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.

Sharp Versus Electric Suction Curettage in Gynecologic Patients Undergoing Evaluation for Abnormal Uterine Bleeding.

STUDY OBJECTIVE: Suction curettage is preferred over sharp curettage in obstetric settings. We compare the quality of operative tissue sampling between sharp curettage and suction curettage using electric vacuum aspiration for nonobstetric abnormal uterine bleeding in reproductive-aged women. DESIGN: A retrospective cohort study. SETTING: Community hospital in Long Island, New York. PATIENTS: Women ages 21 to 45 years (n = 257) who underwent operative curettage procedure for nonobstetric abnormal uterine bleeding. INTERVENTIONS: Independent ratings of specimens from suction curettage using electric vacuum aspiration and sharp curettage by 2 pathologists blinded to method of tissue collection. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percentage of organized tissue, indicative of a higher-quality pathology specimen. Specimens obtained by electric suction curettage (p <.001) had a significantly higher percentage of organized tissue (M = 66.28, SD = 20.33) than sharp curettage (M = 55.51, SD = 24.17). There were no differences between the curettage groups for operative time, blood loss, intraoperative complications, or pathology diagnosis. CONCLUSION: Specimens obtained with suction curettage contained more organized tissue with similar pathologist satisfaction and confidence scores than sharp curettage. We suggest clinicians consider electric suction curettage in the diagnostic workup of abnormal uterine bleeding in reproductive-aged women. In addition, patient-centered benefits include no increase in operative time, blood loss, or complication rate compared with sharp curettage.

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.

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.

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.

Androgen Receptor Immunohistochemical Expression in Undifferentiated/Dedifferentiated Endometrial Carcinoma.

Uterine undifferentiated (UC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They tend to pursue an aggressive clinical course with an advanced stage at presentation. It has been found that androgen receptor (AR) might play a role as a prognostic and therapeutic marker in endometrial carcinoma. However, its expression in UC/DEAC has not been investigated. Herein, the aim of this study was to evaluate the expression of AR along with estrogen receptor (ER), progestin receptor (PR), and HER2 in UC/DEAC and also in other subtypes of high-grade endometrial carcinomas. Review of our pathology database over the period of 2011 to 2019 identified 16 UC/DEAC cases (N=16). We also randomly selected other high-grade endometrial carcinomas including FIGO 3 endometrioid carcinoma (N=9), serous carcinoma (N=8), clear cell carcinoma (N=12) and carcinosarcoma (N=10) for comparison. Immunohistochemical stains for AR, ER, PR, and HER2 were performed on all 55 cases. The protein expression was evaluated both quantitatively and qualitatively. In DEAC cases both the undifferentiated component and the well-differentiated component were recorded separately. Overall, variable degrees of AR reactivity (by Allred scoring method) was present in 63% of UC/DEACs(10/16), 67% of FIGO 3 endometrioid carcinomas (6/9), 88% of serous carcinomas (7/8), 80% of carcinosarcomas (8/10), and 9% of clear cell carcinoma (1/12). AR expression was most often seen with PR (70%) or ER (60%) staining in UC/DEACs. Thirteen cases of UC/DEACs were positive for at least 1 hormone receptor. HER2 was negative in all UC/DEACs. Almost all other high-grade carcinoma cases were negative for HER2 except 20% of carcinosarcoma (2/10) and 13% of serous carcinoma (1/8) which showed 3+ HER2. Loss of AR appears to be associated with worse clinicopathologic parameters in UC/DEAC. AR is highly expressed in UC/DEAC, and in the majority of FIGO 3 endometrioid carcinomas, serous carcinomas, and carcinosarcoma. These findings suggest a potential role for androgen inhibitors in the management of patients with these tumors.

A case of non-HPV related primary endometrioid adenocarcinoma of the cervix.

OBJECTIVE: Primary endometrioid adenocarcinoma of the cervix is a rare subtype of adenocarcinoma that has often been misclassified in the literature due to the lack of clear-cut diagnostic criteria. A new classification system has recently been developed that aims to provide clarity and reproducibility when diagnosing subtypes of endocervical adenocarcinoma. This case report demonstrates the difficulty in diagnosing primary endometroid adenocarcinoma, application of the new diagnostic guidelines, and a review of the literature of this rare non-HPV subtype. CASE: A 76 year-old women presented with postmenopausal bleeding and was found to have an exophytic cervical mass. Biopsies showed an adenocarcinoma of probable endometrial origin. She underwent a robotic-assisted simple hysterectomy with bilateral pelvic lymph node sampling and omental biopsy. Final pathology report demonstrated a primary endometrioid adenocarcinoma of the cervix, measuring 2.4 cm in size, diagnosed using the recently developed International Endocervical Adenocarcinoma Criteria and Classification (IECC) system. Patient was then treated with external beam radiation therapy and concurrent chemotherapy, followed by vaginal brachytherapy. She had no evidence of disease at her 15-month follow-up visit. CONCLUSION: Primary endometrioid adenocarcinoma of the cervix is a rare and diagnostically challenging tumor of the cervix. This case illustrates the challenges associated with diagnosis of this endocervical carcinoma subtype and the need for a multi-disciplinary approach when determining treatment.

Differentiating Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features from Classic Papillary Thyroid Carcinoma: Analysis of Cytomorphologic Descriptions Using a Novel Machine-Learning Approach.

BACKGROUND: Recent studies show various cytomorphologic features that can assist in the differentiation of classic papillary thyroid carcinoma (cPTC) from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Differentiating these two entities changes the clinical management significantly. We evaluated the performance of support vector machine (SVM), a machine learning algorithm, in differentiating cases of NIFTP and encapsulated follicular variant of papillary thyroid carcinoma with no capsular or lymphovascular invasion (EFVPTC) from cases of cPTC with the use of microscopic descriptions. SVM is a supervised learning algorithm used in classification problems. It assigns the input data to one of two categories by building a model based on a set of training examples (learning) and then using that learned model to classify new examples. METHODS: Surgical pathology cases with the diagnosis of cPTC, NIFTP, and EFVPTC, were obtained from the laboratory information system. Only cases with existing fine-needle aspiration matching the tumor and available microscopic description were included. NIFTP cases with ipsilateral micro-PTC were excluded. The final cohort consisted of 59 cases (29 cPTCs and 30 NIFTP/EFVPTCs). RESULTS: SVM successfully differentiated cPTC from NIFTP/EFVPTC 76.05 ± 0.96% of times (above chance, P < 0.05) with the sensitivity of 72.6% and specificity of 81.6% in detecting cPTC. CONCLUSIONS: This machine learning algorithm was successful in distinguishing NIFTP/EFVPTC from cPTC. Our results are compatible with the prior studies, which show cytologic features are helpful in differentiating these two entities. Furthermore, this study shows the power and potential of this approach for clinical use and in developing data-driven scoring systems, which can guide cytopathology and surgical pathology diagnosis.

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.

Clear cell adenocarcinoma of the uterine cervix in an 18 year-old pregnant female.

•An 18 year old nulliparous woman was diagnosed with clear cell adenocarcinoma of the cervix in pregnancy.•LEEP conization at 33.3 weeks gestation led to premature rupture of membranes. Following cesarean section, a radical hysterectomy was performed.

Metanephric stromal tumour: A rare pediatric benign stromal specific renal neoplasm.

A case of incidentally detected Metanephric Stromal Tumour (MST) is reported here. This is a rare, recently recognized pediatric benign stromal specific renal neoplasm. A review of the English literature revealed only five cases after its original description by Argani et al. Recognition of this entity can spare a child from potentially toxic adjuvant chemotherapy that might be used to treat malignant lesions which are part of the differential diagnosis, particularly clear cell sarcoma of kidney (CCSK).