Lung tumours

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Lung tumours comes to pathology to get diagnosed. This article basically deals with core biopsies. Pulmonary cytopathology is dealt with in the pulmonary cytopathology article.

An introduction to lung pathology is found in the pulmonary pathology article.

Lung tumours overview

Schematic overview of lung cancer (clinical)

 
 
 
 
 
 
 
 
Lung cancer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
 
 
 
 
 
 
 
Metastatic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NSCLC
 
 
 
SCLC
 
 
 
 
 
 
 
 
 
 
 
  • NSCLC = non-small cell lung cancer.
  • SCLS = small cell lung cancer.

Basic pathologic approach to lung cancer

 
 
 
 
 
 
Lung cancer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adenocarcinoma
 
Squamous
cell carcinoma
 
SCLC
 
LCLC
  • LCLC = large cell lung cancer.
  • SCLS = small cell lung cancer.

Notes:

  • Most lung cancer fits into one of the above categories.
  • All types may be metastatic. Pathologists usually don't have to sort this out, as the clinican often knows whether a given lesion is metastatic (when correlated with radiology).
  • Lung cancers may have a mixed morphology, e.g. SCLS may have squamous component.[1]
  • Categorization as non-small cell lung cancer (NSCLC) should be avoided, as treatment is now somewhat dependent on subcategorization.[2]

Major types (primary)

Mnemonic ASSL:

Epidemiology

  • Adenocarcinoma is the most common (primary lung cancer).[3]
  • Adenocarcinoma is the non-smoker tumour - SCLC and squamous are more strongly associated with smoking.

Distribution

  • Distribution - think about the location of letters in mnemonic ASSL.
    • Adenocarcinoma is usually periperal, i.e. smaller airways.
    • Squamous cell carcinoma and small cell carcinoma are typically central.

Management of primary lung cancer

Management is currently determined by categorization into:

  • Small cell cancer.
  • Non-small cell cancer (includes adenocarcinoma, squamous cell carcinoma, large cell carcinoma).

Microscopic features overview

Adenocarcinoma

  • Glands or cytoplasm with mucin.

Squamous cell carcinoma

  • Distinct cell borders with intercellular bridges.
  • Eosinophilic cytoplasm.

Small cell carcinoma

IHC

There is a great review paper by Jagirdar.[4]

Small cell carcinoma

  • CD56 +ve - sensitive.[5]
  • CK7 -ve, CK20 -ve.

Note:

  • CD56 - cytoplasmic.[6]

Squamous cell carcinoma

  • CK7 -ve, CK20 -ve.
  • HMWK +ve.
  • Usually TTF-1 -ve.[7]

Primary vs. secondary

  • TTF-1 is considered useful.[4]
    • 75% +ve adenocarcinoma
    • 11% +ve SSC
    • 50% +ve large cell carcinoma
    • 0% +ve mesothelioma
    • significant rates of +ve in some metastatic tumours -- see article by Jagirdar.

Note:

Neuroendocrine tumours

Overview

Classification

The grouping can be divided into four types:[11]

  • Small cell carcinoma.
  • Large cell neuroendocrine carcinoma.
  • Typical carcinoid.
  • Atypical carcinoid.

Cytologic features

Cytologic features useful for differentiation:

  • Small cell carcinoma: necrosis, scant cytoplasm, mitoses.
  • Typical carcinoid: often more cytoplasm, no necrosis, low mitotic rate (MIB-1: scant staining).
  • Atypical carcinoid: higher mitotic rate/MIB-1 than typical carcinoid,[12] no necrosis.

Notes:[11]

  • Large cell and small cell tumours behave in a similar fashion; large cell can be considered a morphological variant of small cell.
  • 9/10 of carcinoids are typical and usually have a good prognosis, i.e. do not metastasize.
    • Central location (vis-a-vis peripheral location) tends favours typical carcinoid over atypical carcinoid.

Malignant tumours

Adenocarcinoma of the lung

  • AKA lung adenocarcinoma.

General

Treatment:

  • Lung adenocarcinoma may be treated with EGFR inhibitors (e.g. gefitinib (Iressa), erlotinib (Tarceva)).[13]

Patients that receive EGFR inhibitors classically are:[14]

  • Non-smokers.
  • Female.
  • Asian. (???)

Microscopic

Features:

  • Nuclear atypia.
  • Eccentrically placed nuclei.
  • Abundant cytoplasm - classically with mucin vacuoles.

Negatives:

  • Lack of intercellular bridges.

Patterns:[15]

  • Lepidic.
  • Acinar.
  • Papillary.
  • Solid.

DDx:

Classification

Classification based on extent:[15]

  1. Adenocarcinoma in situ (AIS) - previously known as BAC.
    • Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
  2. Minimally invasive adenocarcinoma (MIA).
    • Lepidic growth with upto 5 mm of invasion.
    • Subtypes: nonmucinous (most common), mucinous, mixed mucinous/nonmucinous.
  3. Invasive adenocarcinoma:
    • Subtypes: micropapillary, mucinous (previously mucinous BAC), colloid, fetal, enteric.

IHC

  • CK7 +ve.
  • TTF-1 +ve.
  • CK20 -ve.

Molecular

Bronchioloalveolar carcinoma

Abbreviated BAC.

The term is no longer used in the new classification;[20] it is now "adenocarcinoma in situ" - see lung adenocarcinoma.

Squamous cell carcinoma of the lung

General

  • Strong association with smoking.
  • May be treated with surgery.

Microscopic

Features:

  • Central nucleus.
  • Dense appearing cytoplasm, usu. eosinophilic.
  • +/-Small nucleolus.

DDx:

Small cell carcinoma of the lung

General

  • Strong association with smoking.
  • Typically treated with chemotherapy.

Microscopic

Features:

  • Stippled chromatin.
  • High NC ratio, scant basophilic cytoplasm.
  • Typically small cells ~2x RBC diameter.
  • +/-Nuclear moulding.
  • No nucleolus.
  • Necrosis.
  • Mitoses.

DDx:

Malignant mesothelioma

Should not be confused with benign multicystic mesothelioma.
  • AKA mesothelioma.

General

  • Prognosis sucks.

Locations:

  • Lung.
  • Primary peritoneal.

Epidemiology:

  • Strong association with asbestos exposure.

Conditions associated with asbestos exposure (mnemonic PALM):[21]


Possible association with asbestos exposure:

Microscopic

Features:[23]

  • Infiltrative atypical cells - key feature.
    • +/-Epithelioid cells - may be cytologically bland, i.e. benign appearing.
      • Variable architecture: sheets, microglandular, tubulopapillary.
      • +/-Psammoma bodies.
    • +/-Spindle cells.
  • +/-Ferruginous body - strongly supportive.[24]
    • Looks like a (twirling) baton - segemented appearance, brown colour.
    • Thin (asbestos) fiber in the core.

Note:

  • Asbestos body is not strictly speaking a synonym for ferruginous body.

DDx:[25]

Image:

Subtypes

List of subtypes - mnemonic BEDS:[25][23]

  • Biphasic mesothelioma.
    • 10%+ of epithelioid & 10%+ sarcomatoid.
  • Epithelioid mesothelioma.
  • Desmoplastic mesothelioma.
    • Should be 50%+ dense tissue with storiform pattern & atypical cells.
  • Sarcomatoid mesothelioma.

Stains

  • PASD -ve.
  • Mucicarmine -ve.
    • Typically +ve in adenocarcinoma.

IHC

  • Several panel exists - no agreed upon best panel.[26]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[26]

  • Mesothelial markers:
    • Calretinin.
    • WT-1.
    • D2-40.
    • CK5/6.
  • Carcinoma markers:
    • CEA (monoclonal and polyclonal).
    • TTF-1.
    • Ber-EP4.
    • MOC-31.

Malignant potential

Atypical alveolar hyperplasia

  • Abbreviated AAH.
  • AKA atypical adenomatous hyperplasia of the lung.[27]

General

  • Generally considered the precursor lesion to adenocarcinoma in situ.[28]
  • Typically an incidental finding, i.e. asymptomatic.[29]

Microscopic

Features:[29]

  • Enlarged alveolar lining cells with:
    • Hobnail morphology - free (luminal) surface area > attached/basal surface area.
    • Hyperchromasia.
  • Limited extent:
    • <5 mm. †

DDx:

  • Adenocarcinoma in situ.

Note:

Image:

Atypical carcinoid lung tumour

  • AKA atypical carcinoid tumour of the lung.

General

  • Approximately 20% of lung carcinoids.[30]

Microscopic

Features:[31]

  • Nests of cells.
    • Stippled chromatin.
    • Mild-to-moderate amount of cytoplasm.
  • No necrosis/focal necrosis.
  • Moderate mitotic rate (2-10/HPF - definition suffers from HPFitis).

DDx:

IHC

  • MIB-1 moderate staining.

Solitary fibrous tumour of the pleura

See also: Solitary fibrous tumour.

General

  • Common.
  • Benign.
  • Elderly.

Gross/radiology

  • Chest wall.

Microscopic

Features:

  • Spindle cells.
  • Ropy collagen.

Image:

IHC

  • CD34 +ve.

Benign tumours

Pulmonary carcinoid tumourlet

  • AKA carcinoid tumourlet.

General

Microscopic

Features:

  • Nests of cells - classic pattern.
    • Salt and pepper chromatin - key feature.
  • Size criterion: <= 4 mm.[33]

DDx:

Images:

Typical carcinoid lung tumour

  • AKA carcinoid tumour of the lung.

General

  • Approximately 80% of lung carcinoids.[30]

Microscopic

Features:

  • Nests of cells.
    • Stippled chromatin.
    • Moderate cytoplasm.
  • No necrosis.
  • Low mitotic rate.
  • Size criterion: > 4 mm.[33]

DDx:

IHC

  • MIB-1 scant staining.

Clear cell sugar tumour of the lung

  • AKA clear cell sugar tumour.
    • Abbreviated CCST.

General

Microscopic

Features:[34]

  • Sheets or trabeculae.
  • Irregular epithelioid cells with:
    • Focally clear cytoplasm.

Images:

IHC

  • HMB-45 +ve (nuclear & cytoplasmic).

See also

References

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