identified as an oncogene-inducing factor by in vitro

studies, as well as in animal models [10,11]. By

contrast, epidemiological studies among the Gulf

War veterans and UN soldiers did not confirm its

carcinogenic potential [12,13]. Although the hema-

topoetic system is very sensitive to radiation

exposure, the studies conducted to date have not

found an increased incidence of hematologic malig-

nancies among children or soldiers potentially

exposed to DU [12,14]. Our patients, who were

suffering from a rare leukemia, shared a few

important epidemiological characteristics, including

possible exposure to DU. We hope that this

finding will add to recent debate concerning the

possible role of depleted uranium (DU) in leukemo-

genesis.

Branimir Jaksic

Department of Medicine

‘Merkur’ University Hospital

Zajceva 19, 10000 Zagreb, Croatia

E-mail: branimir.jaksic@zg.htnet.hr

References

1. Zarrabi MH, Grunwald HW, Rosner F. Chronic lymphocytic

leukemia terminating in acute leukemia. Arch Intern Med

1977;137:1059 – 1054.

2. Stern N, Shemesh J, Ramot B. Chronic lymphatic leukemia

terminating in acute myeloid leukemia. Revew of the

literature. Cancer 1981;47:1849 – 1851.

3. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN,

Pasternack BS. Clinical staging of chronic lymphocytic

leukemia. Blood 1975;46:219 – 234.

4. Jaksic B, Vitale B. Total tumour mass score (TTM): a new

parameter in chronic lymphocytic leukaemia. Br J Haematol

1981;49:405 – 413.

5. Matutes E, Morilla R, Farahat N, Carbonell F, Swansbury J,

Dyer M, et al. Definition of acute biphenotypic leukemia.

Haematologica 1997;82:64 – 66.

6. Schroers R, Pukrop T, Durig J, Haase D, Duhrsen U,

Trumper L, et al. B-cell chronic lymphocytic leukemia

with aberrant CD8 expression: genetic and immunopheno-

typic analysis of prognostic factors. Leuk Lymphoma 2004;

45:1677 – 1681.

7. Tamul KR, Meyers DC, Bentley SA, Folds JD. Two color

flow cytometric analysis of concomitant acute myeloid

leukemia and chronic lymphocytic leukemia. Cytometry

1994;18:30 – 34.

8. Barresi GM, Albitar M, O’Brien SM. Acute myeloid

leukemia, inversion 16, occurring in a patient with chronic

lymphocytic leukemia. Leuk Lymphoma 2000;38:621 – 625.

9. Mateu R, Bellido M, Sureda A, Gonzalez Y, Rubiol E,

Aventin A, et al. Concomitant chronic lymphocytic leukemia

and acute myeloid leukemia with an uncommon immunophe-

notype. Am J Hematol 1997;56:281 – 287.

10. Durakovic A. Medical effects of internal contamination with

uranium. Croat Med J 1999;40:49 – 66.

11. Miller AC, Brooks K, Stewart M, Anderson B, Shi L,

McClain D, et al. Genomic instability in human osteoblast

cells after exposure to depleted uranium: delayed lethality and

micronuclei formation. J Environ Radioact 2003;64:247 – 259.

12. Gustavsson P, Talback M, Lundin A, Lagercrantz B,

Gyllestad PE, Fornell L. Incidence of cancer among Swedish

military and civil personnel involved in UN missions in the

Balkans 1989 – 99. Occup Environ Med 2004;61:171 – 173.

13. Macfarlane GJ, Biggs AM, Maconochie N, Hotopf M, Doyle

P, Lunt M. Incidence of cancer among UK Gulf war veterans:

cohort study. BMJ 2003;327:1373.

14. Labar B, Rudan I, Ivankovic D, Biloglav Z, Mrsic M,

Strnad M, et al. Haematological malignancies in childhood

in Croatia: investigating the theories of depleted uranium,

chemical plant damage and ‘population mixing’. Eur J

Epidemiol 2004;19:55 – 60.

DOI: 10.1080/10428190500403144

Calcified lymph nodes in Hodgkin’s lymphoma

SERCAN AKSOY, SAADETT_IN K_IL_ICKAP, HUSEY_IN ABAL_I, & MUSTAFA ERMAN

Hacettepe University Institute of Oncology, Ankara, Turkey

(Accepted 18 February 2005)

Calcification of lymph nodes in lymphoma patients

before or after treatment is uncommon. There have

been few reports of calcified masses due to Hodgkin’s

and non-Hodgkin’s lymphomas (NHL), originating

in the main lymphatic chains of the mediastinum and

retroperitoneum [1]. The following case represents

an unusual instance of lymph node calcification

in the supra-clavicular region in a patient with

Hodgkin’s lymphoma (HL).

A 60-year-old man received mantle radiotherapy

with the diagnosis of HL 28 years ago. He was also

treated with chemotherapy for inguinal and intra-

abdominal relapses 13 and 4 years ago. On his last

visit, he was found to be in remission with normal

clinical and laboratory examinations without any

complaints. Interestingly, the plain chest X-ray

showed calcified lesions resembling an eggshell in

the right supraclavicular region (Figures 1 and 2).

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Computed tomography (CT) of the neck revealed

lymphadenopathies with mural calcification, the

largest one of which was 26 2 cm (Figure 3). When

the medical records of the patient were evaluated,

this appeared to have developed following mantle

radiotherapy.

Peripheral calcification of lymph nodes, commonly

referred to as ‘eggshell calcification’, may occur in

patients with post-irradiation HL as well as silicosis

and coal-worker’s pneumoconiosis. Sarcoidosis, blas-

tomycosis, amyloidosis, histoplasmosis and sclero-

derma are other reported causes [2].

One study prospectively evaluated the prevalence,

CT features and clinical significance of pre-therapy

calcification in 956 newly diagnosed patients with

lymphoma (704 with NHL and 252 with HL). Only

eight patients, seven of whom had NHL (0.9%) and

one with HL (0.3%), showed calcifications in the

involved sites; five in mediastinal foci of disease and

three in involved sites in the abdomen [1]. Although

some authors stated that nodal lesions in HL never

calcify before treatment, there are several reports

of calcification in mediastinal and retroperitoneal

tumors of untreated HL. It has been suggested that

the nodular sclerosis sub-type of HL is more prone to

calcification, both before and after treatment. There

appears to be no association between calcification

and stage of disease, irradiation or chemotherapy

type and dose. A study by Apter et al. [3] suggests

that pre-treatment calcifications in NHL portend a

poor outcome, while the development of calcifica-

tions after treatment is thought to be associated with

a good prognosis.

Dystrophic calcification of metastatic sites has

been reported in various tumors. Most cases are

adenocarcinomas originating from the gastrointest-

inal tract and ovaries. Involvement of lymph nodes,

peritoneum or spleen is frequent. It has been

observed that calcification takes place most fre-

quently after radiation or chemotherapy, rather than

at the time of diagnosis [4,5].

Dystrophic calcification of metastases is encoun-

tered in areas of necrosis. Calcium deposits can be

Figure 1. The plain chest X-ray shows calcified lesions resembling

an eggshell in the right supraclavicular region (anterior-posterior

view).

Figure 2. The plain cervical X-ray shows calcified lesions

resembling an eggshell in the right supraclavicular region (lateral

view).

Figure 3. Axial computed tomography of neck revealed lymph-

adenopathies with mural calcification, the largest one of which was

262 cm.

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intra-cellular or extra-cellular or both. This process

has two phases: initiation (or nucleation) and

propagation. Initiation of extra-cellular sites occurs

in vesicles *200 nm in diameter, derived from

degenerating cells. Calcium is concentrated in these

vesicles by its affinity for acidic phospholipids and

phosphates, which have probably accumulated as a

result of membrane-bound phosphatases. However,

when this process takes place intra-cellularly,

calcification occurs in the mitochondrias of dead

cells, which accumulate calcium in the same way.

Propagation of crystal formations occurs, depending

on the concentration of calcium and phosphate in

the extra-cellular spaces and on the presence of

mineral inhibitors and collagen, which appear to

enhance the rate of crystal growth. This phenom-

enon is enhanced by tumoral necrosis. Chemo-

therapy and radiation may induce and promote

calcification of lymph node metastases [6]. No

specific mechanism for the eggshell pattern of calci-

fication has been demonstrated. Calcification seems

to be associated with a good prognosis and long-

term survival.

Although calcification of lymph nodes in HL

may be seen uncommonly in the main lymphatic

chains of the mediastinum and retroperitoneum,

supra-clavicular region calcification has not been

reported. The detection of a calcification is good

news because it may indicate a favorable response to

therapy.

Sercan Aksoy, MD

Hacettepe University Institute of Oncology

06100, Sıhhiye

Ankara, Turkey

Tel: þ90-312 305 2937. Fax: þ90-312 309 2905

E-mail: saksoy07@yahoo.com

References

1. Apter S, Avigdor A, Gayer G, Portnoy O, Zissin R, Hertz M.

Calcification in lymphoma occurring before therapy: CT

features and clinical correlation. AJR — American Journal of

Roentgenology 2002;178:935 – 938.

2. Gross BH, Schneider HJ, Proto AV. Eggshell calcification of

lymph nodes: an update. AJR — American Journal of Roent-

genology 1980;135:1265 – 1268.

3. Apter S, Zaks N, Hardan I, Amitai M, Langevitz P,

Livneh A. Calcification in untreated non-Hodgkin’s media-

stinal lymphoma. Southern Medical Journal 1998;91:212 –

213.

4. Sweeney DJ, Low VH, Robbins PD, Yu SF. Calcified lymph

node metastases in adenocarcinoma of the colon. Australasian

Radiology 1994;38:233 – 234.

5. Ibeas R, Carles J, Miguel A, Gallen M, Busto M. Calcification

of lymph node metastases from prostate carcinoma after

hormonal treatment: a case report. Prostate 1997;33:147.

6. Contran RS, Kumar V, Robbins SL. ‘Robbins’ pathologic basis

of disease. Philadelphia: Saunders; 1989. pp 35 – 36.

DOI: 10.1080/10428190500398948

Brucellosis in all patients with febrile neutropenia

GOKHAN METAN1, YES_IM CET_INKAYA SARDAN2, & GULSEN HASCEL_IK1

Departments of 1Microbiology and Clinical Microbiology, and 2Internal Medicine Section of Infectious Diseases, Hacettepe

University School of Medicine, Ankara, Turkey

(Accepted 5 July 2005)

Brucellosis is a worldwide important zoonosis. The

disease is highly endemic in developing countries,

particularly in the Mediterranean basin [1]. Brucella

melitensis has been reported previously in four

patients with febrile neutropenia from Turkey [2,3].

We report an adult patient with acute lymphoblastic

leukemia (ALL) whose blood culture yielded B.

melitensis during the febrile neutropenia attack.

The patient was a 17-year-old female who was

hospitalized for anemia and fever on 22 July 2002.

After bone marrow aspiration and biopsy, she was

diagnosed as ALL. The first course of the remission-

induction chemotherapy with cyclophosphamide,

vincristine, adriamycin and dexamethasone was

completed in August. Before the second course of

chemotherapy, she was discharged and stayed at

home for 3 days during 6 – 9 September 2002. After

re-admission to the hospital, the second course of

remission-induction chemotherapy was started. On

the 14 September 2002, she developed fever (axillary

temperature of 38,58C). Laboratory test results were:

hemoglobin 6.8 g/dl, hematocrit 19.2%, white blood

cell count 0.96 109/l, platelet count 76 109/l and

absolute neutrophil count was 300/ mm3. Empirical

treatment was started with cefepime and amikasin for

febrile neutropenia. On the second day of therapy,

vancomycin was added for suspected central venous

catheter infection. Acyclovir was also added for

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