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Introduction and Importance: Extra-skeletal Ewing sarcoma (EES) belongs to the family of primitive neuroectodermal tumors (PNET) and arises from soft tissue, with only 30 cases reported in the literature until now. Early diagnosis is crucial, and the management requires a multidisciplinary approach for better patient outcomes and survival., Case Presentation: A 20-year-old female presented to the surgical outpatient department with complaints of shortness of breath and right lower chest pain. Upon physical examination, a lipomatous lesion was observed. Ultrasound and CT scan showed a heterogeneously enhancing soft tissue mass in the right lower hemithorax causing erosion and osteolysis of the right 9th rib, involving intercostal muscles, and exerting mass effect on the underlying hemidiaphragm. Later USG-guided Tru-cut biopsy was performed to confirm the diagnosis, which reported Ewing sarcoma with CD 99, FL-1, and NKX 2.2 positive. En-bloc tumor resection along with a portion of the diaphragm was performed, and a tube thoracostomy was carried out. Chest wall reconstruction was done with mesh and a local muscle rotation flap cover. Adjuvant chemotherapy was initiated., Clinical Discussion: EES often presents with vague symptoms such as shortness of breath or abdominal or chest pain, thus making the diagnosis even more difficult. However, it has a relatively poor prognosis and thus is an important differential to rule out., Conclusion: Extra-skeletal Ewing Sarcoma is a highly aggressive tumor that requires prompt diagnosis and treatment, with surgical resection being the first line of treatment. Adjuvant chemotherapy has also shown better outcomes., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this articles., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To correlate the results of HER2/neu protein overexpression on immunohistochemistry (IHC) and gene amplification on fluorescence in situ hybridization (FISH) and to document the problems faced in performing FISH procedure., Methods: This was an observational retrospective study covering five years from January 1 st , 2015 - December 31 st , 2019 at Histopathology Department of Shifa International Hospital (SIH), Islamabad. All cases of breast cancer that underwent florescence in situ hybridization (FISH) were retrieved. Correlation between HER2/neu overexpression on IHC and its amplification on FISH was analyzed. Problems in application of FISH were recorded., Results: Out of 451 cases submitted for HER2/neu testing by FISH, 68 cases (15%) were rejected. Gene amplification was seen in 139 (36.29%) cases. Total cases with HER2/neu IHC score of 2+ were 330 cases and out of which gene amplification was seen in 98 cases (29.69%) whereas 93.1% (41/44) 3+ IHC cases were amplified. Poor fixation, inadequate amount of tumor with crushing artefacts and dye application to the biopsy fragments were causes of sample rejection., Conclusions: Her2/neu amplification was seen in most Her2/neu 3+ cases and approximately one-third of Her2neu 2+ cases. Proper fixation, adequate biopsy material with standardized processing is required to yield useful results on FISH., Competing Interests: Statement conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification., Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018., Results: One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine tumour (WDNET) in 96(81.4%) patients followed by neuroendocrine carcinoma (NEC) in 11(16.1%) patients. Almost half the cases or 54(45.8%) of WDNET were grade 1, 32 (27.1%) were grade 2, and 10 (8.5%) were grade 3. Distant metastasis at the time of diagnosis was found in 18(15.3%) cases with 14,(77.7%) in liver as the most common metastatic site. Synaptophysin positivity was seen in 60 (96.8%) cases of grade 1, 32(27.2%) of grade 2 WDNET, 8(100%) cases of grade 3 WDNET and 12(92.3%) of NEC and chromogranin was positive in 49(94.2%) of grade 1 and grade 2 WDNET, 5 (83.3%) cases of grade 3 WDNET and 5 (45.4%) cases of NEC., Conclusions: GEP-NETs showed a wide clinicopathological spectrum. Pancreas is the most common site of involvement by the GEP-NET, however, grade 3 WDNET had a predilection for colon. Small cell carcinoma was commonly observed in the oesophagus.

Competing Interests: There are no conflicts of interests.

Introduction: Synovial sarcoma (SS) accounts for 10-15 percent of adult soft tissue sarcomas. Transducin-like enhancer of split 1 (TLE1), a transcriptional repressor, is essential in hematopoiesis, neuronal differentiation, and terminal epithelial differentiation. TLE1 proteins inhibit Wnt signaling and other cell fate determination signals, and so have an established role in repressing differentiation. TLE1 has recently been shown to be a highly sensitive and relatively specific marker of SS., Materials and Methods: Study design is retrospective, descriptive. A total of 25 cases of SS and 28 of soft tissue lesions were retrieved from the record. TLE1 (clone 1F5) expression was evaluated and scored as negative (<5% of cells positive), 1+ (5-25% of cells positive), 2+ (26-50% of cells positive), or 3+ (>50 % of cells positive)., Result: Twenty-four out of twenty-five (96%) cases of SS showed 3+ TLE1 expression. One (4%) case of poorly differentiated SS showed 2+ positivity. 3+ TLE1 positivity was seen in one (100%) case each of infantile fibrosarcoma and low-grade fibromyxoid sarcoma, while two cases (100%) of schwannoma also showed 3+ positivity. All cases of solitary fibrous tumor) (n=2), clear cell sarcoma of tendons and aponeurosis (n=2), embryonal rhabdomyosarcoma (n=1), and de-differentiated liposarcoma (n=2) showed 2+ positivity. 1+ positivity was seen in alveolar soft part sarcoma (n=2), Ewing's sarcoma (n=4), undifferentiated pleomorphic sarcoma (n=1), myxoid liposarcoma (n=1) and malignant peripheral nerve sheath tumor (n=1). TLE1 was negative in all cases of chordomas (n=2), lipomas (n=2), nodular fasciitis (n=2), malignant perivascular epithelioid cell tumor (n=1) and dermatofibrosarcoma protuberans (n=1)., Conclusion: TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Ali et al.)

Langerhans cell histiocytosis (LCH) is a rare entity formerly known as eosinophilic granuloma. It is characterised by clonal multiplication of langerhans cells (LCs) that can occur anywhere in the body, especially in connective tissue of skin, lymph nodes and bone. Although rare, the disorder frequently affects children. A 7-year male child presented with the complaint of swelling at glabella. CT-scan revealed a defect in the middle of both frontal bones with brain herniating out of it. The clinical differential diagnosis included osteomyelitis, Tuberculosis and encephalocele. Fine needle aspiration cytology (FNAC) was performed and diagnosis of LCH was confirmed by typical cytological features, followed by immuno- histochemical staining for CD1a.

Background: Renal cell carcinoma (RCC), accounts for 2-3% of all new cancers diagnosed. Most renal tumours have characteristic histological features, which help in their sub classification. However, some cases do show overlapping morphology which pose a diagnostic challenge for the pathologists. Tumour ancillary studies such as immunohistochemistry (IHC) may play a significant role in segregation of these tumours. This study was undertaken to determine the role of IHC in diagnosing these tumours., Methods: December 2015. It was carried out in histopathology laboratory of Shifa International Hospital, Islamabad. A total of fifty-five (n=55) nephrectomy specimens having RCC subtypes were included. A specific morphological diagnosis was rendered in each case on H&E.. A panel of six immunohistochemical markers CK7, CD10, CD117, CA IX, AMACR and Vimentin was then applied in each case and a final diagnosis considering both morphology and IHC was given. Statistical analysis was done using SPSS version 20.0. Mean and SD were calculated for quantitative variables where as frequencies and percentages were calculated for qualitative variables., Results: Out of a total of 55 cases, 36 (65.55%) were males whereas 19 (34.5%) were females. The mean age of patients was 54.04±14.40 years. Clear cell RCC comprised 70.9% (n=39), Papillary RCC 14.5% (n=8), Chromophobe RCC 10.9% (n=6) and clear cell papillary RCC 3.6% (n=2) of cases on morphology. After application of IHC stains in all cases, 83.6% (n=46) of cases were found to have correct diagnosis on H& E. However, 16.4% (n=9) of cases could not be correctly diagnosed on morphology alone and it was in these cases that IHC played a major role in reaching a final diagnosis., Conclusions: Although most RCC subtypes display a characteristic morphology on H&E, in a significant proportion of the cases there are considerable overlapping morphological features. Our study shows that a correct diagnosis cannot be made on H & E alone in a notable number of cases. Therefore, IHC should be applied in all cases to reach a final diagnosis, which has both prognostic and therapeutic implications.

Primary renal angiosarcoma is a rare tumor. Epithelioid variant of primary renal angiosarcoma is extremely rare and aggressive entity described in literature as a few case reports. It presents as solid looking renal mass as other renal cell carcinomas. Management is not well described due to scarcity of cases and aggressiveness of disease. We hereby report a case of epithelioid renal angiosarcoma in a 62-year female who presented with features of infected perinephric collection. Histopathological and immunohistochemical examinations of the renal specimen revealed lower polar renal tumor with atypical epithelioid cells having eccentric nuclei with coarse chromatin and eosinophilic cytoplasm, which were positive for vascular endothelial (FLI-1, CD 34, CD31 and factor VII) as well as epithelial (CKAE1/AE3) immune markers. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with primary renal epithelioid angiosarcoma.

Background: Margin assessment is done in Whipple procedures which are usually performed to resect tumours of head of pancreas and ampullary/periampullary region. Aims and objective of the study are to determine the concordance between frozen sections (FS) and permanent sections (PS) of surgical margins in Whipple resections., Methods: It is a retrospective study, from January 2008 to January 2015 (07 years). It includes the specimen with malignancy in final report and for which FS of pancreatic and/or CBD margin(s) were requested. Data was retrieved from Laboratory information system (LIS) database., Results: Of the 41 bile duct margins in cases of ampullary tumours, 03 were positive on FS as well as PS, 35 were negative on FS as well as on PS. Results showed 100% sensitivity, 92.1% specificity, 50% PPV and 100% NPV. Results of 36 pancreatic margins in cases of ampullary showed 100% sensitivity, 97.1% specificity, 50% PPV and 100% NPV. In pancreatic carcinoma cases, none of CBD margins were reported as positive on FS, 02 margins reported as negative were found positive on PS, while 17 were negative on FS as well as PS. Results showed 100% specificity and 89.5% NPV. Of the 27 pancreatic margins tested in pancreatic tumours 100% sensitivity, 94.1% specificity, 88.9% PPV and 100% NPV was found., Conclusions: Factors such as absent prior tissue diagnosis and/or inflammatory processes make margin diagnosis difficult. However, a high concordance was observed between our FS and PS diagnosis.

Follicular dendritic cell sarcoma (FDCS) is a rare intermediate grade sarcoma involving a variety of nodal and extra nodal sites. It has two histological subtypes, conventional and inflammatory pseudotumour like variant. We report this interesting case of FDCS presenting colonic intussusception at Shifa International Hospital, Islamabad, Pakistan. Conventional FDCS presenting as a colocolic intussusception is an unusual presentation, and to our knowledge, has never been reported previously. It has wide morphological spectrum on light microscopy and has characteristic immune-reactivity for dendritic cell markers (CD21, CD23, and CD35). Surgical excision is required in all cases while role of adjuvant chemotherapy and radiotherapy is not clearly demonstrated in literature.

This descriptive study was carried out at Pathology Department, Shifa International Hospital from 2007 to 2016; all sex cord stromal tumours diagnosed during this time period were included. Epithelial, germ cell and metastatic tumours were excluded from the study. A total of 1254 Ovarian tumours were brought to Shifa of which47 (4%) were labeled as sex cord stromal tumours. Of these 36( 76 %)were granulosa cell tumour (adult33, juvenile3), 7 were labeled as sertoli leydig cell tumours (15%), 3 as thecoma/ fibroma group (7%)and only one case was labeled as microcystic stromal tumour of the ovary (2%). Overall age range for sex cord stromal tumours was 42 (12-71). Immunohistochemistry was done in 41 out of 47 cases. Sex cord stromal tumours of the ovary are rare tumours comprising 4% of the total. Adult Granulosa cell tumour is the commonest tumour seen in our study.

Extraskeletal osteosarcomas (OSs) are highly malignant soft tissue tumours associated with a poor prognosis. Only a few records of these rare aggressive neoplasms have been reported in the literature.We describe the case of a 49-year-old man, who presented to our tertiary care centre with a painful isolated lump around the umbilicus. After surgical biopsy, imaging and subsequent pathological analysis, the swelling was diagnosed to be a localised extraskeletal OS. He received previous radiation as treatment for testicular seminoma 40 years ago, which has been in remission ever since. He also happens to have testicular hydrocele since 10 years. He was subjected to resection and free flap reconstruction complicated by lower anterior abdominal wall haematoma and large pseudoaneurysm of the left femoral artery. Patient completed 60 Gy of adjuvant electron beam irradiation for close margins and is scheduled for adjuvant chemotherapy. We describe a brief account of his illness., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Encapsulated papillary carcinoma (EPC) is a rare low grade carcinoma of the breast with excellent prognosis. This case series focuses on its histopathological and clinical characteristics in our material. Cases of papillary lesions of breast from 1st January 2012 to 30th December 2014 were retrieved from the hospital database. A total of 8 cases were categorized as EPC. Mean age of patients was 66 years. Breast lump with tumour size ranged from 1.5 to 5.0cm, and was the presentation in 75% of cases. Histopathology showed a well circumscribed lesion within a dilated duct comprising of fibro vascular cores lined by neoplastic cells, surrounded by thick fibrous capsule. Immunohistochemistry, for antibody panel p63, ASMA and CK 5/6 were negative for myoepithelial cells. Invasive carcinoma was seen in 3 (37.5%) with associated DCIS in 4 (50%) cases. Meticulous gross, attention to morphology and correct interpretation of immunohistochemistry are imperative for accurate diagnosis.

Objective: To determine the frequency of IgAnephropathy presenting at a tertiary care hospital., Study Design: Across sectional, observational study., Place and Duration of Study: Pakistan Institute of Medical Sciences, Islamabad and Shifa International Hospital, Islamabad, Pakistan, from November 2008 to November 2014., Methodology: This was a retrospective analysis of renal biopsies for the diagnosis of nephropathy during the study period. Biopsies were stained with fluorescence isothyocyanate (FITC) labelled antibodies against IgG, IgA, IgM, C3, C4 and C1q for fluorescent microscopy. For histopathological examination, the specimens were stained with hematoxylin and eosin, Periodic acid Schiff and methanamine silver stains for light microscopy., Results: Out of total 1,658 renal biopsy cases, 142 (8.6%) were diagnosed as IgA nephropathy on light and immunofluorescence microscopy. Majority of IgAnephropathy patients were young (mean age = 33.2) and presented with proteinuria. The frequency rose from 2% in 2008 to 9.4% in 2014., Conclusion: IgAnephropathy was present in younger population and has a rising trend in our population.

Objective: To evaluate the accuracy of intra-operative frozen section in the diagnosis of various pelvic neoplasms, including ovarian tumours., Methods: The retrospective study was conducted at Shifa International Hospital and comprised records of all patients with lesions of female genital tract who underwent frozen section between January 2010 and December 2012. Comparison was made with the final diagnosis after histopathology was performed on examining permanent paraffin sections., Results: The mean age of the 54 patients was 43.70+/-14.8 years (range: 19-75 years). The frozen section was accurate in 51(92.6%) cases. It had a moderately high sensitivity of 75%, high specificity of 97.6%, high positive predictive value of 90% and high negative predictive value of 93.2%. Lack of agreement was found in cases of ovarian tumours of the mucinous and borderline variety., Conclusions: Frozen section showed a considerable level of accuracy when dealing with suspected pelvic neoplasms.

The cases of two middle age males are presented who were incidentally diagnosed to have atrial myxoma. Both of them underwent successful surgical interventions. Histologically, both myxomas showed abundant multinucleated giant cells, in addition to typical myxoid stroma with stellate and cord-like structures.

Leiomyoma is a benign tumour of smooth muscle origin, which can also affect many organs specially kidneys. In kidneys, it is mostly found in the renal capsule but rarely does it also involve the renal pelvis. It is mostly found in middle-aged women. A 25-year-old man presented with hematuria histologically secondary to proven leiomyoma of left renal pelvis with unusual clinical features underwent minimally invasive surgical management.

Objective: To evaluate human epidermal growth factor receptor 2 (HER2/neu) interobserver variability between specially trained and untrained general histopathologists., Methods: The retrospective study cases of invasive breast carcinoma received at Shifa International Hospital, Islamabad, from June 2010 to December 2011, for assessment of HER2/neu status by immunohistochemistry which were retrieved from the files and, 30 consecutive cases each of score 0, 1+, 2+ and 3+ were selected for a total of 120 cases. Two groups of two histopathologists each examined the cases blindly. One group had attended a short course in Germany, while the other group comprised two qualified histopathologists who had not had any special training. Each histopathologist reported the cases independently according to standard guidelines. Kappa statistics were applied., Results: The trained group of histopathologists showed agreement in 113 (94%) cases. Kappa value was calculated to be 0.96 which means 'perfect agreement. In contrast the untrained group showed agreement in 83 (69%) cases with a kappa value of 0.59 which means 'moderate agreement., Conclusion: Interobserver variability in immunohistochemical scoring of HER-2/neu in breast carcinoma is high among untrained general histopathologists. This may adversely affect the selection of patients with cancers who could benefit from Herceptin therapy.

Objective: To study the immunohistochemical pattern of CD 117, glial fibrillary acidic protein (GFAP), smooth muscle actin (SMA) and CD 43 in pleomorphic adenoma (PA), adenoid cystic carcinoma (AdCC) and polymorphous low grade adenocarcinoma (PLGA) of minor salivary glands., Materials and Methods: Twenty cases of PA, 20 cases of AdCC and 10 cases of PLGA were retrieved from record files along with their paraffin blocks at Armed Forces Institute of Pathology, Pakistan. New histological diagnosis was made on freshly prepared H&E sections followed by application and analysis of immunostains., Results: The mean age of the patients was 44 ± 15 (mean SD) (range; 17-86) years. There were 26 male and 24 female patients with a male to female ratio of 1.08:1. Fourteen cases of PA, 14 cases of AdCC and 6 cases of PLGA were positive for CD117. In case of GFAP, only 9 cases of AdCC and 3 cases of PLGA were positive; however, 16 cases of PA were also positive. Twelve cases of AdCC and 7 cases of PA were positive for SMA and half of the PLGA cases were also reactive. Nonetheless, the least expression was seen in case of CD 43, where only five cases of AdCC were positive. Six cases of PA and three cases of PLGA were also positive., Conclusion: Our results suggest that the use of GFAP, SMA, CD 117 and CD 43 as an adjunct to histological examination is not helpful in differentiating PA, AdCC and PLGA from one another.

Objective: To assess the efficacy of fine needle aspiration cytology in the evaluation of thyroid lesions., Methods: The retrospective study comprised data of all patients who presented for fine needle aspiration cytology at the Shifa International Hospital, Islamabad, between January 2009 and April 2011. The data was retrieved from the departmental records and the results were recorded. All cases who underwent subsequent surgery were also retrieved and histopathology results were compared with the cytology results. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were calculated., Results: Of the 327 patients, the results were inconclusive in 18 (5.5%), benign in 230 (70.3%), suspicious in 64 (19.6%) and malignant in 15 (4.6%) cases. Besides, 59 (18%) of these patients underwent subsequent surgery. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of fine needle aspiration cytology was calculated to be 85.7%, 73.3%, 50%, 94.2% and 76.2% respectively., Conclusion: Fine needle aspiration cytology is a reasonably sensitive, specific and accurate initial diagnostic test for pre-operative evaluation of patients with thyroid swellings. The clinicians should be encouraged to use the procedure as it is minimally invasive and easily performed in an outpatient setting.

Objective: To correlate the findings of immunoflorescence (IF) with morphology in renal biopsies of patients with glomerulonephritis (GN) of both primary and secondary nature., Methods: The cross-sectional analytical study was conducted at the Shifa International Hospital's Department of Pathology form March 2007 to August 2008, during which a total of 207 renal biopsies were done. Of them, the study included 92 cases which were diagnosed as primary or secondary glomerulonephritis under light microscope. Those cases were selected in which both light microscopy (LM) and immunoflorescence were done., Results: Of the 92 patients, 79 (85.8%) were adults (> or = 19 years) and 13 (14%) were children (< 19 years). The mean age of adults was 36.44 +/- 11.55 (range 19-69 years) and that of the children was 10.54 +/- 3.85 years (range 4-18 years). immunoflorescence changed the morphologic diagnosis in 20 (21.73%) cases. The pattern of disease was: membranous glomerulonephritis in 24%, focal segmental glomerulosclerosis (FSGS) in 18.4%, mesangiocapillary glomerulonephritis in 2%, and minimal change disease (MCD) in 16% of the cases., Conclusion: Light microscopy alone can misdiagnose renal disease. This is especially important in cases of early stage membranous, IgA nephropathy (IgAN), Lupus nephritis and IgM nephropathy (IgMN), as these entities can only be diagnosed by correlating the microscopic, immunoflorescence findings and clinical details.

Introduction: Diffuse large B-cell lymphomas (DLBCL) can be divided into germinal centre (GC-DLBCL) and post germinal centre (post GC-DLBCL) groups by applying immunohistochemical antibodies. As these subgroups respond differently to chemotherapy, it is possible at diagnosis to select a poor prognostic subgroup for aggressive treatment., Objective: To determine the frequencies of GC-DLBCL and post GC-DLBCL in patients by immunohistochemistry (IHC) and the clinical response after six cycles of chemotherapy., Subjects and Methods: In this descriptive study conducted in AFIP and CMH, Rawalpindi and NORI, Islamabad, from September 2010 to September 2011, a total of 75 pretreatment cases of DLBCL diagnosed during the study period were included. Cases were segregated in to GC-DLBCL and post GC-DLBCL groups according to results of immunohistochemistry markers CD10, BCL6 and MUM1. Immediate clinical response was assessed after 6 cycles of chemotherapy. Response was divided into complete response, partial response, stable disease or relapse or progression., Results: The mean age was 54.2 ± 15. Males were 53 (70.7%). Forty (53.3%) cases comprised the GC-DLBCL group; 25(62.5%) of them showed a complete response. Most patients of the post GC-DLBCL 19(54%) showed relapse/progression. Results of immediate clinical response in both prognostic subgroups were significant (p<0.05). Results regarding positivity with immunohistochemical antibodies CD10 (p 0.011), BCL6 (p 0.013) and MUM1 (p 0.000) regarding immediate clinical response were also significant., Conclusion: GC-DLBCL group shows better response to CHOP chemotherapy regimen. Immunohistochemistry should be used to further classify DLBCL as this can enable us to select aggressive group for aggressive treatment. This manuscript is important because the study is the first to becarried out exclusively in Pakistan or our part of the world.

Yolk sac tumour is germ cell tumour commonly found in children and infants under three years of age in its pure form with a good prognosis. The commonest location for the yolk sac tumour is gonads i.e. testis and gonads. Yolk sac tumour is rarely reported in extra- gonadal locations. Parapharyngeal space is an uncommon site for mature teratoma and very few cases have been reported in adults and children. Malignant transformation in a mature teratoma in the extragonadal sites has been reported but development of yolk sac tumour has not been reported so far in the world literature. We report to our knowledge, the only and first case of yolk sac tumour arising in a mature teratoma presenting as a parapharyngeal mass in a four year old male child.

To evaluate neurological effects of terbutaline, rats were injected with saline, terbutaline (Sigma or American Pharmaceutical Partners (APP™)) at 0.5 mg/kg-d or 10 mg/kg-d between postnatal days (PND) 2-5 or 11-14. Brains collected 24 h after last injection were used to determine corpus-callosum thickness, Purkinje cell and neuronal number in the cerebellum. Ambulation, distance traveled, resting time and time on rotarod were analyzed. Terbutaline (both doses/grades at PND 11-14) decreased corpus-callosum thickness. Ambulation time was significantly decreased in the 10 mg/kg-d (Sigma) and 0.5 mg/kg-d of terbutaline (APP™) (PND 2-5) juvenile-rats and 10 mg/kg-d-Sigma adult-rats, 0.5 mg/kg-d APP™ (PND 11-14) adult-rats. Resting time was increased in both doses of APP™ (PND 2-5) in juvenile-rats, 10 mg/kg-d Sigma adult-rats. 10 mg/kg-d-Sigma (PND 2-5) decreased distance traveled in adult-rats. 0.5 mg/kg-d-Sigma (PND 2-5 and PND 11-14) decreased the time spent on rotarod (30 RPM) in adult-rats. Sigma terbutaline Sigma had 2× as much free base compared to APP™. In conclusion, APP™ terbutaline did not have a deleterious effect on the developing rat brain., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the diagnostic utility of endoscopic ultrasound guided fine needle aspiration cytology in the diagnosis of mediastinal and abdominal lesions., Methods: Endoscopic ultrasound guided aspiration cytology was carried out on a total of 155 cases during the study period. The lesions were categorized according to the site of needle biopsy. Clinical impression and provisional diagnoses were compared with the final cytological diagnoses and the percentage of inadequate/non diagnostic smears was calculated., Results: Out of 155 cases, 18 cases (11.5%) were reported as inadequate while a definite diagnosis was given in the remaining cases (88.5%). The mean patient age was 49 +/- 14.0 years. There were 105 (68%) males and 50 (32%) females. The most common site biopsied was mediastinal lymph nodes followed by pancreas. The most frequent diagnosis was adenocarcinoma mostly of pancreas followed by chronic granulomatous inflammation of mediastinal and abdominal lymph nodes. The average number of passes made was 3. The size of the lesions ranged from 0.6 cm to 25 cm with mean size of 3 cm as measured by endoscopic ultrasound probe., Conclusion: Endoscopic ultrasound guided aspiration cytology is a useful procedure in the evaluation of deep seated lesions of gastrointestinal tract (GIT), abdominal cavity and mediastinum.

Objective: To study the frequency and distribution of non-cutaneous malignant melanoma in Northern Pakistan using a cross-sectional descriptive design at the Armed Forces Institute of Pathology Rawalpindi, from 1987-2008., Materials and Methods: A total of 234 cases of malignant melanoma reported from 1987-2008 were retrieved from the AFIP tumour registry and analysed for age, gender and site using computer software SPSS 12., Results: Of a total of 58,680 malignant cases reported at AFIP from 1987-2008, only 234 (0.4%) were of malignant melanoma, 142 in males and 92 in females. The age range was 10-97 years, with a mean of 53 ± 16. Only 69 (29.5%) were cutaneous and 165 (70.5%) were non-cutaneous in origin: there were 62 (37.4%) cases from anorectal region, 39 (23.4%)were from eye ball and 17 (10.2%) in the nasopharynx, 13 cases (7.8%) from oral mucosa and 11 (6.6%) from the vagina., Conclusion: Malignant melanoma is markedly less cutaneous in Pakistan as compared to the western world, often being found in the anorectal region followed by the eye, nasopharynx, and oral mucosa in descending order.

Objective: To determine the HER-2/neu status by chromogenic in situ hybridization (CISH) on tissue specimens with a borderline (2+) immunohistochemistry (IHC) score in carcinoma breast by a descriptive, cross-sectional study in the Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jun 2008 to Dec 2009., Methods: Tissue block specimens from 50 consecutive patients having HER-2/neu score of borderline (2+) on IHC assay were tested for HER-2/neu gene amplification by CISH. Mean and standard deviation were calculated for quantitative variables like age and HER-2/neu gene copy signal/clusters by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like type of carcinoma and results of HER-2/neu by CISH (amplified/nonamplified)., Results: HER-2/neu gene amplification by CISH was found in 10 (20%) out of 50 patients with borderline (2+) IHC score. All CISH amplified cases belonged to invasive ductal carcinoma type. No significant correlation was noted between type of carcinoma and HER-2/neu gene amplification., Conclusion: Chromogenic in situ hybridization (CISH) is a practical, cost-effective and reliable method for analysis of HER-2/neu borderline (2+) cases which may be candidates for Herceptin therapy.

Objective: To determine age-related association of Her-2/neu expression with histological and immunohistochemical prognostic markers in female breast carcinoma., Study Design: Cross sectional, observational study., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to December 2007., Methodology: Patients of primary operable female breast carcinoma were categorised as < 40 years (pre-menopausal), 41-50 years (peri-menopausal) and > 50 years (post-menopausal) age groups. Histological type, tumour size, tumour grade and lymph node status were determined while estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu expression were evaluated immunohistochemically. Association of Her-2/neu with histological and immnuohistochemical prognostic markers was determined in pre-menopausal, peri-menopausal and post- menopausal age groups using the x2 test for uni- and multivariate analysis., Results: Out of the 722 patients, 230 (31.9%) were in pre-menopausal, 221 (30.6%) in peri-menopausal and 271 (37.5%) in post-menopausal age group. Infiltrating ductal carcinoma was the pre-dominant subtype in all the age groups. Mean tumour size was 4.3+/-2.3 cm (range 0.4-17 cm) and lymph node metastasis was seen in 310 (70.8%) cases. Her-2/neu showed association with ER in the all the age groups while PR only showed association in the peri-menopausal and postmenopausal women. Her-2/neu showed no association with tumour size, tumor grade and lymph node metastases in pre-menopausal and peri-menopausal women while it showed positive association with tumour size and lymph node metastasis in the post-menopausal women (p < 0.05)., Conclusion: Majority (62%) patients were under 50 years as against the Western epidemiology. Association of Her-2/neu with ER, PR, tumour size and lymph node metastasis was age related as pre-menopausal, peri-menopausal and postmenopausal had variable expression of these prognostic markers with therapeutic and prognostic implications.

Objective: To compare immunohistochemical estrogen receptor expression on formalin-fixed, paraffin-embedded breast carcinoma tissue sections by using regular, extended microwave heating and pressure cooker technique for heat induced antigen retrieval., Study Design: Quasi experimental study., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from August 2006 to July 2007., Methodology: The study was conducted on 40 cases of breast carcinoma diagnosed on histopathology and selected by convenience sampling. One section each of the tumour was separately subjected to regular microwave heating (10 minutes), extended microwave heating (20 minutes) and pressure cooker (heating for 2 minutes after reaching full pressure). A nuclear staining of >10% cells with moderate intensity was considered positive and frequency of ER expression by each technique was compared statistically. Sensitivity and specificity of the techniques was determined using pressure cooker technique as the gold standard for this study., Results: Out of 40 cases, ER expression in 24 (60%) cases was seen by microwave regular heating (MRH) and in 30 (75%) cases by microwave extending heating (MEH) technique. Pressure cooker (PC) technique for antigen retrieval demonstrated 34 (85%) cases with ER expression. Out of 16 which were negative by MRH technique, 6 became positive by MEH while 10 became positive by PC. Statistically significant difference in ER expression by PC and MEH technique was seen in comparison to MRH with a p-value of <0.05. Moreover, 4 cases which were negative by MEH technique turned positive for ER expression by PC. MRH and MEH had 100% specificity but sensitivity was 70.6% and 88.2% respectively taking PC technique as gold standard with diagnostic accuracy of MEH as 90% and MRH as 75%., Conclusion: Pressure cooker antigen retrieval technique is a better method than microwave heating. The increase in duration of heating improves the percentage of positive cells as well as intensity of ER immuno-staining which entitles breast cancer patient to benefit from ER positive treatment protocols which have better prognosis.

Objective: To determine steroid hormone receptor expression and their association with histological prognostic markers and biological profile in female breast carcinoma in Northern Pakistan., Study Design: Cross sectional, observational., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to December 2007., Methodology: Female patients belonging to Northern Pakistan with primary operable breast carcinoma were included in the study. Patient's age, microscopic tumour size, tumour grade, lymph node status and biological profile for Her-2/neu status were evaluated. Immunohistochemical expression for ER and PR was determined individually and conjointly for ER+PR+ and ER-PR- while their association with above prognostic markers was determined using the c2 test for univariate analysis., Results: Out of the 726 cases, there were 657 (90.4%) cases of infiltrating ductal carcinoma with mean age of 48+/-12 years and mean tumour size of 4.2+/-2.3 cm. Tumour was grade-II in 65% and lymph node metastases in 71.5% cases with Her-2/neu+ in 28.1%. ER and PR expression was 74.6% and 68.3% respectively. Conjoint expression of ER+PR+ was 456 (62.8%), ER-PR- in 21.2%, ER+PR- in 86 (11.8%) and ER-PR+ in 30 (4.1%) cases. Individually, ER and PR showed positive association with age, lymph node metastasis, tumour grade and inverse association with Her-2/neu. Conjoint expression of ER+PR+ (62.8%) and ER-PR-(21.2%) showed positive association with age, tumour grade, lymph node metastasis and inverse association with Her-2/neu (p < 0.05)., Conclusion: Hormone receptor expression of ER and PR expression is comparable to the West with ER and PR showing inverse association with Her-2/neu and positive association with age, tumour grade and lymph node metastases.

Neoplasms of the vulva are rare and most commonly reported amongst them are epithelial tumors. Teratomas have been reported in many extragonadal sites. We report the only case of an immature teratoma of the vulva with inguinal lymph node metastasis.

Objective: The rationale of this study is to analyze the demographic distribution and clearance of excision margin in basal cell carcinoma among patients diagnosed at AFIP Rawalpindi., Materials and Methods: Records of a total of 235 cases diagnosed from January 2005 to December 2007 were retrieved from our tumour registry. The following variables were recorded for each patient: age, gender, site of biopsy, type of biopsy (incisional vs excisional) and status of clearance of surgical margins. The data was analyzed using SPSS version 17.0., Results: Among the total of 235 cases, 125 (53.2%) were males and 110 (46.8%) were females (1.2:1). The ages ranged from 32 to 90 years with mean age of 60.0 + 11.7, with a general age-dependent increase. The nose was the most frequent site (28.9%), followed by the eye, including the orbit (24.7%), and the cheek (20.4%). Among the type of biopsies, 140 (59.6%) were excisional and 95 (40.4%) were incisional. With the former, the excision margins were reported as clear in 82 (34.9%) cases and involved in 55 (23.4%) cases., Conclusion: Basal cell carcinoma (BCC) appears to be on the rise in our part of world. Careful clinical assessment, and complete excision with the help of frozen sections can avoid recurrence.

Objective: The study was undertaken to document and highlight the shortcomings of histopathology reporting of breast carcinoma in Pakistan so that improvements can be recommended and a standardized protocol devised., Methods: This was a descriptive cross sectional study and was conducted at Histopathology Department, Armed Forces Institute of Pathology, Rawalpindi from 1st January 2008 to 31st October 2008. Fifty consecutive breast carcinoma reports received for review from different laboratories were analyzed for documentation of patients age, sex, type of procedure/specimen, specimen size, tumour size, invasive tumour type, invasive tumour grade, comment on excision margins, extent of lymph node involvement, insitu component, lymphovascular invasion, necrosis, skin involvement and tabular format. Frequencies and percentages were calculated for presence of these above mentioned variables in different reports, keeping in mind the possible information that could be obtained from a particular sample., Results: It was found that the variable least mentioned in the reports was in situ component commented upon in only 23.2% of reports. Necrosis was mentioned in 35% of reports. Tabular format was found in 36% of reports only., Conclusion: Marked deficiencies are seen in histopathology reports for breast carcinoma due to the lack of any standardized reporting system. Separate checklist formats for trucut biopsies, lumpectomies and mastectomies should be introduced to ensure uniform reporting.

Objective: To compare the histological prognostic markers in breast carcinoma over three decades in Northern Pakistani population and analyse for any change in trends in terms of prognostic markers., Methods: Cross-sectional descriptive study was carried out from January 2004 to December 2006 at AFIP, Rawalpindi on 822 cases of female breast carcinoma. Assessment of tumour size on gross examination followed by microscopic evaluation of tumour type, tumour grade, lymph node metastasis and skin involvement was done. The results of the present data were compared with studies of Wahid et al (January 1994 to December 1997) and Malik et al (January 1984 to December 1986) from the same institute., Results: Total 822 cases of breast cancer were diagnosed with 541 (64.9%) cases of mastectomy. The mean age was 48 +/- 12 years with a mean tumour size of 4.6 +/- 2 cm. Atumour size of >5 cm was seen in 30.6% cases and only 18.8% cases had a size <2 cm. Infiltrating ductal carcinoma was the commonest subtype in 674 (81%) cases with histological grade II in 533 (64%) cases. Lymph node metastasis was present in 74.6% cases and skin involvement in 36% cases. The comparison of the results of the present study with those over the past two decades in Pakistan show that the mean age at diagnosis remains around 48 years. There is statistically significant increase in the tumours of <5 cm at presentation and a higher frequency of tumours with dermal invasion. No significant change is seen in frequency of lymph node metastasis at operation and tumour grade., Conclusion: The comparison of results of other studies done over the past three decades in the region are not very encouraging. The age of presentation remains younger as compared to the West. A positive note is seen in terms of a decreasing tumour size but lack of DCIS cases in our material underlines the need of mammography and launching of effective screening programmes at the national level. Early detection of cases will help in treatment and subsequently improve prognosis in these patients as advocated by the West.

Objective: To determine the morphological profile and association of HER-2/neu expression with histological prognostic markers and hormonal receptor expression in female breast carcinoma in Northern Pakistan., Study Design: Cross-sectional, observational study., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to May 2007., Methodology: A total of 535 patients of primary operable female breast carcinoma with hormonal profile and biological status were included in the study. Patient's age, microscopic tumour size, tumour grade, lymph node status, Estrogen Receptor (ER), Progesterone Receptor (PR) and joint ER/PR status were evaluated and their association was determined with HER-2/neu expression using the x2 test for univariate analysis., Results: Out of 535 cases, there were 481 (89.9%) cases of infiltrating ductal carcinoma with mean age of 48 years and mean tumour size of 4.4 cm. Tumour grade II was seen in 68% cases and lymph node metastases were present in 65% cases. HER-2/neu expression was seen in 31% cases, while ER and PR expression was seen in 72.3% and 62.6% respectively. ER and PR showed inverse association with HER-2/neu while positive association was seen with lymph node metastases (p < 0.05). No association was seen between tumour size and tumour grade. Joint ER and PR expression also showed a higher number (73.5%) of HER-2/neu negative cases., Conclusion: HER-2/neu, ER and PR expression is comparable to the West with inverse association with ER and PR and positive association with lymph node metastases. Since HER-2/neu expression is variable in carcinomas with different tumour characteristics, it is not possible to predict hormone receptor expression in all the cases.

Objective: To study routine histological as well as immunohistochemical prognostic markers including ER, PR, p-53 and Her-2/neu in male breast carcinoma and compare the above parameters with breast carcinoma in female patients of the same population. Association of the immunohistochemical markers with histological prognostic markers was also studied., Methods: Cross-sectional descriptive study was carried out from January 2004 to May 2007 at AFIP, Rawalpindi on 55 cases of male breast carcinoma. Assessment of tumour size on gross examination followed by microscopic evaluation of tumour grade and lymph node metastasis was done. Immunohistochemistry was performed for ER, PR, Her-2/neu and p-53., Results: The male breast cancer patients had a mean age at diagnosis of 57 years with a mean tumour size of 4.25cm, constituting 4.7% of malignancies in men. Infiltrating ductal carcinoma was the predominant subtype with 47 (87.3%) cases. Majority of the tumours were grade II (64.2%) followed by grade III (32.1%). Out of 28 cases with axillary clearance; lymph node metastasis was present in 20 (71%) cases. ER and PR expression was seen in 81% and 79.3% cases respectively while Her-2/neu expression was seen in 24.5%. p-53 was expressed in 14 (26.4%) patients. No association of immunohistochemical markers was seen with lymph node and tumour grade., Conclusion: Male breast cancer has a higher incidence and occurs in a decade younger than the Western population with a larger tumour size and higher number of patients with lymph node metastasis. Men have a higher ER, PR expression as compared to female breast cancer patients without any association with histological prognostic markers. Her-2/neu and p-53 expression in males is comparable to the West but their prognostic role in terms of survival and treatment strategies needs to be ascertained by follow up studies.