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Biomedical subjects

N L Harris

Publications and source records attributed to N L Harris.

At least 181 records · Page 10Linked to original sources

Lymphoma 1987. An interim approach to diagnosis and classification.

When immunophenotyping is used for diagnosis, it is essential to use panels of antibodies, rather than a single marker for a specific tumor type. There is virtually no single marker that is absolutely diagnostic and completely reliable for any particular neoplasm. For the most important clinical differential diagnoses--reactive versus neoplastic lymphoid lesions and lymphoma versus nonlymphoid tumor--relatively simple panels of antibodies are usually sufficient. In the former situation, immunoglobulin heavy and light chains (G, M, kappa, lambda) and a pan-T-cell antibody (Leu-4) will usually provide the answer. For the latter circumstance, kappa and lambda, a pan-leukocyte antibody, a pan-B-cell (B1), and a pan-T-cell antibody (Leu-4) along with cytokeratin constitute the initial panel. Further subclassification of lymphomas and leukemias can proceed using other antibodies as indicated in the preceding specific sections on the lymphomas. The use of specific antibodies for nonlymphoid tumors will be dictated by the morphologic appearance of the tumor. These may be used as a second panel if the initial screening does not establish a diagnosis of lymphoma. Performing and interpreting immunohistologic studies requires experience, and probably should not be attempted by laboratories that do not encounter a large number of lymphomas. Frozen tissue can be obtained and stored at -20 degrees for a few days; if immunohistologic studies are deemed necessary, the frozen tissue can be sent on dry ice to a reference laboratory. In preparing biopsy specimens for immunohistologic studies, and in interpreting the results of these studies, it is necessary to bear in mind the fact that morphology remains the most important tool for the diagnosis and subclassification of hematologic neoplasms. Obtaining tissue for marker studies should not be permitted to interfere with adequate morphologic examination. Similarly, artifacts and technical problems can occasionally lead to misleading results; the immunohistologic studies must be interpreted in light of the case as a whole, and should never be allowed to contradict common sense.

Burkitt Lymphoma↗

Systemic salmonellosis in patients with disseminated histoplasmosis. Case for 'macrophage blockade' caused by Histoplasma capsulatum.

Five patients are described with disseminated histoplasmosis and systemic salmonellosis. Four of these patients were also immunocompromised because of the acquired immunodeficiency syndrome in two patients and renal transplantation in another two patients. Histologic studies in two patients showed histiocytes that were heavily laden with Histoplasma capsulatum yeast-phase organisms. We postulate that diffuse parasitization of the reticuloendothelial system (RES) by Histoplasma organisms may cause "RES blockade," which then predisposes to systemic salmonellosis, as reported in certain other infections and in sickle cell anemia.

Adult↗

Endobronchial involvement with non-Hodgkin's lymphoma. A clinical-radiologic analysis.

Based on experience with three cases of endobronchial non-Hodgkin's lymphoma and a review of cases previously reported, two patterns of lymphomatous involvement of airways are described. The Type 1 pattern is characterized by diffuse submucosal infiltrates occurring in the presence of intra- and extrathoracic lymphoma. In Type 2 cases, central airways are involved by a solitary mass in the absence of clinically apparent systemic lymphoma. The clinical-radiologic picture is characterized by signs of pneumonitis in Type 1 cases, while in Type 2 cases, signs of airway obstruction uniformly occur.

Adult↗

Relapsing central and peripheral demyelinating diseases. Unusual pathologic features.

We treated a patient who had a demyelinating peripheral neuropathy and a central nervous system inflammatory demyelinating disease. The unusual pathologic feature of dense infiltrates of atypical macrophages was observed in many areas of the brain; otherwise the process had several features in common with either multiple sclerosis or chronic relapsing experimental allergic encephalomyelitis. The illness followed "swine-flu" inoculation; exacerbation followed pneumococcal vaccination.

Bacterial Vaccines↗

The predominant lymphocyte in most thymomas and in nonneoplastic thymus from patients with myasthenia gravis is the cortical thymocyte.

Cell suspensions prepared from 12 specimens of nonneoplastic thymus (6 normal and 6 from patients with myasthenia gravis) and from 17 thymomas were investigated with a panel of monoclonal antibodies. The great preponderance of thymocytes from the 12 nonneoplastic specimens and from 13 of the 17 thymomas (2 of 3 predominantly lymphocytic tumors and 11 of 12 mixed tumors) displayed the surface phenotype of cortical or common thymocytes. These cells formed rosettes with unsensitized sheep erythrocytes (E-rosettes) at both 4 and 37 degrees C, and reacted with the following monoclonal antibodies: OKT1 (thymic and peripheral T cells), OKT6 (common thymocytes), OKT10 (replicating lymphoid cells), OKT11 (sheep cell receptor), and both OKT4 (inducer-helper T cells) and OKT8 (cytotoxic-suppressor T cells). Few B cells (lymphocytes with either immunoglobulin or Ia-like antigen on the cell surface), and few cells with receptors for transferrin and interleukin 2 were detected. Thymocytes from 3 of the 4 remaining thymomas (2 predominantly epithelial tumors and 1 mixed tumor) displayed surface marker characteristics of medullary thymocytes or peripheral T cells; i.e., they were reactive with OKT1, OKT3 (peripheral T cells), OKT11, and either OKT4 or OKT8, and were also E-rosette positive only at 4 degrees C and TdT negative. Thymocytes from the final tumor, a lymphocytic thymoma, exhibited an intermediate phenotype. Thus, almost all mixed (11 of 12) and lymphocytic (2 of 3) thymomas were composed predominantly of cortical thymocytes, while the medullary cell was the rule in the two tumors that were predominantly epithelial.

Antibodies, Monoclonal↗

B-cell neoplasms of the lymphocytic, lymphoplasmacytoid, and plasma cell types: immunohistologic analysis and clinical correlation.

The relation between chronic lymphocytic leukemia (CLL, lymphocytic lymphoma (SL), plasmacytoid lymphocytic lymphoma (LP), plasmacytoma (PL), and multiple myeloma (MM) was investigated with cryostat sections stained with antibodies to immunoglobulin heavy and light chains and the B-cell differentiation antigens B1, B2, Ia, T1, and CALLA. Neoplasms were subclassified according to plasmacytoid features, leukemia (CLL) site of involvement (nodal or extranodal), serum monoclonal immunoglobulin, or clinical evidence of MM. The results defined two groups of lymphocytic lymphomas without plasmacytoid features (16 cases). Ten of these lymphomas were associated with CLL. Nine involved lymph nodes, all expressed IgM, five expressed IgD, nine were B2-positive, eight were T1-positive, and all were B1- and Ia-positive. Six of the lymphomas were not associated with CLL. Five of these tumors were extranodal, all were T1- B1+ B2- Ia+, five expressed IgM without IgD, and one contained IgG. These differences in clinical and immunologic phenotypes suggest that CLL and SL without CLL may be related to different stages of B-cell differentiation. T1 appeared to be a marker for CLL, since all T1-positive neoplasms were leukemic. Lymphomas with plasmacytoid features (ten cases) were more often extranodal, and none was leukemic. The immunologic phenotypes were heterogeneous: all of these lymphomas were T1-negative, most were IgM+ IgD-, three were B2-positive, and all were Ia-positive. The plasma cells in five lymphomas with marked plasmacytoid features were B1-negative; they were Ia-positive in four and Ia-negative in one. These data suggest that LP is a heterogeneous group, reflecting B cells at diverse stages of differentiation. Ten plasmacytomas, nine of which were associated with MM, differed from LP in showing heavy chain class switching; all were T1- B1- B2-, and all but one were Ia-negative. These results are consistent with the existence of two pathways or stages of B-cell differentiation: one that generates IgM-producing plasma cells, as seen in the primary immune response or in response to pokeweed mitogen, and one that generates IgG- or IgA-positive plasma cells, as seen in the late primary or secondary immune response. Plasmacytoid lymphocytic lymphoma reflects the first, while PL/MM reflects the second pathway. B1 appears to be lost before Ia in terminal plasma cell differentiation.

Antibodies, Monoclonal↗

Lymphoma-like lesions of the lower female genital tract: a report of 16 cases.

The microscopic differential diagnosis of malignant lymphoma and benign lymphoid infiltrates in the lower female genital tract may be difficult. We have reviewed the clinical and pathological features of 16 lymphoma-like lesions of the cervix (10 cases), endometrium (five cases), and vulva (one case) and compared these features with those of malignant lymphoma. One patient with a cervical lesion and one with a vulvar lesion had infectious mononucleosis. Microscopic examination of the lesions revealed an infiltrate of large lymphoid cells with prominent mitotic activity, including cleaved and noncleaved follicular center cells and immunoblasts; a starry-sky pattern was present in three cases. Plasma cells, polymorphonuclear leukocytes, and small lymphocytes were present within the infiltrate in many of the cases. Immunohistochemical stains were performed in seven cases. In six they indicated the presence of polyclonal plasma cells; most of the atypical large cells did not stain for cytoplasmic immunoglobulin. In the seventh specimen many immunoblasts had cytoplasmic staining of polyclonal type. The microscopic features of the lesions differ from those of lymphomas. Surface ulceration and intralesional acute inflammatory cells and plasma cells are rarely seen in lymphomas, while a large size, deep invasion, cellular monomorphism, and prominent sclerosis were not seen in the reactive lymphoma-like lesions. Follow-up of from 6 months to 12 years was available for 10 of the 16 patients, nine of whom were treated by procedures inadequate for the cure of malignant lymphoma, and has been uneventful in all of them. The clinical and pathologic features of these cases suggest that the atypical appearances in most of them resulted from a focally florid lymphoid proliferation in association with chronic cervicitis or endometritis, or a generalized disorder of lymphoid cells such as infectious mononucleosis.

Adult↗

Thymic cysts in mediastinal Hodgkin disease.

Three cases of proved thymic cysts associated with mediastinal Hodgkin disease are presented. Two illustrate regression of lymphoma with chemotherapy but persistence of thymic cysts. The third case demonstrates a thymic cyst in untreated Hodgkin disease. These cases suggest that such cysts are probably neither coincidental with nor a consequence of therapy but are probably related to initial thymic involvement by Hodgkin disease.

Adult↗

Malignant lymphoma presenting as Kaposi's sarcoma in a homosexual man with the acquired immunodeficiency syndrome.

A homosexual man had Kaposi's sarcoma of the skin and lymph nodes. After a brief response to interferon, the patient developed new skin lesions. Massive bleeding in the gastrointestinal tract prompted endoscopy, which showed tumor involvement of the stomach, believed to be Kaposi's sarcoma. At autopsy, a diffuse lymphoma was found involving the skin and gastrointestinal tract, forming collision tumors in regions that contained Kaposi's sarcoma. Lymphomatous tissue, but not uninvolved lymph node or spleen, contained Epstein-Barr virus DNA, as shown by DNA hybridization studies. Epstein-Barr virus may play a role in the development of lymphoma in immunosuppressed patients. Unusual manifestations of tumors, such as the massive gastrointestinal bleeding seen in this case, may indicate the development of a second neoplasm.

Acquired Immunodeficiency Syndrome↗

Mantle-zone lymphoma. A pattern produced by lymphomas of more than one cell type.

We analyzed the distribution and immunologic phenotype of the neoplastic cells in eight cases of mantle-zone lymphoma. Although in all the cases the follicle centers appeared reactive on routine histologic examination, polyclonal staining for immunoglobulin was found in the follicle centers in only five of the eight cases; in the other three cases the follicle centers were monoclonal. In three cases, the immunologic phenotype was that of centrocytic (diffuse small cleaved cell) lymphoma: IgM+IgD+B1+B2+Ia+Tl+. In one case the phenotype was that of a follicular (centroblastic/centrocytic) lymphoma: IgG+B1+B2+Ia+CALLA+. In the other four cases, the phenotype was IgM+B1+B2+ or B2-Ia+; this phenotype can be seen in diverse B cell lymphomas. The phenotype of normal mantle-zone cells (IgM+IgD+B1+B2+Ia+) was not reproduced by any of the lymphomas. A mantle-zone pattern may be produced by either follicular or diffuse lymphomas of predominantly small cleaved cell type, and does not indicate an origin from the cells of the normal mantle zone.

Antibodies, Monoclonal↗

Malignant lymphoma of the thyroid gland: a clinical and pathologic study of twenty cases.

Among 20 patients with malignant lymphoma of the thyroid gland, the mean age at diagnosis was 63 years and the male to female ratio was 1:6. All patients had a firm, rapidly enlarging neck mass. In 90% of the patients the mass had been present for less than 1 year; in 40%, for less than 1 month. Approximately half of the patients tested had hypothyroidism; three fourths had elevated antithyroid antibodies. There was one nodular lymphoma. The remaining 17 cases available for review were diffuse. Thyroid lobectomy was performed in seven patients, limited excision in eight, and needle biopsy alone in five. External irradiation was administered in 11 cases (55%). Chemotherapy was used alone in one patient (5%) and in combination with radiotherapy in eight (40%). Six patients (30%) were alive without evidence of recurrent disease at follow-up ranging from 1 to 12 years. Eleven patients had died of lymphoma, all but one dying within 1 year. One patient died of other causes and two were lost to follow-up study. There was no appreciable effect of patient age or sex, lymphoma histology, or extent of surgical resection on survival. Treatment of choice for primary lymphoma of the thyroid gland appears to be external irradiation or chemotherapy, alone or in combination. The role of surgery is limited to making a tissue diagnosis of lymphoma, unless the tumor is completely intrathyroidal.

Adolescent↗

Diffuse large cell (histiocytic) lymphoma of the spleen. Clinical and pathologic characteristics of ten cases.

Ten patients with diffuse large cell (histiocytic) lymphoma of the spleen had a characteristic clinical presentation and pathologic findings. Patients presented with left upper quadrant pain, fever, weight loss, and an elevated sedimentation rate. Imaging studies revealed an enlarged spleen with a discrete mass in all cases. Moderate to massive splenomegaly (average weight, 1025 g) was found at laparotomy; a single large mass or multiple confluent nodules with extensive central necrosis replaced 85% to 90% of the parenchyma. The tumor transgressed the splenic capsule in nine of ten cases, and either invaded or was adherent to the diaphragm, stomach, pancreas, or abdominal wall. Lymph nodes in the splenic hilum or retroperitoneum were frequently involved. Seven patients were in Ann Arbor Stage II, and three were in Stage I. Eight of the ten lymphomas were subclassified as centroblastic (large noncleaved cell) and two were immunoblastic. The B-cell lineage of six tumors was established by the presence of monoclonal immunoglobulin. Despite combination chemotherapy, with or without radiation, three of the seven patients whose follow-up was adequate died in less than 2 years; four are alive at 7, 12, 12, and 81 months, respectively, the last two with recurrent lymphoma. Large cell lymphoma of the spleen is a likely diagnosis in patients who present with left upper quadrant pain, fever, and radiographic evidence of a splenic mass.

Adult↗

Radiation therapy of Waldeyer's ring lymphoma.

Forty-nine patients with biopsy-proven Waldeyer's ring lymphoma were treated with radiation therapy between 1968 and 1979; 45 to 50 Gy were given to Waldeyer's ring structures with a 5- to 10-Gy boost to the primary site. Uninvolved low cervical nodes received 40 to 50 Gy. Chemotherapy was reserved for treatment failures. Actuarial 5-year survival was 53%, disease-free survival was 48%, and local control was 98%. Patients with Stage I disease fared better than patients with Stage II disease, and unilateral adenopathy conferred a better prognosis than bilateral adenopathy. When classified by the Rappaport system, nodular lymphomas had a better prognosis than diffuse lymphomas, and of the diffuse lymphomas, histiocytic lymphoma was a more lethal disease than lymphocytic lymphoma. Patients with diffuse undifferentiated lymphomas in the Rappaport system, or high-grade lymphomas in the Working Formulation, fared poorly. Most relapses were systemic, and actuarial 5-year survival after salvage was only 20%. A logical approach to the treatment of this disease can be based on these prognostic features.

Actuarial Analysis↗

Malignant lymphoma and granulocytic sarcoma of the uterus and vagina. A clinicopathologic analysis of 27 cases.

Twenty-five cases of malignant lymphoma of the uterine corpus or cervix and the vagina, and one case of granulocytic sarcoma of the cervix were analyzed. The patients typically presented with vaginal bleeding and a subepithelial mass without obvious ulceration or other epithelial abnormality. Twenty-one of the 27 tumors appeared to originate in the cervix, 4 in the vagina, and 2 in the endometrium. Seven of them were nodular lymphomas, 17 diffuse large cell, or "histiocytic" lymphomas, 1 was a Burkitt's tumor, and 2 were granulocytic sarcomas. Sclerosis was a prominent histologic feature in lymphomas of the cervix and vagina. Twenty-one patients had disease confined to a single extranodal site (Ann Arbor Stage IE), and six had lymph node or ovarian involvement (Stages IIE + IV). The overall actuarial 5-year survival was 73%. The survival of patients with Stage IE tumors was 89%, compared with 20% for patients with lymph node or ovarian involvement. None of the 12 patients with Stage IE lymphoma of the cervix or vagina who received definitive initial local treatment (surgical and/or radiation therapy) relapsed. Nodular lymphomas and diffuse lymphomas with a preponderance of large cleaved cells were more often localized and had a better prognosis than large or small noncleaved and immunoblastic types. Lymphoma of the lower female genital tract is a rare, but treatable malignancy, which must be distinguished microscopically from inflammatory lesions and nonlymphoid tumors arising in this site.

Adult↗

Characterization of immature sinus histiocytes (monocytoid cells) in reactive lymph nodes by use of monoclonal antibodies.

The distinctive mononuclear cells that appear in the cortical sinuses of lymph nodes in toxoplasma lymphadenitis and other conditions have been termed "immature sinus histiocytes," although these cells have neither enzyme histochemical nor ultrastructural features of histiocytes. The authors stained these cells in frozen sections of six reactive lymph nodes, using the immunoperoxidase technique, with monoclonal antibodies to T cell, B cell, and monocyte antigens and with heteroantisera to immunoglobulin and lysozyme. The immature sinus histiocytes stained with a monoclonal antibody to B cells (anti-B1) and had immunoglobulin of the IgG class. They did not react with monoclonal antibodies to T cells or monocytes or with antilysozyme. In contrast, medullary sinus histiocytes in three additional lymph nodes were B1-negative and reacted with anti-T4, anti-M1, and anti-lysozyme. These results indicate that immature sinus histiocytes are IgG-bearing B lymphocytes rather than histiocytes. Their role in the immune response remains enigmatic.

Antibodies, Monoclonal↗

Immunohistologic diagnosis of orbital lymphoid infiltrates.

The distinction between benign and malignant lymphoid infiltrates of the orbit may be impossible on routine histopathologic sections. However, the detection of monotypic immunoglobulin is useful in distinguishing neoplastic from benign infiltrates. Since diagnostic frozen sections are often performed on biopsies of orbital masses to determine the adequacy of the biopsy and to provide a preliminary diagnosis, we stained additional frozen sections of 20 predominantly lymphoid infiltrates by an immunoperoxidase technique with antisera to immunoglobulin heavy and light chains. On routine sections, nine cases were malignant lymphoma, three were follicular hyperplasia, and eight (42%) were dense lymphocytic infiltrates of indeterminate nature. The nine lymphomas had monotypic immunoglobulin staining. The three histologically benign lesions had polytypic immunoglobulin. Six of the eight indeterminate lesions had monotypic immunoglobulin, supporting a diagnosis of lymphoma; two had polytypic staining. There was evidence of disseminated lymphoma at the time of diagnosis in five of nine patients with histologically malignant lesions and three of five with monoclonal indeterminate lesions for whom the information was available. Staining with monoclonal antibodies to T-cells revealed variable numbers of T-cells in all cases; their number and distribution did not distinguish benign from malignant lesions. The immunoperoxidase technique on frozen sections permits optimal use of small biopsy specimens for both morphologic and immunologic diagnosis. The majority of histologically indeterminate orbital lymphoid infiltrates were shown to be monoclonal.

Diagnosis, Differential↗