bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triple Crown: A Single Autopsy Case with Alzheimer’s Disease, Parkinson’s Disease, and Progressive Supranuclear Palsy
Authors: Piya G , Kumar G , Iqbal S , Cai D 
Published: October 2024

Abstract

Introduction/Objective
Neurodegenerative diseases such as Alzheimer’s Disease(AD), Idiopathic Parkinson’s disease (PD), and Progressive Supranuclear Palsy (PSP), manifest with progressive cognitive and motor deterioration. While each condition traditionally presents distinct clinical features, overlapping symptoms among them make antemortem clinical diagnose less accurate. Concomitant proteinopathies are frequent among neurodegenerative diseases. Here, we report a single autopsy case demonstrating the simultaneous presence of PSP, PD and AD.

Methods/Case Report
A 70- year- old male, with dementia and a familial history of progressive supranuclear palsy in his brother, underwent autopsy due to concern for progressive supranuclear palsy. The histopathological examination revealed the presence of “ C” age- related plaque score providing definite diagnosis of Alzheimer’s disease.
Immunohistochemistry studies on brain sections revealed the presence of Tau positive globose tangles and neurites indicating progressive supranuclear palsy. Furthermore, alpha-synuclein positivity was observed for Lewy bodies and Lewy neurites, confirming idiopathic Parkinson’s disease.

Results (if a Case Study enter NA)
NA

Conclusion
While coexisting neurodegenerative diseases with different proteinopathies have been well documented, this case represents the first report providing pathological confirmation of the simultaneous presence of Alzheimer’s Disease, Parkinson’s Disease, and progressive supranuclear palsy in a single patient. These unique findings underscore the complexity of neurodegenerative processes and highlights the importance of comprehensive diagnostic evaluation in patients presenting with overlapping clinical symptoms. These findings hold significant potential to contribute further in the field.
Suppurative Granulomatous Osteomyelitis with Microcystic Changes Due to Mycobacterium chelonae- abscessus Complex
Authors: Patel N K , Konopka K , Perry W R 
Published: October 2024

Abstract

Introduction/Objective
Mycobacterium chelonae and Mycobacterium abscessus are rapidly growing non-tuberculous mycobacterium found in soil and water, and represent rare causes of skin and soft tissue infection. Treatment typically involves an extended course of antimicrobial therapy and occasionally surgical debridement. Previous reports have described a distinctive pattern of suppurative granulomatous inflammation with microcystic changes in skin biopsies; however, the morphologic changes of M. chelonae-abscessus complex as a cause of osteomyelitis have not been well-documented in the literature.

Methods/Case Report
We searched our database from 2013 to 2024 for bone samples diagnosed as granulomatous inflammation in which M. chelonae or M. abscessus were identified on concurrent microbiology studies. Patient demographics, risk factors for infection, and treatment data were collected.

Results (if a Case Study enter NA)
Three patients with culture- or PCR-confirmed M. chelonae (2) or M. abscessus
(1) were identified. All infections involved bones of the distal extremities. Patients were 57 years and older with risk factors for infection that included: diabetes (1), intravenous drug use (1), and long-term immunosuppressive therapy (1). All patients presented with osteomyelitis refractory to antibiotic therapy for which bone biopsy, bone resection, or amputation was performed. All cases showed suppurative granulomatous inflammation with microcystic changes. Cystic spaces were markedly enriched for acid-fast bacilli on Fite and/or Ziehl-Neelsen stains. In two patients, the antimicrobial regimen was changed as a result of the pathologic findings and microbiologic testing that provided additional information about speciation and susceptibilities.

Conclusion
Suppurative granulomatous inflammation has a broad differential that includes blastomycosis, sporotrichosis, cat scratch disease, non-tuberculous mycobacterial infection, and granulomatosis with polyangiitis, for which there are substantial treatment differences. When this pattern of microcystic suppurative granulomatous inflammation is encountered, it is important to perform special stains for acid-fast bacilli, particularly when seen in distal extremity lesions from patients with infections that are refractory to empiric antibiotic therapy.
Sneaky DCIS-looking Invasive Ductal Carcinoma of the Breast in the Extensive DCIS Background
Authors: Shi W , Ren D , Ifegwu I , Niu C 
Published: October 2024

Abstract

Introduction/Objective
In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much more easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy.

Methods/Case Report
Retrospective analysis of the histologic and immunohistochemical findings of pure DCIS and DCIS-looking invasive ductal carcinoma.

Results (if a Case Study enter NA)
Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas. Immunohistochemical (IHC) staining showed that myoepithelial markers, p63 and smooth muscle myosin heavy chain (SMMHC), were retained at the periphery of all the expanded acini in one area. Unexpectedly and surprisingly, p63 and SMMHC were completely lost at the periphery of part of the DCIS-looking acini in another area, immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS.

Conclusion
Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize sneaky DCIS-looking invasive ductal carcinoma in the extensive DCIS background. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.
Occurrence of high hyperdiploid karyotypes in childhood Acute Lymphoblastic Leukemia
Authors: Sachwani K 
Published: October 2024

Abstract

Introduction/Objective
High hyperdiploidy is defined as the non-random gain of chromosomes, increasing the modal chromosome number from 46 to between 51 and 65 or 67. This condition is the most common finding in childhood acute lymphoblastic leukemia, with a good outcome. It is generally characterized by the gain of chromosomes, typically X, 4, 6, 10, 14, 17, 18, and 21. The objective of this study is to determine the frequency of high hyperdiploidy in childhood ALL.

Methods/Case Report
Cytogenetic results of 435 patients, reported between October 2020 and September 2022 were reviewed retrospectively. All individuals were suspected for ALL between ages 1-15 years. Chromosomal analysis was performed in the Cytogenetics Lab of the Indus hospital and health network. Fluorescent in-situ hybridization (FISH) analysis were also carried out with probes for co-relating the gain of chromosomes.

Results (if a Case Study enter NA)
A total of 435 individuals were successfully karyotyped, 82 karyotypes showed hyperploidy without any additional abnormality, 213 patients showed hyperploidy along with additional structural aberrations, and 143 individuals showed normal karyotype.
Among all the hyperploid karyotypes, chromosomes X, 4, 6, 10, 14, 17, 18, 21 were all gained in approximately 70% of the cases. Whereas, chromosome 21 was gained in 100% of all cases. FISH results also showed the gain of signals for particular probes including chromosomes 8, 9, 11, 12, 21 and 22.

Conclusion
In summary, this study leads to the fact that high hyperdiploidy is the most common abnormality in childhood acute lymphoblastic leukemia. It is assured that the occurrence of constituent trisomies of certain chromosomes is linked with the prognosis of the disease and also helps in determining the differences in treatment of the disease. Furthermore, correlation of karyotypes with the FISH results have also played a vital role in increasing the accuracy of results in this study.
ALK1-negative Epithelioid Histiocytoma
Authors: Hong J , Markidan J , Helm T , Helm K , Thieu T 
Published: October 2024

Abstract

Introduction/Objective
We present a case of epithelioid histiocytoma (EH). The epithelioid nature of this lesion imitates the appearance of neoplastic lesions such as melanocytic, dermatofibroma/histiocytoma, non-Langerhans histiocytosis such as reticulohistiocytoma, atypical fibroxanthoma, and rhabdomyosarcoma.

Methods/Case Report
Due to the unusual morphology and aberrant immunohistochemical staining pattern of this specific case, the sample was analyzed through Next Generation Sequencing (NGS), which showed the presence of a fusion of genes Sequestosome 1 (SQSTM1) and Anaplastic lymphoma kinas (ALK). SQSTM1 gene produces proteins involved in signal transduction pathways as well as autophagy, while ALK mainly serves the role of cellular communication and development. The most well-known ALK fusion partners include SQSTM and Vinculin (VCL), while there are other fusion partners that were more recently discovered such as Dynactin Subunit 1 (DCTN1) and ETS variant transcription factor 6 (ETV6). The spectrum of neoplasms produced through these fusions is wide as seen in lung adenocarcinoma and renal cell carcinoma (EML4-ALK), epithelioid histiocytoma (SQSTM1-ALK and VCL- ALK), pediatric renal cell carcinoma (VCL-ALK) among others.

Results (if a Case Study enter NA)
NA

Conclusion
We hope this case is a helpful addition to the literature to further aid diagnoses of future ALK fusion cases.
Diagnostic And Post-Therapeutic Histopathology Of Hansen’s Disease in a Man With Rheumatoid Arthritis
Authors: Younus A , Fox S 
Published: October 2024

Abstract

Introduction/Objective
Hansen’s Disease (leprosy), caused by Mycobacterium leprae, is a chronic infectious disease primarily affecting the skin and peripheral nerves. In the United States, leprosy remains rare, with less than 200 cases per year reported to the CDC. Diagnosis is often delayed, due to low clinical suspicion and lack of experience among healthcare providers, leading to potentially severe complications and increased transmission risk.

Methods/Case Report
A 71-year-old man presented to dermatology with a progressive, non-tender erythematous rash involving the arms and chest. He denied any travel history, or exposure to armadillos, and had no family history of a similar rash. His medical history was significant for rheumatoid arthritis, for which he was receiving methotrexate. The clinical differential included drug eruption, tinea infection, or sarcoidosis. Skin biopsy revealed extensive infiltration of the dermis by noncaseating granulomas surrounding cutaneous nerves, and AFB stain highlighted numerous bacilli consistent with Mycobacterium leprae, leading to the diagnosis of Hansen’s disease. The WHO classification was multibacillary leprosy, and the Ridley-Jopling classification was borderline tuberculoid (BT) to perhaps mid borderline (BB), based on clinical and histologic features. He was started on triple therapy, and biopsies performed during treatment, as well as at three years follow up showed marked improvement, with some remaining disease detected in unresolved rash.

Results (if a Case Study enter NA)
NA

Conclusion
This case presents a diagnostic challenge given the absence of typical risk factors for Mycobacterium leprae transmission. The patient’s immunocompromised status due to methotrexate therapy may have predisposed him to the disease. Documented cases of Hansen’s disease have more than doubled in the southeastern states since 2013, with concern for endemic regions emerging in Florida. Early recognition, classification, and prompt treatment are essential to prevent disease progression and reduce transmission. Increased education and awareness among healthcare providers are crucial to improving diagnostic accuracy and patient outcomes in cases of leprosy.
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

Abstract

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

Abstract

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

Abstract

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: &gt;/=200) were also associated with low ER (H&lt;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

Abstract

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.