A histopathological and epidemiological study of urothelial carcinoma at a tertiary care centre in Peshawar, Pakistan.

Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.

Immunohistochemical Expression of Epidermal Growth Factor Receptor (EGFR) in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

BACKGROUND: Increased epidermal growth factor receptor (EGFR) expression has been implicated in several tumors and is associated with increased tumor advancement as well as a potential drug target. The objective of the study was to compare the immunohistochemical expression of EGFR in oral squamous cell carcinoma (OSCC) with oral potentially malignant disorders (OPMDs) and their demographic and pathologic parameters. METHODS: This study was a comparative cross-sectional analytical study. It was conducted at the Department of Pathology, Peshawar Medical College, Riphah International University, Islamabad, Pakistan, from March 2021 to February 2022. The sample size was calculated through G Power. Thirty-eight cases of oral squamous cell carcinoma and 38 cases of oral potentially malignant disorders (OPMDs) were included in the study. Statistical analysis was performed using the Statistical Package for Social Sciences version 20.0. χ 2 tests and Fisher exact tests were applied to compare categorical variables. RESULTS: Mean age of OSCC was 61.6±13.9, with age range from 26 to 90 years. The male-to-female ratio for OSCC was 2.16:1. Buccal mucosa was the most common site involved (34.2%). The most common histologic type was well-differentiated OSCC (71.05%) followed by poorly differentiated (16%) and moderately differentiated (13.15%). The mean age of OPMDs cases was 59.16 ± 10.81 with a male-to-female ratio of 1:1.2. Buccal mucosa was the common site (55.3%), followed by the tongue (18.4%). The OPMDs with dysplasia were 55.2%, and without dysplasia were 44.8%. A total of 55.7% of cases of OSCC showed positive EGFR expression as compared with 36.9% OPMDs cases. A higher number of low-grade OSCC cases showed increased EGFR positivity (59.3%) as compared with high grade (45.45%). EGFR positivity in OPMD cases without dysplasia was 41.2% as compared with cases with dysplasia (33.3%). The EGFR expression in OPMD cases was higher in the ≤50 age group ( P =0.001) and in females ( P =0.032), which was statistically significant. CONCLUSIONS: EGFR expression by Immunohistochemistry may not be a helpful prognostic marker to determine the risk of OPMDs progressing to higher grades of dysplasia or invasive cancer. However, further studies relating this tumor marker to stage, lymph node metastasis, hematogenous metastasis, survival outcomes, and treatment response may give useful information regarding the utility of this marker.

Comparison of PD-L1 Expression in Oral Squamous Cell Carcinoma and Premalignant Lesions of Oral Cavity.

OBJECTIVE: Objectives of this study were to compare  expression of Programmed Death-Ligand 1(PD-L1) protein in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorder (OPMD) cases; and to compare the PD-L1 protein expression in histological grades of OSCC and also in OPMD's with Dysplasia and without Dysplasia. MATERIALS & METHODS: In this study,  25 cases of Oral squamous cell carcinoms, 25 cases of Oral Potentially Malignant Disorders and 10 cases of non-neoplastic oral mucosa (control) cases were included. FFPE blocks of OSCC and OPMD cases were contributed by Department of Pathology, Histopathology Division,Pakistan Institute of Medical Sciences, Islamabad. Immunohistochemical staining of cases with PD-L1 monoclonal antibody (1:100; Dako) was carried out at Histopathology division , PMC Labs,  Peshawar Medical College,Peshawar, Riphah International University, Islamabad . Epithelial cells (membranous and cytoplasmic) positivity was observed for PD-L1 Antibody. Data was analyzed in SPSS version20. For qualitative variables frequencies and percentages were calculated whereas for quantitative variables means and standard deviations were recorded. The Chi-square test was applied to evaluate the significant difference in categorical variables . p-value of ≤0.05 was taken as significant. RESULTS: PD-L1 expression in OSCC cases turned out to be 48% (n=12/25) as compared to 8% of OPMD cases (n=2/25) with a significant p value of 0.002 and all non-neoplastic oral mucosa cases were negative. PD-L1 expression in high grade OSCC cases was quite high (61% n=11/18) as compared to low grade OSCC (14% n=1/7) cases with a significant p value of 0.035. CONCLUSION: A statistically significant increased PD-L1 expression was noted in  OSCC as compared to OPMD. Expression of PD-L1 was more intense in high grade OSCC cases. The relation of PD-L1 expression to age ,gender or location of OSCC and OPMD cases , and presence of dysplasia in OPMD cases was statistically not significant.

Comparison of special stains (Giemsa stain and Modified Toluidine Blue stain) with immunohistochemistry as gold standard for the detection of H. pylori in gastric biopsies.

BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) has been extensively implicated in the etiology and pathogenesis of gastric ulcers and carcinomas, which has necessitated its efficient and cost-effective identification in gastric biopsy samples. We have sought to compare various staining methods, namely, Hematoxylin and Eosin (H&E), Giemsa, and Modified Toluidine Blue (MTB), with immunohistochemistry (IHC; gold standard) in terms of efficacy, staining costs, and duration of performing the stains in settings with limited resources. PATIENTS AND METHODS: Gastric biopsy specimens of 50 patients who presented with gastritis symptoms were stained with H&E, Giemsa, MTB, and IHC. The sensitivity, specificity, positive/negative predictive values, and the receiver operating characteristic curve were calculated for each stain. RESULTS: In all, 32 cases of 50 were positive for H. pylori on IHC. The specificity for both H&E and Giemsa was 88.8%, whereas it was lower for MTB (83.3%). The sensitivity of H&E was much lower (46.8%) compared with the other stains (90.6% Giemsa, 93.7% MTB). The most inexpensive and time-consuming stain was H&E followed by MTB and Giemsa. CONCLUSION: When H&E is used alone for H. pylori detection, a significant number of cases may be overlooked, especially mild inflammatory cases and when coccoid forms of the bacteria are present. This study proposes the use of either Giemsa or MTB as reliable alternatives for IHC in resource-limited settings to combat the high prevalence of H. pylori in the developing world.

Safety and Feasibility of Laparoscopic Cholecystectomy in Acute Cholecystitis.

OBJECTIVE: To have an audit of the outcome of laparoscopic cholecystectomy for acute cholecystitis at a tertiary care centre. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Surgery, Prime Teaching Hospital, Peshawar Medical College, Peshawar, KPK, Pakistan, from January 2011 to December 2015. METHODOLOGY: Patients with acute cholecystitis undergoing laparoscopic cholecystectomy were evaluated for conversion rate, morbidity and hospital stay. Early laparoscopic cholecystectomy was defined as done within the same hospital admission. RESULTS: In 83 patients, male to female ratio was 1:1.6 with a median age of 46 years (IQR 15). The median interval between the onset of symptoms and time of surgery was 5 days (IQR 3). Majority of cases (80%) were performed after 72 hours of their presentation as acute cholecystitis. Conversion rate from laparoscopic to open cholecystectomy was 8.4% (7/83 cases), because of difficult dissection and unclear anatomy at the Calot's triangle. Median duration of hospital stay was 2 days (IQR 1). Morbidity rate was 9.6% (8/83 cases), all occurring in late presentations; port-site infection being the commonest (n=6, 7%), followed by port-site hernia and post-cholecystectomy pancreatitis (n=1 each). CONCLUSION: Laparoscopic cholecystectomy is quite safe in acute cholecystitis with a low conversion rate, bile duct injuries, and hospital stay.

Role of benign ovarian cysts in the development of adenomyosis.

OBJECTIVES: To assess the association of adenomyotic foci with co-existing benign ovarian cysts.  METHODS: This prospective cross-sectional study consisted of 100 consecutive hysterectomy specimens referred to Histopathology Section of Pathology Department, Peshawar Medical College, Peshawar, Pakistan by its attached teaching hospitals from January 2011 to December 2012. Hematoxylin and eosin stained sections were examined for adenomyotic foci and the presence of co-existent ovarian cysts. For evaluation of estrogen receptor (ER) status immunohistochemical stains were applied and H-scoring system was used with a score greater than 50 as positive.  RESULTS: Out of the 100 hysterectomy specimens, 25 cases had both adenomyosis and ovarian cysts. The ER status of adenomyotic foci was positive in 20% cases and negative in 80% cases. The commonest type of ovarian cyst was hemorrhagic luteal cyst (28%), followed by serous and mucinous cystadenoma (20%) each. Out of the 28% cases of functional cysts, 71.5% were ER positive and 28.5% were ER negative. The p-value for association of ER status of adenomyotic foci with functional cysts was 0.0004; however, p-value was not significant in comparing cases with controls. All 72% cases of nonfunctional cysts were ER negative. However, 44% of functional cysts were not associated with adenomyotic foci.   CONCLUSION: This study concludes that besides functional ovarian cysts, other local factors may be responsible for the development of adenomyosis.

Is it necessary to submit grossly normal looking gall bladder specimens for histopathological examination?

BACKGROUND: The objectives of the study were to: 1) determine the frequency of incidental malignancy in unsuspected/grossly normal looking gall bladders; 2) determine the frequency of malignancy in suspected/grossly abnormal looking gall bladders. MATERIALS AND METHODS: This prospective, cross sectional study was carried out at a tertiary care hospital in Pakistan, during a four year period (Jan 2009-dec2012). All the cholecystectomy cases performed for gallstone diseases were examined initially by a surgeon and later on by a pathologist for macroscopic abnormalities and accordingly assigned to one of the three categories i.e. grossly normal, suspicious, abnormal/malignant. Frequency of incidental carcinoma in these categories was observed after receiving the final histopathology report. RESULTS: A total of 426 patients underwent cholecystectomy for cholelithiasis, with a 1:4 male: female ratio. Mean age of the patients was 45 years with a range of 17-80 years. The frequency of incidental gallbladder carcinoma was found to be 0.70 %(n=3). All the cases of gallbladder carcinoma were associated with some macroscopic abnormality. Not a single case of incidental carcinoma gallbladder was diagnosed in 383 'macroscopically normal looking' gallbladders. CONCLUSIONS: Incidental finding of gall bladder cancer was not observed in any of macroscopically normal looking gall bladders and all the cases reported as carcinoma gallbladder had some gross abnormality that made them suspicious. We suggest histopathologic examination of only those gall bladders with some gross abnormality.

Phytobezoar in a jejunal diverticulum as a cause of small bowel obstruction: a case report.

INTRODUCTION: Phytobezoars are concretions of poorly digested fruit and vegetable fibers found in the alimentary tract. Previous gastric resection, gastrojejunostomy, or pyloroplasty predispose people to bezoar formation. Small-bowel bezoars normally come from the stomach, and primary small-bowel bezoars are very rare. They are seen only in patients with underlying small-bowel diseases such as diverticula, strictures, or tumors. Primary small-bowel bezoars almost always present as intestinal obstructions, although it is a very rare cause, being responsible for less than 3% of all small-bowel obstructions in one series. Jejunal diverticula are rare, with an incidence of less than 0.5%. They are usually asymptomatic pseudodiverticula of pulsion type, and complications are reported in 10% to 30% of patients. A phytobezoar in a jejunal diverticulum is an extremely rare presentation. CASE PRESENTATION: A 78-year-old Pakistani man presented to our clinic with small-bowel obstruction. Upon exploration, we found a primary small-bowel bezoar originating in a jejunal diverticulum and causing jejunal obstruction. Resection and anastomosis of the jejunal segment harboring the diverticulum was performed, and our patient had an uneventful recovery. CONCLUSION: Primary small-bowel bezoars are very rare but must be kept in mind as a possible cause of small-bowel obstruction.

Situs inversus totalis with perforated duodenal ulcer: a case report.

INTRODUCTION: Situs inversus is an uncommon anomaly. Situs inversus viscerum can be either total or partial. Total situs inversus, also termed as mirror image dextrocardia, is characterized by a heart on the right side of the midline while the liver and the gall bladder are on the left side. Patients are usually asymptomatic and have a normal lifespan. The exact etiology is unknown but an autosomal recessive mode of inheritance has been speculated. The first case of perforated duodenal ulcer with situs inversus was reported in 1986; here, we report the second case of this nature in the medical literature. CASE PRESENTATION: A 22-year-old Pakistani man presented with severe epigastric and left hypochondrial pain. Examination and investigations (chest X-ray and ultrasonography) confirm peritonitis in a case of situs inversus totalis. On exploratory laparotomy, a diagnosis of situs inversus totalis with perforated duodenal ulcer was confirmed. Graham's patch closure of the duodenal ulcer was performed with absorbable sutures, and a thorough peritoneal lavage was also performed; an incidental appendectomy was also performed to avoid further diagnostic problems. Our patient had an uneventful recovery. CONCLUSIONS: A diagnostic dilemma arises whenever abdominal pathology occurs in patients with situs inversus. Although an uncommon anomaly, to choose a proper surgical incision site for abdominal exploration pre-operative recognition of the condition is important.

Mixed epithelial and stromal tumour of kidney.

Mixed epithelial and stromal tumour of kidney is a recently described, rare entity and includes cases previously termed as cystic hamartoma of renal pelvis and adult mesoblastic nephroma. We report a case of 36 years old female who presented with a history of recurrent loose stools for 5 years. During ultrasound abdomen, a solid right renal mass was incidentally found in upper pole of right kidney. On gross examination it was a 3.5 cm diameter mass which was microscopically composed of both epithelial and stromal components in the form of cystically dilated tubules and fascicles of spindle shaped cells. These cells stained positive for alpha smooth muscle actin, desmin, progesterone receptors and negative for estrogen receptors.

Metaplastic carcinoma of the breast, an intriguing rarity.

Metaplastic carcinoma breast is categorized as a rare heterogenous neoplasm generally characterized by a mixture of adenocarcinoma with dominant areas of spindle cell, squamous and/or other mesenchymal differentiation. To determine the epidemio-demographic and histopathologic characteristics of this rare entity a retrospective study was conducted to review all cases at the Aga Khan University Hospital (AKUH) Karachi, received during 1st January 2000 to 31st August 2005. Twenty-four patients were identified with a mean age at diagnosis of 46.4 (+/-SD 3.8) years, and an age range of 28-68 years. The mean tumor size was 7.9 cm, range 2.0-17.0 cms (+/-SD 4.77). The specimens were mostly obtained by modified radical mastectomy(54.2%) followed by biopsy (29.2%), lumpectomy (8.3%), and total mastectomy (4.2%). Skin ulceration was found in 37.5% cases. Component sub-categorization showed 13 (54.2%) cases of infiltrating ductal carcinoma with squamous metaplasia, followed by 2 (8.3 %) cases with heterologous elements, 4 (16.7%) cases with spindle cell component, 2 cases of matrix producing carcinoma and one case of squamous cell carcinoma. The malignancy was high grade, modified Bloom Richardson's grade III (54.2 %) and grade II (12.5%). Such grading was not applicable to 4 cases of spindle cell component and 1 case with extensive chondroid areas. Twelve patients had information available on the nodal status. Five (41.6%) were node-negative, four (33.33%) had 1-3 lymph node involvement positive, and three (12.5%) had more than 3 lymph nodes positive. The median 3 year Event Free Survival (EFS) was 10% and overall survival was 30%. MCB is an aggressive disease with a poor prognosis. This aspect appears bleaker in our population either due to the biological characteristic of the malignancy in a high risk group or the lack of availability and accessibility of health coverage, resulting in a delayed presentation. MCB is an uncommon breast malignancy and due to the lack of sufficiently large studies there is limited knowledge as to the pathogenesis, progress, best treatment protocols and prognosis. Collaborative studies are therefore recommended to allow for better understanding of this intriguing neoplasm.