The value of wide-needle aspiration in the diagnosis of tuberculous lymphadenitis in Africa.

OBJECTIVES: To evaluate wide-needle (19-gauge) aspiration in the diagnosis of tuberculous lymphadenitis. SETTING: Department of Surgery, University Teaching Hospital, Lusaka, Zambia. PATIENTS: Three hundred and four patients presenting to one surgeon for diagnostic surgical biopsy of a peripheral lymph node during 1989-1990. DESIGN: Prospective study in which wide-needle aspiration routinely preceded open surgical biopsy. MAIN OUTCOME MEASURES: Histology and mycobacterial culture of the surgically biopsied lymph node; HIV-1 serology; successful aspiration of material, naked-eye appearance of aspirate, presence of acid-fast bacilli and/or microscopic caseation in the aspirate. RESULTS: One hundred and eighty-eight out of 304 (61.8%) patients had histologically and/or culture-proven tuberculous lymphadenitis, of whom 155 out of 183 (84.7%) tested HIV-1-seropositive. Material was successfully aspirated from 180 out of 188 (95.7%) of patients with proven tuberculous lymphadenitis. Macroscopic caseation, diagnosable on naked-eye examination alone of the aspirate, was present in 49 out of 120 (40.8%) consecutive aspirates from tuberculous nodes. Acid-fast bacilli and/or microscopic caseation were seen in 116 out of 155 (74.8%) aspirates from tuberculous nodes for which smears stained both by Ziehl-Nielsen and haematoxylin & eosin were available. CONCLUSIONS: It is recommended that all patients with suspected tuberculous lymphadenitis in Africa, undergo wide-needle aspiration before surgical biopsy or empirical treatment.

PIP: This study evaluated wide-needle (19-gauge) aspiration in the diagnosis of tuberculous lymphadenitis. 304 patients presenting to 1 surgeon for diagnostic surgical biopsy of a peripheral lymph node during 1989 and 1990 at the Department of Surgery, University Teaching Hospital, Lusaka, Zambia, were involved in this prospective study in which wide-needle aspiration routinely preceded open surgical biopsy. Histology and mycobacterial culture of the surgically biopsied lymph node, HIV-1 serology, successful aspiration of material, naked-eye appearance of aspirate, and presence of acid-fast bacilli and/or microscopic caseation in the aspirate were the main outcome measures. 188 of 304 (61.8%) patients had histologically and/or culture-proven tuberculous lymphadenitis, of whom 155 of 183 (84.7%) tested HIV-1 seropositive. Material was successfully aspirated from 190 of 188 (95.7%) patients with proven tuberculous lymphadenitis. Macroscopic caseation, diagnosable on naked-eye examination alone of the aspirate, was present in 49 of 120 (40.8%) consecutive aspirates from tuberculous nodes. Acid-fast bacilli and/or microscopic caseation were seen in 116 of 155 (74.8%) aspirates from tuberculous nodes for which smears stained by both Ziehl-Nielsen and hematoxylin and eosin were available. It is recommended that all patients with suspected tuberculous lymphadenitis in Africa undergo wide-needle aspiration before surgical biopsy or empirical treatment.

Computerized diagnostic decision support system for the classification of preinvasive cervical squamous lesions.

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with kappa statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control.

Lymph node hyalinisation in rheumatoid arthritis and systemic sclerosis.

AIMS: To review the histological features of lymph nodes excised from seven patients with rheumatoid arthritis and one with systemic sclerosis. METHODS: Lymph nodes excised from seven patients with rheumatoid arthritis and one patient with systemic sclerosis over a 10 year period were examined using the stains haematoxylin and eosin, periodic acid Schiff (PAS), Masson-trichrome, and Congo red for amyloid. RESULTS: Of the seven nodes examined from the cases of rheumatoid arthritis, three showed definite reactive follicular hyperplasia with a prominence of plasma cells in the interfollicular areas, two showed subtotal replacement of the node by numerous sarcoid like granulomata, and one contained a large central area of necrosis with a surrounding palisade of histiocytes. In all six cases, focal areas of PAS positive eosinophilic hyaline material were present, which did not stain with Congo red. In some cases this hyaline material was focally calcified. In the seventh patient with rheumatoid arthritis the excised lymph node was almost totally replaced by similar PAS positive hyaline material which showed extensive areas of calcification. The lymph node removed from the patient with systemic sclerosis similarly showed almost total replacement by PAS positive hyaline material. CONCLUSION: In all cases the nodes contained PAS positive extracellular hyaline material to a greater or lesser degree. The lymph nodes from two of the patients with rheumatoid arthritis contained numerous sarcoid like granulomata, further indicating a possible association between sarcoidosis and rheumatoid arthritis. Pathologists and clinicians should include rheumatoid arthritis and systemic sclerosis in their differential diagnosis of lymph node hyalinisation of unknown aetiology.

Haemangioleiomyomatous tumour of the lung.

A case of haemangioleiomyomatous tumour of the lung, occurring as a peripheral, solitary nodule in an asymptomatic 54-year-old man is presented. The tumour was well-demarcated and microscopically it was characterised by the presence of vascular spaces with endothelial, pericytic, and, predominantly, smooth muscle proliferation. Islands of cartilage and slit-like spaces lined by bronchial epithelium make this a hamartomatous lesion of a quite distinctive and unusual variety, which does not fit any of the well-recognised patterns of hamartomas previously described. The long-term prognosis after limited excision is considered to be favourable.

Non-neoplastic glandular structures in bone marrow: a technical artefact.

A case of non-neoplastic glandular structures embedded in the centre of a bone marrow trephine biopsy is described. This is a hitherto unreported phenomenon. These glandular structures originated from the dermal sweat gland and represented an artefactual lesion produced by the biopsy procedure. The importance of considering the possibility of non-neoplastic glandular structures in bone marrow is stressed, in order to avoid a misdiagnosis of metastatic adenocarcinoma.

B cell signet-ring cell lymphoma of bone marrow.

A case of signet-ring cell lymphoma affecting the bone marrow and diagnosed by bone marrow trephine biopsy is reported. Normal marrow was replaced totally by cells with large central vacuoles, many of which displaced the nucleus to the periphery of the cell, imparting a signet-ring appearance. Initially, the favoured morphological diagnosis was metastatic signet-ring adenocarcinoma, but on immunocytochemistry the tumour cells were strongly positive for CD45 (leucocyte common antigen) and the B cell marker CD20 (L26). Electron microscopy revealed electron-lucent vacuoles with no discernable internal structure. The tumour was classified as a high grade centroblastic lymphoma using the upgraded Kiel classification. Despite chemotherapeutic treatment, the patient died during an episode of septicaemic shock within two months of presentation.

Malignant lymphoma in congenital dyserythropoietic anaemia type III.

A 60 year old woman with congenital dyserythropoietic anaemia (CDA) type III developed a malignant T cell lymphoma with cutaneous and widespread nodal involvement. Bone marrow aspirates showed erythroid hyperplasia and dyserythropoiesis with multinucleate erythroblasts and gigantoblasts, in keeping with CDA type III. Electron microscopy showed multinucleate erythroblasts with notably irregular nuclear outlines and intranuclear clefts. The development of malignant lymphoma in this patient, together with a documented high prevalence of monoclonal gammopathy and multiple myeloma and a single case of Hodgkin's disease, may indicate an increased incidence of lymphoproliferative disease in CDA type III.

Immunohistochemical staining of plastic embedded bone marrow trephine biopsy specimens after microwave heating.

AIMS: To investigate (1) whether adequate immunohistochemical staining can be achieved on sections cut from plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer; and (2) whether this immunohistochemical staining is comparable with that achieved on routine sections cut from paraffin wax embedded trephine biopsy specimens after decalcification procedures. METHODS: Sixty five consecutive bone marrow trephine biopsy specimens of more than 1 cm in length were divided transversely into two equal parts. One part was processed in paraffin wax followed by decalcification. The other part was embedded in the epoxyresin Polarbed 812 followed by the cutting of 1 micron sections. Both parts underwent immunohistochemical staining by an identical panel of antibodies. With Polarbed 812 plastic embedded sections, microwave heating in citrate buffer was undertaken before the application of antisera. RESULTS: On sections cut from plastic embedded material, immunohistochemical staining was generally satisfactory, easy to interpret and comparable with that achieved with paraffin wax embedded material. Exceptions were antibodies to neutrophil elastase and CD61 where immunostaining was consistently negative on plastic embedded sections. Immunohistochemical staining for CD20 was consistently more reliable on plastic embedded sections. CONCLUSIONS: The results provide evidence that, with few exceptions, satisfactory immunohistochemical staining is possible on plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer. This, combined with the advantage of superior cellular morphology with semi-thin (1 micron) sections of plastic embedded material, make such embedding procedures the preferred method for the processing of bone marrow trephine biopsy specimens.

Interobserver variation in the reporting of cervical colposcopic biopsy specimens: comparison of grading systems.

AIMS: To assess interobserver variation in reporting cervical colposcopic biopsy specimens and to determine whether a modified Bethesda grading system results in better interobserver agreement than the traditional cervical intraepithelial neoplasia (CIN) grading system. METHODS: One hundred and twenty five consecutive cervical colposcopic biopsy specimens were assessed independently by six histopathologists. Specimens were classified using the traditional CIN grading system as normal, koilocytosis, CIN I, CIN II, or CIN III. The specimens were also classified using a modified Bethesda grading system as either normal, low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). Participants were also asked to categorise biopsy specimens by the CIN system with the addition of the recently proposed category "basal abnormalities of uncertain significance (BAUS)". The degree of agreement between participants was assessed by kappa statistics. RESULTS: Using the CIN system, interobserver agreement was generally poor: unweighted and weighted kappa values between individual pairs of observers ranging from 0.05 to 0.34 (average 0.20) and from 0.20 to 0.54 (average 0.36), respectively. With the modified Bethesda system, interobserver agreement was better but still poor: unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36), respectively. There was little or no agreement between observers in the diagnosis of BAUS. CONCLUSIONS: Interobserver agreement in the reporting of cervical colposcopic biopsy specimens using the CIN grading system is poor. Agreement, while still poor, is better when a modified Bethesda grading system is used. There is little or no consensus in the diagnosis of BAUS.

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Pericardial hemangiopericytoma as a cause of dysphagia.

A 68-year-old woman was seen with recent-onset dysphagia. Investigations suggested a large retrocardiac tumor. At thoracotomy, a highly vascular tumor was found, involving the posterior and left aspect of the pericardium with attachment to the heart. The lesion was partially removed, and histopathological analysis revealed a malignant hemangiopericytoma. To our knowledge, this tumor site and its presentation have not been reported before.

Anogenital warts in prepubertal children; sexual abuse or not?

Forty-two prepubertal children presenting with anogenital (AG) warts (15 boys and 27 girls) were prospectively followed up (mean 15.9 months, SD 12.24). Most (73.8%) of these children had perianal condylomatous-type warts and 11 (26.2%) had concurrent non-genital (NG) warts. None had any other AG infections or sexually transmitted disease (STD). Twelve (28.6%) children acquired their AG warts by vertical transmission from an infected maternal birth canal, 3 (7.1%) by autoinoculation from common hand warts and 2 children (4.8%) through sexual abuse. In the remaining 25 children (59.5%) mode of acquisition of AG warts was uncertain but not thought to be sexual. Human papilloma virus (HPV) DNA (types 6/11, 16/18 or 31,33,35-31+) was detected in 10/32 (31.3%) of AG warts biopsied from these children, types 6/11 in the majority of positive biopsies (9/10). Detection of HPV DNA (types 6/11, 16/18 or 31+) in a child's AG warts was significantly associated with either vertical or sexual transmission (P < 0.02). Thirty-one children had their warts treated with a combination of scissor excision and electrocautery under general anaesthesia. Warts recurred in 10 (31.4%) of these children all within 4 months following treatment. Spontaneous resolution of AG warts was seen in 9 (21.4%) children. Of 42 children with AG warts 10 (23.8%) had at least one adult family member with AG warts, 13 (36.9%) on adult family member with another AG infection or STD, and 23 (62.2%) had a mother with cervical intraepithelial neoplasia (CIN). Twenty (47.6%) of these children had a family member with NG warts.(ABSTRACT TRUNCATED AT 250 WORDS)

Mediastinal granulocytic sarcoma: a report of two cases.

We describe the cases of two patients who presented with granulocytic sarcoma with mediastinal involvement 15 and 21 months before development of acute myeloid leukemia. In both cases several bone marrow aspirates and trephine biopsy specimens, obtained at presentation and subsequently, revealed no evidence of leukemic infiltration. One case was originally misdiagnosed as large-cell non-Hodgkin's lymphoma, which resulted in inappropriate therapy. In both cases immunohistochemical staining revealed that tumor cells were positive for leucocyte common antigen but not for conventional B- or T-lymphoid-cell markers. Retrospective analysis revealed that tumor cells in both cases were positive for myeloid markers. Histopathologists should be aware that granulocytic sarcoma may occur in unusual extramedullary sites without evidence of bone marrow involvement. If inappropriate treatment is to be avoided, a diagnosis of granulocytic sarcoma should be considered when hemopoietic tumor cells do not stain with conventional antibodies against B- and T-lymphoid cells. Both histochemical and immunohistochemical staining should be performed in such cases to determine whether the cells are of myeloid lineage. A diagnosis of granulocytic sarcoma is not ruled out when bone marrow biopsy specimens show no evidence of leukemic infiltration.

Florid reactive periostitis of the thumb.

A case of florid reactive periostitis of the thumb is presented. This is a rare pseudosarcomatous lesion which generally has a benign radiographic appearance, but on histology it may be mistaken for a malignant process. The clinical behaviour may simulate a malignant tumour but after local excision there is very little propensity for recurrence. Local resection is the recommended treatment. Surgeons and pathologists should consider the possibility of florid reactive periostitis before making a diagnosis of sarcoma in the hand.

Giant cell tumour of the temporal bone presenting as vertigo.

We report a case of giant cell tumour of the temporal bone arising in a 31-year-old man. The presenting symptoms were unusual, being rotational vertigo, unilateral tinnitus, and hearing loss. A computed tomography (CT) scan showed a large mass within the right temporal bone and the infratemporal fossa. The radiological appearance was suggestive of an aggressive primary neoplasm arising within bone. Biopsy and subsequent resection showed a giant cell tumour of bone. The tumour was histological grade 1. At two-year follow-up, there was no evidence of tumour recurrence or metastasis.

Nosological Inaccuracies in death certification in Northern Ireland. A comparative study between hospital doctors and general practitioners.

We aimed to audit nosological inaccuracies in death certification in Northern Ireland and to compare performance of hospital doctors and general practitioners. Nosology is the branch of medicine which treats of the classification of disease. 1138 deaths were registered in Northern Ireland in a 4-week period commencing 3/10/94. 195 of these were either registered by HM Coroners (HMC) or required further investigation by their staff; these cases were excluded from the study. The remaining 943 were analysed for wording and formulation inaccuracies according to the revised notes (1974), Northern Ireland Medical Certificate of Cause of Death. These are issued in book form by the Registrar of Births and Deaths. The commonest inaccuracies in death certification occur in the areas of poor terminology, sequence errors and unqualified mode. One or more inaccuracies were found in 317 (33.6%) of cases. In 13 of these (4%) cases, the inaccuracies were serious enough to warrant referral by the Registrar of Deaths to HM Coroner. The numbers of general practitioners and hospital doctors were recorded, with general practitioners being responsible for 122 (38%) and hospital doctors being responsible for 195 (62%) of inaccuracies.

Malignant melanoma over a fifty-year period: a histological evaluation.

The incidence of primary cutaneous malignant melanoma is increasing in the developed countries. Cutaneous malignant melanomas diagnosed in our Department over a period of fifty years from 1930 to 1980 were examined to see if there was any change in their histological features. In 1930 and 1955, over 90% of malignant melanomas presented as tumours infiltrating deep into the subepithelial tissue. By 1980, 55% of tumours presented with deeply infiltrating lesions and only 20% occurred at a stage where adequate local excision could provide hope of a cure. There is thus a need for greater awareness among the medical profession and the public if we hope to be able to treat malignant melanomas at an early stage.