Rapid Transformation to Aggressive B-Cell Lymphoma, in a Case of Mixed Cellularity Hodgkin Lymphoma Subtype : A Rare Event

BACKGROUND. Several histological subtypes of lymphoma can occur in the same patient. This event may happen sequentially or simultaneously. We describe a case of sequential diffuse large B-cells lymphoma (DLBCL), occurred shortly after therapy and rapidly fatal, after primary mixed cellularity Hodgkin lymphoma subtype (MCHLs).

CASE REPORT. A 24-year-old woman was admitted in March 2006 to our Unit with fever, loss of weight and left sovraclavear lymphoadenopathy. On admission, chest radiography and total body computerized tomography (TB-CT) evidenced bulky mediastinal disease, lung involment, pericardial and pleural effusion. Left sovraclavear limphoadenopaty biopsy was performed and histology revealed MCHLs. Clinical stage was IVB with mediastinal bulky disease (Ann-Arbor Classification). Chemotherapy with doxorubicin-bleomycin-vinblastin- dacarbazine (ABVD) was starded. After 2 cycles TB-CT and PET showed reduced involvement of mediastinum and middle lobe of right lung. We decided to continue with further 4 cycles of ABVD chemotherapy. At restaging, TB-CT was negative; yet TB-PET was again positive with further strong reduction of mediastinal captation and absence of pulmonary involvment. Radiotherapy involved field (RT-IF) on mediastinum was started. Treatment was not well tolerated because infectious episodes occurred. After 3 weeks since the end of radiotherapy the patient showed fever and catarrhal cough. In the suspect of the bronchopneumonia, we performed cultural examination of sputum and hemoculture, turned out negative; broad-spectrum antibiotic and antimicotic therapy was started. TB-CT, performed after a month, showed an oval lesion on right lung, mediastinal ipercaptation, right pleural effusion, sub-diaphragmatic lymphoadenopathies, cystic lesions of kidneys. The patient underwent medistinal biopsy with histologic diagnosis of DLBCL, but she died a week later for heart and respiratory failure. Overall survival was only of 12 months.

DISCUSSION. Possibility of development in the same patient of various types of lymphomas has been recognized for some time. To explain this occurrence, the term of multiple histology lymphomas (MHL) has been coined. MHLs may be sequential (different lymphomas at different times) or simultaneus (different lymphomas occurring at same time in the same lymphnode or at different sites). This event is mostly observed in non Hodgkin lymphoma (NHL). (Tucci et al, Haematologica 2005). Eventuality of a NHL after a primitive Hodgkin lymphoma (HL) is very rare (less than 1% of cases), with a variable time of insorgence (incidence is higher in the first 2 years from diagnosis of HL). Simultaneous HLs and NHLs are also very rare. All HL subtypes may evolve in a NHL DLBCL is main histology subtype of NHL from primary HL, with frequent extranodal involvement. Prognosis is poorer than primary NHLs. (Rueffer et al, JCO 2001). Our case shows a quick transformation to DLBCL of a MHLs. This event happened 3 weeks about for the end of therapy. Latent period is very short to consider DLBCL like a secondary neoplasm. Most reliable hypothesis is the common B-cellular derivation of HL and B-NHL, such as it has recently been demonstrated (Fraga M et al, Histol Histopathol 2007).

CONCLUSION. The transformation of a HL into a NHL is a very rare event. Since HL is probably a B-cell derived lymphoma, the transformation into an aggressive NHL has to be suspected in presence of dubious images and symptoms and a biopsy has to be performed and standard therapy for NHL quickly started.