Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

The Long-Term Characteristics of Immunity Conferred by COVID-19 Using Antibody Tests.

Introduction Since December 2019, more than 184 Million cases and 3.97 Million COVID-19 related deaths have been reported around the world. Since these statistics are laboratory-based confirmed cases, the true burden of disease may be underestimated. Many populations like those who are regularly visiting health care facilities and those with end-stage renal disease (ESRD) for visiting dialysis units, patients with malignancies, on regular chemo and radiotherapy, and healthcare workers (HCW) are considered high risk for nosocomial COVID-19 re-infections. Objective To understand the long-term behaviour and protective efficacy of already formed anti-SARS-CoV-2 antibody against spike-S protein and nucleocapsid antigen in different populations keeping in view their risk of re-exposure and re-infection is high. To delineate seropositivity with respect to age, gender, and other co-morbidities like diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD)/ESRD as well as the general population. Methodology During the study, 480 cases of COVID-19 with a post-exposure antibody reactive were followed. These patients were followed on telemedicine for the development of reinfection symptoms and persistence of antibody response. Around 115 patients agreed for regular monitoring of their immunity against the COVID-19 virus through testing through the anti-SARS-CoV-2 antibody test. The rest of the patients were followed on telemedicine until the date of development of any re-infection, but none reported to have typical symptoms of COVID-19 along with positive polymerase chain reaction (PCR). Results Among 115 patients, the mean age was 42.44 + 15.755 years. 61.7% of patients were males and 66.1% were non-health workers while 26.1% of patients had DM/HTN or both. Among these patients, 76.5% had mild/no symptoms and antibodies were found present among 51.3% patients for 3-6 months. Only 2.6% of patients were re-infected. Significant association (p<0.05) of age was found with re-infection while insignificant association (p>0.05) of sex, co-morbidities, profession, symptoms, and persistence of antibodies with re-infection. Conclusion The study concluded that natural immune response was adequate to protect against reinfection as long as more than 9 months. It was more pronounced among patients with ESRD and those with severe disease. Surprisingly, among patients with haematological malignancies, either there was no seropositivity or a very weak positive antibody response. All other malignancies had similar seropositivity behaviour compared to the general population or other co-morbidity like DM, HTN, and coronary artery disease (CAD).

Bone Marrow Metastasis in Clear Cell Renal Cell Carcinoma: A Case Study.

Clear cell renal cell carcinoma (RCC) is the most frequently reported renal cell neoplasm, which commonly metastasizes to the lungs, bones, lymph nodes, liver, adrenal gland and/or brain. It is usually diagnosed as an incidental finding on radiological imaging, which can further be confirmed by histological examination of the neoplastic tissue. Bone marrow metastasis of renal cell tumors is a rare event and very few cases have been reported. Here we report an unusual case of a 68-year-male who presented with lytic bone lesions on imaging. This raised the suspicion of a bone marrow involvement by a hematolymphoid malignancy or metastatic disease and a bone marrow biopsy was performed. Incidentally, the biopsy revealed infiltration of bone marrow by clear cell RCC. The patient was referred to the oncology clinic where further workup was done which revealed a primary renal tumor.

Is TLE1 Expression Limited to Synovial Sarcoma? Our Experience at Shifa International Hospital, Pakistan.

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.

Clinical and genetic studies in patients with Lafora disease from Pakistan.

Lafora disease (LD) is progressive myoclonic epilepsy with late childhood- to teenage-onset. Mutations in two genes, EPM2A and NHLRC1, are responsible for this autosomal recessive disease in many patients Worldwide. In present study, we reported two unrelated consanguineous Pakistani families with Lafora disease (Families A and B). Affected individuals in both families presented with generalized tonic clonic seizures, intellectual disability, ataxia and cognitive decline. Diagnosis of Lafora disease was made on histo-pathological analysis of the skin biopsy, found positive for lafora bodies in periodic acid schiff stain and frequent generalized epileptiform discharges on electroencephalogram (EEG). Bi-directional sequencing in family A was performed for EPM2A and NHLRC1 genes but no mutation was found. In family B, Illumina TruSight One Sequencing Panel covering 4813 OMIM genes was carried out and we identified a novel homozygous mutation c.95G>T; p.32Trp>Leu of EPM2A gene which was found co-segregated in this family through Sanger sequencing. Structural analysis of this mutation, through different in silico approaches, predicted loss of stability and conformation in Laforin protein.

Flow Cytometric Analysis: Four-Year Experience in a Tertiary Care Centre of Pakistan.

PURPOSE:   This study summarizes a four-year experience from the analysis of hematolymphoid malignancies in Pakistani population using a database of six-colored flow cytometry. METHODS: A cross-sectional survey of 323 specimens of hematolymphoid malignancies using six-colored flow cytometry (FC) was carried out in Shifa International Hospital, Islamabad, Pakistan from June 2012 to June 2016. The criterion for specimen adequacy was that the cases have abnormal populations by FC, and the specimen age (time from biopsy to being examined by the six-color FC tube) of three days or less was to be included in the study. Clinical follow-up of greater than six months was required for a negative flow cytometric study without a subsequent biopsy. Data analysis was done using  Statistical Package for the Social Sciences (SPSS) version 21. One-way analysis of variance (ANOVA) was used to compare diagnosis with some antibodies used. RESULTS:   The number of specimen within certain age groups included were: 0-15 years; 111 (34.3%), 16-30 years; 65 (20.12%), 31-45 years; 47 (14.5%), 46-60 years; 46 (14.2%) and ≥ 60 years; 54 (16.7%). Hematological malignancies were documented in descending order of sequence with B-cell acute lymphoblastic leukemia (27.9%), acute myeloid leukemia (26.3%), chronic lymphocytic leukemia (13.3%), T cell acute lymphoblastic leukemia (7.7%), non-Hodgkin's lymphomas (5%), hairy cell leukemia (1.9%), chronic myeloid leukemia (0.3%), paroxysmal nocturnal hemoglobinuria (0.6%) and plasma cell dyscrasias (0.6%). The mean number of antibodies used were 12.68 ± 2.97. One-way ANOVA was used to compare diagnosis with some antibodies used. Statistical significance was found between diagnosis and number of antibodies used (F= 5.23 p<0.001). CONCLUSION:   B cell acute lymphoblastic leukemia is most commonly diagnosed at tertiary care units in Pakistan using six-colored flow cytometry. Adoption of these complicated techniques has reinforced the need for optimization and further enhancement of flow cytometric procedures.