Haematogenous dissemination of tuberculous lymphadenitis.

OBJECTIVE: To determine whether Mycobacterium tuberculosis infection spreads through the blood to different lymph-node groups in patients with tuberculous lymphadenitis. DESIGN: Prospective analytical study. SETTING: The patients were recruited, managed and followed at the lymphodenopathy clinic, Central Police Hospital, Burr, Khartoum, Sudan. SUBJECTS: Fifty two sequential patients were enrolled. Thirty patients with FNAC diagnosis of tuberculous lymphadenitis and positive PCR for M. tuberculosis complex had a mean age of 26.9 +/- 11.2 years and similar male, female affection. Nine patients with FNAC tuberculous lymphadenitis, but negative PCR had a slightly higher mean age (32.6 +/- 18.2 years) with similar male: female proportions. Patients with reactive lymphadenopathy (9/52) were older than patients with tuberculous lymphadenitis with a mean age of 45 +/- 24.6 years. RESULTS: None of the patients were positive for HIV or had clinical or radiological evidence of pulmonary tuberculosis. M. tuberculosis DNA was detected in the blood samples of 30/39 (77%) patients with tuberculous lymphadenitis, but in none of the cases with reactive or malignant lymphadenopathy. The presence of M. tuberculosis DNA correlated strongly to multiple lymph-node involvement [OR (odds ratio) = 96.7, 95% confidence interval (CI) 9.0 - 1,039] and to caseating-granulomatous and predominantly necrotic cytomorphological categories [OR = 70, 95% confidence interval (CI) 7.0 - 703]. CONCLUSION: M. tuberculosis most probably disseminates through the blood from one node group to the other in patients with tuberculous lymphadenitis.

FNA of breast fibroadenoma: observer variability and review of cytomorphology with cytohistological correlation.

OBJECTIVE: To determine the observer variability in reporting fibroadenoma of the breast by fine needle aspiration (FNA) and to review the cytomorphological features of the lesion with cytohistological correlation. METHODS: Retrospective analysis of FNA smears from 110 cases diagnosed as fibroadenoma of which surgical pathology follow-up was available in 33. Two pathologists were asked to categorize smears from 67 cases of breast lesions while blinded to the clinical finding as fibroadenoma, epithelial hyperplasia (usual and atypical) and malignant. All fibroadenoma (33) and cancer (15) cases were biopsy-proven. The same set of slides was re-circulated to one of the pathologists, and his first and second round results were compared. RESULTS: Pre-review cytohistological correlation was attained in 32 of 33 cases of fibroadenoma (97%). The overall agreement between the two observers was 87% [Kappa = 0.74, 95% confidence interval (CI) 0.72-0.76]. Cytohistological correlation was achieved in 26 of 33 (79%) cases. Intra-observer agreement was 91% (Kappa = 0.82, 95% CI 0.89-0.93) with cytohistological correlation in 29 of 33 (87%) cases. Causes of diagnostic errors included marked dissociation, pleomorphism, poorly cellular smears from hyalinized fibrodenoma, lacational changes and apocrine metaplasia with cystic changes. Multinucleated giant cells were frequently encountered in FNA smears from fibroadenoma (31.8%), but in none of the lumpectomy specimens. Their histiocytic nature was suggested by immunohistochemistry. CONCLUSION: FNA was a highly sensitive method for the diagnosis of fibroadenoma. Current cytological criteria were reliable and gave high inter- and intra-observer reproducibility.

Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: differentiation by architectural pattern.

Differentiation between benign and malignant follicular lesions is one of the difficult diagnostic areas in thyroid fine needle aspiration (FNA). Nuclear criteria are usually used to distinguish between them. In this study the microarchitectural pattern of common benign follicular lesions, namely nodular hyperplasia (NH) and follicular adenoma (FA) were analysed in comparison with those of follicular variant of papillary carcinoma (FVPC) in order to aid in their differentiation. The FNA smears of histologically proven cases of FVPC, NH and FA were reviewed and compared. The microarchitectural features of FVPC, NH and FA were described. Three cytological features--multi-layered rosettes, branching monolayered sheets and balls of thick pinkish colloid--were exclusively observed in FVPC. Hyperplastic papillae with intact follicles and colloid were frequently seen in NH, 83% and 100%, respectively. Albeit less frequently, they were also noted in FVPC, 25% and 75% of cases, respectively. These overlapping features make the distinction between FVPC and NH sometimes difficult; however, assessing the smears for the specific features of FVPC may help in their differentiation. None of the aforementioned microscopic findings with the exception of the seldom presence of colloid were documented in FA. The crowded clusters of follicular cells were seen both in FA and FVPC; however, they were complex and branching in the latter and round to oval in the former. Finally, smears with good recovery of material are indispensable for the identification of these helpful microarchitectural patterns.

Diagnosis of tuberculous lymphadenitis by FNAC, microbiological methods and PCR: a comparative study.

Despite its usefulness in the diagnosis of tuberculous lymphadenitis, fine needle aspiration cytology (FNAC) faces several limitations, and its sensitivity and specificity are not well established. The diagnostic accuracy and limitations of FNAC were studied in comparison with conventional microbiological methods and polymerase chain reaction (PCR). Sixty patients with lymphadenopathy and a clinical diagnosis of tuberculous lymphadenitis were subjected to FNA. The aspirate was used for cytological examination, Ziehl-Neelsen staining, mycobacterial culture and PCR. PCR was performed using two sets of oligonucleotide primers for Mycobacterium tuberculosis and a single primer for M. bovis species. The results of FNAC, microbiological methods and PCR correlated with the clinical outcome after follow-up for an average period of 24 months. Twenty-five cases (41.6%) were treated and responded well to anti-tuberculosis therapy, among them 17 were correctly diagnosed by FNAC (68%), eight by microbiological methods (32%) and 24 by PCR (96%). When PCR is considered the gold standard, FNAC predicted the correct diagnosis in 62% of cases with a high false negative rate (38%) due to the absence of granuloma/necrosis in smears from cases of early tuberculosis. In the latter group PCR proved to be the most valuable and a diagnostic success of 100% was achieved when FNAC and PCR were combined. In addition, PCR allowed immediate characterization of M. tuberculosis in the vast majority (96.2%) of cases in the study population.

The role of FNA in the initial management of thyroid lesions: 7-year experience in a district general hospital.

Fine needle aspiration (FNA) cytology plays a major role in the diagnosis of the thyroid lesions in university hospitals and tertiary referral institutions. Our aim was to find out if this was possible in small district hospitals with limited resources. Over a 7-year period, from October 1994 to April 2002, 303 patients with thyroid swellings underwent FNA with an overall adequacy rate of 97.7%. FNAs were performed specifically by the pathologists, so that our inadequacy rate, 2.3% was far lower than 11-29% reported elsewhere. The FNA findings were compared with subsequent histology results in 67 cases. The diagnosis of benign and neoplastic lesions was predicted accurately by FNA in 93% and 94.7% of cases, respectively. The latter reached 100% if results of FNA in follicular neoplasms were excluded. Sensitivity and specificity were 85.6% and 97.6%, respectively, which is comparable with results from tertiary institutions. The commonest thyroid lesions in our hospital were nodular goitre (52.4%), followed by thyroiditis (17.6%) and neoplasia (13.9%). We conclude that, with the availability of appropriate personnel, FNA is feasible as the major modality in district general hospitals. FNA in follicular lesions remains challenging but could be overcome in part by recognizing the criteria to differentiate follicular variant of papillary carcinoma and other follicular proliferations. Aspiration, smearing, staining and interpretation should be left to pathologists or other well-trained personnel to ensure good quality and consistency.

Extrauterine placental site trophoblastic tumour in association with a lithopedion.

AIM: We describe an unusual case of extrauterine placental site trophoblastic tumour located in pouch of Douglas in association with a lithopedion. METHODS AND RESULTS: A 35-year-old female presented with acute abdomen and peritonitis following rectal perforation. The patient gave a history of 5 months amenorrhoea followed by vaginal bleeding 5 years prior to admission. At laparotomy, a lithopedion was found in pouch of Douglas with rectal perforation and peritonitis. The lithopedion was removed, rectal perforation was sutured and a colostomy was performed. The colostomy was closed later and tumour was seen in the colostomy wound as well as attached to the lithopedion removed previously. The patient presented with a repeated episode of rectal perforation and the tumour had spread to colon, small intestine, omentum, mesentery and right ovary. CONCLUSION: A high-grade malignant placental site trophoblastic tumour with aggressive clinical course occurred at an extrauterine site. It complicated calcified abdominal pregnancy and resulted in repeated rectal perforation and peritonitis.

Supra-sternal notch tuberculous abscess: a report of three cases.

Extra-pulmonary tuberculosis remains a diagnostic and therapeutic challenge; its clinical presentation can mimic a wide range of pathological conditions. Here we report on 3 female patients who presented with supra-sternal masses that were suspected clinically to be of thyroid origin. By use of fine-needle aspiration cytology (FNAC), they were proved to be tuberculous lesions involving the pre-tracheal lymph nodes. Serological examination for HIV-I/II was not reactive in the 3 patients. The patients responded well to a regimen of multi-drug therapy. It is concluded that extra-pulmonary tuberculosis should be considered in the differential diagnosis of thyroid or para-thyroid swellings and that FNAC is a simple, quick and reliable procedure in the diagnosis of extra-pulmonary tuberculous lesions involving the neck.

Blood supply and vasculature of mycetoma.

The blood supply to the mycetoma lesion and its vasculature were studied in patients with various types of mycetoma using histological, ultrastructural, angiographic and sonographic techniques. The mycetoma lesion proved to be well vascularized. However, certain vascular abnormalities were demonstrated. In histological sections, the small arteries and arterioles showed medial muscular hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed lumen in 7% of the patients. No vascular occlusion, ischaemic changes or arteriovenous shunts were observed. These changes were confirmed ultrastructurally. Angiography of the lesion showed a brisk pathological circulation which was more evident in eumycetoma. The vascular Doppler study showed normal blood flow pattern in the affected limb. Regional intra-arterial chemotherapy for mycetoma is suggested as a possible treatment modality.

Intraspinal mycetoma: report of two cases.

Two cases of intraspinal mycetoma caused by Madurella mycetomatis and Streptomyces somaliensis presenting with paraplegia are reported. In these cases, there was neither skin or bone involvement by the disease. The route of entry of the organisms is not known; however, hematogenous blood vessel invasion by S. somaliensis was identified in the second case.

Fine needle aspiration cytology of mycetoma.

OBJECTIVE: To describe fine needle aspiration cytology of mycetoma and determine its usefulness in diagnosis. STUDY DESIGN: The study group consisted of 14 patients with different types of mycetoma lesions, which were aspirated. Smears were reviewed without knowing the type of mycetoma, and the findings were compared with those observed in histologic sections. RESULTS: In mycetoma, the causative organisms have a distinct appearance on cytologic smears. They are surrounded and infiltrated by neutrophils in a background of polymorphous, inflammatory cells consisting of neutrophils, histiocytes, lymphocytes, plasma cells, macrophages and foreign body giant cells. This allows differentiation from artifacts and inflammatory lesions caused by other bacteria and fungi. The distinction between eumycetoma and actinomycetoma in fine needle aspiration cytology was found to be as accurate as is histopathology when the grains were present. CONCLUSION: These results demonstrate that mycetoma can be accurately diagnosed by fine needle aspiration cytology. The technique is simple, inexpensive, rapid and sensitive. It can be used in the routine diagnosis of mycetoma, in epidemiologic surveys and in material collection.

Liver morphology and function in visceral leishmaniasis (Kala-azar).

AIM: To study the morphology and function of the liver in visceral leishmaniasis (Kala-azar). METHODS: Percutaneous liver biopsy specimens from 18 patients with confirmed visceral leishmaniasis were examined under light and electron microscopy before and after treatment with pentovalent antimony. The tissue was also examined for hepatitis B surface and core antigens using immunoperoxidase staining. Liver function was investigated in nine patients before and after treatment. RESULTS: Specimens before treatment showed Kupffer cells and macrophages colonised by leishmania parasites in 40% of cases. A chronic mononuclear cell infiltrate had affected the portal tracts and lobules. Ballooning degeneration of the hepatocytes, fibrosis of the terminal hepatic venules, and pericellular fibrosis were common findings. The fibrosis was related to Ito cells transforming to fibroblast-like cells. None of the patients had hepatitis B infection. All patients had biochemical evidence of liver dysfunction before treatment. Liver function improved after treatment. CONCLUSION: Visceral leishmaniasis causes morphological and functional disturbance in the liver. Focal fibrosis rather than cirrhosis occurs. The exact aetiology of hepatic damage is unclear but may have an immunological basis.

Degradable starch microspheres in cytostatic treatment of a liver carcinoma; experimental studies in rats with 5-fluorouracil, tauromustine, carmustine, doxorubicin and RSU-1069.

The degradable starch microspheres (DSM) used have a size of 45 microns and are dissolved by amylase in blood. After intraarterial administration of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occurs. Systemic exposure of drugs is decreased. Rats with a carcinoma implanted into the liver were given DSM and drugs via the hepatic artery. DSM did not significantly increase the incorporation of 5-fluorouracil (5-FU) into liver tumor RNA. The incorporation of 5-FU into intestinal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nitroimidazole). Side effects, such as liver and gastric necroses and body weight loss, appeared in some rats. The toxic overspill to the stomach seemed to be reduced by giving the DSM in two parts, with all the cytotoxic drug in the first part. The effect on liver and tumor was not decreased by this procedure. DSM alone had no anti-tumor effect. DSM alone decreased liver UDP-glucuronic acid in tumor-free rats, given either by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activity or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotransferase), indicating that the DSM are inert to the liver, when infused into the tributary vessels.

Incorporation of 5-fluorouracil into rat liver tumor and normal tissues and the liver nucleotide profile after administration by the hepatic artery during portal venous branch ligation.

A therapeutic dose of labelled 5-fluorouracil (5-FU) was infused via the hepatic artery during 30 min with or without ligation of the left portal venous branch in Wistar rats with a secondary liver cancer in the left lateral lobe. After another 60 min, the incorporation of 5-FU into the acid soluble fraction (ASF), ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), was determined in tumor, ligated and unligated liver lobes, small intestine, kidney, and bone marrow. The liver nucleotide profile was examined with isotachophoresis. Portal venous branch ligation (PVBL) caused the following changes, compared with the unligated control group: in the tumor, the incorporation of 5-FU into RNA and DNA decreased and the ratio RNA/acid-soluble fraction labelling decreased. The incorporation increased in intestinal and bone marrow RNA. It was unchanged in liver and kidney. The ratio of tumor to peripheral normal-tissue (small intestine, bone marrow, and kidney) labelling of RNA and DNA decreased. Liver nucleotides (F)UTP, (F)UDP-glucuronic acid, (F)UDP-N-acetylhexosamine, and NAD were lower in the ligated than in the unligated liver lobe. ATP and energy charge did not decrease significantly. In conclusion, PVBL in conjunction with hepatic arterial administration of 5-FU increased systemic drug exposure and possibly decreased hepatic tumor anabolism. It has not been examined how this interferes with the therapeutic effect.

The antitumor effect of a novel nitrosourea, tauromustine, at intravenous administration in rat. Cure of hepatomas.

The effect of intravenously injected tauromustine (TCNU) on tumor growth and body weight was studied in rats with subcutaneously implanted experimental carcinomas. With a colonic tumor, a single dose or that dose split on 4 consecutive days gave the same tumor growth delay but the body weight loss was less at the split dose. Injection of the single dose for 1 min, 30 min or 2 h each had the same effect. Rats of another strain were implanted with a hepatoma. 9 out of 10 rats were cured. A late effect was body weight loss due to disturbed growth of the teeth.