Case 43

A 56-year-old female with a 4.7 cm right breast mass, and here is the core biopsy:

1.What is the morphology impression? What is the IHC panel you would like to order?

IHC

• ER, PR
• CK5/6, calponin, SMMHC
• AR
• S100

See All Options

Answer

The differential diagnosis is either this is a exuberant DCIS with mucinous differentiation or a invasive carcinoma. The tumor was found to be ER, PR negative. Stay tuned for question 2.

2. If this is a invasive carcinoma and the MUC4 is positive, what's the molecular change?

   A: BRCA1

   B: BRCA2

   C: FUS-CREB

   D: MED12

   E: MYB-NFIB

   F: ETV6-NTRK3

Answer

The correct answer is F. This is a case of secretory carcinoma in breast, a type of salivary gland tumors. MUC4 can be a quite good marker in this setting.

Feature

Description

Histology

- Composed of polygonal tumour cells with eosinophilic granular or vacuolated cytoplasm.  - Nuclei are round to oval.  - Growth patterns: microcystic/honeycomb, solid, tubular, papillary.  - Microcystic areas may mimic thyroid follicles and merge into solid sheets.  - Most tumours show mixed patterns.

Secretions

- Intracytoplasmic and extracellular eosinophilic or amphophilic secretions.  - Positive staining with PAS, mucicarmine, and Alcian blue.

Nuclear Features

- Mild to moderate nuclear pleomorphism.  - Low mitotic activity.  - Vast majority are Grade 1 or 2 (modified Nottingham grading).  - High-grade tumours are exceptionally rare.

Stroma

- Often sclerotic.

In Situ Component

- May be present.  - Typically cribriform or solid with low to intermediate nuclear grade.  - Identifiable with myoepithelial antigen staining.

Immunohistochemistry

- Typically positive: CEA (polyclonal), S100, mammaglobin, SOX10, MUC4.  - Basal markers: CK5/6 and/or EGFR (HER1) (may be focal).  - Other markers: GATA3, CK8/18, KIT (CD117), vimentin.  - Hormone receptors: Mostly triple-negative for ER, PR, and HER2.  - Weak ER/PR expression not uncommon.  - Ki-67 proliferation index variable but often < 20%.

Differential Diagnosis

- Carcinoma with apocrine differentiation (usually AR-positive).  - Acinic cell carcinoma.   - Cystic hypersecretory carcinoma in situ.   - Tall cell carcinoma with reversed polarity.   - ETV6-NTRK3 fusion can support the diagnosis of secretory carcinoma.

References: https://tumourclassification.iarc.who.int/chaptercontent/32/28

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD