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.

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.

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.

LigB subunit vaccine confers sterile immunity against challenge in the hamster model of leptospirosis.

Neglected tropical diseases, including zoonoses such as leptospirosis, have a major impact on rural and poor urban communities, particularly in developing countries. This has led to major investment in antipoverty vaccines that focus on diseases that influence public health and thereby productivity. While the true, global, impact of leptospirosis is unknown due to the lack of adequate laboratory diagnosis, the WHO estimates that incidence has doubled over the last 15 years to over 1 million cases that require hospitalization every year. Leptospirosis is caused by pathogenic Leptospira spp. and is spread through direct contact with infected animals, their urine or contaminated water and soil. Inactivated leptospirosis vaccines, or bacterins, are approved in only a handful of countries due to the lack of heterologous protection (there are > 250 pathogenic Leptospira serovars) and the serious side-effects associated with vaccination. Currently, research has focused on recombinant vaccines, a possible solution to these problems. However, due to a lack of standardised animal models, rigorous statistical analysis and poor reproducibility, this approach has met with limited success. We evaluated a subunit vaccine preparation, based on a conserved region of the leptospiral immunoglobulin-like B protein (LigB(131-645)) and aluminium hydroxide (AH), in the hamster model of leptospirosis. The vaccine conferred significant protection (80.0-100%, P < 0.05) against mortality in vaccinated animals in seven independent experiments. The efficacy of the LigB(131-645)/AH vaccine ranged from 87.5-100% and we observed sterile immunity (87.5-100%) among the vaccinated survivors. Significant levels of IgM and IgG were induced among vaccinated animals, although they did not correlate with immunity. A mixed IgG1/IgG2 subclass profile was associated with the subunit vaccine, compared to the predominant IgG2 profile seen in bacterin vaccinated hamsters. These findings suggest that LigB(131-645) is a vaccine candidate against leptospirosis with potential ramifications to public and veterinary health.

Evidence of leptospiral exposure in neotropical primates rescued from illegal trade and a Zoo in Bahia, Brazil / Indícios de exposição a leptospiras em primatas neotropicais resgatados do comércio ilegal e de um Zoológico da Bahia

Few studies have compared the seroprevalence of antileptospiral agglutinins with the demonstration of urinary shedding of leptospires or evidence of active infection in the bloodstreams of non-human primates. The study population consists of 58 animals, including d 42 monkeys from the Zoological Park of Salvador (Parque Zoobotânico Getúlio Vargas), Bahia, Brazil. The study also evaluated 16 primates (Cebus sp.) rescued from illegal trade that were housed in the Wildlife Rehabilitation Center of Salvador (CETAS), Bahia, Brazil. The seroprevalence of antileptospiral antibodies was low (2%) in the animals from the Zoo. A higher rate (31%) was observed among the animals that were rescued from illegal trade in the state of Bahia. Even if all the blood and urine samples were negative for leptospiral DNA fragments, the high frequency of serological evidence of exposure suggests a potential risk of leptospirosis transmission when keeping these animals as pets.(AU)

Poucos estudos compararam a soroprevalência de aglutininas antileptospira com a demonstração de excreção urinária de leptospiras ou evidência de infecção ativa em primatas não humanos. A população estudada consistiu em 58 animais, sendo 42 primatas do Parque Zoobotânico Getúlio Vargas, Bahia, Brasil. O estudo avaliou ainda 16 primatas (Cebus sp.) resgatados do tráfico ilegal e abrigados no Centro de Triagem de Animais Silvestres Chico Mendes, Salvador, Bahia, Brasil. A soroprevalência de anticorpos antileptospira foi baixa (2%) nos animais do Zoológico. Uma taxa mais elevada (31%) foi observada nos animais resgatados do tráfico ilegal. Mesmo que todas as amostras de sangue e urina tenham sido negativas para DNA de leptospiras, a alta frequência de evidência de exposição nos animais de origem selvagem indicam o risco potencial da adoção de primatas como animais de estimação.(AU)

O Novo Currículo e o Fim da Patologia / The New Curriculum and the End of Pathology

RESUMO A gradual adoção de novas diretrizes curriculares afetou dramaticamente a atuação do professor de Patologia no curso médico. O resultado prático das mudanças adotadas foi a redução do espaço do ensino da Patologia na graduação e a perda de espaço do professor médico patologista no curso médico. Como consequência, os novos médicos compreendem menos os mecanismos envolvidos nas doenças, e, pelo menos em algumas regiões do mundo, a perda de visibilidade da Patologia como especialidade médica resultou em falta de patologistas dedicados à carreira acadêmica e à prática diagnóstica. Nesta revisão, discutimos o cenário internacional e comentamos como a nova realidade atingiu, na prática, o ensino da Patologia em duas escolas médicas tradicionais do Brasil.

ABSTRACT The gradual adoption of new directives in medical undergraduate curricula has dramatically changed the role of the pathologist in medical education. The practical consequences of these changes have been a reduction of space dedicated to pathology and the role of the pathology professor in the medical curriculum. As a result, new doctors have less knowledge of the basic mechanisms of diseases and, at least in some parts of the world, a loss of visibility of the specialty has led to a dwindling number of potential new pathology residents and more vacancies in academic and surgical/diagnostic pathology. This review discusses the international scenario and comments on how the new curriculum has affected Pathology Education in two traditional medical schools in Brazil.

Frequency of the morphological criteria of prostate adenocarcinoma in 387 consecutive prostate needle biopsies: emphasis on the location and number of nucleoli / Frequência de critérios morfológicos de adenocarcinoma da próstata em 387 biópsias de agulha da próstata consecutivas: com ênfase na localização e no número de nucléolos

ABSTRACT Introduction and objectives: We evaluated the sensitivity and specificity of morphological criteria for the diagnosis of prostate adenocarcinoma in consecutive, prostate needle biopsies specimens with emphasis on the location and number of nucleoli. Methods: The morphological features of 387 consecutive prostate needle biopsies specimens, in 2013, were systematically examined and stratified according to the final diagnosis of benign, suspicious and malignant lesions. We also tested how well each criterion predicted the final diagnosis after the immunohistochemical evaluation for expression of the basal cell markers (p63 and high molecular weight cytokeratin) and racemase. Results: A prominent nucleoli is the most common feature of carcinoma; however it is also relatively common in benign cases. The frequencies of prominent central nucleoli in malignant, suspicious and benign cases were 99%, 89% and 27%, respectively. Marginated nucleoli (85%, 60% and 7%), double nucleoli (86%, 53% and 10%), and multiple nucleoli (47%, 14% and 2%) were less common in benign cases, with significant difference among the groups. From the 36 cases initially diagnosed as suspicious, the presence of marginated nucleoli and mitoses were associated with the final diagnosis of malignancy. Prominent central nucleoli were more associated with cases which the final diagnosis after immunohistochemistry was benign. Conclusion: The location and number of nucleoli may be valuable morphological markers to identify suspicious lesions, since these features are more specific for malignancy than nucleolar prominence. The presence of prominent nucleoli commonly leads to the initial diagnosis of suspicious lesion that, subsequently, will be resulted in benignity confirmed by immunohistochemistry.

RESUMO Introdução e objetivos: Avaliamos a sensibilidade e a especificidade de critérios morfológicos para diagnóstico de adenocarcinoma da próstata em biópsias de agulha da próstata, consecutivas, com ênfase na localização e no número de nucléolos. Métodos: A morfologia de 387 biópsias de agulha consecutivas do ano de 2013 foi sistematicamente examinada e estratificada como diagnóstico de benigno, lesão suspeita ou maligno. Também testamos como cada critério previu o diagnóstico final após avaliação imuno-histoquímica para expressão de marcadores de células basais (p63 e citoqueratina de alto peso) e racemase. Resultados: Um nucléolo proeminente foi o achado mais comum do carcinoma, mas também foi relativamente comum em casos benignos. As frequências de um nucléolo proeminente central em lesões malignas, suspeitas e benignas foi de 99%, 89% e 27%, respectivamente. Nucléolo marginado (85%, 60% e 7%), nucléolos duplos (86%, 53% e 10%) e nucléolos múltiplos (47%, 14% e 2%) foram menos comuns em casos benignos, com diferenças significativas entre os grupos. Dos 36 casos com diagnóstico inicial de suspeito, a presença de nucléolo marginado e mitoses foi associada ao diagnóstico final de malignidade. Um nucléolo proeminente central foi mais associado a casos cujo diagnóstico final após imuno-histoquímica foi benigno. Conclusão: A localização e o número de nucléolos pode ser um marcador morfológico valioso para identificar lesões suspeitas, uma vez que esses achados são mais específicos para malignidade do que a proeminência nucleolar. A presença de nucléolo proeminente comumente leva ao diagnóstico inicial de lesão suspeita que, posteriormente, terá a conclusão de benignidade confirmada pela imuno-histoquímica.