bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinico-pathologic Features of Esophageal Poorly Differentiated Neuroendocrine Carcinomas, a Case Series and Review of Literature
Authors: Perveze I , Rao D
Published: October 2020

Introduction/Objective

Esophageal neuroendocrine carcinomas (NECs) constitute an extremely rare and distinct group of neoplasms. The clinico-pathologic characteristics are poorly understood and differ starkly from high grade well differentiated neuroendocrine tumors. Only one case series describing clinico-pathologic features of NECs has been described in recent literature.

Methods

We describe a case series of three patients highlighting the typical presentation, diagnostic techniques and pathologic attributes for this rare disease process.

Results

All three patients were middle age to elderly with two males (ages 58 and 83) and one female (age 72). The typical presentation was dysphagia (2/3, 66%) followed by severe GERD (1/3, 33%). Typical locations were distal esophagus (2/3, 66%) and gastro-esophageal junction (1/3, 33%). Computed tomography showed bulky masses in all patients (3/3, 100%) with median size of 5.6 cm. PET imaging showed metastatic disease (mediastinal or epigastric lymphadenopathy and lung metastasis) in 2/3, 66% of the patients. All the patients were found to have necrotic masses on EGD with biopsy showing poorly differentiated neuroendocrine carcinoma in all (3/3, 100%). Immuno- histochemical stains revealed Synaptophysin positivity in 3/3, 100%, Chromogranin in 1/3, 33% and CD56 in 1/3, 33% of the patients. Patients with metastatic disease at presentation (2/3, 66%) opted for palliative care while the patient without any evidence of metastasis (1/3, 33%) underwent surgical resection followed by chemotherapy.

Conclusion

ENCs are an exceedingly rare group of malignant neoplasm with variable presentations posing a diagnostic challenge for the clinician and pathologist alike. Most patients tend to be elderly with advanced disease at presentation and guarded prognosis. This case series underscores the importance of including this entity among the differential diagnosis for poorly differentiated carcinomas of the distal esophagus. IHC with positive neuroendocrine markers particularly Synaptophysin helps make the correct diagnosis when combined with typical morphology.
Schistosomiasis with Duodenal Involvement Presenting as Irritable Bowel Syndrome in a 9-Year-Old Patient
Authors: Ding L , Pape E , Kozielski R
Published: October 2020

Introduction/Objective

Schistosomiasis is extremely rare in the United States. Most patients diagnosed in the US have an international travel history or recently immigrated from endemic areas. We report a case of a 9-year-old boy who presented with a three-month history of daily abdominal pain, decreased appetite, weight loss, and microcytic anemia. The patient had alternating symptoms of constipation and diarrhea mimicking Irritable Bowel Syndrome (IBS).

Methods

CT scans showed distal sigmoid colon with wall thickening and hyperenhancement. Stool Helicobacter pylori antigen test was positive and hemoglobin levels were low (11 g/dL). The blood eosinophil count was initially within the normal range but was significantly elevated three months later (2,115 cells/µL).

Esophagogastroduodenoscopy and colonoscopy were performed, which showed patchy areas of erythema and punctate bleeding within the descending and sigmoid colon.

Results

Gastrointestinal tract biopsies revealed focal, prominent eosinophilic infiltrates in the lamina propria. There were multifocal granulomas and fibrosis surrounding Schistosoma ova in the lamina propria and submucosa of duodenum, cecum, colon, and rectum. Acid-fast stain highlights the shell and spine of the ova. A retrospective chart review revealed that the patient had traveled to Yemen one month before the onset of symptoms. Schistosomiasis is among the top differentials for marked, sustained eosinophilia, especially with relevant travel history. Distortions caused by processing and sectioning can make speciation difficult on tissue sections. Acid-fast staining of the shell would favor S. mansoni over S. intercalatum; however, the S. intercalatum-S. hematobium hybrid also has an acid fast–positive shell. The duodenum is an uncommon location to find Schistosoma ova, which are usually found in the rectum and sigmoid colon.

Conclusion

The symptoms of gastrointestinal schistosomiasis may mimic IBS, and eosinophilia may initially be not evident as in this case. However, a high degree of suspicion is required in diagnosing schistosomiasis in patients from endemic areas.
Mismatch Repair Gene Expression In Testicular Germ Cell Tumors And Retroperitoneal Lymph Node Metastasis
Authors: Youssef M , Rodriguez Pena M , Canete-Portillo S , Al Diffalha S , Magi-Galluzzi C
Published: October 2020

Introduction/Objective

Testicular germ cell tumors (TCGT) with somatic mismatch repair pathway defects have shown to have worse prognosis and response to therapy. Immunohistochemical staining pattern of MMR panel was classified in a previous study as low (absent or minimal) and high staining (moderate or high staining), with the low staining pattern suggestive of poor prognosis and high risk of recurrence. Herein, we studied the MMR staining pattern in TGCT and lymph node metastasis.

Methods

21 TGCT were included in the study: 10 primary testicular tumors and 11 unrelated retroperitoneal lymph node metastasis. All cases were analyzed for MMR protein expression by immunohistochemistry. Clinical, histopathological and follow-up was obtained in all cases. Retained MLH1, MSH2, MSH6, and PMS2 was defined as nuclear staining. Loss of expression was defined as absence of nuclear staining within tumor cells with retained expression in internal control cells, including benign testicular tissue, stromal cells, and infiltrating lymphocytes.

Results

All primary testicular tumors were mixed GCT: embryonal carcinomas was present in 5, yolk sac tumor in 3 and teratoma in 6 cases. One (10%) of the primary tumors showed focal loss of MLH1 and PMS2 expression in a focus of embryonal carcinoma. All lymph node metastases consisted of teratoma. Seven (64%) metastatic cases showed scattered areas of focal MLH1 loss, 5 (45%) of which showed also focal loss of PMS2. High staining for MSH2 and MSH6 was detected in all 21 cases.

Conclusion

In our small cohort, focal loss of MLH1 and PMS2 was detected in 10% of primary TGCT, compared to focal loss of MLH1 and PMS2 is 64% and 45%, respectively, of metastatic tumors, suggesting a possible relationship between heterogeneous MLH1 and PMS2 expression and retroperitoneal lymph node metastasis. The current cohort will be expanded to include additional cases.
Identification Of Strn-Ntrk2 Rearrangement In A High Grade Sarcoma, With Good Clinical Response To Firstline Larotrectinib Therapy
Authors: Lin R , Wang Z , Jiang W , Basu-Mallick A
Published: October 2020

Casestudy

Gene fusions involving tropomyosin receptor kinase genes, NTRK (NTRK1-3), are important in tumorigenesis. Larotrectinib, a selective NTRK inhibitor, is recently approved to treat NTRK fusion positive solid tumors. We herein report a case of soft tissue sarcoma harboring two STRN-NTRK2 gene fusions, with good clinical response to firstline larotrectinib treatment.

Results

A 35 year-old female presented with pain in the right gluteal region, and a large solid mass without overlying erythema, edema and induration was identified. Initial MRI study showed a heterogenous, vascular and partially necrotic mass (16.5 x 12.9 x 10.4 cm) centered in the right gluteus medius and maximus muscles. A core biopsy of the mass showed a cellular mesenchymal neoplasm with round/ovoid cells, high mitosis (21 per 10 HPFs) and focal staghorn type vessels, reminiscent of solitary fibrous tumor. However, STAT6 immunostaining was negative.

Additional immunostains show no specific lineage. Our in-house NGS fusion panel showed two in-frame STRN- NTRK2 fusions, containing the same 5’ partner sequence (exon 1-3) of STRN, with the 3’ fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, larotrectinib was initiated as firstline therapy. The patient noticed a quick amelioration of tumor related pain, and a significant shrinkage of the size of tumor following the initial 7-day treatment. On post-treatment day 52, MRI showed the tumor significantly decreased in size to 7.7 x 7.4 x 6.6 cm with satisfactory symptomatic relief.

Conclusion

NTRK2 fusions are relatively rare when compared with NTRK1 and NTRK3, especially in sarcoma. Of note, the only other report in the literature of NRTK2 fusion- positive sarcoma also showed SFT-like morphology, and the patient responded well to larotrectinib as second line therapy.
Unusual Death; Light Microscopy Solves The Mystery With An Archetypal Depiction Of An Unexpected Rare Cause
Authors: Ibrahim D , Gohara A
Published: October 2020

Casestudy: Hypertrophic cardiomyopathy is a heterogeneous disease with a number of phenotypes. We present the rarest phenotype, 1% of all cases, the midventricular obstructive type. It is characterized by hypertrophy in the mid portion of the left ventricle involving the papillary muscles, resulting in systolic intraluminal obstruction of the mid-ventricle. An unusual case of a 41-year-old male who died suddenly while hiking. He had no past medical history except for hyperlipidemia. He had no history of hypertension, with documented repeated normal blood pressures. No family history of cardiac problems, sudden death, or death at young age. On autopsy examination, his heart weighed 540 grams. The left ventricle was concentrically hypertrophied, 1.8 cm in thickness, with prominent papillary muscles and small lumen. The interventricular septum measured 1.8 cm in thickness, with increase sub-aortic wall thickness. Microscopic examination revealed myocyte hypertrophy with boxcar-like nuclear enlargement and interstitial fibrosis. There was myocardial fiber disarray. Intramural vessels showed dysplastic changes with medial thickening and narrowing of the lumen. Genetic cardiomyopathy panel testing on paraffin-embedded sections was negative; testing-on whole blood is preferred but body was embalmed before autopsy. The immediate cause of death was hypertrophic cardiomyopathy leading to pulmonary edema with potential complications as arrhythmias and low cardiac output. This case highlights the importance of light microscopy in the diagnostic process despite negative genetics. It also underscores the crucially of adopting better strategies to identify the disease since sudden death occurs frequently in those where diagnosis is missed during life.
Naegleria Fowleri Diagnosed with Hospital Autopsy in a Toddler: A Case Study
Authors: Palmer R F , Palavecino E , McLemore J L
Published: October 2020

Casestudy

Naegleria fowleri, an amoeba, is typically found in warm freshwater lakes, ponds, rivers and hot springs. It is responsible for causing the incredibly rare and lethal central nervous system infection called Primary Amoebic Meningoencephalitis (PAM). In the United States, 145 confirmed cases have been documented since 1962. Most cases are associated with freshwater lakes, ponds and reservoirs, while only a handful have been linked to artificial recreational venues such as pools, interactive water play-grounds, and spas. In addition to highlighting a rare amoebic disease, this case illustrates the continued importance of hospital autopsies especially given recent ruling to eliminate the autopsy requirement by the Centers for Medicare and Medicaid Services.

Results

An otherwise healthy toddler had upper respiratory symptoms and otitis media days after returning from an artificial recreational water venue, becoming increasingly lethargic and febrile over the next few days. At the hospital, cerebrospinal fluid (CSF) abnormalities were suggestive but not consistent with bacterial meningitis. A meningoencephalitis panel, a Computed Tomograph (CT) scan of the head, and chest-x-ray were negative for abnormalities. Appropriate antimicrobial therapy was initiated. Three days after hospital admission, his symptoms worsened including development of dysconjugate gaze and signs of cerebellitis. He became increasingly hemodynamically unstable, suffered an arrest, and passed away days later.

Conclusion

Since this death did not fall under the state’s statutes mandating medicolegal autopsy, a hospital- requested autopsy was performed. Cerebral edema and a light gray to light green exudate was along the inferior and lateral left temporal lobe, brain stem, and cerebellum. An exuberant lymphoplasmacytic infiltrate with scattered polymorphonuclear leukocytes expanded the meninges. Small histiocyte-like cells with distinct eccentric nuclei and granular, vacuolated cytoplasm, confirmed by Centers for Disease Control and Prevention (CDC) to be Naegleria fowleri, were best visualized in the Virchow-Robin spaces and deeper parenchyma.
The Pivotal Role Of Coconut Oil Or Liquid Paraffin As Antidote Effective In Reducing Acute Aluminum Phosphide Poisoning In Cardiogenic Shock
Authors: Fyala A S , Fathalla E , Aly S , Fathy A M , Bakhet M
Published: October 2020

Introduction/Objective

Aluminum phosphide (Alp) is a self-poisoning agent for raising the mortality rates in developing countries. Alp is known as “Rice-tablet” which is a cheap solid fumigant pesticide that is used for grain preservation which becomes a common mode of suicidal attempts in the rural community in Egypt. This study aims to identify the mechanism of salient features and management strategies were carried out on acute Alp-poisoned patients at Poison-Emergency-Unit, ElBehira-Hospitals. That was performed between Jan2018-Jun2019.

Methods

Patients were subjected to a full history evaluation of age, sex, Blood gases, and ECG, were demonstrated. Patients were grouped according to their outcome into survivors and non-survivors groups.

Results

The results demonstrated that (93%) of Alp-poisoning cases by oral-ingestion as suicidal attempts which were (54%) survived while (46%) non-survived. The blood-gases were showed that over 50% of the cases had metabolic acidosis with a highly-significant difference between survivors and non-survivors. PH and HCO3 values were significantly lower in non-survivors than those in the survivor group. Furthermore, SaO2 value was significantly higher in survivors than that of non-survivors. So the managing Alp-poisoning should be started for first 6hr since exposure. Treatment includes early gastric lavage with potassium-permanganate-(1:10,000), sodium-bicarbonate or coconut-oil/liquid-paraffin. The mechanism of Alp-poisoning explained that, phosphine gas inhibits 70% of mitochondrial cytochrome-c-oxidase in myocardial-tissue by the effect of free-radicals; electrolyte disturbance, and intracellular acidosis all cause a reduction in cardiac function, and multi-organ damage. These effects may cause arrhythmia and myocarditis which may be the cause of death.

Conclusion

It was concluded that myocardial depression with shock and metabolic acidosis may lead to respiratory failure due to acute Alp-poisoning. This case study reported that coconut oil play a pivotal role in managing acute Alp- poisoning even 6h post ingestion for reducing the oxidative outcomes of phosphine and recommended as antidote for acute Alp-intoxication.
An Unusual Case Of Pernio (Chilblains) With Underlying Cryoglobulinemia – Case Study
Authors: Kanteti A P , Sofronescu A
Published: October 2020

Introduction/Objective

Pernio or chilblains, is a rare condition associated with small pruritic swellings of the extremities triggered by low temperature. Generally, the patients experience a burning and itching sensation in the affected areas that increases with return to warm temperature. The underlying risk factors include autoimmune disorders and cryoglobulinemia. Herein we present an unusual and rare case of chilblains that evaded diagnosis for few years. The general concepts of analytical and clinical evaluations of this condition, with emphasis on accurate diagnosis of gammopathies, along with the importance of laboratory evaluations and accurate interpretation of laboratory results will be discussed.

Methods

Multiple laboratory investigations (CBC, electrolyte analysis, serum protein electrophoresis, free light chain analysis) were pursued together with skin biopsies. Additionally, CT scan under low radiation exposure and bone marrow biopsy were followed. Plasma sample viscosity at room temperature was evaluated.

Results

Skin biopsies from right anterior thigh and left arm revealed leucocytoclastic vasculitis with normal perivascular staining for C3 and fibrinogen. Serum sample at room temperature exhibited increased viscosity and protein electrophoresis identified a highly elevated IgG kappa monoclonal globulin peak whose concentration increased upon warming and dilution of the sample, suggesting that agglutinin precipitated at cold temperature (below body temperature). Analysis of free light chains revealed elevated concentration of kappa light chain whose concentration also increased upon warming the serum sample. Whole body CT scan and bone marrow biopsy analysis further identified lytic lesions. These investigations established the diagnosis of plasma cell myeloma (CD138 staining) with expression of monoclonal immunoglobulin precipitating at temperatures below that of the body.

Conclusion

Given the above findings this case of chilblains can be classified as cryoglobulinemia vasculitis. The importance of attention to details (e.g. characteristics of serum samples), accurate interpretation of laboratory findings and analysis clinical information are all very crucial to arrive at a differential diagnosis.
HPV 16/18/45 Are Not The Most Frequent Genotypes In Women Of African-American Descent: Analysis In Cervical Pap Smears Of Women In An Inner-City Hospital
Authors: Dababneh M , Birdsong G , Mosunjac M , Krishnamurti U
Published: October 2020

Introduction/Objective

HPV-driven cervical cancer is one of the leading causes of cancer-related deaths in women. More African American (AA) and Hispanic women are reported to get HPV-associated cervical cancer than women of other ethnicities, possibly because of decreased access to testing or treatment. High variation has been reported in the attribution of specific HPV genotypes among various ethnicities and races. Here we report the distribution of high- risk (HR) HPV genotypes in an inner-city hospital that primarily serves an AA population.

Methods

Genotyping of HR-HPV+ (encompassing 14 genotypes) cervical cytology specimens commenced in October 2018 at our institution. The presence of genotypes 16, and 18/45 (combined) are separately reported; 11 other high-risk genotypes are pooled in cases that were HR-HPV+. The HR-HPV and HPV genotyping assays were performed by the Aptima method (Hologic, Inc.) Distribution of HPV genotypes by the Bethesda diagnostic categories for the period October 2018 to March 31, 2020 was evaluated.

Results

A total of 13,160 cervical Pap smear cases were screened, and 10,060 cases were tested for HR-HPV. HR- HPV positive rate was 14% (1412/10060), of which 78% were in African Americans (AA), 14% in Hispanics, 4% in Caucasians, and 4% in others. HPV genotyping results were available for 1136 of the HR-HPV + cases. The cytology diagnoses (n) with their corresponding HPV genotyping results and distribution (HPV16, HPV18/45, and other HPVs), respectively, are as follows: NILM (270), 3.7%, 5.9%, and 90.4%; ASCUS (415), 8.2%, 6.8%, and 84.8%; LSIL (247), 8.1%, 13.0%, and 78.1%; ASCH (100), 18.0%, 13.0%, and 67.0%; HSIL (74), 20.3%, 14.9%, and 60.8%; AGC (30), 6.66%, 3.33%, and 90.0%, respectively. Co-infection with both HPV 16 and HPV 18/45 was seen in only 0.7% of all cases (4.0% of HSIL).

Conclusion

Overall, the HR-HPV positive rate was 14.0%. HPV 16/18/45 positivity accounts for ~18% of all HR-HPV positive cases. HPV 16/18/45 positivity is lowest in Pap-negative cases (9.6%) and highest in cases with HSIL (39.2%). Co-infection with HPV 16 as well as 18/45 is rare. This study highlights that in women of AA descent, it is not HPV genotypes 16/18/45 but other HPV genotypes that are more frequent.
Pancreatic/Peripancreatic Spindle Cell Lesions Cytology: A 15-Year Review
Authors: Aldrees R , Rosenblum F , Eltoum I
Published: October 2020

Introduction/Objective

Spindle cell lesions (SCL) are diagnostically challenging, especially on cytology specimens where entities have overlapping features. Neoplastic and non-neoplastic SCL are uncommonly encountered in the pancreas/peripancreatic tissue. The sensitivity and specificity of EUS-FNA of pancreatic lesions both approach 95%. In this study, we assess the frequency of SCL found in pancreas/peripancreatic tissue on cytology specimens, the frequency of performing IHC stains and the most useful IHC panels. We also evaluate histology-cytology discrepancies and pitfalls.

Methods

A retrospective analysis of all pancreas/peripancreatic cytology specimen results between January 2004 - August 2019 was conducted. A total of 5,132 cases were identified. The number of spindle cell lesions was 27 (0.52%), with surgical pathology results available for 15 cases (55%). IHC stains were performed on 18 cell blocks (66%) and 9 surgical pathology specimens (60%).

Results

Of the 27 SCL identified, 22 lesions were neoplastic (81%), and 5 lesions were non-neoplastic (19%). The Neoplastic cases were: 10 GISTs (37%), 4 spindle cell lesions, NOS (14.8%), 2 metastatic sarcomas (7.4%), 1 pheochromocytoma (3.7%), 1 leiomyoma (3.7%), 1 schwannoma (3.7%), 1 malignant fibrous histiocytoma (3.7%), 1 granular cell tumor (3.7%), and 1 neuroendocrine carcinoma (3.7%). Of the neoplastic cases, 10 were lesions originating in a different organ with direct extension/distant metastasis to the pancreas (71%), with the most common organ being the stomach, 6 cases (60%). The non-neoplastic cases were: 4 granulomas (14.8%), and 1 accessory spleen (3.7%). IHC stains were performed on 18 cell blocks (66%), and attempted unsuccessfully on 2 cell blocks.

The most commonly utilized stains were: CD117, 15 cases (83%), SMA, 11 cases (61%), S-100, 9 cases (50%), CD34, 5 cases (27%) and Cytokeratin, 5 cases (27%). IHC stains assisted with proper classification in 9 cytology cases (50%). There was one interpretation error*, and the histology-cytology discrepancy rate was 6%.

Conclusion

Pancreatic and peripancreatic spindle cell lesions are uncommon (520/100,000), and are particularly challenging on cytology specimens. If neoplastic, the majority originate in an organ other than the pancreas. If non- neoplastic, the majority are granulomas. Immunohistochemical staining is required for proper classification. And in this small series, cytology is highly accurate for diagnosis (96%).
A Case Series Describing The Cytomorphology And Clinical Features Of Follicular Dendritic Cell Sarcoma
Authors: Bailey C A , Weimholt R C
Published: October 2020

Introduction/Objective

Follicular dendritic cell sarcoma (FDCS) is the malignant counterpart of the germinal center follicular dendritic cell. Cytomorphological descriptions are few, with only 24 prior cytology reports from 22 publications. We present 4 cases with the aim of adding to this small body of literature.

Methods

Our database was searched for “dendritic cell.” Patients diagnosed with FDCS that had a cytology specimen were included. Clinical and cytologic features were tabulated.

Results

Case 1 was an 87-year-old man with a retroperitoneal mass. Aspiration rendered a new diagnosis of FDCS, supported cell block immunohistochemistry. Case 2 was an aspiration of metastatic FDCS to the lung in a 40 year-old- man with a known neck primary. Case 3 was a 46-year-old-man with a left neck mass. Aspiration rendered a misdiagnosis of “atypical epithelioid cells in a background of granulomatous inflammation”. Subsequent needle biopsy confirmed FDCS. Case 4 was an aspiration of metastatic FDCS to the liver in a 66 year-old-woman with a known splenic primary. Comparison of cytomorphology show identical features in all cases. Smears were hypercellular and composed of variably sized syncytial aggregates as well as individually dispersed cells. Tumor cells were variably epithelioid to spindled, had fine chromatin and small nucleoli, displayed frequent bi- and multinucleated forms, and had abundant pale cytoplasm with long, slender fibrillar processes. All cases demonstrated many small lymphocytes intermixed both within the syncytial aggregates and dispersed in the background.

Conclusion

Cytomorphological features of FDCS appear conserved from case to case. Knowledge of these features may aid in its recognition in aspiration material.
Efficacy of HLA-compatible Platelet Transfusion for Patients with Acute Myeloid Leukemia Refractory to Platelet Transfusion
Authors: Tsai T , Perez-Alvarez I , Woo J , Tran M
Published: October 2020

Introduction/Objective

Acute myeloid leukemia (AML) patients often require transfusion support during induction chemotherapy. Platelet transfusion refractoriness (PTR) may develop due to HLA alloimmunization. Management of immune-refractory patients with HLA-compatible platelet transfusions is labor intensive and associated with increased costs. The purpose of this study is to evaluate the efficacy of HLA-compatible platelet units in AML patients.

Methods

Newly diagnosed AML patients undergoing induction chemotherapy in our institute between 2015 and 2018 were identified. Platelet counts and platelet transfusion data from initiation of chemotherapy until platelet recovery (> 20K/µL and increased consistently) were extracted. A 24-hour posttransfusion corrected count increment (CCI) was calculated to evaluate the efficacy of each platelet transfusion. PTR was declared if a patient had a 24-hour CCI < 4K following two consecutive transfusions. Student’s t-test was used for statistical analysis. Results were presented as mean ± SE, * if p < 0.05.

Results

We identified 39 patients with newly diagnosed AML. PTR developed in 22/39 (56%) patients during induction chemotherapy. The average CCI was higher among those without PTR compared to those with PTR (8,408 ± 585 vs. 2,923 ± 360*), and overall platelet transfusion burden (in number of units) was lower (7.29 ± 1.0 vs. 18.55 ± 1.71*). HLA antibodies were identified in 3/22 (14%) PTR patients, as 6/22 (27%) were tested. The average CCI during HLA matched transfusions for these 3 patients was higher than that with random units (2,059 ± 149 vs. -126 ± 306*). Compared to HLA-negative PTR patients receiving random units, the average CCI for HLA-compatible transfusions was still lower, though not significantly (2,059 ± 149 vs. 3,099 ± 390, p = 0.33), while the number of HLA- compatible units transfused was significantly higher (31.0 ± 3.0 vs. 16.6 ± 1.45*).

Conclusion

In a cohort of newly diagnosed AML patients undergoing induction chemotherapy whose PTR was associated with detectable HLA antibodies, transfusion support with HLA-matched products did not lead to reduced overall platelet transfusion rates and CCI remains in the refractory range. This suggests that use of HLA matched platelets among newly diagnosed AML patients with PTR, even in the setting of detectable HLA antibodies, does not appear to result in reduced overall product utilization.
The Rare First Manifestation Of Mantle Cell Lymphoma As Immune Complex Glomerulonephritis With Crescents And Membranoproliferative Features
Authors: Dehghani A , Wang D , Alshal M , Wieczorek R , Gosmanova E , Der Mesropian P
Published: October 2020

Introduction/Objective

Initial presentation of Non-Hodgkin Lymphoma (NHL) with immune complex glomerulonephritis (ICGN) is rare. Mantle cell lymphoma (MCL) is a rare aggressive lymphoma comprising 3–7 % of all NHL and ICGN as the first manifestation of MCL is very unusual.

Methods

We report a 73 year-old-man with increased serum creatinine (2.1 mg/dl) from normal baseline 3 months ago. Urinalysis showed the presence of dysmorphic RBCs, RBC casts and 300 mg/dl of protein. Physical examination revealed diffuse lymphadenopathy. Hepatitis C and B Ab, HIV screen, ANA, ANCA, Anti dsDNA Ab, Anti GBM Ab, and Serum protein electrophoresis were normal or negative.

Results

The renal biopsy showed Immune complex glomerulonephritis with (25%) fibrocellular/cellular crescents and focal membranoproliferative (MPGN) features. There were foci of dense monomorphic lymphoid aggregates of small lymphocytes and 30% interstitial fibrosis with corresponding tubular atrophy. No tubulitis was present. Direct Immunofluorescence showed 2+ to 4+ granular mesangial and capillary loop staining for Total Ig, IgG, IgA, IgM, C1q, C3 and C4. The lymphoid aggregate was monoclonal Kappa. Electron microscopy showed widespread podocyte foot process effacement, subendothelial and rare mesangial dense deposits. Excisional lymph node biopsy flow cytometry showed a monoclonal population of CD19+, CD20+, CD22+, CD5+, skappa-restricted, CD10-, CD11c-, CD23-, CD25- CD38-, CD103-, CD200- B- cells. Cyclin D1 was positive on immunostain, consistent with stage IV (renal) MCL. He received chemotherapy with steroids, bendamustine, and rituximab leading to resolution of lymphadenopathy and proteinuria and improvement in serum creatinine.

Conclusion

It is important to recognize that the first manifestation of MCL may present as renal involvement in the form of ICGN and, as in this case, with fibrocellular/cellular crescents and a focal MPGN pattern. This is an extremely rare, but important, cause of renal insufficiency that can be successfully treated with lymphoma chemotherapy.
Non-Acute Myeloid Neoplasms With CD34(-) Blasts: Immunophenotypic And Clinical Analysis Of 5 Cases
Authors: Shponka V , Kroft S , Harrington A M , Monahan K , Atallah E
Published: October 2020

Introduction/Objective

Non-acute myeloid neoplasms (NAMNs) comprise clonal hematopoietic disorders, characterized by ≤20% myeloblasts in the peripheral blood (PB) and/or bone marrow (BM). The blasts of NAMN are almost exclusively CD34(+), contrasting with blasts in some acute myeloid leukemias (AML). We detail the clinicopathologic features of NAMN with CD34(-) blasts.

Methods

We searched 981 NAMN pathology reports for CD34(-) blasts by flow cytometry (FC). 8-color FC data was analyzed using cluster analysis to identify all relevant cell populations with a comprehensive antibody panel. CD34(-) blast populations were defined as reproducible clusters with similar light scatter properties across antibody tubes, after exclusion of other cell populations (e.g. basophils, neutrophils, mast cells). Blast aberrancies were defined as differences from established normal antigen expression patterns. PB and BM morphology was reviewed and chart reviews were performed.

Results

We identified 5 NAMN patients with CD34(-) blasts (2M, 3F; 57-84y/o) including 3 myelodysplastic syndrome (MDSs) with excess blasts, 1 therapy-related MDS, and 1 chronic myelomonocytic leukemia-1 (CMML). Blasts ranged from 0-1.5% in PB and 2.8-8% in BM. CD34(-) blasts accounted for 0.85-8.2% of BM events by FC, with all showing other aberrancies. The CMML patient had CD34(-) blasts with monocytic differentiation; all other CD34(-) blast populations showed expression of CD13, CD33, and CD117 and aberrant under-expression of CD38. Aberrancies were also present in the CD34(+) blasts in all patients (1-4/patient), accounting for 0.01-0.55% of events; 3/5 pts had under-expression of CD33, CD38, CD45, and/or HLA-DR. No cases had adverse cytogenetics. Patient outcomes included: indolent disease (1); died from disease 3 years post-diagnosis and chemotherapy (1); transformed to AML (2; 1-alive in complete remission; 1-died); and alive following allogeneic stem cell transplant (1).

Conclusion

Our data confirm that CD34(-) blasts are rarely observed in NAMN, and these patients have variable outcomes. Interestingly, all cases showed a concomitant aberrant CD34(+) blast population.
Biological Factors Affecting Thrombocytopenia In Hepatitis C Infected Patients
Authors: Bhuyan R , Tiburcio J
Published: October 2020

Introduction/Objective

Thrombocytopenia is one of the major extra-hepatic manifestations of Hepatitis C virus (HCV) infection. There are numerous studies suggesting several pathophysiology mechanisms explaining the association of thrombocytopenia with HCV infection; however occasional presence of thrombocytopenia with normal liver function, or presence of significance hepatic damage with normal platelet count has not been well explained. Biological factors, such as ethnicity, age, smoking status and gender have been suggested as the probable causes, but not enough studies exist showing such predispositions. The goal of this study is to evaluate the association of degree of thrombocytopenia with liver function abnormalities in different ethnicity in HCV infected patients.

Methods

Forty -five patients with thrombocytopenia and HCV infection were included. Data was collected on ALT level, ethnicity, platelet count, and liner regression study was performed. Clinical predictors included in the analysis were age, gender, liver fibrosis stage, smoking status and ALT level. Results: Severe thrombocytopenia (<80,000) is associated with severity of liver function. Moderate and mild thrombocytopenia does not depend on liver function abnormalities. Moreover, there is an increases incidence of moderate and severe thrombocytopenia among Hispanics Latinas. Also, the incidence of mild thrombocytopenia (>110,000/ µL) is not significantly different among people of different ethnicity infected with HCV.

Results

Our study suggests that chronic HCV infection is associated with variable degree on thrombocytopenia., and only severe thrombocytopenia (platelet count < 80,000/ µL) can be explained by liver function abnormalities.

Conclusion

As liver disease advances, platelet count decreases only in patients with platelet count is below 80,000 / µL and, it is more prominent in Hispanic/Latina population.
Improvement on the Use of 3-aminopropyltriethoxysilane and Poly-L-lysine Coated Slides for Immunohistochemical Staining of Lifting Tissue Sections
Authors: Iyiola S , Aremu O , Onifade J A
Published: October 2020

Introduction/Objective

Lifting of tissue section during antigen retrieval occasionally occur most especially with the brain tissue. therefore, this work seeks to provide solution on how to use locally charged 3-aminopropyltriethoxysilane (APES) and poly-l-lysine coated slides for brain immunohistochemistry (IHC).

Methods

This laboratory experimental control study was carried out in Obafemi Awolowo University Teaching Hospital Complex, Nigeria owing to section lifting associated with our brain tissue during IHC. Two tissue blocks of lifting brain section were cut at 5um. 30 sections were cut from each block. 10 sections from each block were floated onto APES coated slides, poly-l-lysine and superfrost plus. The sections were allowed to stand for two hours before putting them on hot plate at 370C overnight. The slides were arranged on 4 slide carrier containing 15 slides from each block, 5 slides from each group. The slides were dewaxed and hydrated to distilled water. Then, a set of 15 slides in a carrier from each block was allowed to air dry under ceiling fan on hot plates at 30OC until no traces of water was found on them. All the slides were then subjected to heat mediated antigen retrieval protocol using citrate buffer solution. Three slides from each block consisting of a non-post hydration air dried tissue section on superfrost plus as a control, post hydration air dried tissue section from APES and poly-l-lysine were stained with GFAP.

Results

All the sections on superfrost plus did not lift. All the post hydration air dried tissue sections on locally charged slides did not lift. Approximately one tissue section from non-air dried post hydration locally charged slides did not lift. There was no difference in the staining pattern of GFAP on all the tissue sections.

Conclusion

We propose that air dried tissue section after dewax and hydration could be used for GFAP study, most especially in a population that cannot afford commercially charged slides.
Innovating With the Times: Pathology Education in Context of Physician Burnout
Authors: Saxena R , Crum R , Moore N , Warha S
Published: October 2020

Introduction/Objective

Learning a boundless volume of information, preparing for multiple exams, and getting involved in several other academic activities are just a few things that the current medical students need to tackle in a finite duration. While these challenges encourage learners to be their best, and prepare them for their careers as future physicians, they can also result in a largely unnoticed issue — burnout. Curricular reform targeted at developing skills to mitigate burnout is the need of the hour. To combat this issue in the pathology classroom, we used our tried and tested strategy of algorithms in combination with fun activities, particularly keyword mnemonics, to evaluate the impact on reducing burnout in medical students.

Methods

Lectures were delivered and recorded for students of semester 4 and 5, and sample algorithms and mnemonics were included. We also used pathophysiology case sessions comprising clinical vignettes and questions. Students were divided into small groups to solve questions and had to frame their own algorithms and mnemonics to help them. The method’s effectiveness was assessed using performance in past and current exams. Feedback was performed to gauge students’ perceptions

Results

Feedback evaluation showed that 86% of students indicated that algorithms and mnemonics not only strengthened the rote memory but also helped lessen the stress during exam preparation. 59% of students expressed that teamwork made it easier and fun to work. Almost 11% felt that mnemonics should be included as part of new lectures but they found it difficult and ineffective to make their own. Further assessment will be performed to analyze the strategy’s impact on burnout.

Conclusion

Classroom traditions that encourage shared problem-solving and decision-making leads to reduced burnout rates among medical students, with the added benefit of enhanced retention of complicated material and improved clinical correlation capabilities. The relationship between stress and memory is well-documented, and feedback revealed that this technique helped alleviate negative stress on the students. Our project underlines the essence of research studies to minimize burnout in medical students, for design and development of future interventions to prevent burnout at the outset in the training of future physicians.
Nonconcordance of E, N, and RdRp Genes in SARS-Coronavirus-2 Nucleic Acid Amplification Test Among Patients Older than 60 Years
Authors: Caulkins H , Rand K , Harris N , Beal S
Published: October 2020

Introduction/Objective

During the COVID-19 pandemic, the FDA authorized emergency use of nucleic acid amplification (NAA) testing. Accurate and rapid testing identifies infected persons, especially among at-risk populations. In our institution, the InGenius platform detects three gene targets of SARS-Coronavirus-2: envelope (E), nucleocapsid (N), and RNA-dependent RNA polymerase (RdRp). Nonconcordance of these components present accuracy or precision errors or may correspond to varying expression of viral genes with disease progression.

Methods

We retrospectively analyzed the result components from 93 nasopharyngeal swabs from 50 patients older than 60 years and positive for SARS-Coronavirus-2 (SARS-CoV-2). The symptom onset date was determined by chart review.

Results

We found a significant 26% nonconcordance rate, with a predominant pattern demonstrating positive N with negative RdRp and E (χ2 = 27.25, P < 0.0005). This nonconcordant pattern was more prevalent at longer symptom durations. In 7 patients with serial testing, the transition from concordant to nonconcordant results occurred 12 days (95% CI 3.5 – 20.3 days) after symptom onset.

Conclusion

This may be caused by several mechanisms. Possibilities include decreased expression of E and RdRp over time, inhibition of expression by treatments or host immune response, or lower viral titers by clearance or migration to the lower respiratory tract. Presence of a different viral strain or systematic processing errors are less likely causes of nonconcordance. Future directions of study would determine whether a similar decline in RdRp and E detection is seen in tracheal samples or if this correlates with changes in symptom severity.
Strongyloidiasis Of Duodenum Clinically Mimicking As Celiac Disease: A Case Report
Authors: Shah J
Published: October 2020

Casestudy

Strongyloides stercoralis is classified as a roundworm or nematode. S. stercoralis is unique and different from other intestinal nematodes because of its ability to complete its life cycle within the host through an asexual auto infective cycle, allowing the infection to persist in the host indefinitely. It is usually asymptomatic can be symptomatic in immunocompromised individual leading to disseminated disease. Serology and stool microscopy are the investigations of choice. Though histopathology is the gold standard it is invasive procedure and has its own complication. strongyloidiasis is easily treatable with oral anthelminthic drugs. To date, only a limited number of cases has been published in our part of the world.

Strongyloidiasis is often asymptomatic in immunocompetent individuals. We present the case of a 34-year old man from hilly region of Nepal with complaints of on and off abdominal pain since one and half year. Over the last week his symptoms worsened with bilious vomiting, nausea, abdominal pain, loss of appetite and weight loss. Patient was short statured with multiple pruritic lesions over skin. A clinical diagnosis of celiac disease was suspected clinically. Blood examination was performed shows Microcytic Hypochromic Anemia with mild increase in eosinophils. Stool examination and serology was performed it was negative. An endoscopic biopsy from duodenum was performed and histopathologic examination revealed gastrointestinal strongyloidiasis.

Conclusion

Helminthic infections can clinically mimic large number of non-neoplastic and neoplastic diseases like celiac sprue, IBD, GI malignancy etc. The present case highlights the importance of basic investigation like multiple stool examination in patient with GI symptoms before subjecting the patient to invasive procedures.
Isolation Of Anticancer Drug Taxol Producing Endophytic Fungus Alternaria Alternata By Using HPLC And LC- MS
Authors: Ghaly M , Talat I E , Abeer A , Mohamed M , Elmetwalli A W
Published: October 2020

Introduction/Objective

In the exploration of an alternative source, optimum and numerous solvents with different percentage were exploited to extract Taxol from plant palm branche. The fungal endophytes producing secondary metabolites that are effective against the human infections have fascinated many researchers across the world.

Among these, the exploration for novel cancer therapeutic agents is of countless reputation due to upsurge in the number of cancer deaths, high worth of the drugs and the side effects concomitant with cancer treatments.

Accordingly, in the current study, an endophytic fungal strain was isolated from its host plant palm branche and identified as Alternaria Alternata based on its morphological features and internal transcribed spacer sequence analysis.

Methods

Firstly, palm branche were collected for the isolation of endophytic fungi. The samples were placed on PDA plates and after 72 h, the mycelium produced were isolated and sub-cultured. Secondly, further analysis for the presence of Taxol by using chromatographic and spectrometric techniques. Illustratively, ethanol or acetone and 50% and 20% of ethanol. Then, the residues were dissolved in 5 ml of methanol and filtered. By using the internal standard, the resulting solution was subjected to the HPLC to determine the extraction efficiencies of tested solvents. Finally, filtrate was also subjected to the LC-MS – ESI using water/acetonitrile (10/90) as mobile phase to identify the authenticity of Taxol

Results

HPLC analysis revealed that Taxol could be quantified by UV detection using standard curve. Furthermore, the standard curve covering the concentration was linear (r2= 0.9992) and CV% ranged from 0.52 to 15.36. The peaks of fraction 5 obtained by HPLC analysis were quite similar to that of standard taxol confirming the presence of taxol. A parent ion peak of m/z 851.85 was observed in the LC–ESI–MS spectrum which was similar to paclitaxel with reported m/z of 854 [M+H] + ion. A. Alternata produced about 113.193 mg/L taxol as quantified through HPLC

Conclusion

we are recording for the first time the production of taxol by an endophytic fungus Alternaria Alternata. In a final word, present study results advocate that the endophytic fungus A.Alternata aids as a potential source for the production of taxol isolated from Palm branche plant
Ethnic Differences in Infection with SARS-CoV-2; a Veteran Affairs Medical Center (VAMC) Experience
Authors: Petersen J M , Dalal S , Jhala D
Published: October 2020

Introduction/Objective

An Institute of Medicine (IOM) report from 2002 has documented that racial and ethnic minorities have tended to receive worse health outcomes compared to non-minorities. This pattern has been demonstrated for many chronic and acute injuries and illnesses, but to the author’s knowledge, there is sparse literature on this study on outcomes related to the novel coronavirus (SARS-CoV-2). SARS-CoV-2 has become a pandemic of global importance with significant impact on all elements of society. As part of quality assurance, as becoming confirmed positive for SARS-CoV-2 would be adverse clinical news, a review was undertaken to see if there were ethnic differences in the veteran population being tested at the Veteran Affairs Medical Center (VAMC) on the risk of testing positive for SARS-CoV-2.

Methods

As part of a quality assurance/quality improvement project, a manual retrospective review of all SARS-CoV- 2 RT-PCR tests performed at the VAMC from March 11th, 2020 to April 13th, 2020. These tests were reviewed within

the computerized medical record system to determine the age, gender, ethnicity of the patients, and test result of the patient.

Results

There were 571 patients who had tested for SARS-CoV-2. Out of these patients, 99 of these patients had a positive test result. The ethnic breakdown of the unique patients with a positive test result was 67 were African- American (68% of positive results), 2 Asian-American (2%), 1 Native Hawaiian or other Pacific Islander/Hispanic mixed (1%), 17 Caucasian (17%), and 12 declined to answer or left ethnic field unanswered. Among the 471 who had negative results, only 197 or 42% were African American and 118 were Caucasian (25%).

Conclusion

African Americans had more infections with SARS-CoV-2 compared to the other ethnic groups. Caucasians had many of the negative results, and positive results were otherwise not common in the other ethnic groups in the VAMC cohort. Given this first report in the literature of the disproportionate impact SARS-CoV-2 is having on those of African American ethnicity, appropriate clinical access and low threshold to test is essential.