Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity.

AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (≥85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

Is there a role for adjuvant hysterectomy after suboptimal concurrent chemoradiation in cervical carcinoma?

AIMS: Failure to carry out intracavitary brachytherapy (ICBT) in cervical carcinoma results in suboptimal chemoradiation and increases the risk of recurrence. The aim of this study was to investigate the role of adjuvant hysterectomy after unsuccessful ICBT. MATERIALS AND METHODS: A retrospective analysis was carried out of all women referred with cervical carcinoma between January 1999 and July 2007 where ICBT insertion was unsuccessful after the initial chemoradiation. The data collected and analysed included histology, stage of disease, causes for unsuccessful ICBT insertion, the response to the initial chemoradiation, subsequent treatment, morbidity, recurrence rates and survival rates. Kaplan-Meier and Log-rank methods were used to analyse recurrence-free and overall survival rates. RESULTS: ICBT insertion was unsuccessful in 19 of 208 (9%) patients. The causes of failure were: inability to dilate the cervix; uterine perforation; vesicovaginal fistula; patient refusal; other problems, including the presence of pyometrium, patient not fit for general anaesthetic, and narrow vagina; and consultant choice with no obvious reason. Fourteen of 19 patients (74%) received further pelvic external beam radiotherapy (EBRT) alone; five (26%) patients underwent adjuvant hysterectomy. The median follow-up for all patients was 63 months; 60 months for patients treated with adjuvant hysterectomy (range 31-68 months) and 85 months for patients treated with further EBRT. None of the patients treated with adjuvant hysterectomy developed any significant late toxicity. Seven patients (50%) treated with EBRT have relapsed compared with none in the adjuvant hysterectomy arm (P=0.068). Six patients (43%) in the EBRT arm have subsequently died of recurrent disease compared with none in the adjuvant hysterectomy arm (P=0.152). CONCLUSIONS: Adjuvant hysterectomy after unsuccessful ICBT does not seem to increase late toxicity and reduces the risk of pelvic recurrence and may improve survival. The role of adjuvant hysterectomy after suboptimal chemoradiation merits further investigation in clinical trials.

NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life.

The NEAT trial reported considerable benefit for ECMF (epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil) of 28% for relapse-free survival (RFS) and 30% for overall survival (OS), when compared with classical CMF in early breast cancer. To assess tolerability, toxicity, dose intensity and quality of life (QoL) analyses were undertaken. All 2021 eligible patients had common toxicity criteria (CTC), delivered chemotherapy and supportive treatments details and long-term morbidities recorded. The QoL substudy used multiple validated measures. ECMF produced low CTC scores, although higher than CMF for nausea, vomiting, alopecia, constipation, stomatitis (P<0.001), infection (P=0.001) and fatigue (P=0.03). Supportive treatments required, however, were similar across randomised treatments. On-treatment deaths were more common with CMF (13) than ECMF(5). Optimal course-delivered dose intensity (CDDI > or =85%) was received more often by ECMF patients (83 vs 76%: P=0.0002), and was associated with better RFS (P=0.0006). QoL over 2 years was equivalent across treatments, despite minimally worse side effects for ECMF during treatment. ECMF benefit spanned all levels of toxicity, CDDI and QoL. There are no reported acute myeloid leukaemias or cardiac dysfunctions. ECMF is tolerable, deliverable, and significantly more effective than CMF, with no serious long-term toxicity or QoL detriment.

tAnGo: a randomised phase III trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation.

tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), following epirubicin(E) and cyclophosphamide(C) in women with invasive higher risk early breast cancer. To assess the safety and tolerability of adding G, a detailed safety substudy was undertaken. A total of 135 patients had cardiac, pulmonary and hepatic function assessed at (i) randomisation, (ii) mid-chemotherapy, (iii) immediately post-chemotherapy and (iv) 6 months post-chemotherapy. Skin toxicity was assessed during radiotherapy. No differences were detected in FEV(1) or FVC levels between treatment arms or time points. Diffusion capacity (TL(CO)) reduced during treatment (P<0.0001), with a significantly lower drop in EC-GT patients (P=0.02). Most of the reduction occurred during EC and recovered by 6-months post treatment. There was no difference in cardiac function between treatment arms. Only 11 patients had echocardiography/MUGA results change from normal to abnormal during treatment, with only five having LVEF<50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients post-chemotherapy (AST P=0.03, ALT P=0.003), although the majority was low grade. There was no correlation between transaminitis and other toxicities. Both treatment regimens reported temporary reductions in pulmonary functions and transient transaminitis levels. Despite these being greater with EC-GT, both regimens appear well tolerated.

Delaying radiotherapy for the delivery of adjuvant chemotherapy in the combined modality treatment of early breast cancer: is it disadvantageous and could combined treatment be the answer?

Women with early stage breast cancer are increasingly being treated with both adjuvant chemotherapy and radiotherapy. The optimal sequence of these two treatment modalities is yet to be defined. It remains controversial whether delaying radiotherapy in order to deliver chemotherapy compromises local disease control and survival. Consequently, clinical practice in the UK is divided, with a number of different combination schedules being used in an effort to bring forward the start of radiotherapy. In practice, however, any benefit in local control must be balanced against a potential increase in toxicity. A review of the current literature on the effect of radiotherapy delay is presented, together with data on the toxicity of combined chemo-radiotherapy schedules and recent data from clinical trials designed to determine the optimal sequencing of chemotherapy and radiotherapy.

The role of radiotherapy in patients undergoing mastectomy for carcinoma of the breast.

Several factors, including T stage, nodal involvement, grade, the presence of lymphovascular invasion, and possibly involved or close surgical margins, have been found to affect local recurrence after mastectomy. The majority of recurrences will occur in the first 5 years and 50% of patients will have metastatic disease at the time of recurrence. Early studies on the use of adjuvant radiotherapy are difficult to interpret owing to poor radiotherapy techniques, inadequate dose or a variety of confounding variables within a particular trial. More recent reports have confirmed that adjuvant radiotherapy will reduce the risk of local recurrence and in tumours of <5 cm with involved nodes, produce a reduction in breast cancer deaths. Improvements in breast cancer mortality may however be counterbalanced by increases in cardiac events and deaths caused by second malignancies. This stresses the importance of using megavoltage irradiation and avoiding excess cardiac doses particularly when treating left-sided tumours. Adjuvant radiotherapy combined with tamoxifen has been shown to produce an improvement in both local control and survival in postmenopausal node-positive patients who have undergone mastectomy. Adjuvant radiation combined with systemic chemotherapy has a significant effect on local recurrence and probably on survival in node-positive patients after mastectomy. There is little controversy over its role in patients with tumours >5 cm, with more than four nodes involved or with one to three nodes with extracapsular extension, or in those in whom axillary surgery has been deemed inadequate (i.e. <10 nodes). Debate still exists concerning T1/T2, G1/G2 tumours with only one to three nodes involved when the axillary surgery has been satisfactory (>10 nodes). The ongoing Intergroup trial may answer this question but until then other factors such as tumour grade and the presence of lymphovascular invasion can be included in the equation to determine which of the patients in the latter group should receive postoperative radiotherapy. Controversy still exists about what fields should be irradiated and in particular whether the supraclavicular fossa and internal mammary node chain should be included in adjuvant therapy. The EORTC is presently conducting a randomized trial, which should give us the answer. Treatment at relapse on the chest wall may require a combination of surgery, radiotherapy and chemotherapy, depending on previous therapy. If radiotherapy has not previously been used, then wide-field irradiation should be administered, including both chest wall and supraclavicular fossa with or without the axilla, depending on the extent of previous axillary surgery and the risk of lymphoedema. Re-irradiation after radical adjuvant radiotherapy can be considered only for selected patients when an adequate discussion with them has taken place with regard to the relative benefits versus toxicity.

Cytological evaluation of biological prognostic markers from primary breast carcinomas.

This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.

Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas.

Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer. Ninety patients (median age 56 years; range, 28-69 years) with primary operable breast carcinoma were studied. They were treated with four 3-weekly cycles of chemotherapy with mitozantrone, methotrexate (+/- mitomycin C), and tamoxifen prior to surgery. Fine-needle aspiration was used to obtain samples from patients prior to therapy, and the following parameters were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, Bcl-2, and c-erbB-2 measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow cytometry. The tumors of 78% of the subjects responded (complete response, 9%; partial response, 69%) and 22% did not (no change, 20%; progressive disease, 2%). Response rates according to disease stage and patient age were as follows: T1, 74%; T2, 79%; T3/T4, 78%; age 50, 79% (P = not significant). Response rates for other parameters were as follows: ER-positive, 82%, and -negative, 70%; PgR-positive, 86%, and -negative, 71%; p53-positive, 74%, and -negative, 81%; Bcl-2-positive, 85%, and -negative 61%; c-erbB-2-positive, 57%, and -negative, 93%; Ki67 high, 77%, and low, 81%; SPF high, 77%, and low, 77%; aneuploid, 71%; and diploid, 85%. Only the difference for c-erbB-2 was statistically significant (P = 0.007). A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER, PgR, and Bcl-2 was observed but did not reach statistical significance. Tumors negative for c-erbB-2 had a higher response rate, which was statistically significant. In contrast, Ki67, ploidy, SPF, and p53 failed to predict for response.

Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: a prospective study of treatment practice at the Royal Marsden Hospital.

The results are presented of a prospective study of acute skin toxicity in 197 patients with early stage breast cancer, who were treated by conservative surgery and postoperative radiotherapy. We have examined the factors determining the severity of the acute skin reaction with particular reference to the degree of dry or moist desquamation at the completion of treatment. One hundred and ten patients had treatment with radiotherapy alone. The remaining 87 received synchronous chemotherapy with breast irradiation, using either the 3M or the 2M regimen, consisting of mitoxantrone and methotrexate, with (3M) or without Mitomycin-C (2M). Patients were analysed according to both the severity and the site of the skin reaction, age, dose, dose variation across the central outline, treatment technique, beam energy, field separation and breast size. A univariate analysis of these results, which has been presented as an odds ratio of the likelihood of developing a moderate or severe reaction in comparison with those scored as mild, has shown that several factors are associated with an increase in the acute skin reaction. These include the use of the semi-supine technique (odds ratio (OR) = 7.3 (95% CI 3.7-14.6)), beam energy (60Co: 6-10 MV photons OR = 5.9 (95% CI 2.6-13.4)), field separation (> or = 20 cm: < 20 cm OR = 4.1 (95% CI 2.2-7.8)), dose variation across the central outline (> or = 10%: < 10% OR = 9.7 (95% CI 2.6-36.4)), inclusion of the axilla (OR = 4.6 (95% CI 2.4-8.9)), and bust size (bra cup size C and D: A and B OR = 4.6 (95% CI 2.7-11.9)). Using multivariate logistic regression, the technique of radiation delivery and bust size were shown to be independently significant variables affecting acute skin reaction. In view of the high correlation between variables (e.g. radiotherapy technique and beam energy) it is still not possible to specify with definite certainty which is the primary variable causing the skin reaction. However 20/57 (35%) of patients treated by the semisupine technique sustained a severe skin reaction, with > 10% dry or moist desquamation in the treatment field. This compares with only 6/140 (4%) patients treated by the supine method. A possible mechanism by which treatment using the semisupine technique may enhance acute toxicity is discussed. We conclude that there are both treatment and patient related factors that will increase the acute skin reaction after breast irradiation.

An acute toxicity study on the effects of synchronous chemotherapy and radiotherapy in early stage breast cancer after conservative surgery.

One hundred and ninety-seven patients with early stage breast cancer, who were treated initially with conservative surgery, were evaluated prospectively for acute toxicity after completing post-operative irradiation. Eighty-seven of these patients had synchronous chemotherapy with the 3M regimen (mitoxantrone, methotrexate and Mitomycin-C) during radiotherapy. The results indicate that patients receiving chemotherapy and radiotherapy (CRT) showed no significant difference in acute skin toxicity (AST) when compared with those treated with radiotherapy alone (RTO), with an odds ratio (OR = 0.6) and 95% confidence intervals (0.3-1.1) of developing either a moderate or severe, compared with a mild, skin reaction. Even after controlling for other confounding factors, such as treatment technique and beam energy, patients treated with the supine technique using 6-10 MV photons still displayed no significant difference in AST, with 12/74 (16%) patients in the CRT group and 14/66 (21%) in the RTO group developing a moderate or severe skin reaction (OR = 0.7 (95% CI 0.3-1.7)). Four of the 87 patients treated with CRT developed symptomatic acute radiation pneumonitis, three of whom were found to have > 3 cm of lung length on their simulator or check films. The volume of lung included within the treatment field was found to be statistically significant (P = 0.005) in predicting the onset of radiation pneumonitis in the CRT group. None of these patients has suffered any symptomatic late lung toxicity. We conclude that synchronous chemotherapy and radiotherapy, when using the 3M regimen, is feasible for patients having adjuvant treatment for early stage breast carcinoma and there is no significant increase in AST. However, it is associated with an increase in acute radiation pneumonitis when a significant volume of lung is included within the radiation treatment field.

Determining factors which predict response to primary medical therapy in breast cancer using a single fine needle aspirate with immunocytochemical staining and flow cytometry.

The increasing use of neoadjuvant chemotherapy and endocrine therapy in the management of breast cancer has lead us to evaluate and optimise the standard technique of cytocentrifugation of a single fine needle aspirate (FNA) taken from a breast tumour in-vivo, to determine a range of both immunocytochemical and flow cytometric factors which are predictive of response to primary medical therapy. Some of these factors are also of prognostic significance in early stage disease. An analysis of the cellularity and immunocytochemical staining characteristics of FNAs obtained from a series of 206 patients with palpable breast cancers indicate that in a sample of 46 cases it is possible to measure oestrogen receptor, progesterone receptor and c-erbB-2 providing over 400 cells per slide are obtained, with material obtained in a single FNA prepared by cytocentrifugation, using standard immunocytochemical methods. The staining results obtained were comparable to those obtained using frozen or paraffin embedded tissue sections taken from the same tumour. In addition an estimate of the proliferation indices could be made by flow cytometric analysis of the residual cell suspension fluid with measurement of DNA index and S-phase fraction in 131/164 (80%) and 110/164 (67%) of cases respectively. Providing all FNAs obtained for cytocentrifugation were taken at first presentation rather than immediately following a standard FNA, then it was possible to obtain adequately cellular (> 400 cells/slide) samples in 96 out of 126 (75%) of the last cohort of breast aspirates. These effects may be independent of T stage but not histological type as patients with lobular tumours only produced cellular aspirates in 1/7 (14%) of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of head and neck irradiation on taste dysfunction: a prospective study.

Taste loss is a major cause of morbidity in patients undergoing head and neck irradiation. In a prospective study, 26 patients undergoing radical head and neck irradiation at the Royal Marsden Hospital, Sutton, and the Queen Elizabeth Hospital, Birmingham, were assessed for taste loss and xerostomia. Taste was tested using a subjective questionnaire and by objective taste testing with a series of solute solutions (sucrose, sodium chloride, urea and hydrochloric acid) at increasing concentrations, to determine the threshold level of taste sensation, both before and after radiotherapy. Xerostomia was assessed using a patient questionnaire. The volume of tongue and parotid contained within the high dose volume of the radiation treatment field was determined for each patient and correlated with the degree of objective and subjective taste loss as well as the degree of xerostomia. The results have shown that both objective (r = 0.59; P = 0.0016) and subjective taste loss (r = 0.78; P = 0.0001) was significantly associated with the proportion of tongue, but not parotid, contained within the radiation treatment field. The data gave no evidence to suggest any relationship between recovery of taste loss and volume of parotid or tongue irradiated. However, recovery of subjective taste loss, 1 month after completing radiotherapy was seen in two patients, both of whom had been treated using a wedge pair technique to avoid the contralateral area of the tongue. Changes in xerostomia were significantly correlated with the proportions of both tongue (r = 0.54; P = 0.004) and parotid (r = 0.82; P = 0.0001) within the radiation treatment fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of S-phase fraction and ploidy in sequential fine-needle aspirates from primary human breast tumours treated with tamoxifen.

Sequential fine-needle aspirates (FNAs) for cytodiagnosis and flow cytometry were taken from 21 patients with primary breast carcinoma at intervals ranging from 1 to 3 months after the commencement of first-line tamoxifen therapy. Nine patients achieved a sustained complete or near complete response over a 3-9 month period. The tumour cells from seven out of nine of these patients were initially aneuploid, while the remaining two patients had diploid tumours. An analysis of sequential FNAs showed that, in three out of the seven aneuploid tumours, only benign epithelial cells could be detected by cytology in the post-tamoxifen sample. In the remaining six cases, including the two diploid tumours, there was no change in ploidy but a reduction in S-phase fraction (SPF) to approximately 50% of the pretreatment level. In all cases, these changes in ploidy or SPF were seen with a mean lead time of 4 months before the tumour had reached clinical complete remission. None of these patients have relapsed after a mean follow-up period of 18 months. The tumours of 12 patients achieved no more than a temporary partial response to primary tamoxifen therapy. In seven out of eight of these cases, which were all initially aneuploid, sequential FNAs during tamoxifen therapy revealed either an increase or no change in the SPF with the tumour remaining aneuploid. In the remaining four cases the tumours were all recorded as being diploid in the pretreatment sample. However, although three of these cases had a temporary partial response to tamoxifen, an aneuploid component was picked up in repeat sequential FNAs with a mean lead time of 5 months before clinical confirmation of eventual disease progression. We conclude that changes in ploidy and SPF detected by flow cytometry may predict initial response and the likelihood of relapse of breast tumours to tamoxifen before clinical changes become evident. These data justify a larger study.

Is there still a role for lymphography in the management of early stage carcinoma of the cervix?

The value of lymphography in the management of carcinoma of the cervix is controversial and in many institutions has ceased to be used as part of routine staging. We present the results of 103 patients with carcinoma of the cervix treated by radical radiotherapy alone at the Royal Marsden Hospital between 1984 and 1990 all of whom had a staging lymphogram and computed tomography (CT) of the abdomen and pelvis as part of their routine staging prior to therapy. Our results show that 72 patients (70%) had no involved nodes detected on either CT or lymphography (LG--ve/CT--ve) while 16 patients (15.5%) were thought to have involved lymph nodes on lymphography alone but not on CT (LG+ve/CT-ve). The remaining 15 cases (14.5%) had involved lymph nodes on both CT and lymphography (LG+ve/CT+ve). There were no patients shown to have involved lymph nodes on CT with a negative lymphogram. Survival analysis on these three groups showed that patients in the LG+ve/CT+ve group did worse than the other two groups with only a 28% 5 year survival compared with 60% (LG-ve/CT-ve group) and 64% (LG+ve/CT-ve group) (p < 0.1). This effect of lymph node involvement disappeared in a multivariate analysis using Cox regression when stage came out as the strongest factor affecting survival. After controlling for stage, a further analysis of patients with only stage I and II disease has shown that patients who were LG+ve/CT+ve still did significantly (p < 0.05) worse (30% 5 year survival) than the other two groups: LG-ve/CT-ve group altered clinical management in 5/6 patients with stage I or IIA disease who avoided radical surgery and who were given a parametrial boost to the site of lymph node involvement. The possible benefit of this additional treatment to explain the higher survival rate of patients in the LG+ve/CT-ve group is discussed further. We conclude that lymphography still has a limited role to play in patients with early stage disease (I or IIA) who do not appear to have involved lymph nodes on CT scanning.

Immunocytochemical staining for the c-erbB-2 gene product in breast aspirates: a preliminary report.

The results of the determination of c-erbB-2 gene expression by immunocytochemical staining of cytological aspirates, prepared by cytocentrifugation, have been compared with paraffin-embedded tissue sections from the same tumour. Our results show equivalent staining in 20/22 cases, with six cases being both scored positive and fourteen cases being both negative. Two samples gave conflicting results. One case was scored as being positive on the cytological aspirate, whereas in the tissue sections taken from the same tumour positive staining was only seen in areas of non-invasive intraduct carcinoma. This sample was scored as being negative. In another case, cytoplasmic staining with less than 50% of the cells showing any positivity was observed in the cytospin sample, with negative staining in the corresponding tissue section. We conclude that expression of c-erbB-2 immunostaining is detectable on cytological preparations prepared by cytocentrifugation but must be interpreted with caution in tumours which may have a large intraduct component or which give predominant cytoplasmic staining.

Malignant nerve sheath tumour arising in a ganglioneuroma.

A malignant nerve sheath tumour arising within a thoracic ganglioneuroma is described. This is only the seventh such case described in the literature and the first at this site. The previously documented cases are reviewed.