Vitamin D pathway related polymorphisms and vitamin D receptor expression in breast cancer.

Vitamin D deficiency is an emerging risk factor for breast cancer suggesting its role in breast cancer pathogenesis. Recent evidence suggests vitamin D receptor (VDR) expression is a prognosis predictor in breast cancer. We set out to determine the status of VDR expression in histologically characterized breast cancers, and whether common genetic variants modify VDR expression in breast cancer. One-hundred and twenty Kuwaiti female breast cancer fixed tissues were assessed for VDR expression to identify the level and location of its expression by immunohistochemistry. VDR variants (rs731236, rs2228570), and vitamin D binding protein (VDBP) variants (rs4588, rs7041) genotypes were ascertained in breast cancer specimens using Taqman genotyping assays. VDR nuclear expression correlated with low grade tumors (p = 0.01), whereas cytoplasmic expression correlated with lymph node positive tumors (p = 0.03). Absence of VDR expression was a marker for high-grade dedifferentiated tumors (p = 0.01). VDBP rs7041 associated with breast cancer risk (OR 1.92, 95% CI: 1.34 - 2.73; p = 0.0004), and VDR rs2228570 correlated with increased VDR cytoplasmic expression (p < 0.0001). In conclusion, VDR expression is altered in breast cancer confirming its involvement in breast cancer progression. Genetic factors appear to play a role in breast cancer risk, and may modify tumor sensitization to vitamin D.

Synthesis and characterization of amine functionalized silylated clay for heavy metal adsorption: Thermodynamic and kinetic studies on Fe(III) ion.

Amine functionalized bentonites were used as adsorbents for the bioremoval of Fe(III) ions, which led to the inclusion of functional groups such as -OH, -NH2, -OCH3, etc. FTIR, XRD, SEM, AFM, TG, BET, XRF, and CHNS analyzer were used to analyze the surface and textural characteristics. The influence of adsorption factors, such as pH, contact time, temperature, and initial concentration, have been investigated and tailored in batch adsorption experiments of Fe (III) metal ions. The maximum adsorption efficiency and capacity of modified BNT-APTMS is 100.90 % and 103.91 mg/g respectively. The adsorption process is best fit with Freundlich model (R2 = 0.998) than Langmuir model (R2 = 0.788) and the Temkin model D-R isotherm parameters indicating a physisorption process. A mechanism of spontaneous complexation was accomplished, because of the heterogeneity of the surface, electrostatic forces, pore filling, and π-π stacking. Follows PSO kinetics and favours Freundlich isotherm. The adsorbent substance showed a remarkable capacity for regeneration, assuring the substance's stability and reusability.

Fine-Needle Cytological Characteristics of Carcinoma Breast with Medullary or Medullary-like Features Masquerading as Dendritic Reticulum Cell Sarcoma: An Attempt to Explore the Reasons for Erroneous Cytologic Interpretation.

BACKGROUND: Infiltration of tumors by dendritic reticulum cells (DRC) reflects the host immune defense mechanism. We observed three breast carcinomas cases with dense tumor-infiltrating DRC and lymphocytes in fine-needle aspiration (FNA) smears, leading to cytodiagnosis or differential diagnosis of dendritic reticulum cell sarcoma (DRCS). An attempt was made to find out the reason behind such an erroneous interpretation. MATERIALS AND METHODS: Between 2009 and 2014, two cases were diagnosed as DRCS of the female breast by FNA cytology and in one case possibility of DRCS was considered along with medullary breast carcinoma (MBC). We compare and contrast the cytomorphological features of these three cases with those of nine cytologically diagnosed MBC. RESULTS: Cases diagnosed as DRCS or MBC showed singly dispersed tumor cells, nuclear pleomorphism, bare nuclei, prominent nucleoli, and presence of lymphocytes. There was no significant difference between the two groups for discohesive clusters, syncytial clusters, plasma cells, neutrophils, foamy histiocytes, and necrosis. However, there was significant difference for presence of cohesive clusters (0% DRCS and 100% MBC, P = 0.00485), severe degree (+++) of pleomorphism (100% DRCS vs. 11.1% MBC, P = 0.01818), +++ DRC (P = 0.04697), and DRC with ++ to +++ enlarged nuclei (P = 0.03333), and pleomorphic nuclei (P = 0.00833). Two of the three cytologically diagnosed DRCS cases proved to be MBC or MBC-like and one as invasive ductal carcinoma. Six of nine cytologically diagnosed MBC cases with histology proved to be invasive breast carcinomas. CONCLUSION: Criteria for cytodiagnosis MBC need a fresh look. Cases with numerous dendritic cells possibly represent MBC.

Anaplastic large cell lymphoma: Report of two cases with rare patterns (carcinomatous and sarcomatous) in fine needle aspiration cytology and histopathology.

Anaplastic large cell lymphoma (ALCL) is a non-Hodgkin lymphoma of T-cell or null-cell lineage with variable cytomorphology. We report two rare ALCL cases with carcinomatous and sarcomatous patterns, respectively, in fine needle aspiration (FNA) cytology and histopathology. The first case was a 56-year-old man with enlarged left inguinal lymph node. FNA smears showed a malignant small round cell tumor with nuclear molding. In addition, there were large bi-nucleated and multinucleated cells with wreath-like arrangement of nuclei. ALCL and small cell (neuroendocrine) carcinoma were the possibilities considered. Immunocytochemical studies on FNA smears showed positive reaction for leukocyte common antigen (LCA) and negative results for cytokeratin (CK) and chromogranin. Histopathological examination of the lymph node showed features of ALCL with following immunohistochemical staining results: LCA+, CD30+, CD45RO+, CD20-, CD3+ (weak), and Alk1-. During review of sections, areas resembling a small cell anaplastic carcinoma were observed. The second case was a 24-year-old woman with right cervical lymphadenopathy. FNA smears showed an ALCL with highly atypical large cells including bi-nucleated and donut shaped cells, which were positive for CD30, EMA, and Alk-1 protein, and negative for CD20, CD3, and CK. Histopathological examination corroborated the cytodiagnosis of ALCL, and with positive immunohistochemical staining for CD30, EMA, Alk-1 protein+, BCL6+, and Ki67+ (40% cells) and negative results for CD20, CD10, CD3, CD5, CD15, BCl2, CD79a, and CD68. Sarcomatous components were noticed during review of cytologic and histopathological specimen. Awareness about these unusual cytomorphological patterns in ALCL may be of help in proper diagnosis of this neoplasm.

Papillary carcinoma in thyroglossal duct cyst: Diagnosis by fine-needle aspiration cytology and immunocytochemistry.

Carcinoma associated with thyroglossal duct cyst (TDC) is extremely rare and when it occurs it is invariably papillary carcinoma. A 36-year-old man presented with a midline swelling in the upper part of neck, which was a cystic lesion with multiple septae in ultrasonogram, indicating a thyroglossal duct cyst. The CT scan findings also corroborated the ultrasound report. Fine needle aspiration (FNA) smears showed hemosiderin laden cyst macrophages and occasional papillary cluster of neoplastic cells with central psammoma body and rare intranuclear cytoplasmic inclusions. The neoplastic cells revealed positive reaction for thyroglobulin, galectin3, and CD44. FNA cytodiagnosis was thyroglossal duct cyst with cytologic features suggestive of papillary carcinoma. The histopathological diagnosis of the resected lesion, however, was metastatic papillary thyroid carcinoma in lymph node with cystic changes; there was positive reaction for thyroglobulin, galectin3, HBME1, and CK. Following this histopathology report, thyroidectomy was performed, which revealed lymphocytic thyroiditis and no evidence of papillary carcinoma. Review of paraffin sections of upper midline neck mass showed a cavity bound by thick fibrocollageneous wall and lined partly by epithelium consistent with papillary carcinoma. The cyst wall showed dense lymphomononuclear cell infiltration and germinal center formation. There were foci of papillary carcinoma in the cyst wall with frequent nuclear grooves, cerebriform nuclei and intranuclear cytoplasmic inclusions. The reviewed histopathological diagnosis was consistent with papillary carcinoma in thyroglossal duct cyst. Thus, the FNA cytodiagnosis of a rare case of papillary carcinoma in thyroglossal duct cyst, led to review and change in histopathological diagnosis achieving cyto-histopathological correlation.

A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to diffuse large B-cell non-Hodgkin lymphoma: Diagnostic difficulty in fine-needle aspiration cytology.

A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) progresses to diffuse large B-cell lymphoma (DLBCL). There have also been rare reports of gray zone lymphoma with features intermediate between classical Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic difficulty faced during its fine-needle aspiration (FNA) cytology diagnosis. A 65-year-old woman presented with a right axillary swelling which was subjected to FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell lymphoma (ALCL) but immunocytochemistry did not support this diagnosis completely. The histopathological diagnosis of the excised lymph node was NLPHL with progression to DLBCL in our hospital but in a hospital abroad where the patient was treated, the reviewed diagnosis was CHL. The patient had a rapid downhill course with development of terminal pleural effusion and died approximately one year from initial diagnosis.The review of the cyto-histologic material along with additional immunocyto/histochemical studies and the clinical course of the disease support the diagnosis of a composite lymphoma (CHL and NLPHL) with progression to DLBCL. It is suggested that all the three lesions were clonally related. Diagn. Cytopathol. 2017;45:262-266. © 2016 Wiley Periodicals, Inc.

Relationship between the expression of various markers and prognostic factors in breast cancer.

The immunohistochemical detection of six markers of breast cancer has been compared in the present study with known prognostic factors of the disease to establish locally a standard panel of markers for the management of breast cancer. Sections of tissue of 114 consecutive breast cancer cases were studied immunohistochemically, using antibodies against oestrogen receptor (ER), progesterone receptor (PR), androgen receptor, c-erbB2, cathepsin D, and cyclin D. Marker labelling was graded as recommended in the literature. Using the chi(2)-test, relationships were determined between marker labelling and histological type of cancer, tumour grade, tumour size, axillary lymph node status and age of patient. A p value below 0.05 was considered significant. A positive relationship was found between ER and PR and lower grades of cancer, and a negative relationship was found with medullary and atypical medullary carcinoma. The four other markers showed no relationship with grade or type of cancer. All markers showed no significant relationship with size of tumour, presence of axillary node metastasis or age of patient. There was positive correlation between c-erbB2 and cathepsin D. Our study confirms the association between ER and PR and histological type and grade of breast cancer, both known parameters of good prognosis. We found no consistent relationship between the other four markers and prognostic factors studied, other than the suggestion that c-erbB2 and cathepsin D may be useful markers for poor prognosis and can be usefully applied locally, especially in the light of the current availability of trastuzumab (Herceptin) for management of c-erbB2-positive cases. We found no relationship between the markers and tumour size, axillary lymph node status or age.

Molecular characterization of a population-based series of endometrial stromal sarcomas in Kuwait.

Endometrial stromal sarcomas (ESSs) frequently harbor genetic fusions, including JAZF1-SUZ12 and equivalent fusions in low-grade ESS (LGESS) and YWHAE-NUTM2 in high-grade ESS (HGESS). This study aims to classify a population-based series of ESSs in Kuwait based on the 2014 World Health Organization classification system and to assess the diagnostic use of interferon-induced transmembrane protein 1 (IFITM1) immunomarker for ESSs. Twenty ESSs including 19 LGESSs and 1 HGESS treated during the period between 2002 and 2013 were identified, and the cases were reviewed and characterized using fluorescence in situ hybridization and immunohistochemical studies. Thirteen (81.3%) of 16 LGESSs with interpretable results showed JAZF1 and/or PHF1 genetic rearrangements by fluorescence in situ hybridization, and the only HGESS in the series showed YWHAE genetic rearrangement. All LGESSs with interpretable results showed positive immunostaining for CD10 compared with 11 (61%) of 18 that showed positive immunostaining for IFITM1; 4 of 7 IFITM1-negative LGESSs showed JAZF1 and/or PHF1 rearrangements. A series of uterine leiomyomas, leiomyosarcomas, adenosarcomas, and carcinosarcomas were included for comparison, and positive IFITM1 staining was found in 1 of 10 leiomyomas, 3 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 3 of 8 carcinosarcomas, compared to 0 of 10 leiomyomas, 9 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 5 of 8 carcinosarcomas that were positive for CD10. Our results demonstrated characteristic genetic rearrangements in a high percentage of LGESSs in this Middle Eastern population, and IFITM1 antibody appears to be less sensitive than CD10 for LGESS.

T-cell prolymphocytic leukemia (T-PLL) with overlapping cytomorphological features with T-CLL and T-ALL: a case initially diagnosed by fine-needle aspiration cytology and immunocytochemistry.

T-cell prolymphocytic leukemia (T-PLL) is a very unusual form of chronic lymphoproliferative disorder, which has rarely been diagnosed by fine needle aspiration (FNA) cytology. We report one such case with some overlapping cytomorphological features with chronic lymphocytic leukemia and acute lymphoblastic leukemia. A 91-year-old man presented with generalized lymphadenopathy, pleural effusion, ascites, and an ulcerated growth in rectum. FNA smears from the left cervical lymph node showed a monotonous population of small lymphoid cells having small but distinct nucleoli that was initially diagnosed as chronic lymphocytic leukemia (CLL). Smears from the left axillary lymph node contained both small and medium-sized lymphoid cells with frequent hand-mirror cell appearance, which has been described in acute lymphoblatic leukemia (ALL). Immunocyto/histochemical stainings on smears and cell block preparations of the aspirate showed the following immunophenotype: CD3+, CD4+, CD5+, CD7+, CD8-, CD20-, CD23-, and Tdt-. Total peripheral blood leukocyte count was 26.4 × 10(9) /L and total lymphocyte count, 8.3 × 10(9) /L with predominance of small lymphocytes. T-cell nature of the neoplasm was confirmed by biopsies from the cervical lymph node (T-cell lymphoma), bone marrow (T-cell lymphoid neoplasm/chronic lymphocytic leukemia), and the ulcerated rectal lesion (atypical T-cell lymphoproliferative disorder). The patient developed deep vein thrombosis, heparin-induced thrombocytopenia and bleeding from duodenal ulcer. By the time the reports of all the investigations were ready, the patient succumbed to bronchopneumonia. To the best of our knowledge, this T-CLL/T-PLL which was diagnosed initially by FNA cytology with immunocytochemical support is first of its kind to be reported.

T-cell-rich B-cell lymphoma (TCRBCL): limitations in fine-needle aspiration cytodiagnosis.

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T-cell-rich B-cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B-cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkin's lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non-Hodgkin lymphoma (NHL) T-cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology.

Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis.

Tubulolobular carcinoma (TLC) is a rare tumor of the breast in which histologic features of both tubular and lobular carcinoma are combined. We report a case of TLC, in which the specific subtype was missed at routine cytologic and histopathological examination. A 69-year-old woman presented with a right breast lump. Imaging studies indicated a malignant lesion in right upper quadrant. Routine fine needle aspiration (FNA) cytology diagnosis was a duct cell carcinoma (small cell type). In a setting of cystic thyroid lesions, presence of excessive nuclear grooves, and rare intranuclear cytoplasmic inclusion, metastatic papillary thyroid carcinoma was also considered. However, both these possibilities were not supported by immunocytochemical findings (estrogen receptor+, thyroglobulin-, and chromogranin-). The histopathology diagnosis was invasive duct cell carcinoma. Review of FNA smears and paraffin sections led to the diagnosis of TLC, which was supported by positive immunohistochemical stainings for markers like e-cadherin and ß-catein.

Hodgkin's lymphoma: diagnostic difficulties in fine-needle aspiration cytology.

It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non-Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed-Sternberg (R-S)-like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine-needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty-one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin-like cells and typical R-S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnosis of HL.