Granulomatous reactions cause symptoms or clinically imitate treatment resistance in small lymphocytic lymphoma/chronic lymphocytic leukaemia more frequently than in other non-Hodgkin lymphoma

Institute of Pathology, Innsbruck Medical University, Muellerstrasse 44, 6020 Innsbruck, Austria.
Journal of Clinical Pathology (Impact Factor: 2.92). 09/2005; 58(8):815-9. DOI: 10.1136/jcp.2004.023911
Source: PubMed


The electronic database of the institute of pathology, Medical University of Innsbruck, was reviewed and patient histories studied to analyse systematically the coincidence of granulomatous reactions and lymphomas in a large patient collective, and to find distinct clinicopathological correlations. Five cases of small lymphocytic lymphoma/chronic lymphocytic leukaemia (CLL) associated with granulomatous reactions in lymph nodes and bone marrow were identified, all clinically associated with signs of progressive disease.
Cases were acquired by reviewing an electronic database comprising approximately 715,000 patients diagnosed between 1993 and 2003. Histochemical, immunohistochemical, and molecular techniques were used to verify diagnosis and associated infectious diseases. Clinical data were obtained from reviewing the charts.
Of 2044 bone marrow and 411 lymph node non-Hodgkin lymphoma biopsy samples, CLL was most frequently associated with bone marrow (two cases) and lymph node granulomas (three cases). These granulomas were mostly composed of epithelioid cells, with or without giant cells, and in all but one case did not show necrosis. All patients with CLL had clinical symptoms primarily caused by the granulomatous disease: two suffered from acid fast bacilli infections (Mycobacterium tuberculosis and mycobacteria other than tuberculosis) and three presented with clinical manifestations of sarcoidosis (the reason a diagnostic biopsy was performed).
Granulomatous reactions in patients with CLL might obscure diagnosis and imitate disease progression and Richter's transformation. Careful histological examination, exclusion of infectious agents, and a detailed clinical history are essential for correct diagnosis.

Download full-text


Available from: Andrea Brunner, May 15, 2014
23 Reads
  • Article: Milzruptur
    [Show abstract] [Hide abstract]
    ABSTRACT: Obwohl selten, stellen Milzrupturen die häufigste Splenektomieindikation dar. Bei der überwiegenden Mehrzahl der Fälle (traumatische Rupturen) lässt sich eine klare Kausalität mit Gewalteinwirkung feststellen, bei einem anderen Teil (pathologische Rupturen) liegt eine Vorerkrankung der Milz vor, bei einem kleinen Teil der Patienten (spontane Rupturen) lässt sich kein Zusammenhang mit Traumen oder anderen Grunderkrankungen eruieren. Bei etwa 10% der rupturierten Milzen ist mit Iatrogenie im weitestem Sinne (inklusive Medikamentennebenwirkungen) sowie mit relevanten pathologischen Befunden (die Hälfe davon unerwartet) zu rechnen. Kenntnisse der Pathophysiologie, die Erhebung einfacher makroskopischer Befunde wie Größen- und Gewichtsangaben und Angaben sichtbarer Läsionen sowie die sorgfältige histologische Analyse mit gezielter Suche nach wegweisenden Veränderungen, ggf. unter Anwendung histo- und immunhistochemischer Zusatzuntersuchungen am gut vorbereiteten Material, sind die Schlüssel zur adäquaten Diagnostik. Though rare, splenic rupture is the most common indication for splenectomy. In the vast majority of cases ruptures are clearly related to trauma (traumatic ruptures); in other cases there is a pre-existing disease affecting the spleen (pathologic ruptures); and in a minority of patients no obvious reason can be identified (spontaneous ruptures). In approximately 10% of cases an iatrogenic cause, in the broadest sense (including side effects of drugs), and relevant histological findings (approximately half of which will be unexpected) can be anticipated. Knowledge of pathophysiological aspects of splenic rupture and assessment of simple macroscopic findings such as splenic dimensions and weight, and information on macroscopically visible lesions are of key diagnostic importance, as is accurate microscopic examination with targeted histological pattern analysis, supplemented as appropriate by histo- and immunohistochemical studies on adequately prepared material.
    Der Pathologe 03/2007; 29(2):148-157. DOI:10.1007/s00292-007-0948-0 · 0.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Trephine bone marrow biopsy is a frequent routine investigation, particularly important in cases with an unsuccessful aspirate. In addition to a representative trephine biopsy length and quality, the patient's clinical history is of critical importance. Especially drug-induced bone marrow changes are often difficult to interpret without prior knowledge of exposure to respective agents. Since some of these changes mimic malignancies, this can lead to serious misinterpretations. Drugs in general can induce a wide spectrum of bone marrow reactions. Immunosuppressants such as Azathioprine and Methotrexate cause morphological bone marrow changes that can not be distinguished from myelodysplastic syndromes, while cytokines and growth factors induce an overall increase in cellularity and, in particular, a left shift of myelopoiesis with increased myeloblasts and monoblasts, mimicking acute myeloid leukaemia. Moreover, drugs with immuno-allergic- (such as Allopurinol, Carbimazole, Crabamazepine, Clozapine, non-steroidal anti-rheumatics, Phenytoin, Sulfonamides) or direct myelotoxic potential can lead either to T-cell-mediated bone marrow stem cell destruction with the morphological pattern of aplastic anaemia, to direct toxic or immunological burst- or colony-forming units' destruction with isolated erythro- or myelopoietic hypoplasias or to other changes such as eosinophilia, (haemo)phagocytosis, T-cell lymphocytosis (which can be very severe, resembling lymphoma/leukaemia), perivascular plasmacytosis, siderosis or stromal oedema. In summary, clinical information on drug exposure is at least as important as a good quality biopsy for comprehensive histology-based bone marrow diagnostics, helping to avoid not only misinterpretation but also expensive additional examinations. KeywordsBone marrow-Trephine biopsy-Pitfalls-Drug-induced changes
    memo - Magazine of European Medical Oncology 10/2010; 3(3):132-135. DOI:10.1007/s12254-010-0215-6
  • Source
    Indian Journal of Gastroenterology 05/2008; 27(3):123-9.
Show more