nodular lymphocyte predominant Hodgkin lymphoma
ICD-10:C81.7 ICD-9:201.9 ICD-O:M9659/3 HP:4923
Tuesday 7 December 2004
NLPHL, nodular lymphocyte predominance Hodgkin’s disease, NLPHD, nodular lymphocyte predominance Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin disease, nodular paragranuloma, Popema paragranuloma
Definition: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct type of Hodgkin lymphoma (HL) representing approximately 5% of all HL cases. Clinical, morphologic, immunophenotypic, and molecular features set NLPHL apart from other types of HL, the latter collectively referred to as classical HL.
NLPHL is characterized by expansile nodules composed of sparse, relatively large neoplastic cells, referred to as lymphocytic and/or histiocytic (L&H) cells, intermixed with numerous reactive lymphocytes and a variable number of histiocytes.
The L&H cells are CD20-positive cells that carry immunoglobulin gene rearrangements with somatic hypermutations and, therefore, are thought to be derived from follicular center B cells.
Most patients with NLPHL present with localized lymphadenopathy, either stage I or II disease, and have an excellent prognosis with at least 80% overall survival at 10 years.
According to the recent World Health Organization classification and the European Task Force on Lymphoma, the diagnosis of NLPHL requires identification of a nodular growth pattern, that may or may not be associated with a diffuse pattern.
minority of large atypical cells, lymphocytic and/or histiocytic (L&H) cells or popcorn cells
scattered in nodular infiltrates of small lymphoid and epithelioid cells
network of follicular dendritic cells (CD21+)
IHC and molecular evidence for a germinal center B-cell origin
Usually total replacement of nodal architecture by expansive vague nodules of small lymphocytes with sparse, relatively large tumor cells with multilobulated or round nucleus, thin nuclear membrane, finely granular chromatin and variable small nucleoli
large B cells / popcorn cells / L&H cells (lymphocytic & histiocytic cells)
- The large cells are called LP cells (previously known as popcorn cells or L&H (lymphocytic & histiocytic) cells
- LP cells are admixed with numerous small B lymphocytes, epithelioid histiocytes and CD21+ dendritic reticulum cells
Post-capillary venules may be prominent
Often T-cell rosettes surrounding LP cells (Am J Surg Pathol 2008;32:1252)
May have rim of normal lymph node
Scant eosinophils, plasma cells or fibrosis
Prominent sclerosis is unusual but may occur in older lesions
Small germinal centers are rare between the nodules and usually present only at the compressed edge of normal lymph node tissue
No / rare classic Reed-Sternberg (RS) cells, although LP cells may occasionally resemble R-S cells / variants
No well-formed granulomas, although epithelioid histiocytes may be prominent
Diffuse cases have background of reactive T cells
Syncytial variant is rare (Am J Surg Pathol 2009;33:1725)
- B-cell markers+ : CD20+
Morphological variants (14508396)
"classic" (B-cell-rich) nodular
serpiginous/interconnected nodular (14508396)
nodular with prominent extranodular popcorn cells (L&H cells) (14508396)
T-cell-rich nodular (14508396)
diffuse with a T-cell-rich background (T-cell-rich B-cell lymphoma [TCRBCL]-like) (14508396)
(diffuse) B-cell-rich pattern (14508396)
focal changes of sinus histiocytosis with massive lymphadenopathy (8522313)
Nodular Lymphocyte Predominant Hodgkin Lymphoma With clusters of LP cells, acute inflammation, and fibrosis: a syncytial variant. (19730363)
bone marrow (15087668)
monoclonal B cell population with clonal rearrangement of Ig genes and somatic mutations of the variable region of the Ig heavy chain genes cluster
heterogeneous BCL6 rearrangement (15339680)
- t(3;22)(q27;q11) (BCL6 at 3q27 and IGL at 22q11) 15339680)
- t(3;14)(q27;q32) (BCL6 at 3q27 and IGH at 14q32) (16049307)
- t(3;9)(q27;p13) (PAX5 at 9p13) (15339680)
- t(3;4)(q27;q32) (15339680)
- complex t(3;7;3;1) (15339680)
- The biologic significance of a diffuse component in NLPHL, particularly if this component is substantial, is not known.
- However, a purely diffuse form of LPHL is very rare, as most cases are now classified as either T-cell/histiocyte-rich large B-cell lymphoma (T/HRLBCL), a variant of diffuse large B-cell lymphoma, or classical HL.
- As diffuse areas in NLPHL resemble T/HRLBCL morphologically and immunophenotypically, many pathologists think that large diffuse areas in NLPHL may be a sign of transformation to a higher-grade neoplasm.
Nodular Lymphocyte Predominant Hodgkin Lymphoma With Clusters of LP Cells, Acute Inflammation, and Fibrosis: A Syncytial Variant. Drakos E, Rassidakis GZ, Leventaki V, Cotta CV, Vega F, Medeiros LJ. Am J Surg Pathol. 2009 Aug 28. PMID: 19730363
Pijuan L, Vicioso L, Bellosillo B, Ferrer MD, Baro T, Pedro C, Lloreta-Trull J, Munne A, Serrano S. CD20-Negative T-Cell-Rich B-Cell Lymphoma as a Progression of a Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma Treated With Rituximab: A Molecular Analysis Using Laser Capture Microdissection. Am J Surg Pathol. 2005 Oct;29(10):1399-1403. PMID: 16160485
Khoury JD, Jones D, Yared MA, Manning JT Jr, Abruzzo LV, Hagemeister FB, Medeiros LJ. Bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma. Am J Surg Pathol. 2004 Apr;28(4):489-95. PMID: 15087668
Boudova L, Torlakovic E, Delabie J, Reimer P, Pfistner B, Wiedenmann S, Diehl V, Muller-Hermelink HK, Rudiger T. Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma. Blood. 2003 Nov 15;102(10):3753-8. PMID: 12881319
Fan Z, Natkunam Y, Bair E, Tibshirani R, Warnke RA. Characterization of variant patterns of nodular lymphocyte predominant hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol. 2003 Oct;27(10):1346-56. PMID: 14508396
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Ferry JA, Zukerberg LR, Harris NL. Florid progressive transformation of germinal centers. A syndrome affecting young men, without early progression to nodular lymphocyte predominance Hodgkin’s disease. Am J Surg Pathol. 1992 Mar;16(3):252-8. PMID: 1599017
Grossman DM, Hanson CA, Schnitzer B. Simultaneous lymphocyte predominant Hodgkin’s disease and large-cell lymphoma. Am J Surg Pathol. 1991 Jul;15(7):668-76. PMID: 2058762
Chittal SM, Alard C, Rossi JF, al Saati T, Le Tourneau A, Diebold J, Delsol G. Further phenotypic evidence that nodular, lymphocyte-predominant Hodgkin’s disease is a large B-cell lymphoma in evolution. Am J Surg Pathol. 1990 Nov;14(11):1024-35. PMID: 2240355
Sundeen JT, Cossman J, Jaffe ES. Lymphocyte predominant Hodgkin’s disease nodular subtype with coexistent "large cell lymphoma". Histological progression or composite malignancy? Am J Surg Pathol. 1988 Aug;12(8):599-606. PMID: 3041849
Wlodarska I, Stul M, De Wolf-Peeters C, Hagemeijer A. Heterogeneity of BCL6 rearrangements in nodular lymphocyte predominant Hodgkin’s lymphoma.
Haematologica. 2004 Aug;89(8):965-72. PMID: 15339680