Romana Idrees

Secretory carcinoma of breast: clinicopathologic study of 8 cases

Our aim was to describe clinicopathologic features of secretory carcinoma on a cohort of cases. We retrieved reported cases of secretory carcinoma of breast (SCB) in the Section of Histopathology, Department of Pathology & Microbiology, Aga Khan University Hospital Karachi, from May 2004 to December 2011. The slides were reviewed, and clinicopathologic features were noted. A total of 8 cases of SCB were found. The age ranged from 17 to 60 years (median, 41 years) with a female to male ratio of 7:1. Lumpectomy was done in 6 cases, and mastectomy, in 2 cases. The tumor size ranged from 2.5 to 10 cm (mean, 5.5 cm). Histologically, abundant extra- and intracellular secretory material was seen in all cases. Most of the tumors showed mixtures of patterns with dominant microcystic and papillary patterns. In situ component was seen in only 1 case. Lymph node metastases were seen in both cases with lymph node sampling. In conclusion, SCB is a rare type of ductal breast carcinoma. The papillary pattern of SCB is rare according to published data but was seen in most of our cases. In situ secretory carcinoma is even rarer, and to date, we have seen a single case only. Although most occur in women, these can be seen in men as well.

Effect of formalin fixation on surgical margins in breast cancer surgical specimen.

Margin analysis in breast surgery is an important predictor of local recurrence and can have vital impact on the postoperative treatment planning. Objective. The aim was to assess the mean reduction in the closest tumor-free surgical margin in millimeters of breast cancer specimens following formalin fixation. Materials and Methods. We conducted a cross-sectional study at the Aga Khan University Hospital from March 30, 2010 to January 20, 2011. One hundred consecutive breast tumour surgical specimens which had macroscopically visible tumour were included. The cancer type included both in situ and invasive cancers. Excluded were the patients who had previous surgery or systemic/radiation therapy. The closest tumor-free margin was recorded and compared with the margin after formalin fixation. P value of <0.05 was considered significant. Results. The mean age of our 100 patients was 53 years with the majority of the patients having undergone mastectomy for predominantly invasive ductal carcinoma. Following formalin fixation, the mean reduction of the closest tumor-free margin was noted as 2.14 mm which was found statistically significant. Conclusion. Considerable shrinkage of tumor-free surgical margins of breast cancer specimen was noted after formalin fixation. This inference can have implications on the postoperative management plan.

Gastrointestinal, liver and biliary tract pathology: a histopathological and epidemiological perspective from Pakistan with a review of the literature.

AIM To present an epidemiological and histological perspective of diseases of the gastrointestinal tract (including liver and biliary tract) at the Section of Histopathology, Department of Pathology, AKUH, Karachi, Pakistan. MATERIALS AND METHODS All consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included. RESULTS A total of 2,323 cases were included. Carcinoma was overwhelmingly the commonest diagnosis on esophageal biopsies (69.1%); chronic helicobacter gastritis (45.6%) followed by adenocarcinoma (23.5%) were the commonest diagnoses on gastric biopsies; adenocarcinoma (27.3%) followed by ulcerative colitis (13.1%) were the commonest diagnoses on colonic biopsies; acute appendicitis (59.1%) was the commonest diagnosis on appendicectomy specimens; chronic viral hepatitis (44.8%) followed by hepatocellular carcinoma (23.4%) were the commonest diagnoses on liver biopsies; chronic cholecystitis was the commonest diagnosis (over 89%) on cholecystectomy specimens. CONCLUSIONS Squamous cell carcinoma comprised 88.8% of esophageal cancers. About 67% were in the lower third and 56.5% were moderately differentiated; mean ages 49.8 years for females and 55.8 years for males; 66% cases were from South West Pakistan. Over 67% patients with gastric adenocarcinoma were males; mean ages 59 and 44 years in males and females respectively, about 74% gastric carcinomas were poorly differentiated; and 62.2% were located in the antropyloric region. About 63% patients with colorectal adenocarcinoma were males; mean ages 46.1 and 50.5 years for males and females respectively; tumor grade was moderately differentiated in 54%; over 80% were located in the left colon. In 21.2% appendicectomies, no acute inflammation was found. Acute appendicitis was most common in young people. Hepatitis C (66.3%) was more common than hepatitis B (33.7%); about 78% cases of hepatocellular carcinoma occurred in males; females comprised 76.7% patients with chronic cholecystitis; and 77.8% patients with gall bladder carcinoma. All resection specimens showed advanced cancers. Most cancers occurred after the age of 50 years.

Ovarian sex cord stromal tumours in children and young girls - a more than two decade clinicopathological experience in a developing country, Pakistan.

BACKGROUND Ovarian sex-cord stromal tumours (SCST) are rare, and relatively infrequent in children. These have to be distinguished from more common germ cell tumors in children and also from benign epithelial neoplasms. OBJECTIVES The purpose of our study was to report the clinical and pathological findings in young patients with these tumours in our population. MATERIAL AND METHODS The present observational cross-sectional study included all subjects <21 years of age diagnosed with ovarian SCST, in Aga Khan University Hospital Histopathology Laboratory, Karachi, Pakistan, from January 1992 till July 2013. RESULTS Of the total of 513 SCSTs presented during the study period, 39 fulfilled inclusion criteria and were assessed. The age range was 4-250 months. Most of the tumours presented at stage-1 and an abdominal mass was the most common presenting symptom, along with menstrual disturbance. The left side ovary was slightly more affected (53.5%). Of the total, 15 were juvenile granulosa cell tumours (JGCT), 11 sclerosing stromal tumours (SST), 10 of the fibrothecomas spectrum, 2 Sertoli leydig cell tumours (SLCT) and one a sex cord tumour with annular tubules (SCTAT). Detailed immunohistochemical analyses were performed in 33 cases. Recurrence/metastasis was noted in 4/21 cases with follow-up data. CONCLUSIONS Ovarian sex cord stromal tumours are very rare in young age in our population, and usually present at an early stage. Most common among these are juvenile granulosa cell tumours, although surprisingly sclerosing stromal tumours were also common. Clinical symptoms due to hormone secretion in premenstrual girls and menstrual disturbance in menstruating girls are common presenting features.

Is fascin really a useful marker in distinguishing between classical Hodgkin's lymphoma and various types of Non-Hodgkin's lymphomas in difficult cases?

Background Fascin is an actin cross-linking protein, which is part of the cytoskeleton and involved in cell motility in several cell types. The differentiation of epithelial cells is greatly influenced by cell–matrix and cell–cell interactions, which play an important role in the normal organisation and stabilisation of epithelial cells and maintain the cells in a non-migratory state. The malignant conversion of epithelial cells results from a phenotypic switch to a migratory state, which allows tumour invasion beyond the basement membrane, as well as metastasis. Such a switch requires complex rearrangements of the actin cytoskeleton and is governed by multiple actin-binding proteins including fascin. In non-neoplastic lymphoid tissue, fascin expression is highly selective and is predominantly localised in dendritic cells, while lymphocytes, plasma cells, etc are uniformly non-reactive. However, all or nearly all Reed–Sternberg cells and their variants in all types of Hodgkins lymphoma express fascin and are strongly immunoreactive for fascin. Conclusion Lymphomas (Hodgkins and non-Hodgkins) are among the commonest malignancies seen in our practice. The Section of Histopathology at the Aga Khan University, Karachi is the largest centre for histopathology in Pakistan, a densely populated country with an estimated population of 170 million. The authors wanted to test the utility of Fascin in distinguishing between Hodgkins lymphoma and morphologically closely related forms of non-Hodgkins lymphoma such as diffuse large B cell non-Hodgkins lymphoma and anaplastic large cell lymphoma in difficult cases. If found useful, this antibody could help us in reaching a correct diagnosis in difficult cases and allow appropriate patient management.

Gastrointestinal Stromal Tumors: A Clinicopathologic and Risk Stratification Study of 255 Cases from Pakistan and Review of Literature

PURPOSE To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota. MATERIALS AND RESULTS We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletchers consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasotas algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection. CONCLUSIONS Epidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category.

Commonest Cancers in Pakistan - Findings and Histopathological Perspective from a Premier Surgical Pathology Center in Pakistan.

CONTEXT There are no recent authoritative data about incidence and prevalence of various types of cancers in Pakistan. AIM To determine the frequency of malignant tumors seen in our practice and provide a foundation for building a comprehensive cancer care strategy. MATERIALS AND METHODS 10,000 successive cases of solid malignant tumors reported in 2014 were included. All cases had formalin fixed, paraffin embedded specimens available and diagnosis was based on histological examination of H and E stained slides plus ancillary studies at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. The latest WHO classifications were used along with the latest CAP protocols for reporting and the most updated TNM staging. RESULTS There were 9,492 (94.9%) primary tumors while 508 (5.1%) were metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in males. The commonest malignant tumors in females were breast (32%), esophagus (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%) and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th decades. About 8% were seen under 20 years of age. CONCLUSIONS Oral cavity and gastrointestinal cancers continue to be extremely common in both genders. Breast and esophageal cancers are prevalent in females. Lung and prostate cancer are less common than in the west. Ovarian cancer was very common but cervix cancer was less so.

Diagnostic Performance of Breast MRI in the Evaluation of Contralateral Breast in Patients with Diagnosed Breast Cancer

AIMS The purpose of our study was to evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in the evaluation of contralateral breast in patients with diagnosed breast cancer. A secondary objective was to determine accuracy of breast MRI in diagnosing multi-focal and multicentric lesions in the ipsilateral breast. MATERIALS AND METHODS Using a non-probability convenience sampling technique, patients with histopathologically diagnosed breast cancer with MRI of breast performed to exclude additional lesions were included. MRI findings were correlated with histopathology. In addition, follow-up imaging with mammography and ultrasound was also assessed for establishing stability of negative findings and for the detected of benign lesions. RESULTS Out of 157 MRI breast conducted during the period of 2008 to 2013, 49 were performed for patients with diagnosed breast cancer. The sample comprised of all females with mean age 50.7 ± 11.0 years. The patient follow-up imaging was available for a period of 2-5 years. The sensitivity, specificity, and positive and negative predictive values of MRI in the detection of multifocal/multicenteric lesions was 85.7%, 88.8%, 60% and 96.6% respectively and for the detection of lesions in the contralateral breast were 100%, 97%, 83.3% and 100% respectively. CONCLUSIONS Our study highlights the diagnostic performance and the added value of MRI in the detection of multifocal /multicenteric and contralateral malignant lesions. In patients with diagnosed breast cancer having dense breast parenchyma and with infiltrating lobular carcinoma as the index lesion MRI is particularly useful with excellent negative predictive value in the exclusion of additional malignant foci in the ipsilateral and contralateral breasts.

How Our Practice of Histopathology, Especially Tumour Pathology has Changed in the Last Two Decades: Reflections from a Major Referral Center in Pakistan

Continued advances in the field of histo-pathology (and cyto-pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube and Facebook where anyone can obtain any information one desires at the push of a button. The practice of histo (and cyto) pathology has also evolved in line with these changes. For those practicing this discipline in a poor, developing country these changes have been breathtaking. This is an attempt to document these changes as experienced by histo (and cyto) pathologists practicing in the biggest center for Histopathology in Pakistan, a developing country in South Asia with a large (180 million) and ever growing population. The Section of Histopathology, Department of Pathology and Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistans largest city has since its inception in the mid-1980s transformed the way histopathology is practiced in Pakistan by incorporating modern methods and rescuing histopathology in Pakistan from the primitive and outdated groove in which it was stuck for decades. It set histopathology in Pakistan firmly on the path of modernity and change which are essential for better patient management and care through accurate and complete diagnosis and more recently prognostic and predictive information as well.

Invasive Micropapillary Carcinoma of Breast: An Under-recognized Entity. A series of Eight Cases

Abstract:  Invasive micropapillary carcinoma (IMPC) of breast is a morphologically distinct and relatively uncommon variant of invasive ductal carcinoma. It is characterized by small clusters of tumor cells with surrounding clear stromal spaces; a tendency for vascular permeation and therefore, an aggressive clinical course. This morphologic pattern can be easily missed especially in a small biopsy specimen because pathologists may disregard the clear spaces as artifactual. With a tendency of presenting at a higher stage, this morphological pattern needs to be mentioned in the histopathology report whenever it is encountered, either in its pure form or admixed with conventional ductal carcinoma. We describe eight cases of IMPC of breast along with their variable clinical presentations.