Fig. 1 Neoplastic lymphoid cells in the peripheral blood (Wright–Giemsa stain). (A) Neoplastic lymphoid cells at diagnosis in the patient displaying large granules. (B) Neoplastic lymphoid cells at transformation displaying irregular shaped nuclei.

bone marrow study revealed a hypercellular marrow with 49.6% neoplastic lymphoid cells. Flow cytometry revealed surface and cytoplasmic CD3þ, CD4þ and CD2þ. IHC on bone marrow biopsy material revealed the neoplastic cells to be CD30þ, CD3þ, CD4þ, granzyme Bþ, TIA1þ, EMAþ, ALK– and CD56–. Cytogenetic analysis of a marrow sample revealed the abnormal clonal karyotype 47,XY,inv(3)(p21q27),del(6) (q21q23),add(9)(p22),add(10)(p11.2),t(12;17)(q24.1;q21),del (13)(q14q22),þ19[17]/48,idem,þ19[2]/49,idem,þdel(13) (q14q22)[1]. Right axillary lymph node biopsy findings were consistent with ALK– ALCL. IHC testing of a lymph node biopsy disclosed CD30þ, CD4þ, ALK– and CD56–. The patient was diagnosed with leukaemic manifestation of ALK– ALCL transformed from CD4þ T-LGL, but did not survive despite salvage chemotherapy. Clear clinical differences exist between CD4þ T-LGL and CD8þ T-LGL, particularly with regard to the absence of neutropenia, anaemia, splenomegaly, rheumatoid arthritis and the higher incidence of association with malignant diseases in CD4þ T-LGL.4,7 In our current case, neutropenia, anaemia and rheumatoid arthritis were absent. Only one case of CD4þ T-LGL displaying skin lesions has been reported to date.4 In our present case, the skin lesions demonstrated atypical T-cell infiltration on skin biopsy. Generally, T-LGL involves the peripheral blood, bone marrow, liver and spleen, but our present CD4þ T-LGL case involved the skin. ALK– ALCL involves the lymph nodes and extranodal tissues such as bone, soft tissue and skin. A genetic evolution to a more complex karyotype was noted from our present case of CD4þ T-LGL transformation to ALK– ALCL. Our current report likely describes the first case of leukaemic manifestation and skin involvement of ALK– ALCL transformed from CD4þ T-LGL with skin lesions.

Contact Chan-Jeoung Park. E-mail: [email protected]

Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose.

Sir, Laboratory confirmed shigellosis is a national notifiable infection in Australia. While most cases are associated with recent overseas travel, locally acquired cases have been reported in men who have sex with men (MSM).1 Antibiotic therapy is recommended in all cases, both to treat severe disease, and to reduce the period of asymptomatic carriage.2 Increasingly, azithromycin is being used empirically for the treatment of bacterial gastroenteritis because of increasing antibiotic resistance in other gastrointestinal pathogens such as Salmonella species and Campylobacter species.3 While there are no official breakpoints for azithromycin against Shigella species, a

Jaewook Kim1 Chan-Jeoung Park1 Eul-Ju Seo1 Cheolwon Suh2 Departments of 1Laboratory Medicine, and 2Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

1. Semenzato G, Zambello R, Starkebaum G, et al. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 1997; 89: 256–60. 2. Morice WG, Jevremovic D, Hanson CA. The expression of the novel cytotoxic protein granzyme M by large granular lymphocytic leukaemias of both T-cell and NK-cell lineage: an unexpected finding with implications regarding the pathobiology of these disorders. Br J Haematol 2007; 137: 237–9. 3. Morice WG, Kurtin PJ, Tefferi A, Hanson CA. Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxidase stains for CD8, TIA-1, and granzyme B. Blood 2002; 99: 268–74. 4. Lima M, Almeida J, Dos Anjos Teixeira M, et al. TCRalphabetaþ/CD4þ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. Am J Pathol 2003; 163: 763–71. 5. Matutes E, Wotherspoon AC, Parker NE, et al. Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma. Br J Haematol 2001; 115: 801–6. 6. Tagawa S, Mizuki M, Onoi U, et al. Transformation of large granular lymphocytic leukemia during the course of a reactivated human herpesvirus-6 infection. Leukemia 1992; 6: 465–9. 7. Garrido P, Ruiz-Cabello F, Barcena P, et al. Monoclonal TCRVbeta13.1þ/CD4þ/NKaþ/CD8-/þdim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin. Blood 2007; 109: 4890–8.

DOI: 10.1097/PAT.0000000000000204

Outbreak of locally acquired azithromycinresistant Shigella flexneri infection in men who have sex with men

Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.


Pathology (2015), 47(1), January


Number of cases


Serotype 1b 2a


2b 3a

surveillance of emerging antibiotic resistance in Shigella species is warranted, and clinical laboratories should be aware of possible azithromycin-resistant Shigella species locally acquired in Australia when providing advice to clinicians regarding empiric therapy.




20 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 1 20 0 1 20 1 1 20 2 1 20 3 14 *


Year Fig. 1 Number of cases of Shigella flexneri serotypes in Victoria tested at MDU PHL, from 2000. *Data for 2014 is January to June inclusive.

minimum inhibitory concentration (MIC) 16 mg/mL is considered susceptible in the normal wild-type distribution.3,4 The Microbiological Diagnostic Unit Public Health Laboratory (MDU PHL) routinely performs identification, serotyping and antimicrobial susceptibility testing of Shigella isolates from clinical cases in Victoria and selected isolates from NSW.5 Recent reports of increasing antibiotic resistance in Shigella species, including a cases of infection where high-level resistance to azithromycin was demonstrated,3,6 and an increase in local laboratory confirmed cases of Shigella flexneri, prompted our investigation for local azithromycin resistance. Between 1 May 2013 and 30 June 2014, the number of Shigella flexneri 3a cases reported in Melbourne and Sydney was 29 and 16, respectively, a significant increase compared to previous years, with the major increase seen in 2014. Figure 1 summarises the serotype prevalence data for cases notified in Victoria from 2000 and where isolates were characterised at MDU PHL, demonstrating the significant increase in Shigella flexneri 3a cases in the first half of 2014. The number of infections caused by other Shigella flexneri serotypes was unchanged over the same time period. Thirty-eight of 45 isolates (14 from 2013, 12 males; 24 from 2014, all males) were submitted for azithromycin susceptibility testing, using azithromycin Etest according to the manufacturer’s instructions (bioMerieux, France). Susceptibility to azithromycin (MIC 16 mg/mL) was only seen in four 2013 isolates from two males and two females. Of the 34 remaining azithromycinresistant isolates (89% of isolates tested), 33 were resistant to azithromycin (MIC >256 mg/mL), ampicillin, and tetracycline, while one isolate was resistant to azithromycin (MIC 128 mg/ mL), ampicillin, tetracycline and exhibited decreased susceptibility to ciprofloxacin (0.25 mg/mL). Approval to include de-identified demographic data summarising risk factors for Shigella infection was granted by Department of Health, Victoria. The median age for the azithromycin resistant cases was 40 years (range 21–65 years), with most cases reported as occurring in MSM without overseas travel, indicating local acquisition in the MSM population in Melbourne and Sydney. These data are the result of passive surveillance of notifiable infections undertaken during this period, and not active surveillance in this risk group. Emerging azithromycin resistance in Shigella species further highlights the growing burden of antibiotic resistant bacterial infections, and has significant implications for the empiric treatment of severe bacterial gastrointestinal disease. Particularly in the MSM community, possible cases of shigellosis should not be empirically treated with azithromycin. Active

Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. Mary Valcanis1 Jeremy D. Brown2 Briony Hazelton2 Matthew V. O’Sullivan2,3 Alex Kuzevski1 Courtney R. Lane4,5 Benjamin P. Howden1,6 1

Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Vic, 2Centre for Infectious Disease and Microbiological Laboratory Services, Institute for Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW, 3Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, 4Victorian Department of Health, Communicable Disease Epidemiology and Surveillance, Health Protection Branch, Melbourne, Vic, 5National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT, and 6Infectious Diseases Department, Austin Health, Heidelberg, Vic, Australia Contact Professor Benjamin Howden. E-mail: [email protected] 1. Rowe SL, Radwan S, Lalor K, et al. An outbreak of shigellosis among men who have sex with men, Victoria, 2008. Vic Infect Dis Bull 2010; 13: 119–23. 2. Gastrointestinal Expert Group. Therapeutic Guidelines: Gastrointestinal. Version 5. Melbourne: Therapeutic Guidelines Limited, 2011. 3. Hassing RJ, Melles DC, Goessens WHF, Rijnders BJA. Case of Shigella flexneri infection with treatment failure due to azithromycin resistance in an HIV-positive patient. Infection 2014; 42: 789–90. 4. European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters, Version 4, 2014. Cited 20 Jul 2014. 5. Valcanis M. Laboratory testing of Shigella. Vic Infect Dis Bull 2010; 13: 114–8. 6. Heiman KE, Karlsson M, Grass J, et al. Notes from the field: Shigella with decreased susceptibility to azithromycin among men who have sex with men – United States, 2002-2013. MMWR Morb Mortal Wkly Rep 2014; 63: 132–3.

DOI: 10.1097/PAT.0000000000000207

Direct identification of bacteria from positive BD-Bactec blood culture bottles on the Vitek MS Sir, Timely and the appropriate choice of antimicrobial therapy is associated with lower mortality in patients with bacterial sepsis.1 Unfortunately there is often a delay of days before

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Outbreak of locally acquired azithromycin-resistant Shigella flexneri infection in men who have sex with men.

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