Breast Pathology in Clinical Practice

© Springer Nature Switzerland AG 2020

S. ShoushaBreast Pathology in Clinical PracticeIn Clinical Practicehttps://doi.org/10.1007/978-3-030-42386-5_1

1. Introduction

Sami Shousha¹   

(1)

Imperial College, Imperial College Healthcare NHS Trust, London, UK

Sami Shousha

Email: [email protected]

Deceased

The role of the Surgical Pathologist in dealing with breast diseases has changed enormously during the last few years. The introduction of mammographic screening, conservative breast surgery and core, vacuum-assisted and sentinel lymph node biopsies, have changed the type of material received by the Pathologist for diagnosis, and the type of information required from him. Requests for frozen sections have markedly diminished, but new challenges have arisen, particularly in respect of diagnosing border-line lesions which are being increasingly detected by mammography, confirming the complete excision of malignant lesions, interpreting core and vacuum-assisted biopsies and examining and reporting specimens from patients who had neo-adjuvant chemo or hormone therapy.

This book is based on my experience at Charing Cross Hospital, London; and is aimed at presenting concise practical information for practising and trainee pathologists. It can also be of interest to other clinical practitioners looking after patients with breast disease who would like to know how pathologists work to reach up a diagnosis on which management of the disease is based. It also provides those practitioners with a ‘glossary’ of terms used and names given to various breast lesions and what they mean. I have previously published some of the discussed aspects in several review articles [1–4] and in an edited book [5].

References

1.

Shousha S. Histopathology of breast carcinoma and related conditions. In: Hoogstraten B, Burn I, Bloom HJG, editors. Breast cancer. Berlin: Springer; 1989. p. 13–44.Crossref

2.

Shousha S. New aspects in the histological diagnosis of breast carcinoma. Semin Surg Oncol. 1996;12:12–25.Crossref

3.

Shousha S. Reporting breast biopsies. Curr Diagn Pathol. 2000;6:140–5.Crossref

4.

Shousha S. Issues in the interpretation of breast core biopsies. Int J Surg Pathol. 2003;11:167–76.Crossref

5.

Shousha S, editor. Breast pathology. Problematic issues. Switzerland: Springer International Publishing; 2017.

© Springer Nature Switzerland AG 2020

S. ShoushaBreast Pathology in Clinical PracticeIn Clinical Practicehttps://doi.org/10.1007/978-3-030-42386-5_2

2. Core Biopsy

Sami Shousha¹   

(1)

Imperial College, Imperial College Healthcare NHS Trust, London, UK

Sami Shousha

Email: [email protected]

Deceased

Keywords

FNAStereotacticUltrasound and MRI guided and vacuum-assisted biopsiesB-scoringMulti-disciplinary team meetings

The Patient

To be a good breast pathologist you have to put yourself in the position of the patient. She, as patients with breast disease are mostly women, is anxious and frightened; either because she herself has discovered a lump in her breast, or she was told, after a routine screening, that she has an abnormal area in her breast that needs further investigation. This entails introducing a needle in the breast to get a sample of the lesion for microscopic examination. The first thing that will come to the patent’s mind would be the dreaded breast cancer. Whatever re-assuring the radiologist or surgeon is, the patient will not settle down until she is told the ‘Pathologist’s’ confirmed diagnosis. Hence the need for a fast and accurate diagnosis.

The Lesion

This could be either a palpable mass or a non-palpable lesion in the breast that was discovered by radiology in the form of abnormal microcalcification, a shadow of a soft tissue mass or an area of architectural distortion. The patient might also have abnormal axillary lymph nodes that need examination. The abnormal lymph node may have been detected by palpation or by abnormal radiological appearance.

The Doctor

Core biopsies are usually taken by Radiologists guided by x-ray, ultrasound, or less commonly, magnetic resonance imaging (MRI) machines. Surgeons sometimes do free, unaided, clinical cores for palpable lesions. Some Pathologists carry out fine needle aspirations.

The Needle

Hollow needles of different widths are used. Fine needles are used to get fluid aspirates from cysts or from patients who cannot tolerate the introduction of bigger needles. The most commonly used needle for getting a core biopsy, particularly for palpable lesions, is the 14 Gauge (G) needle. Needles with wider bores (11 or 10 G) are used with vacuum assistance, particularly for mammographic lesions with microcalcifications.

Type of Biopsies

Fine needle aspiration was the only technique available to get samples of breast lesions for microscopic examination until the introduction of core biopsies. It is mainly used now to aspirate cysts. The sample obtained usually contains some desquamated cells that can be examined microscopically to determine whether they are benign or malignant. The technique is also sometimes used to get samples from solid lesions in patients with bleeding disorders. Only a limited number of cells is obtained by this technique, and the amount of information provided can be very limited. Core biopsies are now the most widely used method for obtaining a non-operative/pre-operative diagnosis of breast lesions. They have superseded the use of fine needle aspiration cytology for that purpose mainly because of their higher specificity and sensitivity, their ability to differentiate, in most cases, between invasive and non-invasive, in situ, tumours, and because most pathologists are more familiar with diagnosing tissue sections, which a core can provide, than dealing with cytology preparations.

Stereotactic biopsies are taken by Radiologists using mammograms with a stereotactic attachment that can pinpoint the location of the radiologic abnormality, mostly microcalcifications, and accurately direct the core biopsy needle to it. Local anaesthetic is applied and a small incision is made in the skin before the introduction of the needle or the vacuum assisted probe.

Ultrasound guided core biopsies are also usually taken by Radiologists using an ultrasound device that produces accurate image of the structure of the breast. This helps accurate localisation of the abnormal area where the needle can then be inserted to get the required samples from the lesion. x-rays can be taken to show the needle within the lesion.

MRI guided biopsies are less commonly used usually to locate or exclude the presence of suspected lesions that were not seen using the other above-mentioned methods. MRI captures multiple cross sectional images of the breast and then combines them, using a computer, to generate a detailed three-diminsional images that can localise minute areas of abnormalities in the breast. The technique is so sensitive that not-uncommonly would pick up slightly worrying lesions that later prove to be benign by microscopic examination.

Either fine needle aspiration or an ultrasound guided core biopsy can be used for getting samples from abnormal lymph nodes.

The Sample

If the core biopsy was carried out for microcalcification, the radiologist should x-ray the cores to confirm the presence of calcification in them [1]. It would be useful if the cores’ x-ray is available for the pathologist to review, either digitally or as a hard copy, or at least for the radiologist to mention in the request form that the presence of calcification in the cores has been confirmed. It may be also useful to provide the cores containing calcium in a separate container, so that they can be embedded separately and if calcification is not seen microscopically in the first few sections, further sections can be cut from this particular paraffin block. The number of cores taken usually depends on the size and type of lesion, whether it is a mass or an area of calcification, as well as on the size of the needle used. It has been found that for stereotactic 14-gauge needle biopsy, 5 cores will achieve diagnosis of 99% of masses and 6 cores will lead to a diagnosis in 92% of microcalcification cases [2]. More cores have to be taken if the x-ray shows no microcalcification in the removed ones. A higher percentage of diagnosis in microcalcification cases can be achieved by using the 11 or 10-gauge vacuum-assisted device [3]. The cores should be dropped in formalin immediately after removal to ensure proper fixation.

The Request Form

The biopsy should be sent to the Pathology Laboratory with a completed request form carrying the patient’s full information, the reason for carrying the biopsy, the technique used, the number of cores and the suspected diagnosis. It is also important to indicate in the form the degree of suspicion, in a scale varying from 1 to 5, where 1 is probably normal and 5 is highly suspicious of malignancy. The prefix P is used if the degree of suspicion was based on clinical examination, M if based on mammography and U if based on ultrasound. Figure 2.1 shows an example of a request form used in our institution.

Fig. 2.1

An example of a request form that can be used for core biopsies and fine needle aspirates

The Laboratory

In the pathology Lab, for each case the number of cores received, their length and colour is recorded. All cores are processed, preferably not more than four cores in each cassette. We cut three shallow levels from each paraffin block for staining with haematoxlyn and eosin (H&E). We keep three intervening sections unstained to be used for immunohistochemistry if needed. Usually this is sufficient for making the diagnosis. Further sections are cut and examined if calcification was seen in the cores by the radiologist but has not been detected in the original sections. In a study of 168 cases of core biopsies with mammographic calcification, routine examination of 3 levels detected the calcification microscopically in 112 (67%) cases. Further sectioning (up to 10 sections) of 50 of the remaining cases, yielded calcification in 21 cases (42%). Out of these 21 cases, the diagnosis was changed in 11 cases (22%) after examining the new sections [4]. If the specimen x-ray was sent with the cores it is important to make sure that the calcifications in the sections correspond to those present in the x-ray. Very fine microcalcifications (less than 100 μm in diameter) which are sometimes detected in sections, are unlikely to be the ones seen in a mammogram; as the latter are usually coarser than that [5]. Lastly, it should be remembered that calcium oxalate crystals (Weddelite) do not stain with haematoxylin and can be easily missed during microscopic examination [6]. They usually appear as unstained faintly refractile crystals which are birefringent with polarised light. They are commonly present within relatively large benign cysts lined by apocrine epithelium [7, 8], and are seen only very rarely in association with DCIS [9].

The laboratory staff should be engaged in the process and understand the importance of their work. Good collaboration between the Laboratory staff and the pathologist are essential to guarantee getting timely, high quality, good stained sections that can be used in reaching the correct diagnosis.

The Pathologist

The diagnostic process starts by checking the patient’s name and the case number, followed by reading the clinical and radiological information provided. The number of cores in the slide is compared with the number noted in the request form and in the Lab. It is important to remember that cores can sometime fragment during processing. A look at the stained sections by the naked eye can sometimes provide an idea about what to expect to see under the microscope. This also helps identifying where the cores are on the slide, ensuring that on using the microscope all cores and fragments are examined.

The pathologist then examines the sections carefully and makes the diagnosis. The most important step is to decide whether the lesion is benign, malignant or border-line. The lesion is then named and given a ‘B’ score to convey a clear message to the treating physician about the nature of the lesion and how it should be managed (B refers to the use of a wide ‘Bore’ needle, compared with the C score used in Cytology for fine needle aspirate). The score extends from B1 to B5 as follows:

B1, Normal: indicates that the biopsy consists of normal breast tissue or shows minimal changes like fibrosis, mildly dilated ducts or minimal fine microcalcification. If these microscopic findings do not correspond to the radiological ones, further sections may have to be cut and if they are still negative, a repeat biopsy would be indicated.

B2, Benign: A specific benign diagnosis can be made that corresponds to the radiologic findings. This would include lesions like fibroadenoma, fibrocystic, fibroadenomatoid and columnar cell change, benign cyst, sclerosing adenosis, duct ectasia, peri-ductal mastitis, granulomatous mastitis, abscess, fat necrosis or post-operative scars. These are usually lesions that do not need surgical intervention.

B3, Benign with uncertain malignant potential: These are lesions that are known to be sometimes associated with the presence of malignancy or with a high risk of developing malignancy in the future. Examples include Atypical intraductal epithelial proliferations (atypical ductal hyperplasia), flat epithelial atypia, in situ lobular neoplasia, benign or atypical papillary lesions, microglandular adenosis, cellular fibroepithelial lesions, all non-malignant spindle cell lesions, granular cell tumours and complex sclerosing lesions. These lesions will usually need further clinical intervention in the form of vacuum-associated needle excision or surgical excision.

B4, Suspicious, probably malignant: These are core biopsies where there are a few atypical cells most likely malignant, but their number is too small, or their morphology is markedly distorted by crush artefact hindering a definite diagnosis of malignancy. A repeat biopsy is usually indicated in such cases.

B5, Malignant: Malignant cells are present in the core. This is subdivided into B5a for in situ carcinomas and B5b for invasive tumours whether they are carcinomas, sarcomas, malignant phyllodes or lymphomas.

The Multi-disciplinary Team Meeting (MDT)

All cases have to be then discussed in a multi-disciplinary meeting in the presence of Radiologists, Surgeons, Oncologists, Pathologists and Breast Care nurses. The clinical, radiological and pathological findings are presented and compared. If there are discrepancies a re-biopsy may have to be carried out. If the diagnosis is agreed, a plan is drawn for treatment (or no treatment in B2 cases). The Pathologist role in the meeting is essential and there should be facilities in the MDT room for projecting pictures of the cases under discussion, particularly for border-line lesions and for cases with unexpected findings.

References

1.

Liberman L, Evans WP III, Dershaw DD, Hann LE, Deutch BM, Abramson AF, Rosen PP. Radiography of microcalcifications in stereotaxic mammary core biopsy specimens. Radiology. 1994;190:223–5.Crossref

2.

Liberman L, Dershaw DD, Rosen PP, Abramson AF, Deutch BM, Hann LE. Stereotaxic 14-gauge breast biopsy: how many core biopsy specimens are needed. Radiology. 1994;192:793–5.Crossref

3.

Philpotts LE, Shaheen NA, Carter D, Lange RC, Lee CH. Comparison of rebiopsy rates after stereotactic core needle biopsy of the breast with 11-gauge vacuum suction probe versus 14-gauge needle and automatic gun. AJR. 1999;172:683–7.Crossref

4.

Grimes MM, Karageorge LS, Hogge JP. Does exhaustive search for microcalcifications improve diagnostic yield in stereotactic core needle breast biopsies? Mod Pathol. 2001;14:350–3.Crossref

5.

Dahlstrom JE, Sutton S, Jain S. Histologic-radiologic correlation of mammographically detected microcalcification in stereotactic core biopsies. Am J Surg Pathol. 1998;22:256–9.Crossref

6.

Tornos C, Silva E, El-Naggar A, Pritzker KPH. Calcium oxalate crystals in breast biopsies. The missing microcalcifications. Am J Surg Pathol. 1990;14:961–8.Crossref

7.

Gonzalez JEG, Caldwell RG, Valaitis J. Calcium oxalate crystals in the breast. Pathology and significance. Am J Surg Pathol. 1991;15:586–91.Crossref

8.

Truong LD, Cartwright J Jr, Alpert L. Calcium oxalate in breast lesions biopsied for calcification detected in screening mammography: incidence and clinical significance. Mod Pathol. 1992;5:146–52.PubMed

9.

Singh N, Theaker JM. Calcium oxalate crystals (Weddellite) within the secretions of ductal carcinoma in situ—a rare phenomenon. J Clin Pathol. 1999;52:143–5.Crossref

© Springer Nature Switzerland AG 2020

S. ShoushaBreast Pathology in Clinical PracticeIn Clinical Practicehttps://doi.org/10.1007/978-3-030-42386-5_3

3. Reporting Core Biopsies: Benign (B2) Lesions

Sami Shousha¹   

(1)

Imperial College, Imperial College Healthcare NHS Trust, London, UK

Sami Shousha

Email: [email protected]

Deceased

Introduction: Is the Lesion Benign or Malignant?

This is the most important question the pathologist is required to answer. In most cases, a straightforward answer can be easily made once the slides have been examined. However, there are certain benign conditions that can be confused with malignancy, e.g. microglandular adenosis, extensive sclerosing adenosis and entrapped glands in the centre of a radial scar. It has to be noted here that the latter two lesions may be associated with smaller malignant elements. There are also border-line lesions where a benign or a malignant decision cannot be easily agreed upon. These include the atypical intraductal proliferative lesions, atypical apocrine lesions and atypical vascular lesions developing in the skin or breast tissue following radiotherapy. However, strict adherence to the standardised criteria for the diagnosis of these lesions can markedly reduce inter-observer disagreements [1].

Benign Lesions That Do Not Usually Need Further Intervention (B2 Lesions)

Fibroadenoma

Fibroadenomas are probably the most common benign lesions seen in core biopsies. They present mostly in young women in their late teens and twenties, although with the introduction of mammographic screening they are also being diagnosed now in much older women. They are usually single lesions that vary widely in size. In a review of 396 cases from Holland in females varying in age between 12 and 81 years (mean 33), the size varied between 1 and 220 mm [2]. In that study, 8% of the patients had multiple tumours that were bilateral in 3%.

In its usual form a fibroadenoma consists of bland hypocellular fibrous tissue and distorted glandular structures. Classically, two microscopic types are described, with no difference in behaviour: peri-canalicular, where the stroma surround the glandular elements (Fig. 3.1), and intra-canalicular (Fig. 3.2) where the epithelial elements are stretched out and the stroma may appear enclosed by the glands. Clefts may occur in the latter form making them confused with phyllodes tumours, but they lack the stromal hypercellularity characteristic of phyllodes tumours. However, recent research suggested the presence of similar gene mutation (recurrent MED12 exon 2) in juvenile intracanalicular fibroadenoma and benign phyllodes tumours [3].

Fig. 3.1

Peri-canalicular fibroadenoma with usual type epithelial hyperplasia

Fig. 3.2

Intracanalicular fibroadenoma

A degree