Clinical significance of MUC1, MUC2 and CK17 expression patterns for diagnosis of pancreatobiliary arcinoma.

Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (-) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (-), MUC2 (+) and CK17 (-), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (-) and CK17 (-) profile. More importantly, the MUC1 (+), MUC2 (-) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (-) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (-) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.

[Renal abscess in childhood: a case report]. / Ascesso renalein età pediatrica:descrizione di un caso.

We describe the case of a previously healthy six-year-old boy with a right renal abscess due to a methicillin-resistant Staphylococcus aureus, which necessitated a radical nephrectomy. Although renal ultrasonography is often the initial tool to identify fluid collection, in our case the diagnosis was obtained only after performing an abdominal CT with intravenous contrast. It is therefore necessary to combine these different imaging techniques in all children with fever and abdominal/lumbar pain without any apparent cause in order to obtain an early diagnosis and minimise organ damage.

[Thrombocytopenia associated with brucellosis: a case report]. / Trombocitopenia in corso di brucellosi: descrizione di un caso.

Brucellosis, a common disease in some areas of the world, beside its typical signs and symptoms, as fever, arthropathy, hepatomegaly and splenomegaly, sometimes can complicate into thrombocytopenia, even in severe forms. The pathogenesis of thrombocytopenia in course of brucellosis is variable, and a main role is played by immunological reactions. Authors describe a case report of an eight years child who presented a severe thrombocytopenia in course of acute brucellosis. The patient responded efficaciously to the antibiotic therapy combined with immunoglobulin intravenous therapy.

PAX-5 is invariably expressed in B-cell lymphomas without plasma cell differentiation.

AIMS: The B-cell-specific transcription factor PAX-5 is physiologically expressed in normal B cells and silenced in plasma cells. The aim of this study was to determine whether PAX-5 expression is universal among B-cell malignancies. METHODS AND RESULTS: A wide spectrum of B-cell malignancies were subjected to immunohistochemical analysis for PAX-5 expression. The study was especially focused on cases lacking CD20, such as precursor B-cell acute lymphoblastic leukaemia (preB-ALL), CD20- B-cell lymphomas, classical Hodgkin's lymphoma (CHL) and B-cell lymphomas with significant plasmacytic differentiation. Strong PAX-5 expression was identified, without exception, in all cases of CD20+ B-lymphoproliferative disorders. It was also invariably detected in 31/31 cases of preB-ALL, 14/14 cases of CD20- diffuse large B-cell lymphoma without plasmacytic differentiation and 26/26 CD20- B-cell lymphoma status post rituximab treatment. The vast majority of CHLs had unequivocal PAX-5 expression of varying intensity (80/86). However, variants of B-cell malignancies with characteristic plasmacytic differentiation exhibited no detectable PAX-5 expression (0/17). CONCLUSIONS: PAX-5 is the most sensitive and reliable immunohistochemical marker for B-cell malignancies. Lack of PAX-5 expression correlates with the presence of marked plasma cell differentiation.

Scleroderma-like disorders.

Fibrosing disorders comprise a wide spectrum of heterogeneous diseases characterized by sclerosis of the dermis, subcutis, and sometimes the underlying soft tissues and bone. The hallmark of this group of diseases is skin thickening as in systemic sclerosis with a different distribution pattern and for this reason they have also been referred to as "scleroderma-like" disorders. These diseases may have a different clinical course ranging from a benign disease with a localized cutaneous involvement, to a widespread, systemic, life-threatening disease. Some of them are associated with autoantibodies and/or autoimmune conditions. An accurate recognition of these scleroderma-like diseases is important for the institution of the most appropriate treatment.

[Recurrent new-onset uveitis in a patient with rheumatoid arthritis during anti-TNFalpha treatment]. / Uveite recidivante di nuova insorgenza in paziente con artrite reumatoide in terapia con anti-TNFalpha

Inflammation involving the uveal tract of the eye, termed uveitis, is frequently associated with various rheumatic disease, including seronegative spondylarthropathies, juvenile rheumatoid arthritis, Crohn's disease and Behçet's disease. Scleritis and keratitis may be associated with rheumatoid arthritis and systemic vasculitides such as Wegener's granulomatosis. Immune-mediated uveitis can have a chronic relapsing course and produce numerous possible complications, many of which can result in permanent vision loss. Treatment typically includes topical or systemic corticosteroids with cycloplegic-mydriatic drugs and/or noncorticosteroid immunosuppressants, but often there is an insufficient clinical effectiveness. Anti-TNFalpha therapy is promising in the treatment of sight threatening uveitis, particularly in patients with Behçet's disease. However, there have been also reports of new-onset uveitis during treatment of joint disease with TNFalpha inhibitors. We describe a case of new-onset uveitis in a patient with rheumatoid arthritis during therapy with etanercept at first and infliximab at last. Although we cannot exclude uveitis as linked to rheumatoid arthritis, it is unlike that the uveitis arises when the joint disease is well controlled. The hypothetical paradoxical effect of anti-TNF is here discussed.

[Buschke Scleredema, case report]. / Scleredema di Buschke, contributo casistico.

Buschke Scleredema is a rare connective tissue disorder of unknown aetiology, characterized by thickening of the dermis whose characteristics may mainly to mime systemic sclerosis, eosinophilic fasciitis and cutaneous amyloidosis. Scleredema may be associated with a history of an antecedent febrile illness, diabetes mellitus, or blood dyscrasia. Scleredema can be classified into three clinical groups; each has a different history, course, and prognosis. Each one of these share reduction in chest articular movements and limitation of limbs movements. The skin histology is characterised by thickened dermis and increased spaces between large collagen bundles due to increased deposition of mucopolysaccharide in the dermis. Differential diagnosis can be made considering the typical clinical features and the histologic peculiarity. No therapy has been found effective. The authors describe a case of Buschke Scleredema successfully treated by steroids and colchicine. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment.

Chronic eosinophilic pneumonia presenting with recurrent massive bilateral pleural effusion : case report.

We describe a rare case of a 29-year-old woman with chronic eosinophilic pneumonia (CEP) presenting with massive bilateral pleural effusion leading to respiratory failure, a complication that was not reported before with CEP. The patient was successfully managed with ventilatory support and steroid therapy. On long-term follow-up, she remained well, receiving a low maintenance dose of prednisone without evidence of relapse of the disease.

Idiopathic hypereosinophilic syndrome: a report of four cases in Arabs, and a review of the literature.

We report four Arab patients with idiopathic hypereosinophilic syndrome (IHES). They presented with varied clinical pictures simulating chronic inflammatory bowel disease (IBD), pulmonary tuberculosis (TB), meningioma, peripheral neuropathy, and infective endocarditis (IE). All had significant peripheral and bone marrow eosinophilia, histological confirmation of eosinophilic infiltration of multiple organs, and clinical evidence of multi-organ dysfunction. Extensive laboratory investigations excluded other possible causes of eosinophilia. All were treated with steroids, with complete response in two. Two others were treated additionally with hydroxyurea, and one with methotrexate, cyclophosphamide, vincristine and alpha-interferon. The pathogenesis, varied clinical, laboratory, and histopathological features, and the management of IHES are reviewed.

"Histiocytic markers" in melanoma.

BACKGROUND: Tumor cells of malignant melanoma, the "great imitator," may morphologically mimic almost any cell, including histiocytes. Immunohistochemical stains for histiocytes are often used to distinguish histiocytic lesions that resemble melanomas, but we have noted and others have reported that these markers may be immunoreactive in melanomas. METHODS: We evaluated 43 primary and metastatic melanomas with traditional markers for melanomas (S100, HMB45, and NKI-C3) and common markers used for histiocytes (alpha-1-antitrypsin or AAT, CD68/KP1, HAM56, Mac387, and Muramidase). The extent (<5%, 5 to 30%, 30 to 60%, 60 to 90%, >90%) and intensity (1+ to 4+) of staining were recorded semi-quantitatively. RESULTS: Melanoma immunoreactivity (>5% of tumor cells) was as follows: S100, 100%; HMB45, 91%; NKI, 91%; AAT, 95%; CD68, 86%; HAM56, 26%; Mac387, 7%; and Muramidase, 30%. Among the histiocytic markers, staining by AAT and CD68 was typically diffuse but weak. Staining by HAM56, Mac387, and Muramidase was usually focal. In contrast, the traditional melanoma markers showed diffuse and strong staining. Interpretation of the histiocytic markers was complicated by scattered atypical histiocytes and pigmented tumor cells. CONCLUSION: Melanomas are commonly immunoreactive for histiocytic markers. AAT and CD68 immunostains are diffusely positive almost as frequently as traditional melanoma markers, although with weaker intensity. HAM56, Mac387, and Muramidase are less commonly positive and exhibit focal staining. Therefore, depending on the context, histiocytic markers may not be helpful in differentiating histiocytes and histiocytic tumors from melanomas.

Immunohistochemical analysis of murine CD95/Fas/Apo-1 receptor and its ultrastructural distribution in the thymus.

CD95/Fas/Apo-1 is a cell surface receptor that, upon contact with its ligand, induces cells to die by apoptosis. In view of the importance of Fas receptor (FasR) in immunologic tolerance, an immunohistochemical analysis of FasR expression was performed in the lymphoid and certain parenchymal tissues of normal and mutant MRL/lpr mice using a rabbit polyclonal anti-Fas receptor antibody. FasR was expressed by immunoperoxidase (IP) in the cortex and at the corticomedullary junction of the thymus of normal mice. By immunoelectron microscopy FasR was detected on the cell membrane of normal thymocytes. In MRL/lpr mice, FasR protein expression could not be clearly detected. FasR protein expression was not detected in the heart, liver or ovary by IP, presumably reflecting the low number of receptors in these tissues.

Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years.

We summarize our experience with 238 cases of Langerhans cell granulomatosis (LCG), 198 of whom were followed for a median period of 10.5 years. Our patients did well unless overtreated, and no deaths were attributed to the disorder itself. The disease may appear in unifocal or multifocal form, and treatment is based on this fact. Virtually all patients recovered completely except for occasional residual orthopedic problems or residual diabetes insipidus. Several of the patients underwent subsequent pregnancies without difficulty. The granulomas primarily occur in bone, but lung, skin, and lymph nodal involvement is not uncommon. Involvement of thyroid, thymus, and other sites is rare. The hallmark of the disease is the accumulation of Langerhans cells (LCs). We review the pathology of LCG by histology, electron microscopy, and immunolabeling. LCs originally were identified in squamous epithelium, but these cells are part of the widespread system of dendritic cells. The latter cells, which arise from CD34+ progenitors, are specialized and efficient antigen-presenting cells for T-cell-mediated immunity. In LCG, however, the major associated cells are not T cells, but mature eosinophils: hence the original name eosinophilic granuloma. Confusion about terminology has been based upon the scanty and rather crude pathology reports in the original literature. The term histiocytosis X was meant to cover a spectrum of three diseases--eosinophilic granuloma, Hand-Schüller-Christian disease (HSC), and Letterer-Siwe disease (LS)--but HSC and LS have no basis in pathology and hence the terms are meaningless. The term HSC has become a synonym for multifocal eosinophilic granuloma (LCG). The term LS has been used in reporting a number of benign, malignant, or unknown conditions. We prefer the term LCG to avoid confusion with the term histiocytosis X because there is evidence that the LC is not a member of the mononuclear phagocyte system and hence not a tissue macrophage, and because the use of the term "histiocyte" has become a convenience in much of the literature when reporting incompletely understood diseases.

CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease.

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage-specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty-two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in four of five cases studied. All nine cases were of T- or null-cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus-positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

Colonic histiocytic neoplasm mimicking malignant histiocytosis and presenting as intussusception.

It is now apparent that distinction between the so-called malignant histiocytosis and lymphoma can be made using panels of established immunohistochemical markers and/or genotypic analysis. Many, if not all, of the previously diagnosed cases of malignant histiocytosis have been shown to be of lymphoid, rather than histiocytic, lineage. We report a rare case of colonic histiocytic neoplasm accompanied by a lymphoreticular dissemination that mimicked that of malignant histiocytosis. In addition, barium studies and computed axial tomography confirmed an intussusception that subsequently developed. The histiocytic nature of the neoplastic cells was supported by immunohistochemical, ultrastructural, and cytochemical studies. To our knowledge our case may represent the fifth documented case of a histiocytic malignancy reported in the literature. The relationship among the various cases will be discussed as well as the significance of the focal S-100 immunoreactivity observed in the present case.

Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23).

Deletions of the long arm of chromosome 6 have been described in acute and chronic lymphocytic leukemia (ALL and CLL) and prolymphocytic leukemia (PLL), and have been associated with t(14;18)(q32;q21) in non-Hodgkin's lymphoma (NHL). Of 55 cases of small lymphocytic (sm lym) NHL, deletions of 6(q21q23) were the most common recurring cytogenetic abnormality. Among 14 sm lym NHL with del(6)(q21q23), this abnormality occurred as a solitary change in 3 cases. Each of these 3 cases, and 5 additional cases with del(6q) and other abnormalities, showed atypical larger forms with the morphologic appearance of prolymphocytes or paraimmunoblasts in the peripheral blood. In comparison, of the 11 cases without del(6q) and circulating abnormal cells, prolymphocytoid forms were observed in 4 cases (P < .001). Of the 31 sm lym without del(6q), trisomies of chromosomes 3, 12, or 18, or t(11;14)(q13;q32) occurred in greater than 10% of cases. Proliferation centers or infiltration by larger forms were observed in similar proportions of tissue sections derived from sm lym NHL with or without del(6q). The presence of the larger forms in the peripheral blood did not have an adverse prognostic impact on the survival of the del(6q) cohort, who experienced a median survival in excess of 6 years. All 14 cases of del(6q) sm lym NHL were characterized by a mature B-cell phenotype. Expression of CD11c, a feature of a CLL/PLL variant previously described, was not detected in 9 cases analyzed. In 5 cases of del(6q) sm lym NHL, no circulating abnormal lymphocytes were noted. Twelve cases presented with, or developed, clinical splenomegaly. These results suggest that deletion of a gene or genes at 6q21-23 is associated with the pathogenesis of a subset of B-cell sm lym NHL that may display larger prolymphocytoid cells in the peripheral blood, but that follows a clinical course typical of other well-differentiated lymphocytic neoplasms.

Immunostaining of small cytologic specimens. Facilitation with cell transfer.

Immunocytochemical study of cytologic specimens is often limited by the number of slides containing diagnostic cells. This study examined the effectiveness of transferring cells from a single smear to multiple slides in order to perform a battery of immunocytochemical stains on limited material. Immunostaining performed on four effusions and five fine needle aspirates yielded the expected results for most of the antibodies commonly employed in diagnostic pathology. Background staining was generally low following cell transfer, and the morphology of the cells was preserved. These results suggest that cell transfer in combination with immunocytochemistry may prove useful in the cytologic diagnosis of malignant lymphoma, neuroendocrine neoplasms, prostatic and mammary adenocarcinoma, and other malignant tumors.

Immunoperoxidase staining of cervicovaginal smears after radiotherapy.

Cervicovaginal smears from 2 women with postirradiation dysplasia, 4 women with postirradiation squamous cell carcinoma of the cervix, 30 women with irradiation atypia and 5 healthy, nonirradiated women were stained immunohistochemically with six keratin antibodies. For four of the antibodies--CK19 (BA17), EMA, PKK-1 and CAM 5.2--squamous cells showing irradiation atypia, postirradiation dysplasia or postirradiation squamous cell carcinoma were more likely to stain positively than were nonirradiated squamous cells. For three of the antibodies in which multiple squamous cells stained positively, the proportion of squamous cells showing postirradiation dysplasia or postirradiation squamous cell carcinoma staining strongly was equal to or greater than the corresponding overall proportion for squamous cells showing irradiation atypia. This was statistically significant with only one antibody, PKK-1. No statistically significant differences were seen in staining of irradiated and nonirradiated squamous cells by MAK-6 and AE1:AE3. The data show that some keratin antigens are more often expressed in the irradiated groups and that there may be differences in the degree of antigen expression between squamous cells showing postirradiation dysplasia or postirradiation squamous cell carcinoma and squamous cells showing irradiation atypia.

Ki-1 antigen expression defines a favorable clinical subset of non-B cell non-Hodgkin's lymphoma.

Immunohistochemical and immunophenotypic analyses were performed on 278 cases of karyotypically abnormal non-Hodgkin's lymphoma (NHL). Excluding cases of lymphoblastic lymphoma or mycosis fungoides, 20 cases showed evidence of non-B cell lineage. T cell lineage was proven by genotypic and immunophenotypic analyses in 15 of the 20 cases; five were of ambiguous lineage. All of the non-B lineage cases were of diffuse histology with a large cell component (DLCL). Twelve cases expressed the Ki-1 antigen; five of these cases also demonstrated a translocation with a break at 5q35. Patients with Ki-1 positive DLCL and t(5q35) had a younger median age compared with non-B cell DLCL without t(5q35). The Ki-1 positive patients had a higher frequency of skin involvement and lower incidence of bone marrow involvement compared with Ki-1 negative DLCL. Survival analysis was performed on 86 cases of B cell DLCL and 18 cases of non-B cell DLCL which were serially ascertained prior to receiving cytotoxic chemotherapy. Median duration of complete remission was significantly longer in the B cell compared with the non-B cell DLCL groups; there was only a trend for decreased overall survival in the non-B cell group. Among the subset of non-B cell lymphomas, overall survival of patients with Ki-1 expressing DLCL was significantly longer than those with Ki-1 negative DLCL, who had a median survival of less than a year. These results show that immunophenotypic, immunohistochemical, and cytogenetic markers can define subsets of patients with non-B cell lymphomas with differing clinical characteristics and outcome.

Coronary arteries and athlete's heart.

An increase of coronary artery size after endurance training has been suggested by experimental data on animals and anecdotal autopsy reports in men. However, systematic studies on in vivo coronary anatomy of athletes have been lacking so far. We utilized two-dimensional echocardiography (2DE) to explore non-invasively the coronary anatomy of endurance athletes. Twenty long-distance runners (LDR) and 20 matched sedentary controls (SC) were studied initially. Visualization of the ostia and main trunks of-right (RCA) and left coronary artery (LCA) was obtained in 90-100 p. 100 of LDR and 70-75 p, 100 of SC. Collateral branches of LCA (anterior descending artery and circumflex branch) and RCA were visualized respectively in 60-70 p. 100 and 30-40 p, 100 of cases. The very good quality of images made possible the measurement of LCA and RCA size. LDR as a group had significantly larger coronary arteries than SC: this was associated with significant left and right ventricular enlargement and hypertrophy. These results have been further confirmed in a large survey of triathletes, swimmers, water-polo players, young LDR and prepubescent football players. Increase of coronary artery size is a well-documented effect of endurance training which can be easily investigated with 2DE, However, the large interindividual variability and the observation of very large coronary arteries in adolescent subjects suggest that genetic factors may also play a role in determining the final size of the coronary vessels.