Large Cell Carcinoma



Large Cell Carcinoma


Allen P. Burke, M.D.

Borislav A. Alexiev, M.D.



General

Large cell carcinoma, once a relatively large proportion of lung carcinomas, has now greatly dropped in frequency, as immunohistochemical typing has reassigned many of the previous subsets. Currently, large cell carcinoma is defined as lacking immunohistochemical differentiation of squamous cell or adenocarcinoma, as well as lacking histologic features of other carcinoma types. Among the subtypes of large cell carcinoma previously recognized by the World Health Organization, large-cell neuroendocrine carcinoma, basaloid carcinoma, and lymphoepithelial-like carcinoma have been reassigned as separate entities in the newer classification system. Basaloid carcinomas are therefore discussed with squamous cell carcinomas, as well as lymphoepithelial-like carcinoma (see Chapter 78). Large-cell neuroendocrine carcinoma is a separate entity within the spectrum of neuroendocrine carcinomas (see Chapter 80). The “rhabdoid” and “clear cell” subtypes are now considered histologic variations that may occur in defined histologic types of non-small cell lung carcinoma (especially adenocarcinoma and squamous carcinoma) (Tables 82.1 and 82.2).








TABLE 82.1 Terminology of Poorly Differentiated Lung Carcinomas







































Old Designation

Current Designation

Distinguishing Features


Adenocarcinoma, solid growth pattern

Adenocarcinoma, solid growth pattern

Histologic features (not small cell or LCNEC) and mucin vacuoles or TTF-1 or napsin-A expression


Large cell carcinoma, basaloid type

Basaloid carcinoma (variant of squamous cell)

Histologic features and IHC evidence of squamous differentiation


Large cell carcinoma, neuroendocrine type

Large-cell neuroendocrine carcinoma

Endocrine histologic features and endocrine differentiation (by IHC)


Rhabdoid carcinoma

Nonea

Light microscopic features


Clear cell carcinoma

Noneb

Light microscopic features


Large cell carcinoma, null type

Large cell carcinoma


Large cell undifferentiated carcinoma

Histologic features (not small cell or LCNEC) and absence of histologic features of sarcomatoid carcinoma and absence of IHC evidence of adeno- or squamous carcinoma


Lymphoepithelioma

Lymphoepithelial-like carcinomac

Histologic features and ISH positivity for EBER


IHC, immunohistochemistry; EBER, EBV-encoded small nuclear RNAs.


a Now a descriptive designation; diagnosis is based on areas of differentiation (adenocarcinoma, squamous carcinoma, etc.), or if all rhabdoid without evidence of specific differentiation, then “large cell carcinoma, rhabdoid type.”

b Also a descriptive designation; diagnosis is based on adenocarcinoma or squamous carcinoma differentiation or rarely large cell (undifferentiated).

c Variably classified separately (e.g., WHO) or as a variant of squamous cell carcinoma.


The rationale behind narrowing the scope of “large cell carcinoma” lies largely in the realization that molecular classification of many histologically undifferentiated carcinomas corresponds to immunohistochemical profiles.1,2,3,4 Although “large cell carcinoma” now denotes absence of immunohistochemical evidence of differentiation (“large cell carcinoma with null phenotype” or “large cell undifferentiated
carcinoma”), it must be noted that “large cell carcinoma” is still occasionally applied to TTF-1-positive tumors.5








TABLE 82.2 Immunohistochemical Staining of Undifferentiated Lung Carcinomas

Antibody

Note


Squamous differentiation

p40

Preferred


p63

Less specific than p40

Cytokeratin 5/6

Less specific than p40

Desmocollin-3

Not in wide use

Cytokeratin 903 (34βE12)

Lacks sensitivity and specificity


Adenocarcinoma differentiation

TTF-1

Preferred


Napsin-A

Occasionally positivity in TTF-1-negative tumors

Cytokeratin 7

Not specific



Tissue Sampling

Because “large cell carcinoma” is a diagnosis of exclusion, it should not be made on small biopsy samples, including cell blocks or cytologic preparations. To conserve tissue for molecular studies, the term “non-small cell carcinoma,” with modifiers favoring squamous or adenocarcinoma, is preferred, after utilizing only a small panel of immunohistochemical stains (usually TTF-1 and p40; see Chapter 86).


Incidence

The frequency of large cell carcinoma is difficult to determine, as it is based on negativity for TTF-1 and squamous markers. There is variation in published reports regarding the type of squamous marker used (p63, p40, cytokeratin 5/6, desmocollin-3, among others) as well as threshold for positivity. One series of tumor resections found that only 0.4% of lung carcinomas were large cell,1 which compared to over 9% in a series of microarray samples.6 Among undifferentiated or poorly differentiated tumors, there is a range of 2% to 31% of tumors that do not show evidence of squamous or adenocarcinoma by immunohistochemical study,1,2,3,5,6,7,8 again the higher numbers representing series of small tissue samples.

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Aug 19, 2016 | Posted by in CARDIOLOGY | Comments Off on Large Cell Carcinoma

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