Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan. MATERIALS AND METHODS: PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations. RESULTS: A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated. CONCLUSION: Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

Clinicopathological study of solid pseudopapillary tumor of pancreas

Objective: To study the morphological and immunohistochemical features of solid pseudopapillary tumor of pancreas. Study Design: Retrospective study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre from Jun 2016 to Mar 2017

Material and Methods: Sixty-four patients [n=64] including 61 females and 3 males with pathological diagnosis of solid pseudopapillary tumor were selected from archives of Shaukat Khanum Memorial Cancer Hospital and Research Center for the period of 2000-2017. For the sample selected, their morphological features and immunohistochemical profile were reviewed and analyzed. The morphological features are considered as gold standard for the diagnosis

Results: The mean age was 33 years [range 8-50 years]. Immunohistochemical stains were performed on formalin fixed paraffin embedded section of 55 cases. Pancytokeratin was performed on 8 cases, out of which only 2 cases showed positivity. CD10 was performed on 14 cases, out of which only 12 cases showed positivity. Neuron specific enolase [NSE], CD56, vimentin, progesterone receptor [PR] and beta catenin were performed on 8, 5, 3, 13 and 16 cases respectively and showed positivity in majority of cases. Neuroendocrine markers [chromogranin and synaptophysin] were performed on 25 and 6 cases, from which it showed weak positivity in 3 cases. CD99 was performed on 19 cases and showed characteristic dot like staining

Conclusion: Among the immunohistochemical stains, CD99 had a specific dot like staining pattern and was used as a first line marker in diagnosis

Correlation of histological risk assessment/ scoring system with lymph node metastasis and recurrence/progression of diases in oral squamous cell carcinoma

To correlate the scoring system using histopathologic parameters; worst pattern of invasion [WPOI], lymphocytic host response [LHR] and peri-neural invasion [PNI], with disease recurrence, overall survival and cervical lymph node metastasis in OSCC patients. Study Design: Cross sectional. Department of Histopathology, Shaukat Khanam Memorial Cancer and Research Hospital, Lahore in collaboration with Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi. Study completed in 2 years. A "Risk Scoring system" was applied to 50 cases of OSCC with 2 years follow-up data, based on histopathologic parameters WPOI, LHR and PNI. The cases were divided into High risk and Non- High risk categories according to the specified parameters and then correlated with disease recurrence, overall survival and cervical lymph node metastasis. Results: There were 7 low risk, 17 intermediate risk and 26 high risk cases. No correlation was seen between the risk groups and disease recurrence, overall survival or cervical lymph node metastasis. However, when assessing the individual parameters, significant correlation was observed between PNI with disease recurrence [p = 0.03], and between WPOI and overall survival [p = 0.02] and cervical lymph node metastasis [p = 0.005]. The individual parameters, peri-neural invasion and worst pattern of invasion are observed to be significant prognostic indicators in OSCC patients. A study with a larger number of cases is required to truly assess the value of the scoring system in Pakistani patients

Diagnostic utility of endoscopic ultrasound guided aspiration cytology in evaluation of pancreatic masses

To determine the sensitivity and specificity of endoscopic ultrasound [EUS] guided fine needle aspiration cytology [FNAC] in the evaluation of pancreatic masses. Analytical study. Department of Pathology, Shaukat Khanum Cancer Hospital and Research Centre, from January 2006 to June 2011. Patients of either gender aged above 18 years who underwent EUS guided FNAC of pancreatic masses detected on abdominal CT, were included in the study. Biphasic abdominal CT scans were carried out for all the patients, followed by EUS guided FNAC. All material aspirated for cytologic evaluation was assessed for sample adequacy on-site, followed by formal examination for diagnostic purposes. The mean age of patients tested was 58.94 +/- 12.84 years with age ranging from 23 to 78 years. Regarding gender 23/42 [54.76%] patients were male and 19/42 [45.24%] were female. Out of 42 cases, 27 [64%] cases were diagnosed as adenocarcinoma, 4 [9.5%] as benign, 4 [9.5%] as mucinous cystic neoplasm, 2 [4.7%] as chronic pancreatitis, 2 [4.7%] as non-diagnostic, 2 [4.7%] as atypical cells seen and 1 [2.38%] as non-Hodgkin's lymphoma. The results were in full concordance with radiologic findings. EUS guided FNA is an excellent procedure for evaluation of pancreatic masses. The overall sensitivity of this procedure is 89% and the specificity is 67%

Dengue fever outbreak in Lahore

Dengue fever has now affected all the major cities of country. About 41,354 patients underwent antibody screening for dengue fever from Shaukat Khanum Memorial Cancer Hospital, Lahore, during the epidemic period [October 1st 2010 to December 20[th] 2010]. Out of them, 1294 [3.1%] patients were positive for IgM antibodies, and 124 [0.3%] for IgG antibodies. A total of 722 [1.7%] patients were borderline positive for IgM antibodies and 108 [0.26%] were borderline positive for IgG antibodies. Dengue fever has emerged as a global problem over the last 5 years. It has also hit Lahore badly especially after the floods in 2010. High index of suspicion should be there in case of related symptoms

Solid neuroendocrine carcinoma of the breast

Primary neuroendocrine carcinoma of the breast is a rare disease that accounts for less than 5% of all cancers arising from the breast. The tumour cells stain positively for chromogranin and synaptophysin. This report describes the occurrence of infiltrating ductal carcinoma of breast with neuroendocrine differentiated tumour in 37 year old female. Early small cell neuroendocrine cancer of the breast that is treated with surgery and adjuvant chemotherapy shows an increased disease-free survival. She is planned for anthracycline/cyclophosphamide based chemotherapy followed by etoposide/platinum based chemotherapy. As her tumour showed ER/PR positivity, she will be given hormonal therapy subsequently, however, more extensive review is required to define a standard treatment protocol for this rare neoplasm.