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Context.— Breast carcinoma grade, as determined by the Nottingham Grading System (NGS), is an important criterion for determining prognosis. The NGS is based on 3 parameters: tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). The advent of digital pathology and artificial intelligence (AI) have increased interest in virtual microscopy using digital whole slide imaging (WSI) more broadly. Objective.— To compare concordance in breast carcinoma grading between AI and a multi-institutional group of breast pathologists using digital WSI. Design.— We have developed an automated NGS framework using deep learning. Six pathologists and AI independently reviewed a digitally scanned slide from 137 invasive carcinomas and assigned a grade based on scoring of the TF, NP, and MC. Results.— Interobserver agreement for the pathologists and AI for overall grade was moderate (κ = 0.471). Agreement was good (κ = 0.681), moderate (κ = 0.442), and fair (κ = 0.368) for grades 1, 3, and 2, respectively. Observer pair concordance for AI and individual pathologists ranged from fair to good (κ = 0.313–0.606). Perfect agreement was observed in 25 cases (27.4%). Interobserver agreement for the individual components was best for TF (κ = 0.471 each) followed by NP (κ = 0.342) and was worst for MC (κ = 0.233). There were no observed differences in concordance amongst pathologists alone versus pathologists + AI. Conclusions.— Ours is the first study comparing concordance in breast carcinoma grading between a multi-institutional group of pathologists using virtual microscopy to a newly developed WSI AI methodology. Using explainable methods, AI demonstrated similar concordance to pathologists alone.

Primary Bartholin gland carcinoma (BGC) is an extremely rare disease. It typically presents in elderly women. It can be confused with Bartholin gland cyst, which is a benign condition leading to a delay in diagnosis and treatment. We are presenting a case report of BGC in a 35-year-old woman, which has created a diagnostic as well as therapeutic dilemma.

Breast carcinoma grading is an important prognostic feature recently incorporated into the AJCC Cancer Staging Manual. There is increased interest in applying virtual microscopy (VM) using digital whole slide imaging (WSI) more broadly. Little is known regarding concordance in grading using VM and how such variability might affect AJCC prognostic staging (PS). We evaluated interobserver variability amongst a multi-institutional group of breast pathologists using digital WSI and how discrepancies in grading would affect PS. A digitally scanned slide from 143 invasive carcinomas was independently reviewed by 6 pathologists and assigned grades based on established criteria for tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). Statistical analysis was performed. Interobserver agreement for grade was moderate (κ = 0.497). Agreement was fair (κ = 0.375), moderate (κ = 0.491), and good (κ = 0.705) for grades 2, 3, and 1, respectively. Observer pair concordance ranged from fair to good (κ = 0.354-0.684) Perfect agreement was observed in 43 cases (30%). Interobserver agreement for the individual components was best for TF (κ = 0.503) and worst for MC (κ = 0.281). Seventeen of 86 (19.8%) discrepant cases would have resulted in changes in PS and discrepancies most frequently resulted in a PS change from IA to IB (n = 9). For two of these nine cases, Oncotype DX results would have led to a PS of 1A regardless of grade. Using VM, a multi-institutional cohort of pathologists showed moderate concordance for breast cancer grading, similar to studies using light microscopy. Agreement was the best at the extremes of grade and for evaluation of TF. Whether the higher variability noted for MC is a consequence of VM grading warrants further investigation. Discordance in grading infrequently leads to clinically meaningful changes in the prognostic stage.

Oral squamous cell carcinoma (OSCC) comprises most of head and neck neoplasms and is one of the highest-ranking and lethal cancers in Pakistan due to prevailing mouth habits. Several types of receptors act as prognostic markers and targets for therapy in some cancers, but their application in OSCC is largely unexplored. This study aimed to evaluate the expression of hormonal receptors and Her-2 in OSCC patients and correlate it with 10-year, overall and disease-free survival. To achieve this objective, immunohistochemistry for Her-2, AR, ER and PR was performed on 100 formalin-fixed paraffin-embedded primary OSCC specimens. Receptor expression was correlated with mouth habits and clinicopathological features and patient survival was analyzed using Kaplan-Meier method and Cox regression univariate analysis. We observed that in 100 patients, there were 57 males and 43 females. Immunopositive Her-2 expression was observed in 21% of patients, AR in 13%, ER in 3% and 0% for PR. Patients with betel quid/areca nut mouth habits had significantly absent Her-2 expression (P = 0.035). Also, Her-2 negative patients were also negative for AR expression (P = 0.002). Her-2 positive patients had poor 10-year survival (P = 0.041). A trend of low survival and high recurrence rate was observed in AR positive patients, but this was not significant (P = 0.072). No statistically relevant correlations were seen in the case of ER and PR. In conclusion, Her-2 may be a valuable marker for predicting long-term prognosis of OSCC patients.

Objective: This study describes a case of disseminated phaeohyphomycotic lymphadenitis in a young female with delayed diagnosis and good clinical response after appropriate treatment. Methods: A 32-year-old female presented with erythematous to violaceous papules with oozing discharge bilaterally in her inguinal region for a few months. History revealed tuberculous meningitis 4 years earlier treated with first line anti-tuberculous therapy for 18 months, and 2 years previously she developed pigmented discharging lymph nodes bilaterally in her axillae. The histopathology of the biopsy of the axillary nodes showed chronic granulomatous inflammation with multiple branching septate fungal hyphae. She received amphotericin B for 21 days but without improvement. Biopsy from the inguinal lesions was sent for histopathology and culture. Results: Histopathology of the biopsy material showed chronic granulomatous inflammatory process with multinucleate giant cells, epithelioid cells, histiocytes, and lymphocytes with multiple branching septate fungal hyphae. Gram stain revealed moderate septate hyphae with numerous pus cells. Culture on Sabouraud dextrose agar yielded velvety olive–black colonies in the fourth week. Microscopic slide examination of culture material was suggestive of Cladophialophora species. The patient was started on voriconazole, which was continued for 6 months, and showed clinical improvement. Conclusion: Incomplete investigation of infectious lesions may delay diagnosis. Furthermore, clinical presentations are greatly influenced by the immune status of the host. Both histopathological and microbiological assessments are equally important for making a conclusive diagnosis. Anti-fungal therapy may delay the growth of fungi that normally grow within a week; thus, a longer incubation time may be warranted for fungal smear-positive samples.

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > −1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = −0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology., Author summary EED is a subclinical condition of compromised gut integrity secondary to frequent and repeated exposure to enteropathogens in global settings with a high prevalence of undernutrition. In this study, we reported association of gut mucosal architecture with a dual sugar intestinal permeability assay (lactulose-rhamnose) in Pakistani children. In the presence of duodenal enteropathogens, features such as chronic inflammation, intra-epithelial lymphocytosis, enterocyte injury and Paneth cell reduction were consistently observed. When comparing undernourished cases and controls living in the same setting, we found urinary excretion of the sugars was similar among groups; however, variability in HAZ among children at 24 months was partially explained by a model that includes excretion values.

Background Neo-adjuvant chemotherapy (NAC) is frequently administered in breast carcinoma patients. The clinical response to NAC guides further treatment. The pathological response is not only an independent prognostic factor, but it also guides further treatment and prognosis. Objectives The aim of our study was to find the degree of concordance between clinical and pathological response assessments after NAC in Invasive lobular Carcinoma (ILC) cases by using World Health Organization (WHO) criteria and different pathological systems, respectively. We also tried to identify any useful parameter of clinical assessment that could better correlate with pathologic assessment and provide a better estimation of residual tumor. Methods This retrospective study was conducted on 26 ILC tumors diagnosed in 24 patients who were treated with NAC followed by surgical resection between January 2009 and December 2020. Medical records and microscopy glass slides were reviewed for clinical and pathological response assessments, respectively. Results The pre-treatment tumor area ranged from 1.8-255 cm2 and the mean±SD was 52.2±66.8 cm2. After NAC, complete clinical response was observed in four (15.3%) cases. The clinically assessed mean tumor area significantly reduced from 52.2±66.8 cm2 to 17.2±22.6 cm2 (p-value

Encapsulated Papillary Carcinoma (EPC) is a rare breast tumor with excellent prognosis. Treatment and stage of EPC is influenced by invasion and high nuclear grade. Our aim was to study the clinicopathological features of EPC, especially high grade tumors and to compare the features of invasive and non-invasive tumors. We reviewed clinicopathological features of 25 cases of EPC diagnosed at our institution from 2006 till 2020. Patients' age ranged from 21 to 75 years (median 55 years). Tumor size ranged from 1 to 9 cm (median 3.5 cm). Overall, invasion was present in 44% cases. High nuclear grade was observed in 24% cases. Majority of these high grade tumors were below 40 years. All of these tumors were 4 cm or larger in size. Two third of these tumors were invasive. Hormone receptor negativity and lymph node involvement was observed in 1 out of 3 cases, when performed. Clinicopathological and histological features of invasive and non-invasive tumors were compared and only lymph node involvement was found to be significantly more frequent in invasive tumors (p = 0.049). Median follow up duration was 18 months. All patients were alive and disease free except for a single patient who died of cerebrovascular accident. EPC has excellent clinical course. Invasion and high nuclear grade should be carefully searched for as these features determine tumor stage and treatment.

Background The debate whether breast cancer in women under 40 years of age is distinct from breast cancer in women above 40 is still inconclusive with various published studies providing conflicting evidence. The majority of studies however suggest that breast cancer in younger women (

Objective The aim of the current study is to determine the feasibility and accuracy of ultrasound-guided core biopsy for staging the axilla in clinically node-negative patients with invasive breast cancer. Introduction Historically, in breast cancer patients, axillary lymph node dissection was performed to stage axilla. Because of the high morbidity of axillary lymph node dissection, sentinel lymph node biopsy (SLNB) became the standard of care in patients with clinically node-negative breast cancer. However, SLNB is expensive, time consuming, can cause morbidity and can be complicated by seroma formation, sensory nerve injury, lymphedema, etc. Many centers rely on the availability of frozen section on sentinel lymph nodes to avoid a second procedure with the accuracy of procedure ranging from 73 to 96%, however, the availability of frozen section is limited in our part of the world. Pre-operative identification of axillary node positivity in patients with clinically negative nodes by ultrasound imaging of the axilla would allow one-stage axillary clearance and can decrease the need for SLNB from 21% to 70%. The aim of the present study is to determine the accuracy and feasibility of ultrasound-guided core biopsy to stage the axilla in clinically node-negative breast cancer patients, comparing with final histopathology as gold standard. Material & methods This was a non-randomized, prospective interventional study, done at Radiology Department of Aga Khan University Hospital. All patients diagnosed with breast cancer (histologically proven) with clinically negative axilla and ipsilateral positive axillary ultrasound were included. These patients underwent axillary lymph node core biopsy. If the result was negative they were subjected to SLNB. Histopathology result was taken as gold standard. Results The sensitivity of ultrasound-guided core biopsy was 88%, specificity 100%, positive predictive values (PPV) 100%, negative predictive values (NPV) 89.28%, diagnostic accuracy 94%. Conclusion In conclusion, the present study demonstrated high accuracy of ultrasound-guided axillary lymph node core biopsy in breast cancer patients with clinically node-negative axilla. Positive core biopsy results can thus obviate the need for sentinel lymph node biopsy and allow breast surgeons to directly proceed to axillary lymph node dissection.

Solid papillary carcinoma (SPC) is an uncommon breast tumor whose prognosis depends on invasive component. We studied clinicopathological features of SPC by reviewing 65 cases. Invasive component was seen in 75.4% cases. Almost all tumors with grade III nuclei had invasive component. Mean patients' age of invasive tumors was significantly higher than that of non-invasive tumors (P = .036). All patients were alive and disease free except for a single patient who developed distant metastasis and died of disease. SPC have excellent clinical course. Careful search for invasive component is mandatory, especially in tumors with older patient's age and higher nuclear grade.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare disease with incidence of less than 1%. MBC present with a larger tumor size, less number of nodes involved, mostly undifferentiated triple negative tumors. We aimed to determine progression-free and overall survival and reported hospital-based incidence of MBC. MATERIAL AND METHODS: A retrospective closed Cohort study elicited data of 42 patients with MBC from January 2008 to December 2013; followed till August 2016. Kaplan-Meier method was applied to compute overall and progression-free survival analysis. Cox Proportional hazard ratios were computed to assess associations between survival and independent variables. RESULTS: Hospital-based incidence of MBC was 1.92% (42/2187), 95% CI [1.41-2.56]. The median age at tumor diagnosis was 54 years (range, 25–81 years). Thirty-nine (92.9%) patients had Grade III tumor. The most common histopathology was squamous (69%). The median tumor size was 4.5 cm (range, 0.8–17 cm). Nineteen (45.2%) patients had nodal involvement at diagnosis. Four patients (9.5%) had metastatic disease at presentation. Hormone receptors were positive in 19 (45.2%) patients. Her-2 neu receptor was positive in 9 (19%) patients. Sixteen (38.1%) patients had triple negative disease. Neoadjuvant and adjuvant chemotherapy was received by 10 (31.25%) and 19 (45.2%) patients respectively. Both median progression-free and overall survival was 38 months. CONCLUSION: Five-year progression-free and overall survival was 79.5% and 76.3%, respectively. We report better survival outcomes when compared to series described earlier despite our patient population presenting mostly with high grade, large tumors, and half of them exhibiting nodal and hormonal involvement.

Background & Aims Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED. Methods The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease. Results After accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization. Conclusions Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013), Graphical abstract

Hydatid cyst commonly affects liver followed by lung, but rarely affects both organs simultaneously. Here we presented a patient who presented with concurrent involvement of both lungs and liver. Patient presented with dyspnoea and generalised weakness with bilateral rounded opacities throughout the lung field of variable sizes. CT scan chest with contrast showed multiple rounded soft tissue density in both lungs and liver. Patient underwent mini thoracotomy which revealed multiple cystic lesions throughout lung. ELISA for anti-Echinococcus antibodies shows positive titres. Due to extensive involvement, patient was started on medical treatment albendazole. The patient showed significant improvement both clinically and radiographically on treatment. Thus long-term medical treatment helps in such cases where surgery is not possible.

Introduction: Androgen receptor (AR) expression has been shown to correlate with improved survival in luminal A, B and triple negative (TN) breast cancer (BCa). Cancer stem cells (CSC) with CD44+/CD24- and ALDH1+ phenotype is associated with pro-invasive gene signature in BCa. Aim of our study was to evaluate prognostic significance of AR expression in relation to CD44, CD24 and ALDH1 in invasive BCa. Methodology: Immunohistochemical expression of AR, CD44, CD24 and ALDH1 was evaluated in 180 FFPE blocks of BCa cases from one institution. Clinico-pathological details and follow-up data were collected from medical charts. Data was analyzed on SPSS 19. Five-year survival was estimated by Kaplan Meier. Results: Median age of patients was 55 years (range: 28-87). Fifteen percent of patients were diagnosed with stage I, 52.2% with stage II, 25% with stage III and 7.8% with stage IV disease. Mean duration of follow-up was 4.5 years (SD+ 2.7) and 29% mortalities were attributed to BCa. AR was expressed in 63.9%, ER in 61%, PR in 51% & HER-2/neu in 30% of tumors. CD44, CD24 and ALDH1 were expressed in 60%, 43.3% & 28.3% of tumors respectively. AR expression was associated (p-value Five year survival of patients with AR+ versus AR- expressing tumors, showed that patients with AR+ tumors had significantly better outcome (p-value=0.03) with survival advantage of 39.6 months. Survival advantage decreased by 9.6 months in tumors expressing CD44+/CD24-/AR- (p-value=0.01) phenotype and by 12 months in patients whose tumors were phenotypically ALDHI+ /AR- (p-value=0.12). We stratified TN tumors into 2 groups: A. TN/CD24+/AR+; B. TN/CD24-/AR- and found that group A tumors had a trend towards better 5 survival (p-value=0.09). Conclusions: Three individual markers (CD44, CD24, AR) may afford prognostic information. Combinations of CD44, CD24 and AR permitted patient stratification into 3 risk categories: poor risk CD24-/AR-; intermediate risk CD44+/CD24-/AR- and good risk CD24+/AR+. Stratification of TN group showed that loss of AR and CD24 was associated with poorest outcome. These results underscore the relevance and importance of AR and CD24 as prognostic markers in invasive BCa. Citation Format: Nazia Riaz, Romana Idress, Sadia Habib, Azhar Hussain, El-Nasir Lalani. Expression of androgen receptor and CD24 correlates with improved 5-year survival in Pakistani patients with invasive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3822. doi:10.1158/1538-7445.AM2017-3822

Introduction: A sub-population of cells referred to as cancer stem cells has been identified utilizing specific markers such as aldehyde dehydrogenase 1 (ALDH1) amongst others in solid tumors including breast cancers. Evidence from in vitro studies has shown that high ALDH1 expression identifies tumorigenic cell population which is capable of self-renewal and generating tumors which recapitulate the heterogeneity of the primary tumors. Expression of androgen receptor is present in 70-90% cases of invasive breast cancers at a frequency that is higher than the expression of estrogen or progesterone receptors. However, prognostic relevance of androgen receptor expression in relation to the expression of ALDH1 has not been investigated. Methodology: Immunohistochemical expression of ALDH1 and AR was evaluated in formalin fixed paraffin embedded blocks from 177 invasive breast cancer cases at a single institution in Pakistan from 2006-2010. Clinico-pathological details and follow-up data were collected from patients' medical charts. Data analysis was performed on SPSS version 19. Over-all survival and 5-year disease free survival were estimated by Kaplan Meier. Results: The mean age of the patients was 53.9 (+ 12.40) years. Fifteen percent patients were diagnosed with stage I disease, 52% with stage II, 25% and 8% presented with stage III and stage IV disease, respectively. Twelve percent patients presented with T1 tumors, 49.7% patients presented with T2 tumors whereas 23.7% and 14.6 % patients presented with T3 and T4 tumors respectively. Fifty-seven percent patients were node positive. Estrogen and progesterone receptor expression was present in 62% and 52% of tumors respectively. HER-2/neu was overexpressed /amplified in 30% tumors. Immunohistochemical expression of androgen receptor (AR) was present in 63.8% tumors whereas ALDH1 expression was present in 28.8% tumors. Lack of androgen receptor expression was associated with high expression of ALDH1 ( p= 0.009). Cases were divided into two groups: Group1: ALDH1-/AR+ and Group 2: ALDH1+/ AR-. No significant differences were observed between these groups with respect to age, tumor size, stage of disease, HER-2 neu over-expression/amplification or nodal status. Group 1 phenotype correlated with nuclear grade I and II tumors (p Conclusions: 1. Group 1 phenotype correlated with better prognostic features such as well to moderately differentiated and endocrine responsive tumors. 2. Group 2 phenotype correlated with poor prognostic features such as higher nuclear grade and lack of expression of hormone receptors. 3. Expression of stem cell marker, ALDH1, in group 2 phenotype correlated with poor over-all and 5-year disease free survival. Citation Format: Nazia Riaz, Romana Idress, Sadia Habib, Syed Zulfiqar Naqvi, Shaista Masood Khan, Anwar Ali Siddiqui, El-Nasir Lalani. Lack of androgen receptor expression correlates with high expression of ALDH1 and poor overall and 5-year disease free survival in patients with invasive breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A67.

Intraoperative consultation of CNS lesions provides accurate diagnosis to neurosurgeons. Some lesions, however, may cause diagnostic difficulty. In this study accuracy of intraoperative consultations of CNS lesions and discrepancies in diagnosis and deferrals were analysed.All CNS cases from May 1, 2004 to September 20, 2010 in which intraoperative frozen section had been performed, and which were reported in the Section of Histopathology, Aga Khan University Hospital, Karachi Pakistan were retrieved. The diagnoses given on FS were compared with the final diagnosis given on permanent sections (and additional material if received), as indicated in the frozen section and final pathology report.During the study period, 171 CNS cases were received for intraoperative consultation. In all cases, cryostat sections (FS) plus cytology smears were prepared. The ages of the patients ranged from 03 to 77 years. 106 were males and 65 were females. Out of these 171 cases, 160 cases (94.1 %) were concordant, 10 cases (5.8 %) were discrepant, and one case was deferred until permanent sections. The diagnostic accuracy of frozen section was 88.9%. The sensitivity and specificity were 94.8% and 87.5% respectively. The positive predictive value was 98.6% and negative predictive value was 63.6%. All our cases in which intraoperative consultation was requested were sent for primary diagnosis. Adequacy per se was not a criterion for sending cases for intraoperative consultation.Our results show a reasonably high percentage of accuracy in the intraoperative diagnosis of CNS lesions. However, there are limitations and some lesions pose a diagnostic challenge. There is a need to improve our own diagnostic skills and establish better communication with neurosurgeons.

Introduction: Breast carcinoma is the most common malignant tumor and the leading cause of cancer death in women. In western countries, a sharp increase in the detection of breast carcinoma, largely due to widespread use of mammography, has recently led to a fall in breast cancer mortality. This, however, is not true for less developed countries, in which mortality continues to rise. Objective: The aim of this study was to acquire information about the extent and spread of breast carcinoma in our patients by grading the tumors, determining the tumor size, and axillary lymph node status, staging of the tumors and Nottingham Prognostic Index (NPI) scoring on the available material. Materials and Methods: One hundred and twenty consecutive mastectomy specimens with axillary lymph node sampling removed for breast carcinoma and received in the section of histopathology, Aga Khan University, in the year 2005, were included in the study. Standard protocols were used for the processing of the specimens, and reporting was done using a standard format incorporating all relevant tumor parameters. NPI was applied to the cases. Results: Out of the 120 cases, 5 (4.17) were grade 1, 91 (75.83) were grade 2, and 24 (20%) were grade 3. Also, 9 cases (7.5%) were T1 (4 were T1b, and 5 were T1c); 53 (44.16%) were T2; 50 (41.66%) were T3; and 8 (6.66%) were T4. Axillary lymph nodes were available in 107 cases. In 13 cases, no lymph nodes were recovered. Out of 107 cases 27 (25.23%) lymph nodes were negative for metastases pN0; 29 (27.10%) cases were pN1; 26 (24.30) were pN2; and 25 cases (23.36%) were pN3. Extranodal spread was present in 56 (70%) out of the 80 cases in which lymph nodes were positive. The average microscopic size of nodal metastasis was 1.7 cms. Significant statistical association was found between the number of positive nodes and perinodal extension (P = 0.001). Tumor necrosis was present in 76 out of 120 cases (63.33%). Vascular invasion was present in 43 out of 120 cases (35.83%). NPI scores were greater than 5.4 in 60 out of 107 cases (56.1%) indicating poor prognosis. Conclusion: The large majority of the cases were grade 2 tumors. Most cases (all grades) were T2 or T3, and were axillary lymph node positive. Large majority of cases with nodel metastases showed extra nodal spread. The majority of patients had NPI scores greater than 5.4 indicating poor prognosis. Significant statistical association was found between the number of positive nodes and perinodal extension (P = 0.001). The findings show extensive and advanced disease trends in our patients.

Colon cancer is a common malignancy with its incidence reportedly rising in Asian countries, including Pakistan. There are no comprehensive data available from Pakistan which focus on associations of various factors with long-term survival of colon cancer. We therefore present an analysis of findings from our centre.In this retrospective study adult patients with colon cancer diagnosed through 2000-2003 were included. A comprehensive questionnaire was filled for each individual through review medical and pathology reports. Long term survival data was collected from contactable patients or their relatives.A total of 93 patients were assessed, 57 males and 36 females (M: F= 1.58: 1). Mean age of diagnosis was 54 years. Of the total, 49.5% of the patients had right sided (mortality rate 51.6%), 10.8% had transverse colon, (mortality rate 37.5%), 7.5% had descending colon (mortality rate 66.7%) and 32.2% had sigmoid colon (mortality rate 40.9%) cancers. Stage I disease on diagnosis was found in 16%, stage II in 42.7 (mortality 40 %) and stage III in 41.3% (mortality 70 %). Tumors were well differentiated in 20.2% (mortality 42.9%), moderately differentiated in 61.9% (mortality 43%) and poorly differentiated in 17.9% (mortality 70%). In 36.3% of the patients less than 12 lymph nodes were removed (mortality 55% Vs 43% in patients with12 lymph nodes removed). Margins were free in most patients but a radial margin was reported in only 44%. Most patients had pure adenocarcinoma while a mucinous type differentiation was seen in 19.7%, 3% had signet ring morphology, 1.5% adeno-squamous carcinoma and similar number with neuroendocrine differentiation. Overall 5 year all cause mortality for all stages combined was 46.9%.Colon cancer in Pakistan commonly presents at an advanced stage, there is a male preponderance, and relatively mean younger age at presentation for males is seen. Advanced stage and lymph node involvement along with poorly differentiated pathology, signet ring or mucinous morphology, location in descending colon, positive surgical margins and removal of less than twelve lymph nodes are factors associated with poor long term survival. There is a need to reinforce information about colon cancer and larger studies from the region are needed to confirm the factors analyzed here.

Epidermoid cysts of the ovary are rare lesions and are uniformly incidental findings in hysterectomy specimens. They must be differentiated from mature cystic teratomas of the ovary, and some authors believe them to be monodermal teratomas. The histogenesis is still uncertain. We report an epidermoid cyst of the ovary which was an incidental finding.

BACKGROUND Importance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa. METHODS This study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82). RESULTS Expression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P

Introduction Chemotherapy Induced neutropenia is a frequent and serious complication of cytotoxic cancer treatment. Granulocyte colony stimulating factors (G-CSF) are frequently used to counter neutropenia, attempt rapid recovery of patients and allow for continuation of treatment without compromise on dose, especially in curative malignancies. Generally regarded as safe, G-CSF use has been very rarely reported to have resulted in serious side effects, such as, splenic rupture. Case presentation We are reporting a case of a twenty years old man, who was being treated for T cell acute lymphoblastic leukemia and received colony stimulating factors for treatment of severe neutropenia and suffered from splenic rupture, He was treated with splenectomy. Conclusion Although extremely rare, splenic rupture can be a serious and sometimes life threatening complication of high dose colony stimulating factors therapy.