bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal Stromal Tumor (GIST) masquerading as undifferentiated gastric carcinoma; a potential diagnostic pitfall
Authors: Pham J M , Graham S M , Hamza A
Published: October 2024

Introduction/Objective

Epithelioid variant of the GIST can mimic carcinoma and misdiagnosis has grave implications in patient management. The purpose of this report is to describe such a case and to remind pathologists to keep epithelioid GIST in the differential.

Methods/Case Report

A 66-year-old male presented with melena for 2 weeks. Endoscopy showed a large, infiltrative, and ulcerated mass in the gastric fundus. CT imaging showed a 16 x 12 cm mass-like gastric wall thickening, most compatible with gastric carcinoma. The mass was biopsied, which showed sheets and clusters of anaplastic, large to medium sized polygonal epithelioid cells with areas of rhabdoid phenotype characteristic of an undifferentiated gastric carcinoma. Initial immunohistochemical stains including pancytokeratin and p40 showed negativity, prompting additional stains including Cam5.2, SOX10, CD45, synaptophysin, INSM1, EMA, CK7 and CK20- all of which were also negative. At this point the main diagnostic consideration was undifferentiated gastric carcinoma. However, for completion purposes, DOG1 stain was added that came back positive. Since rhabdoid morphology is a bit unusual, even for epithelioid GISTs, and literature review suggested that DOG1 positivity can be seen in up to 11% of carcinomas, confirmatory NGS testing was performed. This demonstrated a KIT W557R gene mutation, confirming the diagnosis of GIST. The patient was treated with imatinib and subsequent imaging showed decreased size and hypermetabolism of the gastric mass. Patient is alive with disease 6 months after the diagnosis.

Results (if a Case Study enter NA)

NA

Conclusion

Using a panel of appropriate immunohistochemical stains and keeping epithelioid GIST in the differential can help avoid this diagnostic pitfall.
Primary Tumor Histology is a Potential Independent Predictor of Oncological outcomes in Colorectal Cancer
Authors: Tanko N M
Published: October 2024

Introduction/Objective

Evaluation of the primary tumor histology can identify features in the tumor microenvironment (TME) that are intricately linked to molecular changes and aggressive tumor behavior in colorectal cancer (CRC). In this study, we evaluated the primary tumor histology such as the tumor histologic subtype, the presence of poorly differentiated clusters (PDCs), and stromal desmoplastic reaction (SDR), and determined their relationship with tumor grade, stage, and DNA mismatch repair (DNA MMR) gene status.

Methods/Case Report

This was a retrospective study. Hematoxylin and eosin-stained microarray sections of CRC tissues in 208 patients were pathologically evaluated. PDC was defined as a cluster of ≥ 5 nuclei in the stroma with no glandular differentiation. SDR was defined as stromal connective tissue remodeling. Parallel sections were stained with antibodies against the MLH1, PMS2, HMS6, and HMS2 for their expression. Statistical analysis was performed for the association between the variables

Results (if a Case Study enter NA)

There were 208 patient samples, 113 were males (54.3%) and 95 were females (45.7%). 61.5% were ≥ 50 years and 38.5% were less than 50 years. 59.4% and 37.5% of stages II and III tumors had PDCs. Univariate analysis showed a strong association between tumor grade, stage, and SDR (p=0.005 and p= 0.013 respectively) but not with PDC and MMR deficiency. 16.8% of tumors had MMR deficiency which was more prevalent in adenocarcinoma with mucinous components (27%). Multivariate analysis showed a strong association with PDC and tumor stage (p=0.026), tumor subtype and stage and grade (p=0.007, p= 0,023), stage, and SDR (p = 0.026). Grade, stage, SDR, and MMR all showed very strong association (p=0.005, p=0.019).

Conclusion

Our data shows that tumor histology is an independent predictor of oncological outcomes in CRC. Future longitudinal studies on prospective cohorts are required to validate our observations and increase the power of our deductions.
Gastric and Gastrointestinal-like Immunophenotypes In Conventional Endometrial Endometrioid Adenocarcinomas Including Endometrioid Adenocarcinomas with Mucinous Differentiation: Frequency and Diagnostic Implications
Authors: KHAEFPANAH D , ZARE S , HASTEH F , AISAGBONHI O , ROMA A , FADARE O
Published: October 2024

Introduction/Objective

Mucinous carcinomas of the gastric/gastrointestinal type (MCG) are now recognized as a rare, clinically aggressive subtype of endometrial cancer [EMCa]. However, neither their full morphologic spectrum, nor their defining immunophenotype, has been clearly defined. Previous proposals for their recognition include at least focal immunohistochemical expression of gastrointestinal markers, minimality or absence of ER and possibly PAX8 expression, and the absence of an endometrioid carcinoma component. Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in conventional endometrioid carcinomas without any discernible gastric/gastrointestinal-type morphology.

Methods/Case Report

Immunohistochemical analyses for CK7, CK20, CDX2, ER, SATB2, MUC6, PAX8 were performed on 81 EMCa, comprised of consecutively archived cases of low grade endometrioid carcinoma (n=47), FIGO grade III endometrioid carcinoma (n=12), and endometrioid carcinomas with mucinous differentiation (n=22). None showed goblet cells or gastric-type morphology. Expression levels were quantified as H-scores on a standardized 0-300 scale.

Results (if a Case Study enter NA)

Significant subsets of all 3 groups showed expression of MUC6, CDX2, SATB2 and CK20, without any significant differences between the groups. 56%, 62%, 23% and 25% of cases expressed MUC6, CDX2, CK20 and SATB2 respectively. 37% co-expressed MUC6 and CDX2, 12% co-expressed CDX2 and CK20, 6% co-expressed MUC6, CDX2 and CK20 and 2.5% co-expressed CDX2, CK20 and SATB2. The expression levels were generally low across all groups, with average H scores for positive cases being 49.5 [range 1-250] for MUC6, 33.7 [range 1-285] for CDX2, 24.0 [range 1-270] for CK20, and 30.5 [range; 2-220] for SATB2. There was no statistically significant correlation between the expression of any of the 4 markers (CK20, CDX2, SATB2 or MUC6) and low ER or PAX8 expression. However, the only 2 cases with high CDX2 expression (H: >/=200) were also associated with low ER (H<50) expression, and one of these concurrently showed high CK20 (H: 270) and low PAX8 (H: 2) expression, suggestive of true intestinal differentiation.

Conclusion

MUC6, SATB2, CDX2, and CK20 are not uncommonly expressed at low levels in endometrioid carcinoma. As such, the expression of these markers cannot be the sole basis for defining the clinically aggressive EMCa with true gastric/gastrointestinal differentiation, and for distinguishing them from conventional endometrioid carcinomas.
Clear Cell Carcinoma Arising in Vaginal Endometriosis in a Patient 33 Years after Total Hysterectomy and Bilateral Salpingo-oophorectomy: A Case Report
Authors: Zhou X , Bian F , Husson M
Published: October 2024

Introduction/Objective

Endometriosis, a common gynecological disorder characterized by ectopic endometrial tissue, is associated with an increased risk of extraovarian malignancies. Vaginal endometriosis is a rare condition, and the occurrence of vaginal malignancies arising from endometriosis is anticipated to be exceedingly rare. Here, we present a rare case of clear cell carcinoma arising in vaginal endometriosis, occurring three decades post-total hysterectomy and bilateral salpingo-oophorectomy.

Methods/Case Report

A 71-year-old female presented with abnormal Cologuard results, leading to a colonoscopy revealing a mass in the recto-sigmoid colon. She had undergone total hysterectomy and bilateral salpingo- oophorectomy for leiomyoma and endometriosis 33 years prior. Histopathological examination revealed clear cell carcinoma arising in vaginal endometriosis, with tumor extension through the colon wall to the colonic mucosal surface (Figure 1). Notably, the vaginal mucosal surface was negative for tumor. Immunohistochemistry staining demonstrated positivity for Pax8, CK7, AE1/3, racemase, and p16, while negtive for ER, PR, CDX2, CK20, CAIX, SatB2, RCC, WTI, Napsin, and calretinin (Figure 2). The staining for p53 was patchy (wild type, not mutated). Cancer-type relevant biomarkers reveal BRAF mutation (p.D594G), ARID1A mutation (p.M1564fs), PD-L1 mutation (Positive, CPS:80), and PIK3CA mutation (p.H1047L). The histologic and immunohistochemistry findings are consistent with clear cell carcinoma arising in a long-standing area of endometriosis (previous surgery in 1990).

Results (if a Case Study enter NA)

NA

Conclusion

Clear cell adenocarcinoma arising from endometriosis is exceptionally rare. Pathologists must consider the possibility of tumors arising from endometriosis when evaluating bowel or mesenteric neoplasms, even decades post-total hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemistry plays a crucial role in the differential diagnosis between carcinoma arising from endometriosis and primary colonic carcinoma. Additionally, Sampson’s criteria are valuable for diagnosing malignant transformations in endometriosis. The identification of specific cancer-type relevant biomarkers, such as BRAF, ARID1A, PD-L1, and PIK3CA mutations, provides additional insights into the molecular characteristics of the tumor, which may have implications for prognosis and treatment selection.
Clonal Bronchopulmonary B-Cell Proliferations of Indeterminate Malignant Potential in Patients with Common Variable Immune Deficiency (CVID) associated Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)
Authors: De la Riva-Morales I , Yeldandi A , Wolniak K , Chen Y , Chen Q , Tariq H
Published: October 2024

Introduction/Objective

Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is often challenging to distinguish from reactive nodular lymphoid hyperplasia, and assessing B-cell clonality in such cases is crucial in making the distinction. However, patients with common variable immune deficiency (CVID) can harbor clonal or oligoclonal lymphoid populations in their tissues, particularly in association with granulomatous lymphocytic interstitial lung disease (GLILD), making the distinction from MALT lymphoma extremely challenging. We report six cases of GLILD with clonal or oligoclonal B cell infiltrates in lung wedge resection specimens and describe their clinicopathologic characteristics, management, and outcomes.

Methods/Case Report

A retrospective review was performed to collect lung wedge resection specimens from patients with CVID showing atypical B-cell infiltrates associated with GLILD between 01/2015 and 08/2023. The clinicopathologic findings, management, and response to treatment were studied.

Results (if a Case Study enter NA)

A total of six GLILD cases were identified with variable degrees of architectural and cytologic lymphoid atypia. Clonality of the lymphoid infiltrate was assessed by kappa/lambda in situ hybridization staining in all six, flow cytometry in 3/6, and IGH gene rearrangement in 4/6 cases. The infiltrate showed frank lambda restriction in 1/6, lambda predominance in 1/6, polytypic expression in 1/6, and no significant plasmacytic component in 3/6 cases. Flow cytometry detected atypical light chain skewed B-cell populations in 3/3 of cases. IGH was positive for clonality in 3/4 and oligoclonal in 1/4 cases. Four patients received therapeutic intervention for GLILD, including one with Rituximab monotherapy, two with Rituximab+Azathioprine, and one with Rituximab+Mycophenolate leading to marked symptomatic and radiologic improvement in all four patients. The remaining two patients were observed to have stable disease.

Conclusion

Patients with CVID can harbor clonal B-cell populations due to their underlying immune dysfunction. Studies have shown that these can be transient and may not always progress to overt lymphoma. In the setting of GLILD, detecting these populations makes the distinction from MALT lymphoma very challenging. Given that the first- line therapy for both GLILD and MALT is anti-CD20 therapy, the malignant potential of these clones remains uncertain and can only be determined with long-term clinical follow-up.
Advancing Diagnostic Accuracy and Quality of Patient Care Through the Implementation of a Flow Cytometry Quality Assurance Program
Authors: Wang D , Ok C , Jorgensen J , Medeiros L , Wang W , Wang S
Published: October 2024

Introduction/Objective

Flow cytometry immunophenotypic analysis plays an important role in the diagnosis, classification and disease monitoring of hematological neoplasms. However, interpretation of flow cytometry testing can be challenging, especially when using highly complex antibody panels. Thus exploring ways to improve diagnostic accuracy and in turn improving quality of patient care is needed.

Methods/Case Report

A flow cytometry quality assurance (QA) program was developed. Cases from various complex flow cytometry panels were randomly selected and cross-reviewed by a second pathologist on a daily basis. The outcomes of the QA review were categorized into three groups: complete agreement, minor discrepancy and major discrepancy. Each discrepancy, once identified, underwent a process of documentation, discussion and resolution. The reports were then modified in a timely manner and the clinical teams were notified of the changes.

Recurrent issues and common pitfalls were reviewed and discussed at a weekly QA meeting. Here we summarize our 3-years’ experience with this program.

Results (if a Case Study enter NA)

In total, 6,166 cases were evaluated by the QA program; 6,028 (97.7%) cases showed complete concordance, 120 (2.0%) cases showed minor discrepancies and 18 (0.3%) cases showed major discrepancies. Antibody panels designed to evaluate mature and immature T-cell abnormalities showed the highest rate of discrepancy, 2.8%, whereas panels designed for evaluation of myelodysplastic syndromes showed the lowest discrepancy rate, 1.7%. When analyzing the trends of concordance and discrepancy over time, we found a statistically significant decrease in discrepancies over time, from 4% at the beginning of the QA program to 1.5% in the most recent time interval.

Conclusion

The overall concordance rate was 97.7%. The remaining 2.3% cases showed discrepancies that required a correction, underscoring the value and necessity of having a QA program. The overall discrepancy rates exhibited a gradual decline over time, indicative of the positive impact of the QA program on enhancing diagnostic competency and accuracy over time.
Kimura Disease: An Atypical Presentation
Authors: Brown H , Nwadukwe A , Leffew M
Published: October 2024

Introduction/Objective

Kimura disease is a benign, chronic inflammatory process which presents with enlarged, painless lymphadenopathy. The etiology is currently unknown. It is most commonly seen in young males of Asian descent and is rare in other populations. It typically affects the subcutaneous tissue and regional lymph nodes, as well as the orbit and adnexal tissues. Clinically, peripheral eosinophilia and increased levels of immunoglobulin are commonly seen. Histologically, the disease presents with follicular hyperplasia with germinal center formation, hyperplastic vasculature, increased eosinophilic inflammatory infiltrate, and characteristic Warthin-Finkedly cells.

Methods/Case Report

A 70-year-old white male with no significant past medical history presented to an outpatient clinic with a painless right eyebrow mass. The mass had grown in size which prompted the patient to seek evaluation. The decision to excise the mass was made. Upon pathologic review, hematological workup was performed, and the case was subsequently diagnosed as Kimura disease.

Results (if a Case Study enter NA)

The specimen was excised and H&E showed background benign fibroadipose tissue with prominent, lymphoid follicles. Within the follicles, there was a significant increase in eosinophils. Warthin- Finkeldey cells were commonly identified within germinal centers as well. Immunohistochemical staining was performed with appropriate controls which ruled out other common lymphoid malignancies and to the diagnosis of Kimura Disease.

Conclusion

Kimura disease is a rare, benign inflammatory disorder that most commonly affects the lymph nodes. It may be overlooked histologically when the patient does not fit the typical clinical picture. It can closely resemble neoplastic, hematologic conditions, and it should be distinguished from a more aggressive entity due to its benign, indolent behavior. From a pathologist’s point of view, because it occurs almost exclusively in young, Asian males, it is important to consider when presented with an atypical demographic to avoid unnecessary additional workup.
Progression of Mast Cell Activation Syndrome to Systemic Mastocytosis
Authors: Zhou X , Caponetti G , Johnson E
Published: October 2024

Introduction/Objective

Mast cell activation syndrome (MCAS) is characterized by the abnormal release of mast cell mediators, leading to symptoms such as flushing, abdominal pain, and allergic reactions. In some cases, MCAS progresses to systemic mastocytosis (SM), a mast cell disorder marked by organ infiltration and dysfunction.

However, predictors of MCAS progression to SM remain poorly understood, and long-term prognosis data are limited.

Methods/Case Report

We conducted a retrospective study of patients diagnosed with MCAS at Penn Medicine from January 1, 2019, through December 30, 2021. The primary endpoint was progression to SM, defined by World Health Organization criteria, with a secondary endpoint set for September 24, 2023.

Results (if a Case Study enter NA)

We identified 47 patients with MCAS (Table 1). Of these, 11 patients (23.4%) progressed to SM. Notably, all five patients with c-KIT mutations progressed to SM (100%, 5/5), while six out of 22 patients without c-KIT mutations also progressed (27.2%). Additionally, baseline serum tryptase levels were identified as a significant predictor of progression at two years.

Conclusion

The relative risk of progression varied depending on the subtype of MCAS, with higher rates observed in those with KIT D816V presence. Compared to the incidence of SM in the general population, our findings suggest a higher risk of progression from MCAS to SM, even without a c-KIT mutation.

Identification of prognostic factors, such as specific genetic mutations and baseline serum tryptase levels, may aid in risk stratification and early intervention strategies for individuals with MCAS. HaT mutation testing should be considered in future studies on this topic. Our findings have important implications for the clinical management and understanding of MCAS progression to SM.

Additionally, our data imply the importance of recognizing MCAS in the early phase and proper monitoring, considering the low rate of MCAS diagnosis. Patients with MCAS may need annual monitoring, including serum tryptase levels, to detect progression to SM and related complications. Early detection and intervention may improve outcomes and quality of life for individuals with MCAS.
MALTomas of the lung: A Clinicopathologic Review
Authors: Findley J , Ehyaee V , Gattuso P , Reddy V , Furci F
Published: October 2024

Introduction/Objective

MALTomas of the lung are the most common primary lymphoma of the lung. They are rare in clinical practice and have an indolent nature with a good prognosis and are often asymptomatic upon diagnosis. We undertook a retrospective study to assess the clinical and pathologic features of primary MALTomas of the lung.

Methods/Case Report

A search for lymphomas of the lung was done in our institutional archive of pathology from 1993-2023. The clinical and pathological data were reviewed in detail.

Results (if a Case Study enter NA)

There were a total of 51 cases of MALTomas recorded. Ages ranged from 35-88 years with an average age of 65 years old. 32 of the patients were female and 19 were male. Twenty eight of these cases involved the right lung, 18 affected the left lung, 5 cases had synchronoous involvement bilaterally. Thirteen (13/51) cases had extrapulmonary involvement, including the bone marrow, stomach, lymph nodes, thyroid, endometrium, eye, small bowel and pleura. 1/51 had synchronous follicular lymphoma and 2/51 had metachronous lymphoma (one large cell and one small lymphocytic lymphoma). 15/51 patients had bone marow biopsies, one of which developed multiple myeloma 7 years later. 10/51 patients had synchronous gastrointestinal epithelial lesions (9 tubular adenomas and 1 carcinoid tumor). 1/51 patients had a synchronous adenocarcinoma of the lung. 18 of the cases showed plasmacytic differentiation (8 kappa restricted and 10 lambda restricted).

Conclusion

Primary MALTomas of the lung are low grade malignancies that can have a more complex clinical scenario, such as multifocality or synchronous/metachronous lesions which can complicate clinical management.
Identifying and Addressing Errors in Anatomical Pathology: A Survey Analysis
Authors: Satturwar S , Singh R , Ullah E , Poombal F
Published: October 2024

Introduction/Objective

To get an update on potential sources of pre-analytical, analytical, post-analytical and other sources of errors in anatomic pathology and strategies to mitigate such errors.

Methods/Case Report

The authors designed a 5-question survey in Google software and shared it widely on social media platforms.

Results (if a Case Study enter NA)

The survey, which garnered 43 responses from staff across various areas of the anatomic pathology laboratory, revealed significant insights. Labeling and fixation/preservation errors emerged as the most prevalent pre-analytical errors, while discrepancies between gross and microscopic examinations were common analytical errors. Specimen handling, inadequate clinical information, and transportation were the most frequently perceived other potential sources of errors. The implications of these findings are clear: robust protocols with multiple identifiers, staff training, and barcode labeling can significantly reduce patient identification errors. Similarly, standardized collection instructions, pre-labeled containers, and meticulous verification processes can effectively minimize such errors. Validated tests, standardized scoring systems, and proper investigation of quality control discrepancies are key to reducing analytical errors. Documented procedures, staff training, regular equipment calibration, and reagent testing are also crucial.

Conclusion

This study contributes to the literature on the current state of potential sources of errors in anatomic pathology. The study findings and recommendations on strategies to address such errors would improve the performance of the anatomic pathology laboratory and eventually improve patient care.
Immunohistochemical Glutamine Synthetase As a Surrogate Marker for Beta Catenin (Exon 3 Deletion) in a Rare Case of Hepatic Adenomatosis with Early Malignant Transformation to Well Differentiated Hepatocellular Carcinoma
Authors: Tan J S , Guzman G , Sonawane S S
Published: October 2024

Introduction/Objective

Hepatic adenomatosis (HA) is a rare entity defined by ≥ 10 hepatocellular adenomas (HCAs). About half of HA cases are asymptomatic and incidentally found. Compared to individual HCAs, HA carries a higher risk of complications including: tumor rupture, bleeding, and an approximate 4.2% overall frequency of malignant transformation.

Methods/Case Report

A 29-year-old woman presented to the emergency department (ED) requesting a CT scan. She was seen by a gastroenterologist days prior to her ED visit for ongoing sharp rectal pain for 2-3 months. After a recent rectal exam, she was recommended to have a CT abdomen/pelvis to rule out a potential abscess. CT did not show a perianal or perirectal abscess but instead identified a 9.1 cm right hepatic lobe mass. A liver MRI showed a 6.4 x 8.5 cm mass with arterial enhancement. The patient had a prior history of OCP use. She underwent robotic wedge resection of liver segment 6 with cholecystectomy. Gross examination showed a 6 cm tumor with many smaller nodules ranging in size from 0.5-2.2 cm. Our case was submitted entirely for histologic examination. Microscopy demonstrated well differentiated hepatocellular carcinoma (WDHCC) confirmed with positive immunohistochemical (IHC) staining for HepPar1 and Arginase. Tumor cells showed mild patchy cytological atypia, occasional pseudoglands, and architectural atypia with “nodule in nodule growth.” There was reticulin loss in multiple areas and CD34 showed strong diffuse sinusoidal staining. Glypican 3, CRP, and HAA were negative. Low Ki-67, LFABP retention, and absent nuclear staining of beta catenin (BC) were noted. Glutamine synthetase (GS) was diffuse and homogeneous. The gallbladder was unremarkable.

Results (if a Case Study enter NA)

NA

Conclusion

This case emphasizes that, despite negative nuclear BC staining, diffuse homogenous staining of GS is a quality surrogate marker for BC mutations (ex. exon 3 deletions). Thorough gross, microscopic, and molecular examination in HA cases is essential for identifying transformation to WDHCC.
Histologic Patterns of Ribociclib-induced Liver Injury
Authors: Centeno L , Szeto W , Mannan R , Misra S , Singh D
Published: October 2024

Introduction/Objective

Ribociclib, a cyclin dependent kinase (CDK) 4/6 inhibitor, used in the treatment of advanced breast carcinomas, can cause liver injury, often manifesting as elevated liver enzymes. However, the histologic patterns of liver injury caused by Ribociclib have not been well-documented. Our study aims to explore these patterns in patients undergoing Ribociclib treatment.

Methods/Case Report

Five female patients receiving Ribociclib treatment for breast carcinomas and undergoing liver biopsy post-transaminitis in the past seven years (2017-2024) were identified using our institution’s electronic medical record. Clinical information was collected, and liver biopsies were reviewed for histologic injury patterns.

Results (if a Case Study enter NA)

The mean age of the patients was 47 years (range 38-68). All patients had liver enzyme abnormalities after starting with Ribociclib: mean time to peak of ALT and AST was 75 days (range 36-125). Mean peak enzyme levels (IU/L) for ALT and AST were 685 and 420, respectively. Liver biopsy showed an acute hepatitis pattern of injury in all five patients: centrizonal confluent necrosis (n=3) and lobular spotty necrosis (n=2).

Other findings included: mild cholestasis (n=1), interface hepatitis (n=2), focal bile duct injury (n=2), and mild macrovesicular steatosis without steatohepatitis (n=1). Portal inflammation was mild to moderate, comprising a mixed lymphoplasmacytic infiltrate. One patient had moderate periportal fibrosis without bridging. Ribociclib was withdrawn in all patients; three patients received prednisolone treatment. Three patients were rechallenged with Abemaciclib and two with Palbociclib. All patients had resolution of liver function tests after cessation of Ribociclib therapy. Mean time to normalization of ALT and AST was 46 days (range 30-72) and 62 days (range 30-96), respectively, after holding Ribociclib.

Conclusion

Ribociclib predominantly causes an acute hepatitis pattern of liver injury and of varying severity. Drug cessation, with or without steroid therapy, and switching to a less hepatotoxic CDK 4/6 inhibitor can be sufficient to restore normal liver function. Screening for liver dysfunction with baseline enzyme tests prior to Ribociclib treatment, as well as serial testing to trend enzyme levels, may help prevent severe liver injury.
Molecular Profiling and Surgical Outcomes in Indeterminate Thyroid Nodules: Experience from a Tertiary Care Center
Authors: Geetha S , Ali A , Vele O , Gimenez C , Chau K , Hagan T , Kasturi D , Rosca O C
Published: October 2024

Introduction/Objective

This study examines molecular results(MR) and surgical follow-up(SFU) of cytologically- indeterminate thyroid nodules.

Methods/Case Report

Atypia-of-undetermined significance/suspicious-for-follicular-neoplasm cases that underwent Quest/ThyroSeq molecular testing between 2015-2022 were analyzed for MR, SFU and lymph node metastasis(LNM).

Results (if a Case Study enter NA)

417 cases(Quest=192, ThyroSeq=225). 59% had SFU. 43% malignancy rate.SFU for Quest(49%): non-neoplastic(NNP)=20%, neoplastic(NP)=80%. MR in these cases:NRAS=48, HRAS=19, BRAF=15, KRAS=8, RET/PTC=3, PAX8=2. SFU: papillary thyroid carcinoma(PTC)=35, non-invasive-follicular-thyroid- papillary-neoplasm with papillary-like nuclear features(NIFTP)=20, thyroid nodular follicular disease(TFND)=18, follicular adenoma(FA)=10, follicular carcinoma(FC)=5, oncocytic carcinoma(OC)=1, lymphocytic thyroiditis(LT)=1.

Surgical-molecular correlation(SMC): PTC in 3/3 RET/PTC-mutated, 14/15 BRAF-mutated cases. 1 TFND was BRAF- positive. RAS-mutated category: NIFTP=20,PTC=18,TFND=17,FA=9, OA=5, FC=5, LT=1. In RAS-mutated PTCs, NRAS was most common(n=13), followed by HRAS(n=4) and KRAS(n=1). 2 PAX8-mutated cases showed FA and OC. 9/41 malignant cases, all PTC, had LNM, MR:BRAF=6, HRAS=2, RET/PTC=1.SFU for ThyroSeq(68%): NN=10%, NNP=90%. MR:NRAS=34, copy number alterations(CNAs)=25, HRAS=14, BRAF=13, KRAS=11, gene expression alterations(GEA)=7, THADA+IGF2BP3=7, CNAs Hurthle cell type(HCT)=6, EIF1AX=6, DICER1=4, PAX8- PPARG fusion=4, CNAs+GEA=3, NTRK3=3, TERT=2, RAS+EIF1AX=2, TERT+CNAs=2, EIF1AX=1, EZH1=1, RET/PTC1 fusion=1, ALK=1, BRAF K601E=1,RAS+TERT=1, RAS+TERT+PTEN+EIF1AX=1, TERT+BRAF=1, TERT+EIF1AX=1,TP53+CNAs=1. SFU:PTC=39, NIFTP=31, OA=21, FA=20, papillary microcarcinoma(PMiC)=13, TFND=10, OC=7, LT=6, FC=5, poorly differentiated carcinoma(PdC)=1.10/13 BRAF-mutated cases were PTC, other 3 PMiC. SFU of RAS-mutated cases(n=59):TFND=6, LT=4, NIFTP=19, FA=8, OA=4, PTC=13, PMiC=2, FC=2. RAS mutations in PTC: KRAS=6, HRAS=4, NRAS=3. SFU of CNAs-HCT: OA=3, OC=2, TFND=1. Infrequently detected mutations with SFU of PTC:RET/PTC(1/1), ALK(1/1), RAS+TERT(1/1), TERT+BRAF(1/1), BRAF K601E(1/1), RAS+EIF1AX(1/2). SFU of RAS+TERT+PTEN+EIF1AX:PdC. 11/65 malignant cases, all PTC had LNM:BRAF=5, KRAS=3, CNAs=1, EIF1AX=1, TERT+BRAF=1.

Conclusion

Substantial proportion of cases with positive MR underwent surgical resection. BRAF-positive and CNAs- HCT correlated with PTC and oncocytic neoplasms, respectively. BRAF-positive PTCs had a higher incidence of LNM compared to wild-type cases(46% vs.18%).
Carbonic Anhydrase IX (CA9) Overexpression and Negative PAX8 Staining Can Be Used to Confirm Hemangioblastomas
Authors: Holmes C J , Fullmer J , Zhang P L
Published: October 2024

Introduction/Objective

Hemangioblastomas are indolent brain tumors consisting histologically of atypical stromal cells and a large number of blood vessels lined by endothelial cells. The tumors are often associated with either von Hippel- Lindau (VHL) syndrome or sporadic mutation of VHL genes. As CA9 is a marker of the hypoxic inducible factor-alpha1 cascade, its overexpression has been well known to present in clear cell renal cell carcinoma that involves the mutation of VHL gene. A few studies demonstrate overexpression of CA9 in hemangioblastomas, but not in other primary brain tumors such as gliomas and meningioma. Our two cases were used to determine if positive CA9 and negative PAX8 immuno-stains were useful markers to support the diagnosis of hemangioblastomas.

Methods/Case Report

One patient was a 50-year-old man and the other patient was a 75-year-old man. Two lesions were identified in the cerebellum with typical appearance of vascular channels intermingled with atypical stromal cells showing clear cell cytoplasm. The endothelial cells were positive for CD34 and ERG. The stromal cells were weakly positive for inhibin but negative for the endothelial markers GFAP, pancytokeratin and PAX8, ruling out primary glioma and metastatic clear cell renal carcinoma. The atypical stromal cells with clear cytoplasm in both tumors, however, showed strong and diffuse membranous staining for CA9 (3+). The overall findings supported the morphologic diagnosis of hemangioblastomas in both patients.

Results (if a Case Study enter NA)

NA

Conclusion

Our preliminary data indicates that positive CA9 and negative PAX8 stains are a useful pair of markers to support a diagnosis of hemangioblastoma and differentiate them from metastatic clear cell renal cell carcinoma.

Additionally, CA9 can help confirm the diagnosis of hemangioblastoma when inhibin is weak or nearly negative.
Bacterial Contamination of Donor Blood Units in a Ghanaian Blood Bank: A Critical Concern for Transfusion Safety
Authors: Aidoo N B
Published: October 2024

Introduction/Objective

Background: Blood transfusions, while life-saving, pose a significant risk to patient safety, with transfusion-associated bacterial sepsis emerging as a persistent and potentially fatal threat. The prevalence and severity of bacterial contamination in donor blood units necessitate regular surveillance to ensure safe and effective transfusion therapy.

Aim

This study aimed to identify and assess the susceptibility of bacterial isolates in whole blood donor units at the blood bank of Cape Coast Teaching Hospital in the Central Region of Ghana.

Methods/Case Report

Method(s): One hundred and three (103) units of stored whole blood units, declared safe for transfusion (testing negative for HIV I&II, HBsAg, HCV, and syphilis), were inoculated into Brain Heart Infusion Broth and incubated for 24 hours. The inoculated broths were then cultured on MacConkey agar (MAC), Chocolate agar (CHOC), and Blood agar. Gram-negative and Gram-positive isolates were identified using standard biochemical tests. Antimicrobial susceptibility testing was performed using the disc diffusion method.

Results (if a Case Study enter NA)

Results: Of the 103 donor blood units tested, 33 (32.03%) were found to have bacterial isolates. Gram-positive organisms accounted for 67.14% of the isolates, including Coagulase negative Staphylococcus, Bacillus spp, and S. aureus. Gram-negative bacteria constituted 32.86% of the isolates, with Citrobacter freundii, Serratia marcescens, E. coli, and Providencia stuartii identified. Notably, 62.9% of the bacterial isolates were skin commensals, while 25.7% were of enteric origin and 11.4% were of nosocomial origin. Resistance to commonly used antibiotics varied among isolates, with Coagulase-negative Staphylococcus exhibiting resistance to amoxicillin (92.86%) and erythromycin (76.19%), while Citrobacter freundii showed resistance to levofloxacin (75.00%) and ofloxacin (75.00%).

Conclusion

Conclusion(s): The high incidence of bacterial contamination in donor blood units highlights the need for improved phlebotomy procedures and decontamination practices at blood banks in Ghana to reduce the risk of sepsis in transfusion recipients. Furthermore, this study provides valuable information regarding antibiotic resistance patterns in bacterial isolates, emphasizing the importance of antibiotic stewardship in Ghana.

In conclusion, this study underscores the urgency of addressing bacterial contamination in donor blood units in Ghanaian blood banks to enhance transfusion safety.
Comparison of low-density lipoprotein cholesterol (LDL-c) estimates by in-lab and point-of-care devices in the context of emerging LDL-c equations
Authors: Hubler Zita , Roper Stephen
Published: October 2024

Low-density lipoprotein cholesterol (LDL-c) and lipid measurements are used for hyperlipidemia diagnosis, cardiovascular disease risk classification, and medication management. Millions of lipid panels are performed annually. Given the widespread need for lipid testing, there are two CLIA-waived point-of-care (POC) lipid testing devices. These devices were FDA-approved using the Friedewald equation to estimate LDL-c based on measurements of (triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC). By contrast, for laboratory-based LDL-c estimation, the Friedewald equation is being replaced by newer, more accurate equations such as the NIH-Sampson equation. These equations use the same lipid panel results to estimate LDL-c and only differ in the arithmetic of the estimation. This study evaluates how differences between the in-clinic POC machines and in-laboratory lipid measurements affect the estimated LDL-c results and are compounded by differences in the equations used for LDL-c estimation. This retrospective observational study collected deidentified lipid results (TG, HDL-c, TC, LDL-c) and demographic data (age, gender) for all samples that had lipid panel results from in-lab and POC within twenty-four hours of each other in a single hospital system between 2014 and 2023. Three hundred twenty samples were identified; samples with non-numerical values or results outside of the reportable range for TG, HDL-c, or TC were not included in subsequent LDL-c calculations using the Friedewald and NIH-Sampson equations (69 results). Patients under the age of 18 were excluded (2 results). Two hundred and forty-nine samples met inclusion criteria; this cohort showed non-significant differences in lipid, age, and gender distributions relative to all POC results tested in the same time frame. Consistent with prior reports, we observed discordance between POC and the in-lab lipid measurements, particularly for TG (Bland-Altman: bias:-23.04 mg/dL, standard deviation:61.3 mg/dL). These analytical differences may not change clinical management if the cardiovascular risk classification using estimated LDL-c is unchanged. However, the risk classification based on the in-lab versus in-clinic testing differed for 20% of patients. The most pronounced difference in LDL-c estimation occurred when the POC machine used Friedewald and in-lab testing used NIH-Sampson, and resulted in 5% more patients differentially classified. Regardless of testing platform, more patients are categorized as higher risk on an individual and population-based level with the NIH-Sampson equation. This study highlights the need for transparency in lipid panel reports regarding which LDL-c equation is used in both POC and in-lab testing formats, and the need for readily available tools for conversion between different LDL-c estimation equations.
Effect of Pre-Analytical Line Settings on Artefactually Elevated Anion Gap Results
Authors: Cooke Tyler , Cullen Regina , D’Ambrosia Christopher , Hod Eldad
Published: October 2024

Introduction

When the core lab at a large tertiary care hospital introduced an automated laboratory system from a major manufacturer, the automated line aliquoted patient serum into open cups for all chemistry testing. It was subsequently discovered that if sample testing was delayed, electrolyte abnormalities could be introduced from evaporation, resulting in an increased anion gap (presumably due to a loss of bicarbonate with evaporation of carbon dioxide). To address this issue, the core lab changed the sample processing protocol in April 2023 from an open cup system to testing primary tubes on the analyzers. The purpose of this study was to evaluate the impact of switching to a primary tube testing system on artefactually elevated anion gap results.

Methods

Equivalent ten-week blocks of anion gap, creatinine and sample turnaround time (from receipt on the line to analyzer perform time) results from pre- to post-primary tube conversion were collected from the laboratory information system. Data from weekend testing and from repeat samples from the same patient were excluded. Data was cleaned and analyzed using R.

Results

Multivariable linear regression showed that when adjusted for the turnaround time and creatinine result, the open cup system was significantly associated (p<0.0001) with a 0.95 [95% CI 0.69-1.21] increase in anion gap. There was a positive relationship between turnaround time and anion gap, with a slope of 0.017 (i.e., a 0.017 increase in anion gap per minute delay; p<0.0001). Overall, the proportion of abnormal results (defined as anion gap >=16) decreased from 26% to 10% after switching to a primary tube testing system. Furthermore, there was an association between the times of day in which the lines were overloaded with specimens, turnaround time, and an increase in abnormal anion gap results. Overall, the mean anion gap decreased by 1 with a turnaround time of one hour and 2 after two hours by switching to the primary tube system. This trend in anion gap was largely driven by a corresponding decrease in bicarbonate. Sodium and chloride levels did not show any relationship with turnaround time.

Conclusions

Using an open cup system for electrolyte testing can cause spuriously elevated anion gap levels, especially with testing delays. Switching to a primary tube testing system largely resolved the issue; however, the data still showed a weakly positive relationship between turnaround time and anion gap for the primary tube testing system, so additional work is needed to identify potential causes of this relationship.
scDRMAE: integrating masked autoencoder with residual attention networks to leverage omics feature dependencies for accurate cell clustering
Authors: Zhang Tianjiao , Zhang Hongfei , Ren Jixiang , Wu Zhenao , Zhao Zhongqian , Wang Guohua
Published: October 2024

Motivation

Cell clustering is foundational for analyzing the heterogeneity of biological tissues using single-cell sequencing data. With the maturation of single-cell multi-omics sequencing technologies, we can integrate multiple omics data to perform cell clustering, thereby overcoming the limitations of insufficient information from single omics data. Existing methods for cell clustering often only consider the differences in data patterns during the analysis of multi-omics data, but the dependencies between omics features of different cell types also significantly influence cell clustering. Moreover, the high dropout rates in scRNA-seq and scATAC-seq data can impact the performance of cell clustering.

Results

We propose a cell clustering model based on a masked autoencoder, scDRMAE. Utilizing a masking mechanism, scDRMAE effectively learns the relationships between different features and imputes false zeros caused by dropout events. To differentiate the importance of various omics data in cell clustering, we dynamically adjust the weights of different omics data through an attention mechanism. Finally, we use the K-means algorithm for cluster analysis of the fused multi-omics data. On commonly used sets of 15 multi-omics datasets, our method demonstrates superior cell clustering performance on multiple metrics compared to other computational methods. In addition, when datasets exhibit varying degrees of dropout noise, our method shows better performance and stronger stability on multiple metrics compared to other methods. Moreover, by analyzing the cell clusters classified by scDRMAE, we identified several biologically significant biomarkers that have been validated, further confirming the effectiveness of scDRMAE in cell clustering from a biological perspective.
SurvBal: compositional microbiome balances for survival outcomes
Authors: Li Ying , Lee Teresa , Marin Kai , Hua Xing , Srinivasan Sujatha , Fredricks David N , Lee John R , Ling Wodan
Published: October 2024

Identification of balances of bacterial taxa in relation to continuous and dichotomous outcomes is an increasingly frequent analytic objective in microbiome profiling experiments. SurvBal enables the selection of balances in relation to censored survival or time-to-event outcomes which are of considerable interest in many biomedical studies. The most commonly used survival models—the Cox proportional hazards and parametric survival models are included in the package, which are used in combination with step-wise selection procedures to identify the optimal associated balance of microbiome, i.e. the ratio of the geometric means of two groups of taxa’s relative abundances.

Availability and implementation

The SurvBal R package and Shiny app can be accessed at https://github.com/yinglia/SurvBal and https://yinglistats.shinyapps.io/shinyapp-survbal/.
Trichomycosis axillaris
Authors: Bao Fangfang , Wang Shufen , Chen Chenchen , Zhang Yong , Li Jianke , Liu Xinzhou , Zhang Furen
Published: October 2024

We report a case of trichomycosis axillaris caused by Corynebacterium glaucum, a rare clinical pathogen.
Future implications of artificial intelligence in lung cancer screening: a systematic review
Authors: Quirk Joseph , Mac Donnchadha Conor , Vaantaja Jonathan , Mitchell Cameron , Marchi Nicolas , AlSaleh Jasmine , Dalton Bryan
Published: October 2024

Objectives

The aim of this study was to systematically review the literature to assess the application of AI-based interventions in lung cancer screening, and its future implications.

Methods

Relevant published literature was screened using PRISMA guidelines across three databases: PubMed, Scopus, and Web of Science. Search terms for article selection included “artificial intelligence,” “radiology,” “lung cancer,” “screening,” and “diagnostic.” Included studies evaluated the use of AI in lung cancer screening and diagnosis.

Results

Twelve studies met the inclusion criteria. All studies concerned the role of AI in lung cancer screening and diagnosis. The AIs demonstrated promising ability across four domains: (1) detection, (2) characterization and differentiation, (3) augmentation of the work of human radiologists, (4) AI implementation of the LUNG-RADS framework and its ability to augment this framework. All studies reported positive results, demonstrating in some cases AI’s ability to perform these tasks to a level close to that of human radiologists.

Conclusions

The AI systems included in this review were found to be effective screening tools for lung cancer. These findings hold important implications for the future use of AI in lung cancer screening programmes as they may see use as an adjunctive tool for lung cancer screening that would aid in making early and accurate diagnosis.

Advances in knowledge

AI-based systems appear to be powerful tools that can assist radiologists with lung cancer screening and diagnosis.