Basal Cell Carcinoma With Metastasis to the Thoracic Spine: An Uncommon Case Report and Review of the Literature.

Basal cell carcinoma is an exceedingly rare cause of spinal metastatic disease for which the treatment algorithm is poorly defined. We present a positive patient outcome after treatment of T8 metastatic basal with posterior decompression and fusion followed by later anterior reconstruction, in addition to targeted radiation therapy and pharmacologic therapy. In general, a personalized and comprehensive treatment approach should be used, incorporating surgical, oncologic, and pharmacologic methods as able. Moreover, primary preventive medical and mental health care can help prevent delayed presentation and increased access to timely care.

Strong Annexin A10 Expression Supports a Pancreatic Primary and Combined Annexin A10, Claudin 18, and SOX2 Expression Supports an Esophagogastric Origin in Carcinomas of Unknown Primary.

Primary tumor site determination for gastrointestinal (GI) tract and pancreaticobiliary (PB) tree carcinomas that present as metastasis of unknown primary can be problematic. Annexin A10 (ANXA10), claudin 18 (CLDN18), and trefoil factor 1 (TFF1) have been identified through expression profiling as markers of gastric lineage commitment; sex-determining region Y (SRY)-box transcription factor 2 (SOX2) expression has been reported in several tumor types, including gastric adenocarcinomas. We evaluated the diagnostic utility of immunohistochemistry for ANXA10, CLDN18, SOX2, and TFF1 for determining the site of origin for GI/PB adenocarcinomas. Immunohistochemistry for all 4 markers was performed on tissue microarrays including 559 GI/PB tumors and 421 other tumors. H-scores were calculated as the product of the intensity (0 to 3) and extent (percentage, 0% to 100%) of staining. Positive staining was defined as >5% staining. ANXA10 expression was most frequent in pancreatic adenocarcinomas when compared with all other GI/PB tumors (96.4% vs. 43.5%, P <0.001). Strong staining for ANXA10 (H-score ≥200) distinguished pancreatic ductal adenocarcinoma from intrahepatic cholangiocarcinoma and adenocarcinomas of the gallbladder and colorectum (69.6% vs. 0%, P <0.001). Triple positivity for ANXA10, CLDN18, and SOX2 was more frequent in esophagogastric tumors than in other GI/PB tumors (22.6% vs. 4.1%; P <0.001). TFF1 expression was observed in nearly all tumor types. Staining for ANXA10, CLDN18, and SOX2 as part of a panel may aid in distinguishing esophagogastric adenocarcinomas from lower GI/PB tumors. ANXA10 staining may be particularly useful in distinguishing pancreatic adenocarcinomas from intrahepatic cholangiocarcinoma and adenocarcinomas of the gallbladder and colorectum.

GATA3 expression in clear cell adenocarcinoma of the lower urinary tract: a potential diagnostic pitfall.

BACKGROUND: Clear cell adenocarcinoma of the lower urinary tract (CCACLUT) is a rare primary malignant neoplasm with heterogenous morphology. There is a paucity of data in the literature regarding its immunohistochemical profile. METHODS: The immunohistochemical features (extent and intensity) of a multinational cohort of CCACLUT were evaluated with comparison between clear cell adenocarcinoma of the female genital tract (CCACFGT, tissue microarray) and nephrogenic adenoma (NA). RESULTS: 33 CCACLUT (24 female, 9 male; mean age 59 years) were collected. CCACLUT most commonly arose from the urinary bladder (26/33, 78%), particularly from the trigone (10/33, 30.3%) followed by the urethra (8/33, 22%). All 12 NA cases were located at the urinary bladder, whereas the most common CCACFGT location was the ovary (29/56, 52%). None of the CCACLUT patients had, intestinal metaplasia, NA, or urothelial carcinoma. One patient had concurrent endometriosis of the sigmoid colon. Most frequently observed morphology in CCACLUT was papillary/tubulocystic (9/3; 27.3%), followed by papillary/tubular (6/33; 18.2%) and papillary/solid (5/33; 15.2%). GATA3 expression was significantly higher in CCACLUT (18/33, 54.5%) and NA (6/12, 50%), when compared to CCACFGT cases 6/56, 11.7%)(p = 0.001 and p = 0.022, respectively). The extent of GATA3 was significantly higher in CCACLUT group (19.2 ± 16.6%) than the other groups (9.6 ± 22.5% in NA and 2.6 ± 9% in CCACFGT group) (p = 0.001). 4/33 patients (12.1) had weak, 10/33 patients (30.3%) had moderate, and 4/33 patients (12.1%) had strong GATA3 intensity in CCACLUT group. In NA group, one patient (8.3%, 1/12) had weak, one patient (8.3%, 1/12) had moderate and 4 patients (33.3%, 4/12) had strong GATA3 intensity. Most cases (CCACLUT 29/33, 88%; NA 11/12, 92%; CCACFGT 46/56, 82.1%) had positive Napsin A expression, by which CCACLUT had significantly more cases with Napsin A expression (p = 0.034). p63 was consistently negative in all cases (30/33 (91.9%) CCACLUT; 12/12 (100%) NA; 42/56 (75%) CCACFGT. Ki67 (MIB) proliferation index was significantly higher in CCACLUT group (54.6 ± 21%) when compared to NA group (4.5 ± 2.7%) and CCACFGT group (35.5 ± 25.8%) (p = 0.001). CONCLUSION: CCACLUT has consistent GATA3 expression, which may cause challenge in the diagnosis of urothelial carcinoma but can be used to distinguish CCACLUT from CCACFGT.

Reference Intervals for Clinical Chemistry Analytes for Transgender Men and Women on Stable Hormone Therapy.

BACKGROUND: Gender-affirming hormone therapy with either estradiol or testosterone is commonly prescribed for transgender individuals. Masculinizing or feminizing hormone therapy may impact clinical chemistry analytes, but there is currently a lack of published reference intervals for the transgender population. METHODS: Healthy transgender and nonbinary individuals who had been prescribed either estradiol (n = 93) or testosterone (n = 82) for at least 12 months were recruited from primary care and internal medicine clinics specializing in transgender medical care. Electrolytes, creatinine, urea nitrogen, enzymes (alkaline phosphatase, ALK; alanine aminotransferase, ALT; aspartate aminotransferase, AST; gamma-glutamyltransferase, GGT), hemoglobin A1c, lipids [total cholesterol, high-density lipoprotein (HDL), triglycerides], and high-sensitivity C-reactive protein (hsCRP) were measured on 2 clinical chemistry platforms. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. RESULTS: There was minimal impact of gender-affirming hormone therapy on electrolytes, urea nitrogen, hemoglobin A1c, and hsCRP. In general, the enzymes studied shifted toward affirmed gender. Creatinine values for both transgender cohorts overlaid the reference interval for cisgender men, with no shift toward affirmed gender for the estradiol cohort. The effects on lipids were complex, but with a clear shift to lower HDL values in the testosterone cohort relative to cisgender women. CONCLUSIONS: Transgender individuals receiving either masculinizing or feminizing hormone therapy showed significant changes in some analytes that have sex-specific variation in the cisgender population. The clearest shifts toward affirmed gender were seen with enzymes for the estradiol and testosterone cohorts and with creatinine and HDL in the testosterone cohort.

Outflow graft foreign body reaction and thrombosis in HeartMate 3 left ventricular assist device.

Outflow cannula occlusion is an infrequent complication occurring among recipients of continuous flow left ventricular assist devices. Hereby, we present a case of a 66-year-old man with a HeartMate 3 left ventricular assist device that presented 18 months after implantation and during his admission, evidence of poor left ventricular unloading and forward flow uncovered intrinsic and extrinsic outflow cannula obstruction. The patient's course was complicated by cardiogenic shock, diffuse alveolar hemorrhage and multiorgan failure. Post-mortem examination suggested foreign body reaction as a potential contributor of outflow graft obstruction at the level of the bend relief.

Temporal changes in medical student perceptions of their clinical skills and needs using a repeated self-assessment instrument.

BACKGROUND: Medical student needs in clinical skill training may change over time, but data on this topic are limited. This study uses repeated self-assessments on clinical rotations during medical school to evaluate students' perceptions of their clinical skill growth. METHODS: A self-assessment rating was completed by students during each clinical rotation as they progressed through their core clinical rotation year. The instrument consisted of questions on 5 clinical skill categories where students rated their performance as "below", "at" or "above" expected, and open-ended questions on strengths and challenges. We evaluated changes in self-ratings between the first (n=136) and third (n=118) quarters by matched-pair analysis of the shift in responses between time points using a Sign Test. We also identified the main themes from the students' responses to open-ended questions. RESULTS: We found 22.4 % and 13.3 % of students increased their self-assessment ratings on "Oral Presentation Skills" and on "Differential Diagnosis", respectively. In contrast, perceived ability to communicate with patients saw the largest negative shifts. "Patient Interaction" was the most commonly identified area of strength and "Knowledge and Organization" was most frequently cited as a barrier. CONCLUSIONS: Students demonstrated a positive shift in perceived competence in some core clinical skills that are not strongly emphasized in the preclinical curriculum, likely reflecting increased exposure over time. However, their perceived competence in communication skills declined. This may reflect initial over-estimation or true decline due to competing needs/interests. These patterns of change can inform the design of longitudinal curricula that anticipate and address students' needs during clinical rotations, such as placing increased emphasis on presentation skills and differential diagnosis earlier in the curriculum, and adding more emphasis to communication skills in later phases.

Practical Considerations for Implementation of SARS-CoV-2 Serological Testing in the Clinical Laboratory: Experience at an Academic Medical Center.

Molecular techniques, especially reverse transcriptase polymerase chain reaction (RT-PCR), have been the gold standard for the diagnosis of acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Serological tests for SARS-CoV-2 have been widely used for serosurveys, epidemiology, and identification of potential convalescent plasma donors. However, the clinical role of serologic testing is still limited and evolving. In this report, we describe the experience of selecting, validating, and implementing SARS-CoV-2 serologic testing for clinical purposes at an academic medical center in a rural state. Successful implementation involved close collaboration between pathology, infectious diseases, and outpatient clinics. The most common clinician concerns were appropriateness/utility of testing, patient charges/insurance coverage, and assay specificity. In analyzing test utilization, serologic testing in the first month after go-live was almost entirely outpatient and appeared to be strongly driven by patient interest (including health care workers and others in high-risk occupations for exposure to SARS-CoV-2), with little evidence that the results impacted clinical decision-making. Test volumes for serology declined steadily through October 31, 2020, with inpatient ordering assuming a steadily higher percentage of the total. In a 5-month period, SARS-CoV-2 serology test volumes amounted to only 1.3% of that of reverse transcriptase polymerase chain reaction. Unlike reverse transcriptase polymerase chain reaction, supply chain challenges and reagent availability were not major issues for serology testing. We also discuss the most recent challenge of requirements for SARS-CoV-2 testing in international travel protocols. Overall, our experience at an academic medical center shows that SARS-CoV-2 serology testing assumed a limited clinical role.

Reproductive Endocrinology Reference Intervals for Transgender Men on Stable Hormone Therapy.

BACKGROUND: Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but interpretation of results can be difficult due to the lack of published reference intervals. METHODS: Healthy transgender individuals who had been prescribed testosterone (n = 82) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, SHBG, prolactin, progesterone, anti-Müllerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. RESULTS: When evaluating general endocrine laboratory tests in people using masculinizing hormones, reference intervals for cisgender men can be applied for total and free testosterone and SHBG and reference intervals for cisgender women can be applied for prolactin. Reference intervals for estradiol, LH, FSH, AMH, and DHEAS differ from those used for cisgender men and cisgender women, and therefore should be interpreted using intervals specific to the transmasculine population. For testosterone and estradiol, results from immunoassays were clinically equivalent to mass spectrometry. CONCLUSION: Masculinizing hormones will alter the concentrations of commonly evaluated endocrine hormones. Providers and laboratories should use appropriate reference intervals to interpret the results of these tests.

Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy.

BACKGROUND: Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy. METHODS: Healthy transgender individuals who had been prescribed estrogen (n = 93) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, sex hormone binding globulin, prolactin, progesterone, anti-mullerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. RESULTS: The distribution of results for transgender women was different than what would be expected from cisgender men or women across all measurements. Use of spironolactone was associated with changes in the result distribution of AMH, FSH, LH, and progesterone. Compared to liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), immunoassay was sufficient for the majority of estradiol and total testosterone measurements; free testosterone added little clinical value beyond total testosterone. CONCLUSION: Reference intervals specific to transgender women should be applied when evaluating reproductive endocrine analytes. Spironolactone is a significant variable for result interpretation of some tests.

Common Hormone Therapies Used to Care for Transgender Patients Influence Laboratory Results.

BACKGROUND: Many laboratory tests are reported and interpreted with sex-specific reference intervals. However, transgender individuals receiving masculinizing or feminizing hormone therapy experience physiological changes predisposing some laboratory tests to shift outside of existing reference intervals. In this study, we review laboratory testing of a large cohort of transgender individuals who were prescribed hormone therapy for at least 6 months at an academic medical center. METHODS: Transgender patients were identified using a search function within the electronic health record with gender identity status verified by chart review. Patients were grouped based on type of hormone therapy administered. All laboratory studies were ordered for medical purposes as part of clinical care; as a result, the exact laboratory tests differed among the patients. Some of the patients had sufficient data for both 6- and 12-month comparisons with baseline laboratory values. RESULTS: Statistically significant changes were observed at 6- and 12-month comparisons in basic chemistry, endocrine, and hematologic parameters for transgender individuals receiving masculinizing or feminizing hormones. Chart review demonstrated variation in route of administration of hormone therapy and frequency of gender-affirming surgery within the study population. CONCLUSIONS: Transgender individuals receiving hormone therapy experienced significant changes in components of basic chemistry, endocrine, and hematologic parameters following administration of hormone therapy. Variability in hormone dosing and route of administration for gender-affirming treatment warrants further investigation.

Hematology reference intervals for transgender adults on stable hormone therapy.

BACKGROUND: The complete blood count (CBC) is a cornerstone of patient care. Several of the normal values for the components of the CBC differ by sex and, therefore, male-specific and female-specific reference intervals are required to interpret these laboratory results. Transgender individuals are often prescribed hormone therapy to affirm their gender, with resulting serum hormone concentrations similar to those of cisgender individuals. Gender-specific reference intervals for transgender men and women have not been established for any laboratory measurements, including hematology. We established clinically relevant hematological reference intervals for transgender individuals receiving stable hormone therapy. METHODS: Healthy transgender individuals prescribed testosterone (n = 79) or estrogen (n = 93) for ≥12 months were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Concentrations for hemoglobin, hematocrit, MCV, MCHC, and RDWCV, as well as counts for red cells, white cells, and platelets, were evaluated. Results were interpreted in reference to the overall distribution of values and relative to serum estradiol and total testosterone concentrations. Calculated reference intervals were compared to established cisgender reference intervals. RESULTS: Regardless of serum hormone concentration, individuals prescribed testosterone or estrogen had hematology parameters that were not clinically different from cisgender males and females, respectively. CONCLUSION: The hematology parameters for transgender men and women receiving stable hormone therapy should be evaluated against the cisgender male and cisgender female reference ranges, respectively and does not require concurrent sex hormone analysis. Care providers can utilize this observation to aid in interpretation of hematology laboratory values for transgender people.

Preferred Names, Preferred Pronouns, and Gender Identity in the Electronic Medical Record and Laboratory Information System: Is Pathology Ready?

BACKGROUND: Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. METHODS: We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. RESULTS: Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. CONCLUSIONS: Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology.

Therapeutic Drug Monitoring of Pentobarbital: Experience at an Academic Medical Center.

BACKGROUND: Pentobarbital is used for management of intractable seizures and for reducing elevated intracranial pressure. Dosing of pentobarbital can be aided by therapeutic drug monitoring (TDM). There is no commercially available automated assay for measurement of pentobarbital serum/plasma concentrations; consequently, chromatography-based assays are often used. METHODS: Pentobarbital TDM was studied over a 14-year period at an academic medical center. 154 patients (94 adult, 60 pediatric) were identified who had pentobarbital levels ordered at least once during a hospital encounter. Chart review included patient diagnosis, indication for pentobarbital therapy, recent or concomitant medication with other barbiturates, patient disposition, organ donation, pentobarbital dosing changes, and neurosurgical procedures. Pentobarbital serum/plasma concentrations were determined on an automated clinical chemistry platform with a laboratory-developed test adapted from a urine barbiturates immunoassay. RESULTS: Chart review showed therapeutic use of pentobarbital generally consistent with previously published literature. The most common errors observed involved confusion in barbiturate names (eg, mix-up of pentobarbital and phenobarbital in test ordering or in provider notes) that seemed to have minimal impact on TDM effectiveness, with pentobarbital serum/plasma concentrations generally within target ranges. The laboratory-developed pentobarbital immunoassay showed cross-reactivity with phenobarbital and butalbital that was eliminated by alkaline and heat pretreatment. The immunoassay was linear to 20 mcg/mL and correlated closely with gas chromatography-mass spectrometry measurements at a reference laboratory. CONCLUSIONS: Pentobarbital TDM can be performed by immunoassay on an automated clinical chemistry platform, providing an alternative to chromatography-based methods. Confusion in barbiturate names is common, especially pentobarbital and phenobarbital.

Impact of add-on laboratory testing at an academic medical center: a five year retrospective study.

BACKGROUND: Clinical laboratories frequently receive orders to perform additional tests on existing specimens ('add-ons'). Previous studies have examined add-on ordering patterns over short periods of time. The objective of this study was to analyze add-on ordering patterns over an extended time period. We also analyzed the impact of a robotic specimen archival/retrieval system on add-on testing procedure and manual effort. METHODS: In this retrospective study at an academic medical center, electronic health records from were searched to obtain all add-on orders that were placed in the time period of May 2, 2009 to December 31, 2014. RESULTS: During the time period of retrospective study, 880,359 add-on tests were ordered on 96,244 different patients. Add-on testing comprised 3.3 % of total test volumes. There were 443,411 unique ordering instances, leading to an average of 1.99 add-on tests per instance. Some patients had multiple episodes of add-on test orders at different points in time, leading to an average of 9.15 add-on tests per patient. The majority of add-on orders were for chemistry tests (78.8 % of total add-ons) with the next most frequent being hematology and coagulation tests (11.2 % of total add-ons). Inpatient orders accounted for 66.8 % of total add-on orders, while the emergency department and outpatient clinics had 14.8 % and 18.4 % of total add-on orders, respectively. The majority of add-ons were placed within 8 hours (87.3 %) and nearly all by 24 hours (96.8 %). Nearly 100 % of add-on orders within the emergency department were placed within 8 hours. The introduction of a robotic specimen archival/retrieval unit saved an average of 2.75 minutes of laboratory staff manual time per unique add-on order. This translates to 24.1 hours/day less manual effort in dealing with add-on orders. CONCLUSION: Our study reflects the previous literature in showing that add-on orders significantly impact the workload of the clinical laboratory. The majority of add-on orders are clinical chemistry tests, and most add-on orders occur within 24 hours of original specimen collection. Robotic specimen archival/retrieval units can reduce manual effort in the clinical laboratory associated with add-on orders.