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Interpreting HER2 IHC with an extensive in situ component

Case contributed by Hannah Wen, MD, PhD

The importance of reporting discrete HER2 IHC scores

Hannah Wen

MD, PhD

Case details

Age
68
Gender
Female

Tumor grade
2
Primary/metastatic breast cancer
Primary
Type of breast cancer
Invasive lobular carcinoma
Hormone receptor status
ER: Positive (90%, strong intensity)
PR: Positive (90%, strong intensity)
HER2 by IHC
0
Specimen type in primary setting:
Mastectomy

This case is a mastectomy specimen of primary invasive lobular carcinoma, grade 2. There was an extensive in situ component present along with the invasive carcinoma, and HER2 IHC scores were discordant between the two. In situ components may be ductal or lobular in nature. Regardless, it is important to only evaluate the invasive component of the specimen and ignore all in situ components when determining a patient’s HER2 IHC score.^1-3

Case summary

A total mastectomy was performed on a 68-year-old female with primary invasive lobular carcinoma.
The cold ischemic time for the specimen was under 1 hour and fixation was in 10% NBF for 24 hours. Biomarkers were performed on the sample, and controls were all appropriate.

Figure 1. H&E and HER2 IHC staining (IHC 0, 20X).

View whole slide image

What does the HER2 IHC staining indicate?

On the whole slide image (Figure 1), the area of invasive carcinoma shows no staining of HER2 (IHC 0). However, there is an extensive carcinoma in situ that shows complete and intense circumferential membrane staining. This can lead to misinterpretation of the specimen as HER2-positive, if not recognized as an in situ component.

The 2023 ASCO-CAP guideline update states that only the invasive component of a tumor should be evaluated for HER2 expression.1 In situ components should never be included in this evaluation.² To aid in differentiating invasive and in situ components it is helpful to always review the H&E and IHC slides in conjunction.³

A visual guide with examples of whole slide images corresponding to each HER2 IHC score may help with HER2 assessment. HER2 differentiation in practice: a quick visual guide can be found in the Supporting Resources.

Discussion

This case is challenging as there is discordance between HER2 IHC scores of the invasive carcinoma and the in situ component, with the in situ component potentially giving the appearance of a positive HER2 IHC result (false positive result). In situ components can be ductal or lobular in nature, DCIS or LCIS, respectively.⁴ It is important to be cognizant of the in situ components in invasive breast cancer IHC evaluation, as this component may be extensive in nature, and intermingled with the invasive component.^2,3

It is important to always review the corresponding H&E slide together with the IHC slide and determine the invasive components of the specimen that should then be evaluated.³ In situ components can be apparent on H&E sections, however, in difficult cases IHC for myoepithelial markers can be used to distinguish the invasive and in situ components.⁵

Considerations:

Discordance between the HER2 IHC score of the invasive carcinoma and in situ component can make case interpretation challenging*

HER2 staining of the in situ component should not be included in the HER2 IHC interpretation^2,3

Always review the corresponding H&E slide with the IHC³

Scroll through more Clinical Case Reviews for guidance on approaching challenging clinical cases.

*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; DCIS, ductal carcinoma in situ; ER, estrogen receptor; H&E, hematoxylin and eosin stain; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; LCIS, lobular carcinoma in situ; NBF, neutral buffered formalin; PR, progesterone receptor.

1. Wolff AC, et al. Arch Pathol Lab Med 2023;147(9):993-1000. 2. Hicks DG and Schiffhauer L. Laboratory Medicine 2011;42(8):459-467. 3. Wolff AC, et al. J Clin Oncol 2007;25(1):118-145. 4. Makki J. Clinical Medicine Insights: Pathology 2015;8:23-31. 5. Zaha DC. World J Clin Oncol 2014;5(3):382-392.

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In this series of articles, the Pathology Faculty share their experience with complex clinical cases and highlight practices that help to aid consistency in HER2 IHC scoring.

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.

by Savitri Krishnamurthy, MD

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.

by Gary Tozbikian, MD

The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with primary breast cancer classified as HER2-negative.

by Marilyn Bui, MD, PhD

Interpreting HER2 IHC with an extensive in situ component

Hannah Wen

MD, PhD

Case details

Age

Gender

Tumor grade

Primary/metastatic breast cancer

Type of breast cancer

Hormone receptor status

HER2 by IHC

Specimen type in primary setting:

Case summary

Figure 1. H&E and HER2 IHC staining (IHC 0, 20X).

What does the HER2 IHC staining indicate?

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.

The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with primary breast cancer classified as HER2-negative.

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Interpreting HER2 IHC with an extensive in situ component

Hannah Wen

MD, PhD

Case details

Patient information

Age

Gender

Case information

Tumor grade

Primary/metastatic breast cancer

Type of breast cancer

Hormone receptor status

HER2 by IHC

Specimen type in primary setting:

Case summary

Figure 1. H&E and HER2 IHC staining (IHC 0, 20X).

What does the HER2 IHC staining indicate?

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.

The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with primary breast cancer classified as HER2-negative.

Quick Links

Breast Cancer Links

Gastric Cancer Links

About Us

Legal

What is a Daiichi Sankyo Company or AstraZeneca authorized person?