bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends of Fecal Calprotectin and Lactoferrin Results for Infants
Authors: Goold Eric , Johnson Lisa
Published: September 2019

Calprotectin and lactoferrin can be measured in stool to test for inflammation in the gastrointestinal tract associated with inflammatory bowel disease (IBD) versus irritable bowel syndrome (IBS). The clinical specificity of these markers decreases in children versus adults because of the broader differential diagnosis for intestinal inflammation in children. Surprisingly, these tests are frequently ordered for infants (age = 0 years). Therefore, we wanted to assess our historical data in order to understand how infant calprotectin and lactoferrin concentrations change over time and review literature for the potential differential diagnosis for intestinal inflammation in infants. Data were analyzed on 19,543 infants/toddlers ages 0 to 2 years who had a stool test result of either the quantitative ELISA calprotectin PhiCal assay (Eurospital) or qualitative ELISA Lactoferrin Chek assay (Techlab). For the quantitative calprotectin test, the averages and medians were graphed over time in infants. And for the qualitative lactoferrin test, the positivity rate was graphed over time in infants. Both were compared to toddlers of ages 1 to 2 years old. The average level of calprotectin in neonates (0-1 months old) was 336 ± 348 μg/g with a median of 192 μg/g. While these values were dramatically above the adult normal reference range of 0 to 50 μg/g, the average level decreased over time to 119 ± 218 μg/g with a median of 39 μg/g for toddlers 2 years old. The presence of elevated lactoferrin was detected in 89% of neonates versus 34% of toddlers age 2 years. These trends demonstrate that both calprotectin and lactoferrin may be elevated early in life for many infants, but rapidly decline with time. Ordering trends show that, for infants/toddlers age 0 to 2 years, fecal calprotectin ordering has grown rapidly, whereas fecal lactoferrin has remained stable. In conclusion, while fecal calprotectin and lactoferrin are widely used markers of pathologic intestinal inflammation in adults, results in infants must be interpreted with great care. An elevated calprotectin or lactoferrin concentration in infant stool may be pathological, perhaps due to necrotizing enterocolitis or food-associated enteropathy, but is also associated with nonpathological reasons such as intestinal exposure to food antigens or commensal bacteria. Literature studies have shown associations of elevated calprotectin or lactoferrin with diet, gestational age at birth, and even mode of delivery. Thus, it is essential that clinicians interpret calprotectin levels or the presence of elevated lactoferrin in the context of the entire clinical picture and understand the lack of specificity of these markers for pathological conditions in infants.
Invasive Mammary Paget Disease Without an Underlying Breast Cancer: A Case Report
Authors: Bousamra Alexis , Khatoon Nazia , Sandhu Ariel , Silverman Jan , Malay Mary Beth
Published: September 2019

Mammary Paget disease (MPD) is a malignant lesion of the nipple-areolar complex and considered an intraepidermal sign of an underlying invasive or in situ carcinoma. In rare instances, mammary Paget cells can invade the dermis. Comprehensive literature review identified 33 such cases. Here, we report a case of a 48-year-old female with invasive MPD, without an associated underlying breast cancer. Only five such presentations are reported. With a presentation of right nipple-areolar excoriation for 2 years, skin punch biopsy was performed and reported as “Paget disease.” Further evaluation with bilateral mammograms failed to show any primary mass or calcifications. Bilateral breast MRI revealed focal nonmass enhancement in upper outer quadrant in both breast, the biopsy of which showed benign breast tissue. Right breast nipple areolar complex resection demonstrated MPD extensively involving the epidermis. Multiple foci of invasive ductal carcinoma are present, growing downward into the nipple dermis, the largest focus being 0.2 cm in greatest dimension. No lymphovascular invasion is identified. The mammary Paget cells are positive for Cam 5.2 and epithelial membrane antigen (EMA) and negative for keratins 7 and 20. The invasive tumor cells are strongly positive for estrogen receptor (100%) and progesterone receptor (75%) and equivocal (2+) for Her2/Neu. FISH analysis showed amplification for HER2 (HER2/CEP17 ratio: 2.75). Four right axillary sentinel lymph nodes are negative for carcinoma. Two of the five patients with invasive MPD described in the literature, and without underlying breast cancer, had a sentinel lymph node biopsy performed. Isolated tumor clusters were present in one of these two cases. In summary, we describe a rare case of invasive MPD without an underlying breast cancer. Although sentinel lymph nodes are important to assess metastasis, further cases are required to evaluate the significance and prognosis of this rare entity.
Malignant Biphasic Adenomyoepithelioma: A Rare Entity
Authors: Law Timothy , Veran-Taguibao Sonia , Ibe Ifegwu , Goreal Wamda
Published: September 2019

Objectives

Adenomyoepithelioma of the breast is an uncommon biphasic breast lesion characterized by a cytologically bland epithelial and myoepithelial proliferation. It is often considered benign and thought to represent a variant of intraductal papilloma. However, rare cases of adenomyoepitheliomas have been reported to show malignant transformation. Features that favor malignancy include increased mitoses, necrosis, atypia, cellular pleomorphism, and infiltrative borders. Most reported cases of malignant adenomyoepithelioma demonstrate carcinomas arising in a benign adenomyoepithelioma.

Methods

A 74-year-old woman presented to the hospital with an 8-month history of a palpable right breast mass. Mammogram demonstrated an irregular marginated mass, and a needle core biopsy of the mass showed atypical sclerosing adenosis. A lumpectomy revealed a firm, tan-white, ill-defined 2.7-cm mass abutting the anterior and posterior margins.

Results

Histologic examination showed an infiltrative proliferation of epithelial-lined tubules surrounded by myoepithelial cells with clear cytoplasm. There were focal areas of hypercellularity with marked cytologic atypia in both the epithelial and myoepithelial components. Focal necrosis and increased mitoses (12/10 HPF) were also identified. On immunohistochemical studies, the epithelial cells were positive for CK7 while the myoepithelial cells were highlighted by p63, SMMHC, SMA, and CK5/6. Ki-67 showed an increased proliferative index (35%). ER, PR, and HER-2 immunostains were negative. The overall histologic and immunohistochemical findings support a diagnosis of malignant biphasic adenomyoepithelioma. No in situ carcinoma was identified. After the diagnosis was reported, a follow-up reexcision with axillary sentinel lymph node excision was performed. Both specimens were negative for malignancy.

Conclusion

Malignant adenomyoepithelioma of the breast is an uncommon entity and it is strongly associated with local recurrence and distant metastases. Awareness of its distinctive histologic and immunohistochemical features will be helpful in initiating the appropriate medical management for patients with this entity, which is crucial for improving prognosis and overall survival.
Invasive Mammary Carcinoma With Paneth Cell–Like Eosinophilic Cytoplasmic Granules: Is It an Entity?
Authors: Sakshi Sakshi , Persidsky Yuri , Reilly Kathleen , Taraif Suad
Published: September 2019

Breast carcinomas with Paneth cell–like eosinophilic cytoplasmic granules are rare and commonly reported in association with acinic cell carcinoma or microglandular adenosis. Paneth cell–like differentiation has been described outside the GI tract, including lung, liver, pancreas, lacrimal glands, and prostate. Very little is known about the significance of these granules and whether they represent a metaplastic or possibly a therapy-related change. There are only 45 reported cases involving the breast, mostly individual case reports or 2 to 3 case series. Although the clinical experience is limited, most of the reported cases seem clinically indolent.

Here we present a 74-year-old female with a mammographically detected 1.1-cm left breast retroareolar mass for which she underwent a biopsy and subsequent lumpectomy with axillary dissection. Histology revealed an invasive ductal carcinoma, with Paneth cell–like eosinophilic PAS-positive cytoplasmic granules in the background of extensive ductal carcinoma in situ (DCIS). Similar granules were seen in some ducts involved by DCIS. Invasive carcinoma and DCIS were present throughout the 5.5-cm lumpectomy beyond the grossly measured 4.0-cm mass. There was extensive lymphovascular invasion and tumor was present at all the surgical resection margins. Twelve of the 13 axillary lymph nodes had macrometastases. The tumor was ER and PR positive and HER2 negative. Clinically, there were extensive bony metastases involving the skull, spine, sternum, iliac bones, and femur. There were also multiple lung nodules and mediastinal lymph nodes that were positive for metastasis on biopsy. The patient is still undergoing chemotherapy and radiotherapy 6 months following surgical excision.

Our case demonstrates the heterogeneity of this entity as the clinical course in our patient has been very aggressive. A collaborative effort must be established to compile a larger case series to better our understanding of this increasingly reported histological observation and whether it represents a distinct entity.
Can You Detect Spread Through Air Spaces (STAS) in Lung Needle Core Biopsies? An Initial Investigation
Authors: Pillappa Raghavendra , Robila Valentina , King Caleb , Kraft Adele
Published: September 2019

Objectives

The debate of spread through air spaces (STAS) as a newly described pattern of invasion in lung cancer is ongoing. Some authors argue that the inclusion of STAS in the CAP synoptic template is premature and controversial as it is difficult to exclude an artifactual process. However, assessment of STAS in needle core biopsies has not been pursued. Hence, we intended to evaluate STAS in needle core biopsies, with an added emphasis on the specimen requirements for detection. Finally, correlation with the corresponding available resections was performed.

Methods

Fifty-four needle core biopsies of adenocarcinomas were examined by three pathologists. For each case, the extent of both tumor (1-12 mm) and nonneoplastic alveolated parenchyma (NNT) (2-6 mm) was measured. STAS was defined as presence of only micropapillary clusters, solid nests, and single cells in NNT adjacent to the main tumor. Corresponding lung resections available in 12 cases were also examined.

Results

Nests highly suspicious for STAS were demonstrated in 4 (7%) cases, predominantly micropapillary clusters and single cells. Of those, only one case had a surgical resection and showed STAS. When the NNT was present, then absence of STAS was determined in 20/54 (37%) tumors, all exhibiting a lepidic/acinar growth pattern. Finally, the presence of STAS could not be evaluated in 30 (55%) cases. This was due to extensive core fragmentation, sampling only from the center of the tumor, with no adjacent NNT, necrosis, or fibrotic background.

Conclusion

STAS evaluation may be performed in core needle biopsies and depends on the core quality and tumor/NNT content. Despite appropriate material, STAS was not identified in approximately one-third of cases. Rare cases with small groups suspicious for STAS were seen. These findings may provide additional information for further therapeutic/surgical guidance.
Analysis of Amplified Genes in Samples of Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma by CGH-Array Technique
Authors: Egal Erika , Sabino Welligton , Scarini João , Souza Reydson , Altemani Albina , Tincani Alfio , Del Negro Andre , Kowaski Luiz Paulo , Mariano Fernanda
Published: September 2019

Introduction

Pleomorphic adenoma (PA) is a benign lesion of the salivary glands that can suffer malignant transformation to carcinoma ex adenoma pleomorphic (CXPA). The pathogenesis of CXPA has been attributed to the accumulation of genetic disorders in preexisting PAs. However, there is no confirmation whether there is a common target gene involved in all histopathological subtypes or the decisive factors for malignant transformation in a histopathological subtype are specific.

Objectives

To further analyze genes found in PA and CXPA using the CGH-array technique. The genes found were analyzed using the InteractiVenn virtual tool (http://www.interactivenn.net/) and grouped into a Microsoft Excel worksheet.

Results: Of the 460 genes amplified in the studied samples, 287 (62.4%) were related only to CXPA, whereas 144 (31.3%) were related to residual PA. Twenty-nine (6.3%) of these genes were common between residual PA and CXPA. Regarding the degree of invasion of CXPA, there was an increase in the number of genes amplified as the degree of invasion and aggression increased: 8 genes related to intracapsular CXPA, 65 to minimally invasive CXPA, and 373 to weakly invasive. Moreover, when comparing residual AP and intracapsular CXPA, two genes were common to these groups: ERRB2 and GRB7. As for the histological subtype, the high-grade samples had more amplifications (320 amplified genes) than the low-grade ones (129 genes). Three of these genes were common among residual PAs and CXPA: HMGA2, RPSAP52, and LOC100129940. As for the replicates, MYNC, ERBB2, BRIP1, and HMGA2 were the most repeated amplified genes in the residual PAs. HMGA2, ERRBB2, CDK12, RPSAP52, LOC100129940, and LOC100507250 were the genes with the most replicates in CXPA.

Conclusion

HMGA2, ERRB2, and RPSAP52 may play a key role in PA carcinogenesis, whereas GRB7, CDK12, MYNC, and BRIP1 appear to act as coadjutants.
An Unusual Intracranial Collision Tumor of Anaplastic Ependymoma and Atypical Meningioma
Authors: Harb Zainab , Moral Luis
Published: September 2019

The close geographic association of two or more synchronous primary brain tumors is an unusual occurrence. There are around 50 case reports of these intracranial collision tumors, mostly consisting of malignant astrocytoma (mainly glioblastoma) and meningioma. We present a rare intracranial collision tumor consisting of anaplastic ependymoma and atypical meningioma. To our knowledge, this is the first reported case of intracranial collision tumor with this combination. The patient is a 33-year-old gentleman who presented 2 years ago with new-onset intermittent headaches with increasing severity and associated blurry vision and vomiting. On imaging, he was found to have a 4.2 × 4.1 × 4.1-cm cystic-solid and heterogeneously enhancing extra-axial mass lesion in the left frontal lobe, with an enhancing dural tail. Histologic examination of the surgically excised lesion showed two geographically distinct areas of an extra-axial atypical meningioma (World Health Organization grade II) and an intra-axial anaplastic ependymoma (World Health Organization grade III). The anaplastic ependymoma component showed increased cellularity, pseudorosettes, microvascular proliferation, necrosis, and increased mitoses. It was diffusely positive for GFAP and had a Ki-67 proliferation index of 40%. The atypical meningioma showed 5 mitoses per 10 high-power fields. It had a membranous EMA immunoreaction and a Ki-67 proliferation index of approximately 20%. Recently, the patient had a recurrence of the anaplastic ependymoma component only. So far, no clear explanation has been found in the literature to understand the mechanisms leading to collision tumors. Since our patient does not appear to have any syndrome, it may represent a sporadic phenomenon; however, the sharing of a common oncogenic insult or any underlying molecular/genetic mechanism leading to synchronous tumorigenesis remains to be elucidated in this case.
Succinate Dehydrogenase–Deficient Renal Cell Carcinoma With Sarcomatoid Features
Authors: Erickson Kaia , Lynch Douglas
Published: September 2019

Succinate dehydrogenase (SDH) complex deficiency syndrome is an autosomal dominant syndrome with mutations in the SDH gene characterized by multiple tumor types, including paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, thyroid tumors, testicular seminoma, neuroblastomas, and, less commonly, renal cell carcinoma. SDH-deficient renal cell carcinoma is a distinct and rare subtype of renal cell carcinoma, typically with a good prognosis, that demonstrates histologic features including cytoplasmic inclusions and vacuoles with a loss of SDH subunit B immunostaining. We present a case of succinate dehydrogenase–deficient renal cell carcinoma with sarcomatoid features in a 24-year-old male who initially presented with hematuria and flank pain. An MRI of the abdomen showed a large enhancing mass in the upper pole of the kidney. He underwent a radical nephrectomy and was found to have an 11.0 × 10.5 × 10.2-cm variegated and lobular mass in the upper pole of the kidney. Microscopic examination showed sheets of cells with cleared out cytoplasm, cytoplasmic inclusions, and vacuoles. Areas of the mass showed sarcomatoid features and necrosis. The mass extended into the pelvicalyceal system and metastasized to the adrenal gland. An SDH B immunostain was performed on the specimen and was negative, confirming the diagnosis of SDH-deficient renal cell carcinoma. Subsequently, the patient underwent genetic testing and was found to have an SDHB germline mutation.
Jejunal Atresia Associated With Intramural Calcification in a Newborn
Authors: Mirza Rusella , Mercado Juan
Published: September 2019

Objectives

Jejunal atresia and associated intramural calcification are a rare phenomenon, only few cases have been reported. Jejunal atresia is an antenatal developmental defect causing intestinal obstruction in newborns. In most of the cases, the condition is diagnosed by fetal ultrasound during the period of third trimester. We are reporting a case of neonatal jejunal atresia associated with intramural calcification and extensive foreign body reaction.

Methods

A baby girl was born at a gestational age of 36 weeks, 4 days through spontaneous vaginal delivery with a weight of 2.99 kg. The significant maternal history was gestational diabetes. The baby was diagnosed with jejunal atresia by antenatal ultrasound and received gastric suction immediately after delivery. About 200 mL of dark green fluid was suctioned from the stomach. Postnatal x-ray demonstrated significant distension of bowel loops and stomach. The baby underwent exploratory laparotomy with congenital atresia repair. Morphologically, the proximal portion of jejunum was dilated and small portion of distal segment of jejunum appeared to have type IIIB atresia. The atretic portion was examined grossly and processed as paraffin-embedded tissue for microscopic examination.

Results

The atretic segment was about 1 cm long, the serosal surface demonstrated foci of hemorrhage, and the wall was thickened. Microscopically, the atretic segment and adjacent area showed chronic inflammation, extensive foreign body type giant cell reaction, and abundant intramural calcification.

Conclusion

Some hypothesize that intramural calcification in conjunction with foreign body giant cell reaction associated with multifactorial events including vascular insults during the prenatal period. However, there are no studies directed to elucidate the precise pathogenesis of this combination of findings in the intramural location.
Intestinal Neuronal Dysplasia Type B: Timely Diagnosis and Management
Authors: Deerwester Mona , Drexler Steven
Published: September 2019

A 23-year-old female presented to the emergency department with abdominal pain and constipation. She reported an extensive history of constipation. Imaging showed distended bowel without an obstruction. During laparotomy, no obvious mechanical cause was found and a total colectomy was performed. Gross examination of the colectomy specimen showed cobblestoning in a 10-cm portion of the colon. Microscopic examination demonstrated hypoganglionosis of the myenteric plexus, hyperganglionosis of Auerbach’s plexus, and “giant ganglia.” This case met the 2006 Meier-Ruge criteria and diagnosis of intestinal neuronal dysplasia (IND) was established.

IND was first described in 1971. The frequency of IND varies widely due to lack of consensus of diagnostic criteria and has a geographic distribution with the highest rates in Europe, which correlates to published research in this region. Diagnostic criteria are controversial and require standardization. Meier-Ruge suggests a quantitative analysis of the number of ganglion cells in the submucosal plexuses and the identification of at least 20% giant ganglia with at least 8 neurons each, in 25 analyzed ganglia. More recent diagnostic criteria are conservative with differences, including (1) elimination of increased AChE-positive nerve ﬁbers around submucosal blood vessels, (2) stipulation that a giant ganglion contains more than 8 ganglion cells, (3) the requirement that more than 20% of at least 25 ganglia be giant ganglia, and (4) diagnostic exclusion of patients <1 year. Clinical management is also controversial. Schimpl et al reported satisfactory results in 80% of 105 patients treated with dietary changes, cisapride, and laxatives with a median 7.2 years follow-up. Since colonic peristalsis is impaired by dysganglionosis, subtotal colectomy procedures have been widely successful. Clinicians should be mindful of IND in patients with a history of chronic constipation with abdominal pain and nonspecific imaging, as timely diagnosis can spare the patient from total colectomy and improve quality of life.
Diagnostic Dilemma of Epithelial Signet Ring Cells in Calculous Cholecystitis
Authors: Afsari Ali , Naab Tammey , Hassan Muhammad
Published: September 2019

Classic neoplastic signet ring cells are characterized by peripheral nuclear displacement by accumulation of cytoplasmic mucin in some adenocarcinomas. However, epithelial nonneoplastic signet ring cells may accumulate in the setting of mucosal erosion and ischemia as a reactive change of damaged columnar mucosa. Nonneoplastic signet ring cells may also occur as part of an inflammatory reaction due to histiocytes with signet-ring cell mucicarminophilia.

A 58-year-old female presented with a 3-day history of increasing right upper quadrant abdominal pain. MRI showed distended gallbladder with 2 large stones, thickening of the gallbladder wall, and pericholecystic edema, consistent with acute cholecystitis. Laparoscopic cholecystectomy revealed a 15 × 6.0 × 3.5-cm gallbladder with eroded fundic mucosa, marked wall thickening (2 cm), and two intraluminal yellow stones, measuring 2.5 cm and 2.2. cm in diameter, respectively. The differential diagnosis included incidental gallbladder adenocarcinoma. Clusters of signet ring cells were seen in the fibrinous debris and were focally present in the superficial lamina propria. Intestinal metaplasia but no dysplasia was also observed. Loose clusters of pancytokeratin-positive, CD68-negative signet ring cells contained intracytoplasmic mucicarmine-positive mucin. Negative p53, low Ki-67, and positive E-cadherin supported the diagnosis of reactive signet ring cells. Deeply infiltrating pancytokeratin-positive epithelial cells were not identified. Final diagnosis was acute and chronic calculous cholecystitis with mucosal erosion and reactive signet ring cell epithelial change.

Nonneoplastic epithelial signet ring cells may represent a diagnostic pitfall in chronically inflamed and eroded columnar cell mucosa of the gallbladder. A panel of immunostains and evaluation for cytologic atypia and unequivocal invasion are most helpful in differentiating this unusual reactive epithelial change, which occurs in response to inflammation, erosion, and/or ischemia, from signet ring cell carcinoma.
Ten Years Audit of Neoplastic Colorectal Polyps at Lagos University Teaching Hospital, Nigeria
Authors: Adedotun Adebayo , Odukoya Lateef , Badmos Kabir
Published: September 2019

Introduction

Death from colorectal cancer is still a major concern in low- and middle-income countries. According to GLOBOCAN 2018 report, 1,096,601 new cases of colorectal cancer were reported worldwide and about 551,269 would die from the disease process. Colorectal cancer is the fifth most common cancer and accounts for 5.8% of all new cases seen annually in Nigeria. It has been shown incontrovertibly that neoplastic polyps are precursors to adenocarcinomas, even though the rate is lower among blacks.

The increasing awareness and availability of colonoscopy in Nigeria have resulted in an increased volume of colonic biopsy for histopathologic examination. This has resulted in increased frequency of detection of colorectal neoplastic polyps.

Aim

This study aims at auditing colorectal neoplastic polyps histopathologic reporting in Lagos University Teaching Hospital over a 10-year period (2009-2018).

Methods

All reports of colorectal polyps within the study period (2008-2018) were retrieved from the departmental database. The histologic type, microscopic dimensions, and anatomic locations of these polyps were documented and analyzed.

Results

Seventy-two colorectal neoplastic polyps were reported with an M:F ratio of 2:1. The peak incidence was in the fifth decade, with 98% of the polyps in the colon. A breakdown of the adenomatous polyps showed that most (66.7%) were tubular, and 33.2% were tubulovillous adenoma and a case of villous adenoma. Majority of the lesions had low-grade dysplasia while 30% had high-grade dysplasia. There was no mention of excision margins, and in some cases, the biopsy site was not stated.

Conclusion

Some of these polyps, particularly those with high-grade dysplasia, may likely progress to colorectal carcinoma following the adenoma-carcinoma sequence. Epidemiological data of precursor lesions are relevant as an accurate predictor of colorectal cancer incidence in the coming decade and as a determinant in the evaluation of screening and surveillance practices.
Sudden Death of a 22-Year-Old Female Attributed to Complications of a Colloid Cyst in the Third Ventricle
Authors: Wu Gary , Hammers Jennifer
Published: September 2019

Colloid cysts are rare lesions that account for up to 2% of all intracranial tumors. They are commonly found posterior to the foramen of Monro in the third ventricle and classified as benign lesions due to their slow-growing nature. Diagnosis of colloid cysts are often incidental finds on diagnostic imaging or at autopsy. The strategic location of these cysts primary causes gradual or acute hydrocephalus, as evidenced by flattened gyri and deepened sulci on MRI, nausea, vomiting, and papilledema. Enlargement of the cyst itself can cause a mass effect, which commonly presents with symptoms of ataxia, memory loss, and rapid neurologic deterioration. Microsurgery, endoscopic removal, and stereotactic aspiration are cited to be the most commonly employed treatments in the management of colloid cysts. However, there is no one procedure better than another; the benefits and limitations of several procedures are discussed. Treatment of choice is weighed by clinical judgment and surgical experience that vary between neurosurgeons. Although benign, colloid cysts rarely but can lead to sudden death. Therefore, it is important to consider colloid cysts and other intracranial tumors on the differential diagnosis when presented with acute hydrocephalus and papilledema. We report a case of sudden death in a 22-year-old black female due to obstructive hydrocephalus by a colloid cyst in the third ventricle.
Observations of the Morphological Evolution of Neuronal Intranuclear Rods in the Human Substantia Nigra Across the Age Spectrum
Authors: Khan Osama , Capitano Mario , Fan Susan , Woulfe John
Published: September 2019

Objectives

Parkinson’s disease (PD) is a neurodegenerative disease characterized by a depletion of dopaminergic neurons in the substansia nigra (SN). Loss of SN neurons occurs at a rate of up to 10% per decade in nonpathological aging. Other age-related changes in nigral neurons include accumulation of intranuclear inclusions called Marinesco bodies (MBs). MBs have been shown to associate with a distinct type of neuronal intranuclear body called the intranuclear rod (INR). At what point in the aging process INRs develop, and when they give rise to MBs, are questions that remain unanswered. In this observational study, we set out to determine whether SN INRs display changes in their morphology across the human age spectrum.

Methods

The laboratory information system was searched for hospital and forensic autopsies conducted from 2010-2017 that had midbrain sections taken. Ten slides were cut from each of 11 age groups from ages ranging from 1 month to 80 years of age. Sections were immunostained with glucocorticoid receptor (GR) to identify INRs.

Results

There was a progressive age-associated transition in INR morphology from long, linear intranuclear structures in the youngest age groups (infants), to shorter linear structures at middle ages, culminating in small, dot-like juxtanucleolar structures in elderly subjects. A proportion of short INRs displayed contact with MBs in the middle age groups.

Conclusion

We demonstrated a striking progressive, age-dependent alteration in INR morphology. These results suggest that INRs give rise to MBs in the SN during middle ages. As a follow-up of this preliminary observational study, quantitative analysis of INR frequency and size is currently being performed in our lab. Ultimately, we plan to expand our cases for the creation of a human SN tissue microarray, which we hope will shed light on the cellular mechanisms of neuronal ageing and degeneration in the SN.
Trichomonas Vaginalis (TV) Infection and Its Association With Risk of Cervical Cancer and HPV Status
Authors: Rai Herleen , Dahoud Wissam
Published: September 2019

Background

The prevalence of trichomonas vaginalis (TV) infection is low in developed countries and may be due to its incidental diagnosis and treatment during routine screening. Many countries are adopting a new model based on testing for high-risk (HR) human papillomavirus (HPV) instead of cytology. HPV is known to be associated with squamous intraepithelial lesions (SIL). There is limited and conflicting literature on the relationship between TV and SIL. The aim of this study is to determine the prevalence of TV in different age groups and evaluate the association between TV with SIL, BV (bacterial vaginosis), and HPV infection.

Design

Retrospective study for cytological histologic correlation was performed on 10,546 cases dated between January 2012 and December 2017. HPV results were available in 7,081 cases.

Results

The age range was 15 to 84 with a mean of 49 years; 249 patients were TV positive (2.3%). The prevalence was highest in 30 to 65 age group (71.5%). HPV was present in 4,386/7,081 cases (61.9%). The associated between TV and HPV infection was not significant (P < .07). There was a significant association between TV and BV infection (P < .001). In total, 4,649/10,546 patients showed squamous abnormalities (44%), of which 52.6% were TV positive and 43.9% were TV negative. CIN2-3/SCC was significantly greater in TV-positive versus TV-negative patients (P < .007). HPV-positive patients that were TV positive showed more squamous abnormalities than those that were TV negative (P < .043). TV-positive patients with ASCH showed higher grade lesions (CIN2-3/SCC) on follow-up than TV-negative patients (P < .003).

Conclusion

TV is more common among patients with BV and HPV infection and significantly associated with squamous abnormalities. HPV and ASCH patients with TV showed significant squamous abnormalities. Although TV can be detected incidentally through cytology-based cervical screening, a transition to HPV testing is likely to result in increasing TV prevalence over time.
Tumor-Associated Macrophages Show Consistent Upregulation of Programmed Death-Ligand 1 in Extranodal NK/T-Cell Lymphoma, Nasal Type
Authors: Bernabeu Belen Quereda , Uppal Guldeep , Gong Jerald
Published: September 2019

Objectives

It has been reported that EBV-related lymphomas frequently induce PD-1/PD-L1 upregulation as an adaptive mechanism for tumor immune evasion. Extranodal NK/T-cell lymphomas are strongly associated with EBV infection. We analyzed PD-1/PD-L1 expression in extranodal NK/T-cell lymphoma, nasal type.

Methods

We retrospectively analyzed 11 cases of extranodal NK/T-cell lymphoma, nasal type, diagnosed between 2004 and 2017. Immunohistochemical staining for PD-1 and PD-L1 was performed, and expression was evaluated in tumor cells (TCs) and stromal cells (SCs). Staining of >30% of TCs and >20% of SCs were considered positive. Patient charts were reviewed.

Results

Mean age at diagnosis was 55.6 years (25-81). There were seven males (63.6%) and four females (36.4%). Ten cases (90.9%) were EBV positive (EBER-ISH) and one case (9.1%) was EBV negative. All cases were positive for PD-L1 in SCs, which were tumor-associated macrophages (TAMs) in almost all cases. Two cases (18.2%) also showed PD-L1 overexpression in the TCs. Of these, one case recurred 3 years after diagnosis, with identical PD-1/PD-L1 expression. The other case was lost to follow-up. The remaining nine cases (81.8%) were negative for PD-L1, including the EBV-negative case. All cases were negative for PD-1 in both TCs and SCs. Follow-up information was available for eight patients. Treatments were markedly heterogeneous. None of them received targeted PD-1/PD-L1 blockade. Four patients had no evidence of disease at last follow-up (mean age: 38.3 years). Four patients were deceased or receiving palliative care (mean age: 64.2 years).

Conclusion

In our series of extranodal NK/T-cell lymphoma cases, we observed high frequency of PD-L1 upregulation in TAMs. There was low frequency of PD-L1 upregulation in TCs (18.2%), unlike what has been reported in some studies from Asia (up to 80%). Notably, most of these studies used a cutoff of >5%. All our cases lacked PD-1 expression in both TCs and SCs.
Hematological Parameters Throughout the First Month of Direct-Acting Antivirus (DAA) Plus Ribavirin for HCV
Authors: Shedid Mohamed , Abdelmonem Mohamed , Boraik Ayman , Elmetwalli Alaa , Hassan Dalia
Published: September 2019

Introduction

Hematological complications such as neutropenia, thrombocytopenia, and anemia of DAAs/ribavirin in HCV can result in suboptimal outcomes. This study was aimed to investigate the frequency of hematological variations and their impact on the response to DAA therapy. Patients were defined as having hematological abnormalities if they had the presence of either/or a combination of the following hematological parameters at least once during the first month of treatment: drop in (Hb) level, TLC, and PLT count. Pretreatment, Hb, WBC count, and PLT count were not statistically related to the treatment response. However, lower count of all parameters was associated with moderate or advanced hepatic fibrosis stages according to the METAVIR scoring (P < .001). Static analysis showed that drop in Hb, TLC, and PLT count was significantly associated with response to treatment; P < .001, .21, and .41, respectively.

Methods

Fifty-eight patients for treatment of chronic hepatitis were studied. Their hematological parameters including TLC, Hb, and platelet counts were recorded before starting antiviral therapy and then at 3 monthly intervals. All the patients were given DAAS/ribavirin as antiviral therapy. Data were collected over a period of 3 months.

Results

Fifty-eight patients with mean (SD) age of 54.38 (12.67) years were studied. There was a mean hemoglobin (Hb) fall of 1.5 g/dL at the first 4 weeks of antiviral therapy. Mean TLC fell to 1.03 × 10⁹/L in the first month. A similar downward trend was noted in platelet values with a mean fall of 12.3 × 10⁹/mm in the first month of the antiviral therapy. Of the cases, 41.4% developed clinically significant anemia as evidenced by hemoglobin 11 g/dL after 4 weeks of antiviral therapy; this fall was noted only in first 4 weeks of treatment.

Conclusion

Significant hematological abnormalities occurred within the first 4 weeks of antiretroviral therapy. There was significant decrease in hemoglobin level.
Effect of Vaping on the Oral Cavity
Authors: Abdelmonem Mohamed , Al-Shalchi Noor , August Kirk
Published: September 2019

Introduction

Smoking cigarettes can have negative effects on oral health with a greater risk of periodontal disease and caries. The use of electronic cigarette is often viewed as a safer alternative, but research shows that vaping may be just as toxic. The objective of the study is to test tooth surfaces and determine cariogenic properties after they have been exposed to sweeteners in electronic cigarette aerosols generated while vaping.

Methods/Results

E-liquids containing 20/80 propylene glycol/glycerin, 10 mg/mL nicotine, and flavors were tested on noncariogenic extracted third molars. Aerosols were formed by Universal Electronic-Cigarette Testing devices and mimicked 0, 10, and 150 puffs, respectively. Streptococcus mutans was exposed to the aerosols on the tooth enamel and was shown to have four times more microbial adhesion and decreased enamel hardness of up to 27%. Demineralization is initiated when undisturbed microbes change the oral cavity to a more acidic environment, ultimately leading to caries. The viscous property of the e-liquid allowed S mutans to adhere to pits and fissures and increased biofilm formation by twofold when compared to unflavored controls.

Conclusion

E-cigarettes may increase the risk of dental caries. The sweeteners in the e-liquid have viscous properties comparable to regular soft drinks and a high-sucrose diet. Further studies are needed to understand the possible effects of vaping on the oral cavity.
Effective Utilization of Laboratory Information System to Triage Troponin Critical Value Notification to the Emergency Department
Authors: Pomper Gregory , Hunt Matt , Van Dyke Erica , Waldron Johanna , Hiestand Brian , Wong Steven
Published: September 2019

Objectives

The laboratory received a request to report abnormal troponin (ab-TnI) as critical values (CVs) for ED patients. The laboratory information system (LIS) was programmed to identify only ED patients presenting with an ab-TnI. Only the first ab-TnI on presentation was critical. Unnecessary laboratory CV communications could impair overall turnaround time.

Methods

Mean troponin, ab-TnI test volumes, and ab-TnI from ED patients with suspected acute coronary syndrome were determined. The LIS team constructed a best practice alert in the Beaker module (EPIC, Verona, WI). The ab-TnI CV build filtered patients based on ab-TnI values and ED location. Based on pilot data, the build was adjusted to limit ab-TnI alerts to only the first ab-TnI result. The amended build logic was to trigger the alert if an ED location TnI was abnormal. At trigger, if the lowest TnI result in the last 24 hours is ≤0.040, the return “true.” If true, then no TnI >0.040 in the last 24 hours, call the ED because they currently have a result >0.040. If the answer is “false,” then do not call the ED. If the patient had no TnI in the last 24 hours, then the alert would be triggered as well. The system was piloted after education to the ED and laboratory teams.

Results

The mean TnI per day was 150; the mean ab-TnI was 63 (42%), of which 1.1 ab-TnI originated from the ED. After pilot go-live, the actual number of ab-TnI/day was 14.3. The alert logic was amended to limit the trigger to the first ab-TnI result, reducing the CV volume to 9.6/day.

Conclusion

The LIS can be leveraged to develop a clinically valuable and operationally manageable critical value alert system. Clinical and laboratory teams must be open to amending the process as needed to achieve success.
Blood Culture Contamination in the Clinical Microbiology Laboratory of a Teaching Hospital
Authors: Xu Kemin , Gilani Sarwat , Wang Hank , Fallon John
Published: September 2019

Objectives

Blood culture is one of the most important tests performed in clinical microbiology laboratories. However, blood culture contamination remains a problematic cause of diagnostic errors for laboratory diagnosis and patient management. This aim of this study was to determine blood culture contamination rates and tendency at Westchester Medical Center (WMC), a tertiary teaching hospital in suburban New York City.

Methods

All blood culture tests at WMC received from January 2017 to December 2018, as well as some historical data from 2007 to 2014, were retrospectively retrieved. Blood culture contamination rates were determined according to the laboratory’s predefined criteria.

Results

From 2007 to 2014, a total of 209,750 blood cultures were performed with an average contamination rate of 1.6% (ranging from 0.4% to 3.5% monthly). The total numbers of blood cultures performed in 2017 and 2018 were 27,863 and 28,047, respectively. The overall positive rate of blood culture was 6.8% in 2017 and 7.6% in 2018. The contamination rate of blood culture was 0.6% in 2017 and 0.9% in 2018 with very few variations among different months of the year, which was significantly lower than that of the national benchmark (~2.5%) on blood culture contamination. The majority of contaminants were Staphylococcus epidermidis, accounting for 87% of source contamination, followed by Corynebacterium species (5.5%), Bacillus species and Micrococcus species (3.5% each), and Propionibacterium species (0.5%).

Conclusion

Adherence to current guideline on appropriate blood collection techniques and monthly monitoring and timely feedback to phlebotomists should be continued to keep a low contamination rate for blood culture, which is not only from the perspective of individual patient care but also from the standpoint of hospital epidemiology and public health.
Role of Plasma miRNA-501 Expression Profile as a Marker of Hepatocellular Carcinoma (HCC) Progression With Hepatitis C Virus Infection
Authors: Shedid Mohamed , Abdelmonem Mohamed , Boraik Ayman , Elmetwalli Alaa , Esmael Ahmed
Published: September 2019

Introduction

HCV is a health problem that confronts many countries in the world. Those patients will develop complications like cirrhosis and HCC, which is one of the most common cancers in the world, especially in Egypt, and considered the third leading cause of death worldwide. The prognosis of HCC is still dismal due to the late diagnosis. miRNAs are small, short noncoding RNAs, which have roles in the diagnosis of HCC. In our study, we focus on biological aspects of miRNAs. We report that miR-501 is strongly expressed and observed in the process of HCC development. miR-501 regulation is important as an oncofetal relevant to the diagnosis of HCC.

Method

This study was conducted on 100 adult patients; 25 patients were positive for anti-HCV and 25 patients were negative for HCV and enrolled as a control group. Patients were categorized into three groups: fibrosis (n = 25), CHC (n = 25), and HCC (n = 25) related to HCV evident by CT abdomen. All patients and controls were subjected to full clinical assessment and laboratory investigation. Blood (8 mL) was withdrawn from subjects, and 3 mL was collected in EDTA tubes for processing total RNA extraction and miRNA. The remaining 5 mL was left for determination of biochemical parameters. miRN-501 expression levels were determined by RT-PCR.

Results

The data revealed a significant increase in levels of AST, ALT, ALP, and CBC in both HCC and CHC groups compared to controls. The results of miRNA expression showed that miR-501 was higher in the HCC group than non-HCC group at P1.1.

Conclusion

miR-501 can be used as a noninvasive biomarker for early diagnosis of HCC among patients with HCV on account of its affectability for HCC.
Mentorship Strengthens HIV-1 Viral Load Laboratory Quality and Testing in Mozambique
Authors: Basu Debby , Nhabomba Augusto , Assane Mariamo , Adamo Noorbebi , Benzane Octavia , Pinto Isabel , Macave Admiro , Landgraf Kenneth
Published: September 2019

Objectives

In response to the urgent need for high-quality HIV viral load (VL) testing scale-up to reach the UNAIDS goal of 90% of HIV+ patients on ART treatment and 90% of these patients reaching viral suppression worldwide, the American Society for Clinical Pathology (ASCP) has directed a VL mentorship program across six provinces in Mozambique.

Methods

Through this program, three in-country consultants with advanced molecular biology and quality management system skills have mentored nine molecular biology laboratories conducting VL testing (four new laboratories, five established laboratories) through both in-person and remote mentorship methods. Using external audit evaluations conducted by CDC and Ministry of Health using the CDC VL Scorecard (scored 1-5), mentors have directed targeted interventions to address laboratory needs including (but not limited to) the following: biosafety, document control, quality control, corrective actions, assay troubleshooting, and codevelopment of key technical and quality-based SOPs and job aids with local laboratory management. In-person mentorship visits also focus on skills building of laboratory staff and management.

Results

Excluding two new laboratories with only baseline assessments available, the majority of mentored laboratories (six of seven; 85%) showed improvement at follow-up audits compared to baseline assessment scores, with only one laboratory showing a one-level backslide between sequential audits. Potential reasons for this backslide include more limited in-person mentorship during the time period or interevaluator scoring variability.

Conclusion

These data suggest that mentorship focused on test methodology and quality management is an effective way to promote laboratory quality while scaling up services; however, additional efforts, including integration of methods for improved remote mentorship to in-laboratory mentors and management, are needed in order to sustain high laboratory quality in the absence of an external mentor.
Advocacy Journal Club: Teaching Residents and Faculty About Policy and the Importance of Pathology Societies
Authors: Talmon Geoffrey , Wolf Alejandro , Molani Mariam , Martin Kimberly , Jacobs Jeff , Waibel Liz
Published: September 2019

Objectives

To describe the Advocacy Journal Club, a novel method to expose pathology residents, fellows, and faculty to critical regulatory and policy issues that affect the practice of laboratory medicine and the importance of involvement in advocacy initiatives.

Methods

Six voluntary conferences were held for UNMC faculty, local pathologists, and residents during a 1-year period. Each featured a unique, 50-minute interactive discussion led by a faculty member on a topic related to systems-based practice, public health, and/or legislative reform in health care. The six topics included Stark Law, Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), Laboratory Developed Tests, Executive Branch Influence on Health Care, Local Coverage Determinants, and Protecting Access to Medicare Act of 2014 (PAMA). In addition, all participants completed an 8- to 10-question pre- and posttest. After the completion, a survey to assess the quality and efficacy of the series was administered.

Results

Between 5 and 11 residents attended each session. Both residents and faculty demonstrated a marked increase in their posttest scores. In the final survey, 92% stated they gained an understanding of how policy affects their local laboratory and 100% a better appreciation of how involvement in pathology organizations’ advocacy efforts impacts the laws, rules, and regulations that affect laboratory medicine. Most (92.3%) reported that topics of the Advocacy Journal Club are important to pathology training and 100% reported that the format was effective.

Conclusion

The journal club format is an effective method to teach both residents and faculty about health policy and other issues impacting laboratory medicine and the critical role that participation in the advocacy efforts of pathology societies plays in affecting the future of the specialty.