Haematologica 2002; 87:(12)ECR42
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Work-related acute leukemia and mucor mycosis in a boat-builder
Nicola Magnavita,* Roberta Anna Placentino,* Patrizia Chiusolo,° Alessia Fiorini,° Luca Laurenti,° Simona Sica°
*Institute of Occupational Medicine and °Hematology, Catholic University School of Medicine, Rome, Italy
Correspondence: Dr. Nicola Magnavita, Institute of Occupational Medicine, Catholic University School of Medicine, Largo Gemelli 8, 00168 Rome, Italy. Phone: international +39.3473300367. Fax: international +39.06.3054481. E-mail: nmagnavita@rm.unicatt.it

Increased risks for leukemia and lymphoma have been suggested in studies of workers exposed to styrene in the rubber and plastics industry.1 Reporting of anecdotal cases, with complete occupational histories, might contribute to the recognition of new causes of leukemia.
In August 1994 a 47-year old caucasian man, a boat-builder, was admitted to our Division of Hematology complaining of weakness, fever, purpura, and gingival hypertrophy. He had been exposed for 21 years to styrene in fiber-reinforced plastic shipyards as a laminator. He sprayed styrene with a gun on ship hulls, provided with half-facepiece air-purifying or full-face air-supplied respirators which he shared with his co-workers. Hematologic examination showed severe leukocytosis 80x109/L (blasts 29%), severe anemia (Hb 8.4 g/dL), and thrombocytopenia (PLTs 38x109/L). Bone marrow aspirate showed 65% blasts and 30% monocyte cells. Blasts were of medium size with loose chromatin, thin cytoplasmatic granulations peroxidase-positive and sometimes with single Auer roads. Flow cytometric immunophenotyping demonstrated expression of HLA-DR, CD13, CD33, CD11b, CD14. Cytogenetic analysis showed a normal male karyotype of 46XY. A diagnosis of myelomonocytic acute leukemia (FAB M4) was made. A complete remission was induced by standard chemotherapy (ICE protocol). After chemotherapy the patient showed sepsis by Pseudomonas aeruginosa successfully treated with antibiotic therapy. During the aplastic period, at massive necrosis of mucosa and bone occured in the left maxillary bone. Mucosa biopsy identified hyphae of Mucormycosis. The diagnosis was confirmed by hystologic examination of maxillary and alveolar bones during maxillary surgery. Fungal infections are frequently seen in immunosuppressed patients with neutropenia or prolonged impaired T-cell function, such as bone marrow transplant recipients. Aside from common Candida and Aspergillus species, rare fungi like Mucor may be observed. Anecdotal cases of mucormycosis pneumonia are reported in patients with hematologic neoplasms and iatrogenic immunosuppression after treatment.2-4 Mucor hyphae were later demonstrated in the filter of the mask that he shared with his co-workers. Microbial growth on respirator filters from improper storage in humid environments has been reported.5 Our patient, however, was the sole case of mucormycosis in the boat building factory. Antimycotic therapy with amphotericin-B (total dose 1.34 g) was started with resolution of the mycotic infection after 2 months. In October 1995, with persisting complete remission and resolution of the mycotic infection, he underwent consolidation chemotherapy. After 4 months the patient was in complete remission, so that explantation of bone marrow followed by autologous bone-marrow transplantation was done. The patient is now in continuous complete remission. Several recent studies of the reinforced plastics industry, where high exposure to styrene occurs, have suggested that workers exposed to styrene have increased mortality from lymphatic and hematopoietic cancer. A historical cohort study conducted in Denmark, Finland, Italy, Norway, Sweden and the United Kingdom involving >40,000 workers suggested an association between hematologic malignancies and time elapsed since first occupational exposure to styrene, and a two-fold risk 20 years after first exposure, even if mortality from the lymphatic and hematopoietic tissues was not elevated.6 A Danish nested case-referent study found a 2.5-fold increased risk for myeloid leukemia with clonal chromosome aberrations among workers with styrene exposure.7 These results do not exclude the possibility that styrene causes leukemia. Within the boat-making industry,the job of hull lamination ranks higher in exposure to styrene than other jobs, and frequently exceeds the NIOSH-recommended time-weighted average standard (50 ppm).8 Evidence of exposure, and epidemiological data support the hypothesis that leukemia may have an occupational origin. The case was signaled to the National Institute for Work Accident and Illness (INAIL) for worker's compensation.
Our observation points out that work-related illnesses (i.e.: leukemia and mycosis) may be seen at first and managed by physicians other than occupational medicine specialists. This may pose a knowledge barrier to recognizing occupational disease.9 This barrier may be overcome by systematic referring of doubtful cases to occupational health physicians . Further epidemiological studies will undoubtedly lead to better knowledge of occupational causes of haematological malignancies.  

References

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