Grading pancreatic adenocarcinomas on fine needle aspiration cytology. The outstanding issues.

OBJECTIVE: The three-tier grading scheme described in "The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology" (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC). METHODS: The Papanicolaou and May Grunwald Giemsa-stained smears from 116 cases of PACs were graded using the three-tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi-quantitatively. The inter-observer reproducibility in grading was evaluated using Kappa and Kendall's tau-c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau-b. RESULTS: 31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter-observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours. CONCLUSIONS: The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter-observer reproducibility. Cases often show multiple grades in the same tumour.

Relative Telomere length in cervical exfoliated cells among women with high- risk human papillomavirus.

INTRODUCTION: This study investigates and compares the relative telomere length (RTL) outcome of high-risk (hr) human papillomavirus (HPV)-infected normal, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) cervical samples to HPV-free normal cervical samples. METHODS: This study used archived cervical samples and obtained cytology and histology data. HPV genotyping was conducted using Sanger sequencing and RTL was performed using real-time quantitative polymerase chain reaction. RESULTS: This study investigated 287 cervical samples, including 100 normal and hr-HPV-negative samples from the control group, 44 normal and hr-HPV-infected samples, and 143 SIL and hr-HPV-infected samples. The RTL in hr-HPV-infected samples, including the SIL and normal sample groups, were significantly longer than that in the control group. RTL in HSIL (5.13 ± 3.22) and LSIL (2.86 ± 2.81) were significantly different (P < 0.001). The RTL of cervical intraepithelial neoplasia (CIN1) lesion (3.53 ± 2.53) differed significantly (P < 0.001) when compared to CIN2 and CIN3 lesions combined. The risk of developing cervical cancer was associated with RTL and was decreased with RTL. CONCLUSION: This study revealed the strong potential of the RTL test in identifying women at risk of developing cervical cancer.

Cholangiocarcinoma: A diagnostic dilemma on cytology.

BACKGROUND: Cholangiocarcinoma is a relatively rare form of adenocarcinoma which may resemble adenocarcinoma of pancreatobiliary origin or adenocarcinomas from many other sites in the body. As a result, its diagnosis relies mainly on clinical history and morphology. CASE: A 64-year-old male with cirrhosis and worsening liver failure underwent fine needle aspiration of a radiologically detected liver mass. Cytological material showed a monomorphic population of cells arranged singly and in clusters, reminiscent of a neuroendocrine tumour (NET). Cell block morphology added to the diagnostic dilemma by showing a delicate vasculature among the tumour cells. Immunohistochemistry on the cell block revealed that cells were positive for CK7 and CK19 and negative for synaptophysin and chromogranin, thereby pointing towards a pancreatobiliary origin for the tumour and excluding an NET. CONCLUSION: In the case of liver aspirates, even when encountering confusing morphological entities, it is imperative to keep in mind the possibility of a rare neoplasm such as cholangiocarcinoma. In the absence of core needle biopsy, cell block sections prepared from aspirated material can provide appreciable immunohistochemistry results to resolve the diagnostic dilemma.

Vitamin D pathway related polymorphisms and vitamin D receptor expression in breast cancer.

Vitamin D deficiency is an emerging risk factor for breast cancer suggesting its role in breast cancer pathogenesis. Recent evidence suggests vitamin D receptor (VDR) expression is a prognosis predictor in breast cancer. We set out to determine the status of VDR expression in histologically characterized breast cancers, and whether common genetic variants modify VDR expression in breast cancer. One-hundred and twenty Kuwaiti female breast cancer fixed tissues were assessed for VDR expression to identify the level and location of its expression by immunohistochemistry. VDR variants (rs731236, rs2228570), and vitamin D binding protein (VDBP) variants (rs4588, rs7041) genotypes were ascertained in breast cancer specimens using Taqman genotyping assays. VDR nuclear expression correlated with low grade tumors (p = 0.01), whereas cytoplasmic expression correlated with lymph node positive tumors (p = 0.03). Absence of VDR expression was a marker for high-grade dedifferentiated tumors (p = 0.01). VDBP rs7041 associated with breast cancer risk (OR 1.92, 95% CI: 1.34 - 2.73; p = 0.0004), and VDR rs2228570 correlated with increased VDR cytoplasmic expression (p < 0.0001). In conclusion, VDR expression is altered in breast cancer confirming its involvement in breast cancer progression. Genetic factors appear to play a role in breast cancer risk, and may modify tumor sensitization to vitamin D.

The applicability of Papanicolaou Society of Cytopathology system on reporting endoscopic ultrasound-guided fine needle aspiration cytology specimens of pancreatic lesions in situations with limited availability of ancillary tests. Experience at a single laboratory.

INTRODUCTION: The Papanicolaou Society of Cytopathology (PSC) system of reporting pancreatobiliary cytology is a standardised reporting nomenclature that uses a six-tiered scheme of diagnostic categories utilising routine microscopy and ancillary tests such as biochemical and molecular analysis of cyst fluids and immunochemistry. The objective of this study was to determine the applicability of the PSC system on endoscopic ultrasound-guided fine needle aspiration cytology samples reported at the cytopathology laboratory, Mubarak Al Kabeer Hospital, in Kuwait with special emphasis on situations with limited availability of ancillary tests. METHODS: In total, 132 cases of endoscopic ultrasound-guided fine needle aspiration cytology samples from pancreatic lesions were categorised according to PSC system guidelines after examining the glass slides and reviewing the clinical, imaging and ancillary test findings. These review diagnoses were compared with the diagnoses rendered during initial reporting. Correlation with histopathology reports was done wherever available. RESULTS: In 23 (17.42%) of 132 cases, re-categorisation was necessary between initial and reviewed diagnoses. In 16 cases, re-categorisations were because of non-analogous categories between initial and reviewed diagnosis. In the remaining seven, they were due to identification of newer cytomorphological and imaging findings or because of issues arising from unavailability of sufficient material for ancillary investigations. CONCLUSION: All cases could be categorised using the PSC system with a moderate number of re-categorisations between initial and reviewed diagnoses. In certain circumstances, limited availability of ancillary tests, resulted in non-diagnostic categories whereas in other such circumstances, diagnostic categories could be assigned with certain conceptual modifications to the PSC guidelines.

Thyroid Ultrasound Reports: Deficiencies and Recommendations.

OBJECTIVE: Thyroid ultrasound plays a major role in the clinical management of patients with thyroid nodules. Comprehensive reporting enables malignant risk stratification and biopsy decisions. In this study, we aimed at a systematic evaluation of the content and completeness of thyroid radiology reports. METHODS: A retrospective study was undertaken. A total of 200 thyroid ultrasound reports of examinations performed over a 1-year period were reviewed. After excluding 18 reports, the remaining 182 were evaluated for the inclusion of the following nodule characteristics: size, 3-axis dimensions, location, presence or absence of five signs suspicious of malignancy, namely microcalcification, hypoechogenecity, irregular margin, height-to-width ratio, and intranodular vascularity. RESULTS: While all reported nodules could be stratified easily as being more or less than 1 cm in size, only 23.6% of these nodules were reported in 3 dimensions, and 33.5% of the nodules were specifically localized. For any described nodule, the frequency of reporting on echogenicity was 50%, on vascularity 19.2%, on margin 10.4%, on calcifications 9.3%, and no report contained a description of the height-to-width ratio. The cumulative frequency of reporting on one characteristic per nodule was 84%, of two characteristics 27%, three characteristics 4.4%, and no report included ≥4 characteristics per nodule. CONCLUSION: Despite easily accessible templates, reporting of thyroid nodule sonogram continues to be incomplete and inconsistent. This in turn constitutes a waste of a significant tool that could otherwise help in making timely informed medical decisions and in providing a significant platform for patients' future follow-up.

The Bethesda System for Reporting Thyroid Fine-Needle Aspiration Cytology: A Kuwaiti Experience - A Cytohistopathological Study of 374 Cases.

INTRODUCTION: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) identifies 6 diagnostic categories in which the risk of malignancy increases respectively. The aim of our study was to assess TBSRTC reporting in our hospital and to evaluate its specificity based on cytohistological correlation. METHODS: A histological diagnosis was available in 374 (110 males and 264 females) out of 7,809 thyroid aspirates examined at Mubarak Al-Kabeer Hospital, Kuwait, from 2004 to 2012. The aspirates were classified in accordance with TBSRTC. RESULTS: Thyroid aspirates were classified as nondiagnostic (n = 18; 4.8%), benign (n = 114; 30.5%); atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; n = 59; 15.8%), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN; n = 17; 4.5%), suspicious for malignancy (SM; n = 80; 21.4%), or malignant (n = 86; 23.0%). In 75 of 86 malignant cases, a papillary carcinoma was detected. There were 3 (1.6%) false-positive aspirates and the sensitivity, specificity, negative predictive value, and positive predictive value were 91.0, 61.9, 84.2, and 75.3%, respectively. CONCLUSIONS: Our results are fairly comparable to those of various previous studies in the SM, AUS/FLUS, and SFN categories. The higher rates observed in the nondiagnostic and benign categories were possibly due to limited guided aspirations and a lack of on-site evaluation for all cases.

Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait.

This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.

Immunocytochemical detection of raf kinase inhibitor protein and human papillomavirus profiling of normal and abnormal cervical ThinPrep samples.

OBJECTIVES: This study investigates the potential value of Raf kinase inhibitor protein (RKIP) as a marker of normal squamous cells in ThinPrep slides. RKIP was evaluated for its ability to distinguish between normal and abnormal cervical samples in the context of human papillomavirus (HPV) infections. STUDY DESIGN: A total of 316 ThinPrep samples were taken from women with normal and abnormal cervices. ThinPrep slides were Papanicolaou stained and reported. Residual samples were used for RKIP immunostaining and HPV PCR-based sequencing. RESULTS: RKIP expression was seen in both nuclei and cytoplasm in 83.7% of samples. RKIP expression was highest (84.6%) in samples with a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse; expression was lower in low-grade squamous intraepithelial lesions (73%) and was lowest in samples with normal cytology (p = 0.0023). A total of 74% of HPV-infected ThinPrep samples were immunopositive, and 67% of samples that did not harbor HPV were also immunopositive (p = 0.414). Sensitivity and specificity of RKIP were 84.6 and 34.6%, respectively, for the detection of samples with HSIL or worse. CONCLUSIONS: This study showed that RKIP expression may be of some value as a marker for abnormal cervical cells. Combined RKIP expression and HPV testing could improve the identification of samples with abnormal cytology.

Associations of adipokines & insulin resistance with sex steroids in patients with breast cancer.

BACKGROUND & OBJECTIVES: Several studies have suggested an important, but conflicting and controversial role for adipose tissue mass in breast cancer risk. Factors such as insulin-like growth factors, sex steroids, adipokines and obesity-related inflammatory markers have been postulated as potential effectors of the mechanisms by which obesity and associated metabolic disorders influence breast cancer risk. In this study we evaluated the associations between obesity indices, insulin resistance, circulating adipokines, sex steroids and breast cancer. METHODS: Fasting adiponectin, leptin, insulin resistance (homeostasis model assessment, HOMA-IR), testosterone, estradiol, sex hormone binding globulin (SHBG), LH and FSH were determined in 144 newly-diagnosed histologically confirmed breast cancer patients and 77 controls. Univariate and multivariate regression analyses were used to find the associations of these variables with each other, indices of obesity and with breast cancer. RESULTS: BMI, waist circumference, HOMA-IR and leptin were significantly (P<0.001) higher in patients than in controls. Adiponectin level was also significantly (P<0.05) higher in patients compared to controls. Adiponectin and leptin showed significant correlations with insulin and HOMA-IR but only adiponectin was significantly correlated with estradiol and SHBG. Logistic regression analyses showed that factors associated with breast cancer were BMI [OR (95% CI) =2.8 (1.4-5.5), P=0.004]; high levels of adiponectin [5.1 (2.2-11.5), P<0.001); hyperinsulinaemia [1.1 (1.0-1.1), P=0.01], leptin [3.1 (1.7-5.7), P<0.0001], estradiol [2.5 (1.3-4.7), P=0.005] and testosterone [1.3 (1.03-1.7), P=0.03]. INTERPRETATION & CONCLUSIONS: Our findings confirm that adipokines, insulin resistance and sex steroids are associated with breast cancer. The paradoxical association of increased adiponectin with breast cancer is a novel finding that deserves further investigation.

Urinary survivin mRNA expression and urinary nuclear matrix protein 22 BladderChek® and urine cytology in the detection of transitional cell carcinoma of the bladder.

OBJECTIVE: To compare the diagnostic performance of urine cytology (UC), survivin mRNA expression, and the NMP22 BladderChek® (NMP22BC) test for the detection, grading and staging of transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: Voided urine samples collected from 25 healthy controls and 80 patients diagnosed with TCC of the bladder were subjected to UC, the NMP22BC test and reverse-transcription real-time PCR for survivin mRNA expression. RESULTS: Survivin mRNA expression showed the highest sensitivity (87.5%) followed by the NMP22BC test (61.3%) while UC exhibited the lowest sensitivity (40%). All three urine markers had a similar specificity of 96% (95% CI 80.5-99.3%). Survivin mRNA expression was the only urine marker that showed a significant difference in relation to tumour histological grade (χ(2) 8.5, p = 0.015). None of the three urine markers was significantly related to tumour pathological stages. CONCLUSION: The diagnostic sensitivity of urinary survivin mRNA expression was superior to that of UC and the NMP22BC test and correlates with tumour pathological grade but not stage.

Recurrence of a Langerhans Cell Histiocytosis bone lesion in a different site: A case report.

INTRODUCTION: Langerhans' Cell Histiocytosis is a rare disease of unknown etiology, the pathogenesis of which involves both reactive and neoplastic processes. Despite potential resolution with conservative management, a rare recurrence in a distant site after 3 years from presentation in this case highlights the variability in the course of the disease and the need for larger studies to enable recognition and evidence-based management. CASE PRESENTATION: We present an unusual case below of a 25-year-old gentleman who presented with sternal pain and tenderness. Imaging showed a lytic lesion in the sternum which resolved spontaneously with oral analgesia. He presented 3 years later with back pain and a similar lytic lesion in the iliac bone was found and diagnosed as recurrent Langerhans Cell Histiocytosis with a biopsy. CLINICAL DISCUSSION: There is a diverse array of documented presentations of Langerhans Cell Histiocytosis involving single or multiple systems, while its progression and outcomes are equally unpredictable from the current literature. In order to facilitate wider recognition, Langerhans Cell Histiocytosis should be considered in the differential diagnosis of recurrent lytic bone lesions. CONCLUSION: Although this is a rare disease, there is currently an unmet need for understanding the determinants of recurrence and response to treatment.

Prevalence of human papillomavirus among women with normal cervical cytology in Kuwait.

This study was undertaken to determine the prevalence and type specific distribution of human papillomavirus (HPV) in women with normal cervical cytology in Kuwait. The study is the first of its type in Kuwait and one of few in the Middle East. The age specific distribution of HPV types was determined in 3,011 ThinPrep samples taken from women seeking routine gynaecological care. ThinPrep samples were screened for HPV DNA by real-time PCR. The type specific distribution of the viruses was determined by PCR-based sequencing. The results showed that HPV DNA was detected in 71 women (2.4%), and 21 different HPV genotypes were detected, comprising eight high-risk (HR) (16, 31, 33, 53, 56, 58, 66, and 73), seven low-risk (LR) (6, 11, 54, 61, 70, 81, and 90), four intermediate-risk (IR) (67, 82, 83, and 84) and HPV 102 and HPV 106. LR HPV types were found in 71.8% of infected samples, HR types in 32.3%, and IR types in 7%. With regard to age, 40.8% of all HPVs were found in women 30-39 years of age, 29.6% in women 40-49 years of age, 19.7% in women over 50 years and 9.9% in women less than 34 years old. The study shows that the prevalence of HPV infection in Kuwait is among the lowest in the world and suggests that HPV vaccine could prevent the development of HPV associated cervical cancer in 1.39% of young females living in Kuwait. However, more extensive population-based studies should be undertaken before implementing HPV vaccination.

Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer.

OBJECTIVE: This study aimed to compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of urine cytology, BladderChek® nuclear matrix protein-22 (NMP22) and UroVysion™ fluorescence in situ hybridization (FISH) tests in patients with newly diagnosed bladder cancer, those with recurrent bladder cancer, and those with bladder cancer but in remission during surveillance. MATERIAL AND METHODS: Voided urine samples obtained from 178 patients with suspected or known bladder cancer about to undergo diagnostic or surveillance cystoscopy and 25 control subjects without the disease were divided into four and used for urine culture and cytology, NMP22 BladderChek and UroVysion FISH tests. The sensitivity, specificity, PPV and NPV for each test were calculated. Comparison was made between the ability of each test to detect bladder cancer in the three category of patients listed. RESULTS: Of the 178 patients with bladder cancer, 43 were newly diagnosed, 58 had recurrent disease and 77 were in remission. The sensitivity of each test in newly diagnosed patients was: urine cytology 28%, NMP22 88% and FISH 80%; and in patients with recurrent disease: urine cytology 33%, NMP22 57% and FISH 85%. The mean specificity for urine cytology, NMP22 and FISH was 95%, 67% and 48%, respectively. CONCLUSION: Of the tests used in the study for detection of bladder cancer, NMP22 appeared to be most cost-effective and rapid, with relatively high sensitivity and specificity in all categories of patients. The NMP22 test may be considered a new gold standard for the assessment of patients with known or suspected bladder cancer.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology of Pancreatic Adenocarcinomas Revisited. A Detailed Cytological Analysis.

BACKGROUND: Early detection of pancreatic adenocarcinomas is essential for improving survival. In this regard, endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) has established itself as the method of choice for its ability to target lesions smaller than those which could be targeted by the traditional imaging methods like transabdominal ultrasound. Identifying these tumors correctly on FNA may be challenging because pancreatic adenocarcinomas may show a wide range of morphological features and the presence of contaminants from the gastrointestinal tract may show up as potential pitfalls. This study presents detailed cytomorphological analyses of 59 cases reported as pancreatic adenocarcinomas on smears and cell blocks. The clinical and histopathology follow-up data wherever available have also been presented. MATERIALS AND METHODS: EUS-FNAC smears and cell blocks from cases reported as pancreatic adenocarcinomas were retrospectively evaluated with individual assessments of a range of features related to cellularity, cellular arrangement, cytoplasmic qualities, and nuclear features. Aspirates from peripancreatic lymph nodes, histopathology sections, and clinical records were reviewed wherever available. RESULTS: Nonneoplastic cells like pancreatic ductal cells and acinar cells, duodenal, and gastric epithelia were detected along with neoplastic cells showing a wide range of variations in different cytomorphological characters. Often, a mixture of features was noted in the same case. Cell block preparations served as useful adjuncts since they made it possible to render unequivocal diagnoses of malignancies in cases where smears were hypocellular. CONCLUSION: The study creates a useful knowledge base of cytomorphological features of pancreatic adenocarcinomas.

Fine needle aspiration cytology of the thyroid in children and adolescents: experience with 792 aspirates.

OBJECTIVE: To determine the distribution of thyroid lesions in pediatric and adolescent patients in Kuwait. STUDY DESIGN: During a 16-year period (January 1993-December 2008) the cytology reports of 792 thyroid aspirates (724 females and 68 males) performed on children and adolescents (ranging from 4 to 21 years) at Mubarak Al-Kabeer Hospital were reviewed. Of these 62, 150, 201 and 379 aspirates belonged to the age group 4-- <12, 12-- <16, 16-- <19 and 19-21 years, respectively. There were 745 satisfactory aspirates (678 [91%] females and 67 [9%] males). The unsatisfactory rate was 5.9%, with 51.1% of the unsatisfactory aspirates in the 19-21 age group. RESULTS: Benign cytology was reported in 578 cases (77.6%), with 522 (70.1%) aspirates from females and 56 (7.5%) from males. Chronic lymphocytic thyroiditis was observed in 121 cases (16.2%), and 7 of these were males. Papillary carcinoma was detected in 20 (2.7%), and 4 of these were males. Suspicious cytology was reported only in females and comprised 7 cases (0.9%) with a suspicion of papillary carcinoma and 19 cases (2.6%) with a follicular lesion. CONCLUSION: Fine needle aspiration cytology of children's and adolescents' thyroid nodules is feasible and reliable. The majority of the nodules in this age group are benign, and fine needle aspiration cytology helps prevent unnecessary surgery.

Expression of estrogen receptor alpha and estrogen receptor beta in fine needle aspirates of breast carcinoma.

OBJECTIVE: To evaluate the expression of estrogen receptor beta (ERbeta) in fine needle aspirates (FNAs) and correlate the findings with its expression in tissue sections. STUDY DESIGN: In 38 cases of breast carcinoma, expression of estrogen receptor alpha (ERalpha) and ERbeta in aspirates and tissue sections was correlated with the cytologic and histologic grade of the tumor. RESULTS: ERalpha and ERbeta were expressed as nuclear staining in 80% and 90% of the cases in tissue sections and 47% and 45% of the cases in aspirates, respectively. Tissue expression of ERalpha (grade 1, 81%; grade 2, 100%) and ERbeta (grade 1, 94%; grade 2, 100%) was greater than in grade 3 tumors (ERalpha, 50%; ERbeta, 70%). In FNAs they were equally distributed in the different cytologic grades. In aspirates 30% of ERalpha negative tumors were positive for ERbeta, while in tissues 75% of ERalpha-negative tumors were positive for ERbeta (p = 0.007). CONCLUSION: Demonstration of ERbeta on FNA smears is feasible. It helps identify the specific subcohort of ERbeta-positive tumors in ERalpha-negative breast cancers; that may have therapeutic importance.

Gynecologic infections seen in cervical smears in Kuwait.

OBJECTIVE: To study the different gynecologic infections seen in cervical smears in Kuwait. STUDY DESIGN: Over a 6-year period (2002-2007), a total of 42,294 cervical smears were studied in Mubarak Al-Kabeer Hospital, Kuwait. Conventional and ThinPrep (Cytyc Corp. Boxborough, Massachusetts) smears were first screened by cytotechnicians and finally reported by cytopathologists, Smears showing inflammation were analyzed with reference to Kuwaiti women. RESULTS: Of the 41,748 (98.7%) patients with satisfactory smears, inflammatory changes were observed in 17, 593 (42.1%). Specific infection was identified in 2,679 (15.2%) cases, of which 60.8% were Kuwaitis. The infections seen were Candida sp (73.8%), Trichomonsa vaginalis (11.9%), human papillomavirus (HPV99) (8.2%), Actinomyces-like organisms (3.4%), Chlamydia trachomatis (2.2%) and herpes simplex virus (0.5%). No significant difference was found in the proportion of infectious agents among Kuwaiti and non-Kuwaiti women except marginally higher T vaginalis (10.9% vs 13.4%, p = 0.05) among non-Kuwaitis. Candida sp was the most detectable infectious agent in both Kuwaiti (74.6%) and non-Kuwaiti women (72.4%). Chi2 for trend revealed an increasing proportion of smears from Kuwaiti women found with specific infections (p = 0.049) as compared to those of non-Kuwaitis over the years. CONCLUSION: The prevalence of infections identified on cervical smears was found to be almost similar in Kuwaiti and non-Kuwaiti women except for T vaginalis, which was higher among non-Kuwaitis as compared to Kuwaitis (10.9% vs. 13.4%, p = 0.051). The Candida sp was the most detectable infectious agent, 74.6% in Kuwaiti and 72.4% in non-Kuwaiti women, followed by T vaginalis, the second and HPV being the third.

Hurthle Cell Adenoma with Micro-Papillary Carcinoma and Parathyroid Adenoma in a Transplant Recipient with Graft Failure: A Case Report.

Chronic immunosuppression is known to cause an increased risk of cancers in organ transplant recipients leading to the rise in morbidity and mortality among these patients. Recent studies have observed that thyroid lesions are more frequently encountered in kidney transplant recipients. A 45-year-old woman with history of chronic hypertension, kidney transplant and graft failure, was admitted for assessment for a second renal transplant and detected to have a thyroid nodule by ultrasound (US). A fine needle aspirate (FNA) on the nodule was reported as Hurthle cell neoplasm. Histopathology revealed a Hurthle cell adenoma with an incidental micro papillary carcinoma. On follow up a year later, US investigation revealed another nodule in the inferior pole of the remnant lobe of thyroid. FNA showed sheets of uniform small round cells arranged in micro follicles, intermixed with Hurthle-like cells with absence of colloid, raising the possibility of a parathyroid lesion. Biochemical tests, clinical history, cytomorphological, immunocytochemical and biochemical tests supported a parathyroid adenoma. Advancements in diagnostic techniques and management strategies have not only improved survival rates in patients with chronic renal disease but have also identified an increasing number of multiple primary tumors in these patients. Thyroid lesions have cytomorphological similarities and may masquerade parathyroid neoplasms. Regular thyroid screening in post- transplant patients, meticulous pathological examination and parathormone assay are crucial in the early diagnosis, management and prevention of morbidity and mortality in these patients. Keywords: Fine needle aspiration, kidney transplant, Hurthle cell neoplasm, parathyroid adenoma, micropapillary carcinoma.

Interpreting a Diagnosis of Atypical Squamous Cells of Undetermined Significance in Cervical Cytology and its Association with Human Papillomavirus: A retrospective analysis of 180 cases in Kuwait.

OBJECTIVES: Atypical squamous cells of undetermined significance (ASC-US) represent a diagnostic challenge during cervical cytology. This study aimed to review and identify high-risk human papillomavirus (HR-HPV) genotypes among previously diagnosed ASC-US cases in Kuwait. METHODS: This retrospective study analysed 180 cases diagnosed as ASC-US between June 2017 and May 2018 at the Mubarak Al-Kabeer Hospital, Kuwait. Cervical specimens were assayed to determine the presence of HR-HPV DNA; subsequently, positive cases underwent genotyping and were categorised into three groups (HPV 16, HPV 18/45 and other HR-HPV types). RESULTS: In total, ASC-US was confirmed in only 105 cases (58.3%), with the remaining cases reclassified as negative for intraepithelial lesions or malignancy (NILM; 32.2%) and epithelial cell abnormalities (ECA; 9.4%). Of these, HR-HPV DNA was present in 20 ASC-US (19%), one NILM (1.7%) and six ECA (35.3%) cases. There were 62 Kuwaiti and 43 non-Kuwaiti women with confirmed ASC-US; of these, three (4.8%), six (9.7%) and four (6.5%) Kuwaitis and one (2.3%), one (2.3%) and five (11.6%) non-Kuwaitis had HPV 16, both HPV 16 and 18/45 and other HR-HPV genotypes, respectively. Of those with HR-HPV DNA, the NILM case had the HPV 18/45 genotype, while the six ECA cases had the HPV 16 (n = 1), both HPV 16 and 18/45 (n = 1) and other HR-HPV (n = 4) genotypes. CONCLUSION: Overall, HR-HPV DNA was present in 19% of ASC-US cases compared to 1.7% of NILM cases initially misdiagnosed as ASC-US. Re-review of cervical cytology diagnoses may reduce unnecessary costs associated with HR-HPV genotyping.