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Shahid Islam, MD, PhD, FRCPC, FCAP
Associate Professor, Faculty of Medicine
Director, Residency Training Program
Anatomic and General Pathology, University of Ottawa
Staff Physician, Ottawa Hospital / EORLA
Clinical Research Investigator, Ottawa Hospital Research Institute (OHRI)
- Breast and Gynecologic Oncologic Surgical Pathology
Eastern Ontario Regional Laboratory (EORLA)
The Ottawa Hospital, General Campus Site
Critical Care Wing, Rm # 4115
501, Smyth Road
Tel: 613-737-8899, Ext 78297
Selected Research Activities
Clinical Relevance and Practice Experience of Reporting Atypical Squamous Cells Cannot Exclude High Grade Squamous Intraepithelial Lesion, (ASC-H)
The current study explored the diagnostic parameters and pitfalls in the follow up of 123 cases of PAP smears diagnosed as ASC-H at our institution. The results of this study are in keeping with previous studies that support the notion that the category of ASC-H is an important entity in the 2001 Bethesda System. In addition, the study concludes that 59.4% of the cases that were diagnosed cytologically as ASC-H were found to have HSIL on subsequent biopsies. Interestingly, this correlation was stronger in patients below the age of 40 years compared to patients above the age of 40 years (65.1% vs. 47.5%). The cytopathologic feature most strongly associated with HSIL was the presence of coarse chromatin (84%).
Cytohistologic Correlation of Benign Pulmonary Nodules with Radiologic Features
The purpose of this study was to evaluate the cytologic features of six cases of biopsy proven benign pulmonary nodules with radiologic and histologic correlation.
The study concludes that the cytological features useful in separating benign pulmonary nodules are: cohesive cell clusters, inflammatory and histiocytic cells with giant cells and myxoid stroma in the smear background. The lack of nuclear atypia with bland chromatin profile is useful in diagnosing benign pulmonary nodules.
Indeterminate for Neoplasia in the Diagnosis of Thyroid FNAB: Cytohistologic Correlation and Diagnostic Pitfalls-a 5 year Retrospective Study in a Tertiary Care Hospital, Ontario, Canada
This is a study of 5-year look back in a Tertiary Care Facility (the Ottawa Hospital) with cyto-histologic correlation to identify diagnostic pitfalls in the diagnosis of follicular lesions (inconclusive/indeterminate). Follow-up of 205 cases showed follicular Adenoma (FA) in 53 (25.8%), hurthle cell adenoma (HA) in 19 (9.2%), multi-nodular goitre (MGN) in 95 (46.3%), papillary carcinoma, follicular variant (PTCFV) in 25 (12.2%), thyroiditis (THY) in 8 (3.9%) and follicular carcinoma (FC) in 5 (2.4%) patients. Hard cytologic features that accurately predict FA (48 specimens), FC (4 specimens) and PTCFV (23 specimens) are tight microfollicle formations (defined as acinar structures formed by crowed enlarged nuclei with chromatin clearing and inconspicuous nucleoli) present >60% in the smears and scant to nil colloid. The most common diagnostic pitfall is follicular cells wrapped up in clotted blood and endothelial cells (MGN, 87 specimens).
The study concludes that the hard cytologic features that will increase diagnostic specificity of FN (FA, FC and PTCFV) are tight microfollicle formations present in more than 60% of the smears and scant colloid. The most common diagnostic pitfall is clotted blood.
Bronchoalveolar Carcinoma of the Lung- A Cytohisto Correlation with Diagnostic Pitfalls:
Demonstration of a well-differentiated, localized tumor with lepidic growth pattern suggests a BAC. But well differentiated adenocarcinoma or an adenocarcinoma of mixed subtype with invasive patterns can also give a similar deceiving picture. The rate of concordance of radiologic and cytologic appearance of BAC with the subsequent final histological diagnosis is not well established. We did a retrospective search of all cases that were diagnosed as 'BAC' following FNAC at the Ottawa Hospital ('00 -'09). All cases had a prior CT scan and needed to have a subsequent wedge resection or lobectomy with evaluations done at our institution. Correlations between radiologic, cytological and subsequent histopathological diagnosis was then evaluated. The study shows that only 35% of lesions appearing as BAC on CT scan are subsequently confirmed by both cytology and histology. A cytologic diagnosis of BAC is inaccurate in >60% of cases.
Missed Malignancy on Breast Biopsy Diagnosed as a Papillary Lesion:
Papillary lesions are a frequent finding from breast biopsy and include intraductal papillomas, papillary lesions with or without atypia and papillary carcinomas. It is controversial whether or not to excise benign papillary lesions diagnosed on biopsy because only a fraction of lesions are later found to contain malignancy. The purpose of this study was to determine the frequency of missed malignancy in papillary breast lesions at our institution and to determine the factors that may have contributed to the missed diagnosis.
Whether or not to excise papillary lesions of the breast continues to be a matter of debate. We have demonstrated that at our institution that nearly half of the women diagnosed with papillary lesions of the breast who go on to surgical resection, will be found to harbour a malignancy. Radiological findings did not predict the discovery of malignancy at resection. Our data indicate that the most common cause for this discrepancy is sampling error with the malignancy not being present within the biopsy material. Due to the high rate of malignancy at resection, our data suggest that women diagnosed with papillary lesions on biopsy should undergo local resection in order to avoid missing a malignancy that may not have been sampled in the biopsy.
Cadherin Expression Profile in Prostate Carcinomas and its Role in Diagnosis and Prognosis
The current study explored the differential expression of E-cadherin, N-cadherin, cadherin-11 and β -catenin in PAC with different Gleason scores. From this study we conclude that prostatic adenocarcinoma with higher Gleason scores is likely to be associated with gradual loss of membranous E-cadherin and β-catenin expression with a shift in cellular localization of β-catenin from membranous to perinuclear cytoplasmic expression. In contrast to earlier studies, we failed to detect N-cadherin expression in any of the 15 adenocarcinomas. In addition, we failed to detect mesenchymal cadherin-11 expression in adenocarcinoma cells.
Gene Expression Profile in Thyroid Neoplasm
The study began with identifying the molecular markers that could help in the differential diagnosis of follicular adenoma vs. follicular carcinoma of the thyroid. In this study we examined the differential cellular localization of E-cadherin, and N-cadherin, along with β-catenin in thyroid follicular adenoma, follicular carcinoma, and papillary carcinoma. The study concludes that 1) localization profiles of cadherins and β-catenin are different in follicular adenoma, follicular carcinoma, and papillary carcinoma, 2) follicular carcinoma and papillary carcinoma express β-catenin in the cytoplasm of the neoplastic cells, but most of the follicular adenomas show co expression of this marker in the membrane and cytoplasm, 3) N-cadherin is positive in most of the follicular adenomas and carcinomas, but negative in most of the papillary carcinomas. Thus cadherins and β-catenin localization may help in differentiating follicular adenomas from follicular carcinomas, and follicular carcinomas and adenomas from papillary carcinomas (follicular and encapsulated variant).
Differential Localization of Cadherin Catenin Complex in Malignant Mesothelioma and Lung Adenocarcinoma
This study explored the differential expression and cellular localization of cadherins, namely E-cadherin, N-cadherin, and cadherin-11 along with β-catenin in malignant mesothelioma and lung adenocarcinoma. The study concludes 1) in general, malignant mesotheliomas are positive for N-cadherin and cadherin-11 and they are negative for E-cadherin, 2) adenocarcinomas are generally positive for E-cadherin and are negative for N-cadherin and cadherin-11 and 3) Expression profile of β-catenin is not useful in differentiating adenocarcinoma from malignant mesothelioma.
Cadherin-Catenin Expression Profile in Primary Invasive Breast and Ovarian Carcinomas by Tissue Micro arrays (TMA) with Clinicopathologic Correlation
By constructing tissue microarrays (TMAs), we investigated the relationship between cadherin and catenin expression in breast and ovarian cancers. To maximize immunohistochemical resources and minimze tissue use, the tissue microarray technique was employed. The study concludes that E-cadherin and beta-catenin expression are not associated with nodal metastases in breast carcinomas. While promising, the relationship between N-cadherin expression and nodal metastases in breast carcinomas should be validated in a larger prospective study. The expression profile of cadherin-catenin in ovarian cancer is under study at this time.
Expression Profile of p16 (INK 4a) and MIB1 (Ki-67) in High Grade Squamous Intraepithelial Lesion (HSIL) and Immature Squamous Metaplasia (ISM) of the Uterine Cervix
The purpose of the current study was to examine p16 and MIB1 expression profile and cellular localization in HSIL and ISM of the uterine cervix. From this study, we conclude that diffuse and strong nuclear and cytoplasmic p16 expression in combination with strong MIB1 nuclear expression in basal, parabasal and intermediate cells favour HSIL over IMS.
- Teaching the Can MEDS Roles to Laboratory Medicine Residents: Residents as Teachers and Development of ePortfolios. S. Strickland and S. Islam Can J Pathol (accepted for publication) 2014
- Frequency of Malignancy at Final Excision in Biopsy-diagnosed Benign Papillary Lesions of the Breast. Petkiewitz, S and Islam, S. Can J Pathol (accepted for publication) 2013
- Amin MS, Senterman M, Islam S. Co-expression and cellular localization of p16 (INK 4a) and Mib1 (Ki-67) help in differentiating high grade squamous intraepithelial lesions from immature squamous metaplasia of the uterine cervix. Canadian Journal of Pathology, Vol 3, Issue 4, pg 22-27, 2012.
- Hilton JF, Amin MS, Daneshmand M, Weberpals JI, Lorimer I, Islam S, Mallick R, Kanji F, Hopkins S, Verma S. Do BRCA1 protein levels and PI3KA mutations predict for response to neoadjuvant chemotherapy: an exploratory analysis. Oncology Letters (Accepted).
- Paget JA, Restall IJ, Daneshmand M, Mersereau JA, Simard M, Parolin DAE, Lavictoire SJ, Amin MS, Islam S, Lorimer IAJ. Repression of cancer cell senescence by PKCi. Oncogene (advance online publication; doi:10.1038/onc.2011.524, November 28, 2011).
- Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, Pelletier LB, O'Brien AM, Hoskins PJ, Eisenhauer EA. Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study. Annals of Oncology, 22(11): 2403-2410, 2011.
- K. T. Mai, Ahmed Itrat, S. J. Robertson, E. C. Belanger, J. Veinot and S. Islam. 2008. Immunocytochemical study of urine cytological preparations from secondary prostatic adenocarcinoma involving the urinary bladder. Diagnostic Cytopathology, vol 36, #10, pg 715
- G. Mokhtar, N. Dilatour, A. Assiri, M. Gilliat, M. Senterman and S. Islam 2008. Atypical Squamous Cells, Cannot Exclude High Grade Squamous Intraepithelial Lesion, ASC-H: Cytohisto correlation and Diagnostic Pitfalls. Acta Cytol. Vol 52: 169–177
- G. Mokhtar, N. Dilatour, K. Mai, M. Senterman and S. Islam 2008. Benign Solitary Pulmonary Nodules: Cytologic Features with Radiologic and Histologic Correlation. ActaCytol. 52
- K. T. Mai, I. Teo, E. C. Belanger, S. Robertson, E. C. Marginean and S. Islam. Progesterone Receptor in Renal Oncocytoma and Chromophobe Renal Cell Carcinoma. Histopathology. 2008 Feb; 52(3): 277-82.
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