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Guidelines for the pathological management of mammographically detected breast lesions
The Breast (1995) 4.52-56 0 Pearson Professional Ltd 1995
Guidelines for the pathological management of mammographically detected breast lesions B. Zafrani, G. Contesso,* V. Eusebi,? R. Holland,* R. R. Millis,§ and J. L. Petersell Department of Pathology, Institut Curie, Paris, France, *Department of Pathology, Institut Gustave Roussy, Villeju$ France, fistituto di Anatomia e Istologica Patologica, University of Bologna, Italy, #National Expert and Training Centre for Breast Cancer Screening, Nijmegen, The Netherlands, jlmperial Cancer Research Fund, Clinical Oncology Unit, Guy’s Hospital, London, UK “Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
S U MM A R Y. In order to evaluate adequately mammographically-detected breast lesions, adherence to a strict protocol is essential. Otherwise, small lesions may be missed and difficult differential diagnosis made harder. In the handling of these lesions, good communication between the pathologist, radiologist and surgeon is essential. INTRODUCTION
SPECIMEN
As with any biopsy of the breast, it is essential that biopsies performed for a mammographic abnormality be sent immediately, uncut, to the pathology laboratory. The specimen should be orientated by markers (nipple and pectoral sides), and accompanied by relevant clinical and mammographic information, and a specimen X-ray. The specimen should be measured in three dimensions and in some centres specimens are also routinely weighed. Information about the treatment procedure (diagnostic incision, or diagnostic/therapeutic excision) is helpful in accurately evaluating these specimens.
When dealing with biopsies performed for screendetected non-palpable lesions of the breast, the pathologist faces several different problems. Firstly, it is necessary to identify the histological lesion corresponding to the mammographic abnormality. Often, there is no palpable or grossly evident lesion, which means that samples for histological examination cannot be selected by the usual methods. The abnormality needs to be located by other means. Secondly, the histological analysis can be difficult given the high proportion of borderline lesions and in situ carcinomas which are detected by screening.’ Thirdly, in the case of a malignant lesion, the pathologist has to assess the adequacy of the surgical excision and to measure the extent of the lesion which was invisible on macroscopic examination. For all these reasons, it is essential to handle these biopsies according to a precise protocol.‘-” Good communication between the pathologist, the radiologist and the surgeon is the keystone for proper management of these lesions. Some specimens which are excised because of a mammographic abnormality will prove, on initial macroscopic examination, to contain a grossly evident tumor. Such specimens may be handled as if they were palpable masses and not necessarly as outlined in the following guidelines. Specimen radiography, however, can prove helpful even for palpable lesions when assessing margins of excision.12
Address correspondence 75005 Paris, France
to: B. Zafrani,
Institut
Curie,
SUBMISSION
SPECIMEN
X-RAY
All specimens excised after localization procedures for non-palpable, screen-detected lesions should be Xrayed intact to confirm the presence of the abnormality and to assess its localization in relation to resection margins. ‘-We Magnification views and specimen compression may be of help as they result in enhanced image resolution. In order to properly interpret the specimen radiograph, the pre-operative mammograms must be available. Ideally, confirmation that the mammographic abnormality has been removed should be undertaken by the radiologist who interpreted the clinical mammograms. A specimen radiograph must, however, always be made available to the pathologist. Some tissue opacities are difficult to demonstrate on specimen X-rays because the relationship of the abnormality to the surrounding breast tissue, which helps to identify the abnormal area on the mammogram, is lost. It is essential to discuss
26 rue d’Ulm,
52
Pathological
these difficulties with the radiologist and the surgeon. A second specimen X-ray of the sliced specimen may be very helpful for precise mammographic - histologic correlation (see below).
PLANES OF SURGICAL
EXCISION
Before processing these biopsies further, as with all breast specimens, it is essential that the surface of each be marked prior to slicing: this will permit the histological evaluation of the surgical margins.3.7.9-‘1,13With the trend towards conservative treatment for malignant lesions it is important to give precise information on the adequacy of excision. Different materials have been suggested for marking surgical planes of excision including: India ink, India ink mixed with acetone, artists’ pigments, coloured gelatins, Tipp-Ex and Alcian blue.‘“lR Artist’s pigments and Tipp-Ex being radio-opaque should not be used as they may confuse radiological details on the sliced specimen radiograph. Although slow to dry, India ink is used in many laboratories, but the choice of a marker should depend on local preference. Whatever method is used several steps must be followed carefully in order to ensure that the marker stays on the surface of the specimen. The specimen should be rinsed free of blood and moisture: this can be done easily with alcohol which will also dry the surface. It should then be blotted dry and the marker applied with a small paint brush. The specimen can then be blotted dry again or immersed in Bouin’s solution for approximately 30 s. This will serve to fix the marker onto the surface. The
Fig. l-Radiograph
of a sliced
specimen.
Microcalcifications
of breast
lesions
53
specimen should then be rinsed briefly in cold water and blotted dry again.
LOCALIZATION MARKING
management
OF THE ABNORMALITY
Two methods are currently used to localize precisely the mammographic abnormality in order to select the areas to be sampled: the first one is the slicing method, the second is the grid method.
Slicing
~~th~23;1~9,10,1~,19”0
The tissue is cut into 34 mm parallel slices which are identified in a consecutive order. This can be done on the fresh specimen, using a good quality sharp knife. Freezing of the tissue for 15 min at -20°C will help to make fatty specimens firmer. The slices should then be re-X-rayed (Fig. 1). Sectioning can be done perpendicular to the plane of the specimen X-ray which is usually the long axis of the specimen. This has the advantage of yielding small slices easy to fit into cassettes, but does not help correlation with the mammographic picture. Alternatively, slicing parallel to the plane of the specimen X-ray permits more precise correlation between the X-ray of the slices and the mammogram, but has the disadvantage of yielding large slices that must be recut to fit into cassettes. The slices on the radiograph are labelled and the tissue slices placed in correspondingly labelled cassettes which enables histologic-radiologic correlation.
are identified
in several
sites (arrows).
54
The Breast
Fig. 3-Ductal in situ carcinoma (0) observed in sections from slices C, D, E, F. Four slices of approximately 3 mm each, therefore extent of lesion is approximately 12 mm.
Fig. S-Radiograph of a needle localization specimen within a Plexiglas device. X and Y axes with radio-opaque alpha-numeric markers permit precise localization of the microcalcifications.
scribed above and shown in the diagram (Fig. 3), the serial slices of the specimen are consecutively labelled. The extent of the lesion can be assessed by relating the involved sections to the X-ray of both the slices and the whole specimen.
Grid methodz1J2 This method uses a special Plexiglas device with a grid of small holes to which the intact specimen is attached. Specimen radiography is performed on the Plexiglas board and radio-opaque markers permit the precise localization of the lesion (Fig. 2). Sections can be taken directly from the specimen. The advantage of this method is that only one radiograph needs to be taken and the radiologist can indicate on the specimen radiograph the area to be sampled. However, the disadvantage in comparison with the previous method is that exact correlation between the radiographic features and the histological slides is not so precise. As with the slicing method, labelled samples should be placed in correspondingly labelled cassettes. Specimen radiograms can be performed either using a self-contained table-top unit (Faxitron, Hewlett Packard or JKJ Micro specimen unit, Xerox Medical systems) or with a clinical mammogram machine. Although, in many of these specimens no gross abnormality will be detected, careful macroscopic examination of the intact and sliced specimen should be carried out.
SIZE OF THE LESIONS The extent of malignant lesions can be assessed either directly in the histological slides or more accurately with a combined radiographic-histologic approach which is much easier to perform with the slicing method which permits ‘spatial reconstruction’ of the lesions. As de-
IDENTIFICATION CORRESPONDING ABNORMALITY
OF THE LESIONS TO THE MAMMOGRAPHIC
It is essential to verify that the lesions observed in the histological sections correspond to the mammographic abnormality, particularly in the case of microcalcifications. The most common type of microcalcification is composed of amorphous calcium phosphate or hydroxyapatite and is readily recognized as opaque basophilic deposits on hematoxilin and eosin stained sectionsT3 Calcium oxalate or weddellite, the other type of microcalcification sometimes present, does not stain with the conventional dyes. Therefore, it can be overlooked on initial histologic examination. The use of polarized light microscopy is necessary to reveal them as birefringent crystals.24-26 If calcification cannot be identified in the sections, then the blocks and any reserve tissue should be X-rayed in order to see whether it lies deeper in the blocks or has not be sarnpled.r2
PARTICULAR PROBLEMS WITH SPECIMENS CONTAINING MAMMOGRAPHKALLY DETECTED LESIONS Biopsies in multiple fragments If biopsies are sent in multiple fragments, this may preclude the correct identification of lesions on spe-
Pathological
cimen radiography, the evaluation of margins and the measurement of the extent of the lesions.’
Frozen section examination Indications for frozen section examination depend on the treatment protocol in each institution, but as a rule it is inappropriate to perform frozen section examination on mammographically-detected non-palpable lesions and it is definitively contraindicted in cases of soft tissue densities measuring less than 0.5 cm and in all cases of microcalcifications.3~4~7-” Indeed, most mammographically detected lesions are very small and it may be impossible to perform a frozen section and leave enough unfrozen tissue for permanent sections. The strictly focal nature of borderline lesions and microinvasion makes the loss of diagnostic tissue a distinct possibility. Furthermore, freezing of the tissue may produce major artefacts which can render the specimen unsuitable for obtaining a definitive diagnosis after paraffin-embedding. This is particularly undesirable in mammographically-detected lesions which often present diagnostic problems. Additionally frozen section examination may preclude the precise assessment of the surgical margins and also the measurement of the size of malignant lesions.
management
of breast
lesions
55
is performed. Although time consuming, the advantage of keeping the whole biopsy in labelled cassettes is 2-fold: firstly, the ease with which this two step procedure can be done which means a reduction in the number of blocks processed in the case of benign lesions and secondly, in the case of malignant lesions it is possible to precisely analyse the surgical planes of excision and the extent of the tumor.
Large specimens Particular problems are encountered in the sampling of large specimens. The use of large histological sections has been recommended by some authors to assess disease extent and excision margins.6s31Although an attractive method, it has several disadvantages precluding its routine use in many laboratories. This method requires specialized equipment (microtome, cassettes, tissue stainer), and the quality of the sections obtained may be inferior due to the difficulties of cutting large sections. The slicing method described above, as it permits spatial reconstruction of the lesions and margins assessment, can overcome the problems of sampling large specimens.
References Sampling of the specimen: to what extent? Ideally, each specimen should be totally embedded for histological examination. Several studies have shown that in up to 30% of breast excisions performed for microcalcifications, the calcifications are identified only in benign lesions adjacent to a carcinoma.27-28 However, in practice, submission of the entire specimen is incompatible with the routine workload in busy laboratories. Recent studies addressing this issue have shown that histologic examination restricted to the areas of radiographic calcifications and the immediately surrounding tissues results in a high level of detection of clinically significant lesions and a considerable reduction in the amount of tissue processed.29s30However, in cases of malignant lesions, and particularly in situ ductal carcinoma, this sampling method does not always allow for accurate measurement of the lesion or assessment of the margins. A practical alternative approach is a two step procedure. The entire specimen is sliced and placed into cassettes which are precisely labelled, corresponding to the labelling of the sliced or grid radiograph. The first step consists of selecting only the cassettes containing the manunographic abnormality and the adjacent tissue, as well as any other suspicious area, for processing. The remaining cassettes are kept in fixative. If the histological sections show only benign lesions, no further processing is performed. If the histological sections reveal carcinoma or atypical hyperplasia, as a second step, processing of the tissue in the remaining cassettes
1. Elston C W, Ellis I 0. Pathology and breast screening. Histopathology 1990; 16: 109-l 18. 2. Anderson T J. Breast cancer screening: principles and practicalities for histopathologists. Recent advances in histopathololgy 14. Edinburgh: Churchill Livingstone, 1989; 43-61. 3. Armstrong J S, Davies J D. Laboratory handling of impalpable breast lesions: a review. J Clin Path01 1991; 44: 89-93. 4. Association of Directors of Anatomic and Surgical Pathology. Immediate management of mammographically detected breast lesions. Am J Surg Path01 1993; 17(8): 850-851. 5. Fechner R E, Mills S E. Breast pathology. Benign proliferations, atypias and in situ carcinomas. Chicago: ASCP Press 1990; pp 15-20. 6. Gad A. Screening for breast cancer: examination and reporting of histopathological preparations. Lancet ii 1988; 953. I. Lagios M D, Bennington J L. Protocol for the pathologic examination and tissue processing of the mammographically directed breast biopsy. In: Bennington J L, Lagios M D, eds. The mammographically directed biopsy. Philadelphia: Hanley and Belfus, 1992, pp 23-45. 8. Royal College of Pathologists Working Group. Pathology reporting in breast cancer screening. J Clin Path01 1991; 44: 710-725. 9. Schnitt S J, Connolly J L. Processing and evaluation of breast excision specimens. A clinically oriented approach. Am J Clin Path01 1992; 98(l): 125-137. 10. Schnitt S J. Specimen processing. In: Tavassoli F A. Pathology of the breast. Norwalk, CT: Appleton and Lange, 1992, pp 63-78. 11. Zafrani B, Laurent M. Microcalcifications mammaires sans tumeur palpable decouvertes par mammographie. Technique d’etude anatomo-pathologique. Ann Path01 1990; 10: 282-284. 12. Holland R. The role of specimen X-ray in the diagnosis of breast cancer. Diagn Imag Clin Med 1985; 54: 178-185. for breast cancer. Hum 13. Carter D. Margins of ‘lumpectomy’ Path01 1986; 17: 330-332. J S, Wiensweig P, Davies J D. Differential marking 14. Armstrong excision planes of breast lesions by coloured gelatin. J Clin Path01 1990; 43: 604-607.
56 TheBreast 15. Birch P J, Jeffery M J, Andrews M I J. Al&n blue: a reliable rapid method for marking resection margins. J Clin Path01 1990; 43: 608-609. 16. Chart K W, Lui I, Chung W B. Marking planes of surgical excision with a mixture of India ink and acetone. J Clin Path01 1989; 42: 893. 17. Harris M D. Tipp-Ex: a novel marker for resection margins. J Path01 1990; 160: 168. 18. Paterson D A, Davies J D. Marking planes of surgical excision on breast biopsy specimens: use of artists’ pigments suspended in acetone. J Clin Path01 1988; 41: 1013-1016. 19. Charpin C, Bonnier P, Habib M C et al. X-raying of sliced surgical specimens during surgery: an improvement of the histological diagnosis of impalpable breast lesions with microcalcifications. Anticancer Res 1992; 12: 1737-1746. 20. Going J J, Anderson T J. Optimal handling of breast carcinomas and breast localisation bioosies. J Path01 1989; 157: 164. 21. Champ C S, Mason C H, Coghill S B, Robinson M. A perspex grid for localization of non-palpable mammographic lesions in breast biopsies. Histopathology 1989; 14: 31 l-315. 22. Gauvin G P. Shortsleeve M J, Ostheimer J T. A rapid technioue for accurately localizing n&calcifications in breast biopsy specimens. Am J Clin Path01 1990; 93: 557-560. 23. Frappart L, Remy I, Hu Chi Lin et al. Different types of microcalcifications observed in breast pathology. Correlations with histopathological diagnosis and radiological examination of operative specimens. Virchows Arch A 1986,410: 179-187. 24. Going J J, Anderson T J, Cracker P R, Levison D A. Weddellite
25. 26. 27.
28. 29. 30.
31.
calcification in the breast: 18 caseswith implications for breast cancer screening. Histopathology 1990; 16: 119-124. Gonzalez J E G, Caldwell R G, Valaitis J. Calcium oxalate crystals in the breast. Pathology and significance. Am J Surg Path01 1991; 15(6): 586-591. Tomos C, Silva E, El-Naggar A, Pritzker K P H. Calcium oxalate crystals in breast biopsies. The missing microcalcifications. Am J Surg Path01 1990, 14(10): 961-968. Prorok J J, Trostle D R, Scarlato M, Rachman R. Excisional breast biopsy and roentgenographic examination for mammographically detected microcalcitications. Am J Surg 1983; 145: 684686. Sickles E A. Mammographic features of 300 consecutive nonpalpable breast cancers. A J R 1986; 146: 661-663. De Mascarel I, Trojani M, Bonichon F, Coindre J M. Histological examination of 2859 breast biopsies. Analysis of adequate sampling. Path01 Annu part I 1993: 1-13. Owings D V, Harm L, Schnitt S J. How thoroughly should needle localization breast biopsies be sampled for microscopic examination? A prospective mammographic/pathologic correlative study. Am J Surg Path01 1990; 14(6): 578-583. Gibbs N M. Large paraffin sections and chemical clearance of axillary tissues as a routine procedure in the pathological examination of the breast. Histopathology 1982; 6: 647-660.
Date received 28 February 1994 Date accepted after revision 6 June 1994
Guidelines for the pathological management of mammographically detected breast lesions B. Zafrani, G. Contesso,* V. Eusebi,? R. Holland,* R. R. Millis,§ and J. L. Petersell Department of Pathology, Institut Curie, Paris, France, *Department of Pathology, Institut Gustave Roussy, Villeju$ France, fistituto di Anatomia e Istologica Patologica, University of Bologna, Italy, #National Expert and Training Centre for Breast Cancer Screening, Nijmegen, The Netherlands, jlmperial Cancer Research Fund, Clinical Oncology Unit, Guy’s Hospital, London, UK “Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
S U MM A R Y. In order to evaluate adequately mammographically-detected breast lesions, adherence to a strict protocol is essential. Otherwise, small lesions may be missed and difficult differential diagnosis made harder. In the handling of these lesions, good communication between the pathologist, radiologist and surgeon is essential. INTRODUCTION
SPECIMEN
As with any biopsy of the breast, it is essential that biopsies performed for a mammographic abnormality be sent immediately, uncut, to the pathology laboratory. The specimen should be orientated by markers (nipple and pectoral sides), and accompanied by relevant clinical and mammographic information, and a specimen X-ray. The specimen should be measured in three dimensions and in some centres specimens are also routinely weighed. Information about the treatment procedure (diagnostic incision, or diagnostic/therapeutic excision) is helpful in accurately evaluating these specimens.
When dealing with biopsies performed for screendetected non-palpable lesions of the breast, the pathologist faces several different problems. Firstly, it is necessary to identify the histological lesion corresponding to the mammographic abnormality. Often, there is no palpable or grossly evident lesion, which means that samples for histological examination cannot be selected by the usual methods. The abnormality needs to be located by other means. Secondly, the histological analysis can be difficult given the high proportion of borderline lesions and in situ carcinomas which are detected by screening.’ Thirdly, in the case of a malignant lesion, the pathologist has to assess the adequacy of the surgical excision and to measure the extent of the lesion which was invisible on macroscopic examination. For all these reasons, it is essential to handle these biopsies according to a precise protocol.‘-” Good communication between the pathologist, the radiologist and the surgeon is the keystone for proper management of these lesions. Some specimens which are excised because of a mammographic abnormality will prove, on initial macroscopic examination, to contain a grossly evident tumor. Such specimens may be handled as if they were palpable masses and not necessarly as outlined in the following guidelines. Specimen radiography, however, can prove helpful even for palpable lesions when assessing margins of excision.12
Address correspondence 75005 Paris, France
to: B. Zafrani,
Institut
Curie,
SUBMISSION
SPECIMEN
X-RAY
All specimens excised after localization procedures for non-palpable, screen-detected lesions should be Xrayed intact to confirm the presence of the abnormality and to assess its localization in relation to resection margins. ‘-We Magnification views and specimen compression may be of help as they result in enhanced image resolution. In order to properly interpret the specimen radiograph, the pre-operative mammograms must be available. Ideally, confirmation that the mammographic abnormality has been removed should be undertaken by the radiologist who interpreted the clinical mammograms. A specimen radiograph must, however, always be made available to the pathologist. Some tissue opacities are difficult to demonstrate on specimen X-rays because the relationship of the abnormality to the surrounding breast tissue, which helps to identify the abnormal area on the mammogram, is lost. It is essential to discuss
26 rue d’Ulm,
52
Pathological
these difficulties with the radiologist and the surgeon. A second specimen X-ray of the sliced specimen may be very helpful for precise mammographic - histologic correlation (see below).
PLANES OF SURGICAL
EXCISION
Before processing these biopsies further, as with all breast specimens, it is essential that the surface of each be marked prior to slicing: this will permit the histological evaluation of the surgical margins.3.7.9-‘1,13With the trend towards conservative treatment for malignant lesions it is important to give precise information on the adequacy of excision. Different materials have been suggested for marking surgical planes of excision including: India ink, India ink mixed with acetone, artists’ pigments, coloured gelatins, Tipp-Ex and Alcian blue.‘“lR Artist’s pigments and Tipp-Ex being radio-opaque should not be used as they may confuse radiological details on the sliced specimen radiograph. Although slow to dry, India ink is used in many laboratories, but the choice of a marker should depend on local preference. Whatever method is used several steps must be followed carefully in order to ensure that the marker stays on the surface of the specimen. The specimen should be rinsed free of blood and moisture: this can be done easily with alcohol which will also dry the surface. It should then be blotted dry and the marker applied with a small paint brush. The specimen can then be blotted dry again or immersed in Bouin’s solution for approximately 30 s. This will serve to fix the marker onto the surface. The
Fig. l-Radiograph
of a sliced
specimen.
Microcalcifications
of breast
lesions
53
specimen should then be rinsed briefly in cold water and blotted dry again.
LOCALIZATION MARKING
management
OF THE ABNORMALITY
Two methods are currently used to localize precisely the mammographic abnormality in order to select the areas to be sampled: the first one is the slicing method, the second is the grid method.
Slicing
~~th~23;1~9,10,1~,19”0
The tissue is cut into 34 mm parallel slices which are identified in a consecutive order. This can be done on the fresh specimen, using a good quality sharp knife. Freezing of the tissue for 15 min at -20°C will help to make fatty specimens firmer. The slices should then be re-X-rayed (Fig. 1). Sectioning can be done perpendicular to the plane of the specimen X-ray which is usually the long axis of the specimen. This has the advantage of yielding small slices easy to fit into cassettes, but does not help correlation with the mammographic picture. Alternatively, slicing parallel to the plane of the specimen X-ray permits more precise correlation between the X-ray of the slices and the mammogram, but has the disadvantage of yielding large slices that must be recut to fit into cassettes. The slices on the radiograph are labelled and the tissue slices placed in correspondingly labelled cassettes which enables histologic-radiologic correlation.
are identified
in several
sites (arrows).
54
The Breast
Fig. 3-Ductal in situ carcinoma (0) observed in sections from slices C, D, E, F. Four slices of approximately 3 mm each, therefore extent of lesion is approximately 12 mm.
Fig. S-Radiograph of a needle localization specimen within a Plexiglas device. X and Y axes with radio-opaque alpha-numeric markers permit precise localization of the microcalcifications.
scribed above and shown in the diagram (Fig. 3), the serial slices of the specimen are consecutively labelled. The extent of the lesion can be assessed by relating the involved sections to the X-ray of both the slices and the whole specimen.
Grid methodz1J2 This method uses a special Plexiglas device with a grid of small holes to which the intact specimen is attached. Specimen radiography is performed on the Plexiglas board and radio-opaque markers permit the precise localization of the lesion (Fig. 2). Sections can be taken directly from the specimen. The advantage of this method is that only one radiograph needs to be taken and the radiologist can indicate on the specimen radiograph the area to be sampled. However, the disadvantage in comparison with the previous method is that exact correlation between the radiographic features and the histological slides is not so precise. As with the slicing method, labelled samples should be placed in correspondingly labelled cassettes. Specimen radiograms can be performed either using a self-contained table-top unit (Faxitron, Hewlett Packard or JKJ Micro specimen unit, Xerox Medical systems) or with a clinical mammogram machine. Although, in many of these specimens no gross abnormality will be detected, careful macroscopic examination of the intact and sliced specimen should be carried out.
SIZE OF THE LESIONS The extent of malignant lesions can be assessed either directly in the histological slides or more accurately with a combined radiographic-histologic approach which is much easier to perform with the slicing method which permits ‘spatial reconstruction’ of the lesions. As de-
IDENTIFICATION CORRESPONDING ABNORMALITY
OF THE LESIONS TO THE MAMMOGRAPHIC
It is essential to verify that the lesions observed in the histological sections correspond to the mammographic abnormality, particularly in the case of microcalcifications. The most common type of microcalcification is composed of amorphous calcium phosphate or hydroxyapatite and is readily recognized as opaque basophilic deposits on hematoxilin and eosin stained sectionsT3 Calcium oxalate or weddellite, the other type of microcalcification sometimes present, does not stain with the conventional dyes. Therefore, it can be overlooked on initial histologic examination. The use of polarized light microscopy is necessary to reveal them as birefringent crystals.24-26 If calcification cannot be identified in the sections, then the blocks and any reserve tissue should be X-rayed in order to see whether it lies deeper in the blocks or has not be sarnpled.r2
PARTICULAR PROBLEMS WITH SPECIMENS CONTAINING MAMMOGRAPHKALLY DETECTED LESIONS Biopsies in multiple fragments If biopsies are sent in multiple fragments, this may preclude the correct identification of lesions on spe-
Pathological
cimen radiography, the evaluation of margins and the measurement of the extent of the lesions.’
Frozen section examination Indications for frozen section examination depend on the treatment protocol in each institution, but as a rule it is inappropriate to perform frozen section examination on mammographically-detected non-palpable lesions and it is definitively contraindicted in cases of soft tissue densities measuring less than 0.5 cm and in all cases of microcalcifications.3~4~7-” Indeed, most mammographically detected lesions are very small and it may be impossible to perform a frozen section and leave enough unfrozen tissue for permanent sections. The strictly focal nature of borderline lesions and microinvasion makes the loss of diagnostic tissue a distinct possibility. Furthermore, freezing of the tissue may produce major artefacts which can render the specimen unsuitable for obtaining a definitive diagnosis after paraffin-embedding. This is particularly undesirable in mammographically-detected lesions which often present diagnostic problems. Additionally frozen section examination may preclude the precise assessment of the surgical margins and also the measurement of the size of malignant lesions.
management
of breast
lesions
55
is performed. Although time consuming, the advantage of keeping the whole biopsy in labelled cassettes is 2-fold: firstly, the ease with which this two step procedure can be done which means a reduction in the number of blocks processed in the case of benign lesions and secondly, in the case of malignant lesions it is possible to precisely analyse the surgical planes of excision and the extent of the tumor.
Large specimens Particular problems are encountered in the sampling of large specimens. The use of large histological sections has been recommended by some authors to assess disease extent and excision margins.6s31Although an attractive method, it has several disadvantages precluding its routine use in many laboratories. This method requires specialized equipment (microtome, cassettes, tissue stainer), and the quality of the sections obtained may be inferior due to the difficulties of cutting large sections. The slicing method described above, as it permits spatial reconstruction of the lesions and margins assessment, can overcome the problems of sampling large specimens.
References Sampling of the specimen: to what extent? Ideally, each specimen should be totally embedded for histological examination. Several studies have shown that in up to 30% of breast excisions performed for microcalcifications, the calcifications are identified only in benign lesions adjacent to a carcinoma.27-28 However, in practice, submission of the entire specimen is incompatible with the routine workload in busy laboratories. Recent studies addressing this issue have shown that histologic examination restricted to the areas of radiographic calcifications and the immediately surrounding tissues results in a high level of detection of clinically significant lesions and a considerable reduction in the amount of tissue processed.29s30However, in cases of malignant lesions, and particularly in situ ductal carcinoma, this sampling method does not always allow for accurate measurement of the lesion or assessment of the margins. A practical alternative approach is a two step procedure. The entire specimen is sliced and placed into cassettes which are precisely labelled, corresponding to the labelling of the sliced or grid radiograph. The first step consists of selecting only the cassettes containing the manunographic abnormality and the adjacent tissue, as well as any other suspicious area, for processing. The remaining cassettes are kept in fixative. If the histological sections show only benign lesions, no further processing is performed. If the histological sections reveal carcinoma or atypical hyperplasia, as a second step, processing of the tissue in the remaining cassettes
1. Elston C W, Ellis I 0. Pathology and breast screening. Histopathology 1990; 16: 109-l 18. 2. Anderson T J. Breast cancer screening: principles and practicalities for histopathologists. Recent advances in histopathololgy 14. Edinburgh: Churchill Livingstone, 1989; 43-61. 3. Armstrong J S, Davies J D. Laboratory handling of impalpable breast lesions: a review. J Clin Path01 1991; 44: 89-93. 4. Association of Directors of Anatomic and Surgical Pathology. Immediate management of mammographically detected breast lesions. Am J Surg Path01 1993; 17(8): 850-851. 5. Fechner R E, Mills S E. Breast pathology. Benign proliferations, atypias and in situ carcinomas. Chicago: ASCP Press 1990; pp 15-20. 6. Gad A. Screening for breast cancer: examination and reporting of histopathological preparations. Lancet ii 1988; 953. I. Lagios M D, Bennington J L. Protocol for the pathologic examination and tissue processing of the mammographically directed breast biopsy. In: Bennington J L, Lagios M D, eds. The mammographically directed biopsy. Philadelphia: Hanley and Belfus, 1992, pp 23-45. 8. Royal College of Pathologists Working Group. Pathology reporting in breast cancer screening. J Clin Path01 1991; 44: 710-725. 9. Schnitt S J, Connolly J L. Processing and evaluation of breast excision specimens. A clinically oriented approach. Am J Clin Path01 1992; 98(l): 125-137. 10. Schnitt S J. Specimen processing. In: Tavassoli F A. Pathology of the breast. Norwalk, CT: Appleton and Lange, 1992, pp 63-78. 11. Zafrani B, Laurent M. Microcalcifications mammaires sans tumeur palpable decouvertes par mammographie. Technique d’etude anatomo-pathologique. Ann Path01 1990; 10: 282-284. 12. Holland R. The role of specimen X-ray in the diagnosis of breast cancer. Diagn Imag Clin Med 1985; 54: 178-185. for breast cancer. Hum 13. Carter D. Margins of ‘lumpectomy’ Path01 1986; 17: 330-332. J S, Wiensweig P, Davies J D. Differential marking 14. Armstrong excision planes of breast lesions by coloured gelatin. J Clin Path01 1990; 43: 604-607.
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Date received 28 February 1994 Date accepted after revision 6 June 1994