Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) represents a rare diagnosis in the gastrointestinal tract. Only a few cases of MiNEN occurring in the small bowel had been previously reported. Here we report the first case of mixed high grade neuroendocrine carcinoma with villous adenoma arising in the duodenum. The patient is an 87-year-old female who presented for management of a 3.4 cm polypoid-like duodenal mass that was noted on a prior abdominal CT scan. PET scan showed intense uptake within the second portion of the duodenum consistent with a neoplasm. A biopsy previously performed showed tubulovillous adenoma. The patient had a remote history of breast cancer. Esophagogastroduodenoscopy was performed which showed fungating mass occupying 50% of the duodenal lumen and polypectomy was done. Grossly, the duodenal mass appeared as a pink-tan polypoid fragment of tissue. Microscopically, a villous adenoma is seen with focal area of high-grade dysplasia. Admixed with the villous adenoma, there are sheets of homogeneous small cells with high nuclear-cytoplasmic ratio, nuclear molding, high mitotic activity, and finely granular chromatin which stained positive for synaptophysin, CD56, CAM5.2, and CK8/18 while stained negative for chromogranin A, CK7, CK20, and CDX2. These findings support the diagnosis of high-grade neuroendocrine carcinoma arising in a background of villous adenoma. We report a first case of mixed high grade neuroendocrine carcinoma with villous adenoma arising from the duodenum. [N A J Med Sci. 2021;1(1):004-007. DOI: 10.7156/najms.2021.1401004]
Primary testicular diffuse large B-cell lymphoma is a well-recognized entity known for its indolent clinical course. Rapid dissemination and extensive dermal infiltration are not commonly encountered sequelae of this malignancy. Only one case report exists about its extensive dissemination and involvement of skin and bone. Here, we report a case of primary testicular diffuse large-B cell lymphoma treated with orchiectomy and adjuvant chemotherapy and recurred with widespread dermal involvement as non-blanching violet papule and nodular lesions clinically mimicking Kaposi sarcoma. Histopathological examination confirmed the lesion to be a recurrence of the original lymphoma with similar morphology and immunophenotype. Despite the adjuvant chemotherapy and radiotherapy, the disease progressed from stage-I to stage-IV within 16 months from the date of diagnosis, making it an unusually aggressive clinical course for primary testicular lymphoma. [N A J Med Sci. 2021;1(1):008-011. DOI: 10.7156/najms.2021.1401008] Key Words : primary testicular diffuse large B-cell lymphoma, Kaposiform lesion
Foreign bodies used during surgeries and endoscopy procedures may elicit inflammatory reactions and granuloma formation. The resultant lesion may mimic polyps or tumors, which require cautious interpretation. Here we reported that 69-year-old patient with history of treated rectal cancer underwent surveillance colonoscopy where a tubular adenoma was found in the cecum. A follow-up endoscopy found a flat polyp at the ileocecal valve. Right hemicolectomy was performed. On examining the specimen, two lesions were identified in the wall of the ileocecal valve area. Microscopically, there were foreign body giant cell granulomas filled with eosinophilic amorphous material which is consistent with an inflammatory reaction caused by submucosal lifting material injection used during colonoscopy for polypectomy. The granulomas mimicked recurrence of colorectal carcinoma. Therefore, surgeons and pathologists should be aware of the inflammatory reaction elicited by the new lifting agents that may resemble polyps or tumors. [N A J Med Sci. 2021;1(1):001-003. DOI: 10.7156/najms.2021.1401001]
The interpretation of colonic biopsies can be challenging if the histologic presentation is not characteristic. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Collagenous colitis has been most frequently reported in association with ulcerative colitis either before or many years after ulcerative colitis is established. There are few reports of Lymphocytic colitis in association with Crohn’s disease. To the best of our knowledge however Crohn’s disease presenting as lymphocytic pattern colitis with granulomas has rarely if ever been reported. We present a case of a 34 year old male who presented initially with perianal abscess and fistula-in-ano and subsequent colonoscopic biopsies demonstrated minimal active chronic colitis with granulomas that progressed to lymphocytic colitis pattern inflammation with granulomas within a period of 6-8 months of suboptimal compliance with therapy. [N A J Med Sci. 2020;1(1):009-013. DOI: 10.7156/najms.2020.1301009] Key Words : Microscopic colitis, Collagenous Colitis, Lymphocytic Colitis, Ulcerative Colitis, Crohn’s disease
Background and Aims : Management of common gastrointestinal diseases by non-gastroenterologists often includes diagnostic tests that do not positively impact patient care but increases cost of care. Our study aimed to determine the prevalence of common inpatient practices by non-gastroenterologist providers. Methods : A validated anonymous survey was designed using ‘Google Forms’ (google.com/forms) and responses were collected on a handheld tablet. The questions included basic demographics, level of training, training specialty and practices related to common gastrointestinal diseases. The practices included fecal occult blood testing (FOBT), recognition of melena, use of lipase in management of acute pancreatitis, placement of nasogastric tube in cirrhosis, duration of nil per oral (NPO) before procedures and international normalized ratio (INR) threshold for paracentesis. Descriptive analysis was performed. Results : We collected 150 responses from 4 different residency training hospitals in the United States. Of the respondents, 84% were resident trainees. Primary specialties of practice were internal medicine (82%), family medicine (11%), and others (7%). Inpatient FOBT was available in 95% of the facilities surveyed. With regards to melena, 77.5% correctly identified it as black tarry stool, but 17% also considered FOBT positive brown stool as melena. 21% correlated high lipase levels with more severe acute pancreatitis.19% considered history of cirrhosis a contraindication for placement of nasogastric tube. Only 35% performed abdominal paracentesis regardless of INR value. Discussion : Low value tests and procedures related to common gastrointestinal diseases are prevalent among non-gastroenterologists. Better communication between primary team and specialist and education is needed to optimize patient care.
Coronavirus disease-2019 (COVID-19) is a novel pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). It presents with wide variations in disease severity, and certain populations appear to be more susceptible than others. The mechanisms of such heterogeneity in disease presentation and susceptibility are largely unclear, and this review article aims to examine the existing evidence for the involvement of the human Major Histocompatibility Complex (MHC) system, which is also known as the Human Leukocyte Antigen (HLA) system, as potential effectors of such heterogeneity. We critically examined peer-reviewed case-control, cohort, and in-silico studies, and classified HLA class 1 and 2 alleles into risk and protective alleles based on existing evidence. Furthermore, we summarized the relationship between HLA-DR expression and COVID-19 pathophysiology based on functional studies. We postulate that the identification of HLA alleles that confer risk or protection for COVID19 will not only shed light on understanding disease epidemiology but will also help to guide vaccine development and predict vaccine efficacy across populations. [N A J Med Sci. 2020;1(1):032-038. DOI: 10.7156/najms.2020.1301032] Key Words : SARS-CoV-2, COVID-19, human leukocyte antigen, major histocompatibility complex
Lentigo maligna may not progress to invasive disease for many decades. We present the unusual case of a woman who underwent well documented periodic evaluations and occasional biopsies of a nasal lesion that gradually progressed from lentigo, to melanoma in situ of lentigo maligna type, to invasive disease, and finally to fatal metastatic melanoma. She had declined curative resection of her tumor for cosmetic reasons. Her clinical course is unusual in that photographs and biopsies document the progression from solar lentigo to fatal disease. [N A J Med Sci. 2020;1(1):028-031. DOI: 10.7156/najms.2020.1301028] Key Words : melanoma; lentigo maligna; metastasis; squamous cell carcinoma; solar lentigo; unstable lentigo *Corresponding Author: Penn State Milton S. Hershey Medical Center, Department of Dermatology HU14, 500 University Drive, Suite 100, Hershey, PA 17033. Tel: 717-531-6820, Fax: 717-531-4702. (Email: mhelm2@pennstatehealth.psu.edu)
Primary leiomyosarcoma of bone is rare, with < 0.7% incidence of all primary malignant bone tumors. Here we report a primary leiomyosarcoma of bone arising in a patient with multiple myeloma. The patient is a 72-year-old male who was initially diagnosed with multiple myeloma (IgG Kappa) in 2007 which presented as a large plasmacytoma involving his thoracic vertebrae. He was treated with chemotherapy and eventually had a stem cell transplant in 2015. In 2017, a routine skeletal survey demonstrated a solitary lytic lesion in the right distal femur. The lesion grew fast and doubled in size to 7.9 cm within one year. The lesion was biopsied and proven to be a leiomyosarcoma. A total body PET/CT scan showed no evidence of other primary tumors or metastatic disease. The patient then underwent a distal femur resection. Grossly, majority of the tumor involved distal femur cortical bone and medullary cavity with focal extension into the surrounding soft tissue. Microscopically, the tumor consisted of fascicles of spindle cells with a focal storiform growth pattern. The tumor cells had eosinophilic cytoplasm and focally pleomorphic nuclei. The tumor cells were positive for SMA and Calponin and negative for Desmin, Myo-D1, Myogenin and S-100 immunohistochemical stains. The morphology and immunoprofile favored a diagnosis of pleomorphic leiomyosarcoma. Primary leiomyosarcoma of bone is a rare tumor and this patient’s history of multiple myeloma made it even more challenging to make an early clinical diagnosis. [N A J Med Sci. 2020;1(1):024-027. DOI: 10.7156/najms.2020.1301024] Key Words : primary leiomyosarcoma, femur, multiple myeloma
Glypican-3 (GPC-3) is a glycoconjugate protein of heparan sulfate proteoglycan family and is important for embryogenesis but silenced in adult healthy tissue. GPC-3 protein is abnormally expressed in hepatocellular carcinoma (HCC) and has been used as a marker for pathological diagnosis of primary and metastatic HCC. However, GPC-3 expression has also been found in some tumors other than HCC. This study is to investigate the expression of GPC-3 expression immunohistochemically and the staining pattern in poorly differentiated carcinomas of lung primary in order to assess the value of GPC-3 as a marker for diagnosing metastatic HCC in lung. Lung tissue from 44 patients diagnosed with poorly differentiated carcinoma were evaluated, including 23 lung adenocarcinomas, 19 squamous cell carcinomas and 2 adenosquamous carcinomas. Immunohistochemical stains of GPC-3 was performed on tumor tissue samples. The expression pattern of GPC-3 was analyzed. Expression of GPC-3 was found in 45% of primary lung cancers, including 79% of squamous cell carcinomas, 18 % of adenocarcinomas, and 50% of adenosquamous carcinomas. The poorly differentiated carcinomas showed predominantly patchy positivity. The staining pattern ranged from weak granular cytoplasmic positivity to a strong membranous and cytoplasmic positivity, and both cytoplasmic and nuclear positivity. GPC-3 expression was not seen in non-neoplastic lung tissue. GPC-3 is a relatively specific marker for HCC. In this study, we demonstrated the expression of GPC-3 in a significant number of poorly differentiated carcinoma of lung. Therefore, in context of a possible metastatic HCC to the lung, caution should be made by using GPC-3 as a differential marker for HCC, and a panel of stains should be considered. [N A J Med Sci. 2020;1(1):018-023. DOI: 10.7156/najms.2020.1301018] Key Words : glypican-3, lung carcinomas, immunohistochemistry, hepatocellular carcinoma
Solid pseudopapillary tumor (SPT) is a very rare tumor accounting for only 1% of all pancreatic exocrine tumors. In this case, patient is a 15-year-old female with history of obesity and oligomenorrhea. She was admitted with a six-day history of severe upper abdominal pain, non-bloody vomiting and occasional diarrhea with no history of fever or sick contact. MRI abdominal examination with contrast showed a cystic 3.4 x 2.2 x 2.0 cm mass in the tail of the pancreas. Patient then underwent the distal pancreatectomy and splenectomy. Grossly, the tumor mass is well-circumscribed and has a tan/yellow cystic cut surface. Microscopically, most of the tumor tissue is necrotic. Sheets of cells demonstrate pseudopapillary arrangement in the preserved area. The nuclei are uniform without apparent mitotic figures and cytoplasm is moderate and eosinophilic. Immunohistochemistry study revealed that tumor cells are positive for CD10, progesterone receptor, synaptophysin and nuclear beta-catenin staining. Diagnosis of this case is challenging because extensive necrosis of the tumor tissue, however, the small areas of residual tumor still retain the pseudopapillary architecture and nested pattern. Individual tumor cells have monotonous low grade character. Immunoprofile also supports the diagnosis of solid pseudopapillary tumor. [N A J Med Sci. 2019;12(1):021-023. DOI: 10.7156/najms.2019.1201021]
Fruits are important part of dietary pattern and correlated with a lower risk of chronic diseases because they contain many natural antioxidants. The gastrointestinal digestion could affect on antioxidant activities of fruits. In this study, we investigate d the effects of simulated gastrointestinal digestion on the antioxidant activities of individual and mixed fruits. In the gastric digestion, the FRAP values of all 11 fruits exhibited a decrease d tendency, and the TEAC values showed an increase d tendency. The TPC exhibited different results in the 11 fresh fruit samples. In fruits combination groups, no notable difference was found on the interaction with the FRAP values, and different interactions were detected with the TEAC values (p < 0.05). The gastric process did not make any difference on the TPC between the fruit combinations, but after the duodenal digestion the TPC of group 4 were notably decreased, and the TPC of groups 5 and 8 were increased (p < 0.05). Therefore, the different fruit extracts have different behaviors in tests of FRAP, TEAC, and TPC after the simulated digestion process. Further researches should be done to help explore the mechanisms of the different interactions. [N A J Med Sci. 2019;12(1):014-020. DOI: 10.7156/najms.2019.1201014]
The PSA-based prostate cancer (PCa) screening remains a controversial topic. Total PSA (tPSA) levels along with % free PSA (fPSA%) still remain the most widely used screening markers for PCa in clinical practice. To assess tPSA and fPSA% screening performance and threshold to identify high-grade PCa, a large hospital-based cohort study is executed. A total of 853 patients who received 6 or 12 core prostate biopsies between January 2011 and August 2016 were included in the study and the tPSA and fPSA% were evaluated. The highest tPSA and lowest fPSA% levels within the prior 2 years of the biopsies were scrutinized. Both tPSA and fPSA% have the ability to discriminate patients with PCa from men without PCa. Intriguingly, only tPSA levels in patients older than 60 years showed a significant difference between men with and without PCa. More aggressive PCa also tends to occur in older patients ( Ptrend = 0.045). With a level of tPSA > 20ng/mL, the likelihood ratio for detecting PCa with pathologic Gleason score > 8 is 6.43, with 95% specificity and 30% sensitivity. fPSA% did not show a correlation with PCa histological grades or patients’ age. Both tPSA and fPSA% have significant predictive values in PCa screening. The tPSA levels with the highest predictive value for PCa were achieved in patients older than 60 years in our cohort. Furthermore, a higher level of tPSA, such as 20 ng/mL rather than the widely adopted screening cutoffs (i.e. 4.0 or 10.0 ng/mL) is significantly associated with a high-grade PCa. [N A J Med Sci. 2019;12(1):007-013. DOI: 10.7156/najms.2019.1201007]
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma associated with a high mortality rate. A polyomavirus integrated into the genome of most tumors is thought to be pathogenic. MCCs may be difficult to distinguish from other small cell carcinomas, melanoma, lymphoma, and others. Immunohistochemical marker studies are essential for accurate and efficient diagnosis. Although the paranuclear dot-like pattern seen with staining for cytokeratin 20 is considered characteristic, antibodies directed at other cytokeratins such as cytokeratin 8 (CAM 5.2), pancytokeratins (AE1/AE3), and other clones that recognize low molecular weight cytokeratins are also useful for diagnosis. We set out to evaluate which stains are helpful in diagnosing the cases of MCC encountered in our patient population. A retrospective study of 59 cases of MCC from our files was performed. Each MCC was stained with a panel of IHC markers and evaluated for the staining pattern and intensity in an effort to identify the most efficient IHC stains useful in establishing a diagnosis of MCC. [N A J Med Sci. 2018;11(1):34-38. DOI: 10.7156/najms.2018.1101034]
The aim of this paper is to study the prevalence of individuals with normal glucose tolerance-hyperinsulinemia in Nanshan of Shenzhen, determine the cut point values of normal glucose tolerance-hyperinsulinemia, and investigate the risk factors for it. All subjects were followed 75g oral glucose tolerance test (OGTT) and insulin releasing test. Glucose metabolic disorders were determined according to WHO definition (1999). Hyperinsulinemia was determined if fasting serum insulin and/or 2-hour serum insulin ≥ the 90th percentile, so subjects with normal glucose tolerance were divided into two groups: hyperinsulinemia and normoinsulinemia. The islet cell function and metabolic characteristics of individuals with normal glucose tolerance-hyperinsulinemia were analyzed and its related risk factors were investigated by Logistic regression analysis. The cut point values of normal glucose tolerance-hyperinsulinemia in Nanshan of Shenzhen is fasting serum insulin ≥ 13.85 mU/L and/or 2-hour serum insulin ≥ 74.97 mU/L. The prevalence of NGT- HINS in the community was 7.84%. The differences of the prevalence of high blood, HDL, LDL, TG, UA were significant between subjects with NGT-HINS and NGT-NINS ( P 0.05). There were significant differences on 2hPG between subjects with NGT-HINS and IGR ( P 0.05). The differences of the smoking rates, Baecke index, BMI, WHR, TC, FPG, HbA1C, HOMA-IR, and HBCI/R were significant among these groups. There were nonsignificant differences on age, sex, drinking rate among three groups ( P > 0.05). Logistic regression analysis showed that BMI (OR = 14.019 , 95% CI: 4.111 , 47.800 ; P = 0.000 ); TG (OR = 9.336 , 95% CI: 2.697 , 32.313 ; P = 0.000 ); HDL (OR = 0 .181 , 95% CI: 0 .053 , 0 .625 ; P = 0 .007 ); FPG (OR = 5.276 , 95% CI: 1.588 , 17.535 ; P = 0 .007 ); HOMA-IR (OR = 22.727 , 95% CI: 6.895 , 74.915; P = 0.000 ); HBCI/IR (OR = 6.611 , 95% CI: 2.238 , 19.529 ; P = 0.001 ) were the independent predictors for NGT-HINS. Our results show that the cut point values of normal glucose tolerance-hyperinsulinemia in Nanshan of Shenzhen is fasting serum insulin ≥ 13.85 mU/L and/or 2-hour serum insulin ≥ 74.97 mU/L. Individuals with NGT-HINS suffered more metabolic risk factors and had a decreased β-cell function . NGT-HINS is a transitional state between NGT and IGR. BMI, TG, HDL, FPG, HOMA-IR, and HBCI/IR were the independent predictors for NGT-HINS. [N A J Med Sci. 2018;11(1):43-51. DOI: 10.7156/najms.2018.1101043]
Large cell neuroendocrine carcinomas (LCNEC) of the uterus is a rare and very aggressive neoplasm. Herein we report a case of large cell neuroendocrine carcinoma arising from the uterus with extensive carcinomatosis. The patient was a 51-year-old African-American female who presented with increasing worsening abdominal distension and abdominal pain over a period of one month. A computed tomography (CT) imaging study disclosed a 20 x 15 x 10 cm heterogeneous uterine mass with significant ascites and omental thickening. The patient subsequently underwent a total hysterectomy with bilateral salpingo-oophorectomy and omental resection. Histological examination showed a large cell neuroendocrine carcinoma with extensive necrosis and numerous abnormal mitosis. No associated surface epithelial component was identified. Immunohistochemical staining pattern was consistent with the neuroendocrine origin. The patient’s condition rapidly deteriorated postoperatively, and she died one month later due to multi-organ complications. In light of the rarity of LNEC arising from the uterus, a comprehensive review of the literature is discussed. [N A J Med Sci. 2018;11(1):39-42. DOI: 10.7156/najms.2018.1101039]
Ectopic hamartomatous thymoma is a rare benign tumor located at supraclavicular/suprasternal area and is speculated with a branchial anlage origin. There are usually 3 components in the tumor: spindle cells, epithelial cells, and adipose tissue, although proportion of each varies from case to case. The tumor cells present with a unique immunophenotype, with strong positivity for AE1/AE3, CD34, CD10, and variable staining for Bcl-2 and SMA. Here we report such a case in a 61 year old male, with a compatible morphology and immunopattern for this entity. [N A J Med Sci. 201 8 ;11(1):11-14. DOI: 10.7156/najms.2018.110111 ]
Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma arising from neuroectoderm-derived cells comprising the outer coverings of peripheral nerves. Given the diverse cell types comprising the peripheral nerve sheath, both benign and malignant nerve sheath tumors display a wide range of histologic appearances. MPNST can arise either in association with proximal nerve trunks at deep body sites, or from distal nerve branches residing within skin and subcutaneous tissues. Overall, roughly 50% of MPNST arise in patients with neurofibromatosis type I. The remainder occur sporadically. We report herein a rare epithelioid example of MPNST arising sporadically within a cutaneous neurofibroma. We also offer a brief clinico-pathologic review of MPNST, including diagnostic workup, differential interpretation, treatment and prognosis. [N A J Med Sci. 201 8 ;11(1):15-18. DOI: 10.7156/najms.2018.110115 ]
