Analysis of false positive PI-RADS 4 lesions: experience from a single nonacademic center using cognitive fusion.

BACKGROUND: We evaluated pathological findings in targeted biopsies of PI-RADS4 and PI-RADS5 lesions, and clinical data that could predict those patients with benign findings. MATERIALS AND METHODS: A retrospective study was conducted to summarize the experience from a single nonacademic center using cognitive fusion and a 1.5 or 3.0 Tesla scanner. RESULTS: We found a false positive rate of 29 and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Diverse histologic patterns were observed among target biopsies. At multivariate analysis, size ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The small number of false PI-RADS5 lesions precluded further analyses. CONCLUSION: Benign findings are common in PI-RADS4 lesions and most of them do not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict a higher probability of false positive results in patients with PI-RADS 4 lesions.

Clear Cell Papillary Renal Cell Tumors: A Study of 42 Tumors with Emphasis on the Fibrous Capsule, Cystic Component, and GATA3 Immunohistochemistry.

Clear cell papillary renal cell tumor is a common and sometimes underdiagnosed renal cell neoplasm. Its proper recognition is important because its diagnosis implies a remarkably high probability of indolent behavior. This study aimed to evaluate the frequency of a fibrous capsule, a cystic component, and a GATA3 expression in clear cell papillary renal cell tumors. We assessed 419 renal cell neoplasms from three institutions located in northeastern Brazil and identified 42 clear cell papillary renal cell tumors (from 39 patients), which were the fourth most common renal cell neoplasm. These tumors commonly exhibited fibrous capsules (all showed complete or partial capsules) and cystic component (93%). Eighteen out of 42 tumors (43%) showed some expression of GATA3, and weak and focal staining was common among the positive tumors. Clear cell papillary renal cell tumor must always be included in the differential diagnosis of predominantly cystic renal cell neoplasms. As GATA3 is inconsistently expressed in clear cell papillary renal cell tumors, it is not useful in this diagnosis.

The many faces of endometriosis.

Endometriosis is a common disease; however, unusual findings may cause diagnostic difficulties. We present herein three cases illustrating different morphological appearances of endometriosis: 1) endometriosis with atypical hyperplasia associated with bilateral ovarian carcinoma (mixed clear cell/endometrioid in the left ovary and endometrioid in the right ovary); 2) deep infiltrating endometriosis with intravascular spread, polypoid configuration in peritoneal surfaces, and involvement of a lymph node; and 3) decidualized endometriosis with prominent myxoid/mucinous change and multivacuolated (pseudoxanthoma) cells. Awareness of uncommon morphological manifestations of endometriosis is important to avoid improper consideration of malignancy.

Penile Lichen Sclerosus and "Nevus Elasticus".

The association between penile lichen sclerosus and striking accumulation of elastic fibers in deep dermis has been described in rare reports, mostly in vulvar lesions. We describe one case of severe balanopreputial adhesions related to lichen sclerosus and this form of elastosis, with no concomitant neoplasia. Aggregates of elastic fibers were seen in deep dermis and in blood vessels. The lesion mirrors nevus elasticus and nevus elasticus vascularis - a well described cutaneous lesion with no known association with lichen sclerosus.

The many faces of endometriosis

ABSTRACT Endometriosis is a common disease; however, unusual findings may cause diagnostic difficulties. We present herein three cases illustrating different morphological appearances of endometriosis: 1) endometriosis with atypical hyperplasia associated with bilateral ovarian carcinoma (mixed clear cell/endometrioid in the left ovary and endometrioid in the right ovary); 2) deep infiltrating endometriosis with intravascular spread, polypoid configuration in peritoneal surfaces, and involvement of a lymph node; and 3) decidualized endometriosis with prominent myxoid/mucinous change and multivacuolated (pseudoxanthoma) cells. Awareness of uncommon morphological manifestations of endometriosis is important to avoid improper consideration of malignancy.

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables.

Immunotherapy targeting the PD-1-PD-L1 axis yielded good results in treating different immunologically ''hot'' tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11-41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41-50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases.

Real life data of MRI-targeted biopsy - experience from a single nonacademic centre using cognitive fusion and 1.5 tesla scanning.

OBJECTIVES: To date, it is unknown whether systematic biopsies can be safely omitted in patients with unsuspicious MRI findings or if systematic biopsies should be required when targeting focal lesions (PI-RADS 3-5). METHODS: A series of 366 patients (249 without a previous biopsy) were examined in a 1.5 Tesla MRI scanner. All patients were submitted to systematic biopsies (12-14 regions) with additional targeted biopsies (by cognitive fusion) of focal PI-RADS lesions (PI-RADS 3-5). RESULTS: In our series, patients with PI-RADS 1/2 findings had rates of adenocarcinoma of any grade, >GG1 and GG4/5 of 34%, 14% and 3%, respectively. The use of MRI prior to biopsy in our series increased the detection of clinically significant prostate cancer (CSPCa) in 28% of patients with focal lesions, and focal lesions were present in 293/366 (80%) of all patients. For CSPCa (>GG1), targeted biopsies improved the diagnosis in 28% of patients, while systematic biopsies resulted in an additional 19% of cancer cases in the series. CONCLUSION: Systematic biopsies should still be considered in patients with PI-RADS 1/2 findings. Our findings also suggest a stronger benefit of the combined strategy of targeted and systematic biopsies than the findings of previous studies concerning the detection of CSPCa in biopsy-naïve patients.

Seroprevalence and risk factors associated with equineleptospirosis in the metropolitan region of Salvador and Recôncavo Baiano region, Bahia state (NE Brazil).

Equine leptospirosis, although usually asymptomatic, has been associated with recurrent uveitis, abortion, and other systemic signs, constituting a major economic loss in the equine agribusiness sector. The occurrence of anti-Leptospira spp. agglutinins were investigated in 1200 serum samples of horses from 27 municipalities of the Recôncavo Baiano region, Bahia state (NE Brazil), besides the risk factors related to animals and their cattle farms. The microscopic agglutination test (MAT) was performed using 13 serogroups of Leptospira spp. as antigens. From 1200 analyzed equines, 97 (8%) were considered as positive, which obtained titer equal to or higher than 200. In 22 (78.6%) from the 28 properties, at least one animal was detected as seropositive. The most prevalent serogroup in animals, raised in stables, was the Australis (serovar Bratislava) 67%; in mounted police animals was the Sejroe (serovar Wolffi and Hardjobovis) 50%; and equestrian animals was the Australis (serovar Bratislava) 25% and Icterohaemorrhagiae (serovar Copenhageni) 25%. Equine leptospirosis is present in most cattle farms of the region studied. The risk factors of major importance regarded the semi-extensive livestock farming, the land topography of the cattle farm, the contact with animals in neighboring properties, and cohabitation with goats.

Ductal carcinoma in situ of the breast: correlation of architectural, cytological, IHC findings and recurrence analysis / Carcinoma ductal in situ da mama: correlação dos achados arquiteturais, citológicos e IHQ e análise de recorrência

ABSTRACT Objective: This study evaluated the histopathological features of ductal carcinoma in situ (DCIS), including cytological grade, architectural pattern and immunohistochemistry (IHC) in pure DCIS and DCIS associated with invasive carcinoma of no special type (ICNST). Methods: We evaluated a series of 232 cases of pure DCIS and DCIS associated with ICNST from a total of 399 breast carcinomas from a population consisting by women diagnosed with breast cancer and submitted to breast surgery from 2011 to 2015. Results: DCIS presented a mixed architectural pattern in most cases (56%); the solid subtype was the most common morphology (30%). High-grade DCIS was identified in 84/221 cases (38%), and comedonecrosis was present in 106/221 cases (48%). High-grade was more common in the solid subtype (61/155 cases, 39%, p < 0.001). Tumor size was greater in the presence of comedonecrosis than in the absence (mean 27 vs 20 mm, p = 0.009). Estrogen receptor (ER) was positive in 81% of cases with a cribriform pattern (p = 0.013). Greater locoregional recurrence was found in the comedonecrosis (15%) and micropapillary (19%) subtypes in DCIS associated with ICNST. Conclusion: We observed a greater relationship of ER with the low nuclear grade, while Ki-67 was related to the high-grade. DCIS presented a higher nuclear grade compared to ICNST. The less common pure pattern was the micropapillary, and the most common, the solid. Comedonecrosis was more frequent in the solid pattern. Our results showed that high-grade was more common in the solid and comedo subtype, and low-grade was more frequent in the cribriform.

RESUMEN Objetivo: Este estudio evaluó las características del carcinoma ductal in situ (CDIS), incluyendo grado citológico, patrón arquitectural y inmunohistoquímica en CDIS puro y asociado a carcinoma invasivo tipo no especial (CI-TNE). Métodos: Evaluamos una serie de 232 casos de CDIS puro o asociado a carcinoma mamario invasivo procedentes de una población de mujeres diagnosticadas con cáncer de mama y sometidas a cirugía mamaria, entre 2011 y 2015. Resultados: El CDIS presentó un patrón arquitectural mixto en la mayoría de los casos (56%); el subtipo sólido fue la morfología más común (30%). El CDIS de alto grado fue identificado en 84/221 casos (38%), y comedonecrosis estaba presente en 106/221 casos (48%). El alto grado fue más común en el subtipo sólido (61/155 casos, 39%; p < 0.001). El tamaño del tumor fue más grande en presencia de comedonecrosis de lo que en su ausencia (promedio 27 vs. 20 mm; p = 0.009). El receptor de estrógeno (RE) fue positivo en el 81% de los casos con patrón cribiforme (p = 0.013). Se encontró mayor recidiva locorregional en los subtipos comedonecrosis (15%) y micropapilar (19%) en el CDIS asociado al CI-TNE. Conclusión: Observamos mayor relación del RE con bajo grado nuclear, mientras Ki-67 se relacionó con alto grado. El CDIS presentó grado nuclear más alto de lo que el CI-TNE. El patrón puro menos común fue el micropapilar, y el más común, el sólido. La comedonecrosis fue más frecuente en el patrón sólido. Nuestros resultados mostraron que el alto grado fue más común en los subtipos sólido y comedonecrosis, y el bajo grado, más frecuente en el cribiforme.

RESUMO Objetivo: Este estudo avaliou as características histopatológicas do carcinoma ductal in situ (CDIS), incluindo grau citológico, padrão arquitetural e imuno-histoquímica (IHQ) em CDIS puro e associado a carcinoma invasivo tipo não especial (CI-TNE). Métodos: Avaliamos uma série de 232 casos de CDIS puro ou associado ao carcinoma mamário invasivo de um total de 399 carcinomas mamários provenientes de uma população constituída por mulheres diagnosticadas com câncer de mama e submetidas à cirurgia mamária, entre 2011 e 2015. Resultados: O CDIS apresentou um padrão arquitetural misto na maioria dos casos (56%); o subtipo sólido foi a morfologia mais comum (30%). O CDIS de alto grau foi identificado em 84/221 casos (38%), e comedonecrose estava presente em 106/221 casos (48%). O alto grau foi mais comum no subtipo sólido (61/155 casos, 39%; p < 0,001). O tamanho do tumor foi maior na presença de comedonecrose do que na ausência (média 27 vs. 20 mm; p = 0,009). O receptor de estrogênio (RE) foi positivo em 81% dos casos com padrão cribriforme (p = 0,013). Maior recorrência locorregional foi encontrada nos subtipos comedonecrose (15%) e micropapilar (19%) no CDIS associado ao CI-TNE. Conclusão: Observamos uma maior relação do RE com o baixo grau nuclear, enquanto o Ki-67 relacionou-se com o alto grau. O CDIS apresentou mais alto grau nuclear em comparação com o CI-TNE. O padrão puro menos comum foi o micropapilar, e o mais comum, o sólido. A comedonecrose foi mais frequente no padrão sólido. Nossos resultados mostraram que o alto grau foi mais comum nos subtipos sólido e comedonecrose, e o baixo grau, mais frequente no cribriforme.

Erratum: Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation.

This corrects the article on p. 406 in vol. 10, PMID: 29949837.

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation.

PURPOSE: The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract. METHODS: Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis. RESULTS: Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs. CONCLUSIONS: Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.

Prognostic pathological factors in radical cystectomy after neoadjuvant chemotherapy.

AIMS: We undertook a systematic evaluation of the prognostic value of numerous histological factors in 165 radical cystectomies (RCs) of patients with invasive urothelial carcinoma (UC) who underwent surgery after neoadjuvant chemotherapy (NAC). METHODS AND RESULTS: Tumour regression grade (TRG) and therapy-related stromal and epithelial changes were also recorded. Locally advanced disease (≥pT2 and/or pN+) was present in 64% of patients, 22% had no evidence of residual carcinoma (pT0 + pN0), and 28% had no evidence of residual muscle-invasive carcinoma (≤pT1 + N0). TRG1, TRG2 and TRG3 were found in 32%, 15% and 50% of patients, respectively. Histological variants of UC were reported in 25% of cases. The most common therapy-related stromal change was fibroblastic reaction (78%), and the most common epithelial change in residual UC was smudgy and poorly preserved chromatin (28%). Prominent stromal and epithelial changes were noted in 41% and 5% of RCs, respectively. Progression was found in 45% of patients, and cancer-related deaths occurred in 30%. Multivariate analysis showed that the only independent prognostic parameters for progression were T stage, N stage, lymphovascular invasion, and margin status. Similarly, only T stage, N stage and margin status correlated with cancer-related deaths. Neither TRG nor any of the stromal-related or epithelial-related variables correlated with outcome. CONCLUSIONS: We confirm that the traditional and routinely reported histological parameters in RC post-NAC remain the most powerful prognosticators of disease course. The significance of TRG in the bladder remains unconfirmed.

The Gleason pattern 4 in radical prostatectomy specimens in current practice - Quantification, morphology and concordance with biopsy.

PURPOSE: The upgrading of a prostate acinar adenocarcinoma grade group 1 (GG1) between needle biopsy and prostatectomy is common. The extent of high-grade tumor and cribriform morphology are currently suggested as prognostic factors. METHODS: We reviewed 159 prostatectomy specimens from a private laboratory and an academic/public institution in Salvador, Bahia. RESULTS: Tumors signed as GG1 at biopsy were upgraded in 59% of all cases. These tumors showed a low frequency of non-focal extraprostatic extension (one case, 3%), extensive positive surgical margins (two cases, 6%) and seminal vesicle invasion (one case, 3%). Among GG2 and GG3 tumors at prostatectomy, the percentage of Gleason pattern 4 (Gp4) involving the gland at ≤1%, 2-5% and >5% was associated with extensive extraprostatic extension (9%, 8% and 42%, respectively) and seminal vesicle invasion (1%, 10% and 31%, respectively). The volume of Gp4 of ≤1ml, >1 to 2ml and >2ml was associated with extensive extraprostatic extension (8%, 26% and 38%, respectively), seminal vesicle invasion (2%, 21% and 33%, respectively) and non-focal positive surgical margins (12%, 26% and 29%, respectively). Some GG2 tumors (~20%) indeed showed at least one measurement of Gp4 higher than one quarter of GG3 carcinomas. Cribriform morphology showed no significant associations for other adverse pathologic prognostic factors. CONCLUSION: Upgrading from GG1 to GG2 is associated with a very low frequency of morphologic features associated with poor prognosis. Routine quantification of Gp4 is feasible in radical prostatectomy products and seems to better stratify tumors regarding the association with other morphologic parameters of prognostic importance.

Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases.

AIMS: To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC. METHODS AND RESULTS: We identified 28 tumours from multiple institutions. They typically showed two cell populations-larger cells with eosinophilic cytoplasm and higher-grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5-100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39-86 years). The median tumour size was 20 mm (range 9-65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low-grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt-Hogg-Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α-methylacyl-CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20; CD10 and 34ßE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow-up was available for 23 patients (median 24 months, range 1-244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes). CONCLUSIONS: Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal.