PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jclinpathJournal of Clinical PathologyCurrent TOCInstructions for authors
 
J Clin Pathol. May 2006; 59(5): 518–522.
PMCID: PMC1860289
The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma
G Cserni, S Bianchi, V Vezzosi, H Peterse, A Sapino, R Arisio, A Reiner‐Concin, P Regitnig, J‐P Bellocq, C Marin, R Bori, J M Penuela, and A Córdoba Iturriagagoitia
G Cserni, R Bori, Department of Pathology, Bács‐Kiskun County Teaching Hospital, Kecskemét, Hungary
S Bianchi, V Vezzosi, Department of Human Pathology and Oncology, University of Florence, Italy
H Peterse, Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands
A Sapino, Department of Biological Science and Human Oncology, University of Turin, Turin, Italy
R Arisio, Department of Pathology, Sant'Anna Hospital, Turin, Italy
A Reiner‐Concin, Institute of Pathology, Donauspital, Vienna, Austria
P Regitnig, Institute of Pathology, Medical University Graz, Graz, Austria
J‐P Bellocq, C Marin, Department of Pathology, Hôpital de Hautepierre, Strasbourg, France
J M Penuela, A C Iturriagagoitia, Department of Pathology, Hospital de Navarra, Pamplona, Spain
Correspondence to: Dr Gábor Cserni
Bács‐Kiskun County Teaching Hospital, Nyiri út 38, H‐6000 Kecskemét, Hungary; cserni@freemail.hu
Accepted October 10, 2005.
Background
Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients.
Objective
To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma.
Methods
The value of IHC, the types of metastasis found by this method, and the involvement of non‐sentinel lymph nodes were analysed in a multi‐institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis.
Results
189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non‐sentinel‐node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general.
Conclusions
IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.
Keywords: sentinel lymph node, immunohistochemistry, lobular carcinoma, breast cancer, cytokeratin
Occult lymph node metastases that are not detected by the commonly used method of assessing a single haematoxylin and eosin (HE) stained level per lymph node have been known for decades,1,2 but their prognostic significance has been debated since their description.3 Such occult metastases can be demonstrated either by examining deeper levels of the tissue blocks, or by using a more sensitive method of detecting cancer cells. Immunohistochemistry (IHC) has been used for this latter purpose, with the aim of demonstrating epithelial markers. Retrospective studies, generally with small case numbers, have proved inconclusive for evaluating the prognostic significance of such occult metastases,3 which generally fall into the category of micrometastasis or isolated tumour cells4,5 (the latter also referred to as submicrometastases6). Examination of step sections is impractical when even moderate numbers of lymph nodes have been removed, and would mean a huge workload.7 The same applies to the use of cytokeratin IHC. In contrast, it is entirely feasible to use step sections and cytokeratin IHC when sentinel lymph node biopsy is undertaken, as these are the lymph nodes that are most likely to harbour metastases.8 If pathological efforts are concentrated on these selectively recovered nodes, an improved staging can be achieved.3,9 Although recommendations vary on the use of IHC for sentinel lymph nodes found to be uninvolved on HE staining,6,10,11,12,13,14,15,16 and most do not recommend its routine use,6,10,13,14,16 application of this technique is widespread both in the USA and in Europe.6,17
Invasive lobular carcinoma (ILC) is known to produce nodal metastasis that can be difficult to detect on HE stained slides, as it is composed of non‐cohesive cells of a similar size to lymphocytes. Occult metastases of this tumour type detected by IHC have been reported to be more common than occult metastases from ductal carcinomas.18,19,20,21,22 Unfortunately the small number of cases of ILC investigated in these papers does not give an indication of the effect of occult metastases on recurrence and survival in this histological tumour type.20 Nevertheless, two later studies with a longer follow up from the same institution suggested that the presence of IHC‐detected occult micrometastases in either ILCs23 or breast cancers in general24 was not of prognostic significance. However, these two follow up studies did not distinguish between isolated tumour cells and micrometastases as currently defined.4,16,25
Our present study was undertaken to assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes from patients with ILC.
A previous study by the European Working Group for Breast Screening Pathology (EWGBSP) evaluated current practice concerning sentinel lymph nodes in European pathology laboratories.17 EWGBSP members working in laboratories where cytokeratin IHC is used routinely for sentinel nodes found negative on multilevel HE assessment were asked to collect data on cases diagnosed as ILC and staged on sentinel node biopsy. The details reported included the metastatic status of the sentinel lymph nodes, the method of detection of sentinel node involvement (HE versus IHC), and further nodal involvement. Patients were not identified during this retrospective data collection and analysis, and therefore no ethics approval was necessary.
For the purpose of this study, any tumour cell in a sentinel lymph node was considered a positive finding. Nodal involvement was then categorised as isolated tumour cells, micrometastases, or macrometastases according to the definitions of these categories within the EWGBSP guidelines.4,5,26
The laboratories contributing cases to the current study had different histological protocols relating to the work‐up of the sentinel lymph nodes, but all departments embedded the whole node if it was considered negative on macroscopy. Nodes greater than 5 mm diameter were sliced into pieces and all departments used the approach of multilevel HE staining and routine cytokeratin immunostains if the HE slides were negative. Further details are given in table 11.
Table thumbnail
Table 1 Methods used for the evaluation of grossly negative sentinel lymph nodes and basic characteristics of contributed cases
Data on sentinel lymph node biopsies from 449 ILCs were collected and analysed. Altogether 189 patients (42%) had sentinel node involvement of any type. This rate varied from institution to institution (range 29% to 55% (SD 9%); table 11).). The rate of nodal involvement increased with increasing tumour size as expected (table 22).). A similar relation with tumour size was seen with HE detected nodal involvement and macrometastases, but not with IHC detected nodal involvement, isolated tumour cells, or micrometastases (table 33).
Table thumbnail
Table 2 Rate of nodal involvement according to tumour size
Table thumbnail
Table 3 Differential rate of nodal involvement according to tumour size
HE staining detected most of the metastases. Although most of these metastases were classified as macrometastases, some micrometastases (24 of 64; 0.38) were also identified by this method, and a few isolated tumour cells were also picked up on HE stained slides (table 44).). IHC alone identified 34% of all cases of nodal involvement. This rate also varied from institution to institution (range 22% to 50% (SD 10%), the latter being an outlier with small amounts of data (table 11)).)). Although the category of nodal involvement where IHC resulted in the greatest increase in the rate of detection was isolated tumour cells (17/19; 0.89), a significant proportion of the micrometastases (40/64; 0.63) were also detected by IHC, and some larger metastases were also demonstrated by this means (8/106; 0.08). The median size of the macrometastases was 2.75 mm (range 2.1 to 7.0 mm), and all could be verified on HE in retrospect, after the IHC results were available ((figsfigs 1 and 22).
Table thumbnail
Table 4 Method of detection and size of nodal involvement
figure cp29991.f1
Figure 1 IHC detected metastasis measuring 2.5 mm in its greatest dimension (Cytokeratin AE1/AE3; original magnification ×400).
figure cp29991.f2
Figure 2 HE stained slide from the same case as shown in fig 11.. Tumour cells could be verified with this stain, but were not as obvious (original magnification ×400).
Data on non‐sentinel lymph nodes were analysed only in cases with sentinel node involvement. The database included one case of a false negative sentinel node biopsy, where axillary dissection revealed a single metastatic non‐sentinel node out of 11 nodes recovered, and this was associated with a negative examination of the sentinel node. Axillary dissection was carried out in 44 patients without sentinel node involvement as part of the validation phase of sentinel node biopsy. By contrast, axillary clearance was omitted in 28 cases with an involved sentinel node ((tablestables 3 and 44).). This was either because of sentinel node involvement by isolated tumour cells or micrometastases only, or because of the participation of several patients in the European Organisation for Research and Treatment of Cancer (EORTC) trial, “After Mapping of the Axilla: Radiotherapy Or Surgery” (AMAROS), randomising patients with positive sentinel lymph nodes between axillary dissection or radiation therapy.
In all, 161 cases with involved sentinel lymph nodes underwent axillary dissection. Isolated tumour cells and micrometastases in the sentinel lymph nodes were associated with a low rate of non‐sentinel node involvement (0 and 0.14, respectively; 0.11 overall), whereas, as expected, the rate of macrometastases associated with non‐sentinel node metastases was higher (0.60). Sentinel lymph node involvement first detected by IHC was associated with a considerable rate of non‐sentinel node involvement (0.24), as some of the involvement detected by IHC was due to macrometastases, five of eight of these cases being associated with non‐sentinel node metastases (table 55).
Table thumbnail
Table 5 Metastases in non‐sentinel nodes v sentinel nodes, and the method of detection
Cytokeratin IHC of unselected axillary lymph nodes from patients with ILC has been shown to upstage these patients more often than those with ductal carcinoma,20,23 and some laboratories have therefore introduced this method as a routine means of evaluating all lymph nodes removed in this subset of patients.27 As sentinel lymph node biopsy selects the nodes which are the most likely sites of regional metastases, it would be wiser to limit the use of IHC to these nodes. Most guidelines do not recommend IHC for the evaluation of sentinel lymph nodes in general practice,6,10,13,14,16 but it may be used in special cases, such as cases of ILC.6 As sentinel node biopsy is as reliable in ILC as in ductal cancers,28,29 we evaluated the role of cytokeratin IHC in a multi‐institutional cohort of ILC patients who underwent sentinel lymph node biopsy.
Our results show that tumour size influences the nodal involvement in lobular carcinoma. This finding is consistent with nodal involvement being more common in larger tumours of any histological type. Although no comparison was made between the rate of nodal involvement in different types of tumour, our results are in agreement with data from the era before sentinel node biopsy. We found that 34% of all cases of nodal involvement were detected by IHC, which is higher than the rate reported for breast carcinoma in general or of ductal carcinoma, and is in the rate range reported for ILC.18,19,20,21,22,29 Although there were institutional methodological variations in this retrospective study, and also differences in the rate of nodal involvement and IHC positive cases, these latter differences can only partly be accounted for by the methodology. Mean tumour sizes were also different (table 11),), and this may have altered the metastatic rates mentioned above. Obviously, the more detailed the histological protocol, the more positive cases will be detected.30,31 Diversity of methods may be a problem with this study, but such variations in methodology can be found when comparing the various studies cited previously,18,19,20,21,22 and are encountered in nearly all reviews dealing with the upstaging role of IHC in breast cancer.32 Owing to the large number of cases, it is felt that the conclusions below can be relied upon, even if there may be some variation in the pathological approach to the reported lymph nodes.
To the best of our knowledge, this is the first report on the differential rates of isolated tumour cells, micrometastases, and larger metastases detected by IHC. Surprisingly, despite the fact that the isolated tumour cell category of nodal involvement was the one in which IHC produced the greatest increase in detection rate (17/19; 0.89), the largest category of IHC‐detected nodal involvement (n = 40) was the micrometastases. This is probably because ILC often produces involvement of the nodal parenchyma,33 and we considered this to represent micrometastasis.25,26 Obviously, a smaller number of macrometastases was also first detected by IHC.
The displacement and passive transport of tumour cells after needling procedures and excision biopsy34,35,36 have been proposed as a mechanism for the lodging of tumour cells in regional lymph nodes, especially in sentinel lymph nodes from breast cancer patients. The phenomenon of artefactual tumour cell seeding has been seen in cases of ductal carcinoma in situ37 and, although this event may be rarer in the less cellular but less cohesive lobular carcinomas, isolated intrasinusoidal epithelial cells may well be of this origin. It has been postulated that these cells are detectable mainly by IHC only, and therefore that the IHC detected cells are irrelevant. Patients undergoing prophylactic mastectomies after biopsies were only rarely found to have IHC detected epithelial cells in their sentinel nodes, however.38 This suggests that cancer needs to be present for there to be an increased rate of IHC positive sentinel nodes after biopsy or other means of physical manipulation of the tumour. These diagnostic or therapeutic procedures alone cannot be responsible for all cases of IHC detected nodal involvement.
A word of caution is required, as cytokeratin positive nodal structures cannot always be equated with metastatic nodal involvement. Besides the artefactually displaced tumour cells discussed above, normal constituents of the lymph nodes may also stain with anti‐cytokeratin antibodies. Interstitial reticulum cells have been reported to be cytokeratin positive, especially when stained by CAM5.2 or an in‐house cytokeratin cocktail, whereas this was much rarer or absent with AE1/AE3.39,40 Plasma cells have also been reported to stain with CAM5.2 and pan‐cytokeratin.40 Rarely, occasional cells compatible with histiocyte morphology also stain weakly with cytokeratin antibodies. Obviously, rare epithelial inclusions of the lymph nodes are also cytokeratin positive.41 Morphology should therefore never be neglected in the face of positive cytokeratin staining, and this will usually help to discriminate cancer cells from the others. Whenever there is doubt as to the nature of cytokeratin positive cells, these should not be called metastases, in line with the general rules of the TNM staging of cancers.42 None of the cytokeratin positive cells in this study was considered to represent inclusions or non‐epithelial cells.
Although the rate of nodal involvement increased with increasing tumour size, and this was also true for the macrometastases; the rate of nodal involvement, isolated tumour cells, and micrometastases detected by IHC tended to decrease with increasing tumour size ((tablestables 2 and 33).). The lack of an association between IHC detected sentinel node involvement and predictors of HE detected sentinel node involvement was reported earlier.37 Although this may be because isolated tumour cells are commonly (although certainly not always) the result not of a true metastatic process but rather of previous procedures and manipulations,37 another possible explanation could be that IHC tends to detect less obvious nodal involvement (generally falling into the category of isolated tumour cells or micrometastases), which is more common with smaller tumours, whereas larger tumours have already established larger metastases that are more likely to be detected by HE staining even in ILC.
Although we were unable to analyse the prognostic significance of these metastases in terms of relapse or survival, we did analyse the status of further lymph nodes in the axilla in the 161 patients who had an axillary dissection after the diagnosis of sentinel node involvement of any type. Twelve of 50 IHC detected sentinel lymph node metastases from ILC, but none belonging in the isolated tumour cell category, were associated with non‐sentinel node involvement, which was higher than our previous meta‐analysis (around 9%) would have suggested for IHC detected sentinel node involvement in breast cancers in general.32 None of the studies included in that meta‐analysis drew conclusions in relation to the histological type of tumour.
Take home message
Immunohistochemistry is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.
Our findings suggest that sentinel lymph nodes should be investigated by IHC if the primary tumour is of lobular type, because this approach may often detect micrometastases and even larger metastases, requiring further axillary treatment by current standards.
Acknowledgements
GC is supported by a János Bolyai Research Fellowship from the Hungarian Academy of Sciences. AS is supported in part by the Ministero dell'Universita e della Ricerca Scientifica es Tecnologica (MURST).
Abbreviations
EWGBSP - European Working Group for Breast Screening Pathology
IHC - immunohistochemistry
ILC - invasive lobular carcinoma
1. Saphir O, Amromin G D. Obscure axillary lymph node metastasis in carcinoma of the breast. Cancer 1948. 1238–241.241. [PubMed]
2. Pickren J W. Significance of occult metastases – a study of breast cancer. Cancer 1961. 141266–1271.1271. [PubMed]
3. Cserni G, Amendoeira I, Apostolikas N. et al Pathological work‐up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines. Eur J Cancer 2003. 391654–1667.1667. [PubMed]
4. In: Sobin L H, Wittekind C. eds. UICC TNM classification of malignant tumours, 6th edition. New York: John Wiley and Sons, 2002.
5. Greene F L, Page D L, Fleming I D. et al, eds. AJCC cancer staging handbook – TNM classification of malignant tumors, 6th edition. New York: Springer Verlag, 2002.
6. Schwartz G F, Giuliano A E, Veronesi U. et al Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19–22, 2001, Philadelphia, Pennsylvania. Cancer 2002. 942542–2551.2551. [PubMed]
7. Anderson T J. Occult axillary lymph‐node micrometastases in breast cancer. Lancet 1990. 336435.
8. Cserni G. Sentinel node biopsy in breast cancer and its implications for histopathological examination. Histopathology 2005. 46697–706.706. [PubMed]
9. Giuliano A E, Dale P S, Turner R R. et al Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995. 180700–704.704.
10. 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. 121026–1033.1033. [PubMed]
11. Australian Cancer Network, Breast Pathology Working Party The pathology reporting of breast cancer. A guide for pathologists, surgeons, radiologists and oncologists. Recommendations of the Australian Cancer Network Working Party, 2nd edition 2001.
12. Lawrence W D., Association of Directors of Anatomic and Surgical Pathology ADASP recommendations for processing and reporting of lymph node specimens submitted for evaluation of metastatic disease. Virchows Arch 2001. 439601–603.603. [PubMed]
13. Kuehn T, Bembenek A, Decker T. et al A concept for the clinical implementation of sentinel lymph node biopsy in patients with breast carcinoma with special regard to quality assurance. Cancer 2005. 103451–461.461. [PubMed]
14. Ellis I O, Pinder S E, Bobrow L. et alPathology reporting of breast disease. NHS Publication No 58. Sheffield: NHS Cancer Screening Programmes and the Royal College of Pathologists, 2005, http://www.cancerscreening.nhs.uk/breastscreen/publications/nhsbsp58‐low‐resolution.pdf (Last viewed 19 July 2005)
15. http://www.pathology.at/sentinel.htm (Last viewed 4 April 2005)
16. Perry N, Broeders M, de Wolf C. et al, eds. European guidelines for breast screening and diagnosis. Luxemburg: European Communities (in press)
17. Cserni G, Amendoeira I, Apostolikas N. et al Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire‐based survey by the European Working Group for Breast Screening Pathology. J Clin Pathol . 2004;57695–701.701.
18. Wells C A, Heryet A, Brochier J. et al The immunocytochemical detection of axillary micrometastases in breast cancer. Br J Cancer 1984. 50193–197.197. [PMC free article] [PubMed]
19. Bussolati G, Gugliotta P, Morra I. et al The immunohistochemical detection of lymph node metastases from infiltrating lobular carcinoma of the breast. Br J Cancer 1986. 54631–636.636. [PMC free article] [PubMed]
20. Trojani M, de Mascarel I, Bonichon F. et al Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance. Br J Cancer 1987. 55303–306.306. [PMC free article] [PubMed]
21. Berry N, Jones D B, Marshall R. et al Comparison of the detection of breast carcinoma metastases by routine histological diagnosis and by immunohistochemical staining. Eur Surg Res 1988. 20225–232.232. [PubMed]
22. Cote R J, Peterson H F, Chaiwun B. et al Role of immunohistochemical detection of lymph‐node metastases in management of breast cancer. International Breast Cancer Study Group. Lancet 1999. 354896–900.900. [PubMed]
23. De Mascarel I, Bonichon F, Coindre J M. et al Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow‐up. Br J Cancer 1992. 66523–527.527. [PMC free article] [PubMed]
24. De Mascarel I, MacGrogan G, Picot V. et al Prognostic significance of immunohistochemically detected breast cancer node metastases in 218 patients. Br J Cancer 2002. 8770–74.74. [PMC free article] [PubMed]
25. Hermanek P, Hutter R V P, Sobin L H. et al Classification of isolated tumor cells and micrometastasis. Cancer 1999. 862668–2673.2673. [PubMed]
26. Cserni G, Bianchi S, Boecker W. et al Improving the reproducibility of diagnosing micrometastases and isolated tumor cells. Cancer 2005. 103358–367.367. [PubMed]
27. Chandler I P, Oommen R, Lawson C W. Invasive lobular carcinoma and cytokeratin immunohistochemistry: an audit. J Clin Pathol 2003. 56240.
28. Classe J M, Loussouarn D, Campion L. et al Validation of axillary sentinel lymph node detection in the staging of early lobular invasive breast carcinoma: a prospective study. Cancer 2004. 100935–941.941. [PubMed]
29. Grube B J, Hansen N M, Ye X. et al Tumor characteristics predictive of sentinel node metastases in 105 consecutive patients with invasive lobular carcinoma. Am J Surg 2002. 184372–376.376. [PubMed]
30. Cserni G. Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol 2002. 55926–931.931. [PMC free article] [PubMed]
31. Torrenga H, Rahusen F D, Meijer S. et al Sentinel node investigation in breast cancer: detailed analysis of the yield from step sectioning and immunohistochemistry. J Clin Pathol 2001. 54550–552.552. [PMC free article] [PubMed]
32. Cserni G, Gregori D, Merletti F. et al Non‐sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer: meta‐analysis of 25 studies. Br J Surg 2004. 911245–1252.1252. [PubMed]
33. Lilleng P K, Hartveit F. “Missed” micrometastases – the extent of the problem. Acta Oncol 2000. 39313–317.317. [PubMed]
34. Diaz L K, Wiley E L, Venta L A. Are malignant cells displaced by large‐gauge needle core biopsy of the breast? Am J Roentgenol 1999. 1731303–1313.1313. [PubMed]
35. Hansen N M, Ye X, Grube B J. et al Manipulation of the primary breast tumor and the incidence of sentinel node metastases from invasive breast cancer. Arch Surg 2004. 139634–639.639. [PubMed]
36. Moore K H, Thaler H T, Tan L K. et al Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma: biologic metastasis or procedural artifact? Cancer 2004. 100929–934.934. [PubMed]
37. Tamhane R, Dahlstrom J E, McCallum D D. et al The clinical significance of cytokeratin‐positive cells in lymph nodes at the time of mastectomy from patients with ductal carcinoma‐in‐situ. Ann Surg Oncol 2002. 9999–1003.1003. [PubMed]
38. King T A, Ganaraj A, Fey J V. et al Cytokeratin‐positive cells in sentinel lymph nodes in breast cancer are not random events: experience in patients undergoing prophylactic mastectomy. Cancer 2004. 101926–933.933. [PubMed]
39. Linden M D, Zarbo R J. Cytokeratin immunostaining patterns of benign, reactive lymph nodes: applications for the evaluation of sentinel lymph node specimen. Appl Immunohistochem Mol Morphol 2001. 9297–301.301. [PubMed]
40. Xu X, Roberts S A, Pasha T L. et al Undesirable cytokeratin immunoreactivity of native nonepithelial cells in sentinel lymph nodes from patients with breast carcinoma. Arch Pathol Lab Med 2000. 1241310–1313.1313. [PubMed]
41. Maiorano E, Mazzarol G M, Pruneri G. et al Ectopic breast tissue as a possible cause of false‐positive axillary sentinel lymph node biopsies. Am J Surg Pathol 2003. 27513–518.518. [PubMed]
42. Wittekind C, Greene F L, Henson D E. et al, eds. TNM supplement: a commentary on uniform use, 3rd edition. New York: John Wiley and Sons, 2003. 7.
Articles from Journal of Clinical Pathology are provided here courtesy of
BMJ Group