Histological types of Lung Cancer: The Use of IHC in pathology and diagnosis

CONTENT: Histological Types of Lung Cancer

6.6.2 Examples of the Use of IHC in Lung Pathology Problem Solving
i. Adenocarcinoma versus Squamous Cell Carcinoma
ii. Small Cell Carcinoma versus Lymphoma
iii. Mesothelioma versus Non Small Cell Carcinoma (NSCLC)
iv. Primary Carcinoma versus Metastatic Melanoma
v. Lymphoid Hyperplasia versus Low-Grade B-cell Lymphoma

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Did you hear about the angry pancake? He just flipped!

6.6.2 Examples of the Use of IHC in Lung Pathology Problem Solving

There are many situations in which immunohistochemistry can support the light microscopic opinion in lung pathology.

i. Histological types of Lung Cancer: Adenocarcinoma versus Squamous Cell Carcinoma

The immunohistochemistry (IHC) markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34βE12) may be used. Two IHC markers of TTF-1/p63 is sufficient for sub-typing of the majority of tumors as adenocarcinomas versus squamous cell carcinoma; addition of CK5/6 may be required in a small subset of cases.

Figure 6.9 TTF-1-Positive IHC for Adenocarcinoma.

A. Photomicrograph of the histology of a non small cell carcinoma
in a small biopsy. (H&E x 40). B. IHC shows nuclear staining (brown)
of the cancer cells with antibodies to TTF-1. This is an adenocarcinoma
of the lung. (IHC for TTF-1 x 40)

This all sounds really complicated.

Not really, it simply means that the staining technique can help distinguish between different types of lung cancers.

I’m not giving up on my dreams, I’m just going to keep sleeping.

ii. Histological types of Lung Cancer: Large Cell Carcinoma versus Large Cell Neuroendocrine Carcinoma (LNEC)

Small cell lung cancer is defined by light microscopy, and the most important stain is a good-quality H&E-stained section. In problem cases, such as the large cell variant of neuroendocrine carcinoma (LNEC), IHC can help in making the distinction from other tumors.

Immuno-staining for pan-cytokeratin, such as AE1/AE3, demonstrates that the tumor is a carcinoma rather than a lymphoid tumor.

The most useful neuroendocrine markers include chromogranin, CD56, and synaptophysin; these are used as a panel with CD56 being positive in up to 90% of cases.

Figure 6.10 Synaptophysin-Positive IHC for LNEC.

A. Photomicrograph of the histology of a ‘large cell’ carcinoma in a small
biopsy. (H&E x 60). B. IHC shows cytoplasmic staining (brown) of the
cancer cells with antibodies to synaptophysin. This is a large cell
neuroendocrine carcinoma (LNEC) of the lung.
(IHC for synaptophysin x 40)

I’m going bananas. That’s what I say to my bananas before leaving the house.

iii. Histological types of Lung Cancer: Mesothelioma versus Non Small Cell Carcinoma (NSCLC)

E-cadherin is expressed in all adenocarcinomas and approximately 20% of mesotheliomas.

TTF-1 expression is found in up to 70% of lung adenocarcinomas and no mesotheliomas. Calretinin immunostaining is positive in 80% of mesotheliomas and 6% of the adenocarcinomas.

Cytokeratin 5/6 expression is detected in 5% of the adenocarcinomas and 60% of the mesotheliomas.

E-cadherin is almost 100% sensitive for pulmonary adenocarcinoma and TTF-1 is almost 100% specific for pulmonary adenocarcinoma.

If E-cadherin is positive and TTF-1 is negative, a secondary panel of antibodies may be used: this panel may include antibodies to BerEP4, LeuM1 (CD15), calretinin, cytokeratin 5/6 and thrombomodulin.

Figure 6.11 Calretinin-Positive IHC for Mesothelioma.

A. Photomicrograph of the histology of nodule in the pleura
shows gland-like structures in a fibrous stroma, possibly
representing a metastatic adenocarcinoma. (H&E x 60).
B. IHC shows cytoplasmic staining (brown) of the cancer
cells with antibodies to calretinin. This is a primary pleural
mesothelioma. (IHC for calretinin x 40)

Coffee, chocolate and men, some things are just better rich.

iv. Histological types of Lung Cancer: Primary Carcinoma versus Metastatic Melanoma

The IHC profile is similar to melanomas elsewhere in the body; melanomas are S100, HMB-45, and Mart-1 positive and negative for keratin.

An IHC panel to be used in the differential diagnosis of melanoma versus lung carcinoma could include pan-cytokeratin, S100, TTF-1, and Mart-1.

Figure 6.12 HMB-45-Positive IHC for Metastatic Melanoma.

A. Photomicrograph of the histology of a poorly differentiated tumor
from a lung nodule in a small biopsy. (H&E x 60). B. IHC shows
cytoplasmic staining (brown) of the tumor cells with antibodies to HMB045.
This is a metastatic melanoma. The patient had multiple lung nodules and
a primary melanoma of the skin. (IHC for HMB-45 x 60)

I see now – IHC helps to diagnose different cancers.

Exactly in the above slide this is a skin cancer that has spread to the lungs, not a primary lung carcinoma.

I’m loving IHC, can we call it the ‘Incredible Hector Charm?

v. Histological types of Lung Cancer: Lymphoid Hyperplasia versus Low-Grade B-cell Lymphoma

The immunophenotype of cells of MALT lymphoma is virtually identical to that of non-neoplastic, marginal-zone B-cells: CD20+, IgD−, CD5−, CD10−, Bcl6−, cyclin D1−.

No specific IHC marker has yet been identified for MALT lymphoma. The presence of a diffuse infiltrate of CD20+ B-cells between (cytokeratin+ glands) is highly suggestive of lymphoma. Staining for CD21 and CD10 can help to identify lymphoid follicles.

Figure 6.13 Low-Grade B-Cell Lymphoma versus
Reactive Lymphoid Hyperplasia.

Sub-bronchial lung nodules biopsied on bronchoscopy. A. Photomicrograph
of IHC on a section from the lung nodule stained for cytokeratin (brown)
shows entrapped epithelial cells in a ‘lympho-epithelial’ lesion. (IHC for
cytokeratin x 40). B. IHC shows staining (brown) of B-cells with antibodies
to CD20. This is low-grade B-cell lymphoma (BALToma). (IHC for CD20 x60).

I might look like I’m doing nothing, but in my head I’m actually quite busy.

References:

Conklin, C.M., Craddock, K.J., Have, C., Laskin, J., Couture, C. & Ionescu, D.N. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J. Thorac. Oncol. 8, 45–51 (2013). (Retrieved 19^th Feb 2015): https://www.ncbi.nlm.nih.gov/pubmed/23196275

Jagirdar J. (2008) Application of Immunohistochemistry to the Diagnosis of Primary and Metastatic Carcinoma to the Lung. Arch Pathol Lab Med 132(3) 384-396. (Retrieved 19^th Feb 2015): https://www.ncbi.nlm.nih.gov/pubmed/18318581

More references for this section are on this page .

Patient Information:

Information on immunohistochemistry: (Retrieved 19^th Feb 2015): http://www.immunohistochemistry.us

Anatomy-Histology Tutorials Special Stains (Retrieved 27^th April 2015):http://library.med.utah.edu/WebPath/HISTHTML/HISTO.html#1

More patient information for this section is on this page .

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