Breast cancer in women under 40 years of age: a series of 57 cases from Northern Ireland.

BACKGROUND: There are few studies examining breast cancer in women under the age of 40 years, particularly in western European populations. Such tumours are reported to be more aggressive, possibly due to a different pathophysiology compared to older patients. METHODS: We performed a retrospective review of all women less than 40 years of age, diagnosed or treated with breast cancer, from June 2001 to June 2007 to assess pathophysiological factors that may influence clinical outcome and prognosis including patient demographics, clinical presentation, pre-operative investigations, surgical and pathological findings, treatment and outcome. RESULTS: Fifty-eight women (mean age 34.9 years, range 27-39 years) were identified. One patient was excluded due to incomplete data; 98.2% (n=56) patients presented directly to our symptomatic clinic; 89.5% (n=51) patients had a palpable lump; 71.9% (n=41) patients had no family history. Mammography was less sensitive than ultrasound (64.3% vs. 82.4%) while fine needle aspiration cytology was 92.5% sensitive for malignancy. Twenty-nine (50.9%) patients underwent breast-conserving surgery (BCS) of which 7 proceeded subsequently to completion mastectomy due to involved margins. Twenty-six (45.6%) patients required total mastectomy primarily while 2 (3.5%) patients were treated palliatively due to metastatic disease. The mean tumour size (nearest resection margin) was 2.13cm (2.58mm) for BCS and 3.95cm (6.38mm) for mastectomy. From a total of 55 primary resections, 85.5% (n=47) of tumours were invasive ductal carcinoma; 57.4% (n=31) and 40.7% (n=22) were grade II and III tumours respectively. Lymphovascular invasion was identified in 50.9% (n=28) while 40.0% (n=22) were lymph node positive for metastatic disease. 76.8% (n=43), 39.3% (n=22) and 30.2% (n=16) were oestrogen, progesterone and human epidermal growth factor receptor-2 positive respectively. The mean Nottingham prognostic index was 4.37 (range 2.2-8.4). Neo-adjuvant and adjuvant chemotherapy was administered to 9.3% (n=5) and 80.0% (n=44) of surgically treated patients respectively while 76.4% (n=42) patients received adjuvant radiotherapy. 76.4% (n=42) of patients were treated with tamoxifen. Four patients received Herceptin therapy. Statistically significant univariate factors adversely associated with overall survival were time from referral to out-patient department attendance (p=0.038), administration of neo-adjuvant treatment (p=0.019), surgical intervention (p<0.001), progesterone receptor positivity (p=0.018) and tumour recurrence (p<0.001). 86.0% (n=49) patients were alive at mean follow-up of 52 months; 82.5% (n=47) remain disease free. CONCLUSION: Our study reports a low familial trait rate combined with a high proportion of hormonally active tumours less than grade III which suggests that breast cancer in this series of young women from Northern Ireland may be less aggressive and more hormonally responsive than anticipated.

Role of polymerase chain reaction and immunocytochemistry in the cytological assessment of lymphoid proliferations.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is used as a screening test to evaluate lymphadenopathy. The combined use of genetic analysis and flow cytometry for immunophenotyping has increased the accuracy of diagnosis and correct categorisation of lymphomas on cytological preparations. AIM: To show the utility of immunocytochemistry and polymerase chain reaction (PCR) in the evaluation of cytological preparations of lymph nodes. METHODS: Fine needle aspirates were obtained from 33 patients (initial presentation, n = 27; recurrence, n = 6). Routine examination was undertaken using immunocytochemistry and DNA PCR to detect clonality and specific translocations. The cytodiagnosis and subclassification of lymphoma was correlated with histological diagnosis in the available follow-up biopsies. RESULTS: 14 patients had a cytological diagnosis of non-Hodgkin's lymphoma (NHL), 4 had suspected NHL, 2 had atypical lymphoid proliferation and 13 had reactive hyperplasia. A World Health Organization (WHO) subtype was suggested in 8 patients. Incorporating the results of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements enabled diagnosis of lymphoma in 17 patients, including 5 of the 6 patients suspected to have NHL or an atypical lymphoid proliferation. Identification of the translocations t (14;18) and t (2;5) helped WHO categorisation in 3 of the patients. The cytological findings were confirmed in 12 out of the 13 patients for whom histological follow-up was available. Seven of the 18 lymphoma patients were managed without a subsequent biopsy. We made one false-positive diagnosis of B-cell NHL on cytology. CONCLUSION: The use of immunocytochemistry and PCR is valuable in the definitive diagnosis and subtyping of malignant lymphomas on cytological preparations. The use of these techniques may avoid lymph node biopsies in some cases and allow definitive treatment based on aspirate findings alone.

Fine needle aspiration cytology (FNAC) in the diagnosis of granulomatous lymphadenitis.

OBJECTIVE: To determine the final histological and clinical diagnosis of patients with granulomatous lymphadenitis on fine needle aspiration cytology (FNAC). METHOD: A retrospective cohort study was carried out over a five year period in a tertiary referral hospital. FNAC of 22 patients with granulomatous lymphadenitis was reviewed and correlated with the final histological diagnosis and clinical outcome. RESULTS: Fourteen cases (64%) underwent surgical biopsy for histological assessment. A definitive diagnosis on FNAC with ancillary investigations was achieved in 82% (18 out of 22) of the cases: four Hodgkin's lymphoma, two non-Hodgkin's lymphoma (NHL), five tuberculosis (TB), two toxoplasmosis, one sarcoidosis and four benign reactive changes. CONCLUSION: A significant number of cases of FNAC diagnosed granulomatous lymphadenitis have an identifiable underlying cause. Patients with reactive cytological changes, who clinically appear benign, can avoid unnecessary surgery.

The effect of ultra violet B (TL-01) phototherapy on epidermal expression of p53 protein in psoriatic plaques.

BACKGROUND: Psoriasis is a genetically determined inflammatory skin disease. It is now recognized that narrow band TL-01 phototherapy is an effective treatment for psoriasis. However, ultraviolet (UV) exposure induces p53 mutations in keratinocytes and repeated exposure of skin to UV radiation results in clonal expansion of these initiated p53-mutant cells within the epidermis. AIM: The present study aims to examine epidermal p53 expression in the skin of psoriatic patients at different time points following TL-01 phototherapy. METHODS: Skin samples from patients suffering from plaque-type psoriasis, collected before, during and at the final stages of TL-01 phototherapy were examined for p53 expression by immunohistochemistry. RESULTS/CONCLUSION: Our results showed an increase in p53 expressing keratinocytes following TL-01 phototherapy. Some of these cells were arranged spatially, as conical clones arising from putative stem cell compartments, suggesting that the chronic TL-01 treatment might have triggered cell growth and clonal expansion, an important step in initiating skin carcinogenesis.

Prognostic significance of glycoprotein pMQ1 in breast cancer.

BACKGROUND: A novel glycoprotein, pMQ1, is positively correlated with increasing histological grade in malignant astrocytomas. Cerebral metastases from breast cancer have also been found to contain pMQ1-positive cells. This study aimed to determine the role of pMQ1 in primary breast cancer. METHODS: Breast cancer specimens were analysed for pMQ1 by immunohistochemistry. The expression of pMQ1 was correlated with conventional prognostic indicators. Kaplan-Meier analyses were performed to compare clinical outcome between pMQ1-positive and pMQ1-negative tumours. RESULTS: pMQ1 was expressed in most of the breast cancer specimens. The surrounding normal tissue margins and benign breast tissues always lacked pMQ1 expression. A significant positive correlation was observed between pMQ1 expression and histological grade, the presence of lymphovascular invasion and Nottingham Prognostic Index. Cancers that were pMQ1 positive were significantly more likely to develop a local recurrence. CONCLUSION: pMQ1 appears to be a tumour-associated protein. The positive correlation of pMQ1 with histological grade, presence of lymphovascular invasion and Nottingham Prognostic Index suggests that it confers an adverse prognosis.

Surgical treatment for invasive lobular carcinoma of the breast.

The management and outcome of 131 women with infiltrating lobular carcinoma treated in the Belfast City Hospital between October 1987 and February 1999 were reviewed. Two patients had primary hormonal treatment and were excluded from the statistical analysis, and 129 patients were followed up. Fifty-four patients (41%) had initial breast conservation surgery, which was followed by re-excision of margins in eight patients (14.8%) and completion total mastectomy in 26 patients (48.1%). The breast conservation surgery group, 28 patients (21.7%), was compared with the total mastectomy group, 101 patients (78.2%), after a median follow-up period of 90 months (range 24-160 months). The overall survival was 68.7%. Survival analysis was performed using Kaplan-Meier and Cox regression which showed that lymph node involvement and tumour grade were the only variables affecting survival (P<0.0001, and 0.01, respectively). The type of surgery performed did not affect survival (P=0.42). The total number of patients who developed local recurrence was 17 patients (13.1%, 12 patients in the breast conservation surgery group and five patients in the total mastectomy group, P<0.0001). Kaplan-Meier analysis of local recurrence showed that the type of surgery (P<0.0001), patient age (P=0.02), tumour grade (P=0.002), adjuvant radiotherapy (P=0.013), chemotherapy (P=0.031) and hormonal treatment (P=0.003) significantly affected local recurrence. Cox regression analysis showed that the only factor significantly affecting local recurrence was the type of surgery performed (P=0.02). Patients who underwent mastectomy had less local recurrence than those who had breast conservation surgery. Local recurrence after breast conservation surgery is high, even with clear surgical margins and post-operative radiotherapy. The authors believe that total mastectomy for infiltrating lobular carcinoma is a safer option to control local disease, especially in younger patients and those with high-grade tumours. Overall survival is not affected by the type of surgical treatment. Local recurrence can be a late event and a long-term follow-up is recommended.

Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant.

Most uterine sarcomas fall into the category of leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma. Pure rhabdomyosarcomas are extremely rare, although a rhabdomyosarcomatous element may be present as a component of an adenosarcoma or carcinosarcoma (malignant mixed müllerian tumor). This report describes two uterine rhabdomyosarcomas in 28- and 67-year-old women. These were of spindle cell and pleomorphic types, respectively. At presentation the pleomorphic rhabdomyosaroma was stage IV, exhibiting massive pelvic and abdominal dissemination that mimicked an ovarian neoplasm. The spindle cell rhabdomyosarcoma was stage I, being confined to the uterus. Grossly, both uterine tumors had a polypoid appearance. Immunohistochemically, tumor cells were positive with the skeletal muscle markers sarcomeric actin, myoglobin, and myoD1. The patient with stage IV disease died within a short time of diagnosis and the other patient is alive and well at 2 years' follow-up. This report adds to the published literature on uterine rhabdomyosarcomas. This is the first reported uterine case of the spindle cell variant of embryonal rhabdomyosarcoma. Based on these cases and the published literature, rhabdomyosarcoma, especially the pleomorphic variant, appears to be a very aggressive neoplasm with an extremely poor prognosis. Immunohistochemical demonstration of skeletal muscle differentiation is necessary for a definitive diagnosis.

Thyroid papillary carcinoma in lateral neck cyst: missed primary tumour or ectopic thyroid carcinoma within a branchial cyst?

We report a case of thyroid papillary carcinoma lying within a lateral cervical cyst for which no occult primary tumour of the thyroid was identified. We explore the possible diagnoses and include a discussion of how ectopic thyroid tissue may come to lie within a branchial cyst.

The role of fine needle aspiration cytology (FNAC) in the investigation of superficial lymphadenopathy; uses and limitations of the technique.

Aspirates (n = 163) from 157 patients with enlarged superficial lymph nodes were obtained over a 5-year period in a combined surgical/FNAC clinic. A definitive diagnosis was achieved in over 77% of the cases: benign 52.7%, malignant 25.1%. The diagnostic accuracy was 94.4%, sensitivity 85.4%, and specificity 100%. The false-negative rate was 12.5% but decreased to 3.5% when lymphoma cases were excluded. There were 36 cases of metastatic disease, the majority of which were from a primary breast carcinoma. The main diagnostic difficulty was in distinguishing low-grade lymphoma from reactive hyperplasia. An added advantage was that aspirated material could be used in ancillary tests to help with the differential diagnosis. FNAC has a well-defined role in the investigation of superficial lymphadenopathy. Used in the proper setting it will provide a definitive diagnosis in the majority of cases, especially relating to recurrent malignancy or metastatic disease. Patients with a reactive cytological picture and no clinically suspicious symptoms could be spared unnecessary surgery and reviewed through follow up. This technique is cost-effective, of high diagnostic accuracy, and results in considerable resource savings.

A 3-year audit of thyroid fine needle aspirates.

Fine needle aspiration (FNA) cytology is an important adjunct to the preoperative management of thyroid swellings. It is a simple and highly cost effective procedure with a higher sensitivity for the detection of malignancy than ultrasound and radio-isotope scans. We audited a total of 208 aspirates performed over a 3-year period. In our experience 61% of solitary thyroid swellings can be diagnosed confidently on FNA cytology as either non-neoplastic (46%) or neoplastic (15%). Based on these two groups the sensitivity is 91% and specificity 94%. The specificity, however, decreases to 40% if the group reactive vs neoplastic, which comprises 10-15% of cases and requires surgical intervention, is included. The positive predictive value for malignant disease is 94% while the false-negative and -positive rates excluding the unsatisfactory and reactive vs neoplastic groups are low at 2.7% and 5.4%, respectively (involving non-neoplastic lesions and benign tumours only). There was no case of malignant cytology with a benign biopsy follow up.

A 3 year audit of fine needle aspirates from a symptomatic breast clinic.

A total of 2431 fine needle aspirates of symptomatic breast lumps was performed on 2096 patients over the last three years at the weekly head, neck and breast clinic at the Belfast City Hospital Trust. Diagnostic accuracy was achieved within the recommended standards although the "insufficient" rate was high at 31.8%. False negative and positive rates were low and the positive predictive value for malignancy was 99%. Excision biopsy for benign breast disease had decreased by almost a third during this period. Fine needle aspiration cytology is a highly accurate and cost-effective technique for the investigation of symptomatic breast lumps and results in significant savings.

An audit of thyroid surgery in a general surgical unit.

A total of 143 patients undergoing thyroid surgery in a general surgical unit over an 8-year period were reviewed. In only two patients did thoracic inlet views or thyroid function tests alter clinical management. Fine-needle aspiration failed to detect one well-differentiated follicular carcinoma (false-negative rate 1.1%). The sensitivity for malignancy of fine-needle aspiration, ultrasound and radioisotope scan were 94%, 53% and 24%, respectively. The corresponding specificity was 59%, 72% and 58% and accuracy 65%, 70% and 49%, respectively. The specificity of fine-needle cytology for detecting neoplastic disease (adenoma or carcinoma) was 86% and accuracy 91%. Combinations of fine-needle cytology, ultrasound and radioisotope scanning increased the sensitivity for malignancy, so that fewer tumours were missed, but at the cost of reduced specificity, positive predictive value and accuracy. Hence, ultrasound was only recommended when fine-needle aspiration was inconclusive. Overall perioperative morbidity was 6.3% (one case of postoperative bleeding, two wound infections, four cases of prolonged hypocalcaemia). There were two proven cases of transient, but no permanent, recurrent laryngeal nerve injuries as a result of surgery. Thyroid surgery may be performed satisfactorily by general surgeons with an interest in thyroid disease. Fine-needle cytology is the most informative preoperative investigation. Although aspiration cytology, ultrasound, and scintigraphy all have appropriate indications and limitations, there is no single test or group of tests that can substitute for careful clinical assessment and follow-up.

Tumours of the spermatic cord and paratesticular tissue. A clinicopathological study.

A total of 85 patients with paratesticular tumours were diagnosed over a period of 36 years at this hospital; 66 patients (78%) had benign tumours, usually either an adenomatoid tumour or a lipoma. Of the remaining 19 malignant cases, 10 were primary neoplasms and 9 were metastases. A rare mucin-secreting epididymal adenocarcinoma was the only primary malignant epithelial tumour, the others being of mesenchymal origin. In 4/9 metastatic cases the initial presentation of a paratesticular swelling led to the discovery of the occult primary neoplasm following histological examination. Clinical features of a painful or painless mass, with or without an accompanying hydrocele, do not help to distinguish a benign from a malignant lesion. The prognosis of malignant tumours of mesenchymal origin depends mainly on the histological grade. Surgical resection remains the mainstay of treatment and adjuvant therapy significantly improves the chances of survival only in young patients with paratesticular rhabdomyosarcomas. Older patients with high grade tumours usually succumb to their disease despite chemotherapy and/or radiotherapy.

Thirty-year review of intrascrotal rhabdomyosarcoma.

Between 1957 and 1987, 6 cases of intrascrotal rhabdomyosarcoma were found in the pathology records for Northern Ireland. Four of these tumours arose from paratesticular tissue and 2 were confined to the testis. Only 1 patient has died of his disease. Two were lost to follow-up after 21 years and are presumed cured. The remaining 3 remain alive and disease-free between 2 and 3 1/2 years after presentation.