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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.

* 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 ([kappa] = 0.471). Agreement was good ([kappa] = 0.681), moderate ([kappa] = 0.442), and fair ([kappa] = 0.368) for grades 1, 3, and 2, respectively. Observer pair concordance for AI and individual pathologists ranged from fair to good ([kappa] = 0.313-0.606). Perfect agreement was observed in 25 cases (27.4%). Interobserver agreement for the individual components was best for TF ([kappa] = 0.471 each) followed by NP ([kappa] = 0.342) and was worst for MC ([kappa] = 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. doi: 10.5858/arpa.2021-0299-OA, Over the years, microscopic evaluation of hematoxylin-eosin-stained slides from patient samples has been the gold standard for cancer diagnosis and grading of malignancy. The Nottingham Grading System (NGS) is widely [...]

Endometrial stromal sarcoma (ESS) is a rare malignancy arising from the stromal cells of the endometrium. We present a case of a 38-year-old female who was admitted to the Emergency Room (ER) with heavy and foulsmelling vaginal bleeding. Further workup (examination) revealed a bulky uterus with a fibroid extending into the cervix. Ultrasound and MRI pelvis showed a large submucosal uterine fibroid with concerning features of possible rupture. The patient underwent total abdominal hysterectomy with bilateral salpingectomy. Intraoperatively, the fibroid was found to be necrotic and macerated, coming out of the cervical os. Histopathology examination revealed a low-grade ESS. The patient was discharged in stable condition. Follow-up imaging and clinical evaluations have shown no evidence of recurrence at three-months post-surgery. [ABSTRACT FROM AUTHOR]

Byline: Zarka. Samoon, Madiha. Beg, Romana. Idress, Adnan. Jabbar BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare disease with incidence of less than 1%. MBC present with a larger tumor [...]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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) [Display omitted] [ABSTRACT FROM AUTHOR]

Background Core needle biopsy (CNB) for fibroepithelial lesions (FELs) of the breast is commonly encountered by histopathologists. The distinction between fibroadenoma (FA) and phyllodes tumor (PT) can be challenging due to overlapping histological features and the limited nature of CNB material.  Objective This study aimed to assess the accuracy of CNB diagnosis of FA and PT by comparing it with a diagnosis on subsequent surgical excision specimen. Materials and methods A total of 166 cases of FELs of the breast who underwent CNB and subsequent surgical excision between January 2001 and December 2020 were included in our study. All microscopy glass slides were reviewed, and diagnosis confirmed. Results While 125 (75%) cases based on CNB received a definitive diagnosis of either fibroadenoma or PT, the remaining 41 (25%) cases were better classified on excision specimens and were descriptively diagnosed as fibroepithelial lesions on CNB. Diagnoses on CNB and on subsequent excision specimens were concordant in 113 (90.4%) cases. Among 12 cases that were discordant, three cases diagnosed as FA on CNB were upgraded to PT on excision specimens. Nine cases diagnosed as PT on CNB were diagnosed as FA on excision specimens. These included conventional, cellular, juvenile, and complex FA types. Three PTs, which were reported as FA on CNB, measured 6, 12.5, and 17.5 cm in the greatest dimension. Among 23 cases of PT which were further categorized on CNB, tumor categories changed on excision specimens in three cases. The diagnostic accuracy of CNB diagnosis was 90.4%. Conclusion CNB diagnosis showed good accuracy. PT diagnosis should be strongly considered in all tumors measuring >5 cm, especially those exceeding 10 cm. Cellular, juvenile, and complex FAs can be misdiagnosed as PT on CNB. Correlation with clinical and radiological findings can be helpful in establishing correct diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Review Committee of Aga Khan University Hospital, Karachi issued approval 2023-6988-24562. The study was performed by reviewing the archived microscopy slides of already diagnosed cases and no identifying information (in the text or image) was included. Exemption from approval was granted by the institutional ethics review committee. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tariq et al.)

Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival., Patients and Methods: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with clinicopathological variables and outcome using univariable and multivariable analysis. Survival data was computed by Kaplan Meier curves., Results: Expression of AR was observed in 62.7% tumors whereas CD44, CD24 and ALDH1 were expressed in 61.4%, 44% and 30.1% tumors, respectively. AR expression was significantly associated with T1-T2 tumors, lower grade, estrogen and progesterone receptor expression (P < .05) and remained an independent prognostic indicator in multivariable analysis (adjusted HR 0.33, 95% CI 0.13-0.81; P = .016). Significant association was observed between concordant expression of AR and CD24 (P = .001) with a favorable impact on survival (P = .007) whereas expression of CSC phenotypes (CD44 + , CD44 + /CD24 - and ALDH1 + ) did not correlate with adverse outcome (P > .05). However, AR expression retained the association with better prognosis even in patients whose tumors exhibited a CSC phenotype., Conclusions: Expression of AR and CD24 in stage I-III invasive BCa correlates with favorable clinicopathological features and delineates a subgroup of patients with better disease-free survival., (Copyright © 2018 BAYLOR COLLEGE OF MEDICINE. Published by Elsevier Inc. All rights reserved.)

Background and Aims: 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., Methods: 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., Results: 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., Conclusions: 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.

Background: 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., Methodology: 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., Results: 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 with <12 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%., Conclusion: 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.