Editorial: COVID-19 pandemic, the second wave, and provision of cancer services.

SARS-CoV 2 (COVID-19) pandemic continues to have a debilitating effect on health worldwide. This editorial provides an overview of the provision of cancer services at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, and Peshawar.&nbsp

INDOLEAMINE 2,3 DIOXYGENASE AS AN IMMUNOTHERAPEUTIC TARGET BRINGS A NEW HOPE FOR CANCER PATIENTS

Therapeutic manipulation of immune system in cancer has been an extensive area of research in the field of oncoimmunology. Immunotherapy helps the immune system to combat against cancer. Tumour cells take an edge of immunosuppressive mechanisms and inhibit antitumour immune responses. Indoleamine 2,3 dioxygenase (IDO) is an immunosuppressive enzyme which is involved in tumour immune escape mechanism in various cancers. IDO can degrade the tryptophan into kynurenines and has an ability to enhance the immune tolerance through mammalian target of rapamycin pathway general control nonderepressible 2 (GCN2) pathway and induction of regulatory T (T-regs) cells. IDO-induced T-regs suppress the local immune responses in the tumour microenvironment and promote metastasis. IDO overexpression in various cancers is associated with poor prognosis. Several preclinical and clinical trials have been proceeding and recommend that IDO inhibitor may be an influential tool against a wide range of cancers. IDO inhibitors as adjuvant therapeutic agents may also have clinical implications. Thus, IDO has the potential to be used as an immunotherapeutic target. This review discusses the promising role of IDO in cancer and its implication in immunotherapy.Key words: Breast cancer, colorectal cancer, haematological malignancies, immunotherapy, indoleamine 2,3-dioxygenase, pancreatic cancer, prostate cance

Cancer in Faisalabad and Nankana Sahib, Pakistan: 2017-2019; an Observational study

Introduction: The Punjab Cancer Registry's catchment area includes the districts of Faisalabad and Nankana Sahib. It is an observational, descriptive study that covers the three years from 2017 to 2019, evaluating the distribution of cancer in these two districts. Material and Methods: Data on incident cancer cases diagnosed between 2017 and 2019 among residents of Faisalabad and Nankana Sahib in Pakistan, reported by the participating centers of the Registry, were reviewed retrospectively. Figures and proportions for adults, children, and adolescents were computed. Results: During 2017 and 2019, 5,678 cases were reported from Faisalabad and 390 from Nankana Sahib, with over 50% seen in females. In both districts combined, among adult females, cancers of the breast, reproductive system, and hepatobiliary system were commonly diagnosed, while cancer of the lip/oral cavity/pharynx, hepatobiliary system, and non-Hodgkin lymphoma were the leading diagnoses among adult males. In children and young adults (0-19 years), acute lymphoblastic leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma were the most common diagnoses. Conclusion: The cancer distribution reported from Faisalabad and Nankana Sahib is of utmost importance. However, the underreporting of cancer cases cannot be ruled out. More input from the collaborators is needed to ensure the completeness of cancer surveillance in the region

THE ROLE OF INTRAOPERATIVE FROZEN SECTION OF SENTINEL LYMPH NODES IN UPFRONT BREAST CONSERVATION CANCER SURGERY

Objective: Sentinel lymph node biopsy is the standard of care in clinically negative axilla in breast cancer patients for which frozen section (FS) is routinely performed intraoperatively. The objective of this study was to justify the use of FS in terms of number of tests performed and their impact on decision-making and cost saving. Materials and Methods: We retrospectively reviewed our prospectively maintained data from January 2014 to January 2018 for intraoperative FS in upfront breast conservation surgery patients. Results: A total of 357 patients were studied. All were female. Median age was 50 years (24–84). Mean tumour size was 29.11 mm. Numbers of sentinel lymph nodes identified were 1 in 50 (14.2%) patients, 2 in 121 (33.89%) patients and ≥3 in 186 (52%) patients. Number of positive sentinel lymph nodes was 0 in 264 (73.9%) patients, 1 in 62 (17.4%) patients, 2 in 20 (5.6%) patients and ≥3 in 11 (3.08%) patients. Axillary lymph node dissection (ALND) was offered to 30 (8.4%) patients as per the American College of Surgeons Oncology Group Z0011. The results for ALND showed that only 8 (2.3%) out of 30 patients had positive nodes identified in the additional axillary nodes dissected. Sensitivity of FS was 97% and specificity was 98.86%. False-negative rate was 3.22%. Conclusion: Intraoperative FS can be safely omitted in early breast cancer patients undergoing upfront breast conservation cancer surgery due to high sensitivity and specificity leading to low false-negative rates. ALND can be performed as a second operation as warranted only in a minority of patients. Key words: American College of Surgeons Oncology Group Z0011 trial, axillary lymph node dissection, intraoperative frozen section, sentinel lymph node biops

Soft Tissue Tumours with Epithelioid Morphoogy

 To study the morphologicalfindings of soft tissue sarcomas with epithelioidmorphology and their distribution with respect tothe age, gender and location

Presentation of Acute Lymphoblastic Lymphoma and Colorectal Carcinoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome (CMMRD): a Case Report with Literature Review

Introduction: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive disease-carrying an increased risk of cancers (pediatric tumors of central nervous system, haemato-lymphoid malignancies along with gastrointestinal (GI) cancer(s), which are usually seen in the second and third decade) leading to syndromic presentation. Causal mutations are detected in DNA mismatch repair (MMR) genes, including MLH1, PMS2, MSH2, and MSH6 that are also known for their established role in Lynch syndrome. We describe a case of CMMRD with an earlier (first decade of life) presentation of mediastinal acute lymphoblastic lymphoma and colorectal malignancy. Case Presentation: A five-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple café au lait macules (CALMs) on the lower back, history of parental consanguinity with the death of three sisters due to brain tumor within 6 months of diagnosis. Computerized tomographic (CT) scan chest revealed a huge mediastinal mass. The patient underwent a trucut-biopsy of the mass. The results were significant for a pre T-cell acute lymphoblastic lymphoma. Suspicion of CMMRD was raised based on a combination of factors described above. A panel of mismatch repair (MMR) proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumor cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed sub-acute intestinal obstruction due to a stenosing polypoidal circumferential tumor in the mid-sigmoid colon found on flexible sigmoidoscopy that was followed by endoscopic biopsies and insertion of a fully-covered self-expanding metallic adult biliary stent with a diameter of 10 mm and length of 6 cm leading to immediate relief of obstruction. Biopsies revealed adenocarcinoma with neuroendocrine differentiation. Metastatic tumor deposits were seen in the omentum, anterior abdominal wall, and the left peritoneal wall. Practical Implications: Earlier (first decade) presentation of gastrointestinal malignancy warrants that an earlier screening through radiological scans for any possible tumors and MMR protein expression analysis (loss in tumor plus normal non-tumor cells) are essential in patients having CALMs and family history of pediatric tumors

Primary Adenosquamous Carcinoma of Prostate: A Rare Aggressive Tumor

Adenosquamous carcinoma is an aggressive tumor of prostate with only 30 cases reported so far in literature. We present a case of this rare entity that was seen in our department. A 70 years old male presented with urinary outflow obstruction and slightly raised PSA levels [5mg/ml (normal; 0-4 mg/ml)]. Transuretheral resection of prostate was done and specimen was sent to our department. Histologically, it composed of both malignant squamous and glandular components. Squamous component showed large tumor cells with abundant cytoplasm and nuclei with prominent nucleoli. Glandular component showed tumor cells arranged in acinar pattern, predominantly in cribriform architecture. As the current guidlines, Gleason grading is not required for adenosquamous carcinoma of prostate. The case was reported as the adenosquamous carcinoma of prostate. This rare tumor has an extremely poor prognosis with most of the patients dying within 1 year of diagnosis

Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan

Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases