Clinico-cytopathological subcategorization in thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance using the TIRADS and Bethesda classifications.

Introduction: Bethesda category III - atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous class of the Bethesda system for thyroid nodules. In order to clarify the therapeutic road for clinicians, this category was subclassified based on the cytopathological features. In this study, we evaluated the risk of malignancy, surgical outcome, demographic characteristics, and correlation of ultrasound features with the final outcome in patients with thyroid nodules based on AUS/FLUS subclassification. Method: After evaluating 867 thyroid nodules from three different centers, 70 (8.07%) were initially diagnosed as AUS/FLUS. The cytopathologists re-interpreted the FNA samples and subclassified them into five subcategories: architectural atypia, cytologic atypia, cytologic and architectural atypia, and Hürthle cell AUS/FLUS, and atypia, which was not specified. Based on the suspicious ultrasound features, an appropriate ACR TI-RADS score was allocated to each nodule. Finally, the malignancy rate, surgical outcomes, and ACR TI-RADS scores were evaluated among Bethesda category III nodules. Results: Among the 70 evaluated nodules, 28 (40%) were subclassified as Hürthle cell AUS/FLUS, 22 (31.42%) as cytologic and architectural atypia, 8 (11.42%) as architectural atypia, 7 (10%) as cytologic atypia, and 5 (7.14%) as atypia which was not specified. The overall malignancy rate was 34.28%, and the architectural atypia and Hürthle cell nodules displayed lower malignancy compared to other groups (P-Value<0.05). Utilizing ACR TI-RADS scores showed no statistical significance between Bethesda III subcategorization and ACR TI-RADS scores. However, ACR TI-RADS can be a reliable predictor for Hürthle cell AUS/FLU nodules. Conclusion: ACR TI-RADS helps evaluate malignancy only in the Hürthle cell AUS/FLUS subcategory of AUS/FLUS. Besides, cytopathological reporting based on the suggested AUS/FLUS subclassification could help clinicians take appropriate measures to manage thyroid nodules.

Invasive Orbital Squamous Cell Carcinoma in a Patient with Multiple Myeloma.

Background: Orbital squamous cell carcinoma (SCC) is a rare entity. It is often a result of local invasion of SCC originating from the skin, nasopharynx, nasal cavity, paranasal sinuses, conjunctiva, lacrimal glands, or sac or less commonly occurs through hematogenous metastasis. Herein, we report a patient with orbital SCC with a history of multiple myeloma (MM). Case presentation. A 45-year-old woman with a history of MM in the past two years presented to our clinic complaining of gradual right eye proptosis for six months. The relative afferent pupillary defect was detected in the right eye on her examination. Ocular movements of the right eye were limited in all directions. Orbital magnetic resonance imaging demonstrated an infiltrative mass in the right orbit extended from the anterior to the orbital apex and the optic canal. The patient underwent debulking, and a histopathology examination revealed SCC results. No other secondary site was found to be the origin of the tumor. Result: The patient underwent chemotherapy and subsequent radiotherapy. To our knowledge, this is the first report of concomitant MM and primary orbital SCC.

Ovarian ectopic pregnancy misdiagnosed as gestational choriocarcinoma: A case report.

INTRODUCTION: and importance: Choriocarcinoma is a highly malignant epithelial tumor with often distant metastasis. The clinical presentation of choriocarcinoma depends upon extend of disease and location of metastasis. CASE PRESENTATION: A 35-year-old multiparous woman was presented with severe pelvic pain, fatigue and cough. She was diagnosed with positive pregnancy due to elevated B-hCG and hyperechoic mass in right adnexa. CLINICAL DISCUSSION: Exploration surgery showed a larger mass on the right ovary. She was diagnosed with choriocarcinoma however CT scan showed metastasis of lungs, brain and pelvis. She underwent multiple session of chemotherapy, nonetheless, after 8 months, she passed away. CONCLUSION: Timely diagnosis and prompt treatment of choriocarcinoma is necessary to prevent mortality and bad prognosis. It should be differentially diagnosed with all the types of pregnancies.

Novel Variants and Copy Number Variation in CDH1 Gene in Iranian Patients with Sporadic Diffuse Gastric Cancer.

INTRODUCTION: The aim of this study was to survey the nucleotide changes and copy number variations (CNV) in the CDH1 gene in Iranian patients with sporadic diffuse gastric cancer (SDGC). MATERIALS AND METHODS: In this study, 28 patients were examined who upon gastrectomy had been diagnosed with SDGC according to the familial history and histopathological criteria which was confirmed by the pathologist. DNA extraction was performed from formalin-fixed paraffin-embedded tissues using a phenol-chloroform method following xylene deparaffinization. Determination of DNA sequence by Sanger was performed using PCR amplification of 16 exons and boundaries of intron/exon of CDH1 gene. Multiplex ligation-dependent probe amplification (MLPA) was performed on patients with pathogenic disorders in the sequence. RESULTS: In total, patients included 20 males and 8 females. Of all patients, 12 patients were under 45 years old (early onset gastric cancer, EODC) and 16 patients were older. The tumor was diagnosed in the early TNM stage (I, II) in six patients and in late stages (III, IV) in 19 cases. Altogether, 16 variants (three exonic with one new variant and 13 intronic with nine new variants) were found in DNA sequencing of the CDH1 gene in five samples. Also, using MLPA, a new duplication in exon 9 and one deletion in exon 2 were detected in two other patients. Altogether, CDH1 variants were identified in seven out of 28 patients (25%). CONCLUSION: Our study revealed several novel somatic variants in the CDH1 gene in Iranian patients with sporadic diffuse GC. Our data supports the hypothesis that mutations in CDH1 gene, and particularly the mutations we describe, should be considered, even in sporadic cases of gastric cancer. The presence of these mutations in patients raises important issues regarding genetic counseling and diagnostic test in DGC patients.

N-acetylcysteine, Ascorbic Acid, and Methylene Blue for the Treatment of Aluminium Phosphide Poisoning: Still Beneficial?

OBJECTIVES: Intentional and accidental intoxication with aluminium phosphide (ALP) remains a clinical problem, especially in the Middle East region. Considering the high mortality rate besides lack of any recommended first option drug for its treatment, this study was aimed to compare the therapeutic effects of N-acetylcysteine (NAC), vitamin C (Vit C), and methylene blue; both in isolate and also in combination, for the treatment of ALP intoxication in a rat model. MATERIALS AND METHODS: In this experimental animal study, 80 male Wistar rats in eight groups were intoxicated with ALP (12.5 mg/kg) and treated with a single dose of NAC (100 mg/kg) or Vit C (500-1,000 mg/kg) or methylene blue (1 mg/kg/5 min, 0.1%) or two of these agents or all three of them (controls were not treated). Rats were monitored regarding the parameters of drug efficacy as increased survival time and reduced morbidity and mortality rate for 3 consecutive days to ensure toxin neutralization. Macroscopic changes were recorded and biopsy sections were taken from brain, cerebellum, kidney, liver, and heart for microscopic evaluation regarding cellular hypoxia. RESULTS: The mean survival times of rats exposed to ALP and treated with VitC + NAC was 210.55±236.22 minutes. In analysis of survival times, there was a significant difference between Group 5 which received VitC + NAC and the other groups (P < 0.01). Serum magnesium levels after death were higher than normal (P = 0.01). CONCLUSIONS: Despite the higher survival rate of antioxidant-treated rats compared with controls, this difference was not statistically significant.

Proliferative index using Ki-67 index in reactive mesothelial versus metastatic adenocarcinoma cells in serous fluid.

BACKGROUND: The cytological diagnoses of serous effusions are usually made by routine cytomorphology with certainty. However, overlapping cases sometimes exist between reactive mesothelial and adenocarcinoma cells. We tried to evaluate the diagnostic utility of proliferative index using a Ki-67 monoclonal antibody in distinguishing between reactive mesothelial cells and adenocarcinoma in serous effusions. MATERIALS AND METHODS: Paraffin blocks and H and E stained slides of peritoneal and pleural fluid cell blocks were retrieved from cytology archive of Alzahra Hospital, Medical University of Isfahan, between 2006 and 2010, from among 1025 slides which were screened to ascertain their appropriate diagnoses. Among of these 80 paraffin-embedded cell blocks, 40 cases for each reactive and adenocarcinoma groups were selected. The proliferative index was calculated by using the Ki 67 monoclonal antibody against nuclear proteins. RESULTS: The mean ages of the patients in the reactive mesothelial and adenocarcinoma groups were 60.58 and 58.45 years, respectively. The gender distribution for the malignant group included 23 cases (%57.5) of females and 17 cases (42.5%) of males. This ratio for reactive group included 14 cases (35%) and 26 cases (65%). The mean of Ki-67 index in adenocarcinomatous cells was 17.15 (SD=15.11) and in reactive mesothelial cells was 3.58 (SD= 3.59) (P=0.001). We consider to using the proliferative marker of Ki-67 on benign and malignant lesions revealed 12% as cut off level. The means of Ki-67 index according to serousal spaces were included: Pleura: 10.56 (SD= 13.06) and peritoneum: 10.03 (SD= 12.78), (P=0.9). CONCLUSION: Ki-67 index is useful immunostaining panel for differentiation of mesothelial and adenocarcinoma cells in malignancy like ovarian carcinoma that sometimes mimics mesothelial morphology.

Diagnostic value of E-cadherin and fibronectin in differentiation between reactive mesothelial and adenocarcinoma cells in serous effusions.

BACKGROUND: One of the problems in studying serous effusion cytological samples is differentiation of reactive mesothelial cells from metastatic adenocarcinoma cells. MATERIALS AND METHODS: In this study, the immunohistochemical diagnostic value of E-cadherin and fibronectin markers for differentiation of these 2 groups of cells was studied. 50 cell block samples prepared from serous effusions were examined. Based on clinical and histological studies, 25 cases had primary carcinoma, and the other 25 were proved to be benign effusion cases. All the cases were studied for E-cadherin and fibronectin immunostaining using an envision technique. Statistical analyzes were performed employing Chi-square and exact Fisher tests, using SPSS software (version 16). RESULTS: 24 of the 25 benign cases were stained with fibronectin and 2 with E-cadherin, whereas from among the 25 metastatic cases, 2 reacted to fibronectin and 22 to E-cadherin. Considering the staining of the 2 markers under conditions that the cells were stained with fibronectin but not with E-cadherin, positive predictive value (PPV) and negative predictive value (NPV) to identify reactive mesothelial cells were 100% and 92.5% while under conditions that had not been stained with fibronectin but with E-cadherin, PPV and NPV to detect adenocarcinoma cells were 95.2% and 82.1%, respectively. CONCLUSION: Employing this short panel can be helpful for better differentiation of adenocarcinoma and reactive mesothelial cells in serous fluids.

Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor VIII-related antigen" (von Willebrand factor) expression in tumor microvessels.

BACKGROUND: Astrocytic brain tumors are the most common primary central nervous system tumors, which are classified into four grades. One of the most important pathologic criteria for the diagnosis of higher-grade astrocytomas (especially glioblastoma multiforme) is microvessel proliferation, particularly in the form of glomeruloid complex. Because tumor angiogenesis is a necessary factor for growth and invasiveness of malignancies, microvessel density (MVD) and intensity of angiogenesis may be used to determine the grade of astrocytomas and plan therapy accordingly. We have planned this study to evaluate the relationship between vwf expression in microvessels and different grades of astrocytoma. MATERIALS AND METHODS: Sixty-four formalin-fixed and paraffin-embedded blocks of surgical specimens with diagnosis of astrocytoma (grades I to IV, each of them 16 blocks) were selected in a simple-nonrandom sampling. Thin sections of tissue blocks underwent immunohistochemical staining for vwf. The stained slides were examined using a light microscope at low (100) and high (400) magnifications. MVD was estimated by calculating the mean number of stained microvessels in three areas of highest vascularization in the high-power field (400). The intensity of staining was determined based on a 3 scale model, in which scores 0, 1, 2, and 3 mean no detectable stain, trace staining, moderate amount of diffuse stain, and strong diffuse staining, respectively. RESULTS: Thirty-six (56%) patients were male and 28 (44%) were female. Scores 0 and 1 of microvessel staining intensity were not observed in any grades studied, but severe staining intensity (score 3) was observed in 18.8%, 37.5%, 56.3%, and 87.5% of grades I, II, III, and IV astrocytomas, respectively. "Vwf vessel index" (MVD staining intensity of microvessels) was 23.84, 25.62, 31.62, and 62.43 in grades I, II, III, and IV astrocytomas, respectively. CONCLUSION: We found a significant relationship between staining intensity of vwf in microvessels and different grades of astrocytomas. The intensity of microvessel stain increases in parallel with increasing tumor grade. Regarding "microvessel density" and "vwf vessel index," the difference is predominantly between grade IV and all other grades. However, there is no other statistically meaningful difference between grades I, II and III.

Prognostic value of insulin- like growth factor-I receptor expression in renal cell carcinoma.

The insulin-like growth factor-I receptor (IGF-IR), a tyrosine kinase receptor over expressed in many tumor cell lines and in some human tumors, plays a critical role in transformation, tumorigenicity and metastasis. The aim of the present study is to investigate the role of IGF-IR expression as a prognostic factor in RCC. This study was conducted in a historical cohort of 82 patients who had RCC treated with radical nephrectomy from 1994 to 2005. Specimens were reevaluated with regard to histological subtype, nuclear grade, stage and IGF-IR expression. The IGF-IR stain was semi-quantitatively evaluated using the Allred score system. Kaplan-Meier analysis demonstrated a significant positive correlation between Fuhrman nuclear grade and IGF-IR Allred score (P< 0.0001). Survival in patients with score IGF-I < or = 4 was 90.21 month and in patients with score IGF-1R> 4 was 33.39 month (P Value < 0.0001). Cox regression analysis indicated that expression of IGF-IR is a prognostic factor in patients with RCC (P Value < 0.0001, odds Ratio = 2.38). In conclusion, a statistically significant correlation was demonstrated between IGF-IR expression and Fuhrman nuclear grading and survival in patients with RCC. In stage-by-stage and grade-by-grade analysis; however, it seems that we cannot consider IGF-IR as an independent prognostic factor.

Bilateral ovarian fibroma associated with Gorlin syndrome.

Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare inherited multisystem disorder. This paper presents a 22-years-old Iranian woman with this syndrome whose past history was multiple keratocysts of maxillary bone. She was referred to gynecology clinic with the chief complaint of irregular menses and vaginal spotting. On examination, frontal bossing and hypertelorism were detected. Physical examination of genitalia disclosed bilateral adnexal masses. Pelvic ultrasound showed two solid, echogenous and calcified masses measuring 100*50*10 & 60*50*45 mm in the left and right ovaries, respectively. The patient underwent right oophorectomy and ovarian mass resection with preservation of intact ovarian tissue on the left side. On frozen and permanent histological sections, bilateral and calcified ovarian fibromas were diagnosed. Surprisingly, during the last follow-up one year after the surgery, we found that our patient was expecting a baby. It can be concluded that in the presence of bilateral and calcified ovarian fibromas, the possibility of GS should be considered. Accurate diagnosis is only possible with close attention to the familial and past medical history and physical examination. In these patients, careful follow up for detecting malignancies and other complications is highly recommended.