All Publications

  • The Diagnostic Impact of C4d, CD68, and NF-κB Expression in the Differentiation Between Recurrent Hepatitis C and Acute Cellular Rejection After Liver Transplantation. Applied immunohistochemistry & molecular morphology : AIMM Abdou, A. G., Asaad, N. Y., Ehsan, N., Younes, S., Gomaa, A. I., Elgendy, W. 2016; 24 (9): 639-647


    Liver transplantation is the selected treatment for patients with advanced liver disease and cirrhosis, mostly as a complication of hepatitis C virus (HCV). Recurrent HCV and acute cellular rejection (ACR) of the graft are the most common causes of graft failure. The distinction between the 2 conditions is essential because they are managed differently. In some cases, the clinical and histopathologic features may overlap between recurrent hepatitis C and ACR, making differentiation difficult. The aim of this study was to investigate the role of C4d, CD68, and nuclear factor kappa-B (NF-κB) in the differentiation between ACR and recurrent HCV in the post-liver-transplant biopsy using immunohistochemistry. C4d expression in endothelial cells of portal or central veins (P=0.001) and the number of macrophages highlighted by CD68 (P=0.02) were in favor of ACR, whereas NF-κB expression by hepatocytes was in favor of recurrent hepatitis C. Vascular injury demonstrated by endothelial expression of C4d and prominent macrophage infiltration identified by CD68 expression were the distinguishing criteria for ACR and representing humoral and cellular-mediated immunity as evoking factors for graft injury. The upregulation of NF-κB in the hepatocytes of recurrent hepatitis C could be an immune response to infection or it may be induced by HCV itself.

    View details for DOI 10.1097/PAI.0000000000000245

    View details for PubMedID 26469325

  • Sensitivity and Specificity of Galectin-3 and Glypican-3 in Follicular-Patterned and Other Thyroid Neoplasms. Journal of clinical and diagnostic research : JCDR Al-Sharaky, D. R., Younes, S. F. 2016; 10 (3): EC06-10


    Diagnosing follicular-patterned thyroid neoplasm can be quiet challenging in some cases, where an immunohistochemical profiling becomes mandatory. Galectin-3 may be a helpful tool for classical PTC diagnosis, but it cannot be considered as a diagnostic marker of malignancy. Glypican-3, in contrast, is not thoroughly studied in thyroid neoplasms.Determine the sensitivity and specificity of galectin-3 and glypican-3 in diagnosing thyroid carcinoma and follicular-patterned thyroid carcinoma.A retrospective study was conducted on archival blocks diagnosed from pathology department between 2010 and 2012 including 17 cases of follicular adenoma, 16 cases of Classic Papillary Thyroid Carcinoma (PTC), 6 cases of Follicular Variant of Papillary Thyroid Carcinoma (FVPTC), 3 cases of follicular carcinoma, 5 cases of medullary carcinoma and 1 case of Hürthle cell carcinoma. The nearby non neoplastic (normal) thyroid follicles present in both adenoma and carcinoma cases were also evaluated.Evaluation of both galectin-3 and glypican-3 expression using standard immunohistochemical techniques.Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS).Five (30%) and 4 (24%) out of the 17 studied follicular adenoma cases, were positively stained by galectin-3 and glypican-3 respectively, while 30 (97%) and 25 (81%) cases out of the studied 31 carcinoma cases were positively stained by galectin-3 and glypican-3 respectively. The sensitivity, specificity and diagnostic accuracy of galectin-3 vs. glypican-3 in discrimination between thyroid carcinoma and adenoma was 96.8%, 70.6%, and 87.5%vs. 81% 76.5% and 79% respectively. As for the discrimination between follicular-patterned thyroid carcinoma and follicular adenoma it was 90%, 71% and 78% vs. 90% 76.5% and 82%.Glypican-3 is more specific while galectin-3 is more sensitive in diagnosing thyroid carcinoma while glypican-3 is more specific than galectin-3 in discriminating follicular-patterned neoplasm.

    View details for DOI 10.7860/JCDR/2016/18375.7430

    View details for PubMedID 27134876

    View details for PubMedCentralID PMC4843262

  • Expression and clinical significance of ghrelin in endometrial hyperplasia and carcinoma of Egyptian patients. Ultrastructural pathology Younes, S. F., Aiad, H., Kandil, M., El Kalashy, F. S. 2015; 39 (3): 207-13


    Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p = 0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p = 0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.

    View details for DOI 10.3109/01913123.2014.983627

    View details for PubMedID 25569277

  • Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal zone lymphomas and is useful in the differential diagnosis with follicular lymphoma HUMAN PATHOLOGY Metcalf, R. A., Monabati, A., Vyas, M., Roncador, G., Gualco, G., Bacchi, C. E., Younes, S. F., Natkunam, Y., Freud, A. G. 2014; 45 (8): 1730-1736


    The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of specific markers that distinguish them from other low-grade non-Hodgkin B-cell lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein that labels myelomonocytic cells as well as B lymphocytes that localize to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in a large series of B-cell lymphomas to assess the sensitivity and specificity of this antigen for the characterization of MZL. A total of 440 tissue sections containing extramedullary B-cell lymphomas and 216 bone marrow biopsies containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67% of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA was also infrequently expressed in other B-cell neoplasms including mantle cell lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%), follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL and one case of MZL. Collectively, these data support the inclusion of MNDA in the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those in which the differential diagnosis is between low-grade FL and MZL.

    View details for DOI 10.1016/j.humpath.2014.04.004

    View details for Web of Science ID 000339642100023

    View details for PubMedID 24925224

  • LMO2 and BCL6 are associated with improved survival in primary central nervous system lymphoma BRITISH JOURNAL OF HAEMATOLOGY Lossos, C., Bayraktar, S., Weinzierl, E., Younes, S. F., Hosein, P. J., Tibshirani, R. J., Posthumus, J. S., DeAngelis, L. M., Raizer, J., Schiff, D., Abrey, L., Natkunam, Y., Lossos, I. S. 2014; 165 (5): 640-648


    Primary central nervous system lymphoma (PCNSL) is an aggressive sub-variant of non-Hodgkin lymphoma (NHL) with morphological similarities to diffuse large B-cell lymphoma (DLBCL). While methotrexate (MTX)-based therapies have improved patient survival, the disease remains incurable in most cases and its pathogenesis is poorly understood. We evaluated 69 cases of PCNSL for the expression of HGAL (also known as GCSAM), LMO2 and BCL6 - genes associated with DLBCL prognosis and pathobiology, and analysed their correlation to survival in 49 PCNSL patients receiving MTX-based therapy. We demonstrate that PCNSL expresses LMO2, HGAL(also known as GCSAM) and BCL6 proteins in 52%, 65% and 56% of tumours, respectively. BCL6 protein expression was associated with longer progression-free survival (P = 0·006) and overall survival (OS, P = 0·05), while expression of LMO2 protein was associated with longer OS (P = 0·027). Further research is needed to elucidate the function of BCL6 and LMO2 in PCNSL.

    View details for DOI 10.1111/bjh.12801

    View details for Web of Science ID 000335826500008

    View details for PubMedID 24571259

    View details for PubMedCentralID PMC4123533

  • FHIT, EGFR, and MSH2: Possible Etiopathologic, Prognostic, and Predictive Role in Non-Small Cell Lung Carcinoma in Egyptian Patients APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Younes, S. F., Aiad, H. A., Asaad, N. Y., Kandil, M. A., Natkunam, Y., Mokhtar, N. M. 2014; 22 (4): 275-283


    The high incidence and mortality of lung carcinoma in Egypt necessitates studying the factors that may be implicated in non-small cell lung carcinoma (NSCLC) pathogenesis and could affect patient management. The aim was to study FHIT, epidermal growth factor receptor (EGFR), and MSH2 protein expression in Egyptian patients with NSCLC. Immunohistochemical staining for FHIT, EGFR, and MSH2 was performed on 64 specimens from NSCLC patients and correlated with prognostic parameters, response to therapy, and overall survival. FHIT loss was observed in 64% of NSCLC patients and was significantly associated with SCC (P=0.003) and poor tumor grade (P=0.043). EGFR overexpression was observed in 47% of NSCLC patients and was significantly associated with SCC (P=0.002). MSH2 was reduced in 23.4% of NSCLC patients and was significantly associated with adenocarcinoma (P=0.024). In a univariate analysis, a significant relationship was seen between the poor overall survival in NSCLC patients and high T-stage (P=0.029), presence of metastasis (P=0.014), advanced-stage grouping (P=0.004), and FHIT loss (P=0.033). Further, FHIT loss was significantly related to disease progression in patients treated with chemotherapy (P=0.038). We conclude that all 3 markers play a role in the development of NSCLC in Egyptian patients. We suggest that FHIT loss be used as a predictor for progression in chemotherapy-treated NSCLC patients.

    View details for DOI 10.1097/PAI.0b013e3182988fa5

    View details for Web of Science ID 000334606700006

    View details for PubMedID 24185125

  • Usefulness of HGAL and LMO2 Immunohistochemistry in the Identification of Follicular Lymphomas of the Non-Gastric Gastrointestinal Tract APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Chapman-Fredricks, J., Younes, S. F., Fan, Y., Sandoval-Sus, J. D., Natkunam, Y., Lossos, I. S. 2013; 21 (3): 200-204


    We studied the sensitivity of 2 relatively new markers of germinal center B-cell origin, namely human germinal center-associated lymphoma (HGAL) and Lim-only transcription factor 2 (LMO2), in the identification of follicular lymphomas (FLs) of the nongastric gastrointestinal (GI) tract.We retrospectively reviewed cases of endoscopically derived primary, nongastric GI lymphomas including FL, grade 1 or 2, and extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue, classified based on morphologic features and immunohistochemical analysis. HGAL and LMO2 immunohistochemical stains were then prospectively performed in each case. When discrepant immunohistochemical results were obtained, fluorescent in situ hybridization was performed for t(14;18) IGH/BCL2 and IGH rearrangement using a dual color fusion and a dual color break-apart probe, respectively.All but one of the CD10-negative ENMZL cases were negative for both HGAL and LMO2. One case originally classified as ENMZL was positive for both HGAL and LMO2. Fluorescent in situ hybridization did not detect either t(14;18) IGH/BCL2 or IGH rearrangement in this case. It is likely, based on positivity of 2 established germinal center B-cell markers, that this represents a FL which was originally misclassified as an ENMZL based on CD10 negativity. Of the cases of FL (all CD10 and/or BCL-6 positive), 8 (80%) were positive for both HGAL and LMO2.Although HGAL and LMO2 did not demonstrate an increased sensitivity in the identification of FL of the nongastric GI tract in this series, they still were helpful in the reclassification of one of our cases, and may therefore be useful adjuncts in the identification of FL of the nongastric GI tract.

    View details for DOI 10.1097/PAI.0b013e31826399aa

    View details for Web of Science ID 000317961100004

    View details for PubMedID 22914613

  • Indeterminate cell histiocytosis with naïve cells. Rare tumors Bakry, O. A., Samaka, R. M., Kandil, M. A., Younes, S. F. 2013; 5 (1): e13


    Histiocytoses are a heterogeneous group of disorders characterized by proliferation and accumulation of cells of mononuclear-macrophage system and dendritic cells. Histiocytoses are categorized according to the cell of origin into Langerhans cell histiocytosis (LCH), Non Langerhans cell histiocytoses and indeterminate cell histiocytosis (ICH). ICH is an extraordinary rare neoplastic dendritic cell disorder that has poorly understood histogenesis and pathogenesis. It is characterized by a proliferation of dendritic cells, which mimic Langerhans cells immunophenotypically (positive for CD1a and S-100 protein), but lack Birbeck granules characteristic of Langerhans cells. Twenty-four year-old Egyptian male was presented with reddish brown chest wall nodule. Clinical, histopathological, immunohistochemical and ultrastructure features are typical for ICH. He was in a good state without any evidence of recurrence or metastasis after 24 months follow up. Peculiar histopathological features were detected in the present case. Many unidentified cells with Hematoxylin & Eosin Langerhans like features showed negative staining for S-100, CD1a, Langerin and CD68. In absence of cellular atypia and mitosis, the infiltrating cells showed epidermotropism that was reported once in ICH as well as neural and perineural invasion that were not previously reported. Therefore we prefer using a tentatively designated diagnosis; dendritic cell tumor, not otherwise specified or newly proposed diagnosis (Indeterminate cell histocytosis with naïve cells) for the present case.

    View details for DOI 10.4081/rt.2013.e13

    View details for PubMedID 23772299

    View details for PubMedCentralID PMC3682452

  • IgG4-Related Systemic Sclerosing Disease of the Ocular Adnexa A Potential Mimic of Ocular Lymphoma AMERICAN JOURNAL OF CLINICAL PATHOLOGY Karamchandani, J. R., Younes, S. F., Warnke, R. A., Natkunam, Y. 2012; 137 (5): 699-711


    IgG4-related sclerosing disease has been described in the orbit and ocular adnexa. Of 164 biopsies of the ocular region for suspected lymphoma, we identified 6 cases of IgG4 disease, 4 of which were previously unrecognized. All 6 cases demonstrated increased plasma cells in a background of sclerosis and increased absolute numbers of IgG4-expressing cells. Our results confirm the difficulty in diagnosing IgG4-related sclerosing disease in the ocular region. Based on the findings, we suggest that specimens from biopsies of the eye and ocular adnexa for which a definitive diagnosis of lymphoma is not established undergo further workup for IgG and IgG4, particularly if increased plasma cells and sclerosis are present. When IgG4-expressing plasma cells account for greater than 50% of IgG-expressing plasma cells, a diagnosis of IgG4 disease should be considered. Timely recognition would benefit patients by allowing appropriate management with corticosteroid therapy and avoiding more aggressive or unnecessary therapeutic options.

    View details for DOI 10.1309/AJCPE1G8DRHXRPIH

    View details for Web of Science ID 000303141300002

    View details for PubMedID 22523207

  • The Efficacy of HGAL and LMO2 in the Separation of Lymphomas Derived From Small B Cells in Nodal and Extranodal Sites, Including the Bone Marrow AMERICAN JOURNAL OF CLINICAL PATHOLOGY Younes, S. F., Beck, A. H., Ohgami, R. S., Lossos, I. S., Levy, R., Warnke, R. A., Natkunam, Y. 2011; 135 (5): 697-708


    We studied the efficacy of 2 germinal center B-cell markers, HGAL and LMO2, in the separation of lymphomas derived from small B cells, particularly follicular lymphoma (FL) and marginal zone lymphoma occurring in nodal, extranodal, splenic, and bone marrow sites using immunohistochemical analysis for CD10, BCL6, BCL2, HGAL, and LMO2. Our results showed that HGAL and LMO2 are sensitive and specific markers for detecting FL in nodal and extranodal sites. In contrast, all markers were down-regulated in FL infiltrates in the bone marrow. CD10 and HGAL were expressed in a subset of FLs in the bone marrow and were highly correlated with each other and with CD21, a marker of follicular dendritic cells. We conclude that HGAL and LMO2 should be considered in immunohistochemical panels used for the routine workup of lymphomas derived from small B cells. In the bone marrow, staining for HGAL or CD10 can be helpful in making a diagnosis of FL, although they are absent in a subset of cases.

    View details for DOI 10.1309/AJCP7Z2BIBUNQPLZ

    View details for Web of Science ID 000289743400007

    View details for PubMedID 21502424

  • Immunoarchitectural Patterns in Follicular Lymphoma: Efficacy of HGAL and LMO2 in the Detection of the Interfollicular and Diffuse Components AMERICAN JOURNAL OF SURGICAL PATHOLOGY Younes, S. F., Beck, A. H., Lossos, I. S., Levy, R., Warnke, R. A., Natkunam, Y. 2010; 34 (9): 1266-1276


    Follicular lymphoma (FL) can exhibit variant histologic patterns that can lead to confusion with other B-cell lymphomas and reactive conditions. Diagnostic markers such as CD10 and BCL2 may be difficult to interpret in variant FL patterns, and are often diminished or absent in the interfollicular and diffuse components. We evaluated 2 recently characterized germinal center B-cell markers, human germinal center associated lymphoma (HGAL), and LIM-only transcription factor 2 (LMO2), in 127 FL patient biopsies (94 nodal, 33 extranodal), and correlated the findings with histologic pattern, cellular composition, grade, and additional immunostains (CD20, CD3, CD21, CD10, BCL2, and BCL6). Architectural patterns included predominantly follicular (75%) and follicular and diffuse components (25%); 10 cases showed marginal zone differentiation and 3 were floral variants. Eighty-nine cases were low grade (38 grade 1; 51 grade 2) and 38 were grade 3 (29 grade 3A and 9 grade 3B). HGAL had the highest overall sensitivity of detecting FL and was superior in detecting the interfollicular and diffuse components compared with BCL2, LMO2, CD10, and BCL6. All 28 cases that lacked CD10, expressed HGAL, and the majority also expressed LMO2. Our results show that HGAL and LMO2 are sensitive markers for FL diagnosis. The addition of HGAL and LMO2 to the immunohistologic panel is beneficial in the work-up of nodal and extranodal B-cell lymphomas and the efficacy of HGAL in detecting the follicular, interfollicular and diffuse components of FL is of particular value in the setting of variant immunoarchitectural patterns.

    View details for DOI 10.1097/PAS.0b013e3181e9343d

    View details for Web of Science ID 000281579800005

    View details for PubMedID 20697248

    View details for PubMedCentralID PMC2929284