were immunologically monoclonal. Each consisted of a predominant B-cell proliferation, greater than 50% of the cells, which were monoclonal with respect to surface light chain determinants. No T-cell proliferations were observed. Our preliminary data indicate that, as in systemic lymphoid neoplasms, benign reactive lymphoid hyperplasias are immunologically polyclonal whereas malignant lymphomas are immunologically monoclonal. The systematic application of immunologic and histochemical techniques to the study of ocular adnexal lymphoid neoplasms may elucidate the natural history of these lesions.

Adult↗

Acid alpha-naphthyl acetate esterase activity in human neoplastic lymphoid cells. Usefulness as a T-cell marker.

Previous studies have shown that a distinctive pattern of acid alpha-naphthyl acetate esterase (ANAE) activity (focal reaction product) characterizes normal human peripheral blood and tissue T lymphocytes but is absent from thymocytes and certain mitogen-stimulated T-cell blasts. In the present study mononuclear cell suspensions prepared from the peripheral blood and tissue specimens of 35 patients with lymphoid malignancies were simultaneously analyzed for surface immunoglobulin, sheep erythrocyte rosette formation, Ia antigens, and ANAE activity. The neoplastic cells from 16 patients with Ia+ SIg+ E- (B cell) malignancies, 4 patients with Ia+ SIg- E- (non-B, non-T) acute lymphoblastic leukemia, and 3 patients with Ia- SIg- E- (null cell) malignancies failed to exhibit ANAE activity. The neoplastic cells from 5 patients with Ia- SIg- E+ (T cell-derived) malignancies, including three cutaneous lymphomas, displayed characteristic T-pattern positivity, and in each case the percentage of E+ and ANAE+ cells was comparable. The neoplastic cells from 4 patients with Ia- SIg- E+ (T cell-derived) acute lymphoblastic leukemia were ANAE-. The expression of ANAE activity in T cell-derived malignancies may parallel its expression in the stages of normal T-cell differentiation and may prove to be a useful marker with which to sort out T-cell phenotypes.

Adult↗

Pleomorphic reticulum cell sarcoma, monoclonal gammopathy and amyloidosis: an immunoperoxidase study.

Pleomorphic reticulum cell sarcoma, a histologic variant of the histiocytic lymphomas, presented as an abdominal mass in a 52-year-old woman. Extensive amyloid deposition was present within the tumor mass and an M-component (IgG Lambda) was identified in the serum. Direct immunoperoxidase staining of tissue sections demonstrated the same monoclonal immunoglobulin to be present within the neoplastic cells, presumptive evidence of their ability to both synthesize and secrete immunoglobulin. The presence of amyloid within this patient was probably the direct result of the tissue deposition of this monoclonal immunoglobulin and may be related to the amyloidogenic nature of Lambda light chains. Immunoglobulin production is a specific property of the B lymphocyte series. Transforming B lymphocytes and their differentiating progeny are engaged in active immunoglobulin synthesis and thus may be distinguished from morphologically identical but functionally distinct cells. The demonstration of cytoplasmic monoclonal immunoglobulin within these "malignant reticulum cells" strongly supports the assertion that at least some "histiocytic lymphomas" are neoplastic analogues of transformed B lymphocytes, and are not derived from phagocytic histiocytes, as previously believed.

Amyloidosis↗

Immunofluorescent and immunoperoxidase characteristics of IgDlambda myeloma involving the orbit.

A biopsy specimen from a 59-year-old man with unilateral proptosis revealed an orbital plasmacytic tumor. In vitro immunoperoxidase and immunofluorescence studies and direct immunoperoxidase staining of Bouin's fixed, paraffin-embedded tissue sections demonstrated that the tumor consisted of plasma cells with surface and intracellular IgDlambda immunoglobulin. Systemic evaluation demonstrated multiple myeloma. A review of previously published reports combined with the case presented here suggests that IgD myeloma has a predilection for orbital involvement. Thus, while IgD myeloma accounts for only 2% of all myelomas, it may account for a significant percentage of myelomas with orbital involvement. The distinctive clinical course of IgD myeloma, particularly its poor prognosis, warrants consideration of the immunologic and serologic findings in patients with orbital involvement by myeloma. The application of immunofluorescence and immunoperoxidase techniques to the study of orbital lymphoreticular neoplasms should result in a clearer understanding of these neoplasms.

Diplopia↗

The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives.

Poor histopathologic documentation and confusing terminology have caused focal nodular hyperplasia (FNH) and liver cell adenoma (LCA) to be categorized together as "benign hepatomas." FNH and LCA are distinguishable grossly, microscopically, and ultrastructurally. In a majority of instances they may be differentiated by combined angiography and liver scan: FNH is hypervascular and exhibits normal uptake on scan whereas LCA is hypovascular and cold on scan. FNH almost always follows a benign course, rarely undergoing hemorrhagic necrosis and rupture. FNH does not possess malignant potential; the prognosis, even if unexcised, is excellent. Resection is indicated only if FNH is symptomatic. LCA often ruptures and its malignant potential remains uncertain; the prognosis is guarded and resection is indicated. The literature reported association between FNH and oral contraceptives is anecdotal. However, the recent marked increase in the incidence of LCA's, their almost exclusive occurrence in young women, and the consistent hormonal history strongly suggests an association between oral contraceptive use and LCA's, although here too, statistical evidence is lacking. Prognostic and therapeutic considerations mandate that a clear distinction be made between FNH and LCA.

Adolescent↗

Tissue localization of T-lymphocytes by the histochemical demonstration of acid alpha-naphthyl acetate esterase.

Nonspecific acid alpha-naphthyl acetate esterase (ANAE) activity has previously been evaluated with the sheep erythrocyte (E) rosette assay and found to be a useful T-cell marker in cell suspension studies. T-lymphocytes display a solitary red brown nodule of reaction product (T-pattern) which can be readily distinguished from the diffuse, cytoplasmic staining of monocytes (M-pattern). Freshly obtained human tissue blocks were fixed with buffered formal sucrose and maintained in Holt's syrup; cryostat sections were cut and incubated under conditions appropriate for the histochemical demonstration of lymphocyte acid alpha-naphthyl acetate esterase activity. The results clearly demonstrate that T-pattern ANAE+ lymphocytes populate the paracortical and interfollicular regions of normal lymph nodes and tonsils and the periarteriolar sheaths of normal spleen, T-cell zones, while nearly every germinal center (B-cell area) lymphocyte is ANAE-. Macrophages and dendritic reticulum cells display diffuse cytoplasmic ANAE activity (M-pattern). Nodular malignant lymphomas (B-cell origin) are ANAE-; an E+ diffuse, cutaneous lymphoma was ANAE+. The histochemical demonstration of ANAE activity may represent the first reproducible, routine technique to localize T-lymphocytes in tissue sections.

Carboxylic Ester Hydrolases↗

Thymoma and chronic myelogenous leukemia: a case report.

A case of epithelial thymoma occurring synchronously with Philadelphia chromosome-positive chronic myelogenous leukemia and urinary bladder carcinoma in a 76-year-old man is described. Thymomas have been associated with numberous hematologic, collagen-vascular and autoimmune disease states, as well as with an increased incidence of nonthymic malignancy. Human thymoma-associated leukemia is, however, extremely unusual, despite the well-documented role of the thymus in leukemogenesis in experimental animals. No previous literature reports of thymoma associated with chronic myelogeneous leukemia were found. A review of long-term followup data of surviving thymoma patients is necessary to determine if an increased propensity to develop leukemia is present in present in patients with thymoma.

Aged↗

Focal nodular hyperplasia of the liver: a clinicopathologic study and review of the literature.

We received the clinical records and pathologic material of 20 patients with biopsy proven hepatic focal nodular hyperplasia. The majority of the patients were females of child bearing age, five of whom had a history of oral use of contraceptives. In every instance focal nodular hyperplasia was an incidental finding; liver function tests were always normal. Focal nodular hyperplasia is a distinct histopathologic entity, distinguishable from liver cell adenoma. Specifically it consists of nodular aggregates of cytologically normal hepatocytes with foci of intranodular bile duct proliferation. Focal nodular hyperplasia appears to be a benign entity, even in patients in whom the lesion was not excised. The association between focal nodular hyperplasia and oral use of contraceptives may be coincidental, although hormonally related vascular changes may be responsible for rupture of the lesion.

Adolescent↗