Anaplastic Variant of Diffuse Large B-Cell Lymphoma: Re-Apprasial As Extra-Mediastinal Grey Zone Lymphoma Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma,

Recently more light has been shed on the overlap in biologic and morphologic features between classic Hodgkin lymphoma (cHL) and B-cell non-Hodgkin lymphoma. This overlap was further substantiated by analyzing the neoplastic nature of the malignant cell of cHL, which was proven to be of B-cell origin in nearly all cases. In addition, the growing recognition of composite and metachronous Hodgkin and non-Hodgkin lymphomas provided a further evidence of such claim. This advocated the term Grey zone lymphoma, which was first introduced in 1998 in the ÔÔWorkshop on HodgkinÕs disease and related diseasesÕÕ. According to WHO classification 2008, the term Ògrey zone lymphomaÓ designates anterior mediatsinal involvement with lymphoma intermediate between DLBCL and cHL. This type of lymphoma is claimed to have a more aggressive course than either cHL or DLBCL. Although the optimum treatment regimen in such cases is not yet well established most authors go for administration of therapy appropriate for DLBCL with the addition of Rituximab. We present a reappraisal of anaplastic variant of diffuse large B-cell lymphoma as an extramediastinal grey zone lymphoma showing morphologic and phenotypic features intermediate between DLBCL and cHL.

Clinical and pathological data of 13 cases were retrieved over 8-year period. The age of the patients ranged from 57 to 86 years old (mean= 75 yeas). Eight of our cases were males and 5 were females with slight male predominance (male: female ratio= 1.6:1). This runs in contradiction with cases of mediastinal grey zone lymphoma which show striking female predominance. All the cases were presented with extramediastinal lymphadenopathy. Six patients showed associated extranodal involvement (e.g. liver, stomach, forearm, bone). None of the cases was associated with EBV activity. Four cases were presented with stage IV disease, 3 cases with stage III and 4 cases with stage II. B symptoms were reported in 6 cases. Histopathologically, tumors showed sheet like growth of pleomorphic cells, some of them are Reed Sternberg like cells, admixed with inflammatory background formed of mature lymphocytes eosinophils and plasma cells. Fibrous strands and geographic necrosis were seen in all cases. B-cell immunophenotyping of the tumor cells was evidenced by positivity for CD20, CD79a and Pax 5 in all cases. On the other hand, Hodgkin-like immunophenotyping was evidenced by positivity for CD30 in 10 cases, positivity for CD15 in 2 cases, positivity for Mum1 in one case and positivity for fascin in 6 cases. All the cases were negative for ALK1, CD10, CD3, κ□Aλ and CD45 RO. Worth to be noted that 69% of the cases (9/13) showed positivity for p53 and 23% (3/13) showed positivity for BCL-6 which are both an unusual finding in cHL. Forty six percent of the cases (6/13) died within the first year of the disease course (mean=8.3 months). Six patients are still alive (46%), 5 of which showed complete remission and one patient showed partial remission.

Anaplastic variant of diffuse large cell lymphoma shows phenotypic and immunotypic features intermediate between cHL and DLBCL. We here propose the term (Extramediastinal grey zone lymphoma) for such cases which represent a distinctive subgroup of aggressive lymphoma. Further future studies of this group could contribute more to unmasking the link between Hodgkin and Non-Hodgkin lymphomas.

Table 1.

Clinical data of the selected cases

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Table 2.

Immunohistochemical data of the selected cases.

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No relevant conflicts of interest to declare.