BMC Cancer 2005, 5:109 http://www.biomedcentral.com/1471-2407/5/109 Case presentation A 60-year-old male was diagnosed with anaplastic astrocy- toma involving the left parietal and temporal lobes. The patient underwent surgical resection with subsequent magnetic resonance imaging (MRI)-proven complete excision. In the context of a clinical trial, exploring the role of high- dose chemo-radiotherapy in malignant glioma, the patient underwent high dose sequential chemotherapy consisting of cyclophosphamide 7 g/m2 plus rhG-CSF (5 µ g/kbw) and hematopoietic cells harvest, followed by methotrexate 8 g/m2 and thiotepa 900 mg/m2. Autolo- gous unfractionated hematopoietic stem cells were administered at doses of 7.5 × 106/kg CD34+ cells and the patient experienced an uncomplicated hematological recovery within 10 days. One month later, the patient received 70-Gy of fractioned whole-brain irradiation, and steroids (dexamethasone 8 mg i.v. bid) were administered for 2 months and than tapered at the end of radiotherapy. On day +105 he was hospitalized because of the occur- rence of right hilum lymphoadenopathy associated with cutaneous lesions, as limited erythematous plaques, with well-demarcated margins and scalings. Surgical nodes and skin excision showed the presence of HD, nodular sclerosis type, with atypical HD-like ele- ments, infiltrating the skin. The staging evaluation, per- formed by CT scan of abdomen and thorax and bone marrow biopsy, was negative for distant involvement (stage IA) and no treatment was administered after radical surgery. Eight months after HSCT, the malignant glioma relapsed and the patient received 2 cycles of carmustine (240 mg/ m2 i.v. q.6 weeks) without clinical benefit, followed by palliative neurosurgical subtotal excision. The steroids treatment was resumed (dexamethasone 4 mg, daily) and chronically administered as supportive care. Six months later, histological-confirmed HD relapse occurred as bilateral hilum lymphoadenopaty. Because of deteriorated neurological clinical conditions, the patient declined any further treatment and died 2 months later for progressive glioma. Lymph node and skin biopsies were fixed in 10% buffered formalin and paraffin embedded. Micron sections were then prepared and stained with hematoxylin and eosin. Paraffin section immunohistochemical stains were per- formed using a biotin-streptavidin technique. The lymph node structure and the skin biopsy were diffusely effaced by a growth consisting of polymorphic features of small T- cell-rich B cell lymphoma/HD-like, and typical Hodgkin's and Reed-Sternberg cells (HRSCs), nodular sclerosis type with limited areas of lymphocyte depletion (REAL) (Fig. 1 and 2). At immunohistochemistry, HRSCs expressed the following molecules: CD30+, CD43+, CD15+/-, CD3+/-; and were negative for EMA, ALK and CD20. EBV latent membrane protein (LMP-1) was weakly posi- tive at HRSCs immunohistochemistry, but EBV-DNA determination by PCR [3] performed in multiple node biopsy fragments and in peripheral blood mononuclear cells (PBMC) yielded negative results. According to the clinical, histological and immunohisto- chemical findings, HD consistent with non EBV-associ- ated PTLD was diagnosed. Conclusion Usually reported after allogeneic transplantation, PTLD is a rare event after autologous HCT (Table 1). In most of cases, the onset is within the first in 3 months after HCT (vs 6 months in allogeneic setting), during the time of immunosuppession. Although HD is not the commonest form of PTLD mani- festation, several reports classified HD as a possible poly- morphic aspect of the post-transplant malignancies, and HD-like lesions are included among the distinctive cate- gories of PTLD [4]. The early time of onset after HCT and the presence of risk factors for immunological impairment are considered critical for distinguishing PTLD from classic form of HD occurring later in the post-transplant period [5]. EBV appears to be the major contributor to the pathogen- esis of PTLD. Uncertain is the promoting role of EBV in EBV-negative PTLDs, while a possible involvement of EBV infection in HD or T-cell PTLD appears controversial. Beside the speculative interest on the pathogenetic mech- anisms of the different presentations of PTLD, EBV-nega- tive forms of the disease pose important questions on diagnosis and treatment of PTLD. In this case, the patient presented a post-transplant EBV- negative HD; the treatment administered for malignat gli- oma, consisting of immuno-suppressive procedures (HDS with autologous HCT, radiotherapy and steroids), played a role in immunologic derailment and exposed the patient to an high risk of PTLD. In our opinion, the rapid onset of HD after HSCT (+105 day), the clinical and the histopathological characteristics Page 2 of 5 (page number not for citation purposes)