Proposed General Classification Framework for Squamous Cell Carcinoma

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6 2 月, 2026

On 6 2 月, 2026

Introduction:

Squamous cell carcinoma (SCC) is widely distributed in the skin and certain tracts (such as from the oral cavity to the esophagus, and from the vulva to the cervix). It is a very common type in pathological diagnosis. However, classification and grading vary across different sites. As frontline pathology practitioners, from a concise and practical perspective combined with clinical needs, it is suggested and agreed upon to establish a universal classification framework. Building on previous discussions, a preliminary proposal is put forward to stimulate further ideas.(See the simplified table below for details)

Grade	Grade I	Grade II	Grade III	Grade IV
Degree of Differentiation	Well-differentiated	Moderately differentiated	Poorly/Undifferentiated	Undifferentiated
Malignancy Degree	Low	Moderate	High	High
Related Types	Keratinizing SCC, Papillary SCC, Verrucous carcinoma	Basaloid SCC	Non-keratinizing carcinoma, Pseudoglandular SCC, Vesicular nucleus cell carcinoma (Large round cell carcinoma, Lymphoepithelioma-like carcinoma), Basal cell carcinoma	Sarcomatoid carcinoma, Spindle cell carcinoma, Clear cell carcinoma, Large cell carcinoma (named by cell morphology, not all have squamous differentiation)
Diagnostic Measures	Adequate sampling, routine sectioning, comprehensive observation, identifying evidence of squamous differentiation, such as keratinization, intercellular bridges, etc.			Add immunohistochemistry and/or electron microscopy examination
Differential Entities	For well-differentiated cases, pay attention to differentiating from pseudoepitheliomatous hyperplasia, keratoacanthoma, actinic keratosis, Bowen’s disease, high-grade intraepithelial neoplasia, etc.; for poorly differentiated cases, differentiate from undifferentiated carcinoma, sarcoma, poorly differentiated adenocarcinoma, etc.			Biphasic differentiated sarcoma, poorly differentiated adenocarcinoma, carcinosarcoma, neuroendocrine carcinoma

This classification framework is primarily based on grading and is divided into four levels. For biopsy specimens, grading should be performed based on the determination of squamous differentiation, but it should not be forced for tiny specimens (limited by specimen constraints). If the direction of differentiation cannot be determined, temporarily classify as Grade IV (undifferentiated), and take auxiliary measures or request re-submission to confirm the diagnosis.

If the specimen is sufficient, then consider typing along with grading. The author summarizes SCC into five major types. During diagnosis, customary names can be used for specific sites or morphologies, such as verrucous carcinoma, basal cell carcinoma, lymphoepithelioma-like carcinoma, etc.

Adenosquamous carcinoma or squamoadenocarcinoma often occurs on the basis of squamous metaplasia of glandular epithelium (columnar epithelium), or when SCC and adenocarcinoma meet and blend together (encounter carcinoma or collision carcinoma). When the same tumor contains both SCC and adenocarcinoma, if SCC is predominant, it is called adenosquamous carcinoma; conversely, it is called squamoadenocarcinoma. The basic principle is that the main component is placed last.

Composite tumors containing SCC components can also include mucoepidermoid carcinoma, anal cloacogenic carcinoma, mature teratoma with SCC transformation, etc. When the SCC component is significant, differential diagnosis is required.

The key distinction between squamous epithelial dysplasia, pseudoepitheliomatous hyperplasia, and carcinoma in situ (including high-grade intraepithelial neoplasia, cutaneous Bowen’s disease, penile erythroplasia of Queyrat, etc.) and SCC is the presence or absence of stromal invasion. Sometimes, due to sectioning, cut epithelial rete ridges may be mistaken for tumor nests or invasion, requiring special caution.

A common method for differential diagnosis is immunohistochemistry. High molecular weight cytokeratin and P63, P40 are decisive for confirming squamous differentiation. For undifferentiated tumors, additional differential markers should be added, such as low molecular weight cytokeratin, vimentin, neural and myogenic markers, etc.

Maixin Related Antibodies

Antibody Name	Product Code	Clone Number	Positive Location
^P40*	RMA-1006	MXR010	Nuclear
P40	RMA-0815	ZR8	Nuclear
P63*	MAB-0694	MX013	CytoplasmicNuclear

*Marked as Maixin clone products

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