bluuebunny/crossref_metadata_2025 huggingface dataset:
Allocating Blood Products During a Time of Remarkable Shortage
Authors: Dent Edward A , Hamilton Ellie , Bodeker Joy , Roback John , Sullivan H Cliff
Published: November 2022

The COVID-19 Pandemic adversely impacted the nation’s blood supply such that blood suppliers could not fill standing orders. To address the dwindling blood supply, the American Red Cross (ARC) implemented daily thresholds, which distributed red blood cells (RBCs) based on clients’ historical blood orders and the ARC’s inventory. The threshold system left the blood bank to devise a process to judiciously allocate the reduced RBC supply across our institution. Herein, we describe an internal RBC utilization audit, the data from which we used to devise an algorithm to predict our ability to meet transfusion requirements for operating room (OR) procedures. An OR adjudication committee used our report to prioritize elective surgical cases taking places the following day. Thirty-one non-consecutive days of blood inventory release slips were reviewed across three months of recent transfusions. Weekdays were disproportionally investigated to predict the blood utilization for days with scheduled OR procedures. For all RBCs released, the blood type requested and the final disposition (transfused vs returned to blood bank) of the units were recorded. Average use was calculated as well as interquartile range (IQR) to account for transfusion variability. Utilization data was then used to develop a worksheet-based tool to predict ability to meet RBC requirements. Overall, the hospital transfused an average of 80 RBC units each weekday (IQR: 64-92 units). Approximately 40% of all requested RBC units were released to the OR. In turn, the OR transfused only 39% of the RBCs released to them, which represented 20% of transfusions hospital-wide. The OR requested an average of 41 RBC units each weekday (IQR: 25-57 units). The OR transfused an average of 16 units of RBCs each weekday (IQR: 9-21 units). The outpatient cancer center infusion clinic used less than 15% of total RBCs. The biggest user of RBCs were inpatients, who were transfused 65% of RBCs during the week and 82% of transfusions during the weekend. These percentages and the average-to-third-quartile range were used to devise a blood allocation algorithm to inform the OR if the blood bank could support anticipated use. The data was also used to devise a blood allocation worksheet for the on-call transfusion medicine physicians to predict our ability to provide adequate blood for emergent, non-elective procedures that require transfusion support such as liver transplants and aortic repairs. The audit of RBC disposition informed blood inventory management practices during a time of remarkable shortage. Within the confines of the threshold system, the transfusion medicine service allocated the expected number of units based on historical request and transfusion data to predict whether inventory levels could support scheduled and nonscheduled OR procedures.
Lupus anticoagulant testing for patients on direct oral anticoagulants
Authors: Girton Mark , Acker Mary , Bazydlo Lindsay
Published: November 2022

As use of direct factor Xa inhibitor (direct oral anticoagulant; DOAC) therapy increases, a modified lupus anticoagulant (LAC) testing method was studied to remove interfering DOACs, allowing clinicians to evaluate patients for antiphospholipid syndrome (APS) without altering anticoagulation treatment.

We evaluated the use of DOAC-StopTM on our LAC testing panel with two assays: dilute Russell viper venom time (dRVVT), a factor X activator, and Silica Clotting Time (SCT), an intrinsic coagulation pathway activator. The plasma specimens were pretreated with DOAC-STOPTM beads by mixing on a rocking platform for 5 minutes and centrifugation at 5000 rpm for 5 minutes. The treated plasma supernatant was used for each step of the assay including the screen, confirm (addition of phospholipid), 50:50 mix (addition of reagent plasma with coagulation factors) and confirm 50:50 mix. The total ratio (ratio between screen and confirm ratios relative to mean of normal ranges) was calculated and used per the package insert in the positive or negative interpretation of each LAC testing panel. The study included patients with one or more of the following characteristics identified during coagulation sign-out and chart review: no evidence of a LAC (NELAC), evidence of a LAC, and whether on apixaban or rivaroxaban therapy. The effectiveness of DOAC removal was characterized with an apixaban spiking experiment for NELAC and LAC patient specimens which showed no change in LAC testing panel interpretation before and after DOAC-STOPTM treatment. A second experiment with apixaban-spiked NELAC samples demonstrated removal of anti-factor Xa activity upon comparison of pre- and post-treatment with DOAC-STOPTM. Of 10 patients taking rivaroxaban, nine had positive dRVVT interpretations; eight of these specimens changed to negative interpretations after DOAC-STOPTM treatment. For SCT, two positive interpretations remained positive, while two of the remaining eight negatives became positive after treatment. Of nine patients taking apixaban, two had positive dRVVT interpretations, one of which became negative post-treatment. Of the seven negative interpretations, one became positive post-treatment. For SCT, three were positive pre-treatment and seven were negative with no change post-treatment. Providing a LAC testing option for patients on DOACs may be of benefit to patients and clinicians in APS assessment, eliminating the risk of suspending anticoagulation therapy. Our study shows DOAC-STOPTM effectively removes DOAC interference in the majority of patient specimens studied, though LAC testing and interpretation in the setting of a high-complexity patient population on DOAC therapy remains challenging with occasional false positives and false negatives.
Making Complex Cancer Reports Easier Using Self-Built Interactive Templates
Authors: Rogers John , Cara Lukas , Hsu Jim , Christensen Paul , Long Scott
Published: November 2022

Surgical pathology reports are becoming increasingly complex, especially with neoplastic cases. Pathologists need to verify all elements are addressed in the CAP synoptics, order proper reflex molecular testing or immunohistochemistry depending on care standards and institutional guidelines, and address key points in the report for clinicians. For example, breast cancer cases at our institution need repeat biomarkers for all cases status post neoadjuvant therapy, oncotype reflex testing for pT2N0, estrogen receptor positive tumors, and tumor bed size with residual tumor burden calculations for all breast cancer only after neoadjuvant chemotherapy. For residents and faculty alike, these expansive reports are challenging, especially for those new to the institution’s policies and conventions. Previous workflow included using Microsoft Word documents with previously signed out cases had significant risk for errors that stem from new updates in the CAP protocols, missing or different reflex testing from the previous case, and updated institutional guidelines. We set out to create a customized library of decision support and interactive templates using a software called PhraseExpander. We created PhraseExpander templates for all cancer resections. The templates included the associated synoptics required for accreditation by CAP, implemented automated staging using logic statements, and provided conditional reminders when reflex testing was indicated. Variable labels were utilized to help clarify notes in the CAP synoptic such as how to grade specific tumors and how many high-power fields to count. The tools were distributed to all surgical pathology fellows, residents, and select faculty who expressed interest in participating. The templates were successfully implemented into the routine workflow for surgical pathology sign out. End-user feedback was overwhelmingly positive. First year and upper level residents appreciate the detailed descriptions on how to complete the report, most notably the reflex molecular testing reminders and many conditional aspects such as in our breast cancer reports. Fellows and attendings have also appreciated these aspects as well as the automated staging and reminders to do administrative tasks, such as adding the case to the Laboratory Information System tumor registry. Interactive templates with built in conditions and calculators are powerful tools that can be used for generating the increasingly complex reports in pathology. They provide pathologists real-time and non-interruptive clinical decision support, allow them to spend less time typing and reduce reliance on remembering the required reflex testing. The most notable disadvantage in coding these complex templates is the considerable build and maintenance time. We plan to expand use to flow cytometry reports, biopsy reports, and routine non-neoplastic cases while incorporating labels to assist in resident education.
Correlation of PDL1 Expression with Genomic Alterations in Non-Small Cell Lung Cancer: a 7-month retrospective analysis
Authors: Sen Siddhartha , Pratt Anna , Harley Susan , Mroz Pawel , Yohe Sophia , Thyagarajan Bharat , Schomaker Matthew , Kincaid Robyn , Michel Stephen , Li Faqian
Published: November 2022

Background

PD1/PDL1 inhibitors have significantly improved overall survival in non-small cell lung cancer (NSCLC). PDL1 is now a standard biomarker along with molecular testing for therapy selection. Checkpoint therapy is given front-line for patients with high PDL1 and no actionable mutations or fusions, or after progression with any PDL1 expression. Studies comparing PDL1 status in the context of actionable mutations or fusions in NSCLC are sparse.

Design

All patients undergoing molecular testing for a next-generation sequencing (NGS) lung cancer panel at our institution in a 7-month period were reviewed. This included an NGS DNA panel for actionable/driver genes: EGFR, ERBB2, BRAF, K/NRAS, PIK3CA, and IDH1/2; and a NGS RNA fusion panel for ALK, ROS1, RET, NTRK1/3, NRG1, and MET e14 skipping. PDL1 expression by IHC was scored for tumor proportion score (TPS). Statistical comparison was performed using Fisher’s Exact test.

Results

186 patients with NSCLC were included (126 adenocarcinoma, 33 squamous/adeno-squamous, 19 poorly differentiated, and 8 NSCLC-NOS); 162 of those had concurrent PDL1 IHC. 121 (65%) patients had a genomic alteration, most commonly RAS [28%], EGFR [24%], ALK [8%], MET [7%], and BRAF [5%]. Cases with genomic alterations were classified into those with and without RAS mutation/s. The prevalence of high PDL1 expression was greater in RAS-driven tumors: 47% vs 22% with non-RAS bearing genomic alterations (p=0.0173). There was no significant difference in the PDL1 expression between the genomically negative tumors and those with non-RAS bearing mutations. Recently, the FDA granted approval to sotorasib, a KRAS G12C inhibitor, in patients with locally advanced or metastatic NSCLC. However, there was no significant difference in the PDL1 expression between the tumors with RAS G12C mutation and those with other RAS mutations.

Conclusion

Our data indicate that close to half of RAS-driven NSCLC have high PDL1 expression, an important consideration for front-line therapy selection. The majority of genomically-actionable tumors have at least low-positive expression of PDL1, highlighting the potential importance of immune checkpoint therapy in the resistant-progression setting. In comparison, only about one third of genomically-negative cases have high PDL1 expression, and a significant percent are completely negative. When the actionable KRAS G12C mutation bearing cases were compared to those with other RAS mutations, no significant difference was noted in the PDL1 expression between these two subsets; further investigations and a larger cohort of patients may be helpful in this case to determine whether PDL1 levels are affected by a specific RAS mutation.
Validation of Neutrophil gelatinase associated lipocalin (NGAL), a urinary biomarker for Acute Kidney Injury and the positive interference from high leukocyturia samples
Authors: Samara Vishnu , Song Lu , Buggs Vincent
Published: November 2022

Acute kidney injury (AKI) is a sudden and serious kidney damage condition that affects more than 1.2 million people every year. KIDNEY DISEASE IMPROVING GLOBAL OUTCOMES (KDIGO) guidelines currently suggest measuring the increase of serum creatinine as a diagnostic marker for AKI. However, the elevation of serum creatinine levels can take up to seven days or when >50% kidney function is lost. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for tubular injury, which can be detected in the urine of AKI patients in as early as three hours. In the current study, we evaluated the performance of BioPorto’s (Hellerup, Denmark) NGAL assay, which uses particle enhanced turbidimetry immunoassay (PETIA) technology on the Roche (Indianapolis, USA) cobas c502 chemistry analyzer. Linearity was determined using linearity material from BioPorto and also verified by serial dilutions of a high NGAL patient sample. The limit of quantitation was determined by running urine samples with values of 20 ng/mL, 25 ng/mL, and 35 ng/mL, respectively in duplicate for 10 days. Within-run precisions were determined by running urine two samples containing 100 ng/mL and 400 ng/mL NGAL 20 times and between–run precisions were determined by running the same samples 2 times a day for 10 days. To determine the accuracy of the NGAL method on cobas 502, 40 samples were used to compare results with those measured on Siemens Atellica using the BioPorto’s NGAL assay. Reference interval was verified in 40 urine samples collected from healthy donors. A urine dipstick test was performed to confirm the normal urine samples did not contain leukocyte esterase activity. Since NGAL is also present in neutrophils, we evaluated the effect of leukocytes in urine with the NGAL assay. Results showed the sample with 75 leukocytes/µL had an NGAL of 68 ng/mL and the sample with 500 leukocytes/µL has an NGAL of 222 ng/mL. The linearity range was determined to be 0 - 3000 ng/mL with a limit of quantification of 26 ng/mL. The within-run precision mean and CV% are 121 ng/mL, 4.3% for Level 1 and 401 ng/mL, 1.8% for Level 2. Between-run precisions mean and CV% are 106 ng/mL, 4.8% for Level 1 and 399 ng/mL, 2.6% Level 2. Method comparison had a slope of 0.90 and an intercept of 32.9. The reference interval was determined to be <50 ng/mL and Leukocytes in urine did cause false-positive NGAL results.
A Rare Case of Primary Cardiac T-cell Lymphoma in Immunocompetent Adult
Authors: Chen J , Jetly R , Connor E
Published: November 2022

Introduction/Objective

Primary cardiac lymphoma (PCL) is an extranodal lymphoma involving only the heart and/or the pericardium. It is exceedingly rare, accounting for <2% of primary cardiac neoplasms in a surgical series and 0.05% of a >12,000 autopsies’ series, and is often associated with an immunocompromised state. Most PCL are of B- cell lineage with T-cell lymphoma constituting < 10%.

Methods/Case Report

We report a case of unexpected sudden death due to primary cardiac T-cell lymphoma in a 48-year-old immunocompetent man without significant medical history who presented in cardiopulmonary arrest following a two-week history of cold-like symptoms. Autopsy revealed an irregular, discontinuous tan plaque on the epicardial surface that extended over the right and left ventricles, and sectioning revealed that extension of the lesion throughout the subvalvular myocardium of the left ventricular wall, interventricular septum, and medial aspects of the right ventricle. The lesion had irregular areas of necrosis and hemorrhage. No lymphadenopathy or other visceral lesions were identified. Histologically, the myocardium had a regionally necrotic, angiocentric infiltrate of atypical, large, pleomorphic lymphoid cells with large, irregular nuclei, vesicular chromatin, and conspicuous nucleoli. Initial immunohistochemical work-up showed a profile of CD45+/CD20-/CD3+ suggesting a T-cell origin with CD8 predominance (CD4-/CD8+). Further work-up demonstrated a profile as CD2+/CD7+/CD25+/CD30+/EBV(EBER- ISH)+/Ki67(70-80%)/ and ALK-1-/BCL6-/CD5-/CD10-/CD56-, supporting extranodal NK/T-cell lymphoma, extranasal type with a cytotoxic T-cell subtype (perforin+/granzyme B+/TIA-1+/TCR Beta F1+).

Results (if a Case Study enter NA)

NA.

Conclusion

Primary cardiac lymphoma with cytotoxic T-cell subtype is extremely rare and fatal. This case is the third report over the past two decades, to our knowledge, of a primary cardiac T-cell lymphoma leading to acute heart failure and sudden death in an immunocompetent adult.
Papillary Renal Cell Carcinoma with Massive Hemorrhage: An Autopsy Case Report
Authors: Naik U , Amin S E , Gehris B T , Wang W , Hunter R L
Published: November 2022

Introduction/Objective

Spontaneous renal hemorrhage is a rare complication of various kidney pathologies. It can be due to renal artery aneurysms, arteriovenous malformations, cystic renal diseases, renal calculus, coagulation disorders, as well as neoplastic lesions like angiomyolipoma and renal cell carcinoma (RCC). Individuals present with sudden flank or scapular pain, hypovolemic shock, termed as Wunderlich syndrome (WS). 30-35% cases of WS are from spontaneously ruptured RCC, commonly clear cell variant (70%) followed by papillary (10-15%) and chromophobe variant (4-6%). We present an autopsy case of a papillary variant RCC identified as a small kidney mass with a pathogenetic correlation behind the intractable bleeding.

Methods/Case Report

An 81-year-old Caucasian man with a history of atrial fibrillation, on long-term Xarelto treatment, was found to have a 1.2 cm incidental mass in the right kidney. He started experiencing right-sided scapular pain, then rapidly became hypotensive, drowsy. CT scan revealed a large right-sided perinephric and retroperitoneal hematoma (17.5 x 5.7 x 8.9 cm) extending in the pelvis. Despite receiving blood products, other supportive treatment, and successful angio-embolization, his condition worsened to acute kidney injury, bowel ischemia, and persistent lactic acidosis leading to death. On autopsy, bloody ascites, clots on mesenteric root insertion, and bulging in retroperitoneal spaces were seen. The perinephric spaces had organized clots. The bleeding originated from a 2.0 x 2.0 cm brown mass in the middle pole of the right kidney. There was a slit-like vessel at the interface of the kidney and the mass. Microscopic examination of the mass shows trabecula of abnormal cells with abundant eosinophilic cytoplasm in the hemorrhagic and necrotic background. These cells are positive for PAX8, CK7, CD10, dim positive for CAIX, and negative for CD117, which is consistent with renal cell carcinoma, papillary variant.

Results (if a Case Study enter NA)

NA.

Conclusion

Papillary RCC is much less vascular and less aggressive than clear cell RCC. However, necrosis or bleeding into renal vessels may occur. In this case, blood-leaks and accumulation in enclosed space followed by necrosis, fibrosis, and hyalinization cause neovascularization forming a negative spiral for re-bleeding. Anticoagulants can lead to profuse sustained bleeding from even very small size RCC.
Unilateral Primary Breast Dermatofibrosarcoma Protuberans with Negative COL1A1-PDGFB Fusion on Fluorescence In Situ Hybridization
Authors: Hosseini H , Sham S , Morrar D , Steinberg J M , Al-Refai R , Jormark S , Vele O , Hajiyeva S , Tongson K C
Published: November 2022

Introduction/Objective

Dermatofibrosarcoma protuberans (DFSP) is a superficial and locally aggressive cutaneous soft tissue sarcoma. In most patients, DFSP arises from the trunk and proximal extremities with breast being an uncommon location. Although they rarely metastasize (<5%), DFSP variants tend to recur locally. Most molecularly characterized cases have been defined by the translocation t(17;22)(q21.3;q13.1), which yields a fusion of the COL1A1 and PDGFB genes. In routine practice, dual fusion or break-apart fluorescence in situ hybridization (FISH) for the COL1A1-PDGFB fusion gene is the most widely used screening method for DFSP. However, in ~4% of typical DFSP cases, routine FISH screening is negative. In some of the DFSP cases negative for COL1A1-PDGFB fusion gene by FISH, RNA sequencing has identified two novel gene fusions, COL6A3-PDGFD and EMILIN2-PDGFD, with the former having a predilection for the female breast.

Methods/Case Report

We present a 32-year-old woman who underwent a biopsy for a 3.4 cm echogenic firm mass in her right breast. Histology showed a cytologically-uniform spindle cell neoplasm with fibroblastic morphology. The neoplastic cells displayed a storiform growth pattern and honeycomb-like infiltration of the adipose tissue. Immunohistochemically, the neoplastic cells expressed CD34 and vimentin and were negative for AE1/AE3, p63, S100, CD31, SMA, β-catenin, and STAT6. PDGFB break-apart FISH was negative. Based on the histologic and immunohistochemical findings, a diagnosis of DFSP was rendered. FISH for PDFGD rearrangements or RNA sequencing targeting PDGFD was not performed at this time.

Results (if a Case Study enter NA)

NA.

Conclusion

Awareness is warranted for the rare variant of DSFP with a predilection for female breast, which is characterized by a novel gene fusion not detectable by routine FISH used for DFSP screening.
A Rare Presentation of Thoracic Intramedullary Chordoma with Adjacent Bone Involvement: A Case Report and Review of the Literature
Authors: Lazim A , Akhtar I , Rong Y , Arriola A , Mollaee M
Published: November 2022

Introduction/Objective

Chordoma originates from remnants of the embryonal notochord, and arise in bones anywhere along the spine and skull base. The most common location was thought to be the sacrum, followed by the clivus, and to a much lesser extent the rest of the spine. However, some studies have suggested an equal distribution among the skull base (32%), mobile spine (32.8%), and sacro-coccygeal bones (29.2%). Here we report a case of chordoma involving the thoracic spine. at the level of T2.

Methods/Case Report

A 63-year-old male with no significant past medical history who presented with 5-6 months of intermittent, bilateral lower extremity weakness and numbness in the trunk and lower extremities. MRI of the thoracic spine demonstrated a contrast enhancing mass at T2 vertebral level with spinal cord compression and adjacent bone destruction. T1-3 laminectomy with debulking of the tumor was performed. Microscopically, the tumor cells have a lobulated architecture and are composed of epithelioid cells arranged in cords, clusters or nests, embedded in a myxoid mucinous matrix. The epithelioid cells have a variably vacuolated cytoplasm ("physaliphorous" cells). The epithelioid cells are positive for CK AE1/3, Cam5.2, EMA and Brachyury (nuclear stain), and S100 (focal). These findings support a diagnosis of chordoma.

Results (if a Case Study enter NA)

N/A.

Conclusion

The most important and difficult differential diagnosis of chordoma is with well-differentiated chondrosarcoma. Although both chordomas and chondrosarcomas express S100, chondrosarcomas do not express cytokeratins, EMA or brachyury. Chordomas have an aggressive clinical course and poor outcome with local extension, recurrence and even metastasis. The treatment is en block surgical resection with adjuvant radiotherapy. The extent of the initial surgical resection is the most significant prognostic factor.
Metastasis of a Primary Sinonasal Alveolar Rhabdomyosarcoma to the Testicle in an Adult Patient
Authors: Chiu R , Dreikorn S , Peng S
Published: November 2022

Introduction/Objective

Alveolar rhabdomyosarcoma is an aggressive tumor of skeletal muscle differentiation that predominantly affects adolescents and young adults, and is rare over 45 years of age. It has poor prognosis with metastasis, and most commonly spreads to the lymph nodes, bone marrow, and lungs. In this report, we describe a middle-aged patient with a primary sinonasal alveolar rhabdomyosarcoma which metastasized to the right testicle, an unusual metastatic site reported only a few times in literature.

Methods/Case Report

Our patient is a 53 year old male who presented in 2020 with recurrent epistaxis and bilateral cervical lymphadenopathy over a 2 month period. Maxillofacial CT/MRI imaging revealed a 4-cm sized mass within the left nasal cavity eroding into the ethmoid sinuses. The patient underwent endoscopic sinus surgery of the sinonasal mass, which on histology, appeared as poorly differentiated small round blue cells with numerous mitoses infiltrating as single cells and nests. These cells stained positive for vimentin, myogenin, desmin, and CD56, and negative for AE1/AE3, chromogranin, S-100, CD99, and CD45. The cells showed very high Ki67 proliferation index (70-80%) and tested positive for FOXO1 gene rearrangement, which supported the diagnosis of alveolar rhabdomyosarcoma. The patient completed chemoradiation therapy, and MRI scans over the next 2 years were negative for residual sinonasal tumor. However, the patient returned in 2022 after having undergone a right orchiectomy at an outside hospital for testicular pain, and abdominal CT showed diffuse retroperitoneal lymphadenopathy concerning for metastasis. On histology, the resected testicle showed seminiferous tubules infiltrated and destroyed by sheets of poorly differentiated small round blue cells with fibrous septae separating the nests of tumor cells into alveolar-like spaces with central loss of cohesion. The tumor cells showed the same immunohistochemical staining pattern as the primary sinonasal lesion, thus confirming it to be metastatic alveolar rhabdomyosarcoma.

Results (if a Case Study enter NA)

NA.

Conclusion

It is unusual for alveolar rhabdomyosarcomas to occur in adults over 45 years old, and is even rarer for these tumors to metastasize to the testicle. Metastases also only account for 1% of testicular tumors. Our report documents a very rare case of an alveolar rhabdomyosarcoma in a middle-aged adult which metastasized to the testicle after chemoradiation therapy.
Paravertebral Pseudoendocrine Sarcoma
Authors: Karimi S S , Gonzalez M F
Published: November 2022

Introduction/Objective

Pseudoendocrine sarcoma is a rare and newly described, emerging entity occurring predominantly in middle-aged to elderly males with apredilection for the thoracic paravertebral soft tissue. Pseudoendocrine sarcoma is a recently recognized intermediate-grade sarcoma with CTNNB1 mutations.

Methods/Case Report

Herein, we present a case of a 66-year-old male with a 10-year history of a progressively enlarging, painful, mid-back lesion. CT scan of the chest demonstrated a right paraspinal soft tissue mass measuring 9.5 x 5.5 x 4.5 cm located at the level of T8-T11. An image-guided biopsy was performed revealing monotonous, epithelioid cells, with round hyperchromatic nuclei, eosinophilic, granular cytoplasm, and indistinct borders arranged in rosettes. Mitoses, necrosis and lymphovascular invasion were not identified.The tumor cells were positive for Beta- catenin, CD56, BCL-2, BCL-6, CD4, CD34 and CD 68, and had a low-proliferative index. The neoplastic cells lacked staining with CK-AE1/AE3, CAM-5.2, NKX3.1, PAX8, Chromogranin, Synaptophysin, NSE, EMA, CD3, CD7, PAX5, and inhibin. The morphology and the immunophenotype support the diagnosis of pseudoendocrine sarcoma.

Results (if a Case Study enter NA)

N/A.

Conclusion

To date, few cases have been described in the literature. Recognition of this entity is important due to the potential for local recurrence (43%), and regional and distant metastasis. Complete excision of the lesion as well as adequate patient surveillance is imperative as we gain more understanding of the metastatic potential and prognosis of this emerging entity.
Hemophagocytic Lymphohistiocytosis Associated with Diffuse Large B-Cell Lymphoma: A Case Report
Authors: Hosseini H , Bendari A , Sham S , Yurovitsky A , Vele O , Ngu S , Futuri S
Published: November 2022

Introduction/Objective

Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune hyperactivation and dysregulation that has been observed in some malignancies. In HLH, natural killer (NK) cells and cytotoxic T-cells fail to control activated macrophages, leading to cytokine-mediated tissue injury and multiorgan failure. Persistent tumor antigenic stimulation and cytokine hypersecretion can trigger HLH. Diffuse large B- cell lymphoma (DLBCL) is uncommonly associated with HLH.

Methods/Case Report

A 50-year-old woman presented with daily fevers and malaise of one-month duration. Imaging showed marked hepatosplenomegaly with no lymphadenopathy. Laboratory studies were significant for pancytopenia (WBC: 3.8 K/µL, Hb: 6.8 g/dL, Plt: 74 K/µL), hypertriglyceridemia (330 mg/dL), hyperferritinemia (1460 ng/mL), and elevated soluble interleukin-2 receptor (CD25) (42351.5 pg/mL). These findings, along with NK cell activity level (not obtained in this case), fever, splenomegaly and hemophagocytosis (bone marrow, spleen or lymph nodes) represent the eight diagnostic criteria by Histiocyte Society HLH-2004. A splenic biopsy showed a nodular proliferation of medium-to-large neoplastic lymphocytes with CD20, PAX5, BCL6, MUM1, BCL2, CD5 (dim) and CD10 (dim) expression and negative for cyclin D1 and p53. CD21 did not highlight any dendritic cell meshwork. The bone marrow biopsy provided similar results. Overall, these findings were consistent with a DLBCL, germinal center subtype. Rearrangements of MYC, BCL2 or BCL6 genes were not detected. Although hemophagocytosis was not noted in the bone marrow or spleen, the patient met six of the eight HLH-2004 criteria (minimum five are required). The H-score was 174 reflecting up to 70% probability of HLH. Treatment with daily intravenous dexamethasone 10 mg/m2 was initiated as a temporizing measure prior to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy which resulted in complete remission.

Results (if a Case Study enter NA)

NA

Conclusion

Physicians should be cognizant of secondary HLH as a rare complication of DLBCL. Prompt initiation of the appropriate therapy could result in rapid and complete resolution.
The Correlation Between Serum Collagen III Levels and APRI in Liver Fibrotic HCV Patients
Authors: Abdelmonem M , Abdelmageed M , Wasim H , Eldaly R , Elhusseny A , Saleh Abdelfattah M
Published: November 2022

Introduction/Objective

Noninvasive Markers (NIM) of Liver Fibrosis help evaluate the stage of fibrosis in patients with no clear indication for a liver biopsy, such as patients with chronic hepatitis C who need monitoring of the stage of fibrosis during or after treatment. The perfect NIM for hepatic fibrosis should be inexpensive, safe, simple, reliable, and well-validated in different forms of chronic liver disease.

Aim of the work

Find if there is a correlation between serum collagen III and APRI as noninvasive markers in patients with HCV-induced liver fibrosis.

Methods/Case Report

118 patients with HCV induced liver fibrosis (60 males and 58 females) and 50 healthy comparable control subjects (27 males and 23 females) were enrolled in the study. Collagen III was identified in serum samples of HCV-induced liver fibrosis patients at 70 kDa using collagen III polyclonal antibody and western blot analysis techniques. Collagen III was purified using the electroelution technique and then quantified using the ELISA technique. AST, ALT, albumin, and total bilirubin were measured. The APRI was calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. The AST-ALT ratio was calculated as [AST/ ALT].

Results (if a Case Study enter NA)

There was a statistically significant difference between the diseased and control groups (P<0.0001) regarding collagen III and APRI. Also, significant positive correlation between serum collagen III, APRI, and ALT levels (r=0.3 and p=0.02). However, there were no correlations between serum collagen III levels and AST, Albumin, Total Bilirubin, and AST/ALT ratio (r=0.15, -0.26, 0.22, and -0.027), respectively.

Conclusion

Collagen III and APRI is a promising diagnostic and prognostic potential in the noninvasive assessment of liver fibrosis as their levels elevate with each other. So, we can powerfully depend on them in liver fibrosis diagnosis in chronic HCV patients.
Ceruloplasmin: A Surrogate Marker of Osteoporosis
Authors: Das S
Published: November 2022

Introduction/Objective

Osteoporosis is a bone disorder and is currently a major global health issue. Ceruloplasmin (CP) is an acute phase reactant and antioxidant, characterized by ferroxidase activity and increases in inflammation. C-reactive protein (CRP), an acute phase protein belonging to pentraxin family of proteins. This study was designed to investigate the role of acute phase reactants Ceruloplasmin and CRP in the screening of osteoporosis. The objective of this paper is to evaluate the role of serum Ceruloplasmin and C-reactive protein as biomarkers of osteoporosis.

Methods/Case Report

This study was conducted in the Bone Clinic and the biochemistry department of a tertiary care hospital. One hundred and twenty participants were included in the study belonging to the age group of 50 to 80 years. Participants in the group were divided into two groups, group I: comprising of patients with osteoporosis, and group II: consisting of patients without osteoporosis (n=56) (control group) (n=64). Patients were classified into two groups on the basis of Bone Mineral Density measurements using dual-energy. X-ray absorptiometry scanning. CRP and serum CP levels were analyzed in blood samples by immunoturbidimetry.

Results (if a Case Study enter NA)

Serum ceruloplasmin levels were significantly higher in Osteoporosis patients as compared to the control group. A significant positive correlation (r= 0.92, p<0.05 ) was observed between higher serum levels of CP and higher levels of CRP in the Osteoporosis patients. There was a significant difference in the CP levels of the osteoporosis group (68.4± 7.2 mg/dl ) and the control group (37.3 ± 4.9 mg/dl) (p<0.05). CRP levels also differed significantly among the osteoporosis patients (2.23± 0.68 mg/dl) and the control participants (1.07± 0.42 mg/dl) (p<0.05).

Conclusion

Our study demonstrates that the measurement of serum ceruloplasmin levels has the potential as a surrogate marker for patients with osteoporosis
Integrating Transgender Medicine Curriculum in Medical Laboratory Sciences
Authors: Ledesma C J
Published: November 2022

Introduction/Objective

Transgender, non-binary, and other gender-diverse individuals experience poor health outcomes as a result of discrimination in health care settings. In order to develop a competent and knowledgeable workforce, a curriculum that will promote the understanding of the health needs of patients with gender incongruence is imperative. Developing a curriculum and its integration into medical laboratory science will increase competency and develop a knowledgeable and culturally-competent workforce of medical laboratory professionals.

Methods/Case Report

To increase the competency of medical laboratory professionals, a 2-part training program will be developed to help address medical laboratory professionals' healthcare encounters with persons who identify as lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI). The curriculum developed will help learners understand the effects of gender-affirming care as it relates to laboratory medicine.

Curriculum Outline

Sex and Gender Orientation

Historical Perspectives in Transgender Health

Epidemiology and Health Outcomes of Transgender Patients

Transgender Medicine

Transgender Medicine in Medical Laboratory Sciences.

Results (if a Case Study enter NA)

NA

Conclusion

Future considerations related to the development of a curriculum to understand the effects of transgender medicine in medical laboratory sciences will include Increased awareness of transgender medicine for all levels of laboratory staff. Ability to understand the needs of the patient population and be patient advocates to improve health outcomes. Understand the physiologic effects of gender-affirming care and its impact on medical lab tests. Determine inadequacies in an institution and help develop processes to help improve data collection important to understand the health care needs of demographic. Update the knowledge base of practitioners to further enhance laboratory services and promote healthcare equity.
Biannual Administration of a Slide Exam to Residents to Prepare them for Board Examinations: A Pilot Effort
Authors: Wu J , Schaberg K
Published: November 2022

Introduction/Objective

To enhance surgical pathology education and allow residents to self-assess their progress, a pilot effort was made to twice a year administer a slide exam simulating the microscopic component of the American Board of Pathology anatomic pathology examination to a cohort of residents.

Methods/Case Report

The subjects were pathology residents in a mid-size academic program typically consisting of 12 residents. The quizzes were held twice a year from fall 2019 to fall 2021. In the fall of 2019, the exam consisted of 20 glass slides with accompanying history for which the residents were required to provide a free text diagnosis. After the onset of the coronavirus pandemic, the exam was transitioned to virtual microscopy using whole slide imaging similar to the board exam. The answers of the trainees were graded in comparison to the clinical diagnoses. The residents’ opinions of the exercise were anonymously assessed via a survey.

Results (if a Case Study enter NA)

Overall, resident performance roughly correlated with post-graduate year with a gradual improvement in performance every year. All residents agreed (with 84.1% of them “strongly” agreeing) that this exercise benefited their education. After two years of seasonal examination, there was an increasing trend showing more residents, including junior ones, becoming more confident in their preparation for the anatomic pathology board exam.

Conclusion

Though the sample size in this study is small, it demonstrates that regular administration of a slide exam to residents can be used to help residents assess their progress and help them feel more confident in their preparation and training for board exams.
An Extremely Rare Variant of Pancreatic Ductal Adenocarcinoma Masquerading as Chronic Pancreatitis
Authors: Smith C J , Scott K , Parrett T , Rao D
Published: November 2022

Introduction/Objective

Primary Pancreatic signet-ring cell carcinoma (PPSRCC) is an extremely rare histologic variant with sparse literature. Herein, we describe a case of PPSRCC in a 75-year-old female with positive family history of pancreatic cancer (47y/o brother). The diagnosis was delayed secondary to diagnostic challenges on initial fine-needle aspiration (FNA).

Methods/Case Report

Diagnosing PPSRCC on FNA can be extremely difficult. Primary, and metastatic neoplasms to the pancreas may exhibit cytomorphological similarities to signet-ring cells, posing diagnostic challenges. Further, sampling of abundant background inflammatory cells during a biopsy can result in incorrect diagnosis of pancreatitis. Given the strong clinical suspicion based on imaging findings, a second FNA was performed which showed few atypical cells suspicious for carcinoma. Subsequently, the patient underwent neoadjuvant chemotherapy and Whipple resection. The tumor morphology is characterized by infiltrating cells with large mucin vacuoles and peripheric nucleus comprising > 50% of the mass lesion with perineural invasion, in a background of chronic inflammation and pancreatic intraepithelial neoplasia, grade III. A diagnosis of PPSRCC was rendered. Notably, lymph nodes (LN) showed no evidence of metastasis.

Results (if a Case Study enter NA)

NA.

Conclusion

Based on limited literature, PPSRCC is considered an aggressive malignancy with low survival rate, because of a high rate of metastasis. However, our case was rather unique given the lack of LN metastasis and the neodjuvant treatment strategy. As of February 2022, <10 cases have been reported with ill-defined characteristics and treatment guidelines.
Serous Cystadenocarcinoma of Pancreas: A Rare Find
Authors: Kumar S , Jabbar K
Published: November 2022

Introduction/Objective

Pancreatic cystic neoplasms comprise 1-2% of pancreatic lesions and most of these lesions are cystadenomas. Serous cystadenocarcinoma is an extremely rare but known malignant condition described in the literature and the diagnosis is restricted to cases with distant metastasis of tumor beyond the pancreas. Per WHO, cytologic atypia, vascular, perineural, and adjacent organ and lymph node involvement by direct spread are insufficient for the diagnosis of serous cystadenocarcinoma.

Methods/Case Report

We report an interesting case of serous cystadenocarcinoma of pancreas in a 55-year-old male with medical history of prostate cancer was found to have a 15 cm mass pancreatic tail suspicious for neuroendocrine tumor and 5 small hepatic lesions suspicious for metastasis. The patient underwent subtotal pancreatectomy and splenectomy, and wedge resection of liver lesions. On gross examination, a yellow cystic mass was present in the pancreatic tail measuring 13.2 cm in the maximum dimension. H&E slides from the pancreas and liver demonstrated a neoplasm composed of cystic and solid areas, within a background of fibrosis and focal hemorrhage. Cystic areas showed microcysts composed of cells with clear cytoplasm and round to oval bland nuclei. Solid areas demonstrated almost no microcysts but sheets and clusters of cells with clear to scant cytoplasm, oval to round nuclei, few areas of atypical hyperchromatic cells, and occasional mitosis. Very focal clusters and cords of neuroendocrine cells, constituting less than 5% of the tumor volume were also identified. Immunohistochemical stains demonstrated the neoplastic cells both in cystic and solid areas were positive for CK7, CK19, MUC6, and inhibin. Ki67 demonstrated an overall proliferation index of 3%. Chromogranin and synaptophysin were negative within the solid and cystic components of the tumor, however, showed positive staining within neuroendocrine foci. Neoplastic cells were negative for all other tested markers including beta-catenin, ER, Hep-par 1, HMB45, IMP3, MART-1, PAX-8, and trypsin. RB1 expression was retained within neoplastic cells.

Results (if a Case Study enter NA)

N/A.

Conclusion

The differentiation between benign and malignant serous cystadenoma both histologically and clinically may be very difficult as some cases of serous cystadenocarcinoma may not show overt cytologic atypia. The presence of metastasis, which most often occurs in the liver is required for the diagnosis of serous cystadenocarcinoma.
Extensive Post-EMR Procedure Related Artifact due to Novel Submucosal Lifting Agent, Mimicking Amyloid – A Diagnostic Pitfall
Authors: Dalal S , Jhala D
Published: November 2022

Introduction/Objective

Endoscopic mucosal resection (EMR) techniques are vital for the management of premalignant lesions and early-stage (T1N0) malignant lesions of the digestive tract. Recently FDA approved submucosal lifting agent “ORISE™” (Boston Scientific, Marlborough, MA) for EMR procedure to enable resection of the polyp or lesion. We herein present two hemicolectomy cases performed for a colon cancer showing an exuberant amyloid-like reaction due to ORISE™ Gel.

Methods/Case Report

At Veterans Affairs Medical Center, two cases of hemicolectomy were performed for colon cancer. Both cases had prior EMR procedure performed for a large cecal polyp. ORISE™ gel was injected with successful lift of the polyp during EMR. Pathology on both cases revealed tubulovillous adenoma with high grade dysplasia; hence right hemicolectomy was performed. Microscopic examination revealed submucosal area with extensive amorphous, eosinophilic/hyaline deposits and surrounding giant cell formation, underlying the cancerous polyp. The deposits were neither refractile nor polarizable. No tattoo pigmentation identified to explain this reaction. The fibrillary eosinophilic deposit raised the concern for concurrent amyloid deposits. This stained pale blue with Masson trichome special stain. Congo red special stain for amyloid was negative and no apple-green birefringence under polarized light was identified. Finally, after extensive ancillary work-up with literature review, the case was signed out as “changes consistent with post-EMR ORISE™ gel artifact”.

Results (if a Case Study enter NA)

N/A.

Conclusion

Knowledge of EMR procedure artifact due to use of ORISE™ gel is crucial in routine hemicolectomy specimens performed for unresectable polyps or colon cancer cases. ORISE™ gel creates amorphous hyaline deposits mimicking amyloid. The deposits encompass larger submucosal area with giant cells mimicking foreign body. Delay in turn around time of the case with additional cost for the ancillary work-up. Extensive amyloid-like reaction is a diagnostic pitfall in routine hemicolectomy specimens and, awareness of prior EMR procedure related artifact is important to avoid misinterpretation and delay in patient care.
Fistula-associated Mucinous anal Adenocarcinoma, a Surprise Diagnosis in a Benign Chronic Peri-Anal Fistula Resection
Authors: Dalal S , Petersen J M , Jhala D
Published: November 2022

Introduction/Objective

Mucinous anal adenocarcinoma arising in a long standing, chronic peri-anal fistula is rare, accounting for 2-3% of the total anal adenocarcinomas with only few cases reported in a literature. These slow growing, locally aggressive neoplasms with a low-grade histologic appearance, clinically manifest late in a disease course. This entity’s pathogenesis and origin remains controversial. As it arises within a chronic fistula, these tumors present a late stage. Hence, this is generally a surprise finding upon fistula excision. Mucinous carcinomas from other sites should be ruled out with ancillary studies before making this diagnosis. Awareness of this rare cancer is crucial.

Methods/Case Report

67-year-old male with a known history of fistula, presented with reports of recent onset of pain and swelling near his anus. He had a history of seton placement, perirectal abscess drainage and past fistulotomy in 2006 and 2008. On physical exam, he had a firm, tender mass with an ostium just right and posterior to his anus. Pre- operative diagnosis was a chronic, recurrent fistula. Immunohistochemical stains showed mucinous adenocarcinoma with anal gland phenotype. Hence, by WHO criteria, this was diagnosed as Fistula-associated mucinous adenocarcinoma. After the diagnosis of cancer, imaging studies for staging did not reveal any metastatic disease, nor was there any residual lesion or fistulous tract as evaluated by the surgeon. Hence evaluation of the margins on the resection specimen was crucial for post-operative radiotherapy.

Results (if a Case Study enter NA)

NA.

Conclusion

1. Mucinous adenocarcinoma arising in a chronic, benign fistula is a rare entity with unsuspected diagnosis, and since the presentation is often delayed, a high degree of clinical suspicion is required for early diagnosis and management. Early detection is crucial as prognosis is worse if size is greater than 5 cm, and/or if there is lymphatic or vascular invasion. Acellular mucinous pool in excision of a benign fistula, should raise the suspicion of this entity. Excision specimen from the long standing chronic, fistulas should be submitted in its entirety for microscopic evaluation to avoid the possibility of missing this underlying malignancy. Most patients can be cured with aggressive surgical and adjuvant chemoradiotherapy, hence, when possible, this specimen should be inked to enable the evaluation of the margins.