Dermatological Manifestations of COVID-19 in Patients Reporting to a Tertiary Care Hospital in Rawalpindi, Pakistan.

Introduction The clinicopathological description of dermatological manifestations of COVID-19 leaves much to be desired. There is a need to determine their association with disease severity, outcome, and other clinical variables. Objectives The objectives of this study are to record and histopathologically examine the cutaneous manifestations of COVID-19 and correlate these to age, disease severity, and mortality. Methods All confirmed COVID-19 patients admitted to a single tertiary healthcare hospital in Rawalpindi, Pakistan, were included. Their diseases were classified as mild, moderate, severe, and critical. The recent onset skin eruptions in these patients were recorded via photographs along with relevant clinical data. The photographs were independently reviewed by a group of three dermatologists without knowledge of the clinical information. The skin manifestations were divided into disease-specific and nonspecific categories using an already defined algorithm. Histopathological examination of skin manifestations was conducted. Results A total of 23% (n=47) had "new" skin manifestations. Specific skin findings were seen in 21.6% (n=44), which consisted of ecchymosis/purpura in 50% (n=22), maculopapular exanthem in 18% (n=8), livedo reticularis in 16.2% (n=7), ischemia/gangrene in 16.2% (n=7), perniosis in 15.9 % (n=7), vesiculo-bullous rash in 9% (n=4) and urticaria in 4% (n=1). Non-specific findings were seen in 6% (n=13) and included bedsores, dermatitis passivata, dryness, herpes labialis, oral ulcerations, and nasogastric tube-induced ulcerations. There was a significant association (p=0.03) between disease severity and specific skin lesions. Ischemia/gangrene was significantly associated with COVID-19 disease severity and mortality. Vesiculobullous lesions were associated with higher mortality, though not with disease severity. Livedo reticularis had a higher-than-expected count in critical disease, albeit statistically insignificant. The association of maculopapular exanthem and ecchymosis/purpura with severe/critical disease was statistically insignificant. Urticaria was significantly associated with low disease severity. Mean age with specific manifestations was 56.86 ± 15.81 and with nonspecific/without any manifestations was 42.58 ± 16.96, a highly significant difference, with p-value < 0.001. Old age (>60 years) was significantly associated with ecchymosis (p=0.038), maculopapular exanthem (p=0.021), and vesiculo-bullous rash (p=0.029). Histopathology varied according to the type of skin lesion. Conclusions Dermatological manifestations coexist in many patients and tend to appear more in severe cases of COVID-19 among the older age group and only minimally in mild/moderate cases. Their presence could help set prognostic criteria of COVID-19 disease in the future.

Next Generation Sequencing-Based Germline Panel Testing for Breast and Ovarian Cancers in Pakistan.

BACKGROUND: Pathogenic germline mutations in BRCA1/2 constitute the majority of hereditary breast and/or ovarian cancers worldwide. Incidence and mortality rate of breast and ovarian cancers in Pakistani women is high. Thus, to establish the diagnosis for targeted therapy in Pakistan, we conducted Next-generation sequencing-based germline testing for the detection of BRCA1/2 oncogenic variants associated with breast and ovarian cancer subtype. METHODS: Peripheral blood of 24 women, diagnosed with breast and epithelial ovarian cancers, was taken from the recruited cases with the consent of performing germline genetic testing. DNA was isolated from the peripheral blood and subjected to indexed BRCA Panel libraries. Targeted NGS was performed for all coding regions and splicing sites of BRCA1 and BRCA2 genes using AmpliSeq for Illumina BRCA Panel and Illumina MiSeq sequencer (placed at AFIP). Analysis of the sequencing results has been done by using Illumina bioinformatics tools. RESULTS: We detected 421 variants having a quality score of 100 in all cases under study. The list of identified variants in BRCA1 and BRCA2 genes was narrowed down after filtering out those which did not pass q30 and those with a minor allele frequency (MAF) > 0.05 based on gnomAD browser. To classify these variants, clinical significance was predicted using external curated databases. As a result, we interpreted (n = 4) 16.7% pathogenic variants in BRCA1 and (n = 6) 25% variants of uncertain significance (VUS) in both genes. Descriptive statistics depicted that the age and BMI of BRCA positive cases are less than BRCA negative cases. CONCLUSION: Our findings exhibit an initial report for the NGS based cancer genetic testing in Pakistan.  This will enable us to pursue screening and diagnosis of hereditary BRCA mutation utilizing the latest state-of-the-art technique locally available in Pakistan ultimately resulting in targeted cancer therapy.

The Frequency of Double Expresser in Selected Cases of High Grade Diffuse Large B-Cell Lymphomas.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCL) are fast-growing non-Hodgkin lymphomas that affect B-lymphocytes. Double expressor DLBCL is the concomitant expression of Myc and Bcl-2 proteins during lymphomas which results in poor prognosis of patients. This study aimed to determine the frequency of double expresser in high grade diffuse large B-cell lymphomas. MATERIALS AND METHODS: The study was conducted on 74 cases (54 males (68.4%) and 20 females (25.3%)) of DLBCL between August 2018 to January 2019. The mean age of the 74 patients was 51.7 years + 18.5. Expression of proteins c-Myc, Bcl-2 and Bcl-6 were evaluated by immunohistochemistry. The involvement of primary lymph node was reported in 38 cases (51.3%) whereas, extra nodal site was observed in 22 cases (29.7%). Among the primary sites, the cervical lymph node enlargement was the most frequent site of presentation. RESULTS: The rearrangement pattern was studied among 74 patients, 35 (47%) were found to have either one of the rearrangements i.e. Myc, Bcl-2, or Bcl-6. On the other hand, 14 (18.9%) had shown double rearrangements i.e. Bcl-2 and c-Myc (11 cases) and Bcl-6 and c-Myc (3 cases). The Bcl-2 and Bcl-6 rearrangements were demonstrated by 12 cases whereas 2 cases (2.7%) indicated all three types of rearrangements i.e. c-Myc, Bcl-2, and Bcl-6. In 11 cases the Bcl-2 and c-Myc rearrangements were found to be Bcl-2 > 50% and c-Myc > 40% and demonstrating the overall frequency of double expressers as 14.8%. The prognosis of the mentioned cases was extremely poor, median survival of 10 months. CONCLUSION: The concurrent expression of Bcl-2 and c-Myc was found to be 14% (level of expression for Bcl-2 > 50% and c-Myc > 40%) which is potentially a significant health burden and an emerging threat.

Squamous Cell Carcinoma Arising in Background of Mature Cystic Teratoma.

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.

Immunohistochemical Expression of Epidermal Growth Factor Receptor and c-Kit in Triple Negative Breast Cancer.

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.

Spectrum of liposarcomas-a study of 106 cases.

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.