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Article: Medullary colonic carcinomas present with early-stage disease and do not express neuroendocrine markers by immunohistochemistry.

Abada, Evi / Jang, Hyejeong / Kim, Seongho / Abada, Othuke / Beydoun, Rafic

2023 Volume 36, Issue 3, Page(s) 321–326

Abstract: Background: Medullary colonic carcinoma (MCC) is a rare and distinct phenotype of colorectal cancers characterized histologically by sheets of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, exhibiting ... ...

Abstract	Background: Medullary colonic carcinoma (MCC) is a rare and distinct phenotype of colorectal cancers characterized histologically by sheets of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, exhibiting prominent infiltration by lymphocytes and neutrophilic granulocytes. We present the clinicopathologic and immunohistochemical characteristics of this rare tumor in our patient population. Methods: Eleven cases diagnosed with MCC from 1996-2020 met the diagnostic histologic criteria and had tissue blocks available for further analysis. Immunohistochemistry for mismatch repair deficiency, CDX2, synaptophysin, and chromogranin, and microsatellite instability testing by polymerase chain reaction were performed. Additional clinical information was obtained from the electronic medical records. Results: The median age at diagnosis was 69 years. MCC was more common in women (64%) than men (36%) and all (100%) cases involved the right colon. The median carcinoembryonic antigen level at diagnosis was 2.8 ng/mL. Lymphovascular invasion and perineural invasion occurred in 64% and 9% of cases, respectively. Synaptophysin and chromogranin showed no expression in any of the cases (0%), and CDX2 was only expressed in 18% of cases by immunohistochemistry. Most patients (73%) presented with stage II disease and 7 (64%) cases were microsatellite instability-high. Only lymph node metastasis showed an association with overall survival (OS) (hazard ratio 0.04, 95% confidence interval 0.0003-0.78; P=0.035). During a median follow up of 1.25 years, the median OS was not estimable as the survival curve did not reach the median point of survival, indicating that more than half of the patients were still alive at the end of the study. Conclusion: Based on our experience, neuroendocrine markers, including synaptophysin and chromogranin, are not expressed in MCC, and many patients present with early-stage disease.
Language	English
Publishing date	2023-04-06
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2032850-3
ISSN	1108-7471
ISSN	1108-7471
DOI	10.20524/aog.2023.0792
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Article: Malignant Eccrine Spiradenoma of the Posterior Scalp: An Odd Presentation.

Lichtman-Mikol, Samuel / Kieft, Aria / Beydoun, Rafic / Joiner, Michael / Miller, Steven

Cureus

2023 Volume 15, Issue 6, Page(s) e40033

Abstract: Malignant eccrine spiradenoma is a rare cutaneous adnexal neoplasm and is often a result of the malignant transformation of a benign eccrine spiradenoma. A woman without a history of skin cancer presented with a mass on her posterior scalp. An excisional ...

Abstract	Malignant eccrine spiradenoma is a rare cutaneous adnexal neoplasm and is often a result of the malignant transformation of a benign eccrine spiradenoma. A woman without a history of skin cancer presented with a mass on her posterior scalp. An excisional biopsy was obtained, and histology was consistent with eccrine spiradenocarcinoma with the lesion extending to all margins of the excision specimen. Physical exam and imaging did not reveal lymph node involvement or distant spread of disease. It was recommended that the patient undergo wide local excision.
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.40033
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Article: A Rare Case of Primary Follicular Dendritic Cell Sarcoma of the Kidney.

Sion, Amanda E / Palka, Josh / Martin, Sarah / Beydoun, Rafic / Maitland, Conrad

Cureus

2023 Volume 15, Issue 12, Page(s) e50337

Abstract: The objective of this case report is to describe a rare case of primary follicular dendritic cell sarcoma (FDCS) of the kidney. FDCS is a rare soft tissue malignancy that most often presents intranodally with lymphadenopathy of the neck, mediastinum, and ...

Abstract	The objective of this case report is to describe a rare case of primary follicular dendritic cell sarcoma (FDCS) of the kidney. FDCS is a rare soft tissue malignancy that most often presents intranodally with lymphadenopathy of the neck, mediastinum, and axilla. One-third of cases present extranodally and most commonly affect the liver, lung, and tonsils. To date, there have been few reports of retroperitoneal FDCS and, to the best of our knowledge, only two other reported cases with primary renal involvement. We present a 56-year-old female with end-stage renal disease on hemodialysis who presented to the hospital with a hypertensive emergency. Computed tomography (CT) of the abdomen was obtained revealing a left-sided renal mass and she subsequently underwent left radical nephrectomy. The pathologic features of the mass revealed oval to spindle cells with eosinophilic cytoplasm, dispersed vesicular chromatin, and small nucleoli found arranged in fascicles, whorls, and storiform patterns with occasional multinucleate forms. The neoplastic cells were immunoreactive to vimentin and expressed cell markers for CD23, CD35, and CD68. These features confirmed a final pathologic diagnosis of primary FDCS of the kidney. To our knowledge, this is the third case of primary renal FDCS reported in the literature. Extranodal FDCS is rare but does occur and needs to be on the differential diagnosis if pathologic features point to its diagnosis.
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.50337
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Article: Sudden Odynophagia and Globus-A Unique Presentation of a Nonsecreting Parathyroid Adenoma: A Case Report and Literature Review.

Srikantha, Luxman / Amjad, Esmael H / Beydoun, Rafic

Case reports in otolaryngology

2020 Volume 2020, Page(s) 6805805

Abstract: Parathyroid adenomas are most commonly diagnosed when symptoms consistent with primary hyperparathyroidism arise. However, certain parathyroid glands may enlarge without such symptoms. Described here is a case in which a patient presented with acute ... ...

Abstract	Parathyroid adenomas are most commonly diagnosed when symptoms consistent with primary hyperparathyroidism arise. However, certain parathyroid glands may enlarge without such symptoms. Described here is a case in which a patient presented with acute signs of unilateral cervical point tenderness, dysphagia, and odynophagia. Calcium and parathyroid hormone levels tested within normal range. Imaging revealed an enlarged right-sided mass, with compression of the trachea-esophageal groove and potentially the right recurrent laryngeal nerve. Surgical excision was performed, and final pathology revealed an infarcted parathyroid adenoma. Clinical symptoms promptly resolved thereafter. Current NIH criteria for parathyroidectomy include various symptoms of hyperparathyroidism but do not include the above findings. Nonsecreting parathyroid adenomas rarely cause laryngeal symptoms, as this has only been documented once before.
Language	English
Publishing date	2020-12-29
Publishing country	United States
Document type	Case Reports
ZDB-ID	2648756-1
ISSN	2090-6773 ; 2090-6765
ISSN (online)	2090-6773
ISSN	2090-6765
DOI	10.1155/2020/6805805
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Article: Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma.

Moein, Hamid-Reza / Rutledge, Brian / Beydoun, Rafic / Ehrinpreis, Murray N

Cureus

2021 Volume 13, Issue 4, Page(s) e14414

Abstract: Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade ... ...

Abstract	Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon.
Language	English
Publishing date	2021-04-11
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.14414
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Article: Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice.

Abada, Evi / Anaya, Ifeoma C / Abada, Othuke / Lebbos, Anthony / Beydoun, Rafic

Journal of pathology and translational medicine

2022 Volume 56, Issue 2, Page(s) 97–102

Abstract: Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 ( ... ...

Abstract	Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.
Language	English
Publishing date	2022-01-21
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	3022395-7
ISSN	2383-7845 ; 2383-7837
ISSN (online)	2383-7845
ISSN	2383-7837
DOI	10.4132/jptm.2021.10.28
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Article ; Online: Integrative deep learning analysis improves colon adenocarcinoma patient stratification at risk for mortality.

Zhou, Jie / Foroughi Pour, Ali / Deirawan, Hany / Daaboul, Fayez / Aung, Thazin Nwe / Beydoun, Rafic / Ahmed, Fahad Shabbir / Chuang, Jeffrey H

EBioMedicine

2023 Volume 94, Page(s) 104726

Abstract: Background: Colorectal cancers are the fourth most diagnosed cancer and the second leading cancer in number of deaths. Many clinical variables, pathological features, and genomic signatures are associated with patient risk, but reliable patient ... ...

Abstract	Background: Colorectal cancers are the fourth most diagnosed cancer and the second leading cancer in number of deaths. Many clinical variables, pathological features, and genomic signatures are associated with patient risk, but reliable patient stratification in the clinic remains a challenging task. Here we assess how image, clinical, and genomic features can be combined to predict risk. Methods: We developed and evaluated integrative deep learning models combining formalin-fixed, paraffin-embedded (FFPE) whole slide images (WSIs), clinical variables, and mutation signatures to stratify colon adenocarcinoma (COAD) patients based on their risk of mortality. Our models were trained using a dataset of 108 patients from The Cancer Genome Atlas (TCGA), and were externally validated on newly generated dataset from Wayne State University (WSU) of 123 COAD patients and rectal adenocarcinoma (READ) patients in TCGA (N = 52). Findings: We first observe that deep learning models trained on FFPE WSIs of TCGA-COAD separate high-risk (OS < 3 years, N = 38) and low-risk (OS > 5 years, N = 25) patients (AUC = 0.81 ± 0.08, 5 year survival p < 0.0001, 5 year relative risk = 1.83 ± 0.04) though such models are less effective at predicting overall survival (OS) for moderate-risk (3 years < OS < 5 years, N = 45) patients (5 year survival p-value = 0.5, 5 year relative risk = 1.05 ± 0.09). We find that our integrative models combining WSIs, clinical variables, and mutation signatures can improve patient stratification for moderate-risk patients (5 year survival p < 0.0001, 5 year relative risk = 1.87 ± 0.07). Our integrative model combining image and clinical variables is also effective on an independent pathology dataset (WSU-COAD, N = 123) generated by our team (5 year survival p < 0.0001, 5 year relative risk = 1.52 ± 0.08), and the TCGA-READ data (5 year survival p < 0.0001, 5 year relative risk = 1.18 ± 0.17). Our multicenter integrative image and clinical model trained on combined TCGA-COAD and WSU-COAD is effective in predicting risk on TCGA-READ (5 year survival p < 0.0001, 5 year relative risk = 1.82 ± 0.13) data. Pathologist review of image-based heatmaps suggests that nuclear size pleomorphism, intense cellularity, and abnormal structures are associated with high-risk, while low-risk regions have more regular and small cells. Quantitative analysis shows high cellularity, high ratios of tumor cells, large tumor nuclei, and low immune infiltration are indicators of high-risk tiles. Interpretation: The improved stratification of colorectal cancer patients from our computational methods can be beneficial for treatment plans and enrollment of patients in clinical trials. Funding: This study was supported by the National Cancer Institutes (Grant No. R01CA230031 and P30CA034196). The funders had no roles in study design, data collection and analysis or preparation of the manuscript.
MeSH term(s)	Humans ; Colonic Neoplasms/diagnosis ; Colonic Neoplasms/genetics ; Adenocarcinoma/genetics ; Deep Learning ; Cell Nucleus ; Genomics
Language	English
Publishing date	2023-07-25
Publishing country	Netherlands
Document type	Multicenter Study ; Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104726
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Article ; Online: The Janus kinase 1 is critical for pancreatic cancer initiation and progression.

Shrestha, Hridaya / Rädler, Patrick D / Dennaoui, Rayane / Wicker, Madison N / Rajbhandari, Nirakar / Sun, Yunguang / Peck, Amy R / Vistisen, Kerry / Triplett, Aleata A / Beydoun, Rafic / Sterneck, Esta / Saur, Dieter / Rui, Hallgeir / Wagner, Kay-Uwe

Cell reports

2024 Volume 43, Issue 5, Page(s) 114202

Abstract: Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the ... ...

Abstract	Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the functions of specific intracellular signaling mediators in this process are less well defined. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate in this study that JAK1 deficiency prevents the formation of KRAS
Language	English
Publishing date	2024-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.114202
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Article ; Online: Expression of Notch Receptors and Ligands in the Coccygeal Body.

Fernandez-Valdivia, Rodrigo / Chammaa, May / Goebel, Dennis / John, Ivy / Beydoun, Rafic

Neuro endocrinology letters

2020 Volume 40, Issue 4, Page(s) 184–194

Abstract: Background: The recent discovery of neural stem cells in the sacrococcygeal end of the filum terminale, the presence of remnants of the most powerful toti-potent stem cell generators and inductors, the primitive streak and node, the existence of the ... ...

Abstract	Background: The recent discovery of neural stem cells in the sacrococcygeal end of the filum terminale, the presence of remnants of the most powerful toti-potent stem cell generators and inductors, the primitive streak and node, the existence of the unique non-mutator sacrococcygeal teratomas, and the recent disclosing of neuroimmunomodulatory and hematopoietic roles of Luschka's body, indicate that the sacrococcygeal region is a distinctive anatomic environment rich in stem cells and instructive signals, and that the coccygeal body may constitute a more complex entity than a mere caudal, vascularly-derived glomic anastomosis. Ascribed as an arterial-venous shunt located at the tip of the coccyx and analog to the glomera caudalia in other vertebrates, the glomus coccygeum has recently revealed a complex organ with peculiar 3D topology, broad innervation, catecholamine-synthesizing activity, and neutrophil-formation and lymphopoietic-regulating properties. Methods: In the present research work, we sought to start exploring the potential cell-functional roles of the glomus coccygeum by conducting a methodical assessment of the expression of Notch pathway receptors and ligands in the human Luschka's body. Results: Our data indicates that Notch receptors are dynamically and distinctively expressed in the coccygeal body and that Notch ligands are markedly differentially expressed in newborn and adult coccygeal glomi. Conclusions: Our observations suggest that Notch signaling may have relevant roles in glomus coccygeum function and biology.
MeSH term(s)	Adult ; Humans ; Infant, Newborn ; Intracellular Signaling Peptides and Proteins/metabolism ; Jagged-1 Protein/metabolism ; Membrane Proteins/metabolism ; Receptors, Notch/metabolism ; Sacrococcygeal Region
Chemical Substances	Intracellular Signaling Peptides and Proteins ; Jagged-1 Protein ; Membrane Proteins ; Receptors, Notch ; delta protein
Language	English
Publishing date	2020-02-21
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	135951-4
ISSN	2354-4716 ; 0172-780X
ISSN (online)	2354-4716
ISSN	0172-780X
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Article ; Online: Improvement of steatotic rat liver function with a defatting cocktail during ex situ normothermic machine perfusion is not directly related to liver fat content.

Raigani, Siavash / Carroll, Cailah / Griffith, Stephanie / Pendexter, Casie / Rosales, Ivy / Deirawan, Hany / Beydoun, Rafic / Yarmush, Martin / Uygun, Korkut / Yeh, Heidi

PloS one

2020 Volume 15, Issue 5, Page(s) e0232886

Abstract: There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available ... ...

Abstract	There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available pool of donated livers. This study demonstrates the ability to improve the function of steatotic rat livers using a combination of ex situ machine perfusion and a "defatting" drug cocktail. After 6 hours of perfusion, defatted livers demonstrated lower perfusate lactate levels and improved bile quality as demonstrated by higher bile bicarbonate and lower bile lactate. Furthermore, defatting was associated with decreased gene expression of pro-inflammatory cytokines and increased expression of enzymes involved in mitochondrial fatty acid oxidation. Rehabilitation of marginal or discarded steatotic livers using machine perfusion and tailored drug therapy can significantly increase the supply of donor livers for transplantation.
MeSH term(s)	Animals ; Bicarbonates/analysis ; Cytokines/genetics ; Disease Models, Animal ; Fatty Liver/genetics ; Fatty Liver/physiopathology ; Fatty Liver/therapy ; Gene Expression Regulation ; Lactic Acid/analysis ; Liver/chemistry ; Liver/physiopathology ; Liver Transplantation ; Male ; Organ Preservation/instrumentation ; Organ Preservation/methods ; Perfusion ; Rats ; Tissue Donors
Chemical Substances	Bicarbonates ; Cytokines ; Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2020-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0232886
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