PATH 5215 MD 7 Respiratory System II Notes

Tumours Classification

  • WHO Classification of Tumours 5th Edition: Thoracic Tumours.

  • International Histologic Classification of Tumours.

ICD-O Coding of Lung Tumours

  • Includes codes for haematolymphoid tumours, epithelial tumours, and mesenchymal tumours.

Epithelial Tumours

  • Papillomas: Squamous cell papilloma (NOS, inverted), glandular papilloma, mixed squamous cell and glandular papilloma.

  • Adenomas: Sclerosing pneumocytoma, alveolar adenoma, papillary adenoma, bronchiolar adenoma, mucinous cystadenoma, mucous gland adenoma.

  • Precursor Glandular Lesions: Atypical adenomatous hyperplasia, adenocarcinoma in situ (non-mucinous, mucinous).

  • Minimally Invasive Adenocarcinoma: Non-mucinous, mucinous.

  • Invasive Non-Mucinous Adenocarcinoma: Lepidic, acinar, papillary, micropapillary, solid.

  • Invasive Mucinous Adenocarcinoma

  • Squamous Precursor Lesions: Squamous cell carcinoma in situ, Mild, Moderate, and Severe squamous dysplasia.

  • Squamous Cell Carcinomas: NOS, keratinizing, non-keratinizing, basaloid, lymphoepithelial.

Lung Neuroendocrine Neoplasms

  • Precursor Lesion: Diffuse idiopathic neuroendocrine cell hyperplasia.

  • Neuroendocrine Tumours: Carcinoid tumour (typical, atypical), small cell carcinoma, combined small cell carcinoma, large cell neuroendocrine carcinoma, combined large cell neuroendocrine carcinoma.

Other Tumours

  • Other Epithelial Tumours: NUT carcinoma, SMARCA4-deficient undifferentiated tumour.

  • Salivary Gland-Type Tumours: Pleomorphic adenoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, mucoepidermoid carcinoma, hyalinizing clear cell carcinoma, myoepithelioma, myoepithelial carcinoma.

  • Mesenchymal Tumours Specific to the Lung: Pulmonary hamartoma, chondroma, diffuse lymphangiomatosis, inflammatory myofibroblastic tumour, pleuropulmonary blastoma, intimal sarcoma, congenital peribronchial myofibroblastic tumour, pulmonary myxoid sarcoma.

Squamous Cell Papilloma

  • Benign tumor arising from an epithelial surface and usually known to grow in an outward direction.

  • Usually occur in large bronchi, often with associated 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

  • 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

  • Leading cause of cancer-related deaths worldwide.

  • Primary prevention (tobacco control measures) can reduce incidence.

  • Smoking is the leading cause (85% of cases).

  • Often diagnosed at advanced stages.

  • Screening high risk individuals improves survival rates.

Types of Lung Cancer

  • Small Cell Carcinoma (SCC/SCLC)

  • Non-Small Cell Lung Cancer (NSCLC): Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma, Combined Small Cell Carcinoma (CSCC).

Squamous Cell Carcinoma

  • Malignant tumor arising from epithelial cells with squamous differentiation.

  • Primarily in patients over 50 years of age.

  • Strong association with tobacco smoking (80% of men, 90% of women).

  • 85% of primary lung cancers are non-small cell, and squamous cell makes up 30% of these.

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: Bone, Liver

Pathophysiology

  • Squamous cells lining the respiratory tract transformed from carcinogen exposure (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 hemorrhage 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 mitosis and often requires IHC studies to differentiate from other poorly differentiated lesions.

Alveolar Adenoma

  • Well circumscribed tumor consisting of cystic spaces lined by a single layer of type II pneumocytes overlying a spindle cell stroma.

  • Rare tumors

  • Solitary and peripheral tumors.

  • Incidental diagnosis.

  • Slightly female preponderance

  • 39-74 y

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.

  • F > M

  • Most common type of lung cancer in male nonsmokers

  • African Americans > Caucasians

  • Age 60 - 70

Sites

  • Upper lobe > lower lobe

  • Peripheral > central

  • Metastasis: brain (often only site) > bone > liver > adrenal

  • Risk for brain metastasis increases with tumor size and lymph node stage

Pathophysiology

  • Toxic cellular exposures → genetic mutations → proliferation of endobronchial cells

  • Genetic events

Etiology

  • 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