Detection of genetic mutations in patients with breast cancer from Saudi Arabia using Ion AmpliSeq™ Cancer Hotspot Panel v.2.0.

Next-Generation Sequencing allows for quick and precise sequencing of multiple genes concurrently. Recently, this technology has been employed for the identification of novel gene mutations responsible for disease manifestation among breast cancer (BC) patients, the most common type of cancer amongst Arabian women, and the major cause of disease-associated death in women worldwide. Genomic DNA was extracted from the peripheral blood of 32 Saudi Arabian BC patients with histologically confirmed invasive BC stages I-III and IV, as well from 32 healthy Saudi Arabian women using a QIAamp® DNA Mini Kit. The isolated DNA was quantified using a Qubit™ dsDNA BR Assay Kit with a Qubit 2.0 Fluorometer. Ion semiconductor sequencing technology with an Ion S5 System and AmpliSeq™ Cancer Hotspot Panel v2 were utilized to analyze ~2,800 mutations described in the Catalogue of Somatic Mutations in Cancer from 50 oncogenes and tumor suppressor genes. Ion Reporter Software v.5.6 was used to evaluate the genomic alterations in all the samples after alignment to the hg19 human reference genome. The results showed that out of the 50 genes, 26 mutations, including 17 (65%) missense point mutations (single nucleotide variants), and 9 (35%) frameshift (insertion/deletion) mutations, were identified in 11 genes across the cohort in 61 samples (95%). Mutations were predominantly focused on two genes, PIK3CA and TP53, in the BC genomes of the sample set. PIK3CA mutation, c.1173A>G located in exon 9, was identified in 15 patients (46.9%). The TP53 mutations detected were a missense mutation (c.215C>G) in 26 patients (86.70%) and 1 frameshift mutation (c.215_216insG) in 1 patient (3.33%), located within exon 3 and 5, respectively. This study revealed specific mutation profiles for every BC patient, Thus, the results showed that Ion Torrent DNA Sequencing technology may be a possible diagnostic and prognostic method for developing personalized therapy based on the patient's individual BC genome.

Unusual Thyroid Nodule: A Case of Symptomatic Thyroid Schwannoma.

Primary thyroid schwannoma is a sporadic non-epithelial tumor of the thyroid gland. Most previous cases reported in the literature presented it as an asymptomatic neck mass. In this report, we describe a rare case of thyroid schwannoma in a 33-year-old female, presented as a left-side neck swelling, accompanied by a change in voice and difficulty swallowing. An ultrasound of the mass showed a large heterogeneous, predominantly cystic, nodule; in contrast to the usual predominantly solid nodule described in the literature. After several pre-operative diagnostic tests, including fine needle aspiration (FNA), the diagnosis remained unclear. In the end, the patient underwent a successful surgical excision of the mass, and the diagnosis of schwannoma was confirmed based on the histopathologic examination which revealed both type A and B Antoni cells as well as positive staining for S-100 protein.

Riedel's thyroiditis as a diagnostic dilemma - A case report and review of the literature.

Riedel's thyroiditis is a rare inflammatory process which not only involves thyroid gland but also the surrounding vital structures. It may also be associated with various forms of systemic fibrotic disorders. The exact etiology is not known, but currently, the most favored view is that of a localized form of the systemic fibrotic process. We report a case of Riedel's thyroiditis in a male patient, highlighting diagnostic challenges and a rare presentation of hypocalcemia and mimicking thyroid lymphoma. Clinical knowledge of such a presentation of Riedel's thyroiditis would enhance our ability to make a speedy diagnosis. Apart from avoiding aggressive surgical intervention, awareness of such a clinical entity may avoid complications and hence morbidity. Our case also highlights the difficulty in histological diagnosis which is vital to rule out malignancy and avoiding any major surgical intervention fraught with complications. Although the patient had a poor tolerance to Tamoxifen and Rituximab, however, his response to high dose steroids is the currently accepted treatment of choice. This case adds to the sparse literature available on the cytological diagnosis of RT and highlights the diagnostic challenge due to suspicious radiology findings.

Gaint phyllodes tumour with axillary & interpectoral lymph node metastasis; A rare presentation.

INTRODUCTION: Phyllodes tumors are rare fibroepithelial neoplasms of the breast, account for less than 1 % of all breast neoplasms, lymph node metastasis is even rare and routine axillary dissection is not recommended. Approximately 20 % of patients with malignant phyllodes tumors develop distant metastasis. CASE DESCRIPTION: A 45 years old premenopausal female, presented with a huge right breast mass for 3 years. Physical examination revealed a 40 × 46 cm, lobulated mass, fixed to the chest wall and multiple enlarged and mobile ipsilateral axillary lymphadenopathy. Core tissue biopsy revealed fibroepithelial & stromal proliferation suggestive of phyllodes tumor. The CT scan of the chest and the abdomen revealed bilateral pulmonary metastasis. She underwent palliative Modified Radical Mastectomy. Pathology demonstrated malignant phyllodes with osseous and chondroid metaplasia, the resection margins were clear and 6 out of 25 nodes were positive. Her post-operative recovery was uneventful and she received adjuvant chemo-radiotherapy. During 12 months follow up, no local recurrence was noted, but despite chemotherapy her pulmonary disease was increasing. DISCUSSION: Only a few cases of cystosarcoma phyllodes with lymph node involvement have been reported in the literature. Treves, Norris and Taylor's series have demonstrated the axillary node metastasis of less that 1 %. Since most sarcomas metastasize hematogenously, this finding explains why axillary metastasis is so rare. Hence most authors have concluded that removal of axillary lymph nodes is not warranted unless there are pathologically involved. CONCLUSION: Management of Phyllodes tumor presents the surgeon with challenges. Core tissue biopsy is a reliable method for pre-operative diagnosis. Imaging like CT scan and MRI help to evaluate the primary lesion as well as distant metastasis. The majority of these cases can be managed by simple mastectomy. Axillary lymph node metastasis is rare and dissection should be limited to patients with pathological evidence of tumor in the lymph nodes.

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study).

BACKGROUND: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. METHODS: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. RESULTS: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. CONCLUSIONS: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Neoadjuvant chemotherapy in locally advanced breast cancer.

OBJECTIVE: To assess the response to Neoadjuvant Chemotherapy (NAC) in Locally Advanced Breast Cancer (LABC) in terms of pathological response, overall survival and feasibility of breast conservation surgery. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: King Fahad Medical City (KFMC), Riyadh, from January 2009 to July 2012. METHODOLOGY: All patients of LABC who received NAC and underwent surgery were included. All these patients received the GORG001 regimen (FEC+Docetaxal+Cisplatin+/-Herceptin). After chemotherapy patients were offered surgery either Modified Radical Mastectomy (MRM) or Breast Conservation Surgery (BCS) +Radiotherapy. Patients were then followed to exclude local or distant metastasis. RESULTS were described in percentage. RESULTS: The median age at the time of diagnosis was 46.8 years. While complete response was achieved in 24 (44.4%) patients, 14 (25.9%) of the patients had partial response and 16 (29.6%) progressed clinically. Surgery was performed in these patients after NAC. Forty (74%) patients had MRM, 14 (25.9%) had BCS; all had axillary lymph node dissection. Invasive ductal carcinoma accounted for 92% of cases. Vascular invasion was present in 12 (22%) of the patients. Estrogen / progesterone receptor positivity was 61%. Thirty nine percent of the patients were Her2 positive. On an average, follow-up of 4 - 51 months in the MRM group, one patient had resection margin (deep) positive and was treated with adjuvant therapy. While in the BCS group after 3 - 26 months of follow-up, one patient had resection margin positive (medial margin) and underwent MRM, while no patient had local or distant metastasis in both the groups. CONCLUSION: NAC caused down staging of disease in LABC making more conservative surgery feasible. BCC should be considered as an option for treatment of LABC, however, longer follow-up is recommended.

Spontaneous gastric ulcer perforation and acute spleen infarction caused by invasive gastric and splenic mucormycosis.

Mucormycosis is a rare life-threatening fungal infection mostly affecting immunocompromised hosts. The main categories of human disease with the Mucorales are sinusitis/rhinocerebral, pulmonary, cutaneous/subcutaneous, gastrointestinal and disseminated disease. Other disease states occur with a much lower frequency and include cystitis, vaginitis; external otitis and allergic disease. We report a diabetic patient with comorbidities, who developed gastric perforation clinically indistinguishable from perforated peptic ulcer due to invasive gastric mucormycosis complicated by spleen infarction.