Experiência no ensino de patologia em tempos de pandemia / Experience in teaching pathology during the pandemic

Resumo: Introdução: A patologia é uma disciplina básica que exerce o link entre ciclos básicos e clínico-cirúrgicos. A partir do início de 2020, com a pandemia provocada pela síndrome respiratória aguda grave do coronavírus 2 (severe acute respiratory syndrome coronavirus 2 - Sars-CoV-2) e a implantação do ensino remoto emergencial (ERE), o curso de patologia em nossa instituição sofreu alterações e adaptações. O presente trabalho tem como objetivos relatar as atividades desenvolvidas em nossa faculdade para o ensino da patologia geral, dentro do contexto do ERE, e discutir como parte dessas estratégias poderá ser incorporada após o término da pandemia. Relato de experiência: Para o ensino das alterações macroscópicas, utilizamos discussões com peças cirúrgicas filmadas, enquanto as alterações microscópicas foram desenvolvidas no chamado "Projeto Atlas". Discussão: Nosso projeto foi bem dinâmico com grande aceitação por parte dos alunos que tiveram atitudes mais proativas, principalmente em relação ao estudo dos casos de microscopia. As estratégias também se prestaram muito bem como forma de avaliação formativa. Conclusão: Muitas das estratégias que têm sido desenvolvidas por diferentes grupos de professores neste momento da pandemia trouxeram alternativas muito interessantes que devem ser incorporadas ao curso mesmo quando ele voltar a ser presencial. Peças filmadas contemplaram o estudo da macroscopia durante esse período de restrições e podem ser incorporadas à rotina presencial, intercalando com as técnicas utilizadas anteriormente. Já o "Projeto Atlas" foi uma experiência positiva, ressaltando o papel do aluno como protagonista do seu processo de ensino/aprendizagem e o trabalho em pequenos grupos como pontos principais.

Abstract: Introduction: Pathology is a basic discipline that acts as a link between basic and clinical-surgical cycles. Since the beginning of 2020, with the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SarsCoV-2) and the implementation of emergency remote education (ERE), the pathology course in our institution has undergone changes and adaptations. This paper aims to report the activities developed in our college for the teaching of general pathology, within the context of ERE and discuss how part of these strategies may be incorporated after the end of the pandemic. Experience report: For teaching macroscopic changes we used discussions with filmed surgical specimens while microscopic changes were developed in the so-called "Atlas Project". Discussion: Our project was very dynamic and widely accepted by students with a more proactive attitudes, especially regarding the study of microscopic cases. The strategies also lent themselves very well as a formative form of evaluation. Conclusion: Many of the strategies that have been developed by different groups of teachers during this pandemic have brought very interesting alternatives that should be incorporated into the course even when face-to-face classes are resumed. The filmed pieces include the study of macroscopy during this period of restrictions and can be incorporated into the classroom routine, interspersed with the techniques used previously. The Atlas Project was a positive experience, highlighting the role of the student as the protagonist of his teaching/learning process and work in small groups as main points.

NEUROENDOCRINE TUMOR IN A CHILD WITH COMMON VARIABLE IMMUNODEFICIENCY.

OBJECTIVE: To report a case of a child with primary immunodeficiency who at eight years developed digestive symptoms, culminating with the diagnosis of a neuroendocrine tumor at ten years of age. CASE DESCRIPTION: One-year-old boy began to present recurrent pneumonias in different pulmonary lobes. At four years of age, an immunological investigation showed a decrease in IgG and IgA serum levels. After the exclusion of other causes of hypogammaglobinemia, he was diagnosed with a Common Variable Immunodeficiency and started to receive monthly replacement of human immunoglobulin. The patient evolved well, but at 8 years of age began with epigastrium pain and, at 10 years, chronic persistent diarrhea and weight loss. After investigation, a neuroendocrine tumor was diagnosed, which had a rapid progressive evolution to death. COMMENTS: Medical literature has highlighted the presence of gastric tumors in adults with Common Variable Immunodeficiency, emphasizing the importance of early diagnosis and the investigation of digestive neoplasms. Up to now there is no description of neuroendocrine tumor in pediatric patients with Common Variable Immunodeficiency. We believe that the hypothesis of digestive neoplasm is important in children with Common Variable Immunodeficiency and with clinical manifestations similar to the case described here in the attempt to improve the prognosis for pediatric patients.

Neuroendocrine tumor in a child with common variable immunodeficiency / Tumor neuroendócrino em criança com imunodeficiência comum variável

ABSTRACT Objective: To report a case of a child with primary immunodeficiency who at eight years developed digestive symptoms, culminating with the diagnosis of a neuroendocrine tumor at ten years of age. Case description: One-year-old boy began to present recurrent pneumonias in different pulmonary lobes. At four years of age, an immunological investigation showed a decrease in IgG and IgA serum levels. After the exclusion of other causes of hypogammaglobinemia, he was diagnosed with a Common Variable Immunodeficiency and started to receive monthly replacement of human immunoglobulin. The patient evolved well, but at 8 years of age began with epigastrium pain and, at 10 years, chronic persistent diarrhea and weight loss. After investigation, a neuroendocrine tumor was diagnosed, which had a rapid progressive evolution to death. Comments: Medical literature has highlighted the presence of gastric tumors in adults with Common Variable Immunodeficiency, emphasizing the importance of early diagnosis and the investigation of digestive neoplasms. Up to now there is no description of neuroendocrine tumor in pediatric patients with Common Variable Immunodeficiency. We believe that the hypothesis of digestive neoplasm is important in children with Common Variable Immunodeficiency and with clinical manifestations similar to the case described here in the attempt to improve the prognosis for pediatric patients.

RESUMO Objetivo: Relatar um caso de criança portadora de imunodeficiência primária que, aos oito anos, desenvolveu sintomas digestivos, culminando com o diagnóstico de tumor neuroendócrino aos dez anos de idade. Descrição do caso: Menino, com um ano de idade, começou a apresentar pneumonias de repetição em diferentes lobos pulmonares. Aos quatro anos, a investigação imunológica mostrou diminuição dos níveis séricos de IgG e IgA. Após exclusão de outras causas de hipogamaglobulinemia, teve diagnóstico de imunodeficiência comum variável, passando a receber reposição mensal de imunoglobulina humana. Evoluiu bem, porém, aos oito anos, começou com epigastralgia e, aos dez anos, diarreia crônica persistente e perda de peso. O quadro culminou com o diagnóstico de tumor neuroendócrino intestinal, de rápida progressão, com óbito do paciente. Comentários: A literatura tem chamado a atenção para tumores gástricos em adultos com imunodeficiência comum variável, alertando para a importância do diagnóstico precoce e da pesquisa de neoplasias digestivas. Até o momento, não há descrição de tumor neuroendócrino em pacientes pediátricos portadores de imunodeficiência comum variável. Acredita-se ser importante a hipótese de neoplasia digestiva diante de crianças com imunodeficiência comum variável e com manifestações clínicas semelhantes ao caso descrito, na tentativa de melhorar o prognóstico para pacientes pediátricos.

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

OBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.

Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness.

Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation.

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness.

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

OBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.

Neuroendocrine tumors: An epidemiological study of 250 cases at a tertiary hospital.

OBJECTIVE: To compare the frequency of neuroendocrine tumors in our service with that reported in the literature considering age, gender, location, degree of differentiation and increase in incidence by means of a retrospective study. METHOD: Search of variables from a database of neuroendocrine tumor cases diagnosed at the Department of Pathological Sciences, Hospital da Santa Casa de São Paulo over the past 10 years, relating them to epidemiological data such as gender, age, distribution across organs, most-used immunohistochemical markers and presence or absence of either lymph node or distant metastases. RESULTS: In all, 250 cases were reviewed, 133 involving females, predominantly in the 61-70 age range. The lung was the most frequent site, followed by the stomach. CD56, synaptophysin and chromogranin were the immunohistochemical markers used most often and to a lesser extent Ki67, a marker of cell proliferation that indicates a higher or lower degree of histological malignancy. Metastases, either in lymph nodes and/or distant sites, were found in 44 cases (17.6%). CONCLUSION: The results were largely consistent with those in the literature, including age group, gender and location. Most metastases originated from high-grade tumors, with high Ki67 levels and greater impairment of the liver. However, only 36.4% of the cases had Ki67 index. Reevaluation of the Ki67 proliferative index using image analysis in doubtful cases will allow for a correlation between progression and prognosis.

Neuroendocrine tumors: An epidemiological study of 250 cases at a tertiary hospital / Tumores neuroendócrinos: estudo epidemiológico de 250 casos em um hospital terciário

Summary Objective: To compare the frequency of neuroendocrine tumors in our service with that reported in the literature considering age, gender, location, degree of differentiation and increase in incidence by means of a retrospective study. Method: Search of variables from a database of neuroendocrine tumor cases diagnosed at the Department of Pathological Sciences, Hospital da Santa Casa de São Paulo over the past 10 years, relating them to epidemiological data such as gender, age, distribution across organs, most-used immunohistochemical markers and presence or absence of either lymph node or distant metastases. Results: In all, 250 cases were reviewed, 133 involving females, predominantly in the 61-70 age range. The lung was the most frequent site, followed by the stomach. CD56, synaptophysin and chromogranin were the immunohistochemical markers used most often and to a lesser extent Ki67, a marker of cell proliferation that indicates a higher or lower degree of histological malignancy. Metastases, either in lymph nodes and/or distant sites, were found in 44 cases (17.6%). Conclusion: The results were largely consistent with those in the literature, including age group, gender and location. Most metastases originated from high-grade tumors, with high Ki67 levels and greater impairment of the liver. However, only 36.4% of the cases had Ki67 index. Reevaluation of the Ki67 proliferative index using image analysis in doubtful cases will allow for a correlation between progression and prognosis.

Resumo Objetivo: Comparar a frequência de tumores neuroendócrinos em nosso serviço com a literatura em relação idade, sexo, localização, grau de diferenciação e aumento da incidência por meio de um estudo retrospectivo. Método: Levantamento em banco de dados de casos de tumores neuroendócrinos diagnosticados no Serviço de Anatomia Patológica do Hospital da Santa Casa de São Paulo nos últimos 10 anos, relacionando com os dados epidemiológicos, como sexo, idade, distribuição pelos diversos órgãos, marcadores imuno-histoquímicos mais utilizados e presença ou não de metástase em linfonodos ou a distância. Resultados: Foram revistos 250 casos, 133 femininos, com faixa etária predominante entre 61 e 70 anos. O pulmão foi o local com maior frequência, seguido do estômago. Os marcadores imuno-histoquímicos mais utilizados foram CD56, sinaptofisina e cromogranina, às vezes complementados pelo Ki67, que permite avaliar o grau de proliferação celular, indicativo de maior ou menor grau de malignidade histológica. Metástases em linfonodos e/ou a distância foram constatadas em 44 casos (17,6%). Conclusão: Os resultados foram em grande parte concordantes com os dados da literatura, como idade, sexo e localização. A maioria das metástases se originou de neoplasias de alto grau, com alto índice do Ki67, com maior comprometimento do fígado. No entanto, o índice proliferativo do Ki67 foi feito em apenas 36,4% dos casos. A reavaliação dos índices proliferativos do Ki67 por meio de análise de imagem, de casos duvidosos, permitirão relacionar com a evolução e o prognóstico dos pacientes.

Traqueobronquite aguda causada por Aspergillus: relato de caso e achados de imagem / Acute tracheobronchitis caused by Aspergillus: case report and imaging findings

Traqueobronquite aguda é uma forma rara da aspergilose invasiva e geralmente ocorre em pacientes com imunodepressão grave. Relatamos o caso de um paciente no pós-transplante de medula óssea com a manifestação desta doença, dando ênfase aos achados tomográficos encontrados.

Acute tracheobronchitis is a rare manifestation of invasive aspergillosis, generally occurring in severely immunocompromised patients. The authors report the case of a patient presenting with this condition after bone-marrow transplantation, with emphasis on tomographic findings.

Acute tracheobronchitis caused by Aspergillus: case report and imaging findings.

Acute tracheobronchitis is a rare manifestation of invasive aspergillosis, generally occurring in severely immunocompromised patients. The authors report the case of a patient presenting with this condition after bone-marrow transplantation, with emphasis on tomographic findings.

Traqueobronquite aguda é uma forma rara da aspergilose invasiva e geralmente ocorre em pacientes com imunodepressão grave. Relatamos o caso de um paciente no pós-transplante de medula óssea com a manifestação desta doença, dando ênfase aos achados tomográficos encontrados.

Cardiac angiosarcoma: an unexpected diagnosis.

Cardiac angiosarcoma is a rare entity. The incidence through autopsy findings ranges between 0.001% and 0.03%. The disease usually presents with non-specific symptoms, although asymptomatic cases are frequent; therefore, diagnosis is unexpected and consequently delayed. The authors report the case of a middle-aged man with a recent onset cough and dyspnea. He sought medical care several times without receiving a definite diagnosis until a plain chest radiography was taken showing a mediastinal enlargement, which was the reason why he was hospitalized for clinical investigation. During the diagnostic workup, an echodopplercardiogram and a thoracic computed tomography were performed, showing a heterogeneous soft-tissue mass infiltrating the pericardium and the anterior atrial wall. Multiple and scattered pulmonary nodules were also present. A pulmonary nodule was biopsied, which revealed an angiosarcoma. The clinical features added to the radiological and histological findings permitted the diagnosis of right atrial angiosarcoma. The authors highlight the unexpected pattern in the presentation of cardiac tumors.

Immunopathological aspects of schistosomiasis-associated pulmonary arterial hypertension.

OBJECTIVES: Pulmonary hypertension is a lethal complication of chronic hepatosplenic schistosomiasis. Little is known of the underlying (immuno-)histopathological characteristics of lung vasculopathy. METHODS: We characterized vasculopathy and inflammation in lung tissue of 10 patients with Schistosomiasis-associated PH (SCH-PH) in comparison to 22 idiopathic pulmonary arterial hypertension (IPAH) patients and 10 normal controls. SCH-PH cases were younger than controls. RESULTS: Plexiform lesions and/or angiomatoid lesions were found in 10/10 SCH-PH, and 19/22 IPAH patients (χ² p = 0.22). Lung granulomas with Schistosoma eggs were found in 2/10 of SCH-PH cases. PAH cases had increased peri-arterial density of CD3+ T cells, chymase+ and tryptase+ mast cells when compared to controls (p ≤ 0.047). SCH-PH showed increased density of CD4+ cells when compared to controls (p = 0.025), paralleled by an increased density of dendritic CD83+ cells when compared to both controls and IPAH patients (p ≤ 0.022). CONCLUSION: Both SCH-PH and IPAH feature plexogenic arteriopathy and increased periarterial T cell and mast cell density. SCH-PH and IPAH differ only with respect to the density of dendritic CD83+ cells. These findings imply ongoing antigenic stimulation in SCH-PH, yet a pattern of pulmonary vasculopathy similar to IPAH, suggestive of a final common pathway in their pathogenesis of PAH.

Minimally invasive adenocarcinoma of the lung in a young patient treated for osteosarcoma.

Although children with osteosarcoma have a higher incidence of a 2nd malignancy than the general population, its development in the lung is rare. The few reported cases belong to examples of carcinomas. Here we present the case of a 13-year-old boy with a primary pulmonary adenocarcinoma diagnosed 3 years after the osteosarcoma diagnosis and present a review of the literature.

Mucosa-associated lymphoid tissue lymphoma of the trachea: case report.

CONTEXT: Mucosa-associated lymphoid tissue (MALT) lymphomas are most commonly found in the stomach, lungs, orbital soft tissue, salivary glands and thyroid. Involvement of the trachea is extremely rare. CASE REPORT: This report describes a rare case of MALT lymphoma of the trachea in a 71-year-old woman who presented with a one-year history of coughing, dyspnea, hoarseness and weight loss. There was an infiltrative lesion in the mid-trachea. The anatomopathological diagnosis was only made from the fifth endoscopic biopsy attempt. Immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisone (R-COP) induced complete remission of the symptoms and endoscopic lesion. CONCLUSIONS: MALT lymphoma of the trachea is extremely rare and indolent disease. It has to be considered in the differential diagnosis of airway lesions. It is crucial to obtain an anatomopathological diagnosis from a specialized pathologist. Immunochemotherapy with R-COP induced complete remission of the disease.

Mucosa-associated lymphoid tissue lymphoma of the trachea: case report / Linfoma do tecido linfoide associado à mucosa de traqueia: relato de caso

CONTEXT: Mucosa-associated lymphoid tissue (MALT) lymphomas are most commonly found in the stomach, lungs, orbital soft tissue, salivary glands and thyroid. Involvement of the trachea is extremely rare. CASE REPORT: This report describes a rare case of MALT lymphoma of the trachea in a 71-year-old woman who presented with a one-year history of coughing, dyspnea, hoarseness and weight loss. There was an infiltrative lesion in the mid-trachea. The anatomopathological diagnosis was only made from the fifth endoscopic biopsy attempt. Immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisone (R-COP) induced complete remission of the symptoms and endoscopic lesion. CONCLUSIONS: MALT lymphoma of the trachea is extremely rare and indolent disease. It has to be considered in the differential diagnosis of airway lesions. It is crucial to obtain an anatomopathological diagnosis from a specialized pathologist. Immunochemotherapy with R-COP induced complete remission of the disease.

CONTEXTO: Linfomas de tecido linfoide associado à mucosa (TLAM) são mais comumente encontrados no estômago, pulmões, órbita, glandulas salivares e tireoide. O envolvimento da traqueia é extremamente raro. RELATO DE CASO: Relato de caso raro de linfoma TLAM de traqueia, em mulher de 71 anos com tosse, dispneia, rouquidão e emagrecimento há um ano. Detectou-se lesão infiltrativa na porção média da traquéia. O diagnóstico anatomopatológico só foi obtido na biópsia do quinto procedimento endoscópico. A imunoquimioterapia R-COP (rituximabe, ciclofosfamida, vincristina e prednisona) induziu remissão completa dos sintomas e da lesão endoscópica. CONCLUSÕES: Linfoma TLAM de traqueia é uma doença indolente e extremamente rara, que deve ser considerada no diagnóstico diferencial das lesões de vias aéreas. O diagnóstico anatomopatológico por um patologista experimentado é fundamental. Imunoquimioterapia com R-COP levou à remissão completa da doença.