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The histopathologic characteristics of the gastrointestinal system in SARS-COV-2 infected patients who underwent biopsy or resection [Meeting Abstract]

Ahmed, S; Hoskoppal, D; Lin, L; Suarez, Y; Liu, W; Cho, M; Thomas, K; Guzzetta, M; Hajdu, C; Theise, N; Jour, G; Sarkar, S; Cao, W
Background: In addition to respiratory distress, GI symptoms have been reported in COVID-19 patients at various stages of the disease. Among the GI symptoms that have been reported, diarrhea, nausea, vomiting, abdominal pain and GI bleeding were often seen. Age and comorbid conditions such as obesity, HTN, DM and/or CAD have been considered as risk factors for COVID-19 patients for severe disease. GI manifestations in COVID-19 patients appeared to act as a sign for a serious condition. The virus has been identified in the stool and in rectal swabs of some infected patients, even after a negative nasopharyngeal test. There is a lack of reports on pathological alterations of the GI tract in COVID-19 infected patients.
Design(s): 16 PCR confirmed COVID-19 patients (11 males and 5 females) were included in the study. Biopsy or resection specimens were taken from the esophagus (4), stomach (6), small intestine (5), appendix (3), colon (5) and gallbladder (3). Clinical information including demographics, comorbidities, GI symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): The age of the patients ranged from 10 to 84 years old, with an average of 47 years. Eight (50%) patients had at least one comorbid condition, two patients (12.5%) had prior history of cancer, and six patients had no significant medical history. Abdominal pain and GI bleeding were the most common presenting symptoms. Histologically, acute and chronic inflammation was seen in 14 of 16, and 15 of 16 cases, respectively. Eight cases showed severe acute inflammation with ulceration. The mucosal changes included nonspecific reactive change, hypermucinous, atrophic/ischemic changes, and necrosis, were indiscriminately noticed in these cases. Four cases showed intraepithelial lymphocytosis. Viral like inclusions were found in four cases. Microthrombi were identified in 5 cases with an average patient age of 60 years. Notably, microthrombi were seen in about 5 out of 8 (62%) patients with comorbidities. The patients with microthrombi had a higher D dimer test value than those without thrombus. Three patients died shortly after operation, and two of them showed microthrombi in the tissue specimens.
Conclusion(s): Acute and chronic inflammation were indiscriminately seen in these cases. Microthrombi were dominantly found in aging patients with comorbidities, suggesting microthrombi in the GI tract may be a histologic indication for severe COVID-19 patients with GI symptoms
ISSN: 1530-0307
CID: 4857062

Rectal SWAB SARS-COV-2 testing and histologic findings in the small intestine of 18 autopsy patients [Meeting Abstract]

Lin, L; Ahmed, S; Thomas, K; Guzzetta, M; Hoskoppal, D; Cho, M; Suarez, Y; Liu, W; Hajdu, C; Theise, N; Jour, G; Sarkar, S; Cao, W
Background: Digestive symptoms are often seen in COVID-19 patients with poor outcomes. The Viral RNA is mostly positive in the stool of these patients, and has a longer delay before viral clearance. However, its diagnostic value and significance for guiding clinical treatment remain unknown. And the pathologic alterations in the GI tract in COVID-19 patients have not been well defined. We evaluated rectal swab SAS-CoV-2 test and histopathologic changes in the small intestine in autopsy patients.
Design(s): 18 autopsy cases with confirmed SAS-CoV2 infection were included. Nasal, bronchial, and rectal swab SARS-CoV-2 PCR were performed at the time of autopsy. Clinical information included demographics, comorbidities, presenting symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): 83% (15/18) of patients were male. Median age is 50 years. 7/18 (38.9%) patients had diarrhea in addition to cough, fever and other symptoms. Except in one case, all patients had underlying comorbidities of diabetes, hypertension and /or obesity. In the small intestine, acute inflammation was not seen in any cases. 5/18 displayed mild and one showed moderate chronic inflammation. Hypermucinous change was found in six patients but not associated with diarrhea. 3 cases had microthrombi identified in the sections. Notably, obviously increased D dimer in lab tests were noticed in all patients. Postmortem 17/17 (100%) nasal, 18/18 (100%) bronchial and 7/16 (43.8%) rectal swabs showed SARS-CoV-2 PCR positivity. 3 of 7 (42.9%) patients with diarrhea are positive in rectal swab for SARS-CoV-2.
Conclusion(s): There are no specific COVID-19 changes in the small intestine. More investigations are needed, especially on tissues from different locations of the GI tract. Data from rectal swab testing suggests that it is not ideal for diagnosing COVID-19, guiding treatment, or predicting small intestinal pathology
ISSN: 1530-0307
CID: 4857032

Clinical and Intestinal Histopathological Findings in SARS-CoV-2/COVID-19 Patients with Hematochezia [Case Report]

Cho, Margaret; Liu, Weiguo; Balzora, Sophie; Suarez, Yvelisse; Hoskoppal, Deepthi; Theise, Neil D; Cao, Wenqing; Sarkar, Suparna A
Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.
PMID: 33976619
ISSN: 1662-0631
CID: 4867392

Tumor Budding in Colorectal Carcinoma Showing a Paradoxical Mitotic Index (Via PHH3) With Possible Association to the Tumor Stromal Microenvironment

Hacking, Sean; Sajjan, Sujata; Angert, Mallorie; Ebare, Kingsley; Jin, Cao; Chavarria, Hector; Kataria, Nidhi; Zhang, Lei; Cho, Margaret; Thomas, Rebecca; Lee, Lili; Nasim, Mansoor
BACKGROUND:Colorectal carcinomas (CC) are one of the most commonly diagnosed malignancies. Tumor budding (the histologic process of dissociation that occurs at the invasive margin of colorectal cancer), has significant prognostic implications, in that higher tumor budding is associated with adverse histopathologic and clinical outcomes. Because of this prognostic significance, more research is needed to further understand the pathologic and immunohistochemical (IHC) associations pertaining to this important prognostic variable. In this study, we will further evaluate selective clinopathologic and IHC variables with possible association to tumor budding. DESIGN/METHODS:A total of 234 cases of CC diagnosed in our health system were retrospectively reviewed and routine hematoxylin and eosin-stained slides of these cases were collected. A representative slide for tumor budding was selected per case and selective IHC staining was performed. Clinicopathologic data were collected for each case and analyzed in relation to tumor budding scores. In exploratory analyses, tumor budding scores per individual investigator and consensus tumor budding scores were compared with selected IHC stains (MLH1, PMS2, and PHH3) as well as numerous clinicopathologic variables. RESULTS:We found a paradoxical association between tumor budding and mitosis score using PHH3 immunostaining in univariate and multivariable analysis. Furthermore, patients with intact nuclear expression for MLH1 and/or PMS2 are more likely to have higher tumor budding compared with patients with lost expression. For multivariable analysis, the following covariates were significantly associated with higher tumor budding: the presence of lymphovascular invasion, higher pathologic tumor stage, and finally infiltrating border was more likely to be associated with higher tumor budding compared with cases with a pushing border. Regarding nonmucinous versus mucinous CC, nonmucinous adenocarcinoma (MCA) was more likely to be associated with higher tumor budding compared with MCA. CONCLUSION/CONCLUSIONS:Numerous clinicopathologic variables were found to be associated with tumor budding including lymphovascular invasion, tumor stage, infiltrating tumor border, non-MCA was more likely to be associated with higher tumor budding compared with MCA, possibly related to MUC-2 and MSI. Furthermore, regarding the paradoxical association between tumor budding and mitosis score using a PHH3 immunostaining (high tumor budding having lower mitosis), this is possibly related to the tumoral stomal microenvironment and cancer associated fibroblasts. An idea for a future study would be to look at the maturity of cancer-associated fibroblasts (immature vs. mature) and the tumoral stroma microenvironment, with regards to markers of tumor aggressiveness such as mitosis. In addition, we found that patients with intact nuclear expression for MLH1 and/or PMS2 were more likely to have higher tumor budding compared with patients with lost expression, possibly related to mismatch repair CC's not being as reliant on tumor budding. Future research will hopefully concede further insight into the variables that affect tumor budding, especially regarding the tumoral microenvironment and variations between different patient populations, inclusive of patients lacking activity of the mismatch repair. Ultimately, this will allow for better prognostic information, and more precise treatment modalities.
PMID: 31567276
ISSN: 1533-4058
CID: 4596272

Ectopic salivary gland found on rectal biopsy-a rare pathological diagnosis

Schulberg, Steven P; Serouya, Sam; Cho, Margaret; Gadangi, Pratap K
BACKGROUND:Heterotopic tissue can be found throughout the GI tract, most commonly being gastric tissue. The finding of ectopic salivary tissue located in the GI tract is an exceedingly rare finding. We present a case of an otherwise healthy 30-year-old male with rectal bleeding who underwent biopsy of a submucosal rectal lesion with pathologic findings of ectopic salivary gland tissue. CASE PRESENTATION/METHODS:Our patient is a 30-year-old male who presented with rectal bleeding. During his workup, he underwent colonoscopy and subsequent endoscopic ultrasound after discovery of a submucosal mass in the rectum measuring approximately 2 × 1 cm. Biopsies were sent which returned showing ectopic salivary gland tissue superimposed on hyperplastic rectal mucosa. The patient's symptoms resolved and he has not had recurrence of bleeding. CONCLUSIONS:Ectopic salivary gland tissue is a rare pathological finding in the rectum. It can present as a symptomatic lesion or be found incidentally. There is no clear reason for its presence, but it is felt to be due to metaplasia, developmental anomalies, or idiopathic in nature. Treatment includes excision and monitoring.
PMID: 32152669
ISSN: 1432-1262
CID: 4348812

Tumor budding in colorectal carcinoma: An institutional interobserver reliability and prognostic study of colorectal adenocarcinoma cases

Hacking, Sean; Angert, Mallorie; Jin, Cao; Kline, Myriam; Gupta, Neha; Cho, Margaret; Thomas, Rebecca; Lee, Lili; Chavarria, Hector; Nasim, Mansoor
BACKGROUND:Colorectal carcinomas are one of the most commonly diagnosed malignancies. There are many prognostic factors relating to clinical course and disease progression, including tumor stage, metastasis, and tumor budding. In 2016, the International Tumor Budding Consensus Conference (ITBCC) created a system to uniformly assess tumor budding. This system includes a 3-tier system for the grading of tumor budding. In the past, there lacked uniform consensus, however the general grading practice was based on a 2-tiered system. Given that tumor budding is considered to have prognostic value, the accuracy and reproducibility of its assessment is vital. Our study aims to look at interobserver agreement in the scoring of tumor budding. DESIGN/METHODS:A total of 233 cases of colorectal carcinoma diagnosed in our health system were retrospectively analyzed and routine H&E stained slides of these cases were collected. A representative slide for tumor budding was selected per case. Four investigators with different levels of experience and expertise evaluated the selected slide of each case for tumor budding. Scoring was based on the ITBCC protocol. Clinico-pathological data was collected for each case and analyzed with tumor budding scores. Tumor budding scores per individual investigator and consensus tumor budding score were compared to patient and tumor characteristics including patient survival, tumor grade, tumor stage, and lymph node status. RESULTS:) and associated 95% confidence intervals was used to compare the ratings made by 4 pathologists. Overall, there was variation among pathologists in tumor budding score (Gwet's agreement coefficient = 0.25 and 0.326 for 3-tier and 2-tier grading system, respectively). Results show higher reliability with the 2-tier system compared to the 3-tier system. Tumor stage was significantly associated with budding score for all individual investigators and the consensus value (p value < 0.001). CONCLUSION/CONCLUSIONS:There is low inter-observer agreement in the assessment of tumor budding in colorectal carcinoma. This suggests that it is difficult to uniformly grade tumor budding and that our classification system needs improvement. We found that the older 2-tier system (Hase et al.) results in slightly higher inter-observer agreement than the recently proposed 3-tier grading system (ITBCC, 2016), though both systems lead to suboptimal agreement. Worth noting is that observers with subspecialty GI training and more work experience had higher inter-observer agreement. Our results showed that subspecialty training tends to increase agreement more than overall work experience. In addition, our exploratory results showed that there is an association of tumor budding score to tumor stage. While increasing refinement in classification, the 3-tiered system resulted in decreased agreement in tumor budding assessment. Clearly, there is more work to be done in the identification and quantification of tumor buds.
PMID: 31731034
ISSN: 1532-8198
CID: 4596282

Papillary thyroid carcinoma metastatic to the pancreas: Case report

Cho, Margaret; Acosta-Gonzalez, Gabriel; Brandler, Tamar C; Basu, Atreyee; Wei, Xiao-Jun; Simms, Anthony
Papillary thyroid carcinoma (PTC) is generally associated with an excellent long-term outcome. Distant metastasis is rare with only 5-7% of patients developing distant disease. Metastasis of PTC to the pancreas is an exceedingly rare occurrence. To date, few cases have been reported. We present the case of an 81-year-old man with past medical history of PTC status post total thyroidectomy with local recurrence treated with radioactive iodine and selective neck dissection. Ten years after his initial diagnosis, PET-CT scan revealed a new hypermetabolic 1.1 cm × 0.9 cm left lower lobe lung nodule and hypermetabolism in the proximal body of the pancreas. Follow-up MRI cholangiogram showed a 1.0 × 0.8 cm T1 hypointense lesion in the proximal body of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic mass showed neoplastic epithelial cells arranged in papillary clusters with fibrovascular cores and syncytial sheets with high nuclear to cytoplasmic ratio, visible nucleoli, nuclear pallor, focal nuclear grooves, and rare intranuclear pseudoinclusions. Immunohistochemical stains performed on the smears showed positive nuclear expression of TTF-1 and PAX-8. The findings were consistent with metastatic PTC. Surgical resection of the lung nodule confirmed metastatic PTC. Pancreatic metastases usually occur after long time intervals with reports of up to 8 years in PTC. This makes the diagnosis more challenging, and metastatic disease should always be in the differential diagnosis in cases presenting with a pancreatic mass, especially in patients with a prior malignancy.
PMID: 30479026
ISSN: 1097-0339
CID: 3657862

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP); An Interobserver Study of Key Cytomorphologic Features From a Large Academic Medical Center

Brandler, Tamar C; Cho, Margaret; Wei, Xiao-Jun; Simms, Anthony; Levine, Pascale; Hernandez, Osvaldo; Oweity, Thaira; Zhou, Fang; Simsir, Aylin; Rosen, Lisa; Sun, Wei
OBJECTIVE:Because of the indolent nature of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) and potential requisite for conservative treatment, it is crucial to identify features of this entity pre-operatively. Our group recently published our findings that there are several cytomorphologic features that may be used as clues to distinguish NIFTP, PTC and follicular adenoma (FA) on fine-needle aspiration (FNA). Therefore, we aimed to determine the interobserver reproducibility of these findings. METHODS:Pre-surgical FNA slides from NIFTP (n=30), classic PTC (n=30) and FA (n=30) collected from 1/2013-8/2016 were reviewed by 7 cytopathologists blindly. Presence of selected cytomorphologic features was recorded and compared to determine percent agreement and inter-rater reliability among study cytopathologists using Gwet's AC1 statistics. RESULTS:For all the cytomorphologic features, the overall percent agreement amongst the pathologists ranged between 65.1% and 86.8% (Gwet's AC1 0.30 to 0.80). There was substantial or almost perfect agreement (Gwet's AC1 >0.60) in seven cytomorphologic features in the classic PTC group, in six features in the NIFTP group, and in five features in the FA group. There were no features with poor agreement (Gwet's AC1<0.0). CONCLUSIONS:The current study supports the reproducibility of our previous findings. The high level of agreement amongst pathologists for these groups, and particularly the NIFTP group, supports the notion that when viewed in combination as a cytologic profile, these cytomorphologic features may assist the cytopathologist in raising the possibility of NIFTP pre-operatively. This can potentially aid clinicians in deciding whether more conservative treatment may be appropriate.
PMID: 30230094
ISSN: 1365-2303
CID: 3300612

Does Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Have a Unique Molecular Profile?

Brandler, Tamar C; Liu, Cheng Z; Cho, Margaret; Zhou, Fang; Cangiarella, Joan; Yee-Chang, Melissa; Shi, Yan; Simsir, Aylin; Sun, Wei
Objectives/UNASSIGNED:Recognizing preoperative characteristics of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is important for clinical management. Therefore, we assessed presurgical NIFTP molecular profiles using fine-needle aspiration (FNA) material. Methods/UNASSIGNED:Presurgical FNA reports of 39 surgically confirmed NIFTP cases from January 2013 through May 2017 were assessed for Afirma and ThyroSeq results. Results/UNASSIGNED:Twenty-one of 39 NIFTP nodules were preoperatively tested with Afirma with two benign and 19 suspicious results. Twenty-seven of 39 nodules were tested with ThyroSeq (nine of 39 had both Afirma and Thyroseq): 18 (67%) had RAS mutations (13 NRAS, four HRAS, one KRAS), and three of 18 had multiple alterations (NRAS + TP53, n = 1; NRAS + PTEN, n = 2). BRAF T599_R603 + EIF1AX mutation (n = 1), PTEN mutation (n = 1), MET overexpression (n = 1), PAX8/PPARG fusion (n = 3), and THADA/IGF2BP3 fusion (n = 3) comprised the remainder. Conclusions/UNASSIGNED:NIFTP cases most commonly displayed suspicious Afirma results and RAS mutations on ThyroSeq, lacking aggressive/BRAF-V600E-like mutations. While NIFTP remains a surgical entity, the lack of aggressive/BRAF-V600E-like mutations can aid in determining the extent of surgery.
PMID: 30052723
ISSN: 1943-7722
CID: 3216572

Does Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Have a Unique Molecular Profile? [Meeting Abstract]

Brandler, Tamar; Cho, Margaret; Zhou, Fang; Simsir, Aylin; Cangiarella, Joan; Liu, Cheng; Hodak, Steven; Yee-Chang, Melissa; Shi, Yan; Sun, Wei
ISSN: 0893-3952
CID: 3049072