Application of the "quaternity" hybrid digital teaching method in the standardized residency training of clinical pathology / 中华医学教育探索杂志

Based on the limitations of certain conditions in the traditional clinical pathology teaching, this paper puts forward the "quaternity" hybrid digital teaching reform practice of clinical medicine, imaging, anatomy and pathology content. This teaching method can optimize the teaching process and improve the teaching efficiency. The specific advantages of this teaching method are as follows: the digital materials of different modules of clinical practice, imaging, anatomy and pathology are integrated to make the teaching content more perfect; it is helpful to improve the cognition of resident doctors on the pathological characteristics and the overall characteristics of the disease, and promote their thinking ability of clinicopathological integration; the combination of hybrid digital teaching and various teaching methods, including clinical pathology discussion, makes teaching more free and is conducive to classroom learning and self-learning. This paper discussed the construction and application of the "quaternity " hybrid digital teaching mode, and provided new ideas and methods for clinical pathology teaching and talent training.

Endometrioid adenocarcinoma with proliferated stromal cells, hyalinization and cord-like formations: A case report / 北京大学学报(医学版)

Corded and hyalinized endometrioid carcinoma (CHEC) is a morphologic variant of endo-metrioid adenocarcinoma. The tumor exhibits a biphasic appearance with areas of traditional low-grade adenocarcinoma merging directly with areas of diffuse growth composed of epithelioid or spindled tumor cells forming cords, small clusters, or dispersed single cells. It is crucial to distinguish CHEC from its morphological mimics, such as malignant mixed mullerian tumor (MMMT), because CHECs are usually low stage, and are associated with a good post-hysterectomy prognosis in most cases while the latter portends a poor prognosis. The patient reported in this article was a 54-year-old woman who presented with postmenopausal vaginal bleeding for 2 months. The ultrasound image showed a thickened uneven echo endometrium of approximately 12.2 mm and a detectable blood flow signal. Magnetic resonance imaging revealed an abnormal endometrial signal, considered endometrial carcinoma (Stage Ⅰ B). On hysterectomy specimen, there was an exophytic mass in the uterine cavity with myometrium infiltrating. Microscopically, most component of the tumor was well to moderately differentiated endometrioid carcinoma. Some oval and spindle stromal cells proliferated on the superficial surface of the tumor with a bundle or sheet like growth pattern. In the endometrial curettage specimen, the proliferation of these stromal cells was more obvious, and some of the surrounding stroma was hyalinized and chondromyxoid, which made the stromal cells form a cord-like arrangement. Immunostains were done and both the endometrioid carcinoma and the proliferating stroma cells showed loss of expression of DNA mismatch repair protein MLH1/PMS2 and wild-type p53 protein. Molecular testing demonstrated that this patient had a microsatellite unstable (MSI) endometrial carcinoma. The patient was followed up for 6 months, and there was no recurrence. We diagnosed this case as CHEC, a variant of endometrioid carcinoma, although this case did not show specific β-catenin nuclear expression that was reported in previous researches. The striking low-grade biphasic appearance without TP53 mutation confirmed by immunohistochemistry and molecular testing supported the diagnosis of CHEC. This special morphology, which is usually distributed in the superficial part of the tumor, may result in differences between curettage and surgical specimens. Recent studies have documented an aggressive clinical course in a significant proportion of cases. More cases are needed to establish the clinical behaviors, pathologic features, and molecular profiles of CHECs. Recognition of the relevant characteristics is the prerequisite for pathologists to make correct diagnoses and acquire comprehensive interpretation.

Solid placental transmogrification of the lung: A case report and literature review / 北京大学学报(医学版)

Placental transmogrification of the lung (PTL) is a very rare benign lung lesion. There are only about 40 cases reported in the literature. The imaging and histological features of PTL cases in the publication are various, most of which are cystic and a few of which are solid. Being extremely rare, the solid PTL is unknown to major pathologists and surgeons. We reported a case of solid PTL in the anterior mediastinum. The patient was a 52-year-old male with no history of smoking and without symptoms. During physical examination, chest CT revealed a circular low-density lesion with a maximum diameter of 2.9 cm beside the spine in the posterior basal segment of the left lower lobe of the lung. The wedge resection was performed by video-assisted thoracoscopy. Grossly, a round nodule was located underneath the visceral pleura. It was about 3.0 cm×3.0 cm×1.6 cm and the cut surface was grey-red, soft and spongy. Microscopically, the nodule was constituted of papillare, which resembled placental villi at low magnification. The axis of papillae was edema, in which some mild round cells with clear cytoplasm and CD10 positive staining aggregated and transitioned to immature adipocytes and amorphous pink materials deposited with a few of inflammatory cells infiltration. The surface of papillae was covered with disconti-nuous alveolar epithelium. Combined with the typical morphology and immunohistochemical characteristics of CD10 positive, the diagnosis was PTL. The patient was followed up for 1 year without recurrence and discomfort. So far, the pathogenesis of PTL is unclear. The major hypotheses include hamartoma, variant of emphysema and clonal hyperplasia of stromal cells. Based on the study of our case and publication, we speculate that the hyperplasia of stromal cells located in the alveolar septa might be the first step to form the solid PTL. With the progression of the disease, a typical unilateral cystic nodule develops as a result of secondary cystic degeneration due to the occlusive valve effect. Surgery is the only option for diagnosis and treatment of PTL. The clinician should make an individualized operation plan according to the clinical manifestations, location and scope of the lesion, and preserve the surrounding normal lung tissue as much as possible while completely removing the lesion. There is a favorable prognosis.

Clinicopathological features of Helicobacter pylori-negative early gastric cancer / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer.@*METHODS@#The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore.@*RESULTS@#The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H+/K+ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp.@*CONCLUSION@#Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.

Mucinous tubular and spindle cell carcinoma of kidney: Clinicopathology and prognosis / 北京大学学报(医学版)

OBJECTIVE@#To investigate and summarize the clinicopathological features, immunophenotype, differential diagnosis and prognosis analysis of mucinous tubular and spindle cell carcinoma (MTSCC).@*METHODS@#The data of thirteen cases of MTSCC were retrospectively analyzed, the clinical and pathological characteristics and immunohistochemical expression were summarized, and fluorescence in situ hybridization was detected.@*RESULTS@#Among the thirteen patients, four were males and nine females, with a male-to-female ratio of 1 ∶2.25. The average age was 57.1 years, ranging from 39 to 78 years. The maximum diameter of the tumor was 2-12 cm. All cases had no symptoms, and were accidentally discovered, 3 cases underwent partial renal resection, 10 cases underwent radical renal resection, 9 cases were located in the left kidney, and 4 cases were located in the right kidney. Most of the cases showed the classical morphological changes, with 11 cases of nuclear grading [World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system] being G2 and 2 cases being G3. There were 6 cases of stage PT1a, 3 cases of PT1b, 2 cases of PT2a, and 1 case of PT2b and 1 case of PT3a. The positive rates of immunohistochemical staining were: vimentin, AE1/AE3, α-methylacyl-CoA racemase (αMACR) and cytokeratin (CK) 8/18, 100% (13/13); CK7, 92.3% (12/13); epithelial membrane antigen (EMA), 92.3% (12/13); CK20, 46.2% (6/13); CD10, 30.8% (4/13); synaptophysin (Syn), 7.7% (1/13); chromogranin A (CgA), CD57, WT1 and Ki-67, 0 (0/13), and fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and 17 were observed in any of the cases. The follow-up period was 6 months to 7 years and 6 months, 2 cases died after lung metastasis (one with ISUP/WHO grade G3, one with necrosis), and the remaining 11 cases had no recurrence and metastasis.@*CONCLUSION@#MTSCC is a unique type of low-grade malignancy kidney tumor, occurs predominantly in females, widely distributed in age, the current treatment method is surgical resection, and cases with necrosis and high-grade morphology are prone to recurrence and metastasis, although most cases have a good prognosis, but they still need close follow-up after surgery.

Clinicopathological characteristics and prognosis of non-Hodgkin lymphoma in oral and maxillofacial regions: An analysis of 369 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics and factors influencing the prognosis of non-Hodgkin lymphoma (NHL) in oral and maxillofacial regions.@*METHODS@#Clinicopathological data of 369 patients with oral and maxillofacial NHL initially diagnosed in Peking University Hospital of Stomatology from 2008 to 2020 were collected and analyzed retrospectively.@*RESULTS@#There were 180 males and 189 females. The median age of the patients was 56 years (3 months to 92 years), and the median duration was three months. Clinically, 283 cases manifested as mass, 38 cases as ulcerative necrotizing lesions, and 48 cases as diffuse soft tissue swelling. The lesions of 90 cases located in face and neck (75 cases neck, 20.3%), 99 cases were of major salivary glands (79 cases parotid glands, 20.9%), 103 cases of oral cavity, 50 cases of maxillofacial bones, 20 cases of Waldeyer's ring, and 7 cases of infratemporal fossa. In the study, 247 of the 369 patients had cervical lymphadenopathy, only 40 cases had B symptoms, and 23 cases had the bulky disease. Of the 369 NHLs, 299 (81%) were B-cell NHL, and 70(19%) were T-cell NHL. Diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, and extranodal natural killer (NK)/T-cell lymphoma nasal type were the most common pathological subtypes. According to Ann Arbor staging, 87, 138, 106, and 38 cases were classified as staged Ⅰ, Ⅱ, Ⅲ, Ⅳ, respectively. The me-dian follow-up time was 48 months, 164 patients died during the follow-up period. The overall survival rates for one year, two years, and five years were 90.1%, 82.4%, and 59.9%, respectively, and the median survival was (86.00±7.98) months. Multivariate analysis showed that age (P < 0.001), Ann Arbor staging (P < 0.001), elevated lactate dehydrogenase (P=0.014), and pathological subtype (P=0.049) were the independent factors influencing the overall survival rate of NHL patients.@*CONCLUSION@#Oral and maxillofacial NHL has unique clinical characteristics and distribution patterns of pathological subtypes. Fewer patients had systemic symptoms. Neck and parotid glands were the most common sites invaded by NHL. Advanced age, Ann Arbor stage Ⅲ-Ⅳ, B symptoms, and T-cell NHL may predict a poor prognosis in oral and maxillofacial NHL patients.

Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, Brazil / Alterações morfológicas em leucócitos de pacientes com infecção aguda por SARS-CoV-2, Amazônia, Brasil

Introduction: The pandemic for the new coronavirus (SARS-CoV-2) brought many uncertainties about which laboratory parameters would be most suitable during the evolution of COVID 19. Objectives: Correlate the results of the blood count (BC), the neutrophil/lymphocyte ratio (N/LR), the C-reactive protein (CRP) and morphological findings of individuals diagnosed with SARS-CoV-2 infection through Polymerase Chain Reaction in Real Time (RT-PCR) in a private laboratory in Belém, Pará, from March to September 2020. Materials and Methods: Retrospective study with 30 individuals, of both sexes, any age and clinical complaint, of home or hospital origin who underwent BC, CRP and RT-PCR for COVID 19 until the 8th day of infection. Morphological changes were analyzed after selecting the slides for these patients. Results: Sample composed of 15 men and 15 women, aged between 7 and 92 years. Of these 12/30 individuals were at home and 18/30 were hospitalized. The main complaints were fever, malaise, diarrhea and respiratory distress. The statistical study showed a direct dependency relationship between increases in N/LR, CRP and the need for hospitalization (p = 0.0005). Morphological analysis showed hyposegmented neutrophils with toxic granulations, vacuolated monocytes, and reactive lymphocytes with basophilic cytoplasm. Conclusion: Our results associate intermediate and elevated levels of N/LR with increased CRP and disease severity, however, unrelated to the morphological findings in neutrophils, lymphocytes and monocytes that were common to all patients diagnosed up to the 8th day of infection (AU)

Introdução: A pandemia pelo novo coronavírus (SARS-CoV-2) trouxe muitas incertezas sobre quais parâmetros laboratoriais seriam mais adequados durante a evolução da COVID 19. Objetivos: Correlacionar os resultados do hemograma (HGM), da relação neutrófilos/linfócitos (R N/L), da proteína C reativa (PCR) e dos achados morfológicos de indivíduos diagnosticados com infecção por SARS-CoV-2 através de Reação em Cadeia da Polimerase em Tempo Real (RT-PCR) em um laboratório particular de Belém, Pará, no período de março a setembro de 2020. Materiais e Métodos: Estudo retrospectivo com 30 indivíduos, de ambos os sexos, qualquer idade e queixa clínica, de origem domiciliar ou hospitalar que realizaram HGM, PCR e RT-PCR para COVID 19 até o 8o dia de infecção. As alterações morfológicas foram analisadas após a seleção das lâminas desses pacientes. Resultados:Amostra composta por 15 homens e 15 mulheres, com idades entre 7 e 92 anos. Desses, 12/30 indivíduos estavam em domicílio e 18/30 internados. As principais queixas foram febre, mal-estar geral, diarreia e desconforto respiratório. O estudo estatístico mostrou a existência de relação de dependência direta entre os aumentos da R N/L, PCR e necessidade de internação (p=0,0005). A análise morfológica mostrou neutrófilos hipossegmentados com granulações tóxicas, monócitos vacuolizados e linfócitos reativos com citoplasma basofílico. Conclusão: Nossos resultados associam os níveis intermediários e elevados da R N/L com o aumento de PCR e a gravidade da doença, porém, sem relação com os achados morfológicos em neutrófilos, linfócitos e monócitos que foram comuns a todos os pacientes diagnosticados até o 8o dia de infecção

Hematologic parameters of captive Bothrops atrox (Squamata: viperidae)

The breeding of venomous snakes in captivity for research purposes and mainly as a source of pharmaceutical products highlights the need to determine hematological parameters for monitoring and ensuring a healthy breeding populationThe complete blood count is used to help diagnose alterations such as anemia, inflammatory diseases, parasitemia, hematopoietic disorders, hemostatic and toxicological changes, as well as bacterial and viral inclusions. Thus, the objective of this study was to define reference parameters for complete blood count in Bothrops atrox snakes. Blood samples were collected from 20 specimens of B. atrox from the Pentapharm do Brasil commercial breeding facility for laboratory examination. Mean values and standard deviation were: hematocrit 33.6 ± 5.47%, hemoglobin 10.81 ± 2.07g/dL, total number of erythrocytes 0.59 ± 0.1 x 106/mm3, leukocytes 11387.5 ± 3279.2/mm3 and thrombocytes 28175 ± 6320/mm3. No significant difference was observed between males and females and heterophils were the predominant leukocyte cell type.

Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, Brazil / Alterações morfológicas em leucócitos de pacientes com infecção aguda por SARS-CoV-2, Amazônia, Brasil

RESUMO: Introdução: A pandemia pelo novo coronavírus (SARS-CoV-2) trouxe muitas incertezas sobre quais parâmetros laboratoriais seriam mais adequados durante a evolução da COVID 19. Objetivos: Correlacionar os resultados do hemograma (HGM), da relação neutrófilos/linfócitos (R N/L), da proteína C reativa (PCR) e dos achados morfológicos de indivíduos diagnosticados com infecção por SARS-CoV-2 através de Reação em Cadeia da Polimerase em Tempo Real (RT-PCR) em um laboratório particular de Belém, Pará, no período de março a setembro de 2020. Materiais e Métodos: Estudo retrospectivo com 30 indivíduos, de ambos os sexos, qualquer idade e queixa clínica, de origem domiciliar ou hospitalar que realizaram HGM, PCR e RT-PCR para COVID 19 até o 8o dia de infecção. As alterações morfológicas foram analisadas após a seleção das lâminas desses pacientes. Resultados:Amostra composta por 15 homens e 15 mulheres, com idades entre 7 e 92 anos. Desses, 12/30 indivíduos estavam em domicílio e 18/30 internados. As principais queixas foram febre, mal-estar geral, diarreia e desconforto respiratório. O estudo estatístico mostrou a existência de relação de dependência direta entre os aumentos da R N/L, PCR e necessidade de internação (p=0,0005). A análise morfológica mostrou neutrófilos hipossegmentados com granulações tóxicas, monócitos vacuolizados e linfócitos reativos com citoplasma basofílico. Conclusão: Nossos resultados associam os níveis intermediários e elevados da R N/L com o aumento de PCR e a gravidade da doença, porém, sem relação com os achados morfológicos em neutrófilos, linfócitos e monócitos que foram comuns a todos os pacientes diagnosticados até o 8o dia de infecção. (AU)

ABSTRACT: Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, BrazilORIGINAL ARTICLEIntroduction: The pandemic for the new coronavirus (SARS-CoV-2) brought many uncertainties about which laboratory parameters would be most suitable during the evolution of COVID 19. Objectives: Correlate the results of the blood count (BC), the neutrophil/lymphocyte ratio (N/LR), the C-reactive protein (CRP) and morphological findings of individuals diagnosed with SARS-CoV-2 infection through Polymerase Chain Reaction in Real Time (RT-PCR) in a private laboratory in Belém, Pará, from March to September 2020. Materials and Methods: Retrospective study with 30 individuals, of both sexes, any age and clinical complaint, of home or hospital origin who underwent BC, CRP and RT-PCR for COVID 19 until the 8th day of infection. Morphological changes were analyzed after selecting the slides for these patients. Results: Sample composed of 15 men and 15 women, aged between 7 and 92 years. Of these 12/30 individuals were at home and 18/30 were hospitalized. The main complaints were fever, malaise, diarrhea and respiratory distress. The statistical study showed a direct dependency relationship between increases in N/LR, CRP and the need for hospitalization (p = 0.0005). Morphological analysis showed hyposegmented neutrophils with toxic granulations, vacuolated monocytes, and reactive lymphocytes with basophilic cytoplasm. Conclusion: Our results associate intermediate and elevated levels of N/LR with increased CRP and disease severity, however, unrelated to the morphological findings in neutrophils, lymphocytes and monocytes that were common to all patients diagnosed up to the 8th day of infection. (AU)

Seroprevalence and hematological abnormalities associated with Ehrlichia canis in dogs referred to a veterinary teaching hospital in central-western Brazil / Soroprevalência e alterações hematológicas associadas com Ehrlichia canis em cães encaminhados a um hospital veterinário-escola no centro-oeste do Brasil

Ticks are significant parasites of dogs in the tropics, where tick-borne pathogens are highly prevalent, especially in areas where tick control measures are frequently neglected. This study investigated the seroprevalence and hematological abnormalities associated with Ehrlichia canis in dogs referred to a veterinary teaching hospital in Central-western Brazil. Out of 264 dogs tested for anti-Ehrlichia canis antibodies by an indirect immunofluorescence assay (IFA), 59.1% (156/264) were positive. Seropositivity was significantly associated to anemia and thrombocytopenia, alone or in combination, and to leukopenia. Conversely, there were no differences in terms of seroprevalence according to sex, breed and age. This study demonstrated that dogs referred to a veterinary teaching hospital in Central-western Brazil are highly exposed to E. canis and that seropositive dogs are more likely to present hematological abnormalities, particularly anemia, thrombocytopenia and leukopenia. To our knowledge, this is the first study on detection of anti-E. canis antibodies by means of IFA among dogs in the state of Goiás. These findings highlighted the need for increasing awareness among dog owners regarding tick control measures in Central-western Brazil, ultimately to reduce the risk of exposure to E. canis and other tick-borne pathogens.

Carrapatos são importantes parasitos de cães nos trópicos, onde patógenos transmitidos por carrapatos são altamente prevalentes, especialmente em áreas onde as medidas de controle de carrapatos são frequentemente negligenciadas. O estudo investigou a soroprevalência e as anormalidades hematológicas associadas à Ehrlichia canis em cães encaminhados para um hospital veterinário-escola no Centro-oeste do Brasil. Dos 264 cães testados para anticorpos anti-Ehrlichia canis por meio da reação de imunofluorescência indireta (RIFI), 59.1% (156/264) foram positivos. A soropositividade foi associada significativamente à anemia e trombocitopenia, isoladamente ou em combinação, e à leucopenia. Por outro lado, não houve diferenças quanto à soroprevalência segundo sexo, raça e idade. Este estudo demonstrou que cães encaminhados a um hospital veterinário-escola na região Centro-oeste do Brasil são altamente expostos à E. canis, e que cães soropositivos têm maior probabilidade de apresentar alterações hematológicas, principalmente anemia, trombocitopenia e leucopenia. Para o nosso conhecimento, este é o primeiro estudo sobre a detecção de anticorpos anti-E. canis por meio da RIFI em cães do estado de Goiás. Essas descobertas destacam a necessidade de aumentar a conscientização entre os proprietários de cães em relação às medidas de controle do carrapato no Centro-oeste do Brasil, em última análise, para reduzir o risco de exposição ao E. canis e outros patógenos transmitidos por carrapatos.

Progress in pulmonary enteric adenocarcinoma / 中华肿瘤杂志

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.

Exploration and practice of specimen sampling teaching in standardized residency training of clinical pathology / 中华医学教育探索杂志

Pathological specimen sampling is not only the prerequisite of a good pathological diagnosis, but also the primary clinical skill that must be mastered by the standardized residency training trainees (resident trainees) in clinical pathology department. In view of the problems and difficulties encountered in the teaching of specimen sampling, through five years of exploration and attempt, this paper has gradually established a new model with five basic elements, including theory teaching, practice teaching, promoting teaching effect by examination, learning from senior students, and review teaching. The results of evaluation analysis and questionnaire survey show that the teaching mode can make the trainees master the methods of specimen sampling quickly and efficiently, learn and improve clinical skills in practice, and lay a solid foundation for the subsequent standardized training of histopathological diagnosis.

Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors / 中华内科杂志

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Clinicopathological Features of Intrathyroid Thymic Carcinoma / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical characteristics,diagnosis,treatment and prognosis of intrathyroid thymic carcinoma.Methods Clinical data of 7 patients with intrathyroid thymic carcinoma were retrospectively reviewed.Histological examination and immunohistochemical staining were performed on the surgically resected tumors.The infection of Epstein-Barr virus(EBV)was detected by EBER in situ hybridization.Results The 7 patients included 5 males and 2 females.The age ranged from 40 to 71 years,with a median of 54 years.The tumors were located in the thyroid gland,with the maximum diameter ranging from 2.2 cm to 6.0 cm and the average maximum diameter of(4.0±1.2)cm.All the patients underwent thyroid gland resection and local lymph node dissection.After operation,all the cases were treated with radiotherapy and five of them additionally received chemotherapy.Six patients were followed up for 10-163 months,all of whom were still alive,including 2 patients with recurrence in situ,1 patient with homolateral cervical lymph node metastasis and the rest with no recurrence or metastasis.CK-pan,P63,CD5 and CD117 were expressed in all the cases,while TTF-1,TG,CT and PAX8 were negative.One case of them expressed SYN and CgA.Ki-67 proliferation index ranged from 10% to 90%.EBER in situ hybridization showed negative results in all 7 cases.Conclusions Intrathyroid thymic carcinoma is a relatively low-grade malignant tumor.The combination of immunohistochemical CD5,CD117 and monoclonal PAX8 is helpful in the diagnosis and differential diagnosis of intrathyroid thymic carcinoma.EBV may not be involved in the development of intrathyroid thymic carcinoma.Thyroid gland resection plus central lymph node dissection is an important treatment measure for intrathyroid thymic carcinoma.For patients with regional lymph node metastasis and obvious peripheral tissue invasion,postoperative radiotherapy with/without chemotherapy can effectively delay the disease progression.

Uses and limits of the clinical laboratory in the COVID-19 pandemic: a didactic review

SUMMARY The world is currently experiencing an unprecedented pandemic of a new disease, the coronavirus disease (COVID-19), which has unusual clinical and immunological presentations. This is especially true regarding the choice and interpretation of laboratory test results. In this review, we have provided didactic information for physicians on the current concepts and practical guidance regarding COVID-19.

David Matto y su contribución a la patología clínica y psiquiatría en el Perú / David Matto and his contribution on clinical pathology and psychiatrics in Peru

RESUMEN El doctor David Matto Usandivaras realizó importantes contribuciones a la medicina peruana, en particular en las especialidades de Patología Clínica y Psiquiatría, hacia finales del siglo XIX e inicios del siglo XX, que coincidió con la corriente cientificista que comenzó a prevalecer paulatinamente en los años posteriores a la Guerra del Pacífico. No obstante, el trascurrir del tiempo difuminó tales aportes, por lo que el objetivo de este artículo es rescatarlos y situarlos en el lugar que merecen para memoria de todos los miembros de la comunidad médica nacional y en especial de los facultativos de ambas especialidades.

ABSTRACT Doctor David Matto-Usandivaras made important contributions in Peruvian medicine, particularly in clinical pathology and psychiatrics, at the end of 19th and at the beginning of the 20th century, coinciding with the scientificist thoughts that became prevalent in the years after the war between Peru and Chile. Nonetheless, time passed by and his contributions became forgotten, so the purpose of this paper is to rescue Dr. Matto-Usandivaras contributions and place them in a proper context so members of the Peruvian medical community - particularly pathologists and psychiatrists - may become more knowledgeable of his valuable work.

Panorama atual do ensino da Patologia Clínica/Medicina Laboratorial nas escolas médicas do Brasil / Current overview of the teaching of Clinical Pathology/Laboratory Medicine in medical schools in Brazil

Introdução: Os testes laboratoriais exercem papel fundamental no atendimento médico de uma maneira geral há muitos anos. Além disso, o gasto com exames laboratoriais representa menos de 3% do custo total em saúde, tornando a relação custo-benefício altamente favorável ao uso dessa ferramenta. A despeito dessa enorme importância, a educação médica em relação a testes laboratoriais no Brasil ainda é incerta não existindo dados concretos sobre o ensino da Patologia Clínca/Medicina Laboratorial até a data do estudo (2019). Objetivo: Pretende-se traçar um panorama atual do ensino da Patologia Clínica/Medicina Laboratorial na graduação das escolas médicas do Brasil, comparando com o ensino da Patologia Geral. Materiais e métodos: Foi realizada uma pesquisa de levantamento ou um inquérito de dados das matrizes curriculares das escolas médicas do Brasil, por meio do acesso ao seu portal eletrônico. A relação de todas as instituições de ensino médico foi obtida junto ao site do Ministério da Educação no ano de 2019. Resultados: No Brasil há um predomínio de escolas privadas sobre públicas, sendo método de ensino tradicional (59%) mais comum em relação ao Problem-Based Learning (39%). Somente 23% das escolas médicas do Brasil possuem a disciplina de Patologia Clínica/Medicina Laboratorial em suas matrizes curriculares. Em contrapartida, a Patologia Geral está presente em 57% das escolas. A região Centro-Oeste possui a menor prevalência (14,24%) quanto ao ensino de Patologia Clínica/Medicina Laboratorial, enquanto que a região Sudeste mostrou a maior prevalência (28,57%). Conclusão: Apenas 23% das escolas médicas no Brasil possuem o ensino da Patologia Clínica/Medicina Laboratorial em suas grades curriculares. (AU)

Introduction: Laboratory tests play, in general, a fundamental role in medical care for many years. In addition, the cost of laboratory tests represents less than 3% of the total spent on the health system, making the cost-benefit ratio highly favorable to its use. Despite this enormous importance, medical education regarding those tests in Brazil is still uncertain, with no concrete data about the teaching of Clinical Pathology/Laboratory Medicine found until the date of the study (2019). Objective: To draw a current overview of the teaching of Clinical Pathology/Laboratory Medicine in undergraduate medical schools in the country, comparing with the teaching of General Pathology. Materials and methods: A survey was conducted by a data collection from curricular matrices of medical schools in Brazil, by the access to their websites. The list of the medical education institutions was obtained by the website of the Ministério da Educação in 2019. Results: In Brazil there is a predominance of private over public schools, the traditional teaching method (59%) is more common in relation to Problem-Based Learning (39%). Only 23% of medical schools in Brazil have the subject of Clinical Pathology/Laboratory Medicine in their curriculum matrix. In contrast, General Pathology subject is present in 57% of the schools. The Midwest region has the lowest prevalence (14,24%) regarding the teaching of Clinical Pathology/Laboratory Medicine, while the Southeast region showed the highest prevalence (28,57%) .Conclusion: Only 23% of medical schools in Brazil have the teaching of Clinical Pathology/Laboratory Medicine in their curriculum.

Immunopathological mechanisms involved in SARS-CoV-2 infection / Mecanismos imunopatológicos envolvidos na infecção por SARS-CoV-2

ABSTRACT Introduction: Coronavirus disease 2019 (Covid-19) has become a global health emergency. Although many scientific advances have been achieved over the last few months, the knowledge about how the etiologic agent SARS-CoV-2 interacts with the host's immune system, regulating the pathogenesis and the outcome of the disease, is not yet fully understood. Objective: This is a narrative literature review to discuss the available evidence on modes of transmission and the main immunopathological mechanisms involved in SARS-CoV-2 infection. Material and method: A search in the indexed journals was carried out in the PubMed/MEDLINE database, during the period from January to May 2020. The following descriptors were used in the research: Covid-19, SARS-CoV-2, transmission, immunity, immunopathogenesis, and pathogenesis. Results and discussion: Transmission of SARS-CoV-2 occurs through contact with airway secretions from a symptomatic patient. However, scientific evidence encourages transmission by asymptomatic and/or oligosymptomatic patients. Immunopathological studies suggest that the hypercytokinaemia promotes lung tissue damage and, subsequently, organ and system involvement, leading to decompensation, organ dysfunction and death. Regarding the humoral response, the high titers of B lymphocytes and antibodies, traditionally, correlated with the protection of the host, may be associated with the severity of the disease by SARS-CoV-2. Conclusion: The host's immune response is determinant in the pathogenesis of Covid-19. However, further in vivo and/or in vitro studies are needed to elucidate the pathogenic mechanisms of SARS-CoV-2 and, thus, assist in the development of a vaccine and/or therapeutic target.

RESUMEN Introducción: La enfermedad por coronavirus 2019 (Covid-2019) se ha convertido en una emergencia sanitaria mundial. A pesar de los muchos avances científicos recientes, el conocimiento acerca de cómo el agente etiológico SARS-CoV-2 interactúa con el sistema inmunitario del huésped, regulando la patogénesis y el resultado de la enfermedad, todavía no está totalmente claro. Objetivo: Revisión de la literatura a fin de discutir la evidencia disponible sobre las formas de transmisión y los principales mecanismos inmunopatológicos involucrados en la infección por SARS-CoV-2. Material y métodos: Se realizó una búsqueda por periódicos indexados en la base de datos PubMed/MEDLINE, desde enero hasta mayo de 2020. Se han utilizado las siguientes palabras clave en la investigación: Covid-19, SARS-CoV-2, transmission, immunity, immunopathogenesis y pathogenesis. Resultados y discusión: La transmisión del SARS-CoV-2 ocurre por el contacto con secreciones de las vías respiratorias de un paciente sintomático. Sin embargo, evidencias científicas indican la transmisión por pacientes asintomáticos y/o oligosintomáticos. Estudios inmunopatológicos sugieren que la tormenta de citocinas causa lesión en pulmones y, posteriormente, daño en órganos y sistemas, que conduce a la descompensación, disfunción orgánica y muerte. Sobre la inmunidad humoral, los títulos elevados de linfocitos B y anticuerpos, tradicionalmente relacionados con la protección del huésped, pueden estar asociados a la gravedad de la enfermedad por SARS-CoV-2. Conclusión: La respuesta inmunológica del huésped es determinante para la patogénesis de la Covid-19. No obstante, se necesitan más estudios in vivo y/o in vitro para aclarar los mecanismos de patogenicidad del SARS-CoV-2 y, así, ayudar en el desarrollo de una vacuna y/u objetivo terapéutico.

RESUMO Introdução: A doença do coronavírus 2019 (Covid-19) tornou-se uma emergência de saúde mundial. Embora muitos avanços científicos tenham sido alcançados nos últimos meses, o conhecimento sobre como o agente etiológico SARS-CoV-2 interage com o sistema imunológico do hospedeiro, regulando a patogênese e o resultado da doença, ainda não está totalmente esclarecido. Objetivo: Revisão da literatura com o objetivo de discutir as evidências disponíveis sobre as formas de transmissão e os principais mecanismos imunopatológicos envolvidos na infecção pelo SARS-CoV-2. Material e método: Realizou-se uma busca de periódicos indexados na base de dados PubMed/MEDLINE, durante o período de janeiro a maio de 2020. Os seguintes descritores foram utilizados na pesquisa: Covid-19, SARS-CoV-2, transmission, immunity, immunnopathogenesis e pathogenesis. Resultados e discussão: A transmissão do SARS-CoV-2 ocorre pelo contato com secreções das vias aéreas de um paciente sintomático. No entanto, evidências científicas fomentam a transmissão por pacientes assintomáticos e/ou oligossintomáticos. Os estudos imunopatológicos sugerem que a hipercitocinemia promove lesão do tecido pulmonar e, posteriormente, comprometimento de órgãos e sistemas, levando a descompensação, disfunção orgânica e óbito. Sobre a resposta humoral, os altos títulos de linfócitos B e anticorpos, tradicionalmente correlacionados com a proteção do hospedeiro, podem estar associados à gravidade da doença pelo SARS-CoV-2. Conclusão: A resposta imunológica do hospedeiro é determinante na patogênese da Covid-19. No entanto, mais estudos in vivo e/ou in vitro são necessários para elucidar os mecanismos de patogenicidade do SARS-CoV-2 e, assim, auxiliar no desenvolvimento de uma vacina e/ou alvo terapêutico.

COVID-19: clinical and laboratory manifestations in novel coronavirus infection / COVID-19: manifestações clínicas e laboratoriais na infecção pelo novo coronavírus

ABSTRACT COVID-19 is a highly contagious disease caused by the coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2). In 2020, due to the outbreak, it was considered by the World Health Organization (WHO) as a pandemic. The infection caused by the novel coronavirus has high mortality in a small portion of the infected population, especially in elderly, immunosuppressed, diabetic, cardiac, and hypertensive individuals. Many infected are asymptomatic (and may be carriers) or present mild or moderate flu-like symptoms. The most severe clinical picture of COVID-19 is characterized by an inflammatory cytokine storm, with hematological changes and coagulation dysfunction, which can lead to tissue damage and death. Nonspecific laboratory biomarkers may be either increased or decreased as the course of the disease progresses and are often useful in predicting complications of the disease, such as the use of D-dimer and platelet/lymphocyte ratio. Specific laboratory diagnosis is based on the detection of viral ribonucleic acid (RNA) by real-time polymerase chain reaction (RT-PCR) of nasal and oropharyngeal swab samples; it is more effective when performed in the first days after symptom onset. Serological tests are useful in detecting the immune response, since both class M (IgM) and class G (IgG) immunoglobulin antibodies can be detected seven days after the onset of clinical symptoms, and may extend for more than 25 days, although not exempting the individual from remaining infectious, depending on their viral load and clinical presentation. The rational use of specific laboratory markers must respect the disease chronology, and the correct interpretation may provide subsidies for a better management of affected patients, as well as identifying asymptomatic carriers or those with mild symptoms.

RESUMEN La COVID-19 es una enfermedad altamente contagiosa causada por el coronavirus del síndrome respiratorio agudo grave (SARS-CoV-2). En 2002, a causa del brote, fue reconocida como una pandemia por la Organización Mundial de la Salud (OMS). La infección por el nuevo coronavirus provoca alta mortalidad en una pequeña parcela de la población infectada, especialmente en ancianos, pacientes inmunodeprimidos, diabéticos, cardiópatas e hipertensos. Muchos infectados son asintomáticos (y pueden ser portadores) o presentan síntomas leves a moderados, como en un estado gripal. El cuadro clínico de la COVID-19 en la forma más grave es caracterizado por una tormenta inflamatoria de citoquinas, con cambios hematológicos y de la coagulación que pueden llevar a daño tisular y muerte. Pruebas de laboratorio inespecíficas pueden presentar tasas más altas o bajas según el curso de la enfermedad, y muchas veces son útiles en la predicción de complicaciones, como el uso del dímero D y la ratio plaquetas/linfocitos. El diagnóstico de laboratorio específico se basa en la detección del ácido ribonucleico (ARN) viral por reacción en cadena de la polimerasa (PCR) en tiempo real de muestras de hisopado nasal y orofaríngeo; es más efectiva en los primeros días tras el inicio de los síntomas. Pruebas serológicas son útiles para detectar la respuesta inmune, pues tanto los anticuerpos de la inmunoglobulina M (IgM) como de la G (IgG) pueden se detectar siete días después del inicio de los síntomas clínicos, y pueden permanecer por más de 25 días, aunque no eximen al individuo de seguir infeccioso, dependiendo de su carga viral y presentación clínica. El uso racional de los marcadores de laboratorio específicos debe respetar la cronología de la enfermedad, y la interpretación correcta puede proporcionar recursos para un mejor manejo de los pacientes afectados, así como identificar portadores asintomáticos o con pocos síntomas.

RESUMO COVID-19 é uma doença altamente contagiosa provocada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Em 2020, devido ao surto, foi caracterizada pela Organização Mundial da Saúde (OMS) como pandemia. A infecção causada pelo novo coronavírus tem alta mortalidade em uma pequena parcela da população infectada, especialmente em indivíduos idosos, imunodeprimidos, diabéticos, cardiopatas e hipertensos. Muitos infectados são assintomáticos (e podem ser portadores) ou apresentam sintomas leves a moderados, semelhantes ao estado gripal. O quadro clínico da COVID-19 na forma mais severa é caracterizado por uma tempestade inflamatória de citocinas, com alterações hematológicas e da coagulação que podem levar ao dano tecidual e morte. Exames laboratoriais inespecíficos podem apresentar-se mais elevados ou diminuídos conforme o curso da doença, e muitas vezes são úteis na predição de complicações, como o uso do D-dímero e a razão plaqueta/linfócitos. O diagnóstico laboratorial específico se baseia na detecção do ácido ribonucleico (RNA) viral por reação em cadeia da polimerase em tempo real (RT-PCR) de amostras de suabe nasal e orofaríngeo; é mais efetivo nos primeiros dias após o início dos sintomas. Testes sorológicos são úteis na detecção da resposta imune, pois tanto os anticorpos da imunoglobulina da classe M (IgM) quanto da classe G (IgG) podem ser detectados após sete dias do início dos sintomas clínicos, podendo se estender por mais de 25 dias, embora não isente o indivíduo de continuar infectante, dependendo de sua carga viral e apresentação clínica. O uso racional dos marcadores laboratoriais específicos deve respeitar a cronologia da doença, e a interpretação correta pode fornecer subsídios para um melhor manejo dos pacientes acometidos, bem como identificar portadores assintomáticos ou com pouco sintomas.

Medical Residency Training in Clinical Pathology/ Laboratory Medicine at the Paulista School of Medicine, Federal University of São Paulo / Residência médica em Patologia Clínica/Medicina Laboratorial na Escola Paulista de Medicina da Universidade Federal de São Paulo

ABSTRACT Teaching and learning in medicine has its own characteristics, requiring from their actors, in addition to intellectual skills, great dedication and personal commitment. The object of study, learning and practice is a person, punctually placed in the position of a patient, that is, someone who must be attended to at the exact moment of his need, making the attendance and the consequent learning opportunity to occur in unconventional moments. This characteristic led, since the beginning of the creation of medical schools, the more dedicate teachers and students to remain at the places of care almost full time, including at night, generating the concept that some of them "lived" in the Hospital, becoming identified as residents.

RESUMEN La enseñanza y el aprendizaje de medicina poseen características propias, exigiendo de sus actores, además de las capacidades intelectuales, gran dedicación y compromiso personal. El objeto de estudio, aprendizaje y práctica es una persona, puntualmente colocada en la posición de paciente, es decir, alguien que debe ser atendido en el momento exacto de su necesidad, haciendo que la atención y la consiguiente oportunidad de aprendizaje ocurran en momentos no convencionales. Esa característica hizo que, desde la creación de las escuelas médicas, profesores y alumnos más dedicados se quedaran en los puntos de atención casi a tiempo completo, incluso en horarios nocturnos, generando el concepto de que algunos de ellos vivían en el hospital, pasando a ser identificados como residentes.

RESUMO O ensino e o aprendizado da medicina possuem características próprias, exigindo dos seus atores, além das competências intelectuais, muita dedicação e empenho pessoal. O objeto de estudo, aprendizado e prática é uma pessoa, pontualmente colocada na posição de paciente, ou seja, alguém que deve ser atendido no momento exato de sua necessidade, fazendo com que o atendimento e a consequente oportunidade de aprendizado ocorram em momentos não convencionais. Essa característica fez com que, desde o princípio da criação das escolas médicas, professores e alunos mais dedicados permanecessem nos locais de atendimento quase em tempo integral, inclusive em horários noturnos, gerando o conceito de que alguns deles "moravam" no Hospital, passando a serem identificados como residentes.