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Early lesions in lymphomas of germinal centre B-cell derivation: evidence and hypotheses
  1. Antonino Carbone1,
  2. Ming-Qing Du2,
  3. Armando Santoro3,
  4. Annunziata Gloghini4
  1. 1Division of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, Aviano, Italy
  2. 2Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK
  3. 3Division of Medical Oncology and Hematology, Humanitas Cancer Center, Milan, Italy
  4. 4Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  1. Correspondence to Dr Antonino Carbone, Chairman of the Division of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, Via F. Gallini 2, Aviano 33081, Italy; acarbone{at}

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Early neoplastic or preneoplastic lesions in follicular lymphoma (FL) and in mantle cell lymphoma have been provisionally termed as ‘intrafollicular neoplasia’/in situ lymphoma by the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.1–3 Interestingly, besides FL, neoplastic lesions restricted to the follicle have been described for other germinal centre (GC)-derived B-cell lymphomas.4 ,5

‘Intrafollicular neoplasia’/ ‘in situ’ follicular lymphoma: immunohistochemical, molecular and clinical evidence

In situ FL

The term ‘intrafollicular neoplasia’/‘in situ’ lymphoma has been adopted to define an early lymphoid neoplasia with an ‘intrafollicular’ growth pattern without invasion of surrounding structures.6 The term, originally coined for FL, properly applies when the neoplastic cells are localised in the ‘place’ that is occupied by the normal counterpart of the tumour cell. In situ FL is derived from GC B cells and displays t (14;18) (q32;q21), the genetic hallmark and initiating event of FL pathogenesis. This early lesion has an uncertain clinical behaviour and unknown risk of progression to overt lymphoma.

Table 1 shows histologic and immunophenotypic criteria to diagnose in situ FL and to distinguish it from overt FL with partial lymph node involvement.7 Immunohistologically, GC B cells of the follicles affected by in situ FL show strongly positive staining for BCL2 and CD10. They are also positive for other B-cell markers including CD20 and BCL6, but not IgD. The BCL2+ and CD10+ cells are confined to GCs and are not seen outside the follicles6 (figure 1).

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Table 1

Histologic and immunophenotypic criteria to distinguish in situ follicular lymphoma (FL) from overt FL with partial lymph node involvement*

Figure 1

Intrafollicular neoplasia/‘in situ’ follicular lymphoma. (A) The involved lymph node shows multiple follicles with large germinal centres and wide mantles. (B–D) Within affected follicles, the strongly stained BCL2+ (B) and CD10+ (D) …

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  • Funding This work was supported in part by funds from the Ministero della Salute, Rome, within the framework of the ‘Progetto Integrato Oncologia-Advanced Molecular Diagnostics’ Project (RFPS-2006-2-339723.2).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.