Allergic fungal rhinosinusitis presented as a unilateral nasal mass: A first case report from Thailand and literature review.

Background: Allergic fungal rhinosinusitis (AFRS) is a relatively new inflammatory sinonasal disease. Prevalence of the disease is reported to be highly different across Asia. Case presentation: A 23-year-old Thai male came to our hospital with left-sided nasal obstruction. Endoscopic examination found a mass originated from the left sphenoethmoidal recess. Incisional biopsy result of the mass indicated an inflammatory process and high level of serum specific IgE to several aeroallergens was found. Based on the biopsy results and other investigations, the diagnosis of AFRS was made and the patient was treated successfully with endoscopic sinus surgery and postoperative systemic/topical steroids. Discussion: While AFRS is quite common in some regions, the disease is rarely encountered in Thailand and can be presented as a unilateral lesion, mimicking a tumor mass, which could lead to an incorrect diagnosis and inappropriate treatment. Conclusion: Even though AFRS is rarely reported in our country, it still can be found and might be recognized falsely as a neoplastic process. High level of awareness of the disease features could help to minimize inappropriate disease management.

Diagnostic power of DNA methylation markers suggestive of cholangiocarcinoma in ERCP-based brush cytology.

BACKGROUND AND AIMS: Accurate differentiation between cholangiocarcinoma (CCA) and benign biliary stricture is of paramount importance. Biliary brush cytology is a simple and safe diagnostic approach that provides relatively high specificity; however, sensitivity is limited. Previous reports indicated the aberrations of DNA methylation in CCA. This study aimed to investigate the diagnostic performance of the methylation index (MI) of HOXA1 and NEUROG1 gene promoters in CCA. METHODS: Patients with biliary stricture who underwent ERCP with brush cytology in Siriraj Hospital from September 2016 to December 2019 were prospectively enrolled. The MI of HOXA1 (MI_H) and MI of NEUROG1 (MI_N) were determined by quantitative methylation-specific polymerase chain reaction. The diagnostic power for CCA was tested for MI from both genes and serum carbohydrate antigen 19-9 (CA19-9). RESULTS: Sixty-seven patients were included in the study; 41 patients had a final diagnosis of CCA, and 26 patients were determined to have a benign biliary stricture. The results showed that both MI_H and MI_N had higher sensitivity and accuracy (95.1% and 82.3% and 90.2% and 89.5%, respectively) than brush cytology (61.5% and 78.1%) and CA19-9 (69.4% and 77.8%). The combination of brush cytology, both methylation markers, and CA19-9 increased the sensitivity and accuracy to 97.4% and 91.0%. Methylation markers were positive in 5 of 6 patients with confirmed CCA whose cytology and CA19-9 were negative. CONCLUSIONS: DNA methylation increased the sensitivity for the diagnosis of CCA; therefore, the use of DNA methylation is promising for diagnosis of CCA in patients with biliary strictures. A future validation study is warranted to assess its role in clinical practice. (Clinical trial registration number: NCT04568512.).

DNA Methylation Markers Improve the Sensitivity of Endoscopic Retrograde Cholangiopancreatography-Based Brushing Cytology in Extrahepatic Cholangiocarcinoma.

Endoscopic retrograde cholangiopancreatography with brushed cytology is still the standard method for the diagnosis of extrahepatic cholangiocarcinoma in obstructive jaundice; however, the diagnostic yield is limited. To improve the diagnostic sensitivity, DNA methylation analysis is an attractive candidate, since this may constitute a stable marker in brushed specimens. Therefore, this study aims to evaluate the importance of such epigenetic markers in brushed biliary cells from patients with obstructive jaundice for the diagnosis of extrahepatic cholangiocarcinoma. The cells examined were those that were left over from brushed cytology done during routine endoscopic retrograde cholangiopancreatography of patients with extrahepatic cholangiocarcinoma. The methylation states of HOXA1, RASSF1A, P16, and NEUROG1 genes in extrahepatic cholangiocarcinoma were measured by quantitative methylation-specific polymerase chain reaction and compared between brushed biliary cells and normal gall bladder epithelial cells. The results showed that the sensitivity of the methylation index measurements of HOXA1 and NEUROG1 genes from brushed samples was markedly superior to that of standard cytology. In conclusion, measurement of the DNA methylation status of HOXA1 and NEUROG1 genes in leftover brushed biliary cells might serve as a useful supplement in the detection of malignant biliary obstruction by increasing the sensitivity of diagnosis by routine cytology.

Hypothyroidism after Hemithyroidectomy: The Incidence and Risk Factors.

OBJECTIVE: To evaluate the incidence of post-hemithyroidectomy hypothyroidism and identify possible risk factors that indicates whether patients require thyroid function monitoring after surgery. MATERIAL AND METHOD: A retrospective review of patients with benign non-toxic thyroid disease undergoing hemithyroidectomy between April 2004 and November 2008 in the Department of Otorhinolaryngology, Siriraj Hospital was conducted All patients were in euthyroid state preoperatively. Thyroid specimens were examined for pathological diagnosis and degree of lymphocytic infiltration in thyroid tissue, and thyroid function was evaluated again six weeks after surgery. RESULTS: One hundred patients who received hemithyroidectomy were recruited for the present study. All had normal preoperative thyroid function. Six weeks after surgery, 27% of the cases developed hypothyroidism (6% overt or symptomatic hypothyroidism and 21% subclinical hypothyroidism). The mean preoperative thyrotropin level was significantly higher in the hypothyroid group than in the euthyroid group (1.9±1.2 vs. 1.1±0.7 micro IU/ml). Fifty-eight point three percent of patients with preoperative thyroid stimulating hormone (TSH) level more than or equal 2 micro IU/ml developed hypothyroidism in comparison to only 17.1% of those with preoperative TSH <2 micro IU/ml (odds ratio 6.8). Fifteen patients had signifcant lymphocytic infiltration (grade 2-4); nine of those (60%) had post-operative hypothyroidism. In contrary, only 18 of 85 patients (21.2%) with minimal infiltrates (grade 0-1) developed hypothyroidism (odds ratio 5.6). CONCLUSION: Twenty-seven percent of the patients in the present study developed hypothyroidism after hemithyroidectomy. Preoperative TSH more than or equal 2 micro IU/ml and significant lymphocytic infiltration in thyroid tissue or thyroiditis warrant post-operative close TSH monitoring. The awareness of such risk factors for post-operative hypothyroidism would improve patients care.

Well-differentiated fetal adenocarcinoma of the lung mimicking adenoid cystic carcinoma on fine needle aspiration: A case report.

Well-differentiated fetal adenocarcinoma (WDFA) of the lung is a rare variant of adenocarcinoma with an unusual morphology. Although the histologic features of this rare neoplasm have been well established, there is a deficit in the literature with regards to its discrete cytomorphologic features. We report the fine needle aspiration (FNA) findings of a case of this unusual malignancy in a 44-year-old man with an incidental lung nodule. FNA revealed three-dimensional clusters of epithelial cells with scant cytoplasm, hyperchromatic nuclei that are associated with an extracellular metachromatic matrix. The original cytology report was signed out as an epithelial neoplasm favor adenoid cystic carcinoma. Consequently, a wedge resection of the lung was done and the histologic diagnosis was WDFA of the lung. The findings of minimal nuclear atypia in association with focally abundant spheres of extracellular matrix can mimic adenoid cystic carcinoma. WDFA has good prognosis and therefore, pre-operative cytologic diagnosis is critical to clinical management. We present the cytomorphologic features of this neoplasm with particular emphasis on a potential diagnostic pitfall of this rare entity. Diagn. Cytopathol. 2016;44:917-920. © 2016 Wiley Periodicals, Inc.

Clinical, Radiologic, and Endoscopic Manifestations of Small Bowel Malignancies: a First Report from Thailand.

BACKGROUND: The symptoms of small bowel malignancies are mild and frequently nonspecific, thus patients are often not diagnosed until the disease is at an advanced stage. Moreover, the lack of sufficient studies and available data on small bowel cancer makes diagnosis difficult, further delaying proper treatment for these patients. In fact, only a small number of published studies exist, and there are no studies specific to Thailand. Radiologic and endoscopic studies and findings may allow physicians to better understand the disease, leading to earlier diagnosis and improved patient outcomes. OBJECTIVE: To retrospectively analyze the clinical, radiologic, and endoscopic characteristics of small bowel cancer patients in Thailand's Siriraj Hospital. MATERIALS AND METHODS: This retrospective analysis included 185 adult patients (97 men, 88 women; mean age = 57.6±14.9) with pathologically confirmed small bowel cancer diagnosed between January 2006 and December 2013. Clinical, radiologic, and endoscopic findings were collected and compared between each subtype of small bowel cancer. RESULTS: Of the 185 patients analyzed, gastrointestinal stromal tumor (GIST) was the most common diagnosis (39.5%, n=73). Adenocarcinoma was the second most common (25.9%, n = 48), while lymphoma and all other types were identified in 24.3% (n = 45) and 10.3% (n = 19) of cases, respectively. The most common symptoms were weight loss (43.2%), abdominal pain (38.4%), and upper gastrointestinal bleeding (23.8%). CONCLUSIONS: Based on radiology and endoscopy, this study revealed upper gastrointestinal bleeding, an intra-abdominal mass, and a sub-epithelial mass as common symptoms of GIST. Obstruction and ulcerating/circumferential masses were findicative of adenocarcinoma, as revealed by radiology and endoscopy, respectively. Finally, no specific symptoms were related to lymphoma.

Accuracy of cytotechnologist evaluation of specimen adequacy and screening interpretation of malignancy in fine-needle aspiration of the liver.

OBJECTIVE: To evaluate the performance of cytotechnologists in assessing the adequacy and accuracy of the preliminary diagnosis for fine-needle aspirates of the liver. STUDY DESIGN: We retrospectively analyzed 10 years of data and found 589 cases of ultrasound-guided fine-needle aspiration (FNA) of the liver with on-site evaluation of adequacy (OSEA). All the OSEA were performed by the cytopathologist because OSEA of liver FNA is not performed by cytotechnologists at our institution at present. After OSEA, the material was seen by cytotechnologists who rendered an adequacy assessment and preliminary diagnosis. We calculated the adequacy and accuracy statistics and compared the performance of the cytotechnologists with the OSEA and final interpretation. RESULTS: There was no statistically significant difference in adequacy downgrade rate for cytotechnologist versus cytopathologist assessment during the study period (5 vs. 3%, p = 0.06). A total agreement of 88% was noted in overall diagnosis with 97% agreement in malignant cases. CONCLUSION: Cytotechnologists assess the adequacy of liver FNA accurately and there is therefore potential for them to perform OSEA for liver FNA.

'Suspicious for papillary thyroid carcinoma' before and after The Bethesda System for Reporting Thyroid Cytopathology: impact of standardized terminology.

BACKGROUND: The high-risk 'suspicious for papillary thyroid carcinoma' (SPTC) is a clinically relevant diagnosis in the cytological interpretation of thyroid aspirates. While The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided invaluable terminology standardization, a performance comparison for this diagnostic category has not been performed. Therefore, this study evaluates the SPTC diagnosis before and after the introduction of TBSRTC in a large meta-analysis and at a single institution. MATERIALS AND METHODS: The meta-analysis analyzed publications of SPTC or similar diagnoses before and after the introduction of TBSRTC. Similarly our own institutional experience was analyzed for the 8 years surrounding the introduction of TBSRTC. A correlation of the cytopathology and surgical pathology diagnoses was performed. RESULTS: The introduction of TBSRTC coincided with a significant decrease in the fraction of cases called SPTC in the meta-analysis (4.5-3.1%, p < 0.00001) and in the institutional review (1.7-0.9%, p = 0.005). Meanwhile, the malignancy risk for those cases increased significantly in the meta-analysis from 62.5 to 80.5% (p < 0.00001) and trended upwards in the institutional review from 69 to 79% (p = 0.4). The follow-up rate was similar in both time periods in the meta-analysis and the institutional review. CONCLUSIONS: The introduction of TBSRTC coincided with a decrease in the fraction of cases called SPTC and an increase in the malignancy risk associated with that diagnosis.

Cytotechnologist-attended on-site evaluation of adequacy for fine-needle aspiration of bone and soft tissue neoplasms.

INTRODUCTION: On-site evaluation of adequacy (OSEA) is commonly used to increase the adequacy rate of fine-needle aspiration (FNA) procedures. OSEA is increasingly necessary with the widespread use of image-guided procedures, which are expensive to perform and repeat. The increased demand for OSEA has prompted an increasing reliance on cytotechnologists for OSEA in many practices, including ours. However, the performance of cytotechnologists has not been compared with that of cytopathologists for OSEA in FNA of bone and soft tissue tumors. MATERIALS AND METHODS: We retrospectively analyzed 10 years of data in which both cytotechnologists and cytopathologists performed OSEA for 632 bone and soft tissue tumor FNA. We calculated adequacy and accuracy statistics in conjunction with other variables including imaging modality, biopsy site, accompanying core biopsy, tissue type, final diagnosis, and number of smears. RESULTS: Of the 632 bone and soft tissue tumor FNA procedures, OSEA was performed in 223 (35.3%) by cytotechnologists and in 409 (64.7%) by cytopathologists. There was no difference in the adequacy downgrade rate for cytotechnologists versus cytopathologists during this study period (4.5 versus 2.4%, P = 0.23). The adequacy rates for procedures in which OSEA was performed by cytotechnologists and cytopathologists did not differ significantly (78.9 versus 84.1%, P = 0.13). CONCLUSIONS: Cytotechnologists and cytopathologists are comparably accurate in OSEA of bone and soft tissue neoplasms.

Reproducibility of the Johns Hopkins Hospital template for urologic cytology samples.

INTRODUCTION: Cytologic screening for urothelial carcinoma is fraught with low sensitivity, a high indeterminate rate, and until recently, poor standardization of terminology. The Johns Hopkins Hospital John K. Frost Cytopathology Laboratory has recently developed and published a template for reporting urine cytopathology; herein, we evaluate its interobserver reproducibility. MATERIALS AND METHODS: Two sets of 100 cases each were deidentified; each set was reviewed by 5 of 10 observers in a randomized order at the direction of computerized data collection software that tracked observation time as well as observer classification of the atypia-no atypia, atypia (AUC-US), or atypia suggestive of high-grade urothelial carcinoma (AUC-H). Specific morphologic features were also recorded. Cases were grouped into low-, intermediate-, and high-agreement based on the number of observers who made the assessment. The findings were correlated against clinical outcomes. RESULTS: High agreement among observers about the presence or absence of high-grade features was possible in approximately two-thirds of indeterminate urine cases. Time and order did not factor significantly into observer propensity for identifying atypical features or favoring either AUC-US or AUC-H, and cases with high agreement about the presence of high-grade features were more likely to have a malignant follow-up. Furthermore, AUC-H diagnoses based on 2 or more high-grade features had a significantly higher malignancy risk than AUC-US diagnoses did. CONCLUSIONS: AUC-H is a valid diagnostic category with specific, reproducibly identified features that portend a higher risk of malignancy than the findings of AUC-US.

Impact of flow cytometry in thyroid cytopathology.

BACKGROUND: Fine-needle aspiration (FNA) is a useful diagnostic tool for preoperative evaluation of thyroid nodules. However, cytomorphology alone has poor accuracy for the diagnosis of lymphoproliferative disorders involving the thyroid. This study reviews our experience with flow cytometry on thyroid FNA and correlation with surgical follow-up at The Johns Hopkins Hospital. METHODS: The 11,118 thyroid FNAs performed over a 20-year period were reviewed for clinical flow cytometry data (n = 62) or a subsequent diagnosis of lymphoma in the thyroid without flow cytometry data (n = 2). RESULT: Sixty-four cases (0.6%) were included out of 11,118 thyroid FNAs collected over a 20-year period. Lymphoma was diagnosed 13 times. In 8 cases, both cytomorphology and flow cytometry arrived at the correct diagnosis. Cytomorphology alone made the correct diagnosis twice in the absence of flow cytometric results; flow cytometry made the diagnosis once in the absence of suspicious morphology. Neither flow cytometry nor cytomorphology made the correct diagnosis in 2 sparsely cellular cases. CONCLUSION: The combination of cytomorphology and flow cytometry is a useful diagnostic modality for the work-up of lymphocyte-rich thyroid nodules that show atypical lymphocyte populations.

Cytotechnologist-attended on-site evaluation of adequacy for metastatic disease involving bone and soft tissue.

INTRODUCTION: Image-guided fine needle aspiration (FNA) of the musculoskeletal system is expensive to perform and repeat, so on-site evaluation of adequacy (OSEA) is increasingly used to ensure an optimal sample. Metastatic disease to the musculoskeletal system is not uncommon and often requires OSEA when sampled. At large academic centers, cytotechnologists have filled the increased demand for OSEA. However, the performance of cytotechnologists has not been compared with that of cytopathologists for OSEA in FNA of metastatic disease involving bone and soft tissue. METHODS: We retrospectively analyzed 10 years of data in which both cytotechnologists and cytopathologists performed OSEA for 1,995 FNAs of bone and soft tissue sites in which metastatic malignancy was suspected or found. We calculated adequacy and accuracy statistics in conjunction with other variables including imaging modality, biopsy site, accompanying core biopsy, tissue type, final diagnosis, and number of smears. RESULTS: A total of 1,995 aspirates of metastatic disease carcinoma, melanoma or lymphoma to bone or soft tissue had OSEA performed by cytotechnologists (681, 33.7%) or cytopathologists (1,314, 66.3%). The adequacy downgrade rate was statistically equivalent (4.1 vs. 3.6%; p = 0.64). CONCLUSION: Cytotechnologists and cytopathologists perform with reasonable equivalence at OSEA of aspirates from metastatic carcinoma, melanoma or lymphoma involving bone or soft tissue.

'Suspicious for a follicular neoplasm' before and after the Bethesda System for Reporting Thyroid Cytopathology: impact of standardized terminology.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) standardized the terminology for indeterminate diagnoses, but the performance of the indeterminate categories before and after TBSRTC has not been compared. This study evaluates the 'suspicious for a follicular or Hürthle cell neoplasm' (SFN/HCN) category before and after the introduction of TBSRTC at a single institution and in a meta-analysis of the literature. METHODS: A meta-analysis compiled findings from publications on SFN/HCN or similar diagnoses before and after the introduction of TBSRTC. The pathology database at our institution identified all SFN/HCN or similar diagnoses in the 8 years surrounding the introduction of TBSRTC, and those cases were correlated with the surgical follow-up. RESULTS: In the meta-analysis, the fraction of cases called SFN/HCN or the equivalent increased from 6.1 to 7.4% (p = 0.0002); the surgical follow-up rate increased from 55 to 61% (p < 0.00001), and the histological malignancy rate among the cases that were resected increased from 22 to 28% (p = 0.03) after TBSRTC. In our institutional experience, the introduction of TBSRTC did not coincide with any significant changes. CONCLUSION: Standardized terminology clearly coincided with increases in follow-up and the malignancy rate of SFN/HCN. A change in the same statistics was not seen in our institutional experience.

A tertiary center's experience with second review of 3885 thyroid cytopathology specimens.

BACKGROUND: Although the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has standardized the diagnostic terminology for thyroid fine-needle aspiration (FNA), morphological interpretation remains subjective, and interobserver discrepancies are expected. This study quantifies the frequency and magnitude of these discrepancies in a single tertiary center's experience and elucidates key factors that are associated with changes in diagnosis. METHODS: Institutional consultation for 3885 thyroid cytological samples over 45 months were reviewed. BSRTC classification made by the sending institution was compared with that of our institution. An ANOVA was performed to determine factors that may be associated with interinstitutional diagnostic differences. Histopathology diagnoses were available for 1049 (27%) nodules; the malignancy rates for inside and outside BSRTC classifications were calculated. RESULTS: There were 937 1-step changes and 301 ≥2-step diagnostic discrepancies comprising 24% and 8% of all cases, respectively. Second review decreased the indeterminate rate 38% to 28% (P < .000001). Indeterminate diagnostic category before second review, low specimen cellularity, Hashimoto's thyroiditis, and low volume of consults from the sending institution were associated with discordance. Of the 1049 thyroid nodules operated for which unequivocal histopathology was available, the malignancy rates for the BSRTC categories before and after second review were compared. Categorical upgrades were associated with a malignancy rate of 84%, whereas downgrades were associated with a malignancy rate of 38% (P < .000001). CONCLUSION: This is the largest series to date of thyroid cytology second review. The BSRTC classification changed 32% of the time, potentially resulting in significant changes in clinical and surgical management. Because certain specimen characteristics (indeterminate diagnostic category before second review, low specimen cellularity, Hashimoto's thyroiditis, and low volume of consults from the sending institution) were particularly associated with a diagnosis change, morphological second review may be of potential benefit in these settings.

Cribriform morular variant of papillary thyroid carcinoma: clinical and cytomorphological features on fine-needle aspiration.

BACKGROUND: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor that may arise in patients with familial adenomatous polyposis (FAP), although sporadic instances of this tumor have been reported. When it arises in FAP, CMV-PTC may present before colonic manifestations are apparent, so proper identification and classification are essential for prompt assessment of the colonic disease status and genetic and familial counseling. METHODS: Nine cases of PTC with cribriform morular cytomorphology were identified at 2 large tertiary-care hospitals; 6 were true CMV-PTC with positive ß-catenin and 3 were CMV-like PTC with negative ß-catenin. A review of the cytomorphology and a cytology-histology correlation were performed. RESULTS: Only 1 patient presented with a known history of FAP. Patients presented with a median age of 41 years (range 19-64 years). There was a clear female predilection; 8 of 9 patients (89%) were female. All cases demonstrated the classical nuclear and architectural features of PTC. In addition, the most salient features were large tissue fragments with cribriform architecture and dense cellular morules. The elongated cellular shape of the tumor cells led to the misclassification of one tumor as a tall-cell variant of PTC on the FNA material. CONCLUSION: CMV-PTC or CMV-like PTC demonstrate cytomorphological features that overlap with classic PTC. ß-Catenin immunostaining plays an important role in making a definitive diagnosis.