Staging primary breast cancer. Are there tumour pathological features that correlate with a false-negative axillary ultrasound?

AIM: To investigate whether the histopathological characteristics of primary breast cancer tumours could predict the likelihood of false-negative axillary ultrasound. MATERIALS AND METHODS: Screening and symptomatic patients were identified from pathology records and imaging and pathology records reviewed. True and false-negative axillary staging ultrasound groups were compared statistically in terms of tumour size, pathological type and grade, lymphovascular invasion, and oestrogen receptor (ER) status. RESULTS: Of 155 women with normal ultrasounds, 45 (29%) were node positive at axillary surgery. Breast tumour size was significantly different with the average size smaller in the true-negative group: 21 versus 30 mm (p < 0.02). The histological type varied significantly between the groups, with more lobular carcinomas in the false-negative group [6/110 (5%) versus 6/45 (13%), p < 0.001]. The false-negative group was also more likely to show lymphovascular invasion in the breast [6/110 (5%) versus 14/45 (31%), p < 0.001]. There was no significant difference in tumour grade or ER status. CONCLUSION: The present study has found significant differences in tumour characteristics between women with true-negative and false-negative axillary staging ultrasound in terms of size, primary tumour histological type and presence of lymphovascular invasion. In particular, axillary ultrasound in primary lobular carcinoma may be less accurate and a negative result is more likely to be spurious than with primary ductal carcinomas.

Incidental breast masses detected by computed tomography: are any imaging features predictive of malignancy?

AIM: To review the outcome of further assessment of breast abnormalities detected incidentally by multidetector computed tomography (MDCT) and to determine whether any MDCT imaging features were predictive of malignancy. MATERIAL AND METHODS: The outcome of 34 patients referred to the Primrose Breast Care Unit with breast abnormalities detected incidentally using MDCT was prospectively recorded. Women with a known diagnosis of breast cancer were excluded. CT imaging features and histological diagnoses were recorded and the correlation assessed using Fisher's exact test. RESULTS: Of the 34 referred patients a malignant diagnosis was noted in 11 (32%). There were 10 breast malignancies (seven invasive ductal carcinomas, one invasive lobular carcinoma, two metastatic lesions) and one axillary lymphoma. CT features suggestive of breast malignancy were spiculation [6/10 (60%) versus 0/24 (0%) p=0.0002] and associated axillary lymphadenopathy [3/10 (33%) versus 0/20 (0%) p=0.030]. Conversely, a well-defined mass was suggestive of benign disease [10/24 (42%) versus 0/10 (0%); p=0.015]. Associated calcification, ill-definition, heterogeneity, size, and multiplicity of lesions were not useful discriminating CT features. There was a non-significant trend for lesions in involuted breasts to be more frequently malignant than in dense breasts [6/14 (43%) versus 4/20 (20%) p=0.11]. CONCLUSION: In the present series there was a significant rate (32%) of malignancy in patients referred to the breast clinic with CT-detected incidental breast lesions. The CT features of spiculation or axillary lymphadenopathy are strongly suggestive of malignancy.

Langerhans cell histiocytosis in sequential discordant lymphoma.

B cell non-Hodgkin lymphoma of the follicular subtype (grade 3/3) affecting the nasopharynx and breast, and containing foci of Langerhans cell histiocytosis, was diagnosed in a 56 year old white woman who was a longstanding heavy smoker. Four years before this she had developed stage 1a mixed cellularity Hodgkin lymphoma affecting the right inguinal region, which was treated by irradiation and chemotherapy without recurrence. Review of the original Hodgkin lymphoma histology demonstrated a small focus of Langerhans cell histiocytosis. This is thought to be the first recorded case of Langerhans cell histiocytosis occurring in a sequential discordant lymphoma. Its importance is discussed.

Candida albicans peritonitis in a patient with Felty's syndrome.

A 53 year old man with Felty's syndrome presented with abdominal pain and fever. He underwent a laparotomy after starting broad spectrum antibiotics. An intestinal biopsy showed skip ulcers with fungal hyphae. Peritoneal exudates grew Candida albicans. He was started on intravenous fluconazole and then switched to liposomal amphotericin to which he showed a good clinical response. After one month at home he was readmitted with candidosis and died of a myocardial infarction.

Immunogold-silver staining: new method of immunostaining with enhanced sensitivity.

A new method for demonstrating antigens in paraffin sections of formol sublimate-fixed tissue is described that utilizes an "indirect" immunohistological technique employing immunoglobulin adsorbed to colloidal gold as the secondary antiserum. The gold particles introduced to antigenic sites are revealed by a silver precipitation reaction. This technique, the immunogold-silver staining method, is of much enhanced sensitivity (up to 200-fold) as compared with standard immunoperoxidase and immunogold staining methods. The results have been confirmed in a study of immunoglobulins in reactive human tonsil. The use of this new method for double immunolabeling is also described.

Fixation, processing, and immunochemical reagent effects on preservation of T-lymphocyte surface membrane antigens in paraffin-embedded tissue.

Fixatives, fixation additives, paraffin processing reagents, and immunochemical reagents were investigated for effects on preservation of T-lymphocyte surface membrane antigens CD3, CD4, and CD8 in human tonsil. Individual reagent effects were assessed in frozen sections by use of monoclonal antibodies and this information was used to optimize T-cell immunostaining in paraffin sections. Harmful factors were fixation delay, fixation at acid pH, fixation and processing at temperatures above 4 degrees C, hot paraffin wax, proteolytic enzymes, methanolic hydrogen peroxide, Triton X-100, and prolonged iodine treatment. Optimal T-cell demonstration in paraffin sections followed tissue fixation in periodate-lysine-paraformaldehyde dichromate at 4 degrees C, pH 7.5; processing through isopropanol, then xylene or chloroform, at 4 degrees C; and embedding in low melting point wax at 45-50 degrees C. Graded antigen stability occurred: CD3 most stable, CD8 least, and CD4 intermediate. CD4 and CD8 antigen preservation in paraffin sections required critical optimal tissue handling. CD3 was more stable and was also demonstrated in tissue fixed in commercial formalin, glutaraldehyde, and Bouin's fluid when fixation and processing conditions were optimized for pH and temperature. Of the fixation additives studied, polyethylene glycol and several potassium and magnesium salts enhanced immunostaining, whereas calcium chloride and lidocaine were deleterious.

Complement component deposition in uteroplacental (spiral) arteries in normal human pregnancy.

There is conflicting evidence for the deposition of complement in spiral arteries in normal and abnormal human pregnancies. The immunogold silver staining (IGSS) technique was used to investigate the distribution of C1q, C3d, C4, C6 and C9 within the spiral arteries of formalin-fixed normal pregnancy hysterectomy specimens ranging in gestational age from 4 to 40 weeks. Deposition of complement components studied was observed in all cases suggesting classical pathway activation. Reactivity was not confined to vessels showing endovascular trophoblast though the latter showed a characteristic linear deposition subjacent to the trophoblast. Reactivity was most intense for C3d and C9. An appreciation of complement deposition as a feature of normal pregnancy is essential before significant immunopathology can be recognised in placental bed vessels in abnormal pregnancy.

Surface membrane staining of immunoglobulins in paraffin sections of non-Hodgkin's lymphomas using immunogold-silver staining technique.

The immunogold-silver staining (IGSS) method is a new immunostaining technique with much enhanced sensitivity for demonstration of antigens in paraffin sections. A series of 10 non-Hodgkin's lymphomas of B cell type were stained for surface membrane immunoglobulins by the IGSS and peroxidase-antiperoxidase (PAP) methods using paraffin sections and polyclonal primary antisera. The resulting staining patterns were compared with those obtained using frozen sections of the same tissues, monoclonal antibodies and the immunoperoxidase technique. The IGSS method gave a clear demonstration of surface membrane immunoglobulins in neoplastic lymphocytes using paraffin sections and the pattern of staining achieved was comparable to that obtained by the immunoperoxidase technique employing frozen sections and monoclonal antibodies. PAP staining of paraffin sections consistently failed to demonstrate the presence of any surface membrane immunoglobulin. The IGSS method provides a new approach to the diagnosis of B cell lymphomas in which routinely fixed and processed tissues may be employed to demonstrate monoclonality.

Major histocompatibility complex class II antigen expression in B and T cell non-Hodgkin's lymphoma.

An immunohistochemical study of 46 B and T cell non-Hodgkin's lymphomas, using monoclonal antibodies to the products of the major histocompatibility complex (MHC) class II antigen subregions, DP, DQ, and DR, showed that most B and T cell lymphomas express these antigens. Both coordinate and non-coordinate expression of MHC class II antigens was observed, but this did not correlate with immunological phenotype, morphological grade, or proliferation index as determined by flow cytometry.

Primary Hodgkin's disease of bone.

Primary Hodgkin's disease of bone is rare. Diagnosis is often delayed and may be mistaken for eosinophilic granuloma. We report such a case where Hodgkin's disease presented as a primary osteolytic bone lesion.

Lesions of uncertain malignant potential (B3) on core biopsy in the NHS Breast Screening Programme: is the screening round relevant?

INTRODUCTION: Most women who have screening mammography and undergo subsequent open biopsy following an indeterminate core biopsy result are eventually found to have benign disease. However, a significant number have malignant disease and the rate of malignancy in such cases may be influenced by various factors. This study examined the effect of the type of screening round (prevalent or incident) on the likelihood of breast cancer being present. METHODS: A total of 199 women who had NHS breast screening mammograms and subsequent indeterminate (B3) core biopsy results followed by excision biopsy over an 11-year period in a single breast screening unit were reviewed. RESULTS: The rate of malignancy following excision of a lesion graded as B3 on core biopsy was 21% for women in the prevalent screening round compared to 33% in subsequent rounds (Fisher's exact test, p=0.038). CONCLUSIONS: The incidence of malignancy associated with a B3 core biopsy result appears to be related to the screening round in which the lesion is detected, being approximately 50% higher in the subsequent incident rounds compared to the initial prevalent round. This finding may be useful in formulating management plans for women who have an indeterminate biopsy result.

Long term follow-up and risk of breast cancer after a radial scar or complex sclerosing lesion has been identified in a benign open breast biopsy.

AIMS: Radial scars (RS)/complex sclerosing lesions (CSL) are rare, benign breast lesions of unknown aetiology. Associations with breast cancer have been suggested particularly with larger lesions. This study aims to identify the risk of developing subsequent breast cancer after excision of a benign RS/CSL with respect to lesion size and compared to expected rates in the normal UK population. METHODS: A prospective cohort analysis was performed on patients diagnosed with RS/CSL in benign, open breast biopsy specimens over a 20-year period. The rate of subsequent breast cancer development was compared to expected rates in the normal UK population. Subjects were divided into two groups according to lesion size and the rates of subsequent breast cancer compared. RESULTS: 149 women without proliferative breast disease were followed for an average of 68 months. Five women developed subsequent cancer, equating to a rate of 0.84% per year. This compares to 0.32% per year in the normal population (RR 2.6, 95% CI 0.86-6.0). There were two subsequent cancers in the RS group and three subsequent cancers in the CSL group, P = 0.64. CONCLUSIONS: The study finds no evidence to suggest that lesions greater than 10 mm (CSL) have any greater risk of developing cancer after excision than those below 10 mm (RS). Women treated for RS/CSL do not need any additional follow-up beyond routine mammographic breast screening. Additional surveillance should only be performed if there is associated pathology indicating an increased risk of subsequent malignancy.

Retinoid-induced haemorrhagic bullae in Darier's disease.

Haemorrhagic epidermal bullae developed in a patient with Darier's disease undergoing long term treatment with the retinoid, etretinate. We suggest that these lesions result from cumulative toxic effects of long term retinoid therapy upon the abnormal keratinocyte found in Darier's disease.

Toxic pustuloderma. A drug induced pustulating glandular fever-like syndrome.

A striking cutaneous eruption developed in a fifty-eight year old woman with bipolar affective disorder three weeks after starting carbamazepine therapy. She had an infectious mononucleosis-like systemic illness associated with myriads of cutaneous micropustules, erythroderma and a high eosinophil count. A similar eruption due to carbamazepine has been reported only twice before, but isolated cases ascribed to other medications exist. We believe that this reaction is a specific class of drug eruption best named Toxic Pustuloderma.

Evaluation of a commercial enzyme-linked immunosorbent assay (ELISA) kit for serological diagnosis of Helicobacter pylori infection in a group of non-ulcer dyspepsia sufferers.

Helicobacter pylori infection of the stomach is associated with gastritis and peptic ulceration and may be causative. A noninvasive test for this organism might be useful in managing some patients with dyspepsia without the need for further investigation. We have evaluated a new commercially available serological test (Helico-G ELISA, Porton Cambridge, UK) for this infection to assess its diagnostic accuracy in a retrospective study of 115 patients with non-ulcer dyspepsia. Sixty-three of these patients (55%) were found to have H. pylori infection and gastritis on histology. A sensitivity of 81% and specificity of 90% were obtained. No significant fall in the antibody titres was found in a subgroup of 15 patients who were selected to complete a course of triple therapy despite significant improvement in their dyspepsia score and confirmed eradication of H. pylori organism in 80% of these patients. We conclude that the test has limited value in aiding clinical decision of managing patients with dyspepsia.

Effect fixation on T and B lymphocyte surface membrane antigen demonstration in paraffin processed tissue.

The identification of lymphoid surface membrane antigens in tissue sections using immunohistochemical techniques is becoming increasingly important for the diagnosis and classification of lymphoproliferative disorders. Many of the lymphocyte specific monoclonal antibodies used, however, can only be applied to frozen tissue sections. In this paper we report the successful application of a number of these antibodies to paraffin processed tissue utilizing alternative fixatives and the highly sensitive immunogold-silver staining method. The best fixatives for this purpose were formol dichromate, periodate-lysine-paraformaldehyde (PLP) and a novel fixative formed from the addition of a dichromate solution to PLP.