Lung
Preinvasive
Squamous cell carcinoma in situ
Editorial Board Member: Matthew J. Cecchini, M.D., Ph.D.
Last author update: 3 June 2024
Last staff update: 3 June 2024
Copyright: 2022-2024, PathologyOutlines.com, Inc.
PubMed Search: Squamous cell carcinoma in situ
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: Olteanu GE, Mataić A, Brčić L. Squamous cell carcinoma in situ. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungsquamouscellcarcinomainsitu.html. Accessed December 26th, 2024.
Definition / general
- Squamous cell carcinoma in situ (SCIS) is a preinvasive lesion originating from the bronchial epithelium and represents a precursor of squamous cell carcinoma (SCC)
- Recognition of SCIS can often be complex because it forms a histologic continuity with severe dysplasia; in SCIS there is a complete loss of maturation, severe cytologic atypia and mitoses in all epithelial levels (basal, middle and upper) with an intact basement membrane
Essential features
- SCIS is a preinvasive squamous lesion that is a precursor SCC of the lung and bronchus
- Histologically there is severe full epithelial thickness dysplasia, mitoses on all levels with complete loss of maturation from the base to the luminal surface
- The most studied and successful treatment choice is endobronchial photodynamic therapy
Terminology
- Recommended: squamous cell carcinoma in situ (SCIS)
- Acceptable: high grade intraepithelial neoplasia
- Not recommended: bronchial premalignancy, early noninvasive cancer
ICD coding
- ICD-O: 8070/2 - in situ neoplasm of the lung (such as squamous carcinoma in situ)
- ICD-10: D02.2 - carcinoma in situ of bronchus and lung
- ICD-11: 2E62.2 & XH7WM7 - carcinoma in situ of bronchus or lung & squamous cell carcinoma in situ, NOS
Epidemiology
- No clear data regarding incidence but epidemiology is similar to lung SCC (Eur Respir J 2009;33:656)
- Data for preinvasive bronchial lesions are scant and tend to involve a population that is at risk (i.e., smokers or are in a screening program for lung cancer) (J Clin Pathol 2001;54:257)
- Risk factors (similar to invasive SCC)
- Smoking combustible tobacco products - the most detrimental
- Radon exposure both indoors and in mines
- Outdoor air pollution
- Asbestos exposure (Chest 2013;143:e1S)
Sites
- Anywhere from the main right or left bronchus to distal bronchioles
- Can be unifocal or multifocal throughout the tracheobronchial tree (Cancer Prev Res (Phila) 2014;7:1)
- Mirrors the localization of SCC; as such, at least two - thirds are centrally located with the remaining one - third in the periphery (Ann Am Thorac Soc 2017;14:118)
Pathophysiology
- Analogous to that of lung SCC
- SCIS is clearly linked to exposure to carcinogens found in cigarettes - tobacco mutation signature
- Causes a series of genetic and epigenetic alterations
- TP53, CDKN2A, SOX2 and AKT2 genes frequently exhibit somatic and copy number alterations
- With cell cycle and DNA repair pathway alterations and chromosomal instability
- Reference: Nat Med 2019;25:517
Etiology
- Like that of lung SCC
- Main etiological factor is smoking combustible tobacco products
- Indoor radon exposure and other ionizing radiation
- Asbestos exposure or other professional exposure
- Underlying chronic lung disease (e.g., pulmonary fibrosis, COPD, etc.)
- Indoor and outdoor air pollution (Clin Cancer Res 2005;11:537)
Clinical features
- SCIS is typically asymptomatic and is incidentally diagnosed during bronchoscopy
- Also seen in resection specimens for lung cancer
Diagnosis
- 40% of SCIS can be detected by white light reflectance bronchoscopy (WLB)
- Combining white light reflectance bronchoscopy with autofluorescence bronchoscopy (AFB) can detect lesions as small as 0.5 mm
- Autofluorescence bronchoscopy has a greater sensitivity than white light reflectance bronchoscopy for diagnosing SCIS, with combination obtaining a sensitivity of 85%
- Using infrared light illumination with optical coherence tomography can provide
- Cross sectional images with a spatial resolution ranging from 3 to 15 μm
- Penetration depth of 2 mm
- Nearly histological in quality
- Diagnosis and exclusion of invasion are through biopsy
- References: Thorac Surg Clin 2013;23:153, J Thorac Oncol 2011;6:1336, Clin Cancer Res 2008;14:2006
Radiology description
- SCIS cannot be visualized on CT or PET
Prognostic factors
- SCIS is very difficult to detect
- Has the potential to be multifocal, with ~30% of patients developing synchronous or metachronous lesions
- Excellent 5 year survival of > 90%
- Reference: Chest 2013;143:e263S
Case reports
- 59 year old man with dyspnea and hemoptysis (J Bronchology Interv Pulmonol 2017;24:67)
- 66 year old man with persistent cough (J Cardiothorac Surg 2012;7:74)
- 75 year old woman with hemoptysis and history of atrial fibrillation and rheumatic mitral stenosis (J Bronchology Interv Pulmonol 2018;25:231)
Treatment
- Endobronchial photodynamic therapy has been the most evaluated technique
- Complete response rates between 32% and 100%
- Other endobronchial therapies include
- Endobronchial brachytherapy
- Bronchoscopic electrocautery
- Cryotherapy
- Nd:YAG laser therapy
- Reference: Chest 2013;143:e263S
Clinical images
Images hosted on other servers:
Right main bronchus
under a) white
light and b) auto-
fluorescence
Gross description
- Polypoid / nodular lesions of 1 - 2 mm in diameter (25%) or flat lesions (75%) that are > 10 mm and appear as a focal thickening with marked irregular mucosa
- Localization
- In the segmental bronchi, close to points of branching
- Spreading to the nearby lobar and subsegmental branches
- Less common in the trachea
- Reference: J Thorac Cardiovasc Surg 1993;106:1098
Microscopic (histologic) description
- Diagnostic criteria are based on epithelial thickness, cell size, maturation / orientation and nuclei
- Thickness
- May or may not be increased
- Cell size
- Markedly increased
- May have marked anisocytosis and pleomorphism
- Maturation / orientation
- No progression from the base to the luminal surface
- Expanded basal area
- Cellular crowding throughout
- No intermediate zone
- Flattening of the surface is limited to the most superficial cells
- Nuclei
- High and variable N:C ratio
- Coarse and uneven chromatin
- Nuclear angulations and folding
- Prominent or absent nuclei
- No consistent orientation to the epithelial surface
- Mitotic figures throughout the full thickness
- Thickness
- Reference: Histopathology 2001;38:202
Microscopic (histologic) images
Contributed by Gheorghe-Emilian Olteanu, M.D., Ph.D., Ana Mataić, M.D. and Luka Brčić, M.D., Ph.D.
Normal respiratory epithelium
Normal respiratory epithelium and SCIS
Upper layer spot necrosis
Flattening of the upper layer
Polypoid growth pattern
Pleomorphic cells
Positive stains
- CK5/6, p40, p63: diffusely and strongly positive - similar staining to that of SCC
- Ki67: diffuse expression, high proliferation index (Histopathology 2004;44:47)
Molecular / cytogenetics description
- 5q loss of heterozygosity
- Somatic and copy number alterations in the TP53, CDKN2A, SOX2 and AKT2 genes
Videos
SCIS histopathology - lung, bronchus
Sample pathology report
- Bronchus, endobronchial biopsy:
- Squamous cell carcinoma in situ (see comment)
- Comment: Severe, full epithelial thickness dysplasia and mitoses on all levels with complete loss of maturation. No invasion noted.
Differential diagnosis
- Severe dysplasia:
- Cellular pleomorphism, coarse chromatin, frequent nucleoli, basal zone to upper third, mitoses confined to lower two - thirds, superficial cell flattening
Additional references
Board review style question #1
Which of the following is true about squamous cell carcinoma in situ (SCIS)?
- SCIS can be visualized on CT or PET
- SCIS does not represent a precursor of squamous cell carcinoma
- SCIS is a preinvasive lesion originating from the bronchial epithelium
- Smoking combustible tobacco products is not a risk factor for squamous cell carcinoma in situ
Board review style answer #1
C. Squamous cell carcinoma in situ (SCIS) is a preinvasive lesion originating from the bronchial epithelium. When the bronchial epithelium is exposed to carcinogens and irritants, it may show squamous metaplasia, which is not considered a preneoplastic lesion. Further accumulation of somatic genetic alterations leads to squamous dysplasia and squamous cell carcinoma in situ, which are considered preinvasive squamous lesions.
Answer A is incorrect because squamous cell carcinoma in situ cannot be visualized on CT or PE but it can be detected in up to 40% of cases by white light reflectance bronchoscopy (WLB); the sensitivity goes up when white light reflectance bronchoscopy is combined with autofluorescence bronchoscopy (AFB). Answer B is incorrect because SCIS does represent a precursor of squamous cell carcinoma. Answer D is incorrect because the main etiological factor for SCIS is smoking combustible tobacco products.
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Reference: Lung - Squamous cell carcinoma in situ
Answer A is incorrect because squamous cell carcinoma in situ cannot be visualized on CT or PE but it can be detected in up to 40% of cases by white light reflectance bronchoscopy (WLB); the sensitivity goes up when white light reflectance bronchoscopy is combined with autofluorescence bronchoscopy (AFB). Answer B is incorrect because SCIS does represent a precursor of squamous cell carcinoma. Answer D is incorrect because the main etiological factor for SCIS is smoking combustible tobacco products.
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Reference: Lung - Squamous cell carcinoma in situ
Board review style question #2
Regarding the histologic features of squamous cell carcinoma in situ (SCIS), which of the following is true?
- Diagnostic criteria are not based on epithelial maturation / orientation
- Epithelial thickness must be increased
- Mitotic figures are found only in the lower third
- There is no progression in maturation from the base to the luminal surface
Board review style answer #2
D. There is no progression in maturation from the base to the luminal surface and no consistent orientation of nuclei to the epithelial surface. Answer A is incorrect because diagnostic criteria for squamous cell carcinoma in situ are based on epithelial thickness, cell size, maturation / orientation and nuclei. Answer B is incorrect because epithelial thickness may or may not be increased. Answer C is incorrect because mitotic figures are present throughout the full thickness.
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Reference: Lung - Squamous cell carcinoma in situ
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Reference: Lung - Squamous cell carcinoma in situ
Board review style question #3
A patient with a nodular mass in the lower left lobe underwent a lobectomy. The tumor was located at 0.5 cm from the resection margin. The histological image above shows part of the bronchial resection margin. Regarding these findings, which of the following statements is true?
- In the report, the resection margins are stated as uninvolved by carcinoma in situ
- Ki67 is positive only in cells located in the lower part of the epithelium
- The lesion is diffusely and strongly positive for p40
- There is a progression in maturation from the base to the luminal surface
Board review style answer #3
C. The lesion is diffusely and strongly positive for p40. The picture shows the part of the bronchial resection margin that is involved by carcinoma in situ. Answer D is incorrect because the lesion shows no progression in maturation from the base to the luminal surface. Answer B is incorrect because on IHC, the lesion is diffusely and strongly positive for p40 and Ki67 shows increased proliferative activity with diffuse expression. Answer A is incorrect because lobectomy specimens contain bronchial and vascular margins and the presence of carcinoma in situ at a surgical margin is an important finding and must be reported as such.
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Reference: Lung - Squamous cell carcinoma in situ
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Reference: Lung - Squamous cell carcinoma in situ
