Histological observations on Montenegro's reaction in man

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections.Foi realizado o estudo histológico do material obtido nas biópsias do local de inoculação do antígeno para teste de Montenegro (T.M.) nos seguintes grupos de indivíduos: I) Seis pacientes com leishmaniose cutânea comprovados parasitologicamente, com Montenegro positivo; II) Cinco indivíduos normais, não residentes em zona endêmica, com Montenegro negativo; III) Nove soldados participantes de ensaios clínicos com vacina anti-LTA - MAYRINK e cols. 1979 e que tiveram o TM positivo 35 dias após vacinação. IV) Um último grupo constituído de quatro soldados, também participantes de ensaio clínico com a mesma vacina acima, dois vacinados que não mostraram TM positivo 35 dias após vacinação e dois que receberam placebo. As biópsias foram realizadas 48 hs após a inoculação do antígeno. O material foi fixado em formol à 10% (pH 7.2). Histologicamente, excetivando o grupo II (controle negativo), os grupos I-I1I-IV mostraram diferenças quantitativas no infiltrado mononuclear. Os quadros histológicos de cada grupo são descritos e discutidos

Histological observations on Montenegro's reaction in man

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections

Ocronose exógena induzida por hidroquinona: relato de quatro casos Exogenous ochronosis hydroquinone induced: a report of four cases

A ocronose exógena é uma dermatose, aparentemente pouco frequente, caracterizada por hiperpigmentação negro-azulada fuliginosa, localizada na região onde foi aplicado o agente causador. Pode ser causada por uso de medicamentos sistêmicos, os antimaláricos e de uso tópico, como fenol, resorcinol, benzeno, ácido pícrico e a hidroquinona - que é um composto fenólico, com propriedade despigmentante, muito utilizado em formulações dermatológicas para o tratamento de melasma e outras hiperpigmentações. A fisiopatogenia deste processo ainda não está esclarecida e as abordagens terapêuticas são insatisfatórias. Relatam-se quatro casos de pacientes do sexo feminino que, após uso de preparados contendo hidroquinona, desenvolveram hiperpigmentação acentuada na face, caracterizadas no exame dermatológico e histopatológico como ocronose. Enfatiza-se a possibilidade de casos de ocronose exógena estarem sendo diagnosticados erroneamente, como falha de tratamento de melasma, e também para os riscos do uso indiscriminado de formulações, contendo hidroquinona, muitas vezes, sem acompanhamento médico.<br>Exogenous ochronosis is an infrequent dermatosis characterized as a dark blue hyperpigmentation localized where the causing agent was applied. It may be caused by the use of systemic medication such as antimalarials and by the use of topic substances such as phenol, resorcinol, benzene, or hydroquinone, which is a fenolic compound with depigmentation action, largely used in the treatment of melasma and other hyperpigmentation. The physiopathology of this process is not well clear up to this moment, and the therapeutic measures are not satisfactory either. Here we present four cases of female patients that developed hyperpigmentation on their faces after the use of hydroquinone containing compounds, characterized clinically and histological as ochronosi. We emphasize the possibility of exogenous ochronosis cases being misdiagnosed as a melasma treatment failure. We also emphasize the risks of the indiscriminated use of hydroquinone containing compounds, used, in many instances, without medical prescription

Caso para diagnóstico Case for diagnosis

Paciente do sexo feminino, 18 anos, apresentando única placa eritemato-descamativa, bem delimitada, na região abdominal com evolução de 1 ano e sem uso anterior de medicação. O histopatológico demonstrou infiltrado linfocítico com atipias acometendo principalmente derme superficial com epidermotrifismo e discreta espongiose. E a imunofenotipagem demonstrou predomínio de células CD3-positivo, confirmando o diagnóstico de Micose Fungóide.<br>An 18-year old female patient presented with a single, erythematous, desquamative plaque. The clearly outlined lesion was situated in the abdominal region. The patient reported that it had been present for the past year and that she had used no previous medication. Histopathology showed lymphocytic infiltration with atypia, principally affecting the superficial dermis with epidermotropism and mild spongiosis. Immunophenotyping revealed a predominance of CD3-positive cells, confirming the diagnosis of mycosis fungoides

Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer

Background: Both clinical and genomic data independently predict survival and treatment response in early-stage HER2-positive breast cancer. Here we present the development and validation of a new HER2DX risk score, and a new HER2DX pathological complete response (pCR) score, both based on a 27-gene expression plus clinical feature-based classifier. Methods: HER2DX is a supervised learning algorithm incorporating tumour size, nodal staging, and 4 gene expression signatures tracking immune infiltration, tumour cell proliferation, luminal differentiation, and the expression of the HER2 amplicon, into a single score. 434 HER2-positive tumours from the Short-HER trial were used to train a prognostic risk model; 268 cases from an independent cohort were used to verify the accuracy of the HER2DX risk score. In addition, 116 cases treated with neoadjuvant anti-HER2-based chemotherapy were used to train a predictive model of pathological complete response (pCR); two independent cohorts of 91 and 67 cases were used to verify the accuracy of the HER2DX pCR likelihood score. Five publicly available independent datasets with &gt;1,000 patients with early-stage HER2-positive disease were also analysed. Findings: In Short-HER, HER2DX variables were associated with good risk outcomes (i.e., immune, and luminal) and poor risk outcomes (i.e., proliferation, and tumour and nodal staging). In an independent cohort, continuous HER2DX risk score was significantly associated with disease-free survival (DFS) (p=0·002); the 5-year DFS in the low-risk group was 97·4% (94·4-100·0%). For the neoadjuvant pCR predictor training cohort, HER2DX variables were associated with pCR (i.e., immune, proliferation and HER2 amplicon) and non-pCR (i.e., luminal, and tumour and nodal staging). In both independent test set cohorts, continuous HER2DX pCR likelihood score was significantly associated with pCR (p&lt;0·0001). A weak negative correlation was found between the HER2DX risk score versus the pCR score (correlation coefficient -0·19). Interpretation: The two HER2DX tests provide accurate estimates of the risk of recurrence, and the likelihood to achieve a pCR, in early-stage HER2-positive breast cancer. Funding: This study received funding from Reveal Genomics, IDIBAPS and the University of Padova

Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer

Background: Both clinical and genomic data independently predict survival and treatment response in early-stage HER2-positive breast cancer. Here we present the development and validation of a new HER2DX risk score, and a new HER2DX pathological complete response (pCR) score, both based on a 27-gene expression plus clinical feature-based classifier. Methods: HER2DX is a supervised learning algorithm incorporating tumour size, nodal staging, and 4 gene expression signatures tracking immune infiltration, tumour cell proliferation, luminal differentiation, and the expression of the HER2 amplicon, into a single score. 434 HER2-positive tumours from the Short-HER trial were used to train a prognostic risk model; 268 cases from an independent cohort were used to verify the accuracy of the HER2DX risk score. In addition, 116 cases treated with neoadjuvant anti-HER2-based chemotherapy were used to train a predictive model of pathological complete response (pCR); two independent cohorts of 91 and 67 cases were used to verify the accuracy of the HER2DX pCR likelihood score. Five publicly available independent datasets with >1,000 patients with early-stage HER2-positive disease were also analysed. Findings: In Short-HER, HER2DX variables were associated with good risk outcomes (i.e., immune, and luminal) and poor risk outcomes (i.e., proliferation, and tumour and nodal staging). In an independent cohort, continuous HER2DX risk score was significantly associated with disease-free survival (DFS) (p=0·002); the 5-year DFS in the low-risk group was 97·4% (94·4-100·0%). For the neoadjuvant pCR predictor training cohort, HER2DX variables were associated with pCR (i.e., immune, proliferation and HER2 amplicon) and non-pCR (i.e., luminal, and tumour and nodal staging). In both independent test set cohorts, continuous HER2DX pCR likelihood score was significantly associated with pCR (p<0·0001). A weak negative correlation was found between the HER2DX risk score versus the pCR score (correlation coefficient -0·19). Interpretation: The two HER2DX tests provide accurate estimates of the risk of recurrence, and the likelihood to achieve a pCR, in early-stage HER2-positive breast cancer. Funding: This study received funding from Reveal Genomics, IDIBAPS and the University of Padova