bluuebunny/crossref_metadata_2025_split huggingface dataset:
SWI/SNF Altered Gastric Carcinoma with Squamous Differentiation in a young patient with aggressive clinical course
Authors: Centeno L , Misra S , Castillo D , Szeto W , Mannan R 
Published: October 2024

Abstract

Introduction/Objective
Inactivation of SMARCA4 (BRG1) protein subunit of the SWI/SNF complex has been reported in various malignancies affecting multiple organs, often associated with a poor prognosis. We report a rare case of gastric SMARCA4-deficient carcinoma in a young patient, showing squamous differentiation and an aggressive clinical course.

Methods/Case Report
A 28-year-old male presented with epigastric pain and 15-lb weight loss over 3 months. Evaluation revealed a gastric cardia mass, liver lesion, and gastro-hepatic lymph-node. Biopsy of gastric and liver lesions revealed a poorly differentiated carcinoma. Following a course of neoadjuvant chemotherapy, and immunotherapy, total gastrectomy and distal esophagectomy were performed. Grossly, there was a 13 cm mass involving his gastric cardia and body, extending into his distal esophagus. On microscopy, the transmural tumor was arranged as solid sheets, syncytial aggregates, and nests with a focal pseudoglandular pattern in a lymphoplasmacytic rich stroma. Scattered bizarre giant cells were noted, along with brisk mitosis and focal necrosis. Focally, the tumor showed abundant glassy eosinophilic cytoplasm reminiscent of squamoid cells. Two of forty-two lymph nodes were positive for metastatic carcinoma. IHC showed focal positivity for AE1/3, OSCAR, CAM5.2, along with areas staining for p40 and p63; negative for CK7, CK20, CDX2, SATB2, synaptophysin, INSM1, SOX-10, LCA ERG, and SALL4. Nuclear expression for mismatch repair proteins was retained. HER2 was negative (score 0), and PDL-1 CPS score was 40. EBER in-situ hybridization was negative, with retention of INI-1. There was complete loss of SMARCA4 by IHC and next generation sequencing confirmed frameshift alteration of SMARCA4. Final pathologic diagnosis was SMARCA4 deficient poorly differentiated carcinoma with squamous differentiation (ypT3pN1). The patient received adjuvant therapy with Paclitaxel and Ramucirumab. However, his disease progressed, and he succumbed to his illness five months after surgery.

Results (if a Case Study enter NA)
N/A

Conclusion
Our case illustrates that SMARCA4 deficient gastric carcinomas can have heterogeneous morphology, with an aggressive clinical course in young patients. This highlights the importance of early diagnosis and consideration of alternative therapeutic approaches, as these tumors typically do not respond to standard treatments.
Atypical Gastric Glomus Tumor of Uncertain Malignant Potential in A 16-Year-Old Female; A Rare Entity with Unique Findings
Authors: Amin S E , Ahmed A A , Aljumaili Z , Thomas-Ogunniyi J O 
Published: October 2024

Abstract

Introduction/Objective
Gastric glomus tumor (GGT) is a rare mesenchymal tumor that is challenging to diagnose, especially when the immunoprofile overlaps with other more common gastric mesenchymal tumors. The majority of GGT are benign, however, rarely it can be atypical or even malignant. Herein, we present a case of a young female with atypical gastric glomus tumor of uncertain malignant potential.

Methods/Case Report
A 16-year-old female presented to the emergency with abdominal pain, coffee ground emesis, and melena. Imaging showed a 3.2 cm well-defined gastric mass arising from the muscularis propria.

Results (if a Case Study enter NA)
The FNA biopsy revealed clusters of tumor cells with uniform characteristics, exhibiting distinct cell membranes and eosinophilic to clear cytoplasm, surrounding prominent vasculature.
Immunohistochemical analysis showed that the tumor cells were positive for SMA, synaptophysin, vimentin, calponin, and caldesmon, with weak, patchy positivity for DOG1. CD34 highlighted the vessels separating the tumor cellular clusters into lobules. CD117 and Desmin were negative. The Ki67 proliferation index varied with hotspot foci 25-30%. Morphology and immunoprofile suggest glomus tumor, however, neuroendocrine tumor and epithelioid GIST needed to be excluded.
Subsequent resection specimen showed that the tumor was located within the muscularis propria with extension into the serosal vessels, suggesting vascular invasion, along with foci of cellular spindling and nuclear irregularity are identified. No necrosis noted. Tumor cells were positive for cyclin D1 while negative for myogenin, chromogranin, and DOG1. Overall, findings were consistent with GGT of uncertain malignant potential.

Conclusion
Although GGT are rare, they should be considered in the differential diagnosis of gastric mesenchymal tumors. The presence of diffuse SMA staining can help distinguishing them from GIST. It is crucial to scrutinize for signs of cellular and nuclear atypia, particularly in deeply seated glomus tumors.
Predicting Metastasis and Mortality Risk in Prostate biopsy using genomics and biopsy related factors
Authors: Chacko D , Fidan-Ozbilgin O , Cai D 
Published: October 2024

Abstract

Introduction/Objective
Prostate cancer, the most prevalent cancer among men, is diagnosed through biopsy, yet its predictive accuracy for metastasis and mortality risk remains limited. An approach to stratifying this risk is by combining biopsy data and genetics. The Decipher genomic classifier aids in estimating such risks. This study investigates the correlation between Decipher, biopsy-related factors, and the risk of prostate cancer metastasis or mortality.

Methods/Case Report
50 prostatic adenocarcinoma biopsies were analyzed. Patient age, average tumor volume in positive cores, PSA levels, and Gleason score were documented. Employing Tobit regression with maximum likelihood estimation, the study examined the link between various factors and metastasis/mortality risk of prostatic cancer. Dependent variables encompassed 5, 10, and 15-year risks, while the independent variable was patient age, positive to total core ratio, average tumor volume in positive cores, PSA level, and grade group of the prostate cancer. The model integrated three dummy variables-Grade Group 1, 3, and 4, with Grade Group 2 as reference. Coefficients gauged the distinct impact of Level 1, 3, and 4 diagnoses on outcomes relative to Level 2. Statistical significance was tested conventionally.

Results (if a Case Study enter NA)
Grade Group 1 (Gleason score: 3 + 3):
2.35 percentage point increase in the risk of metastasis within 10 years.
3.51 percentage point increase in the risk of mortality within 15 years.
Grade Group 2
Base level for comparison with other grade groups.
Grade Group 3 (Gleason score: 4 + 3):
No statistically significant difference in the predicting 5 or 10 year risk of metastasis compared to Grade Group 2. No statistically significant difference in the predicting 15 year risk of mortality compared to Grade Group 2.
Grade Group 4 (Gleason score: 4 + 4):
10.07 percentage point increase in the risk of metastasis within 5 years.
17.27 percentage point increase in the risk of metastasis within 10 years.
18.48 percentage point increase in the risk of mortality within 15 years.

Conclusion
The findings suggest combining genomics and grade group can help predict the risk of metastasis and mortality in prostate biopsy. Grade Group 4 diagnosis greatly impacts metastasis and mortality in all timeframes.While Grade Group 1 has a smaller but still significant impact on the 10 and 15 year risk of metastasis and mortality.
However, Grade Group 3 diagnosis does not significantly impact the risk of metastasis in any of the timeframes considered.
NEUROENDOCRINE TUMORS OF THE GENITOURINARY TRACT - A CLINICAL AND PATHOLOGIC REVIEW
Authors: Yilmaz G , Cheng L , Yan L , Gattuso P 
Published: October 2024

Abstract

Introduction/Objective
Neuroendocrine tumors (NETs) of the genitourinary (GU) tract are rarely seen during daily surgical pathology sign-out sessions and comprise a heterogeneous group of neoplasms. We undertook a retrospective study to assess the clinical and pathologic characteristics of this unusual group of neoplasms involving the GU tract.

Methods/Case Report
We performed a retrospective review of the surgical pathology files for NETs of the GU tract between July 1993 and December 2021. Chart review was performed for the clinical and pathologic findings.

Results (if a Case Study enter NA)
A total of 26 patients were identified. There were 18 males and 8 females ranging in age from 43 to 94 years (mean age 69 years). 19/26 (73%) cases were primary tumors; 9 bladder small cell carcinoma, 5 prostatic small cell carcinoma, 4 bladder paragangliomas, and 1 case of small cell carcinoma of the renal pelvis. 7/26 (27%) cases were metastatic tumors; 5 Merkel carcinoma (3 urinary bladders, 2 testes), and 2 small cell carcinoma of the lung to the kidney.

Conclusion
The majority of NETs of the GU are primary and urinary bladder to be the most common site. Merkel cell carcinoma appears to have a tendency to metastasize to the GU tract, especially to the testis.
Clinicopathological correlation of three cases of metastatic carcinoma to uterine cervix: An institutional experience
Authors: BENDARI A , Al-Refai R , Sham S , Gomez Marti J , Des Jean R , Harshan M , Mohamed H , Bendari T 
Published: October 2024

Abstract

Introduction/Objective
Metastasis to the female genital tract presents a rare occurrence and poses significant diagnostic hurdles. The uterine cervix, although less frequently implicated, presents additional challenges for metastatic spread owing to its diminutive dimensions, limited vascular perfusion, and abundance of fibrous tissue. Clinical manifestations often include abnormal vaginal bleeding in 62–75% of cases, frequently accompanied by involvement in other anatomical sites. Accurate identification of cervical tumor activity and its primary origin holds paramount importance for precise diagnosis, therapeutic stratagem, and prognostic assessment.

Methods/Case Report
Here we are reporting three cases that were encountered in our institution over a 5-year period. The first patient, a 63-year-old female with a history of breast cancer, six years later exhibited metastatic breast cancer in a cervical polyp, confirmed by positivity for AE1/AE3, GATA3, ER, and negativity for TTF-1, chromogranin, synaptophysin, PAX8, inhibin, calretinin, CDX-2, CD10, desmin, smooth muscle actin, S100, and HMB-45. The second patient, diagnosed with pancreatic adenocarcinoma, two years later manifested cervical metastasis confirmed via positive staining for CK7, CDX2, and focal p63, and did not express PAX8, vimentin, ER, p16, synaptophysin, and chromogranin. The third patient, diagnosed with lung adenocarcinoma, one year later presented with a cervical mass, histologically confirmed as metastatic lung adenocarcinoma via positivity for CK7, Napsin A, and TTF1, and negativity for PAX8, p16, p40, p53, GATA3, and ER.

Results (if a Case Study enter NA)
N/A

Conclusion
Given the challenges of identifying metastasis to the cervix, thorough diagnostic evaluation should be undertaken to differentiate primary versus metastatic disease in women with a history of non-cervical malignancy.
Clinicopathological Characteristics of Small Cell Carcinoma of the Ovary, Hypercalcemic Type – a case Series
Authors: Li X , Madabhushi S , Dimo B , Husson M 
Published: October 2024

Abstract

Introduction/Objective
Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare (&lt;0.01%) and aggressive ovarian tumor primarily affecting young women (median of approximately 24 years), characterized by rapid growth, early metastasis, and association with hypercalcemia in two-thirds of cases. The diagnosis of SCCOHT is challenging due to its rarity and lack of specific clinical symptoms or biomarkers. Our study aims to delineate the clinicopathologic characteristics of SCCOHT based on our case series and add to the existing knowledge.

Methods/Case Report
A retrospective review of University of Pennsylvania Health system pathology database was conducted from 2012 to 2024. Our study identified four patients diagnosed with SCCOHT. Clinical information and histopathologic characteristics were reviewed.

Results (if a Case Study enter NA)
Among the four patients identified, the median age was 24 years, with a median tumor size of 14.5 cm, and all patients presented with weight loss, abdomen bloating, and elevated CA125 levels.
Notably, two patients exhibited hypercalcemia, while one initially presented with normal calcium levels but developed hypercalcemia during disease recurrence. One patient maintained normal calcium levels throughout. Surgical intervention involved bilateral salpingo-oophorectomy in all cases, with pathological staging revealing two patients at pT1a, one at pT1c, and one at pT3c. Histopathological analysis consistently revealed similar morphology, including solid and cystic necrotic neoplasms with diffuse growth or nests/cords of undifferentiated small cells, which displaying vesicular chromatin and prominent nucleoli. Immunohistochemical staining demonstrated loss of BRG1 (SMARCA4) expression in two patients and diffuse positivity for WT1 in all patietns, while negative for cytokeratin, germ cell markers, and melanocytic markers. Genetic test revealed SMARCA4 mutation (p.E 717*, c.3169-1G&gt;A) in one patient.

Conclusion
Small cell carcinoma of the ovary, hypercalcemic type, presents a diagnostic and therapeutic challenge due to its rarity and aggressive nature. Adequate treatment options are currently limited, highlighting the critical need for further research and development of targeted therapies in SCCOHT. Testing for mutations in the SMARCA4 gene is essential for accurate diagnosis of SCCOHT and may uncover new avenues for treatment and management strategies.
An extremely Rare Case of Primary Peritoneal Mucinous Cystadenocarcinoma
Authors: Kumar H , Chen W , Sun S , Satturwar S 
Published: October 2024

Abstract

Introduction/Objective
Primary peritoneal mucinous adenocarcinoma is an extremely rare entity with no well- established treatment protocol. It occurs more commonly in females as compared to males which supports its less understood pathogenesis of arising from heterotopic ovarian tissue or mucinous metaplasia of mesothelial cells.

Methods/Case Report
We present a case of a 31-year-old female who presented with right flank pain after a fall. On imaging studies, a cyst measuring 11.4 x 9.6 x 8.8 cm with an enhancing mural nodule was identified in abdomen (Figure 1). Patient underwent exploratory laparotomy. We received 402.1 grams, 12.5 x 10.0 x 8.0 cm cystic mass.
Cut surface showed an unilocular cyst filled with seromucinous fluid and 4.0 x 2.5 x 1.7 cm friable excrescences. Histologic examination showed an adenocarcinoma arising from background mucinous cystadenoma. The tumor cells were positive for AE1/AE3, CK7, CK20, villin (focal), PAX8 (focal), p53 (wild-type) and negative for WT-1, AMACR, CDX-2, TTF-1, GATA-3, inhibin and calretinin. ER and PR immunostains were positive in the ovarian-type stroma in the background mucinous cystadenoma. As the radiology work-up was negative for any other tumor in the pelvis or other sites, the diagnosis of primary peritoneal cystadenocarcinoma was rendered. Molecular analysis showed presence of KRAS and TP53 mutations. Patient is doing well at 6 months follow-up without any recurrence.

Results (if a Case Study enter NA)
NA

Conclusion
This case is an extremely rare case of primary peritoneal mucinous cystadenocarcinoma and thus requires consideration that it should be included in the differential diagnosis of peritoneal tumors.
Reflex Testing of Endometrial Carcinoma For Next Generation Sequencing: An Institutional Experience
Authors: Brunetti A 
Published: October 2024

Abstract

Introduction/Objective
Endometrioid carcinoma is now separated into four subgroups based on molecular profiling. These subgroups (POLE mutant [POLEmut], mismatch repair-deficient [MMRd], p53 abnormal [p53abnl], and no specific molecular profile [NSMP]) have been shown to be diagnostically and prognostically relevant. This is especially highlighted by the inclusion of molecular classification into the 2023 FIGO staging for EMCA. In conjunction with our gynecologic oncologists (gynonc) and colleagues in molecular pathology, we developed and implemented a reflex process by which next generation sequencing (NGS) is done on all hysterectomies performed at our institution for EMCA.

Methods/Case Report
In collaboration between gynonc, molecular diagnostics, surgical pathology and operations personnel, an order set was built within our LIS. At the time of sign-out, the gynecologic pathologist (GYNP) selects the block for NGS testing and orders the cuts for NGS, digital scanning of the corresponding H&E and the NGS testing. Histology in turn processes the cuts, scans the H&E and transfers the material for NGS. The digital slides are stored in an accessible repository and annotated by the GYNP. Results of NGS testing are released into the patient’s EMR and molecular/histologic correlation is subsequently performed by the GYNPs.

Results (if a Case Study enter NA)
In the period between 1/1/23 and 2/28/24, we processed 131 EMCA cases through this pathway. Of 103 endometrioid-type EMCA reflexed during this period, 7 were classified as POLEmut, 23 as MMRd, 13 as p53abnl, and 60 as NSMP. 16 cases required re-review of IHC and/or NGS results due to discrepancies. 4 p53abnl cases required upstaging according to the new FIGO, while no POLEmut cases required downstaging as they were all stage I.

Conclusion
Overall, our pilot pathway was considered a success and continues. We believe our process can serve as a framework for other institutions and can be applied to other malignancies.
A Case Report of Inflammatory Myofibroblastic Tumor Mimicking Leiomyosarcoma of the Uterus
Authors: Poonam F , Devi A , Farooq S , Chen S 
Published: October 2024

Abstract

Introduction/Objective
Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare entity that presents significant diagnostic challenges due to its infrequency and has the potential for being misdiagnosed as a leiomyoma, endometrial stromal tumor, or myxoid leiomyosarcoma, resulting in undertreatment or overtreatment.

Methods/Case Report
We present a case report of a 50-year-old woman with a history of anemia due to heavy menstruation caused by fibroids, who underwent hysterectomy. The concurrent pelvic wash cytology raised suspicious for myxoid leiomyosarcoma.

Results (if a Case Study enter NA)
Macroscopic examination revealed both well and poorly circumscribed nodules, ranging upto 4.7 cm in maximum dimension. Cut surfaces exhibited a spectrum of appearances, including tan-pink, whorled and rubbery, as well as soft, hemorrhagic, edematous, and mucinous areas with necrosis. Microscopically, the tumor exhibited myxoid spindle cell proliferation, in the background of lymphoplasmacytic inflammatory infiltrates. She was diagnosed with IMT metastasis to left fallopian tube, ovary, and omentum. Immunohistochemical (IHC) analysis further confirmed the diagnosis, showing strong and diffuse cytoplasmic positivity for ALK (anaplastic lymphoma kinase), caldesmon, and smooth muscle actin. This case underscores the critical importance of accurate diagnosis in guiding appropriate treatment strategies. Moreover, given the morphological overlap with other uterine tumors, the identification of ALK rearrangement emerges as a pivotal diagnostic marker, distinguishing IMT from its mimics such as leiomyoma, leiomyosarcoma and smooth muscle tumor of uncertain malignant potential (STUMP).
Enhancing our understanding of the histomorphological features and ALK immunostaining of uterine IMT is essential for optimizing patient management and outcomes.

Conclusion
IMT in the female genital tract can mimic other more common benign and malignant tumors like leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and histologic features and the use of ALK immunostaining can be critical for correct diagnosis.
Next-generation sequencing (NGS) of anaplastic thyroid carcinoma identifies unreported mutations in 25 recurring genes
Authors: Jansen S , Zhang X , Chen N , Hammer R , Pavlick D C , Hiemenz M , Dougherty K C , Dooley L M 
Published: October 2024

Abstract

Introduction/Objective
Anaplastic thyroid carcinoma (ATC) is a rare, aggressive form of thyroid cancer. Our prior work identified 6 molecular clusters of ATC with a possible de novo group. Secondary analysis of NGS data from 713 ATC cases was undertaken to identify less frequent and unreported gene mutations.

Methods/Case Report
Deidentified NGS results of 713 ATC cases were obtained from Foundation Medicine (FoundationOne CDx). The results were analyzed for frequency of gene mutations. A search of the literature and genomic databases (TCGA, NCI Genomic Data Commons, and cBioPortal) was performed to determine gene association with thyroid cancers including ATC.

Results (if a Case Study enter NA)
There are 25 gene mutations present in 5 or more cases that have not previously been reported in ATC and one gene found, MTAP, which has been discussed in a limited number of cases. The gene mutations found are listed from highest to lowest frequency (14.77% to 0.69%) as follows: MTAP, LRP1B, ASXL1, NUP93, MUTYH, NOTCH3, RAD21, CRKL, PIK3R1, FANCA, STAG2, BRCA2, FGF4, FGF3, FGF19, FBXW7, BRCA1, BCORL1, QKI, VHL, PRKN, GATA6, NKX2_1, KDM5C, CCND3, and BAP1. There are also 99 other gene mutations with 4 or fewer cases (0.14% to 0.77%) that have not previously been associated with ATC. MTAP was previously reported to be lost by immunohistochemistry in 6/27 (22.2%) ATC cases; MTAP loss was also reported to indicate a potential CDKN2A abnormality. Our larger data set supports that MTAP is lost in ATC with 98.6% of MTAP- deleted ATC also harboring CDKN2A deletion and 92.3% showing CDKN2B deletion (p-values &lt; 0.0001), supporting MTAP and CDKN2A/B are often deleted together. Other significant genes include the hereditary cancer genes MUTYH, FANCA (autosomal recessive), and BRCA1/2 (autosomal dominant) and genes associated with clonal hematopoiesis. ASXL1 and STAG2 have previously been unreported in ATC while others such as DNMT3A, TET2, and BCOR were also present in our dataset.

Conclusion
Our findings demonstrate 124 genes mutated in ATC that have not been previously reported. Besides the previously reported MTAP in 6 cases, genes associated with hereditary cancer and clonal hematopoiesis were identified. MTAP is located adjacent to CDKN2A/B and is often codeleted with MTAP at a much higher frequency than previously reported. Identifying associations with other diseases could improve surveillance and options for earlier therapy of ATC. Finally, these findings warrant further research to determine their role in the pathogenesis and treatment targets of ATC.