Respiratory System II Pathology Flashcards

Respiratory System II: Pathology II (PATH 5215)

WHO Classification of Tumours (5th Edition)

  • Thoracic Tumours
  • International Histological Classification of Tumours No. 21
  • Histological Typing of Tumours of the Central Nervous System

ICD-O Coding of Lung Tumours

Epithelial Tumours
  • Papillomas
    • 8052/0: Squamous cell papilloma, NOS (Not Otherwise Specified)
    • 8053/0: Squamous cell papilloma, inverted
    • 8260/0: Glandular papilloma
    • 8560/0: Mixed squamous cell and glandular papilloma
  • Adenomas
    • 8832/0: Sclerosing pneumocytoma
    • 8251/0: Alveolar adenoma
    • 8280/0: Papillary adenoma
    • 8140/0: Bronchiolar adenoma / ciliated muconodular papillary tumour
    • 8470/0: Mucinous cystadenoma
    • 8480/0: Mucous gland adenoma
  • Precursor Glandular Lesions
    • 8250/0: Atypical adenomatous hyperplasia
    • 8250/2: Adenocarcinoma in situ
    • 6253/2: Adenocarcinoma in situ, non-mucinous
    • 8023/2: Adenocarcinoma in situ, mucinous
  • Adenocarcinomas
    • 8200/3: Minimally invasive adenocarcinoma
    • 8562/3: Minimally invasive adenocarcinoma, non-mucinous
    • 8430/3: Minimally invasive adenocarcinoma, mucinous
    • 8310/3: Invasive non-mucinous adenocarcinoma
    • 8982/3: Lepidic adenocarcinoma
    • 8982/3: Acinar adenocarcinoma
    • 8240/3: Papillary adenocarcinoma
    • 8240/3: Micropapillary adenocarcinoma
    • 8249/3: Solid adenocarcinoma
    • 8256/3: Invasive mucinous adenocarcinoma
    • 8257/3: Mixed invasive mucinous and non-mucinous adenocarcinoma
    • 8041/3: Colloid adenocarcinoma
    • 8333/3: Fetal adenocarcinoma
    • 8144/3: Adenocarcinoma, enteric-type
    • 8140/3: Adenocarcinoma, NOS
  • Squamous Precursor Lesions
    • 8070/2: Squamous cell carcinoma in situ
    • 8077/0: Mild squamous dysplasia
    • 8077/2: Moderate squamous dysplasia
    • 8077/2: Severe squamous dysplasia
  • Squamous Cell Carcinomas
    • 8070/3: Squamous cell carcinoma, NOS
    • 8071/3: Squamous cell carcinoma, keratinizing
    • 8072/3: Squamous cell carcinoma, non-keratinizing
    • 8083/3: Basaloid squamous cell carcinoma
    • 8082/3: Lymphoepithelial carcinoma
  • Adenosquamous Carcinomas
    • 8560/3: Adenosquamous carcinoma
  • Large Cell Carcinomas
    • 8012/3: Large cell carcinoma
  • Sarcomatoid Carcinomas
    • 8022/3: Pleomorphic carcinoma
    • 8031/3: Giant cell carcinoma
    • 8032/3: Spindle cell carcinoma
    • 8972/3: Pulmonary blastoma
    • 8980/3: Carcinosarcoma
  • Other Epithelial Tumours
    • 8023/3: NUT carcinoma
    • 8044/3: Thoracic SMARCA4-deficient undifferentiated tumour
  • Salivary Gland-Type Tumours
    • 8940/0: Pleomorphic adenoma
    • 8200/3: Adenoid cystic carcinoma
    • 8562/3: Mucoepidermoid carcinoma
    • 8430/3: Epithelial-myoepithelial carcinoma
    • 8310/3: Hyalinizing clear cell carcinoma
    • 8982/0: Myoepithelioma
    • 8982/3: Myoepithelial carcinoma
  • Lung Neuroendocrine Neoplasms
    • 8040/0: Diffuse idiopathic neuroendocrine cell hyperplasia (precursor lesion)
  • Neuroendocrine Tumours
    • 8240/3: Carcinoid tumour, NOS / neuroendocrine tumour, NOS
    • 8240/3: Typical carcinoid / neuroendocrine tumour, grade 1
    • 8249/3: Atypical carcinoid / neuroendocrine tumour, grade 2
  • Neuroendocrine Carcinomas
    • 8045/3: Small cell carcinoma
    • 8551/3: Combined small cell carcinoma
    • 8260/3: Large cell neuroendocrine carcinoma
    • 8130/3: Combined large cell neuroendocrine carcinoma
  • Tumours of Ectopic Tissues
    • 8720/3: Melanoma
    • 9530/0: Meningioma
Mesenchymal Tumours Specific to the Lung
  • 6992/0: Pulmonary hamartoma
  • 9220/0: Chondroma
  • 9170/3: Diffuse lymphangiomatosis
  • 8973/3: Intimal sarcoma
  • 9137/3: Pleuropulmonary blastoma
  • 8827/1: Congenital peribronchial myofibroblastic tumour
  • 8842/3: Pulmonary myxoid sarcoma with EWSR1-CREB1 fusion
  • PEComatous Tumours
    • 9174/3: Lymphangioleiomyomatosis
    • 8714/0: PEComa, benign
    • 8714/3: PEComa, malignant
Haematolymphoid Tumours
  • 9699/3: MALT lymphoma
  • 9680/3: Diffuse large B-cell lymphoma, NOS
  • Lymphomatoid Granulomatosis
    • 9766/1: Lymphomatoid granulomatosis, NOS
    • 9766/1: Lymphomatoid granulomatosis, grade 1
    • 9766/1: Lymphomatoid granulomatosis, grade 2
    • 9766/3: Lymphomatoid granulomatosis, grade 3
  • 9712/3: Intravascular large B-cell lymphoma
  • 9751/1: Langerhans cell histiocytosis
  • 9749/3: Erdheim-Chester disease

Benign Tumours

Epithelial Tumours
  • Papillomas
    • 8052/0: Squamous cell papilloma, NOS
    • 8053/0: Squamous cell papilloma, inverted
    • 8260/0: Glandular papilloma
    • 8560/0: Mixed squamous cell and glandular papilloma
  • Adenomas
    • 8832/0: Sclerosing pneumocytoma
    • 8251/0: Alveolar adenoma
    • 8260/0: Papillary adenoma
    • 8140/0: Bronchiolar adenoma / ciliated muconodular papillary tumour
    • 8470/0: Mucinous cystadenoma
    • 8480/0: Mucous gland adenoma

Squamous Cell Papilloma

  • Benign tumour arising from an epithelial surface, growing outward.
  • Usually occurs in large bronchi, often with tracheal or laryngeal lesions.
  • Presentation: Endobronchial exophytic growth
  • Middle-aged male smokers.
  • Associated with HPV 6 and HPV 11; high-risk HPV may be seen in cases associated with carcinoma.
  • Clinical presentation: Hemoptysis, recurrent pneumonia, asthma-like symptoms, dry cough.
Morphology (Gross Description)
  • Tan-white, friable, pedunculated/polypoid, smooth to verrucoid, glistening.
  • Wart-like, cauliflower-like.
  • Less than a few centimeters in size.
Morphology (Microscopic Description)
  • Exophytic, papillary lesion with arborizing fibrovascular cores lined by keratinizing or nonkeratinizing mature squamous epithelium.
  • Rarely inverted pattern.
  • Lesion may grow into adjacent alveolar spaces.
  • May contain areas lined by ciliated or non-ciliated columnar cells with cuboidal cells or mucin-filled cells (mixed squamous and glandular papilloma).
  • May exhibit viral cytopathic effect: enlarged hyperchromatic nuclei, nuclear wrinkling, polychromasia, binucleate forms, perinuclear halos.
  • Mild to moderate stromal inflammation which may be related to airway obstruction.
  • No mitoses, no necrosis.

Lung Cancer: Key Facts

  • Leading cause of cancer-related deaths worldwide (highest mortality rates among men and women).
  • Smoking is the leading cause (approximately 85% of all cases).
  • Often diagnosed at advanced stages when treatment options are limited.
  • Screening high-risk individuals has the potential to allow early detection and dramatically improve survival rates.
  • Primary prevention (tobacco control, reducing exposure to environmental risk factors) can reduce incidence and save lives.

Types of Lung Cancer

  • Small Cell Lung Cancer (SCLC) or Small Cell Carcinoma (SCC)
  • Non-Small Cell Lung Cancer (NSCLC)
    • Adenocarcinoma
    • Squamous Cell Carcinoma (SCC)
    • Large Cell Carcinoma (LCC)
    • Combined Small Cell Carcinoma (CSCC)

Squamous Cell Carcinoma

  • Malignant tumour arising from epithelial cells with squamous differentiation demonstrated either immunohistochemically or morphologically, with the presence of keratinization or intercellular bridges.
  • Strong association with history of tobacco smoking (80% of men and 90% of women).
  • Primarily in patients over 50 years of age.
  • 85% of primary lung cancers are non-small cell carcinomas, and squamous cell makes up 30% of these cases.
Sites
  • Can present in any site of the lungs or bronchus but is more commonly central.
  • Mediastinal lymph nodes are the primary site of metastasis.
  • Hematogenous spread to distant organs:
    1. Bone
    2. Liver
Pathophysiology
  • Squamous cells lining the respiratory tract transformed from carcinogen exposure, most frequently smoking.
  • Occupational heavy metal exposure
Clinical Features

Wide range of nonspecific pulmonary symptoms:

  • Cough
  • Chest pain
  • Shortness of breath
  • Hemoptysis
  • Wheezing
  • Weight loss
  • Recurrent infections
  • Loss of appetite and fatigue
Gross Description
  • Cavitary mass with white, smooth cut surfaces that frequently contain haemorrhage and necrosis.
  • Mass is more often central than peripheral and may be within the bronchus.
Microscopic Description
  • Range from well-differentiated squamous cell neoplasms showing keratin pearls and intercellular bridges to poorly differentiated neoplasms exhibiting only minimal squamous cell features.
  • Poorly differentiated squamous cell carcinoma exhibits severe cellular and nuclear atypia, abundant mitoses and often requires IHC (immunohistochemistry) studies to differentiate from other poorly differentiated lesions.
Development of SCC

Normal epithelium → Hyperplasia → Squamous metaplasia → Dysplasia → Carcinoma in situ → Invasive carcinoma

Microscopic Features

Key features seen microscopically include:

  • Keratinization
  • Intercellular bridges
  • Abundant eosinophilic cytoplasm

Alveolar Adenoma

  • Well-circumscribed tumour consisting of cystic spaces lined by a single layer of type II pneumocytes overlying a spindle cell stroma.
  • Solitary and peripheral tumours.
  • Incidental diagnosis.
  • Rare tumours
  • Slightly female preponderance
  • Age range: 39-74 years
Gross Description
  • Size: 7-60 mm
  • Well demarcated
  • Smooth, lobulated multicystic pale yellow to tan surface cut.
Microscopic Description
  • Cystic spaces filled with eosinophilic granular material.
  • Lined by cytologically bland flattened to cuboidal epithelial cells (pneumocytes type II).
  • Myxoid or collagenous stroma.

Lung Adenocarcinoma

  • Most prevalent non-small cell lung carcinoma.
  • Female > Male
  • Most common type of lung cancer in male nonsmokers
  • African Americans > Caucasians
  • Age: 60-70 years
Sites
  • Upper lobe > lower lobe
  • Peripheral > central
  • Metastasis: brain (often only site) > bone > liver > adrenal
  • Risk for brain metastasis increases with tumour size and lymph node stage
Pathophysiology
  • Toxic cellular exposures → genetic mutations → proliferation of endobronchial cells
  • Genetic events
Aetiology
  • Smoking is the greatest risk factor, including secondhand smoke
  • Radon from soil, usually in residential areas
  • Asbestos exposure
Clinical Features
  • Cough (productive if mucinous adenocarcinoma), hemoptysis, dyspnea, weight loss, chest pain.
  • Paraneoplastic / endocrine syndromes.
    • Paraneoplastic syndromes are disorders that are triggered by an altered immune system response to a neoplasm.
    • Clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease.
Gross Description
  • Tan-white cut surface
  • May have central area of scar or necrosis
  • Usually well-defined but nonencapsulated
Microscopic Description

5 main histologic patterns:

  • Lepidic: type II pneumocytes and club cells proliferate to line alveolar walls; lacks architectural complexity; no lymphovascular or perineural invasion.
  • Acinar: gland forming; round / oval glands invading the stroma (usually fibrous).
  • Papillary: malignant cuboidal / columnar cells replace alveolar lining; contains fibrovascular cores.
  • Micropapillary: ill-defined projection / tufting that lacks fibrovascular cores.
  • Solid: sheets of neoplastic cells