bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic Langerhans Cell Histiocytosis (LCH) Mimicking Antimitochondrial Antibody (AMA)–Negative Primary Biliary Cholangitis (PBC), Presenting as a Harbinger of Multisystem LCH
Authors: Li Hua , Ells Peter , Arslan Mustafa Erdem , Robstad Karl , Lee Hwajeong
Published: September 2019

Objectives

LCH is a rare systemic disorder characterized by an infiltration of CD1a+/Langerin+ histiocytes. LCH commonly involves bone, skin, and lymph nodes in children. Hepatic involvement is rarely observed in multisystem LCH. We describe an exceptional case of hepatic LCH in an adult, mimicking AMA-negative PBC, preceding the diagnosis of multisystem LCH.

Methods

A 65-year-old man presented with intermittent pruritus, weakness, dyspnea, fever, and chills that have been progressive for 4 years. Physical examination was unremarkable. Laboratory work revealed elevated alkaline phosphatase (471 U/L; ref 40-120 U/L), GGT (271 U/L; ref 0-41 U/L), total bilirubin (2.0 mg/dL; ref 0.0-1.2 mg/dL), and direct bilirubin (1.1 mg/dL; ref 0.0-0.3 mg/dL). Indirect bilirubin, AST, and ALT were within normal limits. Liver biopsy was performed.

Results

Liver biopsy showed lobular and portal nonnecrotizing granulomas with one “florid duct lesion” with duct injury, suggestive of PBC. Tests for autoimmune diseases including AMA were negative. ERCP was negative for biliary obstruction. One month after the liver biopsy, he developed flaking, red, and burning rash on the right scalp, forehead, and epigastric skin. A skin biopsy at an outside institution revealed dermal and epidermal infiltration of CD1a-positive histiocytes with indented nuclei and pale eosinophilic cytoplasm, consistent with LCH. Subsequent reexamination of the liver biopsy showed that the histiocytes within the florid duct lesion were positive for CD1a and S-100, while the remaining granulomas were negative. The following day, a small focus of LCH was noted in his gastric biopsy performed for gastritis symptoms.

Conclusion

Hepatic LCH may mimic AMA-negative PBC histologically and clinically, and may present as a harbinger of multisystem LCH. While rendering the diagnosis would be challenging without prior history of LCH and with focal involvement, awareness of such presentation and communication with clinical colleagues may be helpful.
Tubular Entrapment May Be Inconspicuous in Clear Cell Sarcoma of the Kidney in Early Infancy, Compared to Childhood: An In-Depth Case Comparison
Authors: Patel Krutika , Hernandez Sara Avalos , Liu S Shawn , Carter J Elliot , Manci Elizabeth
Published: September 2019

Introduction

Clear cell sarcoma of kidney (CCSK) is a rare malignancy accounting for <0.5% of all primary renal tumors, commonly diagnosed between 2 and 4 years of age and rarely occurring in early infancy. The challenging differentiation between CCSK and blastemal Wilms tumor is important because of the distinct clinical pattern of CCSK to recur and metastasize to bone and brain. The aim of this study is to discern subtle features that could assist pathologists in diagnosing CCSK in infancy.

Method

In-depth comparison of clinical, histological, and immunohistochemical findings in a case of CCSK diagnosed at 5 months of age with two cases of CCSK diagnosed at 2 and 3 years of age.

Results

Both groups were male, and each presented with an abdominal mass. Grossly, a single, firm, well-demarcated tumor, morphologically comprising monotonous small primitive round-to-polygonal/spindle cells, was seen in both groups. The major differences between the study groups were growth patterns and stromal reactions. In infancy, the growth pattern was diffusely uniform sheets of malignant cells with no entrapment of tubules and inconspicuous stromal changes. However, in childhood cases, the growth pattern included well-defined tubular entrapment, as well as focal microcyst formation, myxomatous stroma, palisading bodies, and anaplastic and/or rhabdoid histology. In both study groups, the immunohistochemistry showed strong immunoreactivity with cyclin D1 and nonspecific positivity for vimentin, CD99, and BAF47.

Conclusion

CCSK has notoriously diverse histological heterogeneity and mimics other pediatric renal tumors, making diagnosis treacherous, and commonly erroneous as Wilms tumor with unfavorable histology. Despite the advent of immunohistochemical and molecular techniques, a thorough morphologic analysis remains key in accurately diagnosing CCSK at any age, especially in early infancy. This small in-depth comparison of CCSK by age groups suggests that tubular entrapment and stromal changes may be less conspicuous in CCSK in early infancy than at older ages.
Acute Appendicitis Associated With Schistosoma Species
Authors: Castillo Jesus Rico , Alame Diana , Tuluc Madalina , Nagurney Michelle , Ghusson Noha
Published: September 2019

Objectives

Schistosomiasis is a public health problem in tropical regions of the world, highly endemic in sub-Saharan Africa but uncommon in the United States. It is considered second only to malaria as the most devastating human parasitic diseases, and it is mainly classified as urinary or intestinal. Here we report a rare case of acute appendicitis associated with Schistosoma spp.

Case Presentation

A 28-year-old male presented to our institution in October 2018 with a 2-day history of periumbilical and right lower quadrant abdominal pain associated with nausea, vomiting, fever, and chills. CT scan of the abdomen in the emergency department showed hyperenhancement of the appendix, with an increased diameter of 10 mm and infiltration of the adjacent fat, compatible with appendicitis. The patient was administered intravenous piperacillin-tazobactam and underwent an uncomplicated laparoscopic appendectomy. Histopathological examination of the appendectomy specimen reveals neutrophilic infiltrate of the wall consistent with acute appendicitis, with granulomatous inflammation surrounding parasitic eggs measuring 60 by 37 μm morphologically consistent with Schistosoma spp. within the wall. Additionally, Ziehl-Neelsen stained negative.

Significant travel history included a trip to Lake Malawi approximately 9 years prior to this presentation where he frequently swam in freshwater lakes. He does not recall developing an acute illness associated with this travel.

Discussion

Chronic schistosomiasis is the result of host immune responses to schistosome eggs that become lodged in the capillaries or organs and cause granulomatous reactions. Chronic inflammation can lead to bowel wall ulceration, hyperplasia, and polyposis and, with massive infection, to periportal liver fibrosis, dysuria, and hematuria. Small bowel involvement is very unusual and only rare cases of appendicitis have been reported worldwide. Additionally, Ziehl-Neelsen stained negative favoring other Schistosoma species instead of S mansoni, S intercalatum, or S japonicum. Fortunately, the patient underwent surgery, received praziquantel, and achieved full recovery.
A Rare Case of Sclerosing Variant of Pancreatic Neuroendocrine Tumor-Expressing Glucagon
Authors: Xia Rong , Koloori Maryam Noori , Alshal Mohamed , Dehghani Amir , Xie Qiang , Li Zhonghua
Published: September 2019

Introduction

Sclerosing variant of pancreatic neuroendocrine tumor (PanNET) is a rare variant of PanNET characterized by decreased tumor cellularity and prominent stromal fibrosis, and it is considered associated with serotonin expression. We herein present an unusual case of a sclerosing PanNET expressing glucagon.

Methods

The patient, a 75-year-old woman with refractory diabetes, scaly erythematous skin plaques in the eyelid, bilateral elbows and scalp, and episodes of nausea and poor appetite, presented to emergency department for acute abdominal pain. Abdominal computed tomography showed a 17-mm pancreatic head mass. Endoscopic ultrasound with fine-needle biopsy was performed for histopathological examination, followed by pancreaticoduodenectomy.

Results

Biopsy showed a background of predominantly blood and benign strips of pancreatic parenchyma and scanty fragments of fibrotic hyalinized stroma containing medium-sized atypical monotonous cells with round-to-ovoid nuclei, smooth borders, and inconspicuous nucleoli. These cells were difficult to characterize morphologically due to the scanty sampling. Immunohistochemical stains revealed the atypical cells were positive for AE1/AE2, synaptophysin, chromogranin, and glucagon and negative for insulin, serotonin, and pancreatic polypeptide. The lack of heterogeneous peptide cell composition supported a neoplastic proliferation of neuroendocrine cells. The pancreaticoduodenectomy specimen showed a 1.2-cm white firm mass in the pancreatic head. Histopathological study showed that, in a sclerotic background, the tumor cells grew mostly in trabecular patterns and occasionally in single cells, infiltrating into adjacent pancreatic parenchyma, and showed the same immunoprofile features as in the biopsy specimen. The proliferative index was <3%, supporting the diagnosis of low-grade sclerosing PanNET. The patient recovered well postsurgery. Moreover, the episodes of nausea and loss of appetite improved postsurgery. Patient did not show up for follow-up appointments in the dermatology clinic.

Conclusion

Sclerosing PanNET is challenging for diagnosis, especially on small biopsy specimens. Immunohistochemistry helps establish the diagnosis. Our case demonstrates a rare presentation of sclerosing PanNET expressing glucagon.
Characteristics of Adenocarcinoma of the Gallbladder Following Cholecystectomies in the Hispanic Population
Authors: Gustafson David , Padilla Osvaldo
Published: September 2019

Introduction

Gallbladder adenocarcinoma (GBC) is a rare malignancy. Frequency of incidental adenocarcinoma of the gallbladder in the literature is approximately 0.2% to 3%. Typically, GBC is the most common type and is discovered late, not until significant symptoms develop. Common symptoms include right upper quadrant pain, nausea, anorexia, and jaundice. A number of risk factors in the literature are noted for GBC. These risk factors are also more prevalent in Hispanic populations. This study sought to compare patients with incidental gallbladder adenocarcinomas (IGBC) to those with high preoperative suspicion for GBC. Predictor variables included age, sex, ethnicity, radiologic wall thickening, gross pathology characteristics (wall thickness, stone size, stone number, and tumor size), histologic grade, and staging.

Methods

Cases of GBC were retrospectively analyzed from 2009 through 2017, yielding 21 cases. Data were collected via Cerner EMR of predictor variables noted above. Statistical analysis utilized conditional logistic regression analysis.

Results

The majority of patients were female (n = 20) and Hispanic (n = 19). There were 14 IGBCs and 7 nonincidental GBCs. In contrast with previous research, exact conditional logistic regression analysis revealed no statistically significant findings. For every one-unit increase in AJCC TNM staging, there was a nonsignificant 73% reduction in odds (OR = 0.27) of an incidental finding of gallbladder carcinoma.

Conclusion

This study is important in that it attempts to expand existing literature regarding a rare type of cancer in a unique population, one particularly affected by gallbladder disease. Further studies are needed to increase predictive knowledge of this cancer. Longer studies are needed to examine how predictive power affects patient outcomes. This study reinforces the need for routine pathologic examination of cholecystectomy specimens for cholelithiasis.
Poorly Differentiated Large-Cell Neuroendocrine Carcinoma of the Cecum: A Rare Malignancy
Authors: Rajack Fareed , Afsari Ali , Naab Tammey
Published: September 2019

Poorly differentiated neuroendocrine carcinomas (PDNECs) are rare tumors that can arise anywhere in the gastrointestinal tract. They often present at advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage.

A 65-year-old female presented with progressively worsening bilateral proximal muscle weakness of 3 months’ duration. It was associated with fatigue, decreased appetite, and unintentional weight loss (8 lbs). She was also found to have hypercalcemia (serum calcium 12.1 mg/dL), anemia (hemoglobin 9.9 g/L), and abnormal liver panel (Alk phos 336, AST 85, GGTP 737). CT abdomen showed abnormal thickening and mass-like enhancement in the cecum measuring 2.9 × 3.7 cm and an enlarged 22-cm liver with numerous rounded masses, the largest measuring 4.6 × 8.2 cm. Colonoscopy revealed a large ulcerated mass distal to the ileocecal valve and extending to the proximal ascending colon. Histology revealed an ulcerated invasive pleomorphic large cell neoplasm with focal squamous differentiation and a tubular adenoma. Initial positive immunostains were AE1/AE3, CK5, and p63. CK7, CK20, S100, and calretinin were negative. Strong, diffuse expression of synaptophysin confirmed neuroendocrine carcinoma; high Ki-67 (80%) confirmed grade 3. CDX2 and TTF1 were positive but are not lineage specific in PDNECs. A liver biopsy had identical histology with diffuse expression of CD56, another confirmatory neuroendocrine marker. Elevated random urine 5-hydroxyindoleacetic acid (5HIAA) supported the diagnosis. Mismatch repair (MMR) protein immunostains did not reveal deficient MMR.

Colonic NECs are extremely rare, accounting for 0.6% of patients with colorectal carcinoma; of these, only 0.2% are classified as large cell NECs. A panel of immunostains confirms the diagnosis. They most often arise in the cecum or rectum with early liver metastases and median survival of 9 months. Rare cases have responded to checkpoint inhibitors, which may be a therapeutic option.
Prostate Carcinoma With Overlapping Features of Small Cell and Acinar Adenocarcinoma: A Case Report
Authors: Cordeiro-Rudnisky Fernanda , Sun Yue , Saade Rayan
Published: September 2019

Introduction

Prostate neuroendocrine (NE) cells can stimulate prostate adenocarcinoma (PA) cell growth, but occasionally adenocarcinoma cells themselves acquire NE characteristics, a phenomenon known as NE transdifferentiation of prostate adenocarcinoma. During this process, tumor cells acquire small cell-like morphology and become positive for neuroendocrine markers. NE transdifferentiation is associated with decreased androgen receptor (AR) signaling, a mechanism of resistance to AR-targeted treatments.

Case

A 74-year-old male with a history of cirrhosis, splenomegaly, and thrombocytopenia presented with hematuria and urinary obstruction. PSA was 0.31 ng/mL. CT scan demonstrated bladder wall thickening. Surgery showed a bladder tumor, clinically diagnosed as urothelial tumor. Pathology revealed a poorly differentiated carcinoma, with small cell-like morphology. The tumor cells had high nuclear to cytoplasmic ratio, focal nuclear molding, and high mitotic rate, like small cell carcinoma. But the nucleoli were intermediate between small cell carcinoma and usual adenocarcinoma of the prostate. Immunostains showed that the tumor cells were positive for NKX3.1 and focally positive for NE markers, including chromogranin, synaptophysin, INSM1, and FOXA2. The tumor cells were negative for PSA and GATA3. The morphology and immunoprofile are consistent with Gleason pattern 5 PA in transdifferentiation to small cell carcinoma.

Discussion

The incidence of neuroendocrine phenotype is 1% in primary PA and 25% in metastatic castrate-resistant PA. Typically, NE transdifferentiation occurs in response to androgen deprivation therapy/AR inhibitors. Pretreatment NE transdifferentiation is relatively uncommon. PA depends on androgens for its progression, which is the basis for antiandrogen therapy. Decreased AR expression associated with NE transdifferentiation is a mechanism of resistance to AR-targeted therapy. These tumors are often more aggressive with worse prognosis.

Conclusion

Our patient has Gleason pattern 5 PA with NE transdifferentiation invading the bladder, which is a high-grade, aggressive tumor.
Epithelioid Gastrointestinal Stromal Tumors: A Retrospective Look
Authors: Khandakar Binny , Ghosh Sharmila , Sun Jihong
Published: September 2019

Objectives

Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal tumor of the gastrointestinal tract (GIT). Most tumors are of spindle cell type. Approximately 20% of the cases are of epithelioid histologic variant and approximately 10% are mixed epithelioid and spindle type. We sought to identify the clinical and pathologic features of GIST with epithelioid features diagnosed at our institute.

Methods

The database was searched (2017-2018) and 26 cases were included for the series. The data were analyzed systematically for histologic subtype, age, site, stage, risk group, and immunohistochemical findings.

Results

Pure epithelioid GIST (PE-GIST) was seen in nine cases (35%). Seventeen tumors were mixed subtype (M-GIST). PE-GIST was more common in females. Mean age of patients was similar in both subtypes. PE-GIST most commonly involved stomach (n = 8). Small intestine was the most commonly involved by M-GIST (n = 10). Mixed tumors were larger in size (6.0 cm, mean) compared to PE-GIST (4.2 cm, mean). Tumors showing pure epithelioid subtype were more in the high-risk category, compared to the mixed subtype (33% vs 23%). Most cases of M-GIST were pT3. M-GIST expressed both c-Kit and DOG-1 more frequently than the PE-GIST (70% vs 55%).

Conclusion

Mixed epithelioid and spindled GIST was more common than the pure form. Coexpression of DOG-1 and c-Kit was less frequent in PE-GIST. Mixed tumors tend to have higher stage than the pure type at presentation.
Detecting FLI1 Fusion by Immunohistochemistry (IHC) Stain in Prostatic Adenocarcinoma
Authors: Xu Kemin , Budhai Alexandra , Pattarkine Rugved , Zhong Minghao
Published: September 2019

Objectives

The most common genetic alterations in prostate cancer are fusions of ERG and other members of the E26 transformation-specific (ETS) family of transcription factors, including ETV1, ETV4, and FLI1. Analyzing TCGA data, we found that similar to ERG fusion, FLI1 fusion-associated FLI1 mRNA level increases. ERG IHC stain has been a surrogate test for ERG fusion. Therefore, we hypothesize that FLI IHC stain could also be used to detect FLI1 fusion in prostate cancer.

Methods

In total, 111 primary prostate adenocarcinoma (>10% by volume) cases from our institute were selected for tissue microarray (TMA) construction. The regular full section slides and TMA slides were subject to IHC stain of ERG and FLI1 (Santa Cruz, SC-113). The criteria for positive FLI1 are (1) nuclear staining; (2) only in tumor cells, not in nontumor cells; and (3) FLI1-positive cells should be negative for ERG IHC staining.

Results

For prostate TMA slides, ~50% of cases were positive for ERG; ~30% of cases were weakly positive for FLI1. However, all of the FLI1 weakly positive cases were positive for ERG as well possibly due to cross-reactivity between ERG and FLI1, which was demonstrated in other studies.

Conclusion

Overall, we conclude that the cross-reactivity between FL1 and ERG precluded the detection of FLI1 fusion in prostatic adenocarcinoma under current conditions. We are in the process of selecting some cases to detect FLI1 fusion by next-generation sequencing (NGS) and FISH.
Endoscopically Unresectable Paneth Cell (PC)–Containing Adenomas and the Risk of Developing Colorectal Neoplasia
Authors: Saade Rayan , Fu Zhiyan , Lee Hwajeong
Published: September 2019

Objectives

Whether the presence of Paneth cells (PCs) in colorectal adenomas indicates an increased risk of colorectal neoplasia or not is controversial. We examined the clinicopathologic features of PC-containing adenomas (PCAs) that were surgically removed, focusing on the risk of developing subsequent colorectal neoplasia on follow-up.

Methods

A retrospective cohort of 154 patients with endoscopically unresectable colorectal adenomas who underwent surgical removal was retrieved. Archived pathology slides were evaluated for the presence of PC, villous features, and high-grade dysplasia. Demographic and clinical data were obtained by reviewing electronic medical records. A minimum 12 months of follow-up was considered valid follow-up data. Fisher’s exact test and Student t test were performed when indicated (P < .05 was considered statistically significant).

Results

PCAs were identified in 84 out of 154 cases (54.5%), commonly in the proximal as compared to distal colorectum (60.7% vs 38.1%, P = .018). There was no significant difference in patient age (mean, 66.0 vs 63.8), gender (M:F, 42:42 vs 35:35), adenoma size (mean, 3.18 cm vs 2.78 cm), villous features (69.0% vs 68.6%), and high-grade dysplasia (44.0% vs 35.7%) between PCA and non-PCA groups. After the mean follow-up duration of 65.8 months (range 12-169), 11 out of 30 patients (36.7%) had recurrent colorectal neoplasia, including 2 adenocarcinomas in the PCA group, as compared to 8 out of 27 (29.6%) in non-PCA group with no adenocarcinoma (P > .05). No statistical difference in the risk of developing colorectal neoplasia was noted between proximal PCA (24%), distal PCA (33.3%), and non-PCA (29.6%) groups.

Conclusion

PCAs are more common in the proximal colon, consistent with normal anatomic distribution of PC in the colon. No association was observed between PCA and high-grade dysplasia or colorectal neoplasia risk in endoscopically unresectable adenomas. PCA location was not a significant marker for future adverse outcomes.
Paratesticular Adipocytic Neoplasms Evaluated at a Single Institution
Authors: Mustafa Mohamed , Priemer David , Idrees Muhammad , Chen Shaoxiong
Published: September 2019

Objectives

Some of the scrotal masses are extratesticular neoplasias and develop from paratesticular tissues. Paratesticular region has a complex anatomy and contains epididymal and testicular appendages as spermatic cord, testicular tunicas, epididymis, and vestigial remnants. Therefore, neoplasms originating from this region comprise a heterogeneous group of tumors. Herein, we document paratesticular adipocytic neoplasms and the patient’s mean age and the mean size of tumor at presentation.

Methods

We retrospectively searched our database for paratesticular adipocytic neoplasms from the year 2001 to 2015. A total of 47 cases were identified and reports were reviewed.

Results

Of the total 47 cases, 28 (60%) spermatic cord lipomas, 9 (19%) well-differentiated liposarcomas, and 10 (21%) dedifferentiated liposarcomas were identified. The mean age for presentation for these diseases was of 41, 59, and 68 years, respectively.

Conclusion

The most common paratesticular adipocytic neoplasm in our institution is spermatic cord lipoma (60%), occurring in younger age group (mean age 40 years). However, up to 40% cases are malignant and include well-differentiated and dedifferentiated liposarcoma, occurring at a relatively older age population (59 and 68, respectively).
Results of Baseline Assessments of Two Viral Load and Early Infant Diagnosis Laboratories in Gaza Province, Mozambique
Authors: Nhabomba Augusto , Assane Mariamo , Adamo Noorbebi , Benzane Octavia , Pinto Isabel , Macave Admiro , Basu Debby , Landgraf Kenneth
Published: September 2019

Following the WHO 2013 recommendations for routine HIV viral load (VL) testing as the tool to monitor antiretroviral therapy, countries have prepared for massive testing scale-up. However, developing countries that also bear the highest HIV prevalence often lack qualified human resources and basic infrastructure. Mozambique has established 13 VL laboratories, including 2 in the province with the highest overall HIV prevalence, Gaza. The challenges to VL testing implementation and this rapid scale-up demand an urgent investment toward laboratory accreditation to ensure accurate and reliable VL results. To identify gaps and areas for improvement where additional resources may be needed to provide high-quality VL testing services, the CDC developed a VL and Early Infant Diagnosis (EID) scorecard (106 points; 5 levels). The scorecard evaluates 9 key areas, including (1) Personnel, (2) Facility/Environment, (3) Safety, (4) Procurement/Inventory, (5) Sample Management, (6) Equipment, (7) Process Control, (8) M&E Documents and Records, and (9) Internal Quality Audits/Quality Indicators. These 9 essential areas cover the pretesting, testing, and posttesting phases along the continuum of care for HIV patients. Baseline assessments in the two VL and EID laboratories in Gaza Province, Carmelo Molecular Laboratory and Xai-Xai Molecular Laboratory, were recently conducted. Personnel standards and M&E documentation represented strengths across both laboratories, with over 70% of the master list of M&E documents having been developed and in use. The overall gaps identified included poor segregation and prioritization of higher VL results (>1,000 cp/mL), lack of internal audits, and no follow-up of nonconformities. Both laboratories scored in the level 2 range, with a total of 68 points (Carmelo) and 78 points (Xai-Xai). Considering this is a baseline assessment, we conclude that both labs are on an excellent path toward accreditation; however, additional laboratory quality mentorship is needed in order to reach accreditation standards.
Association of Inflammation With Markers of Atherogenicity in Subjects With New-Onset Atria Fibrillation in a Nigerian Community
Authors: Nwadike Constance , Nwakamma Amarachi , Nwanjo Harrison , Nwosu Denis , Ezekwe Roy
Published: September 2019

Objectives

The evidence supporting the role of circulating markers of inflammation in the pathogenesis of atria fibrillation remains controversial. This study investigated the levels of serum lipids, C-reactive proteins, erythrocyte sedimentation rate, prothrombin time, and platelet count in subjects with new-onset atria fibrillation (NAF), but with no established cardiac disease, in a Nigerian community.

Methods

The case control study involved a total of 200 subjects: 110 subjects with NAF and 90 apparently healthy subjects without AF, as control. AF was confirmed by a 12-lead electrocardiogram (ECG), while excluding subjects with high risk. Blood samples from the subjects were analyzed for the following parameters: C-reactive proteins using ELISA method and serum lipids using an enzymatic, colorimetric method; erythrocyte sedimentation rate, by Westergreen method; platelet count using a Midray hematology auto analyzer; and the prothrombin time using a tissue thromboplastin method. Data collected from the result were analyzed using SPSS version 15.

Results

There was a significant increase in the levels of C-reactive proteins and ESR in subjects with NAF when compared with the control subjects. A significant increase was observed in the mean values of total cholesterol and low-density lipoproteins in subjects with NAF, while that of high-density lipoproteins was lower in NAF than in controls. There was no significant difference in the mean values of triglyceride in NAF and the control. Results also showed significantly reduced prothrombin time, with more platelet count in subjects with NAF. The result demonstrated that females (56.3%) had greater risk of developing AF than males (45.8%), while incidence of AF was observed to increase with age.

Conclusion

The results of the markers assayed suggest marked dyslipidemia, inflammation, and thrombogenesis in subjects with new-onset AF. Hence dyslipidemia and inflammation play critical roles in the pathogenesis of atria fibrillation.
Positive Propoxyphene Test Result for Drug-Free Serum or Plasma Obtained When Using the Roche Cobas c502 Urine Propoxyphene Screening Test
Authors: Jagannathan Geetha , Curtis Mark , Stickle Douglas
Published: September 2019

Introduction

During a recent autopsy case, we were asked to investigate possible surreptitious inpatient use of drugs of abuse (DOA). As serum was the only sample type available for this subject, we initially ran serum samples on our urine drugs of abuse (DOAU) assays. Results were unexpectedly positive for propoxyphene (PPX). We immediately determined, however, that all plasma or serum samples, selected randomly from the hospital laboratory as presumed-negative controls, produced PPX-positive test results on the urine PPX assay. We report our investigation of this finding.

Methods

The PPX urine assay (Roche Cobas c502, Indianapolis, IN) is a semiquantitative screening test based on kinetic interaction of microparticles in solution (KIMS), with a cutoff concentration of 300 ng/mL. The assay was conducted according to manufacturer’s instructions, other than the substitution of plasma for urine as described below. Plasma or urine samples were obtained from to-be-discarded samples residual from routine testing in the hospital laboratory.

Results

Pooled plasma required a 1:4 dilution with drug-free urine to produce a PPX-negative test result. Bovine serum albumin (7 g/dL), mimicking total protein of plasma, produced a PPX-negative test result. Pretreatment of plasma using heterophilic antibody blocking reagent (Scantibodies Laboratory, Santee, CA) did not alter the PPX-positive test result. However, pretreatment of plasma by polyethylene glycol (PEG) to precipitate immunoglobulins altered the test result to PPX negative. PEG pretreatment did not alter PPX-positive results for PPX-spiked urine.

Conclusions

An autopsy case produced an incidental finding of false-positive test results for plasma tested on the Roche urine PPX assay. Based on PEG pretreatment data, it appears that some common component of immunoglobulins in plasma produces a positive interference in this assay. In principle, rare circumstances of severe renal dysfunction to produce plasma-like urine could potentially lead to false-positive results with the Roche urine PPX screening test.
Verification of Access OV Monitor (Cancer Antigen 125) Assay on Beckman Coulter Unicel DXI 800
Authors: Ollila Eric , Cao Liyun , Hardy Robert
Published: September 2019

CA 125 levels are increased in ovarian carcinoma and other benign and malignant conditions. Levels are used to monitor response to therapy and disease progression. The objective of this study was to assess the analytical performance of the Access OV Monitor assay on the Beckman Coulter DXI. CA 125 was quantitatively determined on Beckman Coulter DXI following CLSI guidelines. Performance was evaluated for linearity, sensitivity, reference range, and precision. Within-run and between-run precisions were assessed by analyzing QC material at low and high concentrations. Accuracy was assessed by comparing 147 consecutive values with the previously established Siemens ADVIA Centaur XP. Antigen levels were classified as positive or negative based on the upper limit of the reference range to assess concordance between the two analyzers. The analytic measurement range was linear between 0.5 and 5,000 U/mL with a slope of 0.983 and intercept of 0.46. The reference range was 0 to 35 U/mL. Within-run CVs were 3.4% and 3.5% at low (53.81 U/mL) and high (392.78 U/mL) levels, respectively. Between-run CVs were 3.46% and 3.0% at low and high levels, respectively. The comparison results showed slope was 1.319 with an intercept of 12.61 and correlation coefficient of 0.9868 (Deming regression). The mean bias was 57.36 (33.98%). The correlation coefficient was 0.9633 and 0.9833 when CA 125 was negative and positive, respectively. The bias was 3.51 (25.73%) and 142.12 (34.41%) when CA 125 was negative and positive, respectively. The agreement was 94% (n = 138) and disagreement was 6% (n = 9). In conclusion, CA 125 on Beckman Coulter DXI has good linearity and precision and shows positive bias. There is good correlation and agreement between the two methods. Clinicians can reliably use the assay but should consider the potential bias when interpreting values near the upper end of the reference range.
Real-Time Detection of Analytical Outliers on the Roche Troponin T Generation 5 Assay
Authors: Wockenfus Amy , Hartung Katherine , Kelley Brandon , Katzman Brooke , Donato Leslie , Jaffe Allan , Karon Brad
Published: September 2019

Introduction

Analytical outliers occur with most troponin assays and can adversely affect patient management. We developed a system to detect analytical outliers for the Roche Troponin T (cTnT) Gen 5 assay using repeat analysis of samples manifesting changing values over 2 to 6 hours.

Methods

In our ED practice, troponins are collected at baseline, 2 hours, and at times at 6 hours in plasma separator tubes and processed on the Roche Cobas e411 (Indianapolis, IN). When troponin values change by ≥10 ng/L or ≤10 ng/L in the 2- or 6-hour sample compared to baseline, the sample that produced the result is repeated. If initial and repeat values differ by > ±5 ng/L (cTnT <100 ng/L) or ±5% (cTnT ≥100 ng/L), the initial value is deemed to be an analytical outlier. Outliers are confirmed by a third measurement.

Results

Since March 2018, 19 of 17,154 (0.11%) troponin samples analyzed have been labeled outliers. Outliers were falsely elevated in 14 cases and falsely decreased in 5. Mean (range) of initial cTnT values for outliers was 39 ng/L (18-621 ng/L), with only one initial value >100 ng/L. All changes could affect analysis of change over time. Eleven of 19 outliers were outside gender-specific reference interval on both samples and thus did not cause a change from abnormal to normal. Repeat measurements on 8 of 19 outliers were within the URL, which may have greater clinical consequences.

Conclusions

Repeat analysis upon observation of changing values allows detection of analytical outliers in real time, prior to reporting results. These outliers are almost always clinically significant in terms of interpretation of changing values and at times change patients from above to below the URL. If we tested more than just changing samples, we might detect still more outliers.
Detecting Liver Fibrosis by Recent Reliable Biomarkers in Viral Hepatitis Patients
Authors: Addissouky Tamer
Published: September 2019

Objectives

By far, chronic viral hepatitis and its complications have been considered a fatal health public issue. Liver biopsy has a pivotal role to distinguish patients who need proper care and regular screening. The correlation between alternative biomarkers and liver fibrosis has been studied by current research to avoid histopathology techniques.

Methods

Several biomarkers such as COLL-IV, COMP, and hyaluronic acid besides scoring systems (FIB-4, APRI, NAFLD, and SHASTA) were measured and calculated in 143 infected cases with HCV and HBV. Also, the same parameters were determined in 75 healthy persons as controls. The Metavir system was used to classify infected cases from F0 to F4. Alternative marker levels were determined by using the ELISA technique. HBV DNA and HCV RNA were quantified by implementing the RT-PCR assay. Noninvasive markers were approved by comparison with the mentioned scoring indexes.

Results

Our research has indicated that hyaluronic acid, COMP, Coll-IV, and scoring indexes of fibrosis discriminate fibrosis cases from the nonfibrosis group. The studied biomarkers have high sensitivity from 77.05% to 96.72% and accuracy from 89.71% to 97.79% as well as their cutoff, which approved the aim of this study. Thereafter, the studied markers’ reports assisted in differentiating primary stages F1+F2 from late levels F3+F4 of fibrosis.

Conclusions

According to reports of the current study, serum markers including HA and CO-IV have performed better than biopsy in excluding advanced fibrosis from mild fibrosis patients comfortably as well as differentiating fibrosis patients from healthy individuals, while the COMP test has low accuracy and needs further research. Scoring systems alone are likely not sufficiently sensitive to rule out significant disease. Hence, gathering serological markers and scoring indexes are being perfected to determine all stages of fibrosis definitely. However, further research is needed to prove reliable noninvasive markers of liver fibrosis.
Paroxysmal Nocturnal Hemoglobinuria: Grasping the Flow of Diagnostic Dilemmas
Authors: Nguyen Phuong-Lan
Published: September 2019

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening condition due to an acquired somatic mutation of the PIGA gene, leading to nonmalignant clonal expansion of hematopoietic stem cells, which are deficient in glycosyl phosphatidylinositol-anchored proteins (GPI-APs). Fluorescein-labeled proaerolysin (FLAER) and flow cytometry are key tools in the diagnosis of PNH. While clonal detection of PNH in both tests has a sensitive diagnostic threshold of 0.01% in erythrocytes and 0.05% to 1% in leukocytes, one must be cautious in ruling out the possibilities of myelodysplastic syndrome (MDS) or aplastic anemia. We propose guidelines in the differential diagnosis and evaluation of PNH from these and other hematologic disorders that can arise from GPI-AP deficient cells. These guidelines are based on a meta-analysis of five research literature sources, including four case studies. We also compare and contrast our limits of quantification of the in-house PNH assay at University of Kentucky Healthcare with those of an interlaboratory validation of 11 institutions within the United Kingdom. Our report advocates for thorough evaluation of multiple laboratory and clinical variables affecting sensitivity and accuracy of flow cytometry and FLAER in PNH. Furthermore, we recommend lowering of the in-house limit of quantification from the current 1% to 0.01%. This allows for the critical consideration of conditions such as MDS and aplastic anemia and their disease courses, all of which can present with PNH clones as low as 0.01% on flow cytometry and FLAER.
Primary Chondroblastic Osteosarcoma of the Breast in a Teenager: What Is Changing?
Authors: Yahaya James
Published: September 2019

Background

Nonepithelial tumors of the breast are extremely rare and have an incidence of less than 1%. The most common nonepithelial breast tumor is phyllodes tumor (PT), which accounts for 61%. Primary osteosarcomas of the breast contribute up to only 12.5% of all the extraosseous osteosarcomas, and among young females, they are extremely rare, especially in those without a previous history of primary bone osteosarcoma. A case of a 16-year-old female with primary chondroblastic osteosarcoma of the left breast is herein presented.

Case Description

In this report, we describe and report a 16-year-old female with neither a previous history of bone osteosarcoma nor a family history of breast cancer who was diagnosed with a primary chondroblastic osteosarcoma of the left breast. The mass was shining, warm, firm, and slightly fixed. The excisional biopsy showed a large tumor measuring 11 × 9 × 7 cm, encapsulated, grayish-white, and nodular. The H&E-stained sections showed a tumor composed of atypical spindle cells, large pleomorphic epithelioid cells, and multinucleated cells of osteoclastic type with osteoid formation with abundant areas having malignant chondroid matrix. About 40 atypical mitoses/10 HPF were seen. A diagnosis of primary osteosarcoma was made. Immunohistochemically, the tumor was triple negative, vimentin was strongly positive, SMA was focally positive, and AE1/AE3 was negative. The patient was put under observation. Her postoperative course is generally promising without any complaint of pain. We present a case of a very young female with the rarest diagnosis of primary osteosarcoma involving the left breast.

Conclusion

Primary osteosarcomas of the breast carry poor prognosis by being triple negative, and because of being the rarest tumors, they pose a challenge in managing the patients due to lack of established treatment modalities.
Expression of Estrogen, Progesterone Receptors, and Human Epidermal Growth Factor Receptor 2 in Women With Breast Cancer
Authors: Mlole Angela
Published: September 2019

Introduction

Globally, breast cancer is a leading cause of female cancer-related mortality and most predominant in the premenopausal stage. Expression of hormone receptors and human epidermal growth factor receptor 2, HER2/neu, appears to be different in the premenopausal group. However, there are limited data on hormone receptor expressions among women in Uganda. Therefore, the objective of this study was to determine the expression of estrogen, progesterone receptors, and human epidermal growth factor receptor 2 in women with breast cancer.

Methods

This was a retrospective descriptive cross-sectional laboratory-based study conducted in the Department of Pathology, Makerere University. Paraffin-embedded tissue blocks were retrieved from the archive and stained with H&E for histological confirmation and establishment of histological grade and type. Immunohistochemistry staining using a mouse-derived monoclonal antibody for hormonal receptors and HER2/neu expression was also done. Data were analyzed using STATA version 13.

Results

A total of 103 patients’ tissue blocks were analyzed. The mean ± SD age of the cases was 49 ± 15 years. The majority, 55/103 (53.4%), had intermediate cancer grade and 39/103 (37.9%) had triple-negative breast cancer. The majority, 55/103 (53.4%), were positive for ER hormone expression, 48/103 (46.6%) showed positive PR hormone expression, and only 19/103 (18.5%) were HER2/neu positive. Age of the cases showed statistical significance with hormonal receptor expressions and triple-negative breast cancer (P < .05), with high-grade cancers being more common among premenopausal women.

Conclusion

The study found that the mean age of breast cancer was 49 years, invasive carcinoma of no special type (NST) was the commonest histological type, and the majority were of intermediate cancer grade. In total, 53.4% of patients were ER positive, 46.6% were PR positive, 18.5% were HER2/neu positive, and 37.9% were triple negative. Age was the only factor significantly associated with hormonal receptors and triple-negative breast cancers.
Recurrent Male Breast Cysts in the Absence of Gynecomastia: A Rare Case Report
Authors: Zayko Maria , Rollins Susan
Published: September 2019

Publications focusing on male breast neoplasms are underrepresented in literature as most lesions are benign and less prevalent than their female counterparts. Only one case of benign male breast cyst without gynecomastia has been reported in English literature thus far, although without recurrence. We highlight the case of a 73-year-old male with history of remote non-Hodgkin lymphoma and prostate carcinoma who underwent an ultrasound-guided fine-needle aspiration (US-FNA) of a palpable 4-cm soft, nontender, mobile, left subareolar breast mass. He had no nipple discharge, skin changes, or family history of breast carcinoma. Ultrasound revealed an anechoic mass devoid of blood flow and no lymphadenopathy. US-FNA yielded 13 mL of colorless fluid and no residual lesion was visualized on postprocedural ultrasound. Microscopically, the smears were acellular and the filter preparation demonstrated crystalline debris with rare fragments of epithelial tissue, favoring the diagnosis of cyst fluid with degenerated cyst lining. Due to the lack of lobular units and a less developed ductal system compared to females, cysts are highly unusual in the male breast, and thus close follow-up was recommended. The patient returned 10 months later with a recurrent 4-cm fluctuant mass in the same location. Two adjacent anechoic cysts with a submillimeter mural projection were seen on ultrasound and targeted during US-FNA. Both cysts disappeared after drainage of 13 mL of colorless fluid. Again, cytology showed a predominantly acellular collection with scant morphologically similar epithelial fragments. All breast masses in men warrant evaluation, especially in patients with a history of malignancy. Although rare, benign male breast cysts without associated gynecomastia do occur. The lesions are amenable to both diagnosis and treatment by FNA, allowing for a less invasive procedure, without undermining patient care.
Pancreatic Cyst Cytopathology: Is It Still Worthwhile to Do It?
Authors: Zhao Xiaofeng , Arriola Aileen Grace
Published: September 2019

Objectives

Cystic lesions are relatively common in the pancreas, with pseudocysts accounting for 75% to 90% among other etiologies. In contrast to cysts in other organs, cysts in the pancreas are more likely to be neoplastic rather than benign or insignificant. EUS-guided FNA has served as a minimally invasive and fast diagnosis methodology. However, the efficacy of FNA on pancreatic lesions is controversial.

Methods

A 10-year retrospective study of upper EUS-guided FNA specimens on all cystic lesions in pancreas was conducted at the pathology department of a university hospital. Diagnoses and patient demographics were obtained. The frequency of diagnosis was investigated. When available, the endoscopic findings and CEA levels were obtained for analysis.

Results

A total of 188 pancreatic cyst FNA cases were collected. Approximately 80% of the specimens were satisfactory for cytology evaluation, and the diagnosis of “negative for dysplasia/malignancy” accounted for the majority of the cases (77.6%). The presence of communication with the pancreatic duct or elevated CEA level (>192 ng/mL) does not change the frequency of negative diagnosis significantly (P = .25). Among the 29 cases with a benign impression on EUS, only 1 case was upgraded to a higher lesion on cytology (3.5%) and this cyst measured >3 cm. Among 86 cysts ≤3 cm, only 1 case was diagnosed as an IPMN and high-grade dysplasia was not identified. All 41 cases with unsatisfactory cytology were due to insufficient cellularity, including 14 cases with an impression of a questionable lesion on EUS.

Conclusion

In our patient population, EUS-guided FNA of pancreatic cysts does not add significant diagnostic value to EUS findings of benign-appearing pancreatic cysts ≤3 cm and may not be cost-effective overall. Additional molecular testing on cyst fluid obtained by EUS-FNA, especially on cases with insufficient cellularity, may enhance the value of this minimally invasive procedure and improve its diagnostic performance.
Fine-Needle Aspiration Biopsy of Neuroendocrine Neoplasms in the Liver: A 9-Year Retrospective, Single Institutional Study
Authors: Zhang Lin , Cai Zhenjian , Zhu Hui
Published: September 2019

Objectives

Neuroendocrine neoplasms (NENs) are divided into two major categories according to the 2018 WHO expert consensus proposal: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinoma (NECs). Primary liver NENs are very rare and majority of NENs in the liver are metastatic. In this study, we retrospectively reviewed NENs in the liver diagnosed by fine-needle aspiration biopsy (FNAB).

Methods

We retrospectively reviewed malignant neoplasms diagnosed by imaging-guided liver FNAB performed between 2010 and 2018 in our institution. Patients’ electronic medical records and selective slides were reviewed.

Results

A total of 624 liver FNAB cases with a diagnosis of positive for malignancy were identified. Among those cases, 56 cases (9%) were NENs. Poorly differentiated NECs constituted 71% (40/56) of cases, and well-differentiated NETs constituted 29% (16/56) of cases. The most common primary sites of poorly differentiated NECs were lung (35%, 13/40), followed by pancreas (20%, 8/40), GI tract (17.5%, 7/40), GU (7.5%, 3/40), breast (5%, 2/40), head and neck (2.5%, 1/40), GYN tract (2.5%, 1/40), and CNS (dedifferentiated glioblastoma, 2.5%, 1/40). The remaining three cases (7.5%, 3/40) were diagnosed as primary liver NECs based on the clinical presentation. All three patients presented with a single large liver mass with no other mass lesions identified in other organ systems. For well-differentiated NETs, majority were from the GI tract (81.3%, 13/16), followed by pancreas (6.25%, 1/16) and lung (6.25%, 1/16). One patient was diagnosed with metastatic NET of unknown primary.

Conclusion

NENs in liver are predominantly metastatic, and majority of them are high-grade NECs. Most of well-differentiated NETs are metastases from the GI tract, while more than one-third of poorly differentiated NECs are metastases from the lung. Primary liver NENs also occur and all three cases in this study are poorly differentiated NECs.