CT偶然发现（found accidentally，比如体检，或者由于其他疾病的诊断）的肺部结节（nodule，直径小于30mm，所谓直径是长径和短径的平均值）或者更大的肿块（mass，直径大于等于30mm）绝大多的是良性病变，包括良性肿瘤和非肿瘤性病变，其中非肿瘤性病变（noncancerous lung nodule）部分是肉芽肿（granuloma ）病变。Your healthcare provider will advise monitoring a benign neoplasm (About 95%)  without immediate treatment, what is known colloquially as a “watch and wait” method.

1. 肉芽肿概述

肉芽肿（granuloma）一般源于慢性感染（infection）和炎症（inflammation），俗称良性（benign）病变，可发生在身体各个部分，其中肺最为常见，称为肺部肉芽肿（lung granulomas），或肉芽肿性肺病变（granulomatous lung disease）。Many things can cause benign lung nodules, including infections and scarring. When an infection or illness inflames lung tissue, a small clump of cells (granuloma) can form. Over time, a granuloma can calcify or harden in the lung, causing a noncancerous lung nodule.

Granuloma，肉芽肿，granule，颗粒，词源拉丁语granulum，小颗粒。肉芽肿是大体的形态学描述，镜下可见大量慢性炎症细胞（包括lymphocytes淋巴细胞，巨噬细胞macrophages，Langerhans cells等）的紧密聚集，常提示慢性感染。A granuloma is an area of tightly clustered immune cells, or inflammation. They can form almost anywhere, but they’re most often found in your lungs. 

2. 肺部肉芽肿分类
常见的两种类型是干酪性肉芽肿（caseating granuloma）和非干酪性肉芽肿（noncaseating granuloma）。前者内有坏死细胞(坏死，necrosis)，常见于肺结核（tuberculosis）和其他感染，即使病理学常难以细分；后者常见于非感染性病变（noninfectious causes），比如结节病（sarcoidosis）或异物包裹（foreign objects）。The core needle biopsy pathology report read “necrotic material, fibrosis, and chronic inflammation” but did not indicate a specific diagnosis of necrotizing granuloma.
3. 肺部肉芽肿的常见病因
常见肉芽肿的病因是慢性(长期)感染或炎症（chronic or long-lasting infections or inflammation），比如结核病、组织胞浆菌病（histoplasmosis ）或克罗恩病（Crohn’s disease）以及结节病。形成的原因简单理解为巨噬细胞吞噬（swallow）失败，受炎症的不断刺激，不断聚集（form a tight cluster of cells），或者自身免疫性疾病（autoimmune disorders）引起的过激反应（immune system overreacts and causes inflammation）。
引起肉芽肿的常见感染因素，包括bacterials, fungals, parasites and viruses：
  • The most common infectious cause of granulomas is tuberculosis（结核）.
  • Non-Tubercular Mycobacterium.
  • Fungal Infections，包括Aspergillosis.曲霉病；Cryptococcosis.肺隐球菌病；Blastomycosis.芽生菌病；Candidiasis.念珠菌病；Histoplasmosis.组织胞浆菌病；Coccidioidomycosis (Valley fever).球孢子菌病(山谷热)等等.
  • Parasitic Infections，虽然少见，也包括，Toxoplasmosis.弓形虫病；Dilofilariasis (dog heartworm).双丝虫病(犬心虫)；Ascariasis (roundworms).蛔虫病(蛔虫)等等.
  • Bacterial Infections，包括Aspiration pneumonia.吸入性肺炎；Brucellosis.布鲁氏杆菌病；Nocardia.诺卡氏菌等等.
引起肉芽肿的常见自身免疫性和非感染性原因，包括：
  • Sarcoidosis（结节病）is the most common noninfectious cause of granulomas.
  • Bronchocentric Granulomatosis.支气管中央型肉芽肿病主要影响肺的小气道(细支气管).
  • Inflammatory Bowel Disease.炎症性肠病的肉芽肿除了胃肠道外，有部分（约30%）出现在肺部，包括 Crohn’s disease and ulcerative colitis.溃疡性结肠炎.

  • Environmental Exposures.包括Hypersensitivity Pneumonitis.过敏性肺炎；Exposure to the metal beryllium （berylliosis，铍中毒，工业陶瓷制造中）；其他的暴露包括铝（aluminum）、钛（titanium）、锆（zirconium）、钴（cobalt）、硅（silica）、Talc （云母，滑石）等等.

  • Medications，一些药物的副作用可能是肺的肉芽肿，其中部分是治疗肉芽肿的药物，包括Methotrexate.甲氨蝶呤；氨甲喋呤; Interferon.干扰素; Bacillus Calmette-Guerin (BCG) vaccine.卡介苗; Remicade (infliximab). Enbrel (etanercept). Rapamune (sirolimus). Arava (leflunomide)等等.

  • Autoimmune Diseases，包括Rheumatoid Arthritis（类风湿性关节炎），表现为发生在肺部以及皮下 (subcutaneous)的坏死性肉芽肿（Necrotizing granulomas）；Sjogren’s Syndrome（干燥综合症），除了唾液腺受损外，可有肺结节；Vasculitis（血管炎）， 其中又包括Granulomatosis with polyangiitis（肉芽肿伴多血管炎，旧称 Wegener’s 肉芽肿，考虑医学精神，建议弃用，但仍用）；Eosinophilic granulomatosis with polyangitis (伴有多血管炎的嗜酸性肉芽肿病，变应性肉芽肿性血管炎，过敏性肉芽肿性血管炎，既往称Churg-Strauss syndrome)；Granulomatous Lymphocytic Interstitial Lung Disease（肉芽肿性淋巴细胞间质性肺病）；Granulomatous lymphocytic interstitial lung disease (肉芽肿性淋巴细胞间质性肺病，GLILD，罕见但严重).

  • 肿瘤性肉芽肿少见，包括Lymphomatoid granulomatosis (淋巴瘤样肉芽肿症，associated with leukemia or lymphoma)；Sarcoid-like granulomatosis (肉瘤样肉芽肿，caused by certain blood cancers or cancer drugs)

4. 肺部肉芽肿的影像学

胸部X-ray 和CT（主要是HRCT）影像下肺部肉芽肿表现为一个或多个肺结节。感染性肉芽肿可见坏死（necrotizing granulomas）。肺部非感染性肉芽肿性疾病的影像学也缺少特征性表现，当常规经验抗感染无效或活检结果显示肉芽肿时，影像学需要考虑。Since there are many possible causes, diagnosing granulomas in the lungs can be challenging. In addition to a careful history and physical exam, lab tests, imaging tests, pulmonary function testing, and a lung biopsy might also be needed.

肺部肉芽肿性疾病常见的征象，包括实变（consolidation）、结节（nodules）、空洞（cavitation）、气道受累（airway involvement）、血管壁受累（vessel wall involvement）、胸腔积液（pleural effusion）和淋巴结异常（lymphadenopathy）。The imaging features of noninfectious granulomatous thoracic conditions are rarely specific.

一般地，可以根据肉芽肿病变的形态和分布进行分类，包括：

  • 支气管血管周围分布中的大结节，肿块或实变（macronodules, masses, or consolidation in a peribronchovascular distribution）
  • 随机分布中的肿块（masses in a random distribution）
  • 淋巴管周围分布中的微结节（micronodules in a perilymphatic distribution）

  • 小叶中心分布中的微结节（micronodules in a centrilobular distribution）

简述肺部肉芽肿病变及其影像学表现

PET scan is often done to check for cancer, vasculitis, and inflammatory diseases. However, the rate of false positives is high with this test.

5. 组织病理学检查(Biopsy)

If an FNA or transbronchial biopsy does not provide a large enough sample, surgery might be needed.

6. 治疗(Treatment)

These are some potential treatments for granulomas in the lungs:

  • Many fungal infections (such as histoplasmosis组织胞浆菌病) do not require treatment as the body has already fought off the infection.

  • The treatment of tuberculosis depends on many factors, including whether the strain is considered to be multi-drug resistant. Treatment is often lengthy and may require a combination of drugs.

  • With hypersensitive pneumonitis and exposure to metals, eliminating the exposure is key.

  • When granulomas are related to an autoimmune condition, treatment of the underlying condition is the goal. 

7. 预防(Prevention)
Most people can’t do anything to prevent granulomas. They’re a part of your body’s defenses. If you have an underlying condition, like an autoimmune disorder or a chronic infection, managing it will reduce your risk of developing granulomas. Calcified granulomas that don’t change over time are often harmless.
扩展阅读：

  1. https://my./health/diseases/14799-pulmonary-nodules

  2. https://my./health/diseases/24597-granuloma

  3. https://www./lung-granuloma-overview-4799111

  4. https://pubs./doi/full/10.1148/rg.2020190180

  5. https:///uc/item/30w9846n

  6. https://err./content/25/139/97

  7. https://www./2227-9717/5/4/79

  8. https://www./medical-animation-wegners-granulomatosis-symptoms-causes-treatm

  9. https://breathe./content/14/3/e94

  10. https://lungs./174lu-tb-calcified-granuloma-major-fissure/

  11. https://www./doi/full/10.2214/AJR.07.2389

  12. https://www./figure/Pulmonary-nodule-with-lobulated-margins-Figure-6-Benign-granulom

  13. https:///doi/full/10.14785/lpsn-2014-0020

  14. https:///mesh_info.php?term=Plasma+Cell+Granuloma%2C+Pulmonary&lang=1

  15. https://pubs./doi/full/10.1148/rg.2020190180

  16. https://err./content/26/145/170012.figures-only

  17. https://err./content/30/160/200152