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Focal HER2 expression on IHC 0 breast carcinoma metastatic to the lung

The importance of reporting discrete HER2 IHC scores

Gary Tozbikian

MD

Case details

Age
54
Gender
Female

Primary/metastatic breast cancer
Metastatic
Type of breast cancer
Invasive ductal carcinoma NOS (NST)
Hormone receptor status
ER: Positive (100% nuclear staining)
PR: Positive (2% nuclear staining)
HER2 by IHC
0 with faint, incomplete staining
Pre-analytic variables and technical issues
None
Specimen type in metastatic setting
Lung biopsy
Prior test results
Reported history of primary breast cancer diagnosed 10 years prior. The primary breast cancer was a Grade 1, invasive ductal
carcinoma, ER: 50%, PR: 70%, HER2 IHC 0
(HER2-negative)

In this case, a patient presented with invasive ductal carcinoma that metastasized to the lung. HER2 IHC on the tumor biopsy showed HER2 expression that can be described as IHC 0 with faint, incomplete staining.¹ Examining the entire slide at high power is needed to detect focal staining on tumors with low levels of HER2 expression.^1,2*

Case summary

A 54-year-old female was diagnosed with HR-positive invasive ductal carcinoma that had progressed to metastatic disease.¹ The patient was previously diagnosed with Grade 1, HR-positive, HER2-negative primary breast cancer 10 years prior. At metastatic diagnosis, lung biopsy was obtained and analyzed for key biomarkers.¹

How were pre-analytic and analytic variables controlled for the case?

The lung biopsy sample was immediately placed into neutral buffered formalin and fixed for 12 hours and 49 minutes.¹ HER2 IHC testing was performed with Ventana PATHWAY anti-HER2/neu 4B5 assay.¹

What does the HER2 IHC staining indicate?

Before revealing the answer, attempt interpretation of the slide by viewing the whole slide image here.

The slide shows intratumoral heterogeneity for HER2 expression.¹ We can see focal staining at 40X power of magnification that shows faint/barely perceptible, incomplete membrane staining that is in less than 10% of tumor cells.¹

Figure 1. Focal faint/barely perceptible, incomplete HER2 IHC membrane staining (40X)¹

Click here to view and interact with whole slide images

As recommended by ASCO-CAP guidelines, a second pathologist reviewed the case to confirm the accuracy of the score at the lower end of the spectrum. An emphasis was made that faint cytoplasmic staining, present in this case, should not be considered in the assessment.^2,3

How were the results reported?*

Estrogen receptor:

Positive (100%, strong intensity)

Progesterone receptor:

Positive (2%, moderate intensity)

HER2:

Negative (Score 0 / Membrane staining that is incomplete and is faint/barely perceptible and in less than or equal to 10% of tumor cells (0+/with membrane staining))

Comment:

Per the electronic medical record, the patient's history of breast cancer and colorectal cancer is noted. Immunohistochemical stains show that the tumor is positive for CK7 and GATA3, and is negative for CK20, TTF-1, CDX2, and SATB2. The findings are consistent with a metastasis of breast origin.

“Detecting HER2 IHC 0 with faint, incomplete staining requires careful interrogation of the entire tumor at high power (40X) to identify focal areas of HER2 reactivity.”

Discussion

The current case was reported as HER2-negative (IHC 0 with faint, incomplete staining), which is consistent with the primary breast cancer.¹ While in the metastatic setting there was evidence of focal membrane staining, it is unclear, from the report, if the previous tumor showed any level of HER2 staining.¹

IHC 0 can be defined as membrane staining that is incomplete and is faint/barely perceptible and in ≤10% of tumor cells (0+) or no membrane staining (0). Staining on IHC 0 tumors can often be focal, which can make the assessment challenging.¹ Hence, scanning the entire tumor at high power (40X) is needed to detect focal HER2 reactivity and distinguish IHC 0 with faint, incomplete staining from IHC 0 without membrane staining.^1,2*

Considerations

Assess HER2 IHC at 40X power of magnification to detect faint and incomplete staining patterns²
Scan the entire tumor to detect focal membrane staining^1*
Discount the presence of cytoplasmic (blush) staining when evaluating and scoring HER2 expression by IHC^2,3
Report intensity, pattern and percentage of the tumor cell staining as it may inform clinical decision making⁴

You can find more information on how to approach assessment of HER2 IHC 0 with faint, incomplete staining in the Microscopy Series - Assessment of HER2 IHC in breast cancer: The lower end of HER2 expression, by clicking here.

*These practice considerations represent the opinions of the Breast Pathology Faculty. Members of the Breast Pathology Faculty have been contracted as paid advisors through Daiichi Sankyo and AstraZeneca and have received compensation for their time.

ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists; CDX2, caudal type homeobox 2; CK7, cytokeratin 7; CK20, cytokeratin 20; ER, estrogen receptor; GATA3; GATA binding protein 3; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; NOS, not otherwise specified; NST, no special type; PR, progesterone receptor; TTF-1; thyroid transcription factor -1.

1. Data on file. Daiichi Sankyo, Inc. Basking Ridge, NJ. 2. Wolff AC, et al. Arch Pathol Lab Med. 2023;147(9):993-1000. 3. Grassini D, et al. Pathobiology. 2022;89:278-296. 4. Ivanova M, et al. Virchows Arch. 2024;484(1):3-14.

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Focal HER2 expression on IHC 0 breast carcinoma metastatic to the lung

Gary Tozbikian

MD

Case details

Age

Gender

Primary/metastatic breast cancer

Type of breast cancer

Hormone receptor status

HER2 by IHC

Pre-analytic variables and technical issues

Specimen type in metastatic setting

Prior test results

Case summary

How were pre-analytic and analytic variables controlled for the case?

What does the HER2 IHC staining indicate?

Figure 1. Focal faint/barely perceptible, incomplete HER2 IHC membrane staining (40X)¹

How were the results reported?*

Discussion

Considerations

Explore more Clinical Case Reviews

Assessing HER2 IHC with cytoplasmic staining

In this case, the HER2 IHC on a segmental mastectomy specimen from a primary invasive ductal carcinoma showed an unusual cytoplasmic staining pattern.

Assessing HER2 IHC with edge artifacts

In this case, the HER2 IHC of a core needle biopsy specimen from an invasive breast carcinoma showed signs of edge artifact.

Interpreting HER2 IHC with an extensive in situ component

In this case, there was an extensive in situ component present along with the invasive carcinoma, and HER2 IHC scores were discordant between the two.

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Focal HER2 expression on IHC 0 breast carcinoma metastatic to the lung

Gary Tozbikian

MD

Case details

Patient information

Age

Gender

Case information

Primary/metastatic breast cancer

Type of breast cancer

Hormone receptor status

HER2 by IHC

Pre-analytic variables and technical issues

Specimen type in metastatic setting

Prior test results

Case summary

How were pre-analytic and analytic variables controlled for the case?

What does the HER2 IHC staining indicate?

Figure 1. Focal faint/barely perceptible, incomplete HER2 IHC membrane staining (40X)1

How were the results reported?*

Discussion

Considerations

Explore more Clinical Case Reviews

Assessing HER2 IHC with cytoplasmic staining

In this case, the HER2 IHC on a segmental mastectomy specimen from a primary invasive ductal carcinoma showed an unusual cytoplasmic staining pattern.

Assessing HER2 IHC with edge artifacts

In this case, the HER2 IHC of a core needle biopsy specimen from an invasive breast carcinoma showed signs of edge artifact.

Interpreting HER2 IHC with an extensive in situ component

In this case, there was an extensive in situ component present along with the invasive carcinoma, and HER2 IHC scores were discordant between the two.

Quick Links

Breast Cancer Links

Gastric Cancer Links

About Us

Legal

What is a Daiichi Sankyo Company or AstraZeneca authorized person?

Figure 1. Focal faint/barely perceptible, incomplete HER2 IHC membrane staining (40X)¹