Value of additional sections: Tissue handling of small biopsies in detecting squamous dysplasia of the uterine cervix.

Cervical cancer screening is currently based on high-risk human papillomavirus (HR-HPV) molecular testing, Pap cytology testing, and histologic evaluation of cervical biopsies. As primary HPV screening for cervical cancer becomes widely used, some of the recommended screening guidelines propose colposcopy and biopsies following positivity for HPV16/18 without cytologic triage. In such instances, a biopsy would be the only tissue sample available for informing further management. The use of additional histologic levels on cervical biopsies is commonly employed to achieve a diagnosis, although no set criteria for when to obtain additional levels exist. In this study, we evaluated the value of additional sections in cervical biopsy and endocervical curetting, as well as clinical and histologic features that should be considered when ordering additional levels. Additional levels were obtained for the following scenarios: benign mucosa with Pap discrepancy (HSIL or ASC-H interpretation), size discrepancy with the gross description, suspicious atypia for a high-grade lesion, and long-standing high-risk HPV infection. A change in diagnosis was observed in 21.4% of the cases, with an upgrade to a high-grade squamous intraepithelial lesion (CIN2-3) in 12.1% of cases. An initial impression of atypia significantly correlated with both a change in diagnosis and an upgrade to CIN2-3. In the era of primary HPV screening, when evaluating tissue samples following positive HPV test, small, atypical foci should be followed by additional levels. We recommend six (6) initial levels on all cervical biopsies, particularly if there is no loss of tissue between the levels, to ensure an accurate interpretation. This will be crucial in the timely and accurate identification of HPV-related intraepithelial lesions and proper subsequent management.

Third-trimester placentas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive women: histomorphology, including viral immunohistochemistry and in-situ hybridization.

AIMS: The wide variety of affected organ systems associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the need for tissue-specific evaluation. We compared placentas from SARS-CoV-2-positive and SARS-CoV-2-negative women in our hospital in New York City, which became the epicenter of the coronavirus disease 2019 pandemic in March 2020. To date, some limited studies have been published on placentas from SARS-CoV-2-positive women. The aim of our study, in addition to describing histomorphology, was to utilize in-situ hybridization (ISH) for the S-gene encoding the spike protein and immunohistochemistry (IHC) with the monoclonal SARS-CoV-2 spike antibody 1A9 for placental evaluation. METHODS AND RESULTS: In this study, 51 singleton, third-trimester placentas from SARS-CoV-2-positive women and 25 singleton, third-trimester placentas from SARS-CoV-2-negative women were examined histomorphologically according to the Amsterdam Criteria and with ISH and/or IHC. The corresponding clinical findings and neonatal outcomes also were recorded. Although no specific histomorphologic changes related to SARS-CoV-2 were noted in the placentas, evidence of maternal-fetal vascular malperfusion was identified, with placentas from SARS-CoV-2-positive women being significantly more likely to show villous agglutination (P = 0.003) and subchorionic thrombi (P = 0.026) than placentas from SARS-CoV-2-negative women. No evidence of direct viral involvement was identified with ISH and IHC. CONCLUSIONS: In this study, third-trimester placentas from SARS-CoV-2-positive women were more likely to show evidence of maternal-fetal vascular malperfusion; however, ISH and IHC provided no evidence of direct viral involvement or vertical transmission.

Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF ß2.

Tumor microenvironment (TM) is an essential element in prostate cancer (PCA), offering unique opportunities for its prevention. TM includes naïve fibroblasts that are recruited by nascent neoplastic lesion and altered into 'cancer-associated fibroblasts' (CAFs) that promote PCA. A better understanding and targeting of interaction between PCA cells and fibroblasts and inhibiting CAF phenotype through non-toxic agents are novel approaches to prevent PCA progression. One well-studied cancer chemopreventive agent is silibinin, and thus, we examined its efficacy against PCA cells-mediated differentiation of naïve fibroblasts into a myofibroblastic-phenotype similar to that found in CAFs. Silibinin's direct inhibitory effect on the phenotype of CAFs derived directly from PCA patients was also assessed. Human prostate stromal cells (PrSCs) exposed to control conditioned media (CCM) from human PCA PC3 cells showed more invasiveness, with increased alpha-smooth muscle actin (α-SMA) and vimentin expression, and differentiation into a phenotype we identified in CAFs. Importantly, silibinin (at physiologically achievable concentrations) inhibited α-SMA expression and invasiveness in differentiated fibroblasts and prostate CAFs directly, as well as indirectly by targeting PCA cells. The observed increase in α-SMA and CAF-like phenotype was transforming growth factor (TGF) ß2 dependent, which was strongly inhibited by silibinin. Furthermore, induction of α-SMA and CAF phenotype by CCM were also strongly inhibited by a TGFß2-neutralizing antibody. The inhibitory effect of silibinin on TGFß2 expression and CAF-like biomarkers was also observed in PC3 tumors. Together, these findings highlight the potential usefulness of silibinin in PCA prevention through targeting the CAF phenotype in the prostate TM.

Evaluation of dual p16/Ki-67 immunostaining on anal cytology specimens.

INTRODUCTION: Dual immunostaining for p16/Ki67 is FDA-approved for use on liquid-based cervical cytology specimens; however, the utility of dual staining in anal cytology especially for ASCUS risk stratification is not well established. METHODS: We investigated dual staining performance on anal cytology specimens and correlated with subsequent cytologic interpretation, high-risk HPV status, and anal biopsy results. Dual staining for p16/Ki-67 was performed on all liquid-based anal cytology specimens from December 2021 to June 2022 (n = 43). RESULTS: Three patients had high grade squamous intraepithelial lesion (HSIL/AIN2-3) on biopsy; dual staining was positive in all three cases. All HR-HPV negative cases were negative for dual staining. Among the 12 ASCUS samples with subsequent anal biopsy results all also had HR-HPV testing. Due to small sample size of cases with squamous intraepithelial lesion (SIL) diagnosed on biopsy, the sensitivity and positive predictive value was not calculated. However, the specificity and negative predictive value of p16/Ki-67 dual staining for SIL of any grade on biopsy were 1 (95% CI: 0.66-1) and 0.9 (95% CI: 0.65-0.97) respectively, whereas the specificity and negative predictive value of HR-HPV testing for SIL of any grade on biopsy were 0.44 (95% CI: 0.14-0.79) and 0.8 (95% CI: 0.41-0.96) respectively. CONCLUSION: Dual p16/Ki-67 staining indicates transforming HPV infection and could help serve as an ancillary test for risk stratification for atypical anal cytology specimens. Among ASCUS samples, dual staining was specific for SIL of any grade with a high negative predictive value and therefore could be useful in clinical practices with limited availability for follow-up care.

A six-year comprehensive review of eye cytology cases received at a tertiary level hospital.

BACKGROUND: Ocular cytology is an effective method of diagnosing infective, benign, and malignant ocular disease processes due to easy accessibility and rapid turnaround time. However, these specimens pose significant diagnostic challenges due to rarity of the specimen type, sparse diagnostic material available for ancillary workup, and unfamiliarity of the diagnostic entities by the cytopathologist. METHODS: This study conducted a 6-year comprehensive review of 65 eye cytology cases received at a tertiary level hospital. Cytopathologic diagnoses of "negative for malignancy" and "atypical" were categorized as negative findings (70.8%, n = 46) and diagnoses of "suspicious for malignancy" and "positive for malignancy" were categorized as positive findings (23.1%, n = 15). A 44.6% (n = 29) of cases had subsequent histopathology and/or flow cytometry diagnoses. Premalignant and malignant lesions detected on histopathology were considered as significant findings. Statistical analysis was performed to evaluate the concordance of ocular cytology with associated histopathology and/or flow cytometry diagnoses. RESULTS: The accuracy of final cytology-histopathology and/or cytology-flow cytometry diagnoses in this cohort of cases is 86.2%. The sensitivity and specificity of ocular diagnosis by cytology are 66.6% and 100%, respectively. The positive and negative predictive values of ocular diagnosis by cytology are 100% and 80.9%, respectively. CONCLUSION: Ocular cytology is a fast, effective, and sensitive method for diagnosing ocular pathology specimens. Familiarity with these specimen types by cytopathologists can help in diagnosing ocular diseases effectively on small, challenging cytologic preparations.

CytoLyt fixation impedes insulinoma-associated protein 1 (INSM1) immunoreactivity compared to formalin fixation.

INTRODUCTION: Insulinoma-associated protein 1 (INSM1) is an immunohistochemical marker commonly used to confirm cytomorphological concordant neuroendocrine tumors/carcinomas (NETs/NECs), demonstrating high utility in small samples. Previous reports have suggested comparable INSM1 staining in CytoLyt-fixed cell blocks and formalin-fixed surgical pathology specimens. This study aimed to assess INSM1 immunoreactivity using both fixation methods and investigate potential factors contributing to its variable expression. MATERIALS AND METHODS: A retrospective query was performed (03/31/21-05/31/22) for NET/NEC cases that had both formalin- and CytoLyt-fixed cell blocks. We collected clinical data and reporting of immunostains for each case. INSM1 staining was evaluated in both fixation methods, and reported as positive, negative, or equivocal. Equivocal INSM1 staining was further scored as a percentage of 1%-100% and intensity of weak (faint staining), moderate (darker staining), and strong (dense staining). RESULTS: Our search identified 20 cases from diverse body sites, including mediastinal lymph nodes (40%), pancreas (35%), lung (20%), and porta hepatis lymph nodes (5%). All cases exhibited a widespread positivity (over 90%) in formalin-fixed cell blocks. In contrast, CytoLyt fixed cells showed a negative stain in 65% of cases and 30% exhibited an equivocal positivity. CONCLUSIONS: While INSM1 is previously reported as a sensitive (75%-100%) and specific (82.7%-100%) marker for NET/NECs, our study found a reduced immunohistochemical staining in CytoLyt-fixed cell blocks. Consequently, false negative INSM1 immunohistochemical results in CytoLyt-fixed cell block material may pose a pitfall in the diagnosis of NET/NEC.

Significance of concurrent HPV testing with unsatisfactory Papanicolaou test for prediction of follow-up HPV, Papanicolaou test, and biopsy results.

OBJECTIVES: Approximately 1% to 2% of routine cytologic specimens collected for Papanicolaou testing are unsatisfactory for evaluation. The American Society for Colposcopy and Cervical Pathology 2019 guidelines recommend repeat testing within 2 to 4 months of an unsatisfactory Papanicolaou test (UPT) result. METHODS: We evaluated the utility of follow-up Papanicolaou testing, human papillomavirus (HPV) testing, and biopsy in 258 cases of UPTs. RESULTS: High-risk HPV testing was positive in 17.4% (n = 45) and negative in 82.6% (n = 213) of cases at the time of initial UPT; 8.1% (n = 21) of cases had discordant HPV test results. Similarly, 3.8% (n = 8) of initially HPV-negative cases were reported to be HPV-positive on follow-up; 28.9% (n = 13) of initially HPV-positive cases were reported to be HPV negative on follow-up. In total, 27.1% (n = 70) of cases underwent biopsy. Biopsies with significant findings were present in 40% (n = 12) of HPV-positive cases and 7.5% (n = 3) of HPV-negative cases. Low-grade squamous intraepithelial lesion (LSIL) (low-grade cervical intraepithelial neoplasia [CIN-1]) was the most significant finding in all 3 HPV-negative biopsies; 58.3% (n = 7) of HPV-positive biopsies showed LSIL (CIN-1), 13.3% (n = 4) showed HSIL (high-grade CIN), and 3.3% (n = 1) showed invasive carcinoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of concurrent HPV testing at the time of UPT for predicting follow-up HPV test result within 1 year of initial UPT are 80.0%, 94.0%, 71.1%, and 96.2%, respectively. The sensitivity, specificity, PPV, and NPV of initial HPV test results for predicting follow-up Papanicolaou test results are 67.7%, 89.7%, 48.8%, and 95.0%, respectively. RESULTS: Concurrent HPV testing in the setting of UPT can be a sensitive tool for predicting follow-up HPV status and significant findings of squamous intraepithelial lesions on follow-up Papanicolaou tests and biopsy.

Diagnostic utility of PRAME immunohistochemistry in PEComa family of tumors and morphologic mimics with emphasis on the gynecologic tract.

Perivascular epithelioid cell tumors (PEComas), rare mesenchymal tumors with myomelanocytic differentiation, can be a diagnostic challenge, often requiring a panel of immunohistochemical markers. Preferentially expressed antigen in melanoma (PRAME) is a relatively new antigen with utility in diagnosing melanomas. This study aimed to survey PRAME expression patterns in the PEComa family of tumors and morphologic mimics. Twenty cases of PEComas and 27 non-PEComas (10 leiomyosarcomas, 3 smooth muscle tumors of uncertain malignant potential [STUMPs], 11 leiomyomas, 1 uterine inflammatory myofibroblastic tumor [IMT], and 2 low-grade endometrial stromal sarcomas [LGESSs]) were stained with PRAME and compared to previously performed HMB45 and Melan-A stains, when available. Tumors showing no or barely perceptible PRAME staining at 10× were considered negative. Tumors were considered positive if there was full nuclear staining evident at 10× in at least one 10× field. Diffuse staining was defined as positivity in at least 80% of tumor nuclei. Overall, PRAME was expressed in 70% of PEComas, with diffuse positivity in 60%. However, PRAME was not specific for PEComas, with immunopositivity in the majority (70%) of uterine leiomyosarcoma cases, though negative in STUMP, leiomyoma, IMT, and LGESS cases. PRAME sensitivity was 70% and specificity was 74%, while HMB45 was more sensitive (90%) and specific (100%), but only 15% of PEComas showed diffuse staining. Melan-A staining was less common than HMB45 or PRAME, with only 18.8% sensitivity but 100% specificity. Among gynecologic PEComas, PRAME was expressed in 75% overall and enriched among malignant cases (85.7% positive). As part of an immunohistochemical panel, PRAME could be useful in the workup of PEComa cases. In the future, PRAME-specific immunotherapies may be beneficial in treating patients with malignant PEComas.

An unusual case of carcinoma with mesonephric-like features with a spindle cell component diagnosed on the Pap test of the uterine cervix: Cytomorphologic and immunophenotypic features and diagnostic pitfalls.

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the cervix, endometrium, and ovary. In contrast to mesonephric carcinomas (MC), mesonephric-like adenocarcinomas are not associated with mesonephric remnants. Both entities have a similar appearance with regards to varying histomorphology patterns, including glandular, tubular, spindled, solid, and papillary, and have a specific immunophenotype and molecular features. We present a case of a 54-year-old HPV-negative woman with a Pap test that exhibits high-grade malignancy. The cell block displayed malignant cells with positive stains for PAX8, GATA3, and TTF1 by immunohistochemistry. The diagnosis of adenocarcinoma with mesonephric like features was rendered. MLA can be challenging on the small specimens and often misinterpreted as other endometrial neoplasms. Furthermore, the accurate diagnosis carries a well-described risk of aggressive clinical behavior.

Prophylactic endovascular internal iliac balloon placement during cesarean hysterectomy for placenta accreta spectrum.

BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.

Clinical Correlates of Placenta Accreta Spectrum Disorder Depending on the Presence or Absence of Placenta Previa: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate whether there are differences in risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa. DATA SOURCES: We performed a systematic search in Medline, EMBASE, ClinicalTrials.gov , and Web of Science from inception through April 25, 2022, without language or date restrictions. Search strategy included the key words "placenta accreta," "placenta increta," "placenta percreta," "adherent placenta," "invasive placenta," "abnormal placent*," "placenta previa," and "marginal placent*." METHODS OF STUDY SELECTION: Of the 1,122 articles screened, seven studies were included in the final review. Studies were included if they compared the risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa. TABULATION, INTEGRATION, AND RESULTS: A random-effects model was used to pool the mean differences or odds ratios (OR) and the corresponding 95% CIs using RevMan software. A total of 3,342 pregnancies complicated by placenta accreta spectrum were included in the meta-analysis (2,365 without previa and 977 with previa). Pregnancies complicated by placenta accreta spectrum without previa were more likely to have been conceived by in vitro fertilization (IVF) (OR 3.11, 95% CI 1.93-5.02, P <.001, I 2 =52.0%) and to be associated with prior dilation and curettage (D&C) (OR 1.60, 95% CI 1.15-2.22, P =.005, I 2 =0.0%) and myomectomy (OR 2.47, 95% CI 1.31-4.66, P =.005, I 2 =0.0%), but they were less likely to be associated with prior cesarean delivery (OR 0.15, 95% CI 0.06-0.37, P <.001, I 2 =87.0%). Placenta accreta spectrum without previa was less likely to be diagnosed antenatally (OR 0.07, 95% CI 0.04-0.11, P <.001, I 2 =38.0%). Also, women with pregnancies without previa had lower rates of red blood cell transfusion, intensive care unit admission, risk of hysterectomy, unscheduled delivery, and intraoperative bowel or bladder injuries. CONCLUSION: Pregnancies complicated by placenta accreta spectrum without previa had a more prominent association with IVF and prior D&C and myomectomy but were much less likely to be associated with prior cesarean delivery. Further, placenta accreta spectrum without previa was less likely to be diagnosed antenatally, although it had better maternal outcomes as compared with placenta accreta spectrum with previa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022307637.

Updated Review on Pathology of Endocervical Adenocarcinoma with Emphasis on Clinically Relevant Findings.

In the present review, we summarize and critically appraise recent advances in the pathology of endocervical adenocarcinoma. In recent years, the diagnosis of endocervical adenocarcinoma has shifted from morphologic criteria classification in 2014 World Health Organization (WHO) to etiology- based classification of International endocervical adenocarcinoma criteria and classification (IECC). IECC recommends classifying endocervical adenocarcinoma into Human Papillomavirus (HPV)- associated and non-HPV-associated. Ultimately, this approach may lead to different treatment options based on molecular pathways rather than purely based on the tumor's grade and stage. Recently, the College of American Pathologists (CAP) has incorporated stromal invasion patterns as an optional data set in the synoptic report. The pattern of invasion classification is a valuable prognostic tool in excision specimens. CONCLUSION: IECC is a simple classification system that recognizes and classifies endocervical tumors based on pathogenesis and association to HPV. The pathologists should also be familiar with the pattern-based classification of endocervical adenocarcinoma.

Anal cytology and high-risk human papilloma virus testing in atypical squamous categories: Value of concurrent testing in management of high-risk population.

Anal squamous cell carcinoma is relatively rare, but its incidence and mortality have been increasing worldwide. While anal cytology is a sensitive cancer screening modality, its specificity is low, and data for concurrent high-risk human papilloma virus (HR-HPV) testing are limited. At our institution, anal cancer screening consists of combined anal cytology and high-risk human papilloma virus (HR-HPV) testing on all specimens. The aims of the study were to correlate results of atypical cytological diagnoses [atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)] with HR-HPV testing and determine if co-testing may potentially influence management. A retrospective search over 24-months was performed for anal cytology specimens with diagnoses of ASCUS and ASC-H. Corresponding HR-HPV (HPV 16/18 and Other-31/33/35/39/45/51/52/56/58/59/66/68) results were retrieved, and concordance/discordance was recorded. Cytology results were correlated with anal biopsy diagnoses, when available. A total of 139 patients, including 127 with ASCUS and 12 with ASC-H, were identified. Of the ASCUS cases, 90/127 (70.9%) had HR-HPV, and a squamous intraepithelial lesion (SIL) was evident in 20/39 (51.2%) of biopsies. All 12/12 (100%) ASC-H were associated with HR-HPV and 3/6 (50%) biopsies had a SIL. Our study supports use of concurrent cytology and HR-HPV for anal cancer screening cytology. Co-testing improves specificity of atypical cytology diagnoses and can identify patients requiring further intervention.

Molecular Profiling Reveals Limited Targetable Biomarkers in Neuroendocrine Carcinoma of the Cervix.

Neuroendocrine carcinoma of the cervix (NEC) is a rare and highly aggressive cervical malignancy. Given that no targeted therapy has been approved specifically to NEC, we investigated the presence of novel, potentially targetable biomarkers in a large cohort of NEC. Sixty-two NEC were molecularly profiled for biomarkers of targeted therapies including antibody-drug conjugates [delta-like canonical notch ligand 3 (DLL3), a trophoblast cell surface antigen 2 (TROP-2), and folate receptor 1 (FOLR1)], NTRK1-3 gene fusions, and immune checkpoint inhibitors [programmed death-ligand 1 (PD-L1), tumor mutational burden, and microsatellite instability] using immunohistochemistry and DNA/RNA next-generation sequencing assays. A cohort of squamous cell carcinomas of the cervix (n=599) was used for comparison for immune-oncology biomarkers. DLL3 expression was observed in 81% of the cases. DLL3 expression was inversely correlated with commonly observed pathogenic mutations in PIK3CA (17%) (P=0.018) and PTEN (10%) (P=0.006). Other more frequently seen pathogenic mutations (TP53 17%, KRAS 11%, and CTNNB1 5%) were not associated with DLL3 expression. TROP-2 expression was detected in only 1 case and no case expressed FOLR1. Although NTRK protein expression was observed in 21% of the cases, none of these had an NTRK gene fusion. PD-L1 expression (10%) and high tumor mutational burden (3%) were significantly less frequent in NEC compared with the squamous cell carcinoma cohort (79% and 11%, respectively). None of the NEC exhibited high microsatellite instability status. Despite frequent DLL3 expression in NEC, a potential therapeutic benefit of DLL3-targeted drugs remains uncertain given the recent failure of the Rova-T therapeutic trial in small cell lung carcinomas. Small cohorts of NEC enriched in PIK3CA/PTEN/AKT and programmed cell death protein 1/PD-L1 alterations indicate therapeutic roles for their respective inhibitors.

Detection of STRN-ALK fusion in thyroid nodules with indeterminate cytopathology facilitates papillary thyroid cancer diagnosis.

Thyroid cancer is the most common endocrine malignancy. Approximately 70% of cases of papillary thyroid carcinoma and 50% of poorly differentiated and anaplastic thyroid carcinoma harbor well-characterized driver mutations and chromosomal rearrangements that drive tumorigenesis. Molecular profiling has been helpful in identifying and informing follow-up strategies in tumors with more aggressive trajectories. Here, we report a case of papillary thyroid cancer (PTC) discovered in a patient with thyroid nodules with relatively benign ultrasound and fine needle aspiration (FNA) findings. Molecular testing in this patient identified a rare STRN-ALK fusion in two thyroid nodules with indeterminate and/or benign cytology. This led to the patient undergoing a thyroid lobectomy and a subsequent confirmation of papillary thyroid carcinoma upon resection. The report highlights the role of comprehensive molecular testing in thyroid lesions of indeterminate cytology.

Pretransplant IgG antibodies to polyoma BK virus in pediatric renal transplants.

We retrospectively measured IgG antibody levels to BKV in pretransplant sera and compared levels in children who developed BK viremia to a control group who remained free of infection after transplantation. Sera from 45 renal transplant patients were available for analysis (BK viremia = 23, controls = 22). Serum BKV PCR levels ranged from 3400 to 6.5 million DNA copies/mL (mean +/- s.d.: 978K +/- 1.77 million) and were highest in patients with BK nephritis (p = 0.007). Overall, 35% of children with BK viremia were BKV-seronegative vs. 9% of children in control group (p = 0.04), but mean antibody levels were similar between viremic and control patients (p = 0.15). However, children who developed viremia later than six months post-transplantation had significantly lower antibody levels compared with controls (p = 0.004) and patients with early viremia (p = 0.007), and may represent de novo infection or reinfection, rather than recurrence of latent infection. Pretransplant antibody status was significantly associated with subsequent development of BK viremia. Although our findings identified possible factors for developing BK viremia, there was sufficient overlap of both seropositive status and antibody levels among viremic patients and the control group to question the clinical utility of pretransplant IgG antibodies.

A Synoptic Electronic Order Set for Placental Pathology: A Framework Extensible to Nonneoplastic Pathology.

Accurate pathologic assessment in placental pathology is mostly dependent on a complete clinical history provided by a clinical team. However, often, the necessary clinical information is lacking, and electronic order sets (EOSs), if implemented correctly, create an opportunity for entering consistent and accurate clinical data. In this viewpoint piece, we describe a framework for synoptic EOS in placental pathology. We outline the necessary data and create optional clinical data that get entered as a dropdown menu of free text. While EOSs are the best way to approach and diagnose placenta and other nonneoplastic pathologic specimens, the barriers for implementation include paper requisitions and a cultural mindset resistance. The aspiration for our synoptic EOS is to become an effective tool for communication between proceduralists and pathologists for proper diagnosis of placental specimens. Through our EOS, the appropriate and complete clinical context is conveyed from the clinical teams to the pathologist. The pathologist can easily and rapidly extract the necessary information to render an accurate and precise diagnosis. The captured data likewise become a valuable research resource.

Adamantinoma-like Ewing Sarcoma of the thyroid gland: Cytomorphologic, phenotypic and molecular features.

Adamantinoma-like Ewing Sarcoma (ALES) is a rare subtype of Ewing sarcoma family of tumors (EFTs) which are defined by their EWSR1 gene rearrangements. We present a case of a 15-year old female with a swelling in her anterior neck of 4 months duration which had recently begun to rapidly grow in size. Fine needle aspiration showed a small blue round cell tumor with immunoreactivity for cytokeratin, CD99 and FLI1. Material for molecular testing was available on the resection specimen. Demonstration of t(11;22) (EWS-FLI1) was helpful in establishing the diagnosis.

Utility of Stathmin-1 as a Novel Marker in Evaluating Anal Intraepithelial Neoplasia (AIN).

The aim of this study is to determine whether immunohistochemistry for Stathmin-1 enhances diagnostic accuracy of anal dysplasia. The study included 40 biopsies with diagnosis of benign anal transitional zone (n=10), low-grade anal intraepithelial neoplasia (AIN) (AIN1, n=10), and high-grade AIN (AIN2, n=10, AIN3, n=10). The cases were selected to represent classic features. Immunohistochemistry for Stathmin-1, p16, and Ki-67 was performed and assessed for distribution within epithelial thickness. Stathmin-1 was expressed only in the basal layer of benign anal epithelium. Similar pattern of distribution was seen in all low-grade AIN cases (100%). In total, 40% of AIN2 showed Stathmin-1 staining pattern similar to AIN1. The other 60% of cases showed staining extending into the middle third of the epithelial thickness. Of AIN3 cases, 20% showed staining confined to the lower third epithelium, 20% showed staining extending to the middle third, and 60% showed staining extending into the upper third epithelium. The pattern of stain distribution suggested that staining extending above the lower one-third of the epithelial thickness discriminates between low-grade and high-grade AIN. With this cutoff, the sensitivity for the diagnosis of high-grade AIN was 70%, specificity was 100%, positive predictive value equaled 100%, and negative predictive value equaled 77%. P16INK4a showed 100% sensitivity for AIN2 and AIN3, whereas Ki-67 had 100% sensitivity for any AIN grade. In conclusion, Stathmin-1 has excellent specificity for the diagnosis of high-grade AIN; however, Stathmin-1 alone may not be sufficiently sensitive. Use in conjunction with other sensitive markers, such as p16 or Ki-67 may be considered.

Cytologic smears improve accuracy of frozen sections of ovarian tumors in the community practice settings.

BACKGROUND: The ovaries can be the site for various primary tumors and also the presenting site of metastatic disease. Quick and correct intraoperative diagnosis is crucial for the patient's further management. The aim of this study was to demonstrate the advantages of the combined diagnostic method - ovarian frozen sections in conjunction with cytologic smears. METHODS: From June 2016 to June 2017, we prospectively prepared additional two cytologic smears with Diff-Quik stain on ovarian frozen sections comprised of two hematoxylin and eosin sections. For quality assurance purposes, we compared the results of frozen section discrepancies and deferrals with those that of the previous year from June 2015 to June 2016. RESULTS: With the introduction of cytologic smears to ovarian frozen sections, the number of discrepancies and deferrals combined decreased from 13.75% to 7.85%. The most benefit of smears was observed in primary ovarian malignancies. CONCLUSIONS: In the setting where all the members of the pathology group render cytologic evaluations routinely, smears play an important complementary role.