Naveen Faridi

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

INTRODUCTION Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. METHODS A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. RESULTS Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. CONCLUSION Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification.

Diagnostic role of fine needle aspiration cytology (FNAC) in the evaluation of salivary gland swelling: an institutional experience

BackgroundFine needle aspiration cytology (FNAC) is a cytodiagnostic method based on morphologic findings of individual and small group of cells aspirated using a fine needle. The aim of the present study is to evaluate the spectrum of salivary gland lesions in our setting and to assess the diagnostic accuracy of FNAC for salivary gland lesions.MethodsThe study involved 187 cases of parotid and submandibular swellings of patients who underwent FNAC at our institution. Thirty one (31) patients with a FNAC diagnosis of neoplastic lesion subsequently underwent excision biopsies. The results of FNAC and final histology were compared and accuracy of FNAC was determined.ResultsMean age of patients was 42 (±21) years and male to female ratio was 1:1. Chronic sialadenitis was the most common non-neoplastic lesion (33.8%) followed by acute and chronic sialadenitis (29.7%) and chronic granulomatous inflammation (27.0%). Pleomorphic adenoma was the most common benign neoplasm and non-Hodgkin’s lymphoma was the most common malignant lesion (38.9%) followed by acinic cell (27.8%) and adenoid cystic carcinoma (16.7%). Total 31 patients subsequently underwent surgical excision, out of which 21 were benign and 9 were malignant, 20 cases (64.5%) were of pleomorphic adenoma, 3 cases (9.6%) of acinic cell carcinoma, 2 cases (6.4%) each of warthin tumor, adenoid cystic carcinoma and non-hodgkin lymphoma and 1 case (3.2%) each of mucoepidermoid carcinoma and mucinous adenocarcinoma. The overall accuracy of FNAC in our study was found to be 83.8% with 77.7% sensitivity and 86.3%, specificity. The revised sensitivity and specificity after adjusting verification bias were 68.5% and 91% respectively. False negative diagnosis was rendered in mucoepidermoid carcinoma and acinic cell carcinoma whereas false positive diagnosis was given in cases of pleomorphic adenoma.ConclusionWe found a good concordance between FNAC and histology, however pleomorphic adenoma may impart a diagnostic challenge when inadequately aspirated and therefore we advice either immunohistochemical studies (if cell block material is available) or repeat aspiration in difficult cases.

Molecular Subtypes of Breast Cancer in South Asian Population by Immunohistochemical Profile and Her2neu Gene Amplification by FISH Technique: Association with other Clinicopathologic Parameters

Molecular breast cancer subtypes were defined by gene expression prolife; however, immunohistochemical (IHC) expression can categorize breast cancers analogous to gene expression profiling. We aimed to evaluate distribution of these molecular breast cancer subtypes in our population and their association with clinocopathologic parameters. We retrospectively analyzed 1,104 cases of primary breast cancers over 3 years duration. ER, PR, Her2neu IHC staining, and subsequent fluorescent in situ hybridization studies (Her2neu gene amplification in cases with 2+ IHC staining) were performed to categorize breast cancer subtypes. Luminal A breast cancers were most frequent (45.8%) followed by triple negative (18.6%), luminal B (17.8%) and Her2neu (17.8%) subtypes. We found a strong association of breast cancer subtypes with tumor grade and Ki67 proliferation index with triple negative cancers being associated with higher grade and proliferation index. Significant association was seen with age groups, luminal A subtype occurring at a slightly older age, whereas triple negative and Her2neu cancers were more frequent in younger age group. We found a higher proportion of triple negative cancers in our set up, and they were found to have high‐tumor grade and proliferation index along with presentation at younger age. As these cancers are associated with BRCA 1 mutations and abnormal BRCA 1 pathways, we suggest that large scale studies should be done to evaluate BRCA 1 mutations and abnormal BRCA 1 pathways in our population to establish risk factors for this highly aggressive tumor subtype.

Accuracy of Frozen Section Analysis of Sentinel Lymph Nodes for the Detection of Asian Breast Cancer Micrometastasis - Experience from Pakistan

BACKGROUND Intraoperative sentinel lymph node biopsy has now become the standard of care for patients with clinically node negative breast cancer for diagnosis and also in order to determine the need for immediate axillary clearance. Several large scale studies confirmed the diagnostic reliability of this method. However, micrometastases are frequently missed on frozen sections. Recent studies showed that both disease free interval and overall survival are significantly affected by the presence of micrometastatic disease. The aim of this study was to determine the sensitivity and specificity of intraoperative frozen section analysis of sentinel lymph nodes (SLNs) for the detection of breast cancer micrometastasis and to evaluate the status of non-sentinel lymph nodes (non-SLNs) in those patients subjected to further axillary sampling. MATERIALS AND METHODS We performed a retrospective study on 154 patients who underwent SLN biopsy from January 2008 till October 2011. The SLNs were sectioned at 2 mm intervals and submitted entirely for frozen sections. Three levels of each section submitted are examined and the results were compared with further levels on paraffin sections. RESULTS Overall 40% of patients (62/154) were found to be SLN positive on final (paraffin section) histology, out of which 44 demonstrated macrometastases (>2mm) and 18 micrometastases (<2mm). The overall sensitivity and specificity of frozen section analysis of SLN for the detection of macrometastasis was found to be 100% while those for micrometastasis were 33.3% and 100%, respectively. Moreover 20% of patients who had micrometastases in SLN had positive non-SLNs on final histology. CONCLUSIONS Frozen section analysis of SLNs lacks sufficient accuracy to rule out micrometastasis by current protocols. Therefore these need to be revised in order to pick up micrometastasis which appears to have clinical significance. We suggest that this can be achieved by examining more step sections of blocks.

Breast lesions in adolescents and young women in Pakistan--a 5 year study of significance of early recognition.

BACKGROUND Breast cancer is the most frequent malignant disease amongst young women. If we review local data in Pakistan then breast cancer represents approximately a third of all cancers in females. The age standardized incidence rate (ASR) world per 100,000 is 53.8 and crude incidence rate is 30.9. We have observed during our surgical pathology practice and it is also reported by other Asian studies that breast carcinoma is amongst the leading malignancies in the region and the patients are at least a decade younger than counterparts in developed nations. Age is an important issue in effective screening, diagnosis and management of breast cancer, especially in this geographical region where late presentation and poor prognosis are a hallmark of the disease. OBJECTIVE The aim of this study is to determine the frequency of malignant breast lesions in symptomatic young females presenting with breast lumps. MATERIALS AND METHODS This is a retrospective study conducted at the Pathology Department, Liaquat National Hospital and Medical College, Karachi. Descriptive and pathology data of malignant breast tumors 1st January 2004 to 31st December 2009 were reviewed, using the departmental archived data. It included both male and female patients up to the age of 25 years. RESULTS A total of 714 surgical specimens from/of symptomatic breast lesions were received at the pathology department of Liaquat National Medical, in the five years study period, in young females. There were 575 (80%) benign, 119 (16%) inflammatory and 20 (2.8%) malignant lumps. CONCLUSIONS The obtained data for females only up to 25 years of age suggest a massive burden which requires urgent attention. Early assessment of lesions is essential in order to avoid mortality from malignancies.

Clinical pattern and spectrum of endometrial pathologies in patients with abnormal uterine bleeding in Pakistan: need to adopt a more conservative approach to treatment

BackgroundAbnormal uterine bleeding (AUB) is one of the most common debilitating menstrual problems and has remained one of the most frequent indications for hysterectomy in developing countries. Approximately in 40% of hysterectomy specimens, no definite organic pathology could be established. The problem is common worldwide but causes may vary from one region to another. This study may help gynecologists in our population to improve their therapeutic strategies by promoting minimally invasive uterus sparing modalities such as endometrial ablation and hysteroscopic resection of early proliferative lesions.MethodsIt was a prospective, cross-sectional study conducted at Liaquat National Hospital from 15th January 2010 till 14th July 2011 over a period of 18 months. Women who underwent dilatation and curettage for endometrial sampling with complaints of AUB were included in the study and histopathologic spectrum was determined.ResultsPolymenorrhea was the most common presenting pattern (30%, 72/241) with reproductive age women being the most susceptible (49.3%,119/241). The commonest histopathological spectrum was normal menstrual pattern (34%, 82/241) and the commonest pathology was hormonal imbalance (27%, 65/241), followed by endometrial polyp (14%, 34/241), chronic endometritis (12%, 28/241), atrophic endometrium (6%, 15/241), endometrial hyperplasia (5%, 12/241), and endometrial carcinoma (2%, 5/241). Chronic endometritis was commonly seen in reproductive age (18%, 21/119); hormonal imbalance (45%, 35/77) and endometrial hyperplasia (6.5%, 5/77) in perimenopausal age; endometrial polyp (35.5%, 16/45) and endometrial carcinoma (9%, 4/45) in postmenopausal age.ConclusionFrequency of benign endometrial pathology is quite high in AUB, 236 participants (98%, 236/241). Histopathological spectrum in patients with AUB is quite variable with respect to age. The most common pattern of AUB was polymenorrhea. The most common pathology was hormonal imbalance. It is suggested that age was associated with more progressive lesions found in peri and postmenopausal age group such as endometrial hyperplasia and endometrial carcinoma. Yet endometrial polyp was the most common pathology found in postmenopausal women. Therefore, the management strategy should be individualized, as in most cases a restrictive approach is appropriate in order to avoid unnecessary hysterectomies.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT), case report with literature review

Introduction Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are uterine neoplasms of unknown histiogenesis which show near complete differentiation towards ovarian sex cord elements and are postulated to arise from pluripotential uterine mesenchymal cells or endometrial stromal cells with secondary sex cord differentiation. Case presentation A 48 year old post-menopausal women presented with abnormal uterine bleeding for which she underwent total abdominal hysterectomy with bilateral salpingo-ophorectomy. Gross examination revealed a gelatinous grayish white tumor confined to the myometrium, 7 cm in maximum dimention. Microscopic examination revealed monomorphic round to oval tumor cells in anastomosing cords and trabeculae with myxoid background. Immunohistochemically, tumor cells showed diffuse positivity for vimentin, CD99 and S100, while focal positivity was seen with pancytokeratin immunostain. The case was diagnosed as UTROSCT. No evidence of metastasis was found on systemic clinical and radiologic workup. Conclusion UTROSCT are rare uterine tumors which can be diagnosed with certainty on morphologic and immunohistochemical grounds. It is important to recognize these tumors as they behave differently from endometrial stromal tumors with sex cord like elements (ESTSCLE).

Diagnostic accuracy of Bethesda system for reporting thyroid cytopathology: an institutional perspective

Introduction Thyroid swelling is common problem among South Asian women. Although benign nodules far outnumber cancerous lesions, the risk of malignancy needs to be evaluated preoperatively for which fine needle aspiration cytology (FNAC) is widely used. Bethesda system for reporting thyroid cytopathology (BSRTC) was introduced to streamline the reporting of thyroid aspirates. We aimed to evaluate the disease spectrum of thyroid cytopathology and correlation of BSRTC with final histopathology in our setup. Methods The study was conducted at Histopathology department of Liaquat National Hospital, Karachi, involving 528 patients with thyroid swelling who underwent FNAC. Out of these 528 cases, 61 patients subsequently underwent surgical excision. Results of final histopathology were correlated with cytologic diagnosis. Results Mean age of the patients included in the study was 39.7 ± 13(14–84) and male to female ratio was 1:3.6. Out of total 528 cases, 403 cases were diagnosed as benign (Bethesda 2) and 67 were Bethesda 3 (follicular lesion of undetermined significance, FLUS) while 22 cases were categorized as either malignant or suspicious for malignancy (Bethesda 6 and 5). Histopathologic correlation was done in 61 cases. For Bethesda 5 and 6 categories, 100% concordance was found, however for Bethesda 2 category, 5 out of 45 cases were found to have malignant diagnosis on final histopathology. The incidence of malignancy in Bethesda categories 2 through 4 were 11.1%, 33.4%, 25%, 100% and 100% respectively. Overall accuracy of FNA cytology was 80.3% with 64.3% sensitivity and 85.1% specificity. Conclusion Our study validated the accuracy of BSRTC in our setup. Therefore we recommend routine use of BSRTC for reporting thyroid cytopathology for initial workup of patients with thyroid nodule. However, risk of malignancy was found to be significantly high in Bethesda 3 category to warrant further workup including ultrasound/thyroid scan in addition to repeat FNAC.

Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients

BackgroundPrognosis of breast cancer and success of therapeutic interventions largely rely on the clinico-pathologic and biological characteristics of the tumor and vary due to the heterogeneous nature of breast cancers. The aim of this study was to determine the frequency and prognostic parameters of luminal breast cancers in our population to devise targeted and personalized therapeutic regimens tailored to the needs of the loco-regional population.MethodsA retrospective cross-sectional study including 1951 cases of primary breast cancer treated at Liaquat National Hospital Karachi was conducted during the year 2011–2016. The clinico-pathologic characteristics were observed and semiquantitative immunohistochemical analysis was performed to study the luminal subtypes A and B. The cross-tabulated statistics of the observed characteristics were performed between the two subtypes. The significance level of each characteristic was estimated utilizing the chi-square test.ResultsLuminal cancers comprised 62.7% of the total number of cases diagnosed with breast cancers in the study period. Out of these 1224 cases of luminal cancers, 845 cases (69%) were luminal B, while 379 (31%) cases were of luminal A. Luminal B cancers were significantly more common in younger age groups as compared to luminal A cancers. Comparison of the two subtypes of luminal breast cancers revealed significant differences. Luminal B cancers were associated with higher grade (26% grade III in luminal B compared to 8% in luminal A), micropapillary histology, and high frequency of nodal metastasis (54 vs. 43%).ConclusionsLuminal B comprised the most frequent subtype of breast cancer in our study and they were found more constantly in a younger age group. Moreover, they were associated with adverse clinico-histologic parameters like higher grade and nodal metastasis. Therefore, we suggest that, despite lack of widespread availability of molecular studies in our setup, IHC-based typing should be done in every case of breast cancer to individualize therapy.

Head and Neck Squamous Cell Carcinoma - Comparative Evaluation of Pathological Parameters in Young and Old Patients

BACKGROUND To evaluate pathological features of head and neck squamous cell carcinoma (HNSCC) and to compare these pathological features in patients younger and older than 40 years. MATERIALS AND METHODS All resection specimens of HNSCC between 2010 and 2013 evaluated. Tumor characteristics - grade, location (site) cervical node status, alongwith presence or absence of extranodal extension, lymphovascular invasion, gender and age - were extracted from surgical pathology reports. RESULTS Among these n=19 patients (21.8%) were 40 years or younger and n=68 patients (78.2%) were above 40 years of age. The mean age was 34 (20-40 years) in the younger group and 56 (42-86) in the older group. The most common location of HNSCC in both groups was the oral cavity. The analysis of histopathological features including grade of tumor, tumor size, extranodal extension and comparison between two groups do not show any significant difference. CONCLUSIONS There are no specific pathological characteristics of HNSCC in young patients. An interesting observation is that exposure to expected risk factors is similar in both groups, in younger patients they have less time to act and yet tumors are the same in terms of tumor size, lymph node status and lymphovascular invasion. Therefore further research is recommended to look for potentiating factors.