Histopathologische Beurteilung des
Mammakarzinoms: Grundlage für die lokoregionale und systemische Therapie

Zusammenfassung

In der präoperativen Diagnostik von Mammaläsionen sind Stanzbiopsien eine zuverlässige Untersuchungsmethode auch bei nichtpalpablen, nur mammografisch sichtbaren Läsionen. Sie können die Zahl der offenen Biopsien und intraoperativen Schnellschnittuntersuchungen zur Dignitätsbestimmung vermindern. Resektate sollten einer standardisierten pathologisch-anatomischen Aufarbeitung unterzogen werden, die bei Brust-erhaltender Therapie eine topografische Markierung des Präparates zur Voraussetzung hat. Bei der Exzision von nicht palpablen, mammografisch sichtbaren Läsionen sollte eine Präparatradiografie zur Detektion von Mikrokalk durchgeführt werden, der intraoperative Schnellschnitt ist hier und bei kleinen Läsionen unter 1 cm Größe ungeeignet. Lichtmikroskopisch eruierbare histopathologische Prognosefaktoren beim Mammakarzinom sind Tumorgröße, regionärer Lymphknotenstatus, histologischer Typ, Status der Resektionsränder und histologischer Differenzierungsgrad. Immunhistochemisch werden der Rezeptorstatus (Östrogenrezeptor, Progesteronrezeptor), die Wachstumsfraktion (MIB-1) und die Expression des Onkogens erbB-2 bestimmt. Eine Standardisierung ist hier allerdings zur Erhöhung ihres diagnostischen Aussagewertes nötig. Neuere Staging-Verfahren zur Prognoseabschätzung wie Untersuchung eines Wächter-(„Sentinel”)-Lymphknotens und die Tumorzelldissemination im Knochenmark sind noch in der Erprobung.

Abstract

Core-needle biopsy is a sensitive method in preoperative diagnosis of breast lesions, especially in analysis of nonpalpable, only mammographically detectable ones. This offers the opportunity to reduce the amount of open biopsies for frozen section examination of breast lesions. Topographical orientation of the excision specimen is recommended to perform a standardised pathological examination. This procedure has become more important because of the increasing possibility of breast-conserving therapy. Examining excision biopsies of nonpalpable, only mammographically detectable lesions it is useful to perform a radiography of the specimen to search for microcalcifications. In this case and in case of breast lesions smaller than 1 cm intraoperative frozen sections should not be performed. Prognostic parameters evaluable through simple light microscopic examination are tumour size, staging of axillary lymph nodes, histologic type, histological grading and status of the margins. Immunohistochemical examination is performed for determining receptor status, proliferative activity and expression of the oncogene erbB-2. However, to increase the diagnostic impact, the procedure should be standardised. New staging procedures for determination of prognosis include investigation of the sentinel lymph node and detection of disseminated tumour cells in bone marrow aspirates. These methods are still under investigation.

Schlüsselwörter

Mammakarzinom - präoperative Diagnostik - standardisierte pathologisch-anatomische Aufarbeitung - histologische Diagnostik - Immunhistochemie

Key words

Breast cancer - preoperative diagnosis - standardized pathological examination - histological diagnosis - immunohistochemistry

Literatur

• 1 Kline T S, Joshi L P, Neal H S. Fine-needle aspiration of the breast: diagnoses and pitfalls. A review of 3545 cases.  Cancer. 1979;  44 1458-1464
• 2 Pisano E D, Fajardo L L, Caudry D J. et al . Fine-needle aspiration biopsy of nonpalpable breast lesions in a multicenter clinical trial: results from the radiologic diagnostic oncology group V.  Radiology. 2001;  219 785-792
• 3 Fersis N, Smyczek-Gargya B, Krainick U. et al . [Clinical experience with large-core needle biopsies of the breast and evaluation of histopathology].  Zentralbl Gynakol. 2001;  123 132-135
• 4 Morrow M, Venta L, Stinson T, Bennett C. Prospective comparison of stereotactic core biopsy and surgical excision as diagnostic procedures for breast cancer patients.  Ann Surg. 2001;  233 537-541
• 5 Renshaw A A. Adequate histologic sampling of breast core needle biopsies.  Arch Pathol Lab Med. 2001;  125 1055-1057
• 6 Anton H W, Junkermann H, Wolf G, Teubner J. [Localization of non-palpable lesions by mammography for preoperative marking and tissue removal].  Radiologe. 1993;  33 271-276
• 7 Fechner R E. Frozen section examination of breast biopsies. Practice parameter.  Am J Clin Pathol. 1995;  103 6-7
• 8 D'Angelo P C, Galliano D E, Rosemurgy A S. Stereotactic excisional breast biopsies utilizing the advanced breast biopsy instrumentation system.  Am J Surg. 1997;  174 297-302
• 9 Ammann M, Haid A, Breitfellner G. [Advanced breast biopsy instrumentation (ABBI). Histopathologic evaluation of a new investigation method].  Pathologe. 2000;  21 234-239
• 10 Velanovich V, Lewis F R , Nathanson S D. et al . Comparison of mammographically guided breast biopsy techniques.  Ann Surg. 1999;  229 625-630
• 11 Decker T, Ruhnke M, Schneider W. [Standardized pathologic examination of breast excision specimen. Relevance within an interdisciplinary practice protocol for quality management of breast saving therapy].  Pathologe. 1997;  18 53-59
• 12 Fitzgibbons P L, Connolly J L, Page D L. Updated protocol for the examination of specimens from patients with carcinomas of the breast. Cancer Committee.  Arch Pathol Lab Med. 2000;  124 1026-1033
• 13 Page D L, Dupont W D, Rogers L W, Landenberger M. Intraductal carcinoma of the breast: follow-up after biopsy only.  Cancer. 1982;  49 751-758
• 14 Schwartz G F, Patchesfsky A S, Feig S A, Shaber G S, Schwartz A B. Multicentricity of non-palpable breast cancer.  Cancer. 1980;  45 2913-2916
• 15 Silverstein M J, Lagios M D, Craig P H. et al . A prognostic index for ductal carcinoma in situ of the breast.  Cancer. 1996;  77 2267-2274
• 16 Silverstein M J, Poller D N, Waisman J R. et al . Prognostic classification of breast ductal carcinoma-in-situ.  Lancet. 1995;  345 1154-1157
• 17 Fechner R E. Lobular carcinoma in situ in sclerosing adenosis. A potential source of confusion with invasive carcinoma.  Am J Surg Pathol. 1981;  5 233-239
• 18 Frykberg E R. Lobular Carcinoma In Situ of the Breast.  Breast J. 1999;  5 296-303
• 19 Leal C, Costa I, Fonseca D, Lopes P, Bento M J, Lopes C. Intracystic (encysted) papillary carcinoma of the breast: a clinical, pathological, and immunohistochemical study.  Hum Pathol. 1998;  29 1097-1104
• 20 Silverstein M J, Lewinsky B S, Waisman J R. et al . Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma?.  Cancer. 1994;  73 1673-1677
• 21 Sinn H P, Kellerhoff N M, Kellerhoff R, Bastert G, Otto H F. [Subtyping and prognostic assessment of invasive lobular breast carcinoma].  Pathologe. 1997;  18 37-44
• 22 Gamel J W, Meyer J S, Feuer E, Miller B A. The impact of stage and histology on the long-term clinical course of 163,808 patients with breast carcinoma.  Cancer. 1996;  77 1459-1464
• 23 Eltorky M, Hall J C, Osborne P T, el Zeky F. Signet-ring cell variant of invasive lobular carcinoma of the breast. A clinicopathologic study of 11 cases.  Arch Pathol Lab Med. 1994;  118 245-248
• 24 McDivitt R W, Boyce W, Gersell D. Tubular carcinoma of the breast. Clinical and pathological observations concerning 135 cases.  Am J Surg Pathol. 1982;  6 401-411
• 25 Kader H A, Jackson J, Mates D, Andersen S, Hayes M, Olivotto I A. Tubular carcinoma of the breast: a population-based study of nodal metastases at presentation and of patterns of relapse.  Breast J. 2001;  7 8-13
• 26 Green I, McCormick B, Cranor M, Rosen P P. A comparative study of pure tubular and tubulolobular carcinoma of the breast.  Am J Surg Pathol. 1997;  21 653-657
• 27 Page D L, Dixon J M, Anderson T J, Lee D, Stewart H J. Invasive cribriform carcinoma of the breast.  Histopathology. 1983;  7 525-536
• 28 Marzullo F, Zito F A, Marzullo A. et al . Infiltrating cribriform carcinoma of the breast. A clinico-pathologic and immunohistochemical study of 5 cases.  Eur J Gynaecol Oncol. 1996;  17 228-231
• 29 Rasmussen B B, Rose C, Christensen I B. Prognostic factors in primary mucinous breast carcinoma.  Am J Clin Pathol. 1987;  87 155-160
• 30 Anan K, Mitsuyama S, Tamae K. et al . Pathological features of mucinous carcinoma of the breast are favourable for breast-conserving therapy.  Eur J Surg Oncol. 2001;  27 459-463
• 31 Jensen M L, Kiaer H, Andersen J, Jensen V, Melsen F. Prognostic comparison of three classifications for medullary carcinomas of the breast.  Histopathology. 1997;  30 523-532
• 32 Ridolfi R L, Rosen P P, Port A, Kinne D, Mike V. Medullary carcinoma of the breast: a clinicopathologic study with 10 year follow-up.  Cancer. 1977;  40 1365-1385
• 33 Rigaud C, Theobald S, Noel P. et al . Medullary carcinoma of the breast. A multicenter study of its diagnostic consistency.  Arch Pathol Lab Med. 1993;  117 1005-1008
• 34 Fisher E R, Palekar A S, Redmond C, Barton B, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4). VI. Invasive papillary cancer.  Am J Clin Pathol. 1980;  73 313-322
• 35 Paterakos M, Watkin W G, Edgerton S M, Moore D H, Thor A D. Invasive micropapillary carcinoma of the breast: a prognostic study.  Hum Pathol. 1999;  30 1459-1463
• 36 Abati A D, Kimmel M, Rosen P P. Apocrine mammary carcinoma. A clinicopathologic study of 72 cases.  Am J Clin Pathol. 1990;  94 371-377
• 37 Pastolero G, Hanna W, Zbieranowski I, Kahn H J. Proliferative activity and p53 expression in adenoid cystic carcinoma of the breast.  Mod Pathol. 1996;  9 215-219
• 38 Zaloudek C, Oertel Y C, Orenstein J M. Adenoid cystic carcinoma of the breast.  Am J Clin Pathol. 1984;  81 297-307
• 39 Krausz T, Jenkins D, Grontoft O, Pollock D J, Azzopardi J G. Secretory carcinoma of the breast in adults: emphasis on late recurrence and metastasis.  Histopathology. 1989;  14 25-36
• 40 Rosen P P, Cranor M L. Secretory carcinoma of the breast.  Arch Pathol Lab Med. 1991;  115 141-144
• 41 Chaudary M A, Millis R R, Lane E B, Miller N A. Paget's disease of the nipple: a ten year review including clinical, pathological, and immunohistochemical findings.  Breast Cancer Res Treat. 1986;  8 139-146
• 42 Venkataseshan V S, Budd D C, Un K im, Hutter R V. Intraepidermal squamous carcinoma (Bowen's disease) of the nipple.  Hum Pathol. 1994;  25 1371-1374
• 43 Papotti M, Macri L, Finzi G, Capella C, Eusebi V, Bussolati G. Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases.  Semin Diagn Pathol. 1989;  6 174-188
• 44 Nesland J M, Holm R, Johannessen J V, Gould V E. Neurone specific enolase immunostaining in the diagnosis of breast carcinomas with neuroendocrine differentiation. Its usefulness and limitations.  J Pathol. 1986;  148 35-43
• 45 Maluf H M, Koerner F C. Carcinomas of the breast with endocrine differentiation: a review.  Virchows Arch. 1994;  425 449-457
• 46 Papotti M, Gherardi G, Eusebi V, Pagani A, Bussolati G. Primary oat cell (neuroendocrine) carcinoma of the breast. Report of four cases.  Virchows Arch A Pathol Anat Histopathol. 1992;  420 103-108
• 47 Kaufman M W, Marti J R, Gallager H S, Hoehn J L. Carcinoma of the breast with pseudosarcomatous metaplasia.  Cancer. 1984;  53 1908-1917
• 48 Toikkanen S. Primary squamous cell carcinoma of the breast.  Cancer. 1981;  48 1629-1632
• 49 Zoltan T B, Konick L, Coleman R J. Pure squamous cell carcinoma of the breast in a patient with previous adenocarcinoma of the breast: a case report and review of the literature.  Am Surg. 2001;  67 671-673
• 50 Chevallier B, Asselain B, Kunlin A, Veyret C, Bastit P, Graic Y. Inflammatory breast cancer. Determination of prognostic factors by univariate and multivariate analysis.  Cancer. 1987;  60 897-902
• 51 Fitzgibbons P L, Page D L, Weaver D. et al . Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999.  Arch Pathol Lab Med. 2000;  124 966-978
• 52 Seidman J D, Schnaper L A, Aisner S C. Relationship of the size of the invasive component of the primary breast carcinoma to axillary lymph node metastasis.  Cancer. 1995;  75 65-71
• 53 Rosen P P, Groshen S, Kinne D W, Norton L. Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.  J Clin Oncol. 1993;  11 2090-2100
• 54 Fisher E R, Anderson S, Redmond C, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants.  Cancer. 1993;  71 2507-2514
• 55 Carter C L, Allen C, Henson D E. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases.  Cancer. 1989;  63 181-187
• 56 Fisher B, Bauer M, Wickerham D L. et al . Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update.  Cancer. 1983;  52 1551-1557
• 57 Mambo N C, Gallager H S. Carcinoma of the breast: the prognostic significance of extranodal extension of axillary disease.  Cancer. 1977;  39 2280-2285
• 58 Donegan W L, Stine S B, Samter T G. Implications of extracapsular nodal metastases for treatment and prognosis of breast cancer.  Cancer. 1993;  72 778-782
• 59 de Mascarel I, Bonichon F, Coindre J M, Trojani M. Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up.  Br J Cancer. 1992;  66 523-527
• 60 Rosen P P, Saigo P E, Braun D W , Beattie E J, Kinne D W. Occult axillary lymph node metastases from breast cancers with intramammary lymphatic tumor emboli.  Am J Surg Pathol. 1982;  6 639-641
• 61 Siziopikou K P, Schnitt S J, Connolly J L, Hayes D F. Detection and Significance of Occult Axillary Metastatic Disease in Breast Cancer Patients.  Breast J. 1999;  5 221-229
• 62 Veronesi U, Paganelli G, Galimberti V. et al . Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes.  Lancet. 1997;  349 1864-1867
• 63 Krag D, Weaver D, Ashikaga T. et al . The sentinel node in breast cancer - a multicenter validation study.  N Engl J Med. 1998;  339 941-946
• 64 Krag D. Minimal invasive staging for breast cancer: clinical experience with sentinel lymph node biopsy.  Semin Oncol. 2001;  28 229-235
• 65 Cabanes P A, Salmon R J, Vilcoq J R. et al . Value of axillary dissection in addition to lumpectomy and radiotherapy in early breast cancer. The Breast Carcinoma Collaborative Group of the Institut Curie.  Lancet. 1992;  339 1245-1248
• 66 Fisher B, Redmond C, Fisher E R. et al . Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.  N Engl J Med. 1985;  312 674-681
• 67 Henson D E, Ries L, Freedman L S, Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index.  Cancer. 1991;  68 2142-2149
• 68 Elston C W, Ellis I O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.  Histopathology. 1991;  19 403-410
• 69 Clayton F. Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor.  Cancer. 1991;  68 1309-1317
• 70 Simpson J F, Gray R, Dressler L G. et al . Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189.  J Clin Oncol. 2000;  18 2059-2069
• 71 Sahin A A, Ro J, Ro J Y. et al . Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis.  Cancer. 1991;  68 549-557
• 72 Pinder S E, Wencyk P, Sibbering D M. et al . Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival.  Br J Cancer. 1995;  71 146-149
• 73 Kreipe H, Alm P, Olsson H, Hauberg M, Fischer L, Parwaresch R. Prognostic significance of a formalin-resistant nuclear proliferation antigen in mammary carcinomas as determined by the monoclonal antibody Ki-S1.  Am J Pathol. 1993;  142 651-657
• 74 Toft D, Gorski J. A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization.  Proc Natl Acad Sci USA. 1966;  55 574-581
• 75 Hughes A, Jacobson H I, Wagner R K, Jungblut P W. Ovarian-independent fluctuations of estradiol receptor levels in mammalian tissues.  Mol Cell Endocrinol. 1976;  5 379-388
• 76 Remmele W, Stegner H E. [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue].  Pathologe. 1987;  8 138-140
• 77 Ruiter D J, Ferrier C M, van Muijen G N. et al . Quality control of immunohistochemical evaluation of tumour-associated plasminogen activators and related components. European BIOMED-1 Concerted Action on Clinical Relevance of Proteases in Tumour Invasion and Metastasis.  Eur J Cancer. 1998;  34 334-1340
• 78 Barnes D M, Millis R R, Beex L V, Thorpe S M, Leake R E. Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance.  Eur J Cancer. 1998;  34 1677-1682
• 79 Rhodes A, Jasani B, Barnes D M, Bobrow L G, Miller K D. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems.  J Clin Pathol. 2000;  53 125-130
• 80 O'Leary T J. Standardization in immunohistochemistry.  Appl Immunohistochem Mol Morphol. 2001;  9 3-8
• 81 von Wasielewski R, Mengel M, Nolte M, Werner M. Influence of fixation, antibody clones, and signal amplification on stereoid receptor analysis.  Breast J. 1998;  4 33-40
• 82 Jacobs T W, Gown A M, Yaziji H, Barnes M J, Schnitt S J. Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system.  J Clin Oncol. 1999;  17 1983-1987
• 83 Ellis I O, Dowsett M, Bartlett J. et al . Recommendations for HER2 testing in the UK.  J Clin Pathol. 2000;  53 890-892
• 84 Lebeau A, Deimling D, Kaltz C. et al . Her-2/neu analysis in archival tissue samples of human breast cancer: comparison of immunohistochemistry and fluorescence in situ hybridization.  J Clin Oncol. 2001;  19 354-363
• 85 Press M F, Hung G, Godolphin W, Slamon D J. Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression.  Cancer Res. 1994;  54 2771-2777
• 86 Tubbs R R, Pettay J D, Roche P C, Stoler M H, Jenkins R B, Grogan T M. Discrepancies in clinical laboratory testing of eligibility for trastuzumab therapy: apparent immunohistochemical false-positives do not get the message.  J Clin Oncol. 2001;  19 2714-2721
• 87 Pinder S E, Ellis I O, Galea M, O'Rouke S, Blamey R W, Elston C W. Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up.  Histopathology. 1994;  24 41-47
• 88 Gage I, Schnitt S J, Nixon A J. et al . Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy.  Cancer. 1996;  78 1921-1928
• 89 Schnitt S J, Abner A, Gelman R. et al . The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy.  Cancer. 1994;  74 1746-1751
• 90 Silverstein M J, Lagios M D, Groshen S. et al . The influence of margin width on local control of ductal carcinoma in situ of the breast.  N Engl J Med. 1999;  340 1455-1461
• 91 Recht A, Houlihan M J. Axillary lymph nodes and breast cancer: a review.  Cancer. 1995;  76 1491-1512
• 92 Joensuu H, Pylkkanen L, Toikkanen S. Long-term survival in node-positive breast cancer treated by locoregional therapy alone.  Br J Cancer. 1998;  78 795-799
• 93 Diel I J, Kaufmann M, Goerner R, Costa S D, Kaul S, Bastert G. Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.  J Clin Oncol. 1992;  10 1534-1539
• 94 Diel I J, Kaufmann M, Costa S D. et al . Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.  J Natl Cancer Inst. 1996;  88 1652-1658
• 95 Braun S, Pantel K, Muller P. et al . Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer.  N Engl J Med. 2000;  342 525-533
• 96 Prechtel K, Prechtel D. [Current standards for the diagnosis of breast carcinoma in routine practice].  Pathologe. 2001;  22 281-284