Relationship of tumor grade, stage and host response in a group of breast neoplasms.
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Adenocarcinoma, Mucinous↗
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Hybrid form of hairy cell leukemia and chronic lymphocytic leukemia.
We report a case with mixed features of hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL), which may represent a hybrid form of these two entities. Hairy projections were demonstrated on leukemic cells in the peripheral blood. Surface marker studies of blood and spleen specimens by flow cytometry and immunohistochemistry showed immunophenotype characteristic of HCL, namely, monoclonal IgG-kappa, positive reactions to CD 11c, CD 19, CD 20, Cd 22, and HLA-DR, but negative reactions to CD 3, CD 5, CD 7 and CD 10. The only atypical finding was the absence of CD 25. Immunogenotyping showed rearrangement of heavy-chain and kappa light chain genes. Leukemic cells were also positive for tartrate-resistant acid phosphatase (TRAP). A pseudosinus pattern was demonstrated in the spleen. However, the leukemic cells in the spleen showed atypical cytologic features. Clinically, the patient had generalized lymphadenopathy, high leukocyte counts, Coombs' negative hemolysis, hypoimmunoglobulinemia and IgG-kappa monoclonal gammopathy, features more consistent with CLL than HCL. Although only CD 11c, CD 22, CD 25 and TRAP are characteristic for HLC and CD 5, characteristic for CLL, a panel of eight markers is recommended for the differential diagnosis of HCL, CLL and other low-grade B-cell neoplasms, which may share some common features, making a clear-cut diagnosis difficult.
Antigens, CD↗
Primary carcinoma of the gallbladder: TNM staging and prognosis.
In order to investigate the lethality of carcinoma of the gallbladder and several of the coexisting features, a retrospective analysis of 53 patients with this disease was undertaken. Abdominal pain, obstructive jaundice, and a right upper quandrant mass were present in approximately one-half of the patients. Laboratory and radiological data were frequently nonspecific and did little to identify the diagnosis. The most common preoperative diagnoses were cholelithiasis or chronic cholecystitis. Cholecystectomy was the most frequently performed procedure. Fifteen wedge liver resections were performed. No radical or extended liver resections were done. Eighty-one percent of the patients had sufficient data for staging. Five patients (11.6%) had stage I lesions, three patients (7.0%) had stage II lesions, while 17 (39.5%) and 18 (41.9%) patients had stage III and IV lesions, respectively. Mean survival was 6.4 months for the entire group. Three patients are still alive (two longer than 5 years and one at 2 years) for an overall survival of 5.7%. Both staging and grading of the tumor correlated well with patient survival. Those patients with stage I lesions survived significantly longer (23 months vs. 3 months) than those with stage IV tumors. Also, those with more favorably graded (well-differentiated) neoplasms lived an average of 13 months longer than patients with poorly differentiated lesions.
Adenocarcinoma↗
Expression of blood group antigens in bladder cancer: current concepts.
Blood group antigens are a group of carbohydrate structures bound to membrane lipids or proteins of erythrocytes and certain epithelial tissues including urothelium. The Lewis antigens are structures that are genetically and biochemically related to the ABO blood group. The ABO and Lewis blood group systems are differentially expressed in the normal urothelium of "secretors" versus "nonsector" individuals. The normal urothelium of "secretors" is rich ABH, Leb, and Ley antigens while the urothelium of "nonsecretors" does not express these antigens. Therefore, deletion of ABH antigens, commonly noted in TCC, can only be reliably ascertained in "secretor" individuals. Neoexpression of the Lewis X antigen (which is absent in normal urothelium) is noted in over 85% of TCC regardless of tumor stage and grade. Immunocytological detection of the Lewis X antigen on exfoliated bladder epithelial cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms.
ABO Blood-Group System↗
Extranodal lymphoplasmacytoid lymphoma: spectrum of disease.
Lymphoplasmacytoid lymphomas (LPL) are non-Hodgkin's lymphomas characterized by a proliferation of lymphoplasmacytoid cells or plasma cells with intracytoplasmic monoclonal Ig. The LPL are low-grade B-cell neoplasms close to B chronic lymphocytic leukemia with plasmacytoid differentiation. They show an indolent course, typically affect older men, and present as a disseminated disease with predominantly nodal involvement. Nevertheless, localized forms, some of them extranodal, have been described. The cases that best represent the range of radiographic findings on X-ray, CT, and MR imaging are presented.
Adult↗
Expression of BAFF-R (BR 3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody.
BAFF-receptor (BAFF-R) is required for the successful maturation and survival of B-cells. We developed an anti-human BAFF-R monoclonal antibody (mAb), 8 A 7. The reactivity of 8 A 7 in normal and neoplastic tissue was examined by performing immunohistochemistry on paraffin-embedded sections. 8 A 7 reacted with lymphocytes in the mantle and marginal zones, but not with lymphocytes in the interfollicular area. Lymphocytes in the germinal centers were found to be negative or occasionally weakly positive for 8 A 7. BAFF-R expression was found only in B-cell lymphoma (44/80, positive cases/examined cases): B-lymphoblastic lymphoma 0/3, B-chronic lymphocytic leukemia/small lymphocytic lymphoma 4/4, mantle cell lymphoma 9/11, follicular lymphoma 10/14, diffuse large B-cell lymphoma (DLBCL) 11/25, marginal zone B-cell lymphoma 8/10, lymphoplasmacytic lymphoma 2/2, plasma cell myeloma 0/2, and Burkitt lymphoma 0/9, but not in T/NK cell lymphomas (0/19) or Hodgkin lymphoma (0/10). BAFF-R was expressed in most low-grade B-cell neoplasms and a small number of DLBCL, suggesting that BAFF-R may play an important role in the proliferation of neoplastic lymphoid cells. Thus, the mAb is very useful for further understanding of both healthy B-cell biology and its pathogenic neoplasms.
Antibodies, Monoclonal↗
Gemistocytic astrocytomas: histomorphology, proliferative potential and genetic alterations--a study of 32 cases.
Gemistocytic astrocytomas (GAs) are a distinct variant of astrocytomas, generally classified as WHO grade II, and are associated with an aggressive biological behavior. This study was undertaken to determine the histomorphological spectrum, and correlate these with their proliferative potential and genetic alterations, in order to establish a biological basis for their unfavorable prognosis.A total of 32 GAs diagnosed during an 11-year period (1993-2003) were included in the study. Immunoreactivity for CD3 (T-cells), CD20 (B-cells) and CD68 (macrophages) were evaluated to characterize the perivascular inflammatory infiltrates, while p53, epidermal growth factor receptor (EGFR), cyclin D1 and p27-immunolabeling were studied to analyze the tumor biology.Overall, the mean gemistocytic index in the study was 39.6% (range, 12.2-80.8%), with multinucleation in gemistocytes and mitosis being present in 56.2% and 15.6% respectively. Perivascular mononuclear cell cuffing was seen in 56.2% cases, which was immunopositive for CD3 and CD68 in 14 cases each, with 13 cases being immunopositive for both. Similar type of inflammatory infiltrates was also present within the tumor parenchyma. Proliferation index depicted by MIB-1 LI was low (mean: 3.7%; range: 0.5-10.5%), with 70% cases having LI of <5%. MIB-1 labeling was restricted to the small astrocytic cells, similar to p27 and cyclin D1 immunoreactivity, both of which were present in 71.5% cases. In contrast, p53 protein expression was present in 75% cases, and was strongly positive in both gemistocytes and small cells, denoting neoplastic population. However, EGFR protein expression was consistently negative in all cases. Gemistocytes lack proliferative activity possibly indicating terminal differentiation, while small cells are the proliferating cells and their overall percentage may reflect the biological aggressiveness of these tumors and help to identify GAs of higher grade undergoing malignant progression. Therefore it appears that GAs should not be uniformly graded as grade II but should be subdivided into grades II and III neoplasms based on histological features and MIB-1 LI. The poor prognosis in GAs could be attributed both to the high frequency of p53 mutations and low p27 LI.
Adolescent↗
Recurrent FGFR2 and PIK3CA Mutations in Sialoblastoma.
PURPOSE: Sialoblastoma is an extremely rare low-grade malignant salivary gland neoplasm that presents at birth or early infancy and has heterogeneous clinical behavior. Due to its rarity, the molecular landscape remains incompletely characterized. We aimed to expand the current understanding of the genetic alterations in sialoblastoma through comprehensive molecular analysis. METHODS: Five sialoblastoma cases were retrieved from four institutional archives. Clinical and pathologic review was performed, and targeted next-generation sequencing was conducted using clinically validated panels. Copy number analysis was performed on four cases. RESULTS: The cohort included five patients with tumors located in parotid gland (n = 2), minor salivary glands (n = 2), and submandibular gland (n = 1). Four patients were diagnosed before 6 months of age. Histologically, all tumors showed solid organoid nests with primitive basaloid cells, dense fibrous stroma, and mitotic activity ranging from 8 to 25 per 10 high-power fields. Recurrent FGFR2 p.C382R variants were identified in 80% (4/5) of cases. Additional alterations were seen in FGFR2 p.C382R mutated tumors, including PIK3CA hotspot mutations in two cases (p.R88Q, p.R38H) and a truncating FGFR2 variant (p.L776Rfs) in one. The single tumor that lacked FGFR2 mutations harbored a CTNNB1 p.I35T variant and showed more favorable histologic features. Copy number analysis revealed recurrent whole-chromosome gains of chromosomes 8, 10, and 11. CONCLUSION: A distinct subset of sialoblastoma has FGFR2 p.C382R hotspot mutation as the predominant driver mutation. Tumors with this mutation tend to have solid growth pattern, aggressive histologic features, and clinical behavior. The identification of concurrent genomic alterations expands the molecular landscape of this rare tumor. The detection of alternative drivers, such as CTNNB1 hotspot mutations typical of basal cell adenoma, also suggests that a subset of sialoblastoma may represent other salivary gland tumors presenting in infancy.
Humans↗
Immunotherapy of intraperitoneal cancer with interleukin 2 and lymphokine-activated killer cells reduces tumor load and prolongs survival in murine models.
The control of malignancy disseminated within the peritoneal cavity is an important problem in the management of low-grade gastrointestinal and ovarian neoplasms. A model of peritoneal carcinomatosis in the mouse was used to investigate the potential of lymphokine-activated killer (LAK) cells and exogenous interleukin 2 (IL-2) to control intraperitoneal tumor. LAK cells are splenocytes activated in vitro by IL-2. C57BL/6 mice were injected intraperitoneally with a lethal inoculum of syngeneic MCA-105 tumor. Three days later, the established tumor was treated with adoptively transferred LAK cells and/or exogenous IL-2 administration. LAK cells alone were ineffective in reducing intraperitoneal tumor. Administration of IL-2 alone resulted in limited tumor reduction. Treatment with exogenous IL-2 in conjunction with LAK cells resulted in the greatest reduction of intraperitoneal tumor. The larger the number of LAK cells given, the greater the reduction in tumor. Frequent intraperitoneal bolus administration of IL-2 was more effective than a single daily intraperitoneal injection and intraperitoneal administration of IL-2 and LAK was more effective than systemic treatments. Marked prolongation of life was seen in mice treated with LAK cells plus exogenous IL-2. We conclude that intraperitoneal LAK cells plus exogenous IL-2 is an effective treatment regimen for reducing intraperitoneal tumor in this murine model.
Animals↗
Monocytoid B-cell lymphoma with a distinctive clinical presentation.
Monocytoid B-cell lymphoma (MBCL) is a recently described non-Hodgkin's lymphoma. Patients with MBCL usually present with localized or generalized lymphadenopathy; peripheral blood and bone marrow involvement is rare. Patients with leukemic manifestations typically have advanced disease with extensive lymph node and bone marrow involvement. We report a distinctively unusual case of MBCL with peripheral blood and splenic involvement at presentation and with no evidence of peripheral lymph node disease. This case emphasizes the fact that malignancies of monocytoid B cells should be viewed as a spectrum of disease that ranges from leukemia to lymphoma. This feature is similar to other low-grade B-cell neoplasms, such as chronic lymphocytic leukemia/small cell lymphoma, lymphocytic type.
Aged↗
Cytogenetic studies of composite lymphomas: monocytoid B-cell lymphoma and other B-cell non-Hodgkin's lymphomas.
Monocytoid B-cell lymphoma (MBCL) is a newly recognized, morphologically and immunologically distinct, low-grade B-cell neoplasm that may exist as a pure morphologic entity or as a component of a composite lymphoma. To determine whether cytogenetic abnormalities exist in cases of MBCL, fresh tissue from four lymphoma specimens in which MBCL was a substantial component were analyzed by classic cytogenetics; no pure MBCL cases were available for study. One monoclonal neoplastic population was found in each case by immunophenotyping studies and classic cytogenetics. Clonal cytogenetic abnormalities included -X or +X, t(14;18)(q32;q21), del(6q), t(11;14)(q13;q32), dup(12q), dup(1q), t(2;3)(q13;q29), and der(8)t(8;9)(p11.2;q13). The abnormal clone usually reflected the underlying lymphomatous process, namely, follicular lymphoma [t(14;18)], mantle cell lymphoma [t(11;14)], or small lymphocytic lymphoma (partial trisomy 12). There were no cytogenetic abnormalities common to all neoplasms. Taken together, the cytogenetic and immunologic data suggest that although MBCL may exist as a pure entity, it also may commonly represent a morphologic variant or a component of other primary lymphomatous processes.
Adult↗
Effects of the CD33-targeted drug gemtuzumab ozogamicin (Mylotarg) on growth and mediator secretion in human mast cells and blood basophils.
OBJECTIVE: Mylotarg (gemtuzumab ozogamicin [GO]) has recently been introduced as a novel CD33-targeting drug in clinical hematology. However, despite efficacy, GO produces significant side effects including an infusion syndrome. We have recently shown that mast cells (MCs) and basophils (BAs) express CD33. In the present study, we investigated the effects of GO on growth and mediator secretion in MCs and BAs. METHODS: Growth-inhibitory effects of GO on neoplastic MCs (HMC-1) and BAs (KU812) as well as cord blood-derived MC and BA progenitor cells were determined by counting cell numbers and the numbers of apoptotic cells. The amount of histamine secreted from primary MCs and BAs was measured by radioimmunoassay after incubation of cells with GO alone or GO together with an anti-immunoglobulin E (IgE) antibody. RESULTS: MCs and BAs as well as HMC-1 cells and KU812 cells were found to express CD33 mRNA and the CD33 protein. GO was found to inhibit the growth of HMC-1 cells and KU812 cells as well as stem cell factor-dependent differentiation of MCs and interleukin-3-induced growth of BAs from their cord blood-derived progenitors. The GO-induced inhibition of growth of neoplastic cells was found to be associated with induction of apoptosis. GO neither induced secretion of histamine from MCs or BAs nor upregulated the anti-IgE-induced release of histamine in these cells. CONCLUSIONS: GO counteracts growth of normal and neoplastic MCs and BAs without inducing rapid release of histamine. The exact value of GO as a targeted drug for the treatment of high-grade MC or BA neoplasms remains to be determined.
Aminoglycosides↗
Epithelial-myoepithelial carcinoma of the submandibular gland with a high uptake of 18F-FDG: a case report and image diagnosis.
Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade malignant salivary gland neoplasm typically found in the parotid gland. This report describes a case of EMC that arose from the submandibular gland, and gives special emphasis to the preoperative diagnostic value of positron emission tomography (PET) in combination with computed tomography (CT) and magnetic resonance imaging (MRI). Although a preoperative diagnostically specific image of EMC could not be established, the malignant nature of this tumor was detected by these combined examinations.
Aged↗
Enhanced bladder cancer detection with the Lewis X antigen as a marker of neoplastic transformation.
Recent evidence indicates that the Lewis X determinant is a tumor-associated antigen in the urothelium. Immunohistochemical analyses on frozen and deparaffinized, formalin-fixed tissue sections have demonstrated that the Lewis X antigen is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas and transitional cell carcinomas express this blood group-related antigen in more than 90% of the cases regardless of the grade or stage of the tumor, or the blood type or secretor status of the individual. To determine the presence of Lewis X antigen on exfoliated bladder epithelial cells we used an anti-Lewis X monoclonal antibody (P-12) and the avidin-biotin-peroxidase technique on 129 bladder barbotage specimens. Of 40 controls 34 were negative for Lewis X antigen, for a specificity of 85%. The 89 bladder tumor patients consisted of 14 with papilloma, 13 with flat carcinoma in situ, 49 with transitional cell carcinoma, and 13 with a positive cytology and negative biopsy results. Of these 89 patients 76 were considered positive for Lewis X antigen, for an over-all sensitivity 85.4%. The sensitivity for cytology alone was 61.2%. However, the combination of a positive cytology and/or positive Lewis X antigen result yielded a sensitivity of 93.2%. The data suggest that immunocytological detection of the Lewis X antigen on exfoliated bladder cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms.
Antibodies, Monoclonal↗
Histological characteristics of prostatic biopsies after 125iodine implantation.
There were 39 prostatic needle biopsies obtained from 33 patients with carcinoma of the prostate 1 to 3 years after definitive treatment with interstitial implantation using 125iodine radioactive sources. Of these biopsies 57 per cent obtained at 12 to 18 months and 73 per cent obtained at 19 to 36 months after implantation were negative for malignancy. All biopsies revealed histologic evidence of significant radiation injury. Neither the presence or absence of malignancy on biopsy nor the degree of radiation injury could be related to the initial stage and grade of the prostatic neoplasm.
Aged↗
Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes.
The cell of origin of parafollicular (monocytoid) B cell lymphoma (PBCL), splenic marginal zone lymphoma (SMZL), and hairy cell leukemia (HCL) is controversial. To better understand the relationship between these low-grade B-cell neoplasms, we analyzed the nucleotide sequences of the rearranged immunoglobulin heavy (IgH) chain variable (V) region of the clonal population of cells in five cases of PBCL, four cases of SMZL, and seven cases of HCL to determine whether these neoplasms could be differentiated by the degree of somatic mutation in the IgH V gene or by the IgH V gene family usage. DNA was extracted from diagnostic material and clonality confirmed by PCR. The DNA was reamplified using V heavy chain family specific primers, and the amplicons were sequenced. Sequences were compared with germline IgH V gene sequences, and base changes were determined to be silent or to represent amino acid replacements by using three different methods. Four of five (80%) cases of PBCL, three of four (75%) cases of SMZL, and three of seven (43%) cases of HCL showed evidence of antigen selection, suggesting that these neoplasms involved clonal expansions of postgerminal center memory lymphocytes. Only SMZL showed a preferential usage of V(H)1 family genes.
Adult↗
Overrepresentation of 1q21-23 and 12q13-21 in lipoma-like liposarcomas but not in benign lipomas: a comparative genomic hybridization study.
Twenty lipomatous tumors, including eight lipoma-like liposarcomas and 12 benign lipomas, were analyzed using comparative genomic hybridization (CGH). DNA sequence copy number changes detected in five lipoma-like liposarcomas (mean, 1.1 aberrations/tumor; range, 0-2) consisted of gains of 12q13-21 (five tumors) and 1q21-23 (four tumors). Two of the tumors showed high-level amplification at 12q14-21 and one tumor at 1q21-22. No copy number changes were found in lipomas. Overrepresentation of 1q and 12q sequences was a recurrent finding in lipoma-like liposarcomas but not in lipomas. Thus, CGH may help in the differential diagnosis of low-grade or borderline adipose neoplasms.
Adult↗
[Mammographic stable lesions and carcinomas].
Stable breast carcinomas at mammography are infrequent and typically correspond to low-grade non-invasive neoplasms. Diagnosis may be delayed by several months to a few years. This time delay to diagnosis may be reduced by using optimal mammographic technique and careful image interpretation. These lesions frequently are misclassified as BIRADS class III lesions. Comparison with prior mammograms is mandatory for accurate diagnosis of these lesions.
Breast Neoplasms↗