key: cord-0006290-st2t7a64
authors: nan
title: Abstracts from USCAP 2019: Infectious Disease Pathology (1435-1462)
date: 2019-03-18
journal: Mod Pathol
DOI: 10.1038/s41379-019-0240-x
sha: d83c6b445157b135b1bccacd8f3ad4fc539280b3
doc_id: 6290
cord_uid: st2t7a64

nan

S u z a n n e Di nt zi s Mi c h ell e D o w n e s D a ni el D y e A n dr e w E v a n s Mi c h a el F e el y D e n ni s Fir c h a u L ari s s a F urt a d o A nt h o n y Gill R y a n Gill P a ul a Gi nt er T a m ar a Gi or g a d z e R a ul G o n z al e z P ur v a G o p al A n ur a d h a G o p al a n J e n nif er G or d et s k y R o n d ell Gr a h a m Al ej a n dr o Gr u Nil e s h G u pt a M a mt a G u pt a Kri s zti n a H a nl e y D o u gl a s H art m a n Y a el H e h er W alt er H e nri c k s J o h n Hi g gi n s M ai H o a n g M oj g a n H o s s ei ni A ar o n H u b er P et er Ill ei D oi n a I v a n W ei Ji a n g Vi c ki e J o Kir k J o n e s N e erj a K a m b h a m C hi a h S ui ( S u n n y) K a o Di pti K ar a m c h a n d a ni D ar c y K err A s hr af K h a n R e b e c c a Ki n g Mi c h a el Kl u k Kri sti n e K o n o p k a Gr e g or Kri n g s A s a n gi K u m ar a p eli

Al v ar o L a g a C h e n g-H a n L e e Z ai b o Li H ai y a n Li u Xi uli Li u Y e n-C h u n Li u T a m ar a L ot a n Bit a N ai ni Di a n n a N g T o n y N g Eri c k a Ol g a ar d J a c q u eli n e P ar ai Y a n P e n g D a vi d Pi s a pi a Al e x a n dr o s P ol y d ori d e s St e v e n S al v at or e S o u z a n S a n ati S a n dr o S a nt a g at a A nj ali S a qi Fr a n k S c h n ei d er J e a n n e S h e n Ji a qi S hi W u n-J u S hi e h G a bri el Si c a D e e pi k a Sir o hi K alli o pi Si zi o pi k o u L a ur e n S mit h S ar a S z a b o J uli e T er u y a-F el d st ei n G a et a n o T hi e n e K hi n T h w a y R a s h mi T o n d o n J o s e T orr e al b a E vi V a ki a ni C hri st o p h er V a n d e n B u s s c h e S o n al V ar m a E n di W a n g C hri st o p h er W e b er Ol g a W ei n b er g S ar a W o b k er Mi n a X u S h a of e n g Y a n A nj a n a Y el d a n di Immunohistochemistry was done using Strepatavidin-biotin method, co-localization image analysis and scoring of each marker was done using the quick (Q) score (Leica, Germany). Follow-up of the cases for 5-year cumulative incidence of recurrence (CIR) and cancer-specific death was retrieved from the medical archive of the clinical oncology department of Alexandria University Hospital.

Results: PARP-1 and COX-2 scorings were increased in all carcinoma cases compared to the normal bladder tissue samples, and were co-localized. While, PTEN was lost in carcinomas compared to the normal tissue samples. Schistosomal-positive tumors were found to have higher expression of PARP-1 and COX-2 compared to non-Schistosomal cases and showed lower PTEN (p=0.001) (figure 1). In squamous cell carcinomas, the expression of PARP-1 and COX-2 was higher than in transitional carcinomas (p=0.04). The Schistosomalpositive cases showed significant higher CIR and cancer-specific death. 

Schistosomal-positive urinary carcinoma shows remarkable PTEN loss compared to the non-Schistosomal cases. Schistosomal-positive urinary carcinoma mediates an inflammatory milieu with increased PARP-1 and COX-2 expression, the former known to have targeted therapy, indicating its prognostic as well as predictive role which could be helpful in this endemic disease. Background: A wide variety of parasites can infect the gastrointestinal (GI) tract, resulting in severe diarrhea, anemia, and weight loss. While HIV-related infections have decreased in the late HAART era, the range of organisms associated with immunomodulatory therapies for cancer and autoimmune diseases continues to expand. The gold standard for diagnosis is direct visualization of organisms in stool specimens, which can be aided by antigen testing, and endoscopic mucosal biopsies. The spectrum of histologic findings associated with intestinal parasitic infections in the current era is poorly described.

Design: Stool ova and parasite (O&P) examination and Giardia/Cryptosporidium (G/C) antigen tests were reviewed at an academic medical center with a large cancer and transplant population. Patients with endoscopic GI biopsies performed within six months of stool parasite testing were identified, and cases with positive laboratory findings and representative negative controls were histologically reviewed for the number of intraepithelial lymphocytes (IELs), number of lamina propria eosinophils, and the presence of granulomata, neutrophils, and parasites. Neutrophils present (n, %) 4 (67) 3 (43) 7 (54) Granuloma(s) present (n, %) 3 (50)**** 1 (14) 0 (0) Organisms (n, %) 0 (0) (0) 1 (8)*** *Biopsies included duodenum, ileum, other small bowel, and colon **~20% of negative cases were reviewed by report *** Trichuris trichiura ****Three samples from a single patient with a history of leukemia, status post bone marrow transplant. HPF: high-power field; IELs: intra-epithelial lymphocytes.

Conclusions: Parasitic infections of the GI tract were relatively uncommon, with a positive laboratory test in 1.7% of patients. Concurrent GI biopsies were obtained in 20% of patients and showed no significant difference in the inflammatory response on histologic review. Due to the lack of specificity of the biopsy findings, a low threshold should be used to recommend stool O&P testing in cases of unexplained symptoms, particularly in immunosuppressed individuals.

Javier , raising concern about the potential efficacy of the HPV vaccine program in this population. The aim of this study was to determine the prevalence and distribution of HPV genotypes in a subpopulation of Colombian women screened for cervical cancer in Fundacion Santa Fe de Bogota University Hospital (Bogota, Colombia) in order to ensure the accuracy of HPV vaccines in the target population.

Design: Cervical swabs obtained from 1028 women aged 15 to 74 years old were included in this cross sectional study (2017 -Aug/2018). Samples were collected in BD SurePath™ Collection Vial and 69% had simultaneous BD SurePath™ liquid-based cytology (LBC). HPV detection and genotyping was performed by using HPV direct flow chip (master diagnostica).

The prevalence of HPV was 33.1% (high-risk: 20.33%, low-risk: 10.26%). HR-HPV co-infections were found in 2.54%. HR-HPV prevalence in women aged 15 -20 years was 40%. HR-HPV was detected in 13% (n = 63) of negative LBCs, 87% (n = 45) of low-grade squamous intraepithelial lesion (LSIL) and 100% (n = 10) of high-grade squamous intraepithelial lesion (HSIL). The most prevalent HR-HPV types were 51 (11.4%), 16 (9.8%), 39 (8.9%) and 66 (8.9%). 71.4% of patients that had HR-HPV not present in the non-9 valent vaccine had confirmed SIL (16% had HSIL). Sensitivity and specificity of the HPV-test and LBC was 75% and 56%, and 60% and 76% respectively.

We show that HR-HPV types were different than the ones included in the most recent 9-valent vaccine in 56.8% of all cases and 66.0% of women aged 15 -20 years, and they cause abnormal cytology and histology-demonstrated HSIL. Adding to a growing body of evidence that HPV genotype distribution in Latin America it is not similar to the distribution pattern seen in other parts of the world, thus affecting the potential vaccine impact in this population. ) are often used in the context of characteristic inflammatory patterns, but sensitivity is low and evaluation time-consuming. We recently reported the use of an immunohistochemical (IHC) anti-mycobacteria antibody(CP140; Biocare medical, Concord CA at a 1:500 dilution) as a sensitive, efficient screening tool.

Following clinical validation, we assessed the performance of this new test amongst general, noninfectious disease-trained anatomic pathologists.

Design: All cases in which mycobacterial IHC was ordered during routine diagnostic work-up were retrospectively identified. Results were derived from the finalized pathology report and compared to a composite reference standard in which demonstration of organisms by histochemical stains or isolation in culture was considered positive. The sensitivity and specificity of mycobacterial IHC was calculated in comparison to histochemical staining, culture and a composite reference standard in which demonstration of organisms by any combination of these other techniqes was considered positive. Histochemical stains were also evaluated in comparison to the reference standard. IHC, Immunohistochemistry; AFB, acid-fast bacilli; mAFB, modified acid-fast bacill; n, number; CI, confidence interval.

We found mycobacterial IHC to be well adopted by non-infectious disease trained anatomic pathologists with increased specificity relative to both AFB and mAFB. The sensitivity of this new assay was higher than that of AFB, but lower than mAFB. These results support the use of IHC as an adjunctive tool in the diagnosis of mycobacterial infections in routine practice, and suggest its potential role in the adjudication of equivocal histochemical staining or as a more rapid screening test.

Mia Design: Microbiology laboratory results at a large academic medical center were reviewed, and 32 patients with at least one culture positive for Scedosporium/Pseudallescheria spp. were identified from 1998-2018. Concurrent surgical pathology specimens were obtained in 16 patients and were included in this study. Patient demographics, clinical presentation, treatment, and outcomes were collected from electronic medical records.

Results: All 16 patients (mean age 56 years; 56% female) were immunocompromised: 10 transplant recipients, 3 with cystic fibrosis, 3 with autoimmune disorders. Presentation varied from skin/soft tissue infections (n=5) to pneumonia (n=4); 7 patients were determined to be asymptomatically colonized. Concurrent cultures identified S. apiospermum/P. bodyii in 14 patients and S. prolificans in two patients. Serum (1,3) beta-D-glucan was elevated in 4/9 (44%) patients, while galactomannan was negative in 11/12 (92%). Fungal elements were identified histologically in 8 patients. Periodic Acid-Schiff and methenamine silver stains highlighted branched septate hyphae and conidia, indistinguishable from other hyaline mold species, including Aspergillus and Fusarium. Granulomatous and/or suppurative inflammation, necrosis, and angioinvasion were variably present. Management included surgical debridement, antifungal therapy, and reduction of immunosuppression. Two of the 5 patients with skin/soft tissue infections resolved with treatment, while the remaining 3, including both cases of S. prolificans, developed disseminated disease and died.

Conclusions: Accurate and timely diagnosis of Scedosporium infection in immunocompromised patients is vital to ensure adequate clinical management, especially given the genus' enhanced virulence and drug resistance profile. As clinical presentation, histologic inflammatory pattern, and fungal morphology overlap with other opportunistic fungal infections, correlation with cultures and/or molecular data is critical for diagnosis. Our study, although limited, highlights the rarity of scedosporiosis and suggests that skin/soft tissue infections portend a worse prognosis and that S. prolificans is a more virulent species. Conclusions: Although molecular diagnostic tests for respiratory pathogens are limited in outpatient use, we demonstrated that EZ was more accurate in pathogen identification, decreased appointment duration and allowed for targeted anticipatory guidance. While the cost of this test is more than traditional antigen testing, overall healthcare costs may be lower. Future investigations could be conducted to determine if their usage would also decrease unnecessary antibiotics, radiologic imaging, invasive testing and ED visits. Here, we leverage 10 years of lymph node biopsy pathology and clinical data to systematically evaluate results from the three most commonly ordered pathogen stains: the Gram stain, acid-fast bacilli (AFB), and the methenamine silver stain (MSS), and identify their impact on diagnoses.

Design: Using institutional databases, we analyzed 313 microorganism stains performed on 178 lymph node biopsies received between 9/1/2008 and 9/1/2018 and accessioned to hematopathology, including 123 Gram stains, 154 AFB stains, and 36 MSS stains. We correlated stain results with histologic findings, pathologic diagnosis, and tissue culture results when performed. Manual chart review was undertaken for any case with a positive stain, positive culture, or histology suggestive of inflammation or any reactive changes.

Results: Strikingly, only 1 of the 123 collected Gram stains yielded visible bacteria (0.8%). This specimen yielded no culture growth and the patient was treated empirically with antibiotics. Among specimens displaying inflammatory or other reactive changes (92/123; 74.8%), Gram stains were universally negative. Bacterial culture data was available for only 31 of the 92 reactive specimens (33.7%) and yielded no pathogen growth. In contrast, 9 of the 154 AFB stains (5.8%) identified mycobacteria and corresponded with growth in all cultured cases (8/8; 100%). Among MSS stains, 1 of 36 (2.8%) displayed visible fungi and yielded a positive culture for Histoplasma capsulatum.

Conclusions: Systematic analysis of lymph node biopsies collected over a decade reveals marked differences in agreement rates between routine microbial stains and associated histologic and clinical data. While positive stains for mycobacteria and fungi were often confirmed by positive culture and clinical follow-up, Gram stains yielded no actionable information for any patient in the study period. More judicious use of this stain may be warranted in lymph node evaluation in the future.

David Comparing the etiologies to demographic and clinical variables, non-infectious reactive lymphadenopathy and KS/CD appear to involve relatively younger patients than malignancies (p<0.05). Malignancies including lymphoma were more frequent in patients compliant with HAART therapy (63%, p<0.001), with slightly higher CD4 counts. See Table 1 for summary. 

In this era of HAART therapy, HIV related lymphomas are on the rise, and seen more commonly in patients with therapy compliance and higher CD4 counts. Larger series may be needed to identify variables to clinically predict etiologies of HIV related lymphadenopathy. Background: Higher prevalence of anal HPV in HIV+ patients compared to HIV-patients has been observed. Although highly active antiretroviral therapy (HAART) is effective in controlling HIV, its impact on HPV-induced anal dysplasia is unclear. In this study, we analyzed the impact of HAART on morphologic progression of HPV-induced anal dysplasia using patient specimens before and after their HAART initiation. We performed an extensive case-controlled clinicopathologic and immunohistochemical (IHC) study using our large cohort of patients pre-and post-HAART.

Design: Twenty HIV+ patients with dysplastic anal biopsies collected both prior to HAART initiation ("pre-HAART") and during HAART ("post-HAART") were included. Tissue was graded from anal intraepithelial neoplasia-1 (AIN-1)-AIN-3. Pre-HAART, grade change was measured from a presumed previous grade of 0; post-HAART, grade change was calculated between pre-and post-HAART biopsies. Concurrent viral loads (VL) and CD4 counts were obtained. IHC of Waf1p21 and Ki-67 was performed, scored, and compared pre-and post-HAART. Lymphocytic reaction was also scored: focal minimal=1, focal enhanced=2, lichenoid=3, and intraepithelial=4. Conclusions: HAART has a significant impact on the progression of anal dysplasia, and patients on HAART show smaller grade increases and slower progression. Our mechanistical study suggests this effect may be due to increased CD4 counts and effective immunosurveillance of pre-invasive neoplastic lesions. Our aim is to search for HPV infection in cervical samples, describing the type-specific HPV in Brazilian women from a high-income southeast region which have access to the private health system.

From January 1 st 2015 to August 31 st 2018, 21,017 liquid-based (LBC) cervical specimens were received for cytology and HPV detection. Before the cytology slides performance, an 1,000 μl aliquot were taken from the LBC fixative and submitted to automated DNA extraction using QIAsymphony DSP DNA Mini Kit. Multiplex PCR followed by capillary electrophoresis was used for HPV detection and classification.

Results: The mean age of patients was 36.4 years-old. It was 32.3 yo for HPV positive and 37.1 yo for negative cases. HPV was detected in 895(4.3%) of the cases. All genotypes and their prevalence are exposed in graphic 1. There were 73 cases with multiple HPV-type infection (8.1% of the HPV positive cases), being the majority association of high-risk HPV. From these cases, 47.9% were diagnosed HSIL or LSIL in cytology. Low-risk and high-risk association was identified in 16.4% of cases. Background: Acid fast staining (AFS) for the detection of mycobacteria and other acid-fast organisms provides a rapid way of identifying pathogenic organisms in FFPE tissue in contrast to culture methods, which require weeks to perform. While rapid and straightforward, there are several issues with AFS. First, AFS can be challenging and time-consuming to interpret. Second, standard tissue fixatives and processing alters the lipid-rich cell wall of acid-fast organisms which reduces the detection sensitivity in FFPE samples. Last, AFS does not allow for discrimination between various acid-fast organisms, such as mycobacteria tuberculosis (MTB) vs. non-tuberculous mycobacteria (NTM). To address these issues with AFS, we have developed a highly sensitive and specific RNA in situ hybridization (RISH) assay using the RNAscope technology for the detection of mycobacteria rRNA in FFPE tissues and distinction of MTB and NTM.

Design: FFPE serial sections from 50 clinically diagnosed TB patients were collected from five hospitals in China. Samples were tested with AFS or using the RNAscope probes B-MTB-23s-rRNA-1-C1 and B-MTB-NTM-16srRNA-O1 targeting MTB only or both MTB and NTM, respectively, using a modified RNAscope protocol (Protocol I). A subset of the RISH positive samples were subsequently examined using an alternative protocol (Protocol II), which eliminates one pretreatment step. AFS and RISH slides were then analyzed for the presence of positively stained organisms. 

B-MTB-NTM- 16srRNA-O1 B-MTB-23s-rRNA-1- C1 1 - - - N/A N/A 2 - - - N/A N/A 3 - - - N/A N/A 4 - + + N/A N/A 5 - - - N/A N/A 6 + + + + + 7 + + + + + 8 - + + + + 9 - - - N/A N/A 10 + + + + + 11 + + - N/A N/A 12 + + + N/A N/A 13 + + - N/A N/A 14 - - - N/A N/A 15 - - - N/A N/A 16 - - - N/A N/A 17 - - - N/A N/A 18 - - - N/A N/A 19 - - - N/

We have developed a novel RISH method for the detection of mycobacteria in FFPE tissue. In comparison to AFS, the RISH methodology appears to be more sensitive, detecting 2 additional positive cases. In addition, the RISH method was able to identify 3 cases of probable NTM, a distinction of high clinical relevance owing to the different treatments required for MTB vs. NTM infections. Finally, the RISH signals were easier to visualize and locate compared to AFS. Overall, our results indicate that the RNAscope assay is a sensitive method to detect mycobacteria in FFPE tissues that allows for differentiation of MTB vs. NTM and is easy to interpret. Conclusions: In our cases, we showed that T. pallidum antibody specifically cross-reacts with intestinal spirochetes, and it is useful to confirm the diagnosis of HIS. We also found that there is no cross reactivity between RPR test and intestinal spirochetes infection. Further studies are needed to show if massive spirochetes invasion may affect the serologic results. 

The yield of AFB studies in a region of low endemicity is low for dermatology specimens, but when identified can dramatically impact therapy. Of the 3 TB cases identified, 2 were unexpected, including 1 patient with a negative PPD. NTMs cases were identified and treated, even when granulomas were absent. For cases with both AP and CP studies performed, histopathologic stains beyond H&E only added value for 1 patient thought to have leprosy. These data suggest the utilization of special stains can be reduced if microbiologic tests are performed unless there is a high clinical suspicion for AFB. The study is limited by the retrospective nature and small number of positive cases where multiple diagnostics were performed.

The outbreak largely affected homeless individuals with and without illicit drug use (34% and 15%) and those with a history of drug use only (13%). 20% had no risk factors and 13% lacked history. Mode of transmission was direct person-to-person contact; no common source of food, beverage or drugs was identified. Among male cases, 3.5% were identified as men who have sex with men (MSM), compared to reported 14-84% in other outbreaks. A public health emergency was declared and an education/vaccination campaign with distribution of hygiene kits, deployment of bathrooms and hand washing stations was conducted. The outbreak ended on 1/23/2018 and now provides an opportunity to re-familiarize pathologists with epidemiologic and histologic findings of HAV. These were more commonly seen in biliary dyskinesia (BD) patients compared to calculus cholecystitis. However, very recently Swanson et al performed molecular analysis targeting the internal transcribed spacer (ITS2) in the C. belli ribosomal gene in similar specimens. No amplification was found in the GB specimens as opposed to the positive Cytoisospora infected intestinal specimens from immunocompromised individuals. They suggested that these are epithelial inclusions comprising of cytoplasmic and nuclear material resulting from bile mediated cytolysis. In the current study, we are describing the ultra-structural details of Cystoisospora like inclusions in GB epithelium by electron microscopy.

Design: On review of 1850 consecutive cholecystectomy specimen from immunocompetent patients, we identified 25 cases of these epithelial structures. Two cases with diffuse involvement of the gallbladder epithelium were selected and the representative areas were cored out from the FFPE blocks and were submitted for EM analysis. Also, PCR based molecular analysis by using a primer mix for ITS1, ITS2, and the Universal 18S primer for protozoa was performed on the samples.

Electron microscopic analysis showed cytoplasmic condensations (Fig 1) leading to vacuolization and mimicking the micro and macrogamatocyte forms of Cystoisospora (Fig 2) . In contrast to Cystoisospora, they did not have flagella or other well organized structures. In some of the inclusions, the central part is denser giving the appearance of a nucleus of a microgametocyte. The epithelial cell nuclei were preserved and no degenerated nuclear material was seen in the inclusions. None of these cases showed amplified products on molecular analysis. Conclusions: EM and molecular analysis reveals that these intraepithelial structures are inclusions formed by condensation of the cytoplasm and not of protozoan origin. Reduced ejection fraction in BD patients may lead to prolonged exposure of GB mucosa to bile (cytolytic) and more frequent development of these inclusions. However, prospective studies evaluating the role of preanalytic variables (time to formalin exposure of the gallbladder mucosa, different technical parameters involved in specimen processing etc.) in the development of these inclusions are needed. Awareness of these rare findings is necessary to avoid over-diagnosis of Cystoisospora infection. Conclusions: PCT had a very good diagnostic sensitivity (84.1%) and NPV (77.6%) in ruling out infection. Despite the high sensitivity, the antibiotic use in the PCT<0.25ng/ml group was higher (p<0.05) than PCT≥0.25ng/ml group. Mean PCT levels were significantly higher for gram negative organisms than gram positives (p=0.04). Background: Diagnosis of Helicobacter pylori (HP) infection routinely occurs via identification of organisms during histopathological evaluation of stomach biopsies or resection specimens. In addition to H&E stains, various special stains or immunohistochemistry can be utilized to enhance sensitivity and specificity of detection, but these methods can be costly. Here, we explore the potential of digital image analysis (DIA) to aid in the identification of HP in H&E stained pathological tissue specimens.

We trained an artificial intelligence DIA algorithm based on convolutional neural networks (Nucleai-HP-Algorithm) using 35 H&E slides to identify Helicobacter pylori (HP) organisms. A test image set of 80 cases (including both gastric biopsies and surgical resection specimens) was utilized and included the following diagnoses: 1) normal gastric mucosa or chronic gastritis/reactive gastropathy, HP negative (n=24), 2) chronic gastritis, HP positive (n=48), and 3) HP difficult to determine (n=8). Two methods were used to evaluate HP: 1) whole slide (tissue biopsy) HP detection, or 2) within slide (within tissue biopsy) patch HP detection (1 patch = 22.5 um x 22.5 um) to assist in locating the HP within a slide.

The overall concordance between DIA and the reference pathologist was 91.7%. Slide level sensitivity is 97.9% and specificity is 79.9%. When the patch level is set at 80% sensitivity this leads to an average of 7 false positive areas (less than 0.01% of tissue surface area) for a gastric biopsy slide (where an area is defined as a group of patches with a distance up to 11.25um). Discrepancies include surgical specimens where there is a large amount of tissue or non-gastric tissue types.

The findings demonstrate the capability of DIA to successfully identify HP organisms in gastric tissue samples. Therefore, DIA may have a potential role to reduce time spent by pathologists on HP detection, reduce the need for use of ancillary testing (including IHC stains) or to be utilized in quality assurance/quality control measures. Future improvements of the algorithm can include training with larger data sets with more variety, which will improve performance. In addition, similar algorithms can identify signet ring cells in gastric samples. Background: There are many lesions capable of mimicking testicular or paratesticular neoplasms, occurring in around 6% to 30% of the cases. Possible causes include: vascular or inflammatory lesions, cysts and ectopic tissues. In the particular case of inflammatory lesions, which are represented by granulomatous disease, the main etiological agents are Mycobacterium tuberculosis, Brucella sp., Treponema pallidum, fungi and parasites.

We present a case of a 67-year-old male patient from a rural area in Brazil, with a hardened mass on the right testicle. Orchiectomy was performed and the gross specimen consisted on a testicle weighing 60 g with a homogeneous, whitish solid nodule measuring 4,0 x 3,0 x 2,3 cm. Histologic examination showed a chronic inflammatory process with suppurative granulomatous reaction. Ziehl-Nelseen stain for mycobacteria resulted negative, but periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stain revealed globose cells surrounded by multiple budding yeast cells, exhibiting the characteristic "steering wheel'' appearance of Paracoccidioides brasiliensis. There was no evidence of neoplastic lesions on the specimen.

Results: Figure 1 : Extensive granulomatous reaction in testicular interstitium -H&E 40x. Conclusions: Paracoccidioidomycosis is an underdiagnosed disease, yet paradoxically it is the most prevalent systemic mycosis in Latin America. A review of the literature seems to indicate that only rare reports of paracoccidioidomycosis in the testicular and urological regions have been described in Brazil, most of them indigenous. There seem to be no cases reported in Anglo-Saxon countries. Another important issue to be considered is the legal implications of an orchiectomy in an illness potentially treatable with only clinical management.

In conclusion, our data provides both demographic and clinical information and investigates possible risk factors associated with acquiring Blastomyces. In addition, our data elucidates how all detection modalities for such a life threatening infection are incomplete and can miss the diagnosis at a rate of 27% for anatomic pathology approach alone and 25% for microbiology cultures alone. Authors suggest that any of these methods of detection, especially in endemic areas and in individuals with the above-mentioned risk factors, should not be done as a single modality as there is a high possibility of misdiagnosis if any of these methods are used alone.Our animal data is in progress to compare with our human data and investigate the feasibility of suggesting the same methods of detection in animals with known symptoms to our veterinarian colleagues.

An Unexpected Differential Diagnosis for Testicular Tumor: Paracoccidiodomycosis Pillar Venzon 1 , Ariane Haagsma 2 , Ana Carolina Rodrigues 3 , I-Ching Lee 1 , Pietro Cantú 3 , Sara Kretzer 4 , Marta Vainchenker 5 , Daniella Vieira 6 , Desiree Lovera Castedo 1

Instituto de Anatomia Patológica

Comprehensive Urology/Michigan Healthcare Professionals

The 613 patients were classified by the urologist into the following cohorts based on clinical symptomatology; 582 cystitis, 28 prostatitis, and 2 interstitial cystitis. The cystitis group had a median age of 77 and a male to female ratio of 6:4. The most common presenting symptom was burning on urination in 37% of patients. There was 90.1% positive percentage agreement between the PCR and culture results, which significantly exceeded the non-inferiority threshold of 85% with p=0.03. 22% of cases had significant levels of organisms that were detected by PCR that were missed on traditional culture, and these results were confirmed by NGS in a large number of cases. 75 cases of NGS have been completed and show excellent confirmation of the PCR results: 3/3=100% of culture positive, PCR negative samples were shown to be negative with NGS; 10/12=83% of culture negative, PCR positive samples were shown to be positive with NGS.Conclusions: PCR based UTI analysis can detect significantly more organisms than traditional culture, and is significantly non-inferior in detecting the same organisms as traditional culture. Prospective randomized trials are currently underway that will be required to demonstrate a benefit to detecting and treating these additional organisms in patients. Background: The diagnosis of blastomycosis is challenging. The diagnosis may be confirmed by histologic examination, microbiology cultures or urine antigen detection. Misdiagnosis is relatively common and appears multifactorial. In this study we attempt to uncover common risk factors. We also aim to investigate diagnostic challenges including the most sensitive method of detection in order to avoid treatment delays and possible misdiagnosis.

Design: A retrospective study was performed evaluating all cases of blastomycosis diagnosed at the University of Vermont Medical Center over ten years (2007) (2008) (2009) (2010) (2011) (2012) (2013) (2014) (2015) (2016) (2017) . Data concerning surgical pathology, cytopathology, autopsy, bone marrow and culture reports were obtained for all positive blastomycosis cases. Age and county matched control groups, representing 3x the number of positive specimens, were obtained for comparison. 115 positive specimens, representing 57 patients with the average age of 51 years old, were identified.Results: Our demographic data shows that the there is a higher incidence in males versus females (60% vs 40% respectively). While 83% of patients with blastomycosis had a BMI over 28, just 26% of the control group had this BMI range. The highest concentration of cases is around the Lake Champlain area. All 115 specimens were reviewed to determine the concordance of pathology and culture results. In our positive anatomic pathology cases, 25% had a negative culture report (5% of anatomic pathology specimens were not cultured). Alternatively, 27% of cases with positive cultures, showed no Blastomyces in anatomic pathology specimens (13% of these cases did not have any anatomic pathology specimen).