Immunohistochemistry of mammary Paget's disease. Cytokeratin 7, GATA3, and HER2 are sensitive markers.

OBJECTIVES: To investigate the expression of various immunohistochemical markers in Mammary Paget's disease (MPD) and MPD-associated breast carcinoma and to evaluate their value in establishing the diagnosis. METHODS: This retrospective descriptive study was carried out at King Faisal Specialist Hospital and Research Center and King Khalid University Hospital, Riyadh, Saudi Arabia. All MPD cases reported between January 2010 and June 2016 were selected from the surgical pathology records.  Immunohistochemical staining was carried out for cytokeratin 7 (CK7), GATA-binding protein 3 (GATA3), human epidermal growth factor receptor 2 (HER2), and estrogen, and progesterone receptors. Results: Twenty-two cases of MPD and 20 cases of MPD-associated breast carcinoma were included. CK7 was positive in 95% (21/22) cases of MPD and in all (20/20) cases of associated breast carcinoma. Similarly, GATA3 was expressed in 95% cases of both MPD (21/22) and associated breast carcinoma (19/20). Human epidermal growth factor receptor 2 was also overexpressed in 90% cases of MPD (20/22) and associated breast carcinoma (18/20). Estrogen stained positive in 27% cases of MPD (6/22) and 30% of cases of associated breast carcinoma (6/20). Progesterone receptors was not positive in any case of MPD; however, it was seen positive in 25% cases of MPD-associated breast carcinoma (5/20). CONCLUSIONS: CK7, GATA3, and HER2 are widely expressed in MPD and MPD-associated breast carcinoma. These markers can be used for the immunohistochemical confirmation of MPD including CK7-negative cases.

Clinical comparison of two human papillomavirus detection assays: GenoFlow and reverse line blot.

INTRODUCTION: Human papillomavirus (HPV) infection is typically critical in the oncogenesis of cervical cancer. However, available HPV detection kits differ in their ability and sensitivity to detect various types of HPV, and this variability has led to inconsistencies in the reporting of the geographic prevalence of HPV types, especially in developing countries. Here, we compared results of the recently developed GenoFlow HPV array test, which detects 33 HPV genotypes, to those of the well-established reverse line blot (RLB) assay, which detects 23 HPV types. METHODOLOGY: In total, 608 cervical specimens with cytology results ranging from normal to cancer were collected using an endocervical brush from women attending outpatient clinics in Riyadh, Saudi Arabia. RESULTS: Sixty-nine specimens (11%) were positive for HPV. HPV genotype detection using the GenoFlow test had a sensitivity of 62% and a specificity of 100%. Overall agreement between the two HPV genotyping methods was 97%, with a concordance rate of 95%. Among the GenoFlow test results, 2% indicated additional HPV types that were not detected in the RLB assay, whereas the GenoFlow test missed 0.3% of the HPV types that were detected by the RLB; however, both tests were in agreement in detecting all major HPV types. CONCLUSION: The GenoFlow test was reliable, with results comparable to the RLB test. However, because the GenoFlow test is less labor-intensive and takes less total time (3 hours), it is a promising, affordable alternative to the RLB for HPV diagnosis and screening programs.

Molecular subtyping of mammary Paget's disease using immunohistochemistry.

OBJECTIVE: To evaluate the molecular subtypes of Mammary Paget's disease (MPD) and the associated breast carcinomas. METHODS: This retrospective study was carried out at King Khalid University Hospital and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Data from MPD patient cases from January 2010 to June 2016 were reviewed. The molecular subtypes were determined based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression with immunohistochemical staining. The relative frequencies of the luminal A and B, HER2-enriched and basal-like molecular subtypes were calculated and compared for MPD and the associated breast carcinomas. Results: Among 22 patients with MPD, HER2-enriched was the most frequently occurring molecular subtype and was observed in 11 (50%) patients. Mammary Paget's disease was classified as basal-like in 5 (22.7%) patients, and luminal A and B were each detected in 3 (13.6%) patients. The molecular subtype of MPD corresponded with the subtype of the associated breast carcinoma in 18 out of 20 patients (90%). CONCLUSIONS: The HER2-enriched subtype is the most frequently occurring molecular subtype in MPD. The molecular subtype of the associated breast carcinoma is usually similar to that of MPD. The molecular subtypes vary between MPD associated breast carcinoma and overall breast carcinoma. The HER2-enriched subtype is the most frequently occurring subtype of MPD associated breast carcinoma, while luminal subtypes are more common in overall breast carcinoma.

Spectrum of the KIT Gene Mutations in Gastrointestinal Stromal Tumors in Arab Patients

Background: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract, which originate from the interstitial cells of Cajal. These tumors are characterized by expression of CD117 and CD34 antigens and activating mutations in the KIT and PDGFRA genes. While KIT and PDGFRA mutations have been extensively studied in other populations, the spectrum of mutations in Arab patients remains unknown. The study aimed at determining the distribution of KIT and PDGFRA mutations and phenotypic characterization of the gastrointestinal stromal tumors in Arab patients. Methods: Sanger sequencing was used to analyze 52 archived gastrointestinal stromal tumors for mutations in the KIT and the PDGFRA genes. Tumor descriptions were obtained from the clinical reports of patients. Results: In these patients, most tumors occur in the stomach, followed by the rest of the digestive tract. A vast majority of tumors express the CD117 and CD34 antigens. Sequencing of the KIT and PDGFRA genes identified five non-synonymous mutations and 26 deletions (25 novel) in exon 11 of the KIT gene. All non-synonymous mutations and deletions affect the juxta-membrane domain, which is known to inhibit ligand-independent activation of the KIT receptor. No mutations were found in the PDGFRA gene. Conclusions: Molecular profiling of the gastrointestinal stromal tumors in Arab patients identified a unique spectrum of mutations in exon 11 of the KIT gene. These data are important for the diagnosis and management of patients of Arab ethnic origin.

Clinicopathological features of breast angiosarcoma: A 16-years single-institution experience.

BACKGROUND: Breast Angiosarcoma is a rare type of malignancy arising from endothelial cells lining blood vessels, accounting for 1% of all soft tissue breast tumors. This retrospective study describes the clinical pathological features and clinical management and outcomes of a series of 5 patients with primary and secondary Angiosarcoma of the breast present to King Faisal Specialty Hospital and Research Center during the last 16 years. METHODS: A retrospective review of our institution's pathology database was conducted and all patients who had a pathologically confirmed breast angiosarcoma were included in this study. The patient's data, including demographic characteristics, pathological features, clinical management history and clinical outcomes were collected. RESULTS: Five patients were diagnosed with Breast Angiosarcoma (one secondary and four primary cases). The median age of patients with primary angiosarcoma was 22 years (range 13-25 years). All primary cases were presented late as post-excisional biopsy at local hospitals. Median tumor size was 6cm (range 4.0-17.0cm). All primary angiosarcoma patients had total mastectomy. Three-year disease-free survival (DFS) of patients with primary angiosarcoma was 25%. 5-year surviving rate of primary angiosarcoma was 50%. Recurrence was observed in three of the patients with primary Angiosarcoma and in the case of post irradiation Angiosarcoma. CONCLUSIONS: Our study demonstrates that Breast Angiosarcoma exhibits high recurrence and mortality rates. Early detection, small tumor size, and clear surgical margins seem to be crucial factors for survival. Mastectomy with adequate tumor margin is recommended and close long-term follow-up is of utmost importance. Surgery for local recurrence may be potentially curative.

Recurrent thyroid storm induced by heretofore unrecognised causes in a patient with thyroid cancer.

An unusual encounter of a thyroid storm, on two separate occasions, is reported in a patient with metastatic differentiated thyroid cancer following initially direct trauma to, and later tumour embolisation of, a metastatic skeletal lesion. Shortly after a fall, our patient presented with pain and swelling in the right shoulder, high fever, change in mental status, anorexia, nausea and vomiting, tachycardia and dehydration. The laboratory tests were consistent with hyperthyroidism. As the patient improved, arterial embolisation of the large right humerus metastasis was performed to decrease the tumour burden. The patient, however, developed a similar clinical and biochemical picture to that at her presentation, with a very high free thyroxine (T(4)) level, a few days after successful embolisation. Treatment of the thyroid storm was initiated and the patient eventually improved. Awareness of such occurrences is helpful in early diagnosis and effective management of this potentially fatal complication.

Gene expression profiles of the fibroblasts from breast tumors and normal tissue compared with the tumor expression profiles.

OBJECTIVE: The study was designed to examine whether the gene expression profiles of fibroblast cell lines, established from the tumor and the normal tissue from the same breast, exhibit any similarities with the profiles of the original tissues. METHODS: Fibroblast cell lines were established from invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) of the breast and the adjacent normal tissues. Isolated total RNA from the cell lines and tissues were used to prepare labeled cDNA which was hybridized to Becton Dickinson Atlas microarrays for obtaining profiles of expressed genes. The profiles of tumors and cell lines were compared. This study was carried out at King Faisal specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, during 2004 and 2005. RESULTS: Alterations of expression of most of the genes in the tissues were not detectable in the cell lines. The expression of a lower number of genes was altered in DCIS compared with that in IDC tumors. CONCLUSION: Although the fibroblasts discharge important functions, their gene expression profiles do not represent the breast tissue to the extent that any prognostic decisions could be made.