Cytology smears for DNA extraction: Practical approach for selecting the best slide.

BACKGROUND: Next generation sequencing (NGS) to detect actionable genetic abnormalities is standard of care in advanced stage lung adenocarcinoma. Many studies have shown that the molecular results obtained from fine needle aspiration cytology material are comparable to those obtained from formalin-fixed tissue samples. We undertook this study to validate DNA extraction from cytology material for molecular studies and to find any correlation between DNA yield, pattern of tumour cells and tumour fraction. METHODS: DNA was extracted from 34 cytology slides of pulmonary adenocarcinoma cases with predetermined EGFR mutation status. Cytology slides were reviewed for pattern of tumour distribution and tumour fraction. NGS was performed on five slides with variable DNA and compared with original results. RESULTS: There were 14 alcohol-fixed and 20 air-dried smears. The mean DNA yield was 1.74 µg and median of 0.4 µg (range, 0.02-21 µg). Tumour fractions varied from 10% to 90%. No correlation was found between tumour fraction and DNA yield (P = 0.14). The mean DNA yield was high in slides with tumour throughout the slide (sheets or scattered clusters) as compared to rare scattered clusters and/or single cells. EGFR mutation was found in four of the five cases sent for NGS lung panel while one case revealed BRAF mutation. CONCLUSIONS: DNA with good quantity and quality can be extracted from the cytology slides for NGS irrespective of type of fixation. DNA yield has better correlation with distribution pattern of tumour cells on the slides rather than tumour fraction.

Grading variability of urothelial carcinoma: experience from a single academic medical center.

INTRODUCTION: Tumor grade plays a critical role in the management of papillary non-invasive urothelial carcinoma (UC). Since grading of UC relies on morphologic criteria, variability in interpretation exists among pathologists. The objective of this study was to examine inter-observer variability in the grading of papillary non-invasive UC at a single academic medical center. MATERIALS AND METHODS: One general pathologist and two genitourinary pathologists were blinded to patient identity and graded 98 consecutive UC specimens using the 1973 and 2004 classification systems. Kappa statistics (κ) were used to measure inter-observer reproducibility to account for agreement expected purely by chance. By convention, Ï° values from 0.21-0.4 represent "fair", from 0.41-0.6 represent "moderate", and > 0.6 represent "substantial" agreement. RESULTS: Raw percentage agreement among all three pathologists was only 26% using the 1973 system and 47% using the 2004 system. When measured by kappa, overall agreement was only "fair" for both systems and while higher for the 2004 system than the 1973, this was not significant (: 0.38 versus 0.26, respectively). There were no significant differences in agreement when comparing the specialists agreement between themselves with agreement between each specialist and the generalist (Ï°: 0.31-0.37 versus Ï°: 0.18-0.46). CONCLUSIONS: The current grading system continues to demonstrate challenges in reproducibility among general and specialized pathologists. The degree of variability has significant implications on management decisions for non-invasive UC. Our findings underscore the need to identify molecular markers that can provide a more objective and reliable risk stratification system to guide patient management.

Fine-needle aspiration cytology of mammary analog secretory carcinoma masquerading as low-grade mucoepidermoid carcinoma: case report with a review of the literature.

BACKGROUND/AIM: The primary role of fine-needle aspiration cytology (FNAC) of salivary gland masses is to determine the underlying process and guide further management. The objective of our study is to provide a comprehensive review of cytologic features and ancillary studies of mammary analog secretory carcinoma (MASC), discuss differential diagnosis and review recent advances in the understanding of its biologic behavior. CASE: A 23-year-old female underwent ultrasound-guided FNA of a slowly enlarging parotid mass. Smears displayed branching clusters of bland vacuolated polygonal cells in a secretory proteinaceous background. Eosinophilic cells with eccentric nuclei and inconspicuous nucleoli were also noted. Based on positive intracellular mucin staining and the lack of extracellular-matrix material, the cytologic diagnosis rendered was 'suspicious for low grade mucoepidermoid carcinoma'. Superficial parotidectomy revealed an MASC confirmed by fluorescence in situ hybridization (FISH) studies for ETV6 translocation. CONCLUSION: MASC should be included in the differential diagnosis of mucinous salivary lesions with cystic changes on FNA. Immunohistochemistry for mammaglobin and S-100 helps in excluding morphologic mimics. FISH helps to confirm the diagnosis. Age alone should not be a deterrent in diagnosing a carcinoma.

COVID and cytopathology training: Impact and innovations.

Graduate medical education and training in Cytopathology faced numerous unexpected challenges during the COVID-19 pandemic of 2020. It was caused by the SARS-Co-V2 coronavirus and transmitted by breathing droplets or aerosol particles containing the virus and less commonly by contact with infected surfaces and fomites. To mitigate the rapid spread of disease non-essential services were closed, surgical procedures were prioritized, and "social distancing" was implemented. These measures led to a marked decline in the volume of specimens, number of fine needle aspiration (FNA) and rapid on-site evaluation procedures performed. The trainees in Pathology were required to stay at home either entirely or partly during the early period of the pandemic. This led to re-designing of the cytopathology training program nationwide. Many innovative methods and protocols were put in place to overcome the challenges faced and adjustments made in creating the virtual training program in Cytopathology. On May 5th, 2023, the WHO declared that COVID-19 was no longer a global emergency. Regulations were lifted and healthcare services returned to pre-pandemic era. Graduate medical education and training returned to normal however many changes were incorporated into the training program moving forward. Herein the impacts and innovations that COVID-19 had on Cytopathology training are described.

Granulomatous myocarditis arising from intravesical Bacillus Calmette-Guérin therapy leading to death diagnosed by postmortem examination: a case report.

BACKGROUND: Intravesical Bacillus Calmette-Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach. CASE PRESENTATION: We present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus. CONCLUSION: Granulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

Malignant Pericardial Effusion from Cervical Squamous Cell Carcinoma: A Case Study.

BACKGROUND Cervical cancer ranks fourth globally among women's cancers. Squamous cell carcinoma constitutes 70% of cervical cancer cases, often metastasizing to lungs and paraaortic nodes. Uncommon sites include the brain, skin, spleen, and muscle, while pericardial fluid metastasis is highly rare. We report a case of squamous cell carcinoma of the uterine cervix that was metastatic to the pericardium and was detected on cytologic evaluation of pericardial fluid. CASE REPORT A 42-year-old woman who was previously treated for stage III squamous cell carcinoma of the cervix presented with symptoms of cough, fever, and shortness of breath for 8 days, and chest pain for 3 days. Clinical workup revealed pericardial effusion, with spread to the lungs and mediastinal and hilar lymph nodes. Cytological analysis of the fluid showed malignant cells, consistent with metastatic squamous cell carcinoma. Immunohistochemistry demonstrated cells positive for p63 and p40, while negative for GATA-3, D2-40, calretinin, and WT1. These findings in conjunction with patient's known history of cervical squamous cell carcinoma was consistent with a cytologic diagnosis of metastatic squamous cell carcinoma to pericardial fluid. CONCLUSIONS History and clinical correlation plays a vital role in determining the primary site causing malignant pericardial effusions. While the occurrence of cervical cancer metastasizing to the pericardium is uncommon, it should be considered, particularly in cases involving high-grade, invasive tumors, recurrences, or distant metastases. This possibility should be included in the list of potential diagnoses when encountering pericardial effusions with squamous cells in female patients.

TRPS1 function beyond breast: A retrospective immunohistochemical study on non-breast cytology specimens.

INTRODUCTION: Trichorhinophalangeal syndrome type 1 (TRPS1) has emerged as a reliable immunohistochemistry (IHC) marker for identifying breast origin in metastatic carcinomas. This study investigates the utility of TRPS1 IHC in non-breast cytology specimens. MATERIALS AND METHODS: A retrospective search of our pathology database for the year 2021 identified fluids (pleural and peritoneal) and liver, lung and bone fine needle aspirations (FNAs) with surgical follow-up confirming non-breast metastatic carcinomas. Cell blocks from cases with sufficient neoplastic cells underwent immunostaining using a rabbit polyclonal antibody against human TRPS1. Cases lacking tumor on deeper levels after the original work-up were excluded from the study. Two pathologists independently interpreted the TRPS1 staining. RESULTS: Of 136 cases assessed, 31 (22.79%) exhibited positive TRPS1 staining, while 105 (77.21%) were nonreactive. Positivity rates were observed in tumors of Mullerian cell origin, gastrointestinal tract (GIT), and lung origin at 28.85%, 25%, and 21.57%, respectively. Of the tumors of Mullerian cell origin 10 (66.67%) were serous carcinomas, 4 (26.67%) were endometrioid carcinomas, and one (6.67%) was a clear cell carcinoma. Lung tumors comprised seven (63.64%) squamous cell carcinomas and four (36.36%) adenocarcinomas, while the gastrointestinal tumors consisted of 14 (80%) adenocarcinomas and one (20%) squamous cell carcinoma. CONCLUSIONS: Although recognized as a sensitive marker for mammary carcinomas, TRPS1 immunostaining was also detected in Mullerian, lung, and GIT carcinomas. This highlights the significance of being cautious when depending solely on TRPS1 immunostaining to distinguish metastatic breast tumors.

Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (Milan IVB) and Its Subgroups: A Multi-Institutional Analysis of Risk of Neoplasm and Malignancy.

OBJECTIVES: Fine needle aspiration (FNA) plays a crucial role in their initial assessment of salivary gland neoplasms. In the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the category of Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) categorizes lesions with ambiguous features. This study aims to investigate the risk of neoplasm (RON) and risk of malignancy (ROM) within different subgroups of SUMP lesions using data from three large academic institutions. METHODS: We analyzed salivary gland (FNA) cases from three academic institutions post-MSRSGC implementation. Salivary gland FNA cases categorized as Milan IVB (SUMP) with subsequent surgical pathology follow-up were analyzed. Cases were divided into basaloid, oncocytic, and clear cell SUMP subtypes, with RON and ROM assessed and compared. RESULTS: Out of 1377 MSRSGC cases, 231 were SUMP (16.8%), with 101 subjected to surgical pathology follow-up. The overall ROM for SUMP was 20.8%, with variations of 10% to 29.5% observed amongst institutions, but no significant difference was observed among three institutions (p = 0.15). Basaloid and oncocytic SUMP displayed 17.1% and 20.5% ROM, respectively, without significant disparity. However, all clear cell SUMP cases were malignant on surgical resection. CONCLUSIONS: This study highlights the variability in ROM for SUMP lesions and the significantly higher ROM in SUMP cases with clear cell features. These findings emphasize the importance of accurately subcategorizing SUMP lesions, particularly those with clear cell features, for appropriate clinical management.

Diffusion-weighted imaging of the prostate: Comparison of b1000 and b2000 image sets for index lesion detection.

PURPOSE: To compare tumor detection on acquired diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps, obtained using b-values of 1000 s/mm(2) and 2000 s/mm(2) , using radical prostatectomy as the reference. MATERIALS AND METHODS: In all, 29 prostate cancer patients who underwent 3T magnetic resonance imaging (MRI) including DW imaging using b-values of 1000 s/mm(2) and 2000 s/mm(2) were included. Two radiologists independently evaluated four image sets during different sessions and recorded the location and diameter of the dominant lesion: DW images acquired using b-values of 1000 s/mm(2) and 2000 s/mm(2) and ADC maps calculated using maximal b-values of 1000 s/mm(2) and 2000 s/mm(2) . Findings were correlated with the location and diameter of the dominant lesion at prostatectomy. Tumor-to-PZ contrast was also calculated, unblinded to pathology. RESULTS: Both readers achieved significantly higher sensitivity for DW images obtained using a b-value of 2000 s/mm(2) than 1000 s/mm(2) (P < 0.001), although there was no difference in sensitivity between ADC maps calculated using the two b-values (P ≥ 0.309). Tumor-to-PZ contrast was higher for DW images using a b-value of 2000 s/mm(2) (P = 0.067), although it was not different between the two corresponding ADC maps (P = 0.544). For both readers, correlations with tumor diameters were higher for either ADC map (r = 0.59-0.73) than for either acquired DW image set (r = 0.03-0.57). CONCLUSION: Use of a b-value of 2000 s/mm(2) compared with a b-value of 1000 s/mm(2) resulted in improved tumor sensitivity and higher tumor-to-PZ contrast on the acquired DW images, although performance of the ADC maps corresponding with the two b-values was similar. Correlation with tumor size was greater for either ADC map than for either acquired DW image set.

Periprostatic lymph node metastasis in prostate cancer and its clinical significance.

AIMS: To evaluate the potential of periprostatic lymph node (LN) as a staging indicator, particularly with the use of methods for enhanced detection of micrometastasis. METHODS AND RESULTS: We retrieved cases with periprostatic LN from radical prostatectomy specimens accrued between 1997 and 2007 at our institution. Twenty-one (0.8%) of 2663 radical prostatectomy specimens had periprostatic LNs (total number of LNs = 22). LN size ranged from 0.8 to 4.7 mm. Most of the periprostatic LNs were located close to the posterior base. Seven (32%) of 22 LNs were involved by metastatic prostate cancer (PCa), including five detected on routine haematoxylin and ceosin slides and an additional two detected only by immunohistochemistry. Cases with periprostatic LNs had a significantly higher metastatic rate (29%; six of 21) compared to those with pelvic LNs sampled at radical prostectatomy in our institution (1.9%). When compared to cases with negative periprostatic LNs (n = 15), the tumour characteristics of cases with metastatic periprostatic LNs (n = 6) included higher tumour volume, Gleason score, stage and a greater propensity for prostate-specific antigen (PSA) recurrence. CONCLUSIONS: Despite their infrequent identification, periprostatic LNs if detected in the radical prostatectomy specimen should be evaluated with greater scrutiny (step sections and/or immunohistochemical studies) to evaluate their prognostic potential.

The utility of 'low-grade intraepithelial lesion, cannot exclude high grade' diagnosis: a single institution's experience.

OBJECTIVE: Squamous intraepithelial lesions (SILs) are classified as low-grade SIL (LGSIL) and high-grade SIL (HGSIL). 'LGSIL cannot exclude high grade' (LGSIL-H) interpretive category has been used in cases where findings exceed criteria for LGSIL, but do not fulfill the criteria for HGSIL. This study analyzed follow-up histology of LGSIL-H cases and compared the follow-up results of LGSIL-H with LGSIL to determine the utility of LGSIL-H category using a single institution's experience. STUDY DESIGN: Pap smears with LGSIL-H interpretation from 2005 to 2008 were retrieved. Histological follow-up results for LGSIL-H cases were analyzed and compared to the follow-up results of LGSIL cases. RESULTS: Cases with LGSIL-H interpretation (311) comprised 0.18% of all cases (170,307). Follow-up was available for 144 patients and 13.2% had benign findings, 51.4% had cervical intraepithelial neoplasia (CIN) 1, and 35.4% had CIN 2 or higher. In comparison, of 425 patients with LGSIL, 22.6% had benign findings, 71% had CIN 1 and 6.4% had CIN 2 or higher. CONCLUSION: A significantly greater number of patients with LGSIL-H interpretation had a CIN 2 or higher lesion on follow-up compared to patients with LGSIL. This suggests LGSIL-H may be a useful diagnostic category.

The role of cytology as an effective tool in management of omental and peritoneal lesions: Experience of a large health care system.

BACKGROUND: The aim of this study is to assess the efficacy of cytology in omental or peritoneal lesions. METHODS: A retrospective review of the pathology database for cytology cases of peritoneal or omental nodules over a 3-year period (2016-2018) was conducted. The cases consisted of either FNA only (FO); FNA and Core biopsy (FCB) or Touch prep and core biopsy (TCB). Cases were further divided based on the prior history of carcinoma. Concordance rates of cytologic diagnosis with histologic diagnosis were studied. RESULTS: Out of 104 cytology cases reviewed, 60 (57.7%) had prior history of cancer (PHC) and 44 (42.3%) had no prior history of cancer (NPHC). Of the cases with PHC, 43(71.66%) were recurrence, 10 (16.66%) were second cancer, and 7 (11.66%) were non-neoplastic lesions. Of the cases with NPHC, 38 (86.4%) had a second cancer diagnosis, while 6 (13.6%) were non-neoplastic. For FO only cases, 11 of 35 (31.4%) had follow up and 9 of 11 (81.8%) were concordant. For FCB cases, 6 out of 39 (15.4%) had follow up and 6 (100%) were concordant. For TCB cases, 9 out of 30 (30%) had follow up and 9 (100%) were concordant. A definite diagnosis was reached in 30/35, 39/39, and 29/30 cases in FO, FCB, and TCB, respectively. CONCLUSION: In summary, cytologic evaluation of omental lesions is an effective tool in providing accurate diagnosis and guiding further management. Also, the results based on our study show that the combined techniques are superior at reaching a definitive diagnosis.

Adequacy of pleural fluid cytology for comprehensive molecular analysis of lung adenocarcinoma: Experience of a large health-care system.

Objectives: Pleural fluid evaluation is an effective modality for identifying actionable genetic mutations to guide therapy in lung carcinoma. Clinicians requesting molecular studies often send large volumes of fluid to be processed that is not possible or cost effective and is hence not standard of practice in most cytopathology laboratories. We wanted to establish the characteristics of an adequate specimen that would yield reliable results with current molecular testing platforms. Material and Methods: A review of 500 malignant pleural effusions, from pulmonary and non-pulmonary sources, was undertaken over a 4-year period. Of these 44 cases (from 42 patients) that were positive for primary lung adenocarcinoma were included in the study. Molecular analysis was performed on 42 specimens. A complete next generation sequencing (NGS) panel was performed on 36 specimens. Individual testing for estimated glomerular filtration rate, KRAS, anaplastic lymphoma kinase, and ROS1 was performed on six specimens. The number of malignant cells and proportion of tumor to non-tumor nucleated cells (T: NT) on cell blocks was recorded as <20%, 20-50% and >50%. Results: The minimum volume on which a complete NGS panel could be performed was 20 ml with cell count of 1000 and T: NT proportion of 20-50%. The minimum number of tumor cells required for successful molecular analysis for T: NT proportion of <20%, 20-50%, and >50% was 300, 250, and 170 cells, respectively. Conclusion: We concluded that tumor cell proportion, rather than specimen volume, is of prime importance for determining the efficacy of pleural fluid for molecular studies. Evaluation of both absolute and relative numbers of tumor cells is critical for assessing the adequacy and predicting successful yield for molecular analysis.

Utility of TRPS-1 immunohistochemistry in diagnosis of metastatic breast carcinoma in cytology specimens.

INTRODUCTION: At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens. MATERIALS AND METHODS: MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups. RESULTS: We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1 (5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P = 0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group. CONCLUSIONS: TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.

Clinical efficacy with dabrafenib and trametinib in a T599_V600insT poorly differentiated metastatic thyroid carcinoma.

BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen-activated protein kinase kinase) inhibitors have been shown to improve clinical outcomes in tumours presenting with mutations in the BRAF gene. The most common form of BRAF mutation is V600E/K and has been shown to occur in thyroid cancers. Treatment data for patients harbouring less frequent BRAF mutations are limited. In vitro studies have shown that mutations in codons 599-601 increase kinase activity similar to that in V600E mutations, which suggests that BRAF and MEK inhibitors could be an effective treatment option. Here, we report a case of a patient with thyroid carcinoma harbouring a rare amino acid insertion in codon 599 of the BRAF gene (T599_V600insT) treated with a BRAF and MEK inhibitor.

Cutaneous sarcoidosis in a woman with chronic hepatitis C and interferon therapy: a case report.

BACKGROUND: Sarcoidosis is an autoimmune disease of unknown origin characterized by the presence of noncaseating epithelioid cell granulomas in multiple organs. Sarcoidosislike lesions have been reported in patients who have a history of chronic hepatitis C with interferon treatment. CASE: A case of cutaneous sarcoidosis, clinically presenting with multiple skin nodules, occurred in a woman with a history of relapsed chronic hepatitis C with interferon therapy. Fine needle aspiration biopsy and excisional biopsy showed ill-defined, noncaseating granulomas. On further investigation, the patient was found to have systemic sarcoidosis. Special stains for infectious etiologies were negative. These findings were compatible with morphologic and clinical features seen in sarcoidosislike lesion induced by interferon. CONCLUSION; A nonnecrotizing granulomatous lesion in subcutaneous tissue might have many differential diagnoses, particularly in a cytology specimen. In this condition, understanding of clinical manifestations is critical for diagnosis. It helps practicing cytopathologists to be aware of this phenomenon of cutaneous sarcoidosis occurring in patients with chronic hepatitis C and interferon or antiviral therapies.

Angiosarcoma in Collision With a Merkel Cell Carcinoma: Case Report and Literature Review.

Merkel cell carcinoma (MCC) is a rare entity that most commonly arises from the skin. Angiosarcoma (AS) is a rare malignancy with a predilection for elderly males, has endothelial differentiation and a notoriously poor prognosis despite aggressive therapy. Herein, we report an angiosarcoma colliding with a MCC, in a patient with a past medical history of squamous cell carcinoma, status-post radiation therapy. More specifically, our case represents a collision tumor, a rare entity composed of two histologically distinct neoplasms which coincide together at the same location. This case represents the first documented report of such a presentation. With that being said, its clinical course, prognosis, pathogenesis, and molecular profile, currently remains unclear. Importantly, neoplasms are increasingly being found to be associated with radiation therapy, of which our patient had received. Ultimately, however, with the lack of c-MYC immunohistochemical staining, and a short duration between radiation exposure and presentation, the AS in our case was likely coincidental.

Determining the molecular test for indeterminate thyroid nodules best suited for our practice: A quality assurance study.

INTRODUCTION: Currently, molecular studies are widely used as a guiding tool in further management of cytologically indeterminate thyroid nodules. At our institution, clinicians have recently expressed concern over receiving "less positive molecular results" upon switching from an extended 14 gene mutation panel (EGMP) to a 7 gene mutation panel (GMP). Our goal is to compare outcomes of these two tests in regards to the performance characteristics and clinical impact. MATERIALS AND METHODS: All thyroid fine-needle aspiration (FNA) biopsy specimens sent for molecular studies from 2016 to 2017 were retrospectively studied. Cytopathology diagnosis, pertinent clinical findings, molecular results, and follow-up (F/U) surgical and cytology diagnoses were recorded. RESULTS: Of the total 165 cases sent for molecular tests 86 (52%) were GMP and 79 (47%) EGMP. There were 21 (24%) and 40 (50%) cases with positive GMP and EGMP results, respectively. Within these positive cases (n = 61), there were a total of 33 (54%) patients who underwent surgical resection and 28 (45%) patients had no follow-up. The molecular findings and surgical pathologic diagnoses obtained are illustrated in Figures 1 through 4 for GMP and EGMP, respectively. CONCLUSIONS: The selection of molecular testing should be directed toward optimizing patient care and facilitate clinical management. This quality assurance study helped in understanding the complexities associated with test selection best suited for our institution and in educating clinicians.

Adequate at rapid on-site evaluation (ROSE), but inadequate on final cytologic diagnosis: Analysis of 606 cases of endobronchial ultrasound-guided trans bronchial needle aspirations (EBUS-TBNA).

BACKGROUND: EBUS-TBNA is a minimally invasive, reliable technique with high sensitivity and accuracy. ROSE plays a crucial role in triaging specimens to guide management. This study analyzes aspirates that were deemed "adequate" on ROSE, but inconclusive upon final cytologic interpretation. DESIGN: EBUS-TBNAs from 2015 and 2016 were retrospectively reviewed and analyzed for ROSE adequacy versus final cytologic diagnosis. Concurrent and subsequent procedures were evaluated to determine the outcome of ROSE-adequate cases with inconclusive final cytologic diagnosis of non-diagnostic (ND), atypical (ATY), and suspicious for malignancy (SUS). Interpretation at ROSE was determined to be "appropriate" if published criteria for lymph node adequacy were met. RESULTS: A total of 606 cases of EBUS-FNA with ROSE were obtained of which 61% were deemed adequate. 5% of cases deemed "adequate" at ROSE resulted in inconclusive final interpretation with 4 ND, 7 ATY, and 6 SUS. Their distribution, anatomic location, presence or absence of diagnostic aspirate, appropriateness of ROSE adequacy statement, and any concurrent or subsequent procedures on the same or different site as well as any impact on management was reviewed. Cytotechnologist (CT) experience ranged from 1 to 25 years. CONCLUSIONS: ROSE and final cytology discrepant cases formed a very small fraction of total number of EBUS-TBNA cases with onsite evaluation. None of these discordant cases had any major clinical impact. There will remain a small fraction of cases that will be inappropriately deemed as "adequate" at ROSE due to the challenging nature of the procedure.