RESUMEN

Cerebrovascular accidents (CVAs) are vascular multifactorial, multigenic ailments with intricate genetic, environmental risk influences. The present study aimed to establish affiliation of CVAs/stroke with blood parameters, differences in prescribed drugs consumption, and with differences in homocysteine pathway genes polymorphisms. The participants in study included controls n = 251, transient ischemic attack (TIA) patients n = 16, and stroke cases n = 122, respectively, (total participants, n = 389). The analyzed single nucleotide polymorphisms (SNPs) included C677T(rs1801133), A1298C(rs1801131) of methylene tetrahydrofolate reductase ( MTHFR ), A2756G(rs1805087) of methyl tetrahydrofolate homocysteine methyltransferase/methionine synthase ( MS ), and the A192G(rs662) of paraoxonase 1( PON1 ) genes, all validated by tetra-primer allele refractory mutation system polymerase chain reaction (T-ARMS-PCR). The insertion deletion (I/D; rs4646994) polymorphism in angiotensin converting enzyme ( ACE ) gene was analyzed using routine PCR. All studied traits were scrutinized through analysis of variance (ANOVA), and later through regression analysis. Through ANOVA and multiple comparison, there was association of CVA with serum homocysteine, cholesterol, and with diastolic blood pressure readings. When data was subjected to regression, serum homocysteine and diastolic blood pressure (significant through ANOVA), as well as two additional traits, high-density lipoproteins (HDL), and rs1801133 MTHFR SNP sustained statistical significance and noteworthy odds in relation to CVA and stroke. The ailments affecting cerebral vasculature are mutifactorial, whereby genes, proteins, and environmental cues all exert cumulative effects enhancing CVA risk. The current study emphasizes that SNPs and variation in circulating biomarkers can be used for screening purposes and for reviewing their effects in stroke/CVA-linked risk progression.

RESUMEN

OBJECTIVE: To determine the frequency of expression of epidermal growth factor receptor (EGFR) by immunohistochemistry in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2015 to March 2016. METHODOLOGY: Fifty-two cases of head and neck squamous cell carcinoma diagnosed on H&E stain were included in the study. Patients' gender and age were noted. Immunohistochemistry for EGFR was applied and the results were recorded. The data were analyzed by using computer software program SPSS version 19. Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out of the 52 patients of HNSCC, 37 patients were males and 15 females. The age of the patients was between 21 and 80 years with an average age of 58.58 ±12.63. Out of 52 cases, 45 cases (86.53%) were positive for EGFR while 7 cases (13.46%) were negative for EGFR. Significant statistical association was not seen between the tumour grade and EGFR expression (p=0.162). CONCLUSION: The high expression of EGFR in head and neck cancers among Pakistani patients suggests its value as a therapeutic target. EGFR inhibitors have become well-known part of HNSCC treatment; therefore, patients with EGFR positive HNSCC can be benefitted from the therapy.

Asunto(s)

RESUMEN

Mature cystic teratoma of ovary is a common benign adnexal tumor in females. Malignant transformation in a mature cystic teratoma of the ovary occurs in only 1 - 2% of cases. Most common malignant transformation is squamous cell carcinoma (70-80% of cases), occurring mostly in postmenopausal women with large sized cysts. Here, we report a case of 46-year lady who presented with pain in lower abdomen. Ultrasound and CT scan revealed complex adnexal mass measuring 16x9 cm. Size and older age of the patients should be regarded as important predictors of malignant transformation in mature cystic teratoma. Adequate sampling followed by histopathological examination has important role in diagnosis of such rare tumor.

Asunto(s)

RESUMEN

OBJECTIVE: To determine friend leukaemia integration 1 transcription factor protein expression in cases of Ewing sarcoma. METHODS: This retrospective, descriptive study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, and comprised data of diagnosed cases of Ewing sarcoma related to the period from February 2013 to December 2014. Clinico-pathological features, including patient age, gender and site of biopsy were studied. Positivity of immunohistochemical markers such as cluster of differentiation 99(membranous staining) and Friend leukaemia integration 1 transcription factor (nuclear staining) were noted. SPSS17 was used for data analysis. RESULTS: Of the 50 Ewing sarcoma cases, 26(52%) related to women and 24(48%) to men. The overall mean age was 17+11.53 years (range: 3 to 42 years). Moreover, 30(60%) patients had presented with bone swelling or growth whereas 20(40%) had presented with soft tissue swelling. The site of presentation was upper extremities in 16(32%) patients, lower extremities in 14(28%), maxilla in 7(14%), chest wall in 6(12%), paraspinal region in 4(8%), scalp in 2(4%) and retroperitoneum in 1(2%). Membranous positivity for cluster of differentiation 99 was seen in 48(98%) cases. Nuclear positivity for Friend leukaemia integration 1 transcription factor was seen in 39(78%) cases. CONCLUSIONS: Friend leukaemia integration 1 transcription factor was found to be a useful marker in diagnosing Ewing sarcoma/peripheral primitive neuroectodermal tumour. However, its positivity was more dependable when it was used in combination with other markers such as cluster of differentiation 99.

Asunto(s)

RESUMEN

PURPOSE: Over the past few decades, human papillomavirus (HPV) has been recorded as a key player in the development of various genital cancers, most notably cervical cancer. It has also been associated with some non-genital cancers. A subset of oropharyngeal cancers are known to be caused by HPV. Its aetiological involvement has been suggested for breast and lung cancer as well. However, reports regarding the HPV DNA detection vary widely from different parts of the world. Due to scarcity of local data in this regard, the current study aimed at retrospective detection of HPV presence in the archival samples of breast and lung cancer patients from north part of the country. METHODS: A total of 55 formalin-fixed paraffin-embedded tissue sections of invasive ductal carcinoma of breast (n = 46) and lung (n = 9) were collected for this study. Genotyping for HPV16 and 18 was carried out through PCR. RESULTS: HPV16 DNA was found in both breast and lung carcinoma samples with the prevalence rate of 17 and 11 %, respectively. An interesting association was found between ER/PR (Oestrogen/Progesterone receptor) and HER2/Neu (Human epidermal growth factor receptor-2) positivity with HPV occurrence in breast tumours. CONCLUSION: Current study shows the presence of HPV16 DNA in archived clinical biopsy sections from breast and lung cancers (17, 11 %), respectively. A positive correlation of HPV16 presence was found with ER/PR and HER2-positive breast cancers. These initial findings warrant further investigation in order to determine HPV prevalence and aetiological role in local cancers, especially in ER/PR/HER2-positive breast cancers on a larger scale.

Asunto(s)

RESUMEN

BACKGROUND: Triple negative breast cancers (TNBCs) are high grade aggressive tumors generally with a poor prognosis, not responding to hormonal and anti Her2 Neu therapy. Expression of the antiapoptotic B cell lymphoma 2 gene (Bcl2) is associated with low grade, slowly proliferating hormone receptor positive tumors with improved survival. Anti Bcl2 agents can be used as alternative targeted therapy in triple negative cancers. MATERIALS AND METHODS: The objective of this study was to determine the immunohistochemical expression of Bcl2 in triple negative breast cancers and any correlation with clinicopathological variables in Northern Pakistan. RESULTS: All 52 patients were females, aged between 28 and 80 years(average 48.0±12.1). 28 cases (53.8%) were positive for Bcl2, this being associated with low grade invasive ductal carcinomas, lymph node metastasis and lymphovascular invasion. CONCLUSIONS: Bcl2 may be an important prognostic factor and its expression might be used for targeted therapy using Anti Bcl2 drugs.

Asunto(s)

RESUMEN

OBJECTIVE: To determine the frequency of immunohistochemical expression of epidermal growth factor receptor (EGFR) and c-KITin triple negative breast cancer (TNBC). STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January to December 2014. METHODOLOGY: Fifty cases of triple negative breast cancer diagnosed on immunohistochemistry were included in the study. Patients'gender and age were noted. Immunohistochemistry for EGFR and c-KITwere applied and the results were recorded. The data were analyzed by using computer software programme SPSS version 19. Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out of 50 patients of TNBC, all patients were females. The ages of the patients ranged between 30 and 80 years with an average age of 48.9 years and standard deviation of ±10.0. Out of 50 cases, 29 cases (58%) were positive for EGFR while 15 cases (30%) were positive for c-KIT. Thirteen cases (26%) were positive for both EGFR and c-KIT. Nineteen cases (38%) were negative for both EGFR and c-KIT. CONCLUSION: EGFR expression was observed in 58% and c-KITexpression was seen in 30% of the cases. The results of EGFR expression are almost similar while those of c-KIT are different from international studies which suggest immunohistochemical differences between the studied populations.

Asunto(s)

RESUMEN

PURPOSE: Estimation of HPV-related disease burden lies at the core of effective disease management. HPV testing is heavily reliant on its retrospective detection in archival clinical cancer samples, especially in parts of the world where HPV screening is not routinely practiced. During the last decade, valuable insights were gained through regional reports based on occasional screening of cervical smears or biopsy sections for the presence of high-risk HPV. HPV 16 and 18 were found to be predominant high-risk HPV subtypes with some regional differences and incidences of co-infections, detected mostly through PCR-based methods. In cases of multiple infections, the presence of viral DNA may not signify its etiologic involvement. The current study, therefore, combines PCR-based detection method with the immunohistochemical (IHC) detection of early viral protein E6 expression, in order to obtain a reliable read out for the disease causing viral subtype, especially in cases of co-infections with oncogenic subtypes other than HPV 16 and 18. Immunohistochemistry (IHC) and PCR-based methods are routinely used laboratory techniques in local hospitals. The concordance between IHC and PCR-based analyses may be useful for determining effective method for the retrospective testing of HPV 16 and 18 disease-related burden. METHODS: A total of 49 paraffin-embedded cervical cancer biopsy sections representing patients from the northwest region of the country were collected from the tertiary care hospital for this study. Genotyping for HPV 16 and 18 was carried out through PCR. The HPV 16/18 E6 protein expression was evaluated by IHC and was compared with the clinicopathological features of cervical cancer. RESULTS: Molecular analysis of 33 (67 %), E6-expressing paraffin-embedded cervical cancer biopsy sections revealed the presence of HPV 16 (n = 23; 47 %), HPV 18 (n = 6; 12 %) and co-infection (n = 4; 8 %) in 49 tumors through PCR. Despite the PCR-based detection of viral DNA in 37 cervical cancer samples, IHC analysis of E6 expression revealed the etiological involvement of HPV 16/18 in 33 out of 37 cervical cancer samples. Overall, there was 85 % concordance in the results of the two techniques. CONCLUSION: IHC analysis provides more conclusive evidence regarding the etiological involvement of the viral subtypes, especially in the presence of multiple infections. About two-thirds (67 %) of cervical cancer samples were found to be caused due to HPV 16/18. Latent occurrence of HPV 16 and 18 is suggested in less than 10 % cervical cancer samples which were found to harbor viral DNA without E6 expression. Furthermore, E6 expression was found to be significantly correlated with the tumor grade.

Asunto(s)

RESUMEN

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

Asunto(s)

RESUMEN

A 37-year female presented with complaint of lower abdominal pain and amenorrhoea to the Military Hospital, Rawalpindi. Ultrasound of pelvis showed a right adnexal cystic lesion. On investigation, CA-125 was raised. Her MRI scan of pelvis revealed a right adnexal mass of fluid intensity measuring 15.2 x 12.9 x 9.2 cm. Right ovarian cystectomy was performed and the specimen was sent for histopathological examination. Grossly, the mass was cystic in appearance and measured 13.5 x 10 x 10 cm. On sectioning, it was unilocular and filled with turbid material. The cyst wall showed multiple papillary structures along with a nodule measuring 1.1 x 1 cm. Microscopically, the sections revealed borderline mucinous tumour with a sarcoma-like mural nodule composed of spindle shaped cells and epulis-like giant cells. Sarcoma-like mural nodules are rare nodules which are associated with mucinous tumours of the ovary. However, they have excellent prognosis and should not be interpreted as malignant.

Asunto(s)

RESUMEN

BACKGROUND: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. METHODS: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. RESULTS: Out of 55 patients, 38 (69%) were male and 17 (31%) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80%) were positive for latent membrane protein-1. Among positive cases 32 (72.72%) were male and 12 (27.28%) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3% as well as among both genders. Out of total 55 cases, 79.16% (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33% (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100% (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80% of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16% cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100% of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. CONCLUSIONS: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma and lymphocyte rich classical Hodgkin lymphoma.

Asunto(s)

RESUMEN

BACKGROUND: The incidence of central nervous system (CNS) tumours has rapidly increased over the past few years. There is no accurate nationwide CNS tumour epidemiology in Pakistan that makes policy making for tumour screening and early treatment difficult. The purpose of this study was to provide the spectrum of CNS tumours in a premier diagnostic and referral centre of Pakistan. METHODS: This cross-sectional study was carried out at Histopathology Department, Armed Forces Institute of Pathology over a period of 5 years. A total of 761 cases patients who were diagnosed with CNS tumours on histopathology, both benign and malignant, belonging to both genders, between the ages of 1-85 years, from 11.2009 to 31.12.2013 were included in the study. RESULTS: Seven CNS tumour categories were as follows; tumours of neuroepithelial tissue (56.0%), tumours of the meninges (28.3%), tumour of the sellar region (2.6%), germ cell tumour (0.1), tumour of cranial and paraspinal nerves (5.4%), lymphomas and haematopoietic neoplasm (2.4%), metastatic tumours (4.9%), where histological types by age and gender showed great variability. Astrocytic tumours were the commonest neuroepithelial tumours (69.4%). Glioblastoma multiform forming the largest subtype of neuroepithelial tumours (40.4%) with a mean age at diagnosis being 47.1 years. Overall, males exceeded females in number of most of the CNS tumour types, however meningeal tumours were more frequently noted in females. CONCLUSIONS: Neuroepithelial tumours are commonest tumour and comprise more than half of all operated CNS tumours in our setup, followed by meningeal tumours. Glioblastoma multiforme is largest subtype of neuroepithelial tumour, and comprising 40.4% of all.

Asunto(s)

RESUMEN

BACKGROUND: Liposarcoma is a malignant tumour that arises in fat cells in deep soft tissue. This study was conducted to access the spectrum of liposarcomas METHODS: This descriptive study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January 2008 to 31st December, 2012 and included all the cases diagnosed as liposarcomas. Records of the malignant tumors of soft tissue that presented during this period were analysed and out of this spectrum of liposarcomas were studied. RESULTS: A total of 19367 malignant tumours were diagnosed during study period. Out of these, 615 were malignant soft tissue tumours. Out of these 106 cases were liposarcoma with an overall frequency of 0.54% of the malignant neoplasm and 17.24% of soft tissue sarcomas .The age ranged from 26-85 years. Out of these 106 cases 77 were male and 29 were female with a male to female ratio of 2.6:1. The most common tumour seen was pleomorphic liposarcoma (42.5%) followed by myxoid liposarcoma (22.6%), dedifferentiated liposarcoma (19.8%) and well differentiated liposarcoma (15.1%). Fifty five (51.9%) of liposarcomas originated in lower extremity, the second most commonly involved site was upper extremity (22.6%) CONCLUSION: Pleomorphic Liposarcoma is the commonest liposarcoma of extremities and their frequency is much high in our population.

Asunto(s)

RESUMEN

Extradural arachnoid cyst in the spine is an uncommon cause of spinal cord compression in the paediatric population. Most reported cysts have communication with the intrathecal subarachnoid space through a small defect in the dura. The reported child had spinal cord compression caused by a large spinal extradural arachnoid cyst in dorsal spine that did not communicate with the intradural subarachnoid space. Surgical excision of cyst was done with recovery of neurological deficit postoperatively.

Asunto(s)

RESUMEN

BACKGROUND: This study was carried out to determine the pattern of presentation of Polycystic ovary syndrome (PCOS) in patients presenting at our unit and to compare effects of clomiphene alone and in combination with metformin in management of PCOS. METHODS: This study was conducted from Jan 2001-2003 at Military Hospital, Rawalpindi. All patients presenting with infertility were evaluated with a view to select 100 patients of PCOS with the help of history of oligomenorrhoea, hirsuitism and acne. Diagnosis was confirmed by ultrasonography and hormone analysis (LH, FSH, prolactin, testosterone along with LH:FSH>2). The 100 selected patients were divided into two equal groups. One was given combined clomiphene citrate (CC) and metformin for ovulation induction and the other CC alone. These patients were followed for six cycles for ovulation and conception. Follicle tracking on ultrasonography and day-21 serum progesterone level were used to detect ovulation while conception was confirmed by urine pregnancy test, serum B-HCG level and ultrasonography for gestational sac. RESULTS: Hirsuitism and oligomenorrhoea were the two most common clinical features of PCOS. In the first group 34 patients (68%) ovulated as compared with 18 (36%) in the second group. In the first group 18 out of 34 women (52.9%) conceived as compared with only 8 out of 18 (44%) in the second group. The difference was significant at >0.05 when ovulatory and pregnancy responses were compared among two groups. All patients tolerated metformin well and no teratogenic effects were observed in patients who conceived after treatment with metformin. CONCLUSION: A combination of metformin and clomiphene citrate significantly increases the ovulation and conception rates in these patients.

Asunto(s)

RESUMEN

OBJECTIVE: To identify the risk factors for high altitude pulmonary oedema. DESIGN: A case control study. PLACE AND DURATION OF STUDY: The study was conducted in the Department of Medicine, Military Hospital, Rawalpindi during October 1998 to October 2000. SUBJECTS AND METHODS: One hundred serving army personnel between 20 to 50 years of age were divided in two groups. First group comprised of 50 patients who developed high altitude pulmonary oedema at 4000 meters height and above. Second group consisted of 50 control subjects who accompanied the patients. Detailed history was obtained regarding height of native dwelling, rate of ascent, amount of exertion and preceding respiratory tract infection. The findings of both the groups were compared and statistically analyzed by application of Pearson's chi-square test. Difference was considered significant when p-value was < 0.05. RESULTS: All the subjects were male. Average age of the indexed group was 29.4(+/- 4) years as compared to 27(+/- 5) years in the control group. Six patients (12%) were highland dwellers whereas 44 patients (88%) were inhabitants of lower heights. Average rate of ascent from 4000 meters to 4500 meters of the indexed group was 5(+/- 2) days while in control group it was 10(+/- 3) days. Twenty cases (40%) had history of severe exertion whereas such history was not present in any of the control group subjects. Only 2 patients had signs and symptoms of preceding respiratory tract infection. CONCLUSION: Rapid rate of ascent, extreme physical exertion, low height of native dwelling and preceding respiratory tract infection are important risk factors for the development of high altitude pulmonary oedema. Proper acclimatization with gradual ascent plays important role in preventing this potentially fatal condition.

Asunto(s)