Non-sentinel lymph node involvement in patients with breast cancer and sentinel node micrometastasis; too early to abandon axillary clearance

AIMS: It has been suggested that patients with T1-2 breast tumours and sentinel node (SLN) micrometastases, defined as foci of tumour cells smaller than 2 mm, may be spared completion axillary lymph node dissection because of the low incidence of further metastatic disease. To gain insight into the extent of non-sentinel lymph node (n-SLN) involvement, SLNs and complementary axillary clearance specimens in patients with SLN micrometastases were examined. METHODS: A set of 32 patients with SLN micrometastases was selected on the basis of pathology reports and review of SLNs. Five hundred and thirteen n-SLNs from the axillary clearance specimens were serially sectioned and analysed by means of immunohistochemistry for metastatic disease. Lymph node metastases were grouped as macrometastases (> 2 mm), and micrometastases (< 2 mm), and further subdivided as isolated tumour cells (ITCs) or clusters. RESULTS: In 11 of 32 patients, one or more n-SLN was involved. Grade 3 tumours and tumours > 2 cm (T2-3 v T1) were significantly associated with n-SLN micrometastases as clusters (grade: odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4 to 50.0; size: T2-3 tumours v T1: OR, 15; 95% CI, 2.18 to 103.0). However, no subgroup of tumours with regard to size and grade was identified that did not have n-SLN metastases. CONCLUSIONS: In patients with breast cancer and SLN micrometastases, n-SLN involvement is relatively common. The incidence of metastatic clusters in n-SLN is greatly increased in patients with T2-3 tumours and grade 3 tumours. Therefore, axillary lymph node dissection is especially warranted in these patients. However, because n-SLN metastases also occur in T1 and low grade tumours, even these should be subjected to routine axillary dissection to achieve local control.     

乳腺癌前哨淋巴结不同转移状态下局部淋巴结成熟树突状细胞的研究

目的：研究乳腺癌前哨淋巴结不同转移状态 下前哨淋巴结与非前哨淋巴结成熟树突状细胞密度的改变。方法:回顾 性分析79例符合研究标准的女性乳腺癌患者。根据前哨淋巴结的转移状况分为3组：A组（2 8例），所有淋巴结转移阴性；B组（25例），仅微小肿瘤出现于前哨淋巴结，包括B1组（16 例），仅游离肿瘤细胞出现于前哨淋巴结；B2组（9例），仅微转移出现于前哨淋巴结；C组 （26例），转移出现于前哨淋巴结，非前哨淋巴结有或无转移。所有前哨淋巴结及非前哨淋 巴结蜡块切片均行与DC-LAMP抗体免疫反应的免疫组织学检查以确认成熟树突状细胞。蔡司 图像分析系统定量分析每个淋巴结DC-LAMP阳性细胞的相对密度（DC-LAMP阳性细胞面积/淋 巴结面积）。Wicoxon检验和Mann-Whitney检验分别用于DC-LAMP阳性细胞的相对密度的组内 和组间比较。结果:DC-LAMP阳性细胞密度的组内比较显示A组和B组前哨 淋巴结DC-LAMP阳性细胞平均密度较非前哨淋巴结高（P<0.05，P<0.01）；C组前哨淋 巴结DC-LAMP阳性细胞平均密度与非前哨淋巴结比较无明显差异（P>0.05）。组间比较 显示各组前哨淋巴结DC-LAMP阳性细胞平均密度无显著差异；而B组(尤其B2组)非前哨淋巴结 DC-LAMP阳性细胞密度较A组和C组显著升高（P<0.05，P<0.01）。结论： 前哨淋巴结和非前哨淋巴结DC-LAMP阳性细胞平均密度在淋巴结肿瘤转移形成过程发生改变,揭示前哨淋巴结在肿瘤与引流淋巴结间相互作用中起重要作用。     

Intraoperative frozen section examination of axillary sentinel lymph nodes in breast cancer

The study presents the results from intraoperative frozen section assessment of axillary sentinel lymph nodes (SLNs) in breast cancer. Routine histological frozen sections from one level were used, two sections stained with haematoxylin and eosin. Immunohistochemistry for cytokeratins was applied to the permanent SLN paraffin sections only. Axillary dissection was performed on all SLN-positive cases regardless of the size of the metastatic deposits. With a detection rate of 83%, 272 patients entered the study over a period of 46 months. A total of 61 cases were SLN positive by frozen section analysis. The paraffin sections gave an additional 23 SLN-positive cases. The false-negative rate for frozen sections was then 27% (23/84). Micrometastases were found in 28 of 84 cases, and macrometastases in 56. The false-negative rate of frozen sections for micrometastases was 71% (20/28), and for macrometastases 5% (3/56). A total of 73% (61/84) of the patients underwent axillary surgery as a one-step procedure.     

Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer

AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The intervening material was used for MP-FCM. Cells were immunostained with MNF116, followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of the 98 patients with breast carcinoma showed evidence of metastatic disease in the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2 mm (macrometastasis) and in 14 these foci were smaller than 2 mm (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs, although this was not seen at first glance in the H&E or IHC sections. After revision of the slides, one of these three remained negative. However, MP-FCM analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which was almost identical to that of the primary breast tumour. Duplicate measurements, done in 41 cases, showed a 99% reproducibility. In five of 14 patients with micrometastasis, one or two metastatic foci were found in the non-SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have metastatic tumour. All micrometastases except for the remaining negative one mentioned above showed only diploid tumour cells, despite the fact that their primary tumours contained both diploid and aneuploid tumour cells. In primary tumours with more than 60% aneuploid cells, predominantly aneuploid macrometastasis were found, whereas diploid primary tumours only showed diploid micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases were associated with non-SLN metastases in five of seven patients, whereas diploid cases showed additional non-SLN metastases in only seven of 16 patients. CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour cells in a large volume of lymph node tissue from SLNs. In some cases it was superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are accompanied by additional non-SLN metastases. The size of the aneuploid fraction (> 60%) in the primary tumour may influence the risk of having both SLN and non-SLN metastases.     

Implementation of step sectioning in the examination of sentinel lymph nodes to improve the detection of micrometastases in breast cancer patients

The object of this study was to examine whether a new protocol for examination of sentinel lymph nodes (SLNs) would lead to the detection of more metastases. Sections of 1 mm would identify most SLN macrometastases, and step sections at intervals of 200-250 μm would identify most micrometastases. A total of 111 breast cancer patients who underwent the SLN procedure at St. Olavs University Hospital in Trondheim, Norway in 2008 were included in the study group. Their SLNs were processed according to a new standardized protocol with sections of 2-3 mm being step sectioned at intervals of 200-250 μm. A total of 109 breast cancer patients undergoing the SLN procedure in 2007 were used as a reference group. Metastases were found in 29% of the cases, compared with 26% in the reference group. Step sectioning of SLNs revealed metastases in five cases initially found to be negative. The metastases of the study group were smaller, with a median value of 1.25 mm compared with 4.25 mm in the reference group. Step sectioning led to the detection of metastases in SLNs initially found to be negative. The median size of the metastases was considerably smaller in the study group than in the reference group.     

Metastases in axillary sentinel lymph nodes in breast cancer as detected by intensive histopathological work up

AIM: To assess the value of the intensive histological work up of axillary sentinel lymph nodes (SLN) to demonstrate regional metastatic disease. METHODS: From a series of 58 successful lymphatic mapping procedures, 78 SLN were analysed by serial sections (mean of 49 levels/SLN) and by immunostaining to cytokeratin and epithelial membrane antigen, and the results compared with those obtained by assessing the central cross section. RESULTS: The central cross section would have failed to detect metastases in eight of 26 lymph nodes (31%) in patients with breast cancer metastasising to the SLN only. This would have led to a false negative node status in six of 21 patients (29%). Two micrometastases were detected with the aid of immunostains. CONCLUSIONS: The results suggest the need to examine SLN at multiple levels and to use immunohistochemistry in negative cases. Serial sections are also useful in the case of micrometastases, as some of these may convert to macrometastases at deeper levels. Multiple level investigation of SLN and immunohistochemistry in the event of the negativity of standard stains would result in improved staging and an increase in the proportion of node positive disease detected.     

Use of intraoperative stereomicroscopy for preventing loss of metastases during frozen sectioning of sentinel lymph nodes in breast cancer

Aims:  Optimal detection of metastases in sentinel lymph nodes (SLN) remains controversial. To determine the reliability of intraoperative frozen sections, SLN protocol with one frozen section was compared with macroscopic SLN evaluation with consecutive complete SLN embedding.
Methods and results:  SLN from 135 consecutive breast cancer patients were analysed under a sereomicroscope. Frozen sections were performed in suspicious or clearly involved SLN on cut surface. One control group ( n  = 143) underwent one intraoperative frozen section on each SLN. The second control group ( n  = 90) was subjected to stereomicroscopy and one intraoperative frozen section on each SLN. A conventional SLN protocol with cytokeratin immunohistochemistry was performed postoperatively in all cases. All groups were statistically comparable. In the study group metastases were suspected in 21 SLN (16%) under the stereomicroscope and all were confirmed histologically. The negative SLN rate was significantly lower in the study group than in the main control group (47% versus 64%, P  = 0.008), suggesting loss of metastases during frozen sections. More macrometastases were detected in the study group (30% versus 15%, P  = 0.006); there were no differences in isolated tumour cells or micrometastases. The false-negative rate was significantly lower in the control groups (29% versus 13% and 12%, P  = 0.001).
Conclusions:  Frozen sections potentially lead to loss or reduced size of metastatic deposits in SLN. Avoiding intraoperative frozen sections on grossly inconspicuous SLN may therefore be justified.     

Detection of micrometastases in bone marrow and sentinel lymph nodes of breast cancer patients

Objective: To study the sensitivity and clinical significance of HE-staining,IHC and RT-PCR in detecting breast cancer micrometastases in bone marrow and sentinel lymph nodes (SLNs). Methods:After general anesthesia, all patients underwent bone marrow puncture and sentinel lymph node biopsy (SLNB) by 1% isosulfan blue, and then HE-staining,IHC and RT-PCR were used to detect micrometastases. Results:Of 62 patients with breast cancer whose axillary lymph nodes showed negative HE-staining results, 15 cases presented with positive RT-PCR and 9 cases showed positive IHC results positive in bone marrow micrometastases detection. PT-PCR and IHC showed good uniformity(kappa=0.6945)and there was significant difference in detective rate between these two methods (χ2=4.1667,P=0.0412). In SLN samples, 13 showed positive RT-PCR results, while 7 showed positive IHC results. PT-PCR and IHC showed good uniformity (kappa=0.6483)and significant difference was also found in detective rate between these two methods (χ2=4.1667,P=0.0412). Both bone marrow and SLN samples were RT-PCR positive in 3 cases,which indicated that bone marrow micrometastases did not always accompany SLN micrometastases(χ2=0.067,P=0.796). Conclusion: Even if no axillary lymph node involvement or distant metastases are present in routine preoperative examination, micrometastases can still be detected in bone marrow or SLNs. Because the bone marrow micrometastases and axillary node micrometastses are not present simultaneously, combination test of multiple indicators will detect micrometastases more accurately.     

Sentinel lymph nodes for breast carcinoma: an update on current practice

Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1–T2 disease and cN0 who undergo breast‐conserving surgery and whole‐breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2 mm). Gross sectioning of SLNs at 2‐mm intervals and microscopic examination of one haematoxylin and eosin‐stained section from each SLN block is the preferred method for pathological evaluation of SLNs. The role and timing of SLN biopsy for patients who have received neoadjuvant chemotherapy is controversial, and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists.     

A model for determining the optimum histology of sentinel lymph nodes in breast cancer

AIMS: To create and use a geometrical model for sentinel lymph node (SLN) histopathology in breast cancer. METHODS: The model involves a spherical metastasis randomly situated in an SLN. Two extreme situations are taken as the starting points. In one of these, the metastasis is seen in its largest dimension, whereas in the other it is only just visible, approximating 0 mm in size. Intermediate positions are analysed, with different metastasis sizes and different distances between the levels assessed by histology. RESULTS: The findings suggest that sections taken 1 mm apart afford a reasonable means of identifying almost all metastases measuring > 2 mm (referred to as macrometastases here). For nearly all micrometastases to be identified correctly according to the current TNM definitions (that is, metastases > 0.2 mm), a step sectioning protocol with levels of 250 microm or 200 microm would be adequate. CONCLUSIONS: SLNs are the most likely sites of nodal metastasis. Macrometastases are of recognised prognostic relevance so that all should be identified, preferably correctly as macrometastases; an assessment of levels 1 mm apart appears satisfactory and sufficient for this aim. SLNs also offer an ideal method for the study of the significance of micrometastases; for this, step sections separated by 200 or 250 microm are a good choice.     

Challenging the conventional treatment of colon cancer by sentinel lymph node mapping and its role of detecting micrometastases for adjuvant chemotherapy

All colon cancer patients with lymph node (LN) positive disease are treated with chemotherapy. Patients with node negative disease are usually cured by surgery alone. Yet about 20% of patients develop recurrence within 5 years despite node negative status. This may often be the result of missed micrometastases by conventional examination. Sentinel lymph node (SLN) mapping was developed to find those nodes detected by blue dye which was ultrastaged to detect micrometastases. Consecutive patients, underwent SLN mapping with the blue dye with success rate of 99.2%. Average number of LN was 18.3, average number of SLN was 3/patient and overall nodal positivity was 45%. Ten patients had skip metastases. Overall survival of 235 patients was 84 months with survival of node negative patients 97 months versus 68 months for node positive patients. For stage I–IV patients, overall survival was as follows: stage I—115 months, stage II—90 months, stage III—84 months and stage IV—24 months respectively. Patients with micrometastases after chemotherapy had average survival of 108 months versus those without chemotherapy was 50 months. Thus, SLN mapping techniques is highly successful, easily reproducible and finds micrmoetastases in over 15% of patients which could have been missed by conventional pathological examination. These patients when treated with adjuvant chemotherapy have similar survival as those of node negative disease. Similarly, patients without any nodal metastases after SLN mapping and ultrastaging, may be considered as true node negative disease and may avoid further adjuvant chemotherapy.     

Strategies for optimizing pathologic staging of sentinel lymph nodes in breast cancer patients

Due to the extensive pathologic evaluation of the sentinel lymph node (SLN), micrometastases are frequently observed. If micrometastases are clinically relevant, the histopathologic examination of SLNs should be sensitive enough to detect them. The probability of detecting micrometastases was calculated when examining the SLN according to the current Dutch pathology protocol and strategies evaluated to optimize the chance of detection. The dimensions of 20 consecutive axillary SLNs in patients with cT1-2N0 breast cancer were measured. In a mathematical model, the probability of detecting micrometastases in a SLN was calculated. Similarly, strategies to optimize the probability of detecting micrometastases were explored. When applying the pathology guidelines, the calculated probability to detect a micrometastasis was 18% for a 200-microm micrometastasis and 69% for a 2.0-mm metastasis in a median sized SLN. To detect the smallest micrometastasis in a median-sized SLN with a 95% probability, the interval between the sections must be decreased to 200 microm, and 20 levels from both halves must be examined. Given a prognostic significance of micrometastases, our current pathology guidelines are not sensitive enough. The number of sections should be increased, while the interval between cuts should be no more than 200 microm.     

宫颈癌前哨淋巴结活检的假阴性原因分析

目的探讨染料法识别宫颈癌前哨淋巴结（SLN）活检时出现假阴性的原因。方法选择49例早期宫颈癌患者,术前宫颈瘤周注射亚甲蓝,行广泛子宫切除＋盆腔淋巴结清扫术;进行前哨淋巴结定位及病理学检查。结果SLN识别率为87．8％（43／49）,灵敏度为81．8％,准确率为92％,假阴性率为18．2％。结论本组假阴性与肿瘤大小、淋巴转移的途径、术前放疗、病理检测方法有关。     

Evaluation of axillary sentinel lymph node biopsy by immunohistochemistry and multilevel sectioning in patients with breast carcinoma

BACKGROUND: Axillary lymph node dissection for evaluation of the presence or absence of metastatic disease is the single most important prognostic factor for patients with newly diagnosed primary breast cancer. Recently, sentinel lymph node (SLN) biopsy is being investigated as an alternative to the evaluation of the entire axilla. We evaluated whether the application of multilevel sectioning and immunohistochemistry in SLNs will increase the accuracy of detection of metastatic deposits. METHODS: Between October 1998 and July 1999, 38 patients with breast carcinoma (25 ductal, 5 lobular, 4 tubular, and 4 mixed ductal and lobular) underwent successful SLN biopsy followed by complete axillary node dissection. Sentinel lymph nodes were localized with a combination of isosulfan blue dye and radionuclide colloid injection. Frozen sections and permanent sections of SLNs were examined. All negative SLNs were examined for micrometastases by 3 additional hematoxylin-eosin (H&E)-stained sections and immunohistochemistry with the cytokeratins AE1/AE3. RESULTS: Sentinel lymph nodes were successfully identified surgically in 38 (93%) of 41 patients. There was a 97% correlation between the results of the frozen sections and the permanent H&E-stained sections. Twelve (32%) of 38 patients showed evidence of metastatic disease in their SLN by routine H&E staining. In 7 (58%) of 12 patients with positive nodes, the sentinel node was the only positive node. The 26 patients with negative SLN examination by H&E were further analyzed for micrometastases; 5 (19%) were found to have metastatic deposits by immunohistochemistry. Of these patients, 2 were also converted to node positive by detection of micrometastatic disease by examination of the additional H&E levels. CONCLUSIONS: Sentinel lymph nodes can be accurately identified in the axilla of breast cancer patients. Evaluation of SLNs provides reliable information representative of the status of the axilla in these patients. Immunohistochemistry and, to a lesser degree, detailed multilevel sectioning are able to further improve our ability to detect micrometastatic disease in SLNs of breast cancer patients.     

Comprehensive examination of sentinel lymph node in breast cancer: a solution without a problem?

Although several methods have been devised to examine sentinel lymph node (SLN) specimens in breast cancer, the extent of examination and whether it should routinely include multilevel sectioning to detect micrometastases (MM) (<2.0 mm) is still debated. In this study all "positive' SLN biopsies from 67 consecutive patients with breast carcinoma and evaluated by means of an extended protocol were reviewed. Abnormal findings included micrometastases (MM) between 0.2 and 1.0 mm (14 cases), (MM) between 1.0 and 2.0 mm (8 cases), metastases>2.0 mm (22 cases), and isolated tumor cells (ITCs) (23 cases). The likelihood of finding metastatic deposits was comparable if sections were carried out at 100-, 150-, 200-, 250-, and 500-microm intervals. No metastatic foci>2.0 mm would have been missed. 1 MM (1.1 mm focus) was missed within the 250- and 500-microm levels on hematoxylin-eosin, but not complementary cytokeratin staining. Our data show that SLN step sectioning does not add significant yield if compared to standard examination carried on initial levels, if the minimal target of 1.0 mm micrometastatic deposit is sought.     

Histopathological work-up and interpretation of sentinel lymph nodes removed for vulvar squamous cell carcinoma

Aims:  To evaluate the work-up of sentinel lymph nodes (SLNs) removed for vulvar pT1–pT2 squamous cell carcinoma (SCC). Inguinal lymphadenectomy yields metastases in only 30% of cases. Patients with missed inguinal disease, however, have a risk of dying from systemic disease. SLN dissections reduce morbidity, but work-up should reliably identify metastatic disease.
Methods and results:  All SLNs removed from 38 patients with pT1–pT2 SCC and clinically negative inguinal lymph nodes were submitted for frozen section analysis. When negative, SLN were formalin-fixed, sectioned entirely at 330-μm intervals to produce three slides per millimetre [two haematoxylin and eosin (H&E) stained slides; one slide for immunohistochemistry]. If screening of H&E-stained sections was negative, all remaining slides were subjected to immunohistochemistry with an antibody to cytokeratin. Twenty-five of 38 patients (66%) were pN0, 7/38 (18%) had metastases on frozen sections/H&E stains. Immunohistochemistry detected micrometastases in two patients and single tumour cells and anucleate cell structures in four patients. In 12/13 patients the SLN metastases, including all single-cell deposits, were from lichen sclerosus (LS)-associated SCC. Twelve of 13 patients with metastases had a pT2 SCC.
Conclusions:  Micrometastases and single tumour cell deposits in SLNs are typical of LS-associated vulvar SCC. Single tumour cell deposits in SNLs should be regarded as 'positive'. Identification requires serial sectioning and immunohistochemical analysis of all removed SLNs.     

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

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.     

Assessment of sentinel nodes in breast cancer by rapid peroperative biopsy and immunohistochemistry in serial sectioning

Results of histological examinations of sentinel lymphatic nodes (SLN) obtained by rapid peroperative biopsy (RPB) are presented. Our first experience with 77 patients undergoing localized excision of axillary sentinel nodes is reported. Negative nodes were subsequently examined by means of immunohistochemistry of serial sectioned blocks. The aim of the study was to verify the percentage of identified metastases, and thus define the reliability of the RPB. At the same time we tried to determine the ratio of the negative biopsies of SLN, which were found positive subsequent to immunohistochemistry examination of serial sections, to the total amount of peroperative negative findings or a "false negativity". Our results were compared with those recently published. Particular demands and possibilities of the method used are briefly discussed. In the group of 77 patients with breast cancer, the total number of 193 SLN were examined (average 2.5, in a patient ranging from 1 to 7). Out of all examined SLN, 45 patients (58.4%) were negative. Metastases were identified in 32 patients (41.6%). By rapid preoperative biopsy alone, metastases were found in 24%, which represents 75% sensitivity. The specificity was 100%. The following examination of serial sectioned specimens with or without immunohistochemistry showed 8 more patients with metastases, which represents the false negativity of 15.1%. The metastases found in all 8 patients were small micrometastases, isolated tumour cells or clusters of cells.     

Regional lymph node micrometastases in malignant melanoma of the skin

Histological studies were conducted into 352 primary malignant melanomas of the skin together with 4,003 associated and surgically removed lymph nodes at the Institute of Pathology and Bacteriology of Kaiserin-Elisabeth-Spital, between 1982 and 1987. Particular attention was given to micrometastases of regional lymph nodes. 27 lymph node micrometastases were recorded from 25 patients. Spots of melanin were also found in lymphatic tissue, but no tumour cells were detectable. There is no clinical aid by which micrometastases of lymph nodes might be possibly diagnosed, and, on principle, they are greatly accidental findings even for the pathohistologist. However, undetected lymph node micrometastases may have a deteriorating impact upon the prognosis of malignant melanoma. Complete microscopic elucidation of surgically removed lymph nodes, there fore, is absolutely essential. Capillaries are present in abundance deep inside lymph nodes, and from these points of departure tumour cells may enter into the blood flow and cause haematogenic metastases. That is why the prognostic importance attributed to histologically verified micrometastases is just as great as that attached to macrometastases.