INTRODUCTION

Pulmonary lymphomatoid granulomatosis (PLG) is a rare lymphoproliferative disease associated with Epstein-Barr virus (EBV) infection. It commonly affects adults aged 30–50 years. The clinical manifestations are usually non-specific, occasionally presenting with pulmonary nodular lesions[1,2]. PLG is rarely observed in children. Herein, we present a case of a child diagnosed with PLG following a lung biopsy. This report aims to improve the clinical understanding of PLG in children.

Complete blood cell count showed normal total and differential white blood cell counts;, decreased hemoglobin level (5 g/dL), normal mean corpuscular volume (94.3 fL), mean corpuscular hemoglobin (28.4 pg) values, and increased reticulocyte count (4.98%). The platelet count and C-reactive protein levels were normal. The direct and indirect antiglobulin tests and isopropanol tests were negative. The serum glucose-6-phosphate dehydrogenase, folic acid, and vitamin B12 levels were normal. The serum ferritin and iron levels were normal. She was tested negative for thalassemia. Bone marrow aspiration showed granulocytosis and abnormal lymphocytes (3.5%).

CASE PRESENTATION

Chief complaints

A 4-year-old girl was hospitalized because of a 50-d history of pallor.

History of present illness

Four days before admission, the child developed intermittent fever (1–2 times per day; maximum temperature, 38.5 °C), accompanied by paroxysmal cough and sore throat.

History of past illness

The patient had no history of hemoptysis, hematemesis, hematuria, or hematochezia. She had a history of chronic diarrhea, which was unresolved despite a diet of deep hydrolyzed milk powder. Routine blood examination revealed severe anemia. Emergency infusion of leukocyte suspension (1.5 U) and mezlocillin-sulbactam antibiotics were administered.

Personal and family history

Birth and developmental history were unremarkable.

按0.01 mm/min的位移速度施加軸向應(yīng)力，直至相似試件充分破壞，如圖1所示，記錄應(yīng)力-應(yīng)變曲線和試驗(yàn)力-變形曲線，對(duì)相似試件單軸壓縮曲線進(jìn)行分析。

Physical examination

At present, the diagnosis of PLG is primarily based on histological findings of the lung tissue showing the "triad" of pleomorphic lymphocyte infiltration with necrosis, infiltration of lymphocytes in the arterial and venous walls, and EBV-positive B cells confirmed by ISH. In this case, lung histopathology showed moderate-sized infiltrating cells, lymphoid tissue hyperplasia with necrosis, and small lymphocytes, plasma cells, and histiocytes in the background. A variable number of CD20-positive B cells existed in the background of CD3-positive small lymphocytes and were EBER1/2-ISHpositive, thus, meeting the diagnostic criteria for PLG. Histologically, PLG is graded according to the proportion of EBV-positive large B lymphocytes determined by EBER: Grade 1 Lesion is composed of scattered EBV-positive cells without necrosis; Grade 2 Lesions include an increased number of large B cells and some necrosis; and Grade 3 Lesions consist mainly of many virus-positive cells with extensive necrosis[1,3,4]. This case was classified as Grade 3 because the lesion comprised many EBV-positive cells.

Laboratory examinations

世宗的筑墻和拒絕貢市政策，違背了蒙漢人民向往和平的意愿，延緩了民族交流和民族融合的步伐，是一種兩敗俱傷的“雙輸”的封閉政策。實(shí)際上，這種封閉政策，并未能完全斷絕明蒙之間的交流，特別是蒙方控制的豐州灘地區(qū)建立起“板升”農(nóng)業(yè)聚落，與大同地區(qū)保持著經(jīng)濟(jì)文化交流的渠道。這種軍事對(duì)峙堅(jiān)冰下的潛流，在一定程度上為隆慶和議的轉(zhuǎn)折鋪平了道路。

感恩節(jié)是一個(gè)傳統(tǒng)和分享的時(shí)節(jié)。即使他們住在很遠(yuǎn)的地方，家人也會(huì)聚集在一個(gè)長(zhǎng)輩家里團(tuán)聚。所有人都要感謝他們所擁有的美好事物。

Microbiological identification of the causative agent

Microbiologic examination for antigens of seven respiratory pathogens (influenza A, influenza B, respiratory syncytial virus, adenovirus, and parainfluenza 1, 2, and 3),

IgM and total antibody, and chlamydia IgM antibody were all negative. The serum fungal G, GM tests, and TSPOT test were normal. The serum anti-EBV capsid antigen IgM (> 160.0 U/mL) and IgG (> 750.00 U/mL) were positive; anti-EBV early antigen IgG was also positive (> 150.00 U/mL). The quantity of EBV DNA was significantly high (5.14 × 10

copies/mL). Humoral immunity, IgG subclasses, T lymphocytes, B lymphocytes, and natural killer cells were all within the normal ranges.

Exome sequencing

Exome sequencing revealed a pathogenic, pure heterozygous variant of macrophage-expressed gene 1 (

) (NM_001039396: c.946C>T; p.P316S). Both parents of the patient were genotypically heterozygous. Electronic bronchoscopy revealed many white nodules on the mucosa of the left and right main bronchi, left upper and lower lobe bronchi, and right upper and middle lobe bronchi, as well as mild hemorrhage in the posterior basal segment of the left lower lobe (Figure 1).

producing extended-spectrum β-lactamases were cultured in the bronchoalveolar lavage fluid. Histopathological examination of the resected lung revealed lymphoproliferative lesions with necrosis. The proliferative and infiltrating lymphocytes were moderately sized with round nuclei and occasional nucleoli. Mitosis and infiltration of the blood vessels by these cells were noted. Small lymphocytes, plasma cells, and histiocytes were observed in the background, although Reed-Sternberg cells were absent. Immunohistochemical staining [CD20(+), CD30(+), and CD3(+)] and EBV-encoded small RNA1/2

hybridization (ISH) of small lymphocytes revealed approximately 200 cells/high-power field (Figure 2).

Imaging examinations

Chest computed tomography (CT) findings revealed multiple lower lobe nodules and shadows, multiple bilateral hilar and mediastinal lymph node enlargement, mild left pleural effusion, and bilateral pleural thickening (Figure 3A).

In conclusion, PLG is a rare but potentially fatal disease in children. Children usually present with diffuse pulmonary nodules. Owing to the difficulty of diagnosis using clinical data and chest imaging, histopathology and chest imaging findings should be closely examined. In clinical settings, when the initial diagnosis is pneumonia and the treatment is ineffective, PLG should be considered.

GB 50352—2005《民用建筑設(shè)計(jì)通則》中對(duì)我國(guó)進(jìn)行氣候區(qū)劃分，建筑氣候區(qū)劃包括7個(gè)主氣候區(qū)，20個(gè)子氣候區(qū)。東北地區(qū)按照建筑氣候分區(qū)屬于嚴(yán)寒地區(qū)，氣候特點(diǎn)是冬季嚴(yán)寒且持續(xù)時(shí)間長(zhǎng)，夏季短促且涼爽，冬季冰凍期長(zhǎng)，積雪后太陽(yáng)輻射量大、日照豐富。全年施工周期持續(xù)8個(gè)月，一般從11月末至次年3月末為冬歇期，冬季供暖周期長(zhǎng)，因此，該區(qū)的建筑物總體規(guī)劃與單體設(shè)計(jì)上需要滿足冬季日照和防寒保溫等關(guān)鍵要素，盡量加強(qiáng)建筑物的密閉性，合理利用太陽(yáng)等自然能源的節(jié)能措施，建筑能耗主要以冬季采暖為主。

FINAL DIAGNOSIS

Chen LN and Liu HM concepted the study; Chen LN, Qiu L, Liang P, and Yao JW did the investigation; Yao JW and Liang P did the writing and original draft; Chen LN writing the review and editing.

TREATMENT

After admission, the patient was treated with imipenem-cilastatin and acyclovir antiviral therapy. However, the cough persisted, and chest CT findings showed no significant shrinkage of the pulmonary nodules even 1 mo after treatment (Figure 3B). Suspecting a possible lung tumor, we performed thoracoscopic wedge resection of the lower lobe of the left lung with pleural adhesion cauterization and lung biopsy for histopathological determination (Figure 4).

OUTCOME AND FOLLOW-UP

The patient was transferred to the Department of Pediatric Oncology. She was prescribed a chemotherapy regimen of prednisone, vincristine, and cyclophosphamide. Then, she received bone marrow transplantation. She remained relatively well throughout the treatment without immune deficiency or new infections.

DISCUSSION

Liebow

[2] first identified PLG. Besides multiple lung nodules, some patients with PLG may present with cough, dyspnea, chest pain, subcutaneous nodules, weight loss, and nervous system involvement (ataxia, hearing impairment, and dysarthria). Others may present with extrapulmonary involvement

such as those of the skin and nerves. PLG was renamed as mature B-cell tumor in 2016[3,4,5].

(1)在電子郵件文檔內(nèi)容的特征提取上，本文選取了電子郵件特征中的語言、結(jié)構(gòu)、格式三個(gè)特征進(jìn)行綜合分析，使得識(shí)別的準(zhǔn)確率更高。

Physical examination at admission revealed normal vital signs (temperature, 36.5 °C; pulse rate, 119 beats/min; respiratory rate, 33 cycles/min; blood pressure, 98/64 mmHg; and oxygen saturation, 98% in room air) and a body weight of 13.5 kg. She had pallor and clubbing. Rhonchi were noted in both lung fields. The liver was palpable, 5 cm below the costal margin, with blunt edges. Other physical examination findings were unremarkable.

EBV belongs to the γ subfamily of herpesvirus. The EBV genome is a linear double-stranded DNA molecule, a prototype virus of the genus of lymphofollicular viruses.

, all γ herpesviruses can replicate in lymphoid cells, although only some can replicate lytically in epithelial cells and fibroblasts. Primate B lymphocyte infection usually leads to latent infection, characterized by the persistence of the viral genome and the expression of a series of limited latent gene products, thus, promoting the transformation process and helping to drive cell proliferation[6]. The cleavage-associated gene of EBV has a significant homology with the human genome, and some genes have significant homology with human B-cell leukemia/Lymphoma 2. This gene is involved in the apoptosis of tissue B cells and other lymphocytes. In patients with congenital or acquired immunodeficiency, B cells infected by EBV easily undergo tumorigenic transformation[7,8]. EBV is believed to play an important role in driving PLG. It is speculated that host immune deficiency leads to abnormal clearance response to EBV, consequently leading to abnormal lymphoid tissue proliferation and apoptosis inhibition. This results in a large number of leukocytes infiltrating the blood vessels, followed by injury and tissue destruction[9]. Approximately half of the PLG cases in children are found in those undergoing treatment for leukemia. Some adult PLG cases are reportedly related to the use of certain drugs (methotrexate and imatinib) that, when withdrawn, lead to the disease resolution[10].

The MPEG1 is an ancient postnatal animal protein that belongs to the pore-forming protein of the membrane attack complex/perforin (MACPF) branch of the MACPF/cholesterol-dependent cytolytic cellulose superfamily. The MACPF functions in human immunity and development. The MPEG1 facilitates the entry of numerous antimicrobial effectors into cells, including proteases, reactive oxygen and nitrogen species, and bactericidal peptides, and mediates the harsh acidic environment of phagosomes[11]. No case of

mutations have been reported in patients with PLG. However, one study found this mutation in diffuse large B-cell lymphoma. Notably, a series of genetic mutations coexist with

, including

, all of which occur at a high frequency in the MCD subtype, as defined by Schmitz

[12], which promote nuclear factor-κB activation in a B-cell receptor-dependent manner. These findings confirm that

alone is insufficient to drive the malignant transformation of B cells and may induce lymphoma with other genetic events.

The authors thank Chen ZJ and Zhang PL for their help, guidance, and valuable discussions.

There are few reported cases of PLG in children, including a literature review of 49 published pediatric cases of PLG[13]. The affected patients were usually immunodeficient, and only one case reported hemolytic anemia.

提升學(xué)生的學(xué)習(xí)興趣，必須要遵從以人為本的教學(xué)思想。這既是新時(shí)代數(shù)學(xué)教育的要求，也是數(shù)學(xué)教學(xué)的內(nèi)在需要。教師要摒棄權(quán)威意識(shí)，家長(zhǎng)意識(shí)，放低自己的身段，和學(xué)生交朋友，把課堂交給學(xué)生，通過多種教學(xué)形式，啟發(fā)學(xué)生，引導(dǎo)學(xué)生，以耐心和細(xì)心，去幫助學(xué)生認(rèn)識(shí)數(shù)學(xué)，感受數(shù)學(xué)，進(jìn)而愛上數(shù)學(xué)。

Mild or severe PLG on chest CT usually shows well- or ill-defined bilateral pulmonary nodules mainly located in the lower lung fields. The nodules vary in size (usually 1 cm–2 cm in diameter) and are mostly related to interstitial lung diseases. Nodules are usually distributed along with the bronchovascular bundles or interlobular septa, possibly because of the tendency of lymphocytes to infiltrate the subintimal area of blood vessels. The size of the nodules can fluctuate gradually, and some of the nodules can be matted, in consistency with our observation. Bronchoscopy also revealed many small white nodules of different sizes in the bronchial lumen. Other cases also reported pleural effusion and hilar lymph node enlargement in patients with PLG. Diffuse ground-glass degeneration is uncommon and may be caused by peri-focal hemorrhage or pneumonia[14-17], which is consistent with bronchoscopic observation of the hemorrhage in the basal segment of the lower left lung lobe in this case.

The natural course of PLG varies greatly from spontaneous regression to death. The overall prognosis of PLG is poor, with a high mortality rate (60%–90%) within 5 years. Currently, the main treatments for patients with PLG are similar to those for non-Hodgkin’s lymphoma, including the use of rituximab to eliminate B cells. In previous reports, some patients received hematopoietic stem cell transplantation, and most were also treated with corticosteroids. According to the different grades of PLG, patients in advanced stages are more likely to receive treatment combined with immunochemotherapy, while lowgrade lesions can be treated with interferon-α[13,18].

CONCLUSION

我院與財(cái)務(wù)咨詢公司、餐飲行業(yè)財(cái)務(wù)總監(jiān)合作，指導(dǎo)學(xué)生報(bào)稅。通過學(xué)校教師與企業(yè)財(cái)務(wù)總監(jiān)共同開發(fā)實(shí)驗(yàn)實(shí)訓(xùn)指導(dǎo)書教材，由聘請(qǐng)的企業(yè)人員定期參與指導(dǎo)，提高工作實(shí)踐能力。

ACKNOWLEDGEMENTS

現(xiàn)如今，人類社會(huì)已經(jīng)進(jìn)入到信息化社會(huì)，計(jì)算機(jī)信息系統(tǒng)在各行各業(yè)中應(yīng)用廣泛，但是針對(duì)環(huán)境監(jiān)測(cè)行業(yè)來講，不能充分展現(xiàn)信息技術(shù)的應(yīng)用價(jià)值，因?yàn)樵诃h(huán)境監(jiān)測(cè)行業(yè)中，工作人員對(duì)構(gòu)建網(wǎng)絡(luò)體系不夠了解，不清楚網(wǎng)絡(luò)體系對(duì)行業(yè)發(fā)展的意義。另外，有關(guān)部門對(duì)網(wǎng)絡(luò)系統(tǒng)設(shè)備的投入力度較小，環(huán)境監(jiān)測(cè)人員不熟悉計(jì)算機(jī)系統(tǒng)的操作流程，技術(shù)不佳，甚至害怕使用新型科技，存在網(wǎng)絡(luò)系統(tǒng)存在懼怕心理，仍然使用傳統(tǒng)人工統(tǒng)計(jì)和建檔方法來完成工作，在一定程度上限制了環(huán)境監(jiān)測(cè)行業(yè)的發(fā)展。為了使工作效率有所提升，就要建立環(huán)境監(jiān)測(cè)數(shù)據(jù)體系，優(yōu)化環(huán)境監(jiān)測(cè)網(wǎng)絡(luò)體系。

FOOTNOTES

The patient was eventually diagnosed with PLG and transferred to the Department of Pediatric Oncology for further treatment.

Science and Technology department of Sichuan Province, No. 2020YFS0105; and West China Second University Hospital of Sichuan University, No. KL036.

Informed written consent was obtained from the patient’s guardians for publication of this report and any accompanying images.

The authors declare that they have no conflict of interest

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

China

Jia-Wei Yao 0000-0001-9803-1566; Li Qiu 0000-0001-8484-7062; Ping Liang 0000-0001-8816-9924; Han-Min Liu 0000-0002-4633-911X; Li-Na Chen 0000-0001-9537-8847.

Xing YX

A

Xing YX

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