bromochloroacetic-acid and Lymphoma--Large-B-Cell--Diffuse

Aberrant expression of epithelial and neuroendocrine markers is rare in diffuse large B-cell lymphoma (DLBCL) and can lead to erroneous diagnosis with inappropriate treatment. This case report describes a case of DLBCL with a co-expression of cytokeratins and CD56 that was misdiagnosed as metastatic neuroendocrine carcinoma.

Topics: Carcinoma, Neuroendocrine; CD56 Antigen; Humans; Immunophenotyping; Keratins; Lymphoma, Large B-Cell, Diffuse

Topics: Humans; Keratins; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Receptor Protein-Tyrosine Kinases

Pancytokeratins and TTF-1 are used in working up carcinomas of unknown primary and p63 is expressed in many cell lineages. We present a case of a TTF-1, p63, and cytokeratins positive small round blue cell lesion presenting in a patient with enlarged right supraclavicular lymph nodes and multiple solid pulmonary nodules. The preliminary report to the clinical team was "suspicious for carcinoma." However, after a complete work up the final diagnosis of diffuse large B-cell lymphoma, nongerminal center B-cell phenotype, "double expressor," was rendered (based on Han's algorithm). This case brings up significant diagnostic dilemma as some lymphoid malignancies can morphologically mimic poorly differentiated carcinoma and stain positive for carcinoma markers. Additionally, the frequently used TTF-1 SPT23 antibody clone has strong nuclear staining in rare cases of DLBCL, which is a diagnostic pitfall. To our best knowledge this is the first reported case of DLBCL staining positive for three carcinoma markers.

Topics: Aged; B-Lymphocytes; Biomarkers, Tumor; DNA-Binding Proteins; Humans; Keratins; Lymphoma, Large B-Cell, Diffuse; Male; Membrane Proteins; Transcription Factors

Topics: Biomarkers, Tumor; Cell Proliferation; Diagnosis, Differential; Drug Therapy, Combination; Humans; Keratins; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Polyradiculopathy; Spinal Cord; Spinal Cord Neoplasms; Treatment Outcome

A 40-year-old Japanese man was admitted to our hospital for evaluation of upper abdominal pain. Abdominal computed tomography (CT) revealed a well-circumscribed multicystic mass measuring approximately 7 × 6 cm. The mass contained a solid lesion measuring 3 × 2 cm. Biopsy of a swollen cervical lymph node led to a diagnosis of diffuse large B-cell lymphoma. After initial chemotherapy for lymphoma, the multicystic mass was surgically resected. The tumor was composed of a multicystic lesion and a solid lesion. Histopathologic examination of the multicystic lesion revealed that the locules were lined by biliary epithelium, demonstrating various degrees of cytological atypia. The stroma was fibrous, and the tumor showed marked apocrine snouts. Part of the tumor showed papillary growth with strong cytological atypia. The solid lesion showed tubulocystic proliferation of tumor cells, with prominent apocrine snouts, embedded in dense and partially hyalinized fibrous stroma. The morphology of the solid part was quite similar to that of reported biliary adenofibroma. Despite lengthy discussion, an appropriate pathological diagnosis could not be found among the current classifications of biliary tumor. The tumor was finally diagnosed as unclassified multicystic biliary tumor with adenofibroma features.

Topics: Adenofibroma; Adult; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Combined Modality Therapy; Cystadenocarcinoma; Diagnosis, Differential; Fatal Outcome; Humans; Keratins; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Male; Neoplasms, Multiple Primary

Plasmablastic lymphoma (PBL) is very rare, and predominantly occurs in Human immunodeficiency virus (HIV)-positive individuals. It shows a strong affinity for the oral cavity and for the Epstein-Barr virus (EBV) positive. We investigated the clinicopathologic characteristics of six cases of PBL in Koreans. All patients were HIV-negative and without underlying immunodeficiency. The age distribution was bimodal, and four patients were older than 60 years. Male predominance was observed with male to female ratio of 5:1. The organs primarily involved were the terminal ileum, stomach, oral cavity, tonsil, nasal cavity and meninges. The tumors were histologically typical of PBL. Three of them were composed of monomorphic large immunoblastic or plasmablastic cells, and classified as PBL of the oral mucosa type. Another three cases were classified as PBL with plasmacytic differentiation. Five cases revealed loss of B-cell antigens with CD138 or MUM1 substitution. CD10 was positive in two cases (PBLs of the oral mucosa type), and one of them unexpectedly expressed cytokeratin. EBV was detected in one case (PBL with plasmacytic differentiation). Four patients succumbed to PBL in a relatively short period of time. We suggest that PBL is not strongly associated HIV or EBV in Koreans, and that it shows a variable organ distribution without an oro-nasal predilection.

Topics: Adolescent; Aged; Child; Epstein-Barr Virus Infections; Female; Gastric Mucosa; Gene Rearrangement; Herpesviridae Infections; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Ileum; Immunoglobulin Heavy Chains; Immunohistochemistry; In Situ Hybridization; Interferon Regulatory Factors; Keratins; Korea; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Male; Mouth; Neprilysin; Polymerase Chain Reaction; Stomach

The purpose of this study is to evaluate the value of cytokeratin (CK) MNF116 and vimentin in the differential diagnosis of malignant pleural effusions. There were evaluated smears from 30 patients with pleural effusions stained with May-Grünwald Giemsa and Papanicolaou techniques for the routine cytological diagnosis. Additional smears were immunostained with CK MNF116 and vimentin using LSAB2 technique. Two independent observers evaluated all smears. Smears were classified first by cytological examination in seven cases (23.33%) as benign, and in 23 cases (76.67%) as malignant pleural effusions. Mesothelial cells expressed CK MNF116 in 96.67% (29/30) of cases and vimentin in 33.33% (10/30) of cases. Malignant cells expressed CK MNF116 in 52.17% (12/23) of cases and vimentin in 30.43% (7/23) of cases. The pattern of immunostaining was diffuse cytoplasmic. In conclusion, CK MNF116 and vimentin may be used as a part of the panel of antibodies for differential diagnosis of malignant pleural effusions with primary unknown.

Topics: Adenocarcinoma; Antibodies; Carcinoma, Small Cell; Diagnosis, Differential; Eosine Yellowish-(YS); Female; Humans; Keratins; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Melanoma; Methylene Blue; Pleural Effusion, Malignant; Pleural Neoplasms; Vimentin

Topics: Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymphoma, Large B-Cell, Diffuse; Microscopy, Electron; Middle Aged; Mucin-1; Nasopharyngeal Neoplasms

Topics: Dendritic Cells; Histiocytes; Histiocytosis, Langerhans-Cell; Humans; Keratins; Langerhans Cells; Lymphoma, Large B-Cell, Diffuse; Sarcoma

Based on the histological criteria proposed by the REAL and adopted by the WHO Classification, 30 cases of MALT type lymphoma, 18 cases of diffuse large B cell lymphoma (DLCL), and 17 cases of DLCLs, associated with a MALT type, were identified in a series of 65 surgically treated primary gastric lymphomas. The clinical records of the patients were analyzed retrospectively and the resected specimens were immunostained for bcl-2, p53 and Ki-67. Primary gastric DLBCLs, with or without a MALT type component, disclosed a higher stage of local extension, a more frequent nodal involvement and a significantly worse survival than pure MALT types. High p53 expression and high proliferation rate correlated with the presence of a large cell component and appeared useful for its identification in mixed forms. Low bcl-2 expression discriminated DLCL from DLCL/MALT. Tumor size, stage and Mib-1 index revealed a value in predicting prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Bacterial; Antigens, CD; Antigens, Nuclear; Biomarkers, Tumor; Combined Modality Therapy; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Italy; Keratins; Ki-67 Antigen; Life Tables; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Phenotype; Proto-Oncogene Proteins c-bcl-2; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tumor Suppressor Protein p53

Five cases of clinically aggressive, keratin-positive malignant lymphomas of B-cell type with unusual immunophenotypes were studied. All cases were extranodal: two from the stomach, one from soft tissue, one from the skin, and one from the spleen. These tumors were undifferentiated large-cell neoplasms that showed reactivity for low-molecular-weight keratin 8, but they were negative for keratin 19; three cases were also positive for epithelial membrane antigen. The immunohistochemical diagnosis was complicated by the fact that two of these cases lacked reactivity for leukocyte common antigen and three were CD20 negative. These findings simulated the immunophenotype of a carcinoma and led to an initial misdiagnosis of carcinoma. Although only two cases showed immunohistochemical evidence of B-cell lineage (CD20+), all five cases were documented as B-cell lymphomas on the basis of the clonal immunoglobulin heavychain gene rearrangement, as demonstrated by polymerase chain reaction (PCR) in all the cases and by Southern blot hybridization in three cases; all cases were negative for T-cell markers, and three cases showed germline configuration for T-cell receptor beta-chain. One case was strongly CD30 positive and represented large-cell anaplastic lymphoma of B-cell type. Our results show that some B-cell lymphomas can have unusual and confusing immunophenotypes, including keratin positivity and leukocyte antigen negativity. Use of PCR-based molecular genetic demonstration of clonal immunoglobulin heavychain gene rearrangement is helpful in establishing the correct diagnosis in such cases.

Topics: Aged; Female; Gene Rearrangement; Humans; Immunoglobulin Heavy Chains; Immunohistochemistry; Keratins; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Molecular Biology; Phenotype; Polymerase Chain Reaction

A B-cell anaplastic large cell lymphoma, confirmed by immunohistochemistry and Southern blot immunoglobulin gene rearrangement analysis, contained neoplastic cells that were immunoreactive for cytokeratin using antibodies CAM 5.2, M20, MAK 6, and KS-B17.2. Bands corresponding to cytokeratin 18 and cytokeratins 18 and 8 were seen on Western blot immunoanalysis using antibodies KS-B17.2 and CAM 5.2. The lymph node also contained cytokeratin-positive extrafollicular fibroblastic reticulum cells. Although it is possible that the presence of cytokeratin in the cells of anaplastic large cell lymphoma represented phagocytosed filaments from the reticulum cells, it is more likely that the cytokeratins were synthesized by the malignant cells. The finding of cytokeratin in anaplastic large cell lymphoma, although infrequent, adds to the confusion in the diagnosis of this pleomorphic neoplasm.

Topics: Aged; Biomarkers, Tumor; Blotting, Southern; Blotting, Western; Gene Rearrangement; Genes, Immunoglobulin; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Male

Topics: Child; Humans; Keratins; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron

The clinical, morphological and immunohistochemical features of 27 patients with anaplastic large cell lymphoma (ALCL) of CD30-positive type, with cutaneous lesions as the sole initial clinical manifestation, were analyzed. The neoplasm presented as solitary or multiple, usually ulcerated skin lesions, affecting predominantly elderly patients (median age: 67 years) with a male preponderance (male to female ratio of 6:1). In most patients, there was an excellent response to chemotherapy. The cardinal histological features included diffuse dermal and subcutaneous infiltration by large, anaplastic tumor cells, all or nearly all of which showed diffuse, strong membrane staining and frequently a paranuclear, dot-like reaction with the CD30 marker (Ber-H2). Epidermal ulceration, pseudo-epitheliomatous hyperplasia and dermal vascular proliferation were also observed.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Neoplasm; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Skin Neoplasms

Two cases are reported of cutaneous anaplastic large-cell lymphoma with the suppressor/cytotoxic (CD8) phenotype. In both cases there was a solitary skin tumour in which there was a dense infiltrate with large irregularly shaped cells which on immunophenotyping expressed CD8. DNA hybridization analysis showed rearrangements of the T-cell-receptor gene in both cases.

Topics: Aged; Antigens, CD; Antigens, CD1; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; CD3 Complex; CD8 Antigens; Female; Gene Rearrangement, T-Lymphocyte; Humans; Immunophenotyping; Keratins; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Molecular Probe Techniques; Receptors, Antigen, T-Cell; Skin Neoplasms

The immunophenotypes of 74 malignant lymphomas (9 Hodgkin's disease, 19 low-grade B-cell, 20 high-grade B-cell, 8 T-cell, and 18 large cell anaplastic lymphomas [LCAL]) have been characterized with antibodies against leucocyte differentiation antigens, keratin, and vimentin. All the non-LCAL were CD45 positive and keratin negative. The LCALs had a more varied immunophenotype, with CD45 present only in 11 of 18 cases and keratin present in 5 of 18 of these rare lymphomas. The lymphoid origin of these latter cases was proven by gene rearrangement studies. All LCALs were CD30+, and, where tested, vimentin positive. Of four different vimentin monoclonal antibodies tested, V9 and MVI stained the highest number of lymphomas. Positive staining of tumor cells was seen in 61 of 71 cases. Vimentin-negative cases included Burkitt's as well as some follicular lymphomas.

Topics: DNA; Gene Rearrangement; Humans; Immunoblotting; Immunohistochemistry; Keratins; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Vimentin

The case is reported of a woman aged 60 yrs who presented with systemic symptoms and who was found to have proteinuria of 3.5 g per day. A renal biopsy revealed numerous neoplastic cells filling many of the glomerular capillary lumina. Immunoperoxidase stains revealed that the phenotype of the malignant cells was LCA+, L26+, MB2+, UCHL1-, CD43-, CAM5.2- and S100-, indicating that they were of lymphoid origin and B-cell lineage. The diagnosis of intravascular large cell lymphoma was therefore made. Remission was induced by chemotherapy with CAVP (cyclophosphamide, adriamycin, vincristine and prednisone). A subsequent relapse was treated with cyclophosphamide, VP16 and prednisone, and again remission occurred. This is the first case known to the authors in which the diagnosis of intravascular large cell lymphoma was made on renal biopsy. We confirm the experience of others that chemotherapy with regimens utilized in other varieties of large cell lymphoma may also be appropriate for this unusual neoplasm.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cyclophosphamide; Doxorubicin; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Kidney; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Prednisone; Proteinuria; S100 Proteins; Vincristine

Monoclonal antibodies (mAbs) directed against the leucocyte common (CD45) antigen have been proposed as a useful tool for the differential diagnosis between malignant lymphomas (CD45+) and poorly differentiated nonhemopoietic tumors (CD45-). Thanks to the availability of mAbs directed against fixative-resistant epitopes of the CD45 molecule, this distinction can now easily be made even in routinely processed tissues. However, a small percentage of morphologically poorly defined neoplasms are difficult to diagnose even with the help of immunohistochemistry. The investigators report that 63 out of 165 anaplastic large-cell (ALC) lymphomas did not show any reactivity for the CD45 antigen in paraffin sections. In routine biopsies, the lymphomatous nature of these cases, most of which had been sent for consultation, could be always unequivocally established by demonstrating negativity for cytokeratins (mAb KL1) and clear dot-like and/or surface reactivity with the Ber-H2 mAb, which is directed against a fixative-resistant epitope of the lymphoid cell activation antigen CD30. Strikingly, 54% of the CD45-cases reacted with mAbs directed against fixative-resistant epitopes of the T cell-restricted CD45RO antigen (mAb UCHL1) or the B-restricted molecules CD45RA (mAb 4KB5) and L26 (unclustered). In order to avoid confusion of ALC lymphomas with anaplastic nonlymphoid tumors, pathologists must be aware of the existence of CD30+/CD45- ALC lymphomas, as they can mimic the above-mentioned malignancies both morphologically (due to the sinusoidal growth pattern) and phenotypically (due to the expression of EMA). The investigators conclude that the combined use of mAbs directed against fixative-resistant epitopes of the CD30, CD45RO, CD45RA, and L26 antigens and cytokeratins is essential for the correct diagnosis and treatment of these equivocal cases.

Topics: Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Diagnosis, Differential; Epitopes; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocyte Common Antigens; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Paraffin

Ten cases of "undifferentiated" large-cell tumors were ultrastructurally characterized by cells with abundant filiform cytoplasmic projections without intercellular junctions. These cases were studied by means of the avidin-biotin-peroxidase complex (ABC) technique applied to formalin-fixed, paraffin-embedded sections using antibodies against high- and low-molecular weight keratins (Ker), vimentin (Vi), epithelial membrane antigen (EMA), S-100 protein, leucocyte common antigen (LCA), kappa (K) and lambda (L) light chains, Leu-M1, lysozyme (Ly), alpha-1 antitrypsin (A1AT) and alpha-1 antichymotrypsin (A1ACT). All 10 cases were negative for Ker and EMA but positive for Vi. S-100 was present only in scattered dendritic cells. LCA was identified in seven cases. In the three LCA-negative cases, two stained for Leu-M1, and one of these also showed intracytoplasmic L; one was negative for all markers but Vi. None of the tumors showed any significant staining for Ly, A1AT, or A1ACT. Our findings indicate that these tumors are nonepithelial and nonneuroectodermal, and that they are best classified as non-Hodgkin's lymphomas. The possibility that some of the filiform large-cell lymphomas may be derived from dendritic reticular cells cannot be excluded.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Antigens, Neoplasm; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Immunoglobulin Light Chains; Keratins; Leukocyte Common Antigens; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron; Middle Aged; S100 Proteins; Vimentin

A histological review of 72 undifferentiated thyroid tumors was performed in order to discover small cell anaplastic carcinomas and Non-Hodgkin lymphomas. Cases suspected to be lymphoma were examined for the presence of Ig and keratin and lectins with a PAP-procedure. Among the 72 cases, 68 (94,5%) were anaplastic carcinomas of various types. Four cases (5,5%) were diffuse small cell tumors, which had previously been regarded as anaplastic carcinomas. All four could be identified as Non-Hodgkin lymphomas by histology, immunohistochemistry, repeat biopsy or autopsy. The findings suggest that the majority of small cell anaplastic thyroid tumors are lymphomas and that true anaplastic small cell carcinoma of the thyroid must be extremely rare. Its diagnosis requires electronmicroscopy and/or immunohistochemistry to demonstrate the epithelial nature of tumor cells.

Topics: Adenocarcinoma; Biopsy; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Immunoglobulins; Keratins; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Thyroid Gland; Thyroid Neoplasms

The presence of intracellular keratin was examined in 230 human neoplasms using indirect immunofluorescence on fresh frozen, acetone-fixed sections. The use of antikeratin antibodies raised in rabbits against human callus and purified by affinity chromatography proved to be a rapid, sensitive, and reliable method of demonstrating keratin. Epithelial tissues and epithelial-derived neoplasms were found to contain keratin, whereas tissues and neoplasms of mesenchymal, lymphoreticular, or neural crest origin did not contain intracellular keratin. This technic is a useful adjunct for the surgical pathologist in the diagnosis of poorly differentiated neoplasms. Its application either confirmed, modified, or in several instances, changed the original light microscopic impression. The modified or changed diagnoses were confirmed by transmission electron microscopy.

Topics: Adult; Aged; Antibodies; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fluorescent Antibody Technique; Humans; Keratins; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged; Neoplasms; Skin Neoplasms; Thymoma