Cases Of Neoplasia Research Articles

Cancer incidence and mortality in Uruguay: 2013-2017.

Uruguay has the highest cancer incidence and mortality rates in Latin America. The National Cancer Registry of Uruguay, which has been in operation since 1992, provides epidemiological information on incidence and mortality at the country level. The objective of this article is to update the incidence and mortality figures by reporting the information for the period 2013-2017. All incident cases of invasive neoplasias except non melanoma of the skin and all cancer deaths occurred in from 2013 to 2017 were analyzed. Age standardized rates were calculated by the direct method, using the world standard population. Complementary, incidence (2002-2017) and mortality (1990-2017) trends were studied for the leading sites. Among females, the most common cancers are breast, colon and rectum, lung, cervix and thyroid. The most frequent cancers in males are prostate, lung, colon and rectum, bladder and kidney. Lung, prostate and colorectal cancer are the leading causes of cancer death in males while breast cancer is the first cause of cancer death among females. Although cancer mortality has declined monotonously since 1990, cancer control is a challenge for Uruguay, wherein breast, lung and prostate cancer have very high incidence while the country must still make an effort to reduce other cancers that are very common in economically less favored countries.

Miliary Tuberculosis: Moroccan Series of 101 Cases

Introduction: Miliary tuberculosis is an increasingly rare form (2% to 8%), defined by the hematogenous or lymphatic dissemination of the tubercle bacillus from a pulmonary or extra-pulmonary focus but which remains serious and can lead to acute respiratory failure due lesional pulmonary edema. Patients and Methods: This is a retrospective study of 101 cases of miliary tuberculosis hospitalized between January 1989 and July 2019 in the pneumology department of “20 Aout” in Casablanca. Results: The average age is 43 years with a predominance of men (64%), the history of tuberculosis is found in 8 cases and tuberculosis contagion in 10 cases. The common symptom in all cases (100%) is an alteration of the general condition, fever is present in 76% of cases, dry cough is found in 75.5% of cases and dyspnea is found in 38.3% of cases. Among the causes of immunosuppression, we noted: 3 cases of neoplasia, 5 cases of diabetes, 5 cases of pregnancy and 4 cases of system diseases. The chest X-ray (frontal view) found an aspect of pulmonary miliaria in all cases associated with pleurisy in 18 cases, an excavated opacity in 3 cases and pneumothorax in 1 case. Tuberculin intradermal reaction (tIDR) was positive in 35 cases. Antibacillary treatment was started urgently in all cases. The outcome was good in the majority of cases with 10 deaths. Further work-up allowed confirmation of the diagnosis either by direct isolation of the koch bacillus or by biopsy in 47.52% of cases.

Effective High Grade Cervical Intraepithelial Neoplasia Case Finding in Low Resource Settings.

Background: Visual Inspection with Acetic Acid (VIA) is an inexpensive option for cervical cancer screening. In this study, we evaluated the role of the VIA as well as of the clinical symptoms/signs to find the best case-finding method for Cervical Intraepithelial Neoplasia (CIN) 2+. Methods: In a cross-sectional study, we extracted from records the demographic characteristics, clinical symptoms/signs, and indications for colposcopy referral of patients with CIN 2+ in pathology. Patients were divided into 1- Abnormal Pap smear, 2- Positive VIA, 3- abnormal Pap smear with clinical symptoms/signs, 4-VIA positive with clinical symptoms/signs, 5- only clinical symptoms/signs. The sensitivity of each method was studied to determine their effectiveness as a screening method. Results: Out of 146 patients who underwent colposcopy, 38 patients had it due to abnormal Pap smears, 37 due to positive VIA, 21 due to abnormality of both these tests, and 50 due to clinical symptoms/signs despite having normal screening tests. The sensitivity for VIA and Pap smear was 73.39% (17.48%-83.31%) and 40.41% (32.47%-48.86%) respectively. Presence of at least one of the three clinical symptoms/signs and a positive VIA found 78.8% of CIN 2+ cases. Presence of at least one of the three clinical symptoms/signs and abnormal Pap smear identified 84.2% of the cases. Conclusion: To find high-grade CIN, focused attention to the clinical symptoms/signs, even in the presence of normal Pap smear, can increase the sensitivity of Pap smear and VIA. In low resource settings, a simple, highly sensitive method like VIA can be used in addition to or as an alternative to other means.

Feline Uveal Melanoma Review: Our Current Understanding and Recent Research Advances.

Melanocytic neoplasia is the most common form of ocular tumour in cats, accounting for 67% of cases in an analysis of 2614 cases of primary ocular neoplasia. Feline diffuse iris melanoma (FDIM) is by far the most common form of ocular melanocytic neoplasia, with limbal melanomas and atypical melanoma (melanoma affecting the choroid or ciliary body) infrequently recognised. Early lesions begin as flat areas of pigmentation of the iris, known as iris melanosis. This melanosis is a precursor lesion that can become FDIM when pigmented cells infiltrate the anterior iris stroma, commonly alongside a transition in cell morphology. The differentiation between FDIM and benign iris melanosis is only recognisable though histologic examination, with no in vivo means of identifying the malignant transformation. The behaviour of FDIM is variable and difficult to predict. Some FDIM lesions have a more benign progression and can slowly grow or remain static for years without affecting the ocular or systemic health of the individual, whilst other tumours behave aggressively, invading the ocular structures and significantly affecting the life expectancy of cats through metastatic disease. This makes management and timely enucleation of these cases challenging in practice. This article aims to review our current knowledge of FDIM.

Genitourinary syndrome, local oestrogen therapy and endometrial pathology: a single-centre, randomised study

The objective of this study was to assess the endometrial pathology developed (EP) in postmenopausal women with genitourinary syndrome during and after vaginal oestrogen therapy. The 67 patients included were randomly grouped into group I underwent local oestrogen (oestriol) therapy and group II, underwent no therapy. Each patient’s medical history was taken and clinical and gynecological examination, with transvaginal ultrasound at the time of inclusion and during the control visits, was done. The study results show no statistically higher risk of EP for vaginal oestrogen therapy of genitourinary syndrome users compared to the non-users in menopause. No one atypical endometrial hyperplasia and endometrial intraepithelial neoplasia case during the study period was found. Impact statement What is already known on this subject? Treatment of genitourinary syndrome with oestrogens in menopausal women is the most commonly used and affordable method. Topical vaginal oestrogens do not have the same stimulating effect on the endometrium as oral ones, and therefore the association between them and endometrial hyperplasia or cancer has not been established categorically. What do the results of this study add? This single-center, randomised study found no statistically higher risk of endometrial pathology for vaginal oestrogen (oestriol) therapy of genitourinary syndrome users compared to the non-users in menopause. No one atypical endometrial hyperplasia and endometrial intraepithelial neoplasia case during the study period was found. What the implications are of these findings for clinical practice and/or further research? This study confirms the safety of local oestrogen (oestriol) therapy of genitourinary syndrome in menopausal women with regards to the development of endometrial pathology and especially atypical endometrial hyperplasia and endometrial intraepithelial neoplasia or well-differentiated carcinoma

Ocular surface squamous neoplasia (OSSN) in an 84‐year‐old female patient

AbstractPurposeTo report a case of Ocular Surface Squamous Neoplasia, in an 84 years old woman. The patient referred 4 months of red vascularized elevated corneal lesion.MethodsOur proposal was an exportation of the conjunctival corneal neoformation and histological examination. During the surgical procedure, we found an elevated lesion with feeder vessels, the surgical excision biopsy was done and the specimen was sent for histopathological evaluation, which revealed an invasive, poorly differentiated carcinoma extending to subcutis. Immunohistochemical staining for p63 gave dubious results on the integrity of the basement membrane. These findings associated with the incomplete excision of the lesion did not allow us to express a possible invasiveness in the lateral margin affected.ResultsIn the post‐operative, we used Mitomycin C 0.04% topical treatment, 4 times a day for a week, then 3 weeks off for a total of 3 cycles. During this period the patient did not display any adverse systemic or ocular reactions. At the end of the treatment, we found a complete regression of the disease. During the control at 6 months and 1 year, the patient was asymptomatic.ConclusionsDiagnosis of invasive Squamous Cell Carcinoma mainly rests on the histopathological examination of the excised lesion. No serious ocular or systemic side effects were observed during the Mitomycin C 0.04% eye drops treatment. Mitomycin C 0.04% seems to be a safe and effective treatment for ocular surface squamous neoplasia.

The regression time of ocular surface squamous neoplasia using topical interferon alfa-2b does not depend on the initial tumor size.

The aim of this study was to determine if the initial tumor size correlates with the time to regression after topical interferon alfa-2b (1 million IU/mL) therapy in the treatment of ocular surface squamous neoplasia. A retrospective study was performed in 15 patients clinically diagnosed as having ocular surface squamous neoplasia and treated with topical interferon alfa-2b (1 million IU/mL, four times a day). All the cases of ocular surface squamous neoplasia included in the study had corneo-limbal involvement. The initial extension of the ocular surface squamous neoplasia was measured in square millimeters using the program ImageJ (LOCI, University of Wisconsin, Madison, USA) on images taken from the eyes of each patient immediately before the beginning of the treatment. The time until tumor resolution was measured for each case. Complete tumor resolution was achieved in all the cases, with a mean initial tumor extension of 26.71 mm² (standard deviation ± 17.21 mm²) and a mean time until resolution of 77 days (standard deviation ± 32 days). An increased tumor volume after 15 days of treatment was obser ved in 2 patients, which completely resolved. No significant correlation was found between the time to resolution and the initial tumor extension measured in square millimeters (Spear man test, p=0.347). Our study suggests that the duration of topical interferon alfa-2b treatment required does not depend on the initial tumor size of the ocular surface squamous neoplasia usually found in clinical practice.

Not just weight loss

Renal cancer (RC) – associated increased calcium is rather frequent among cases of kidney neoplasia; it may be the first sign of presentation that allows the detection of the malignancy; typically representing a poor prognostic factor. Weight loss is part of the panel underling hypercalcemia - related signs, but also of the malignancy – associated phenotype. We aim to introduce a male case who was admitted for a clinical picture (including weight loss) correlated with alarming high calcium levels; the biochemistry anomaly was actually a paraneoplastic syndrome due to RC. When admitted as emergency, the assays revealed hypercalcemia of 16.9 mg/dl (normal levels between 8.4 and 10.2 mg/dl) with low PTH (Parathormone) and high CrossLaps as bone turnover marker of resorption. Intravenous contrast computed tomography showed a large left retroperitoneal tumor (involving the kidney and adrenal gland) with iodophil pattern, and post-contrast heterogeneous structure of 8.06/11.09 cm (axial), 10.58/12.16 cm (coronal-reconstruction), 9.12/10.59 cm (sagittal - reconstruction), also associating a mixt structure and micro-calcifications as well as hypodense areas. Whole body bone scintigram did not show metastasis. The calcium levels were controlled under subcutaneous denosumab 60 mg in addition to IV fluids replacement; then the patient was referred to nephrectomy; postoperative confirmation confirmed a clear cell renal cell carcinoma (T4N1Mx). A normalization of calcium and PTH levels was found immediately after surgery. Unintentional weight loss might become a valuable tool in order to assess a routine biochemistry panel that will detect hypercalcemia. Low PTH represents the next step in order to further look for a tumor. Symptomatic control of hypercalcemia in addition to targeted approach of originating tumor are essential to improve the outcome.

Prostate Biopsies and its Correlation with Prostate Specific Antigen in Patients Attending Birat Medical College Teaching Hospital, Morang, Nepal

INTRODUCTION: Prostate cancer is the most common malignant tumor in men over the age of 65 years. It is the second most common cause of cancer related death in men after lung cancer but it can be completely cured if detected at an early stage. Most frequently encountered diseases of the prostate are benign prostatic hyperplasia, prostatitis and carcinoma. Increased prostate specific antigen levels are found to be closely associated with prostate cancer. It is a tumour marker which is a glycoprotein and is expressed by both normal and neoplastic prostate tissue. This study was done to determine the correlation between histopathological diagnosis in prostatic biopsy and serum prostatic specific antigen level. 
 MATERIALS AND METHODS: This is a hospital based cross sectional study carried out in the Department of Pathology, Birat Medical College Teaching Hospital from February 15, 2020 to October 15, 2020. A total of 84 cases were included in this study. All representative tissue sections were taken, paraffin embedded blocks were prepared and stained with hematoxylin and eosin stain. Histopathological examination was done and it’s association with serum prostatic specific antigen level was observed. 
 RESULTS: In the biopsy findings, Benign Prostatic Hyperplasia (BPH) was the most common case seen in 41 (48.8%) cases out of 84 cases with maximum incidence seen in 60-69 years age group (13 cases). A total of 10 (11.9%) cases were those of prostatic adenocarcinoma and were seen in the 70-79 years age group. Majority of benign cases (BPH and BPH with prostatitis) were seen in the PSA range of 0-7ng/ml. Maximum cases of Prostatic Intraepithelial Neoplasia (PIN) were seen in the PSA range of 0-7 or 7.1-14 ng/ml and adenocarcinoma in the range of >20ng/ml. The finding showed that adenocarcinoma is associated with increased level of serum PSA level. 
 CONCLUSIONS: PSA is a specific marker for prostatic tissue. It can be raised in benign lesions of the prostate due to membrane disruption. However, an increased PSA level above 20 ng/ml increases the chance of detecting malignant lesions.

The current state of pathology and immunohistochemistry in gestational trophoblastic disease therapeutic management: A tertiary center experience

Gestational trophoblastic disease (GTD) is derived from the abnormal development of trophoblastic tissue and covers a broad range of benign and malignant disorders. The histological diagnosis of GTD continues to be a challenge, even among expert pathologists. The present study evaluates the roles of pathology and immunohistochemistry in GTD diagnostic and therapeutic approaches. A retrospective study was conducted in Filantropia Clinical Hospital, Bucharest, Romania, involving cases of GTD between 2010 and 2020. We reported 19 clinically diagnosed and histologically confirmed cases of GTD, 15 moles (complete and partial), along with 4 cases of gestational trophoblastic neoplasia (GTN). The mean age of the patients studied was 31.3±7.5 years. The percentage of cases diagnosed after the sonographic evaluation was 94.7%. The rate of progression of GTD to GTN was 5.2%. Seven patients with low-risk GTD (risk score six or less) were treated with first-line chemotherapy (CT), and two cases required second-line CT. Twelve patients with highrisk GTD (risk score seven or more) were treated with first-line CT (n = 4), first-line CT followed by second-line CT (n = 4), first-line CT with adjuvant surgery (n = 3), and first-line surgery (one case). No causal relationship has been established between the forms of gestational trophoblastic disease regarding hCG level, the rate of normalization of hCG, and the rate of progression to GTN. After chemotherapy for GTD, only 42.1% of patients who wanted a future pregnancy could conceive. Underutilized in the current practice (5.2%), the immunohistochemical markers for trophoblasts and DNA genotyping are particularly useful tools in the fast and accurate diagnosis and prognosis of GTD.

Correlation between Prostate Specific Antigen (PSA) Level and Various Prostatic Diseases on Biopsies: A Retrospective Study

Introduction: The prostate is a pear-shaped glandular organ that adds part of fluid to semen. The prostate consists of stromal and glandular components. Prostate needle biopsy is performed either transrectal ultrasound (TRUS) guided or transurethral routes. PSA is a glycoprotein produced by secretory cells. Normally the PSA levels are less than 4.0ng/ml.
 Aim: The main aim of the study is to find out the correlation between various pathological lesions occur in the prostate and serum Prostate Specific Antigen (PSA) level.
 Study Design: A retrospective study.
 Place and Duration of Study: Department of Pathology,Saveetha Medical college and Hospital, between January 2019 and December 2019.
 Methodology: A retrospective study of 84 prostatic biopsies for a period of 1 year in the year 2019 was carried out. All specimens subjected for histopathological examination and the relevant clinical data and Serum PSA values correlation was done.
 Results: Commonest age group being 61-70 years. Difficulty in micturition was the most common presentation .Most common lesion found was Benign Prostatic Hypertrophy(BPH) constituting 67 cases (71.42%) followed by BPH with prostatitis 17 cases (20.23%), adenocarcinoma 6 cases (7.14%) and 1 case of Prostatic Intraepithelial Neoplasia (PIN) (1.19%). BPH patients, had S.PSA levels in the range of 4.1-15 ng/ml. Three cases of adenocarcinoma showed very high levels of S.PSA (>100 ng/ml) with the Gleason score of 9(5+4).
 Conclusion: Both benign and malignant pathologies can cause an increase in serum PSA levels, but the chances of finding malignancy increases with rising values of PSA. But in the management of prostatic cancer the histopathological diagnosis and grading plays a definitive role.

Cost effectiveness of routine histology for haemorrhoidectomy specimens

Background: Routine histology for haemorrhoidectomy specimens remains commonplace in clinical practice, as a method of detecting incidental anal cancer. However, its utility and cost-effectiveness is unclear in the literature. This study aimed to determine the cost-effectiveness of routine histology for haemorrhoidectomy specimens in a regional Australian hospital. The secondary aim was to determine the proportion of specimens sent for histology, and whether individual surgeons had a statistically significant preference for whether to send for histology.Methods: This was a retrospective cohort study of patients who received haemorrhoidectomies at Hervey Bay Hospital between March 2012 and May 2020. Cost effectiveness of routine histology was investigated by weighing the number of incidental anal cancers detected against the cost of analysis. The proportion sent for histology was determined, both as a whole and by individual consultant surgeons.Results: Routine histology was ordered in 65% of patients who received haemorrhoidectomies over the study period (n=119), costing $13,623 AUD ($1,651 AUD per year). No cases of incidental anal dysplasia or neoplasia were found. Only 1 of the 8 most prolific surgeons over the study period demonstrated a statistically significant preference for whether to send for histology.Conclusions: Our study does not support routine histology for haemorrhoidectomy specimens as a cost-effective practice for detecting incidental anal cancer. Most individual surgeons did not display a clear preference for whether to send for histology.

Clinicopathological features of differentiated-type dysplasia of the esophagus

Objective: To investigate the clinicopathological features of differentiated-type (squamous) dysplasia of the esophagus. Methods: A total of 184 cases of esophageal differentiated-type dysplasia were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), and Beijing Chaoyang Hospital, Capital Medical University, China from 2016 to 2019. Their histological characteristics and immunophenotypes were analyzed, and related literature was reviewed. Results: The median age of the 184 patients was 65 years (range 39-83 years), while the ratio of men to women was 1.7∶1.0. There were 17 cases in the upper esophagus, 143 in the middle esophagus and 24 in the lower esophagus. The median diameter of the dysplasia was 15 mm (range 2-50 mm). According to the Paris classification, 2 cases were 0-Ⅰ, 25 cases were 0-Ⅱa, 70 cases were 0-Ⅱb, 74 cases were 0-Ⅱb and 0-Ⅱc and 13 cases were 0-Ⅱc. Macroscopically, the lesional mucosa was reddish with rough surface and white moss; capillary abnormality was found on narrow-band imaging. Histologically, dysplastic cells had distinct features of squamous epithelium, with abundant eosinophilic cytoplasm, round to irregular nuclei, coarse chromatin, obvious nucleolus, and conspicuous mitoses. The cellularity was increased, the arrangement of cells was disordered, and the polarity of cells in basal layer was lost. When the dysplasia did not completely spread to the whole layer of squamous epithelium, a clear boundary was often formed between the dysplasia and the normal epithelium above it. The neoplastic epithelial protrusions often grew toward the lamina propria and were accompanied by conspicuous inflammatory cell reaction at its frontal edge. Sometimes, abnormal mature single epithelial cells or cell clusters infiltrated into the lamina propria. There were high-grade dysplasia of the common type and superficial invasive squamous cell carcinoma in 98 cases of differentiated-type dysplasia. Immunohistochemical staining showed that the mutation rate of TP53 was 47.7% (53/111). The median of Ki-67 labeling index was 50.0% (range 10%-80%), while that of basal tumor cells was 12/HPF (range 3-65/HPF). The abnormal distribution pattern of Ki-67 was seen in 111 (100%) cases. According to the initial pathological diagnosis, there were 16 cases of low-grade intraepithelial neoplasia, 37 cases of atypical epithelial cells and 131 cases of high-grade intraepithelial neoplasia and superficial invasive squamous cell carcinoma. Conclusions: The morphology of differentiated-type dysplasia of the esophagus is unique. Characteristics of highly differentiated dysplastic cells suggest that they may represent a differentiated type in the morphological lineage of esophageal squamous (high-grade) dysplasia. When the knowledge of the lesion is insufficient, it is easy to be misdiagnosed or missed in pathologic examination.

233. Osteomyelitis of the jaw: A retrospective analysis of clinical, microbiologic characteristics and antimicrobial treatment at a Tertiary Care Medical Center

BackgroundOsteomyelitis of the jaw is a relatively rare entity in the post antibiotic era. The aim of this study is to describe clinical characteristics, microbiology and antibiotics use (oral vs intravenous) for treatment. We review 5 years of experience at Banner University Medical Center-Phoenix (BUMC-P) of proven cases of OM jaw by clinical, pathological, radiological criteria.MethodsRetrospective study of cases. From January 2011 to November 2015 ,157 cases of osteomyelitis of the jaw, we excluded cases of radiation therapy or neoplasia to the head and neck region, a history of antiresorptive medication use. A total of 34 patients with diagnosis of osteomyelitis of the jaw were reviewed. All patients met criteria for diagnosis of osteomyelitis and underwent surgical debridement and received antibiotics that included parenteral, orals and combined. We reviewed clinical, microbiology, antibiotic use. A successful outcome was defined as elimination of clinical symptoms, restoration of function and if available radiographic evidence of arrest and resolution of bony necrosis. ResultsThis retrospective study involved 34 patients. Most common organisms were oropharyngeal flora 22 samples (65%): streptococcus anginosus group. 4 samples grew unusual gram negative bacteria. 10 (29%) samples grew fungal species. Antimicrobial regimen was divided in: intravenous (n=14) (41.2%), oral (n=7) (20.6%) and combination intravenous followed by orals as follows: 13 (38.2 %).The average antibiotic duration was 8.1 + 4.7 weeks. We were able to follow up 30 patients, average follow up was 32.1-44.7 weeks. The overall success rate was (n=24) 80% with uneventful healing and. (n=6) (20%) treatment failure. There was more failure in the oral antibiotics group (n=3). ConclusionThis study is limited by small numbers. Surgery and cultures should guide treatment of osteomyelitis of the jaw. The use of oral antimicrobial therapy was associated to a higher likelihood of treatment failure. Although rarely linked as a cause of osteomyelitis, the authors think that the cultivation of candida spp should prompt appropriate coverage. More study is required to understand the efficacy of oral antimicrobial therapy in treating osteomyelitis of the jaw.Disclosures All Authors: No reported disclosures

A case of pancreatic intraepithelial neoplasia detected by pancreatic duct dilation

A case of pancreatic intraepithelial neoplasia detected by pancreatic duct dilation

PROFILE OF ESOPHAGUS NEOPLASMS RELATED TO THE CONSUMPTION OF ALCOHOLIC BEVERAGES:

Introduction: Esophageal neoplasia presents a high morbidity and mortality rate, associated with males and the esolist habit. Objective: to describe the profile of esophageal neoplasia related to alcohol consumption between 2015 and 2019 in Montes Claros, Minas Gerais, Brazil. Methods: A descriptive study of quantitative approach was conducted through data from patients diagnosed with esophageal neoplasia in hospital records of the José Alencar Gomes da Silva National Cancer Institute (INCA). Results and discussion: 525 cases of esophageal neoplasia were recorded in the period evaluated. Alcohol consumption was positive in 88.1% of the cases. Conclusion: The data indicate a positive relationship between alcohol consumption and esophageal neoplasia. These data should encourage the establishment of public policies for health education measures in relation to alcohol consumption and smoking habits.

A case of solitary plasmacytoma of bone showing co-expression of both immunoglobulin light chains

BackgroundSolitary plasmacytoma of bone (SPB) is a rare plasma cell neoplasm. It arises in bone as a single locus in the absence of any plasma cell myeloma lesions. Plasma cell neoplasms intrinsically express only one immunoglobulin light chain (IgL)—kappa or lambda—and using this fact, kappa/lambda deviation is the decisive factor for diagnosis. Co-expression of both IgLs in a single tumor cell is extremely rare.Case presentationWe report a case of SPB that arose in the vertebra of a 52-year-old Japanese woman. Histologically, the resected mass showed diffuse plasma cell proliferation. Dual IgL expression was detected by flow cytometry, immunohistochemistry, and in situ hybridization (ISH) targeting IgL mRNA.ConclusionWe have presented an extremely rare case of SPB showing dual expression of kappa and lambda IgLs. This unusual case of plasma cell neoplasia might represent a possible exceptional example of failure of “IgL isotypic exclusion.”

Immunohistochemical Expression of Preferentially Expressed Antigen in Melanoma (PRAME) in the Uninvolved Background Testis, Germ Cell Neoplasia In Situ, and Germ Cell Tumors of the Testis.

Preferentially expressed antigen in melanoma (PRAME) has a key role in regulating pluripotency of primordial germ cells and in the development of germ cell tumors of the testis (GCTT). However, its immunohistochemical expression in normal testes and its neoplastic counterpart remain largely unknown. We retrospectively investigated the expression of PRAME in 26 cases of GCTT, 21 cases of germ cell neoplasia in situ (GCNIS), and 17 cases of uninvolved background testes. We found that PRAME was expressed more strongly by seminomatous rather than nonseminomatous GCTT (P = .000) and by pure seminoma rather than the seminoma component of seminomatous/nonseminomatous GCTT (P = .025). In addition, GCNIS and uninvolved background testes displayed high levels of PRAME expression. PRAME is an additional marker for the differential diagnosis of GCTT and could play a key role in the transition from seminomatous to nonseminomatous GCTT.

A Questionnaire-Based Survey on the Impact of the COVID-19 Pandemic on Gastrointestinal Endoscopy in Asia

Introduction: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. Methods: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the International Gastrointestinal Consensus Symposium. A total of 166 respondents in Japan, China, Hong Kong, South Korea, Philippines, Thailand, Indonesia, and Singapore participated in this study. Results: The volume of endoscopic screening or follow-up endoscopies and therapeutic endoscopies were markedly reduced during the first wave of the pandemic, which was mainly attributed to the decreased number of outpatients, cancellations by patients, and adherence to the guidelines of academic societies. The most common indications for GI endoscopy during the first wave were GI bleeding, cholangitis or obstructive jaundice, and a highly suspicious case of neoplasia. The most common GI symptoms of COVID-19 patients during the infected period included diarrhea, nausea, and vomiting. The pandemic exacerbated some GI diseases, such as functional dyspepsia and irritable bowel syndrome. There were cases with delayed diagnosis of cancers due to postponed endoscopic procedures, and the prescription of proton pump inhibitors/potassium-competitive acid blockers, steroids, immunosuppressive agents, and biologics was delayed or canceled. The personal protective equipment used during endoscopic procedures for high-risk patients were disposable gloves, disposable gowns, N95 or equivalent masks, and face shields. However, the devices on the patient side during endoscopic procedures included modified surgical masks, mouthpieces with filters, and disposable vinyl boxes or aerosol boxes covering the head. Furthermore, the time for education, basic research, clinical research, and daily clinical practice decreased during the first wave. Conclusion: This study demonstrated that the COVID-19 pandemic profoundly affected the method of performing GI endoscopy and medical treatment for patients with GI diseases in Asian countries.

Mesenchymal Stromal Cells (MSCs) from Myelodysplastic Syndromes (MDS) Are Not Clonally Mutated I n Vivo

IntroductionThere is increasing evidence for an active role of the bone marrow (BM) microenvironment in the pathogenesis of Myelodysplastic Syndromes (MDS). Genetically engineered murine models have shown that isolated mutations in the BM niche can disrupt the non-mutated hematopoietic compartment and induce MDS-like phenotypes. However, it is still unclear whether primary MDS in humans may possibly be associated with acquired mutations non-hematopoietic BM stroma cells. Although chromosomal aberrations and mutations have been described in in ex vivo expanded MSC cultures from MDS and AML patients, little validation has been performed to address whether such molecular lesions were not clonal outgrowths resulting from the strenuous and massively expansive cell culture procedures.Materials and MethodsWe performed whole exome sequencing on paired ex vivo expanded MSCs and native BM samples of n=98 MDS and associated myeloid neoplasia cases treated at the Department of Hematology and Oncology of the Medical Faculty Mannheim, Heidelberg University, Germany (median age 73 years, range 44-86). As controls, we included a cohort of n=28 samples from healthy subjects (median age 75 years, range 36-84). MSCs were expanded adherently on plastic dishes by seeding 5x10e6 mononuclear cells in StemMACS MSC Expansion Medium XF (Miltenyi Biotec) for a median of 34 days, (95% confidence interval 22-50d). Whole exome sequencing was carried out using Nextera DNA Flex Tagmentation kit (Illumina) with IDT xGene Research probe v1 at a median coverage at 88x with BM MNC as germline control accounting for possible LOH in the BM sample. Validation experiments were performed by deep re-sequencing of single CFU-F colonies (n=4 patients), sequencing of serial cultures (n=7 patients) and re-sequencing of primary sorted native bone marrow MSCs from n=9 patients.ResultsIn the exome sequencing analyses of ex vivo expanded MSCs we discovered multiple recurrent mutations in MSCs of MDS patients including but not limited to genes such as ZFX (n=8/98) and RANK (n=5/98). MSCs from MDS patients displayed an overall higher mutational burden and increased replicative stress as determined by gH2AX and RPA staining, which correlated with the mutational burden and shorter telomeres as compared to healthy controls. The analysis of mutational signatures revealed that MDS MSCs were distinct compared to healthy MSCs. Furthermore, we found that MDS MSCs displayed increased senescence assessed by flow bGAL staining and associated inflammatory gene expression determined by IL6 qPCR/ELISA for n=32 cases.To investigate whether acquired mutations in MSCs were driven by the ex vivo expansion we performed individualized amplicon based deep re-sequencing of serial culture passages and different BM aspirations for n=7 patients as well as single colony re-sequencing in n=4 patient cases. Furthermore, we re-sequenced primary sorted CD45-,CD235a-,CD31+/-,CD271+/- BM cells of n=9 cases. All of these validation experiments indicated that the discovered mutations were associated with expansion in culture and but not present in clonally relevant cell populations in the primary BM in vivo.DiscussionTogether with previously published data of the BM niche of myeloid neoplasms, our results add to the notion that MSCs in MDS are molecularly and functionally altered. Nevertheless, our current comprehensive sequencing analyses leave little doubt that if acquired mutations in the stroma of MDS patients play a role in MDS disease initiation at all, then at such a low clonal and possibly locally confined level, that they are not detectable with currently feasible sample acquisition and methodology. In our current study, we discovered no evidence for acquired mutations in BM derived MSCs in MDS. DisclosuresSchmitt: Affimed GmbH: Research Funding. Flach: Gilead: Current Employment. Hofmann: BMS: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Nowak: Pharmaxis: Current holder of individual stocks in a privately-held company, Research Funding; Celgene: Honoraria; AbbVie: Other: Investigator on funded clinical trial; Tolero Pharma, Pharmaxis, Apogenix: Research Funding; Affimed: Research Funding; Takeda: Honoraria.