Pitfalls in breast pathology

Abstract

Accurate pathological diagnosis is the cornerstone of optimal clinical management for patients with breast disease. As non-operative diagnosis has now become the standard of care, histopathologists encounter the daily challenge of making definitive diagnoses on limited breast core needle biopsy (CNB) material. CNB samples are carefully evaluated using microscopic examination of haematoxylin and eosin (H&E)-stained slides and supportive immunohistochemistry (IHC), providing the necessary information to inform the next steps in the patient care pathway. Some entities may be difficult to distinguish on small tissue samples, and if there is uncertainty a diagnostic excision biopsy should be recommended. This review discusses (1) benign breast lesions that may mimic malignancy, (2) malignant conditions that may be misinterpreted as benign, (3) malignant conditions that may be incorrectly diagnosed as primary breast carcinoma, and (4) some IHC pitfalls. The aim of the review is to raise awareness of potential pitfalls in the interpretation of breast lesions that may lead to underdiagnosis, overdiagnosis, or incorrect classification of malignancy with potential adverse outcomes for individual patients.

Keywords: breast cancer mimics; immunohistochemistry pitfalls; overdiagnosis; underdiagnosis.

Figure 1

(A–D) Nipple adenoma with florid UDH (H&E).

Figure 2

(A) Radial scar in which entrapped and collapsed tubules are invested by an attenuated layer of MECs (H&E). (B) MECs may be difficult to appreciate even on IHC (p63 stain).

Figure 3

(A) Sclerosing adenosis can mimic ILC on H&E. (B) p63 stain highlights MECs associated with sclerosing adenosis. (C) DCIS involving sclerosing adenosis, associated with lymphocytes, mimicking IC. (D) p63 stain highlights MECs and aids interpretation as DCIS involving sclerosing adenosis.

Figure 4

Microglandular adenosis. (A) Microglandular adenosis has an infiltrative appearance and tubules are seen in the fat (H&E). (B) The tubules contain eosinophilic secretions (H&E). (C) The tubules lack a peripheral MEC layer, in contrast to admixed normal glandular breast tissue (p63 stain). (D) Microglandular adenosis is S100‐positive.

Figure 5

(A–D) Intraduct papilloma with exuberant UDH may mimic solid papillary carcinoma on H&E. (E,F) The characteristic mosaic staining pattern for CK5/6 and ER demonstrates the polyclonal nature of the epithelial proliferation, supporting the diagnosis of intraduct papilloma with florid UDH.

Figure 6

(A) Spindle cell proliferation with haemosiderin‐deposition (H&E). (B) Associated fat necrosis (H&E). The features support a diagnosis of scar.

Figure 7

Fibromatosis. (A) H&E stain shows a cytologically bland spindle cell proliferation. (B) Nuclear β‐catenin staining of fibromatosis.

Figure 8

Nodular fasciitis. H&E stain shows a cellular spindle cell proliferation composed of fibroblasts with a relatively bland appearance associated with some extravasated red blood cells.

Figure 9

(A,B) Pseudoangiomatous stromal hyperplasia (PASH).

Figure 10

(A) Epithelioid myofibroblastoma may mimic ILC (H&E). (B) Cells of myofibroblastoma express ER. (C) CD34 stains the myofibroblastoma.

Figure 11

(A) Histiocytic inflammation (H&E), which may resemble histiocytoid carcinoma (H&E) shown in B and C.

Figure 12

Granular cell tumour (H&E).

Figure 13

(A) Epithelial displacement may mimic IC (H&E). (B) Epithelial displacement in a lymphatic space mimicking lymphovascular invasion in a patient with a benign intraduct papilloma.

Figure 14

(A) Collagenous spherulosis colonized by LCIS (H&E). (B) E‐cadherin is negative in LCIS.

Figure 15

Lactational change. (A) Lactational change (H&E). (B,C) Lactational change with a deposit of calcium phosphate.

Figure 16

(A,B) Spindle cell DCIS may mimic UDH on H&E. (C) There is an absence of CK5/6 staining in spindle cell DCIS. (D) Spindle cell DCIS shows diffuse strong nuclear expression of ER.

Figure 17

(A) Fragments of encapsulated papillary carcinoma from a CNB (H&E). The proliferation shows diffuse strong nuclear expression of ER (B) and is negative for CK5/6 (C), confirming the clonal nature of this papillary lesion.

Figure 18

(A) Fibromatosis‐like metaplastic breast carcinoma has the appearance of a cytologically bland spindle cell proliferation on H&E. (B) Cytokeratin MNF116 reveals the epithelial nature of the lesion and supports a diagnosis of FLMBC.

Figure 19

(A) Angiosarcoma with a vasoformative growth pattern (H&E). (B) The periphery of the lesion has a more subtle appearance, with delicate thin‐walled vessels infiltrating the fat (H&E).

Figure 20

(A,B) Solid lobular carcinoma, low‐power and high‐power images (H&E). (C) Cytokeratin AE1AE3 IHC confirms the epithelial nature of the tumour cells. (D,E) low‐grade lymphoma, low‐power and high‐power images (H&E). (F) CD20 stains the low‐grade lymphoma.

Figure 21

(A,B) ILC showing loss of E‐cadherin expression. (C,D) ILC showing aberrant E‐cadherin expression with a fragmented pattern of membranous staining, which is decreased relative to background normal ductal epithelium. (E,F) Classical LCIS with negative E‐cadherin. Note also the granular staining of myoepithelial cells.

Figure 22

Myofibroblasts aligned alongside nests of IC cells with non‐specific calponin staining (calponin IHC). This non‐specific staining contrasts with strong cytoplasmic staining of MECs surrounding normal ductal epithelium and DCIS.

Figure 23

(A–C) Low‐grade adenosquamous carcinoma (H&E). (D) Epithelial cells of the small nests within the low‐grade adenosquamous carcinoma show focal p63 staining.