Case 1 -
Nodular Lymphocyte Predominant Hodgkin Lymphoma with Progression to T Cell-rich Diffuse Large B-cell Lymphoma
Department of Pathology
Stanford University School of Medicine
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Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) comprises approximately 5% of Hodgkin
lymphomas and exhibits distinct differences in clinical, histologic and immunophenotypic features from
those of classical Hodgkin lymphoma (CHL). Investigations employing microdissection techniques and
single cell polymerase chain reaction assays have shown that the atypical large cells, also known as
popcorn cells or lymphocyte and histiocyte ("L&H") cells in NLPHL are clonal B-cells.
NLPHL is recognized as an indolent, germinal center-derived B-cell lymphoma with a predisposition for
local recurrence and a low rate (3-5%) of progression to diffuse large B-cell lymphoma (DLBCL).
Its occurrence can be preceded by or be closely associated with florid reactive
follicular hyperplasia and progressive transformation of germinal centers although it is unclear whether
these should be considered precursor lesions.
Clinically, NLPHL occurs in young adults (median age 35 years) and affects men in 75% of cases. Over
half of the patients present with early stage disease and only a small minority demonstrates systemic
symptoms. The disease is often confined to peripheral nodes in the cervical, axillary, inguinal and
epitrochlear regions although other nodal sites such as mesenteric lymph nodes may also be affected.
Bulky disease and mediastinal widening are rare as are the involvement of other organs including spleen,
bone marrow, liver, lung and the skeleton. The disease is slowly progressive with frequent relapses but
it generally remains indolent and sensitive to therapy.
In patients presenting with
early stage favorable disease the five-year overall and event-free survival approximate 95 100% for
both the pediatric and adult age groups.  The overall mortality of patients with NLPHL is
increased in comparison to the general population due primarily to the development of secondary
malignancies and cardiac failure. Thus, radiation and chemotherapy of reduced intensity and monoclonal
antibody therapy (Rituximab) are preferred and have been found to be efficacious in the treatment of
The lymph node is usually significantly enlarged, exhibits a nodular architecture and a varying
number of atypical large (L&H) cells with folded or multilobated nuclei. The background is rich in
reactive lymphoid cells and histiocytes; the latter may be epithelioid and occur singly, in small
clusters or form granulomas. Historically, nodular or diffuse patterns of NLPHL have been described:
the nodular pattern exhibits L&H cells within nodules of small non-neoplastic B-cells and the diffuse
pattern is composed of L&H cells in a diffuse infiltrate of reactive T-cells.  The
World Health Organization (WHO) requires that at least a partial nodular architecture be present for the
diagnosis of NLPHL.  However, several variant immunoarchitectural patterns have since been
recognized: serpiginous/interconnected nodular pattern, nodular with prominent extra-nodular L&H
cells, nodular with T-cell-rich background, diffuse "moth-eaten" with B-cell-rich background as well as a
mixture of these patterns.  The characteristic immunophenotypic profile of the large
atypical cells in NLPHL in comparison to CHL is summarized in Table 1.
Table 1: Comparison of Immunohistologic Features of NLPHL and CHL
NLPHL can occur simultaneously with or progress to DLBCL and their clonal relationship has been well
documented in the literature.
The separation of NLPHL, particularly those with a
diffuse component, from T-cell-rich B-cell lymphoma (TCRBCL) can be extremely challenging. In addition,
NLPHL may also be difficult to distinguish from nodular lymphocyte-rich classical Hodgkin lymphoma
(NLRCHL) and T-cell lymphomas, particularly those complicated by secondary large B-cell proliferations
which are often associated with EBV.
|Marker ||NLPHL - L&H cells ||CHL - Hodgkin/RS cells|
|CD45 (LCA) ||+ ||-|
|CD20 ||+ ||+/-|
|CD30 ||-/+ ||+|
|CD15 ||- ||+|
|EBV ||- ||+|
|EMA ||+ ||-|
|CD57+ T-cells ||+ ||-|
The case selected for presentation was seen at Stanford over a period of approximately 30 years. The
initial diagnosis rendered in 1975 was based on morphologic evaluation of H&E sections. Two
subsequent lymph node biopsies showed no evidence of lymphoma. This case illustrates some of the
complexities involved in differentiating the histologic and immunoarchitectural features of NLPHL and the
overlap of these features with classical Hodgkin lymphoma, progressive transformation of germinal centers
and angioimmunoblastic and peripheral T-cell lymphomas. It is hoped that the recognition of the variant
immunoarchitectural patterns and progression of NLPHL will be diagnostically useful, permit better
understanding of the morphologic continuum from NLPHL to DLBCL and aid in the separation of NLPHL and its
progression from their morphologic mimics.
The patient is a 61-year old man who presented with a mesenteric mass. A 5.0 cm mesenteric lymph
node was excised. Approximately thirty years previously the patient had undergone a supraclavicular
lymph node biopsy and the diagnosis of nodular sclerosis classical Hodgkin lymphoma ("cellular phase")
was rendered for which he received chemotherapy and subtotal lymphoid irradiation. The patient had
undergone two subsequent lymph node biopsies at 4 and 13 years after his initial treatment. Both of
those biopsies had shown reactive follicular hyperplasia with progressive transformation of germinal
Case 1 - Slide 1
Case 1 - Figure 1 - Low magnification image showing that the lymph node architecture is effaced by a nodular lymphoid proliferation studded with scattered atypical large cells.
Case 1 - Figure 2 - Diffuse lymphoid infiltrate associated with sclerosis.
Case 1 - Figure 3 - Nodular and diffuse architecture with residual germinal centers.
Case 1 - Figure 4 - Scattered atypical large cells in a lymphocyte-rich background.
Case 1 - Figure 5 - High magnification image showing atypical large cells in a lymphocyte-rich background.
Case 1 - Figure 6 - CD20 - An immunostain for CD20 highlights B cell-rich nodules within which are atypical large CD20-positive cells.
Case 1 - Figure 7 - CD20 - An immunostain for CD20 highlights atypical large cells within and outside lymphoid nodules.
Case 1 - Figure 8 - CD21 - An immunostain for CD21 highlights dendritic meshworks imparting a nodular architecture.
The lymph node biopsies from 1975, 1979, 1988 and 2003 have
been reviewed and the salient findings are described below:
1975 Right supraclavicular lymph node: Sections show a moderately enlarged lymph node with a
nodular architecture without dense sclerotic bands. The nodules are composed of a mixed background rich
in small lymphocytes, histiocytes and plasma cells within which are variable numbers of atypical large
cells. These large cells show binucleation and prominent nucleoli typical of Reed-Stenberg (RS) cells
and mononuclear variants of RS cells. The morphologic findings are compatible with classical Hodgkin
lymphoma. The spleen was also involved at laparotomy (Stage IIISA).
1979 and 1988 Right and left inguinal lymph nodes : Sections of both inguinal lymph nodes
show enlargement and involvement by an exuberant reactive follicular hyperplasia. Occasional follicles
are markedly enlarged, have disrupted germinal centers and are infiltrated by small lymphocytes a
pattern typical of progressive transformation of germinal centers. These nodules did not exhibit
Hodgkin/RS cells or L&H cells.
2003 Mesenteric lymph node: Sections of the mesenteric lymph nodes show massive enlargement
and effacement of the normal nodal architecture by a mottled diffuse and partially nodular atypical
lymphoid proliferation. The large nodules are filled with an infiltrate of small lymphocytes admixed
with epithelioid histiocytes and are studded with atypical large cells exhibiting an open, vesicular
chromatin pattern and prominent single or multiple nucleoli. Rare large cells showed morphologic
features of classical Hodgkin cells. The atypical large cells were also present outside lymphoid
nodules. In the mottled areas, these atypical large cells formed clusters whilst focally there were
sheets of atypical large cells with numerous mitotic figures and karyorrhectic debris.
No immunohistologic studies were performed on the biopsies from 1975, 1979 and 1988. At the time of
the 2003 review a CD20 stain was performed on the 1975 case; the large cells were positive for CD20
indicating that the original diagnosis was most likely NLPHL and not classical Hodgkin lymphoma.
Immunohistologic features of the mesenteric lymph node biopsy from 2003 are summarized in Table 2.
Table 2: Immunohistologic Features of the Mesenteric Lymph Node Biopsy
|Immunostain ||L&H cells||Description|
|CD20 ||Positive ||Nodular areas: nodules rich in B-cells with scattered large atypical cells within and outside the nodules |
Mottled areas: scattered large atypical cells surrounded by CD20-negative small cells
Diffuse areas: sheets of large atypical cells
|CD3 ||Negative ||Nodular areas: few cells within nodules |
Mottled areas: majority of small cells and particularly those surrounding large atypical cells (ringing or rosetting pattern)
Diffuse areas: majority of small T-cells
|CD30 ||Negative ||Occasional scattered cells|
|CD15 ||Negative ||Occasional scattered cells|
|CD57 ||Negative ||Highlight cells ringing large atypical cells|
|EMA ||Positive ||Highlight large atypical cells (similar distribution to CD20)|
|PAX5 ||Positive ||Highlight large atypical cells (similar distribution to CD20)|
|EBV in situ ||Negative |
|CD45 ||Positive ||Highlight small lymphoid cells in nodular and diffuse areas and large atypical cells|
|CD21 ||Negative ||Nodular areas: intact follicular dendritic cell (FDC) meshworks|
Mottled areas: disruption or lack of FDC meshworks
Diffuse areas: scattered FDCs only
- Progressive transformation of germinal
- Nodular lymphocyte-rich classical Hodgkin lymphoma
- Angioimmunoblastic T cell lymphoma
- Peripheral T-cell lymphoma
complicated by a proliferation of large B-cells (B cell-rich T cell lymphoma)
- Nodular lymphocyte predominant Hodgkin lymphoma with progression to T cell-rich diffuse
large B-cell lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma with progression to T cell-rich diffuse large B-cell
The initial diagnosis of classical Hodgkin lymphoma was based
on the histologic findings on the right supraclavicular lymph node biopsy as well as the clinical
presentation. The patient had multiple sites of involvement including the spleen; an intravenous
pyelogram had also shown displacement of the right kidney from presumed para-aortic disease. He was
treated with MOPP chemotherapy and subtotal lymphoid irradiation and was without disease for
approximately 30 years, although he was at risk for developing a secondary malignancy, particularly a
non-Hodgkin lymphoma from his prior subtotal lymphoid irradiation. At presentation in 2003, he was
diagnosed with NLPHL with progression to TCRBCL. He had high risk disease based on the International
Prognostic Index (IPI) and was treated with RCHOP followed by consolidative high dose chemotherapy with
stem cell transplantation. He developed cardiomyopathy as a complication (probably due to subtotal
irradiation as well as transplantation) but has remained in complete remission since 2003.
The diagnosis of NLPHL can be made challenging by several factors: its intricate immunoarchitectural
patterns, its co-existence with florid follicular hyperplasia and progressive transformation of germinal
centers, its progression to T-cell rich B-cell lymphoma and diffuse large B-cell lymphoma both of which
may be focal and subtle, and its overlap with the histologic and immunophenotypic characteristics of
classical Hodgkin and T-cell lymphomas. The morphologic and immunophenotypic features of each entity
listed in the differential diagnosis are discussed below in the context of the index case.
Progressive transformation of germinal centers (PTGC )
- Follicular structures several times larger than
typically seen in reactive follicular hyperplasia
- Follicles composed of mantle zone B-cells with
significant numbers of CD4 T-cells that often co-express CD57
- Variably sized clusters of residual germinal center
cells without the presence of the L&H cells of NLPHL
- Typically occurs in isolated follicles in a
background of reactive follicular hyperplasia although PTGC may be more frequent in young males
- Most frequently presents as an incidental finding
(about 5% of reactive lymph nodes) may precede, occur simultaneously or follow a diagnosis of NLPHL
Table 3: Comparison of Histologic and Immunohistologic Features of PTGC and
The index case showed multiple enlarged B-cell rich nodules studded with L&H cells highlighted by
CD20 and ringed by CD57+ and CD3+ T-cells. In addition, there were mottled and diffuse areas with CD20+
large cells in a background rich in small T-cells. These features do not support PTGC as a diagnostic
consideration. However, the two prior inguinal lymph node biopsies excised in 1979 and 1988 showed
reactive follicular hyperplasia with features typical of progressive transformation of germinal centers.
| ||PTGC ||NLPHL|
|Low power ||Single large follicle ||Multiple large nodules (mass lesion)|
|High power ||Clusters of germinal center cells (can be highlighted by CD10, BCL6 or Ki-67) ||Rare germinal centers in the nodules in 15% of cases|
|CD20, CD79a, or PAX5 ||No L&H/"popcorn" cells ||L&H/"popcorn" cells|
|CD3 and CD57 ||No ringing of L&H cells but occasional macrophages may be ringed by T-cells ||Ringing of L&H/"popcorn" cells by T-cells|
Nodular Lymphocyte Rich Classical Hodgkin Lymphoma (NLRCHL)
- Comprise 5% of Hodgkin lymphoma (approximately the
same frequency as NLPHL) with a higher median age and a male predominance (also similar to NLPHL)
- Nodular or less commonly diffuse infiltrate of
small lymphocytes with an absence of eosinophils and neutrophils
- May have regressed germinal centers within nodules
- Small lymphocytes within nodules are mantle-zone
- A relatively uniform population of binucleate
classic Reed-Sternberg cells and their mononuclear counterparts both of which usually have prominent
eosinophilic nucleoli similar to other subtypes of CHL
- Immunophenotype of the atypical large cells is
similar to other subtypes of CHL: they express CD30, are usually also positive for CD15 and PAX5 with a
subset expressing CD20. They lack expression of CD45 (LCA) and T-cell associated markers
- Up to 40% of CHL have EBV-positive Hodgkin cells
The low power architecture of a lymph node involved by NLPHL and NLRCHL demonstrate several
similarities that include a nodular architecture usually devoid of sclerotic bands (typical of nodular
sclerosis Hodgkin lymphoma), eosinophils and neutrophils. The cell composition of the nodules is
predominated by small B cells and scattered atypical large cells. The Hodgkin/RS cells however differ
from L&H cells in their immunophenotype (please see Table 1 for comparison of immunohistologic
features of NLPHL and CHL). The index case showed CD20+ and CD45+ large atypical cells morphologically
typical of L&H cells. These cells were ringed by CD57+ CD3+ T-cells and lacked staining for CD30 and
CD15. In addition, the mottled and diffuse areas with increased small T-cells and CD20+ large cells
(indicative of progression), is not compatible with a diagnosis of classical Hodgkin lymphoma.
Angioimmunoblastic T-cell Lymphoma (AITL)
- Effacement of lymph node architecture by a diffuse
or paracortical expansion of immunoblasts, vascular proliferation and admixed eosinophils and plasma
- Expansion of extrafollicular CD21-positive FDC
- CXCL13+ and CD10+ T-cells away from follicles
- Clonal T cell receptor gene rearrangements
- Associated with EBV in 50% of cases
- Clonal B-cell proliferations found in 35% of
Table 4: Comparison of Histologic and Immunohistologic Features of AITL and
The nodular proliferation with mottled and diffuse areas seen in the index case may be
simulated by AITL, particularly an AITL complicated by a large B-cell proliferation. Both exhibit areas
with scattered or clustered atypical large B-cells. However, the paracortical immunoblastic T-cell
proliferation admixed with a mixed inflammatory background (eosinophils and plasma cells) together with
the prominent vascular proliferation and extrafollicular dendritic cells are not characteristic of NLPHL.
The lack of immunostaining for CXCL13 and CD10 on extrafollicular T-cells also exclude AITL as a
diagnostic possibility. In addition, T-cell receptor gene rearrangement studies may be used to confirm a
clonal T-cell proliferation in cases of AITL. In cases of AITL complicated by a secondary large B-cell
proliferation, EBV in situ hybridization studies typically highlight the atypical large B-cells. Clonal
studies for the B-cell antigen receptor (IgH VDJ gene rearrangements) may show a polyclonal, oligoclonal
or clonal pattern. EBV expression is extremely rare in cases of NLPHL.
| ||AITL ||NLPHL|
|Low power ||Nodular or diffuse paracortical proliferation ||Multiple large nodules (mass lesion)|
|High power ||Immunoblastic proliferation associated with prominent vasculature and admixed eosinophils and plasma cells ||Nodules rich in small B-cells|
|CD20, CD79a, or PAX5 ||No L&H/"popcorn" cells|
An associated proliferation of large B-cell may be present singly, in small clusters or as sheets of B-cells
Progression to T-cell rich or conventional diffuse large B-cell lymphoma may exhibit scattered or sheets-like proliferation of large B-cells
|CD3 ||Predominance of T-cells ||Paucity of T-cells within nodules although with increased diffuse areas the is a concomitant increase in reactive T-cells in the background|
|CD21 ||Extrafollicular expansions of follicular dendritic cell meshworks ||Typically intact FDC meshworks are confined to follicles although with progression to DLBCL disrupted and absence of meshworks may be present|
|EBV ||EBV-associated B-cell proliferations in up to 50% of cases ||Negative (very rare positive cases have been reported)|
Peripheral T-cell lymphoma complicated by a proliferation of large B-cells (B cell-rich T cell
- Effacement of lymph node architecture by a diffuse
or paracortical expansion of atypical T-cells admixed with eosinophils and plasma cells
- T-cells may have clear cytoplasm and exhibit
- Clonal T cell receptor gene rearrangements
- Associated with EBV in 57% of cases
- Clonal B-cell proliferations found in 35% of
This is a relatively newly recognized entity in which a peripheral T-cell lymphoma is found in close
association with an EBV-positive large B-cell proliferation. Similar to AITL it may simulate NLPHL
particular one that shows progression to TCRBCL. However, in contrast to AITL no extrafollicular
dendritic cells are present. Immunophenotypic and molecular studies (see Table 4), similar to those
employed in the separation of AITL from NLPHL (with the exceptions of CD21, CXCL13 and CD10 to
demonstrate extrafollicular dendritic and germinal center T-cells) are useful to distinguish this entity
from NLPHL with progression to TCRBCL.
Nodular Lymphocyte Predominant Hodgkin Lymphoma with progression to T-cell rich diffuse large
B-cell lymphoma (NLPHL with progression to TCRBCL)
Traditionally, NLPHL has been described as having a nodular growth pattern with or without a diffuse
component. In a study of 137 biopsies from 118 patients we previously described six distinct
immunoarchitectural patterns of NLPHL (Table 5).  A combination of two or more patterns was
more common than a pure pattern. The presence of a diffuse pattern was more common in patients with
recurrent disease and tended to be associated with progression to an increasingly more diffuse pattern
over time. Sequential biopsies also showed that those with increased extranodular L&H cells were
more likely to progress to TCRLBCL. Small germinal centers and prominent sclerosis, two features
previously associated with CHL, were found in 15% and 20% of NLPHL cases respectively, emphasizing that
these features cannot be reliably used to distinguish NLPHL from CHL.  The recognition of
these immunoarchitectural patterns as features of NLPHL is important for its accurate diagnosis and for
separation of NLPHL from CHL and TCRBCL.
Table 5: Immunoarchitectural Patterns of NLPHL
The immunoarchitectural pattern in the index case reflects a combination of the classical nodular
pattern in some areas whilst other areas show a diffuse TCRBCL-like as well as a mottled or "moth-eaten"
pattern. The extent of the nodular areas was variable and represented 10 - 80% in different sections
examined. Typical L&H cells were highlighted by the immunostain for CD20 and were present within and
outside nodules. They were surrounded by CD57+ T-cells is the nodular areas where intact FDC meshworks
were present (CD21 immunostain). However, in the mottled areas FDC meshworks were disrupted, the
background had increased numbers of T-cells and the L&H cells lacked ringing by CD57+ T-cells. The
presence of a diffuse pattern together with L&H cells outside nodules were found to be associated
with progression of disease in our prior study: these features were evident in this case. The lack of
staining of the atypical cells for CD30 and CD15 together with the areas of TCRBCL-like pattern made the
diagnosis of CHL unlikely. The lack of an atypical paracortical T-cell proliferation and prominent
vasculature make the diagnosis of a T-cell lymphoma less compelling. The TCRBCL-like component seen in
some areas of this case may however mimic secondary EBV-associated large B-cell proliferations arising in
the setting of AITL and PTCL.
|Pattern ||Architecture ||L&H cells ||FDC meshworks|
|1. "Classical" nodular pattern, B-cell-rich ||Nodules with predominance of small B-cells ||Largely confined to nodules and ringed by CD57+ T-cells ||Prominent FDC meshworks|
|2. Serpiginous/interconnected nodular pattern ||Misshapen nodules rich in small B-cells ||Largely confined to nodules and ringed by CD57+ T-cells ||Associated with FDC meshworks|
|3. Nodular with prominent extra-nodular L&H cells ||Background rich in reactive T-cells ||Extend outside nodules and lack ringing ||Lack FDC meshworks|
|4. Nodular with T-cell-rich background ||Nodules with increased T-cells ||Confined to nodules and ringed by CD57+ T-cells ||Associated with FDC meshworks|
|5. Diffuse pattern (T-cell-rich B-cell lymphoma-like) ||Indistinguishable from TCRBCL (requires nodular component elsewhere for diagnosis)||Lack ringing ||Lack FDC meshworks|
|6. Diffuse, "moth-eaten" with B-cell-rich background ||No distinct nodular architecture but has a B-cell rich background ||L&H cells are ringed by CD57+ T-cells - appear "moth eaten" on CD20 stain ||Associated with FDC meshworks|
The immunoarchitectural features of this case captures the morphologic continuum between NLPHL and
DLBCL and illustrates the complexity and overlap it shares with CHL and TCRBCL on one hand and with AITL
and PTCL complicated by large B-cell proliferations on the other. Additionally, the presentation with
NLPHL in this patient was preceded by PTGC on two prior lymph node excisions and occurred as a
therapy-related secondary malignancy approximately 30-years after the diagnosis and treatment for
presumed classical Hodgkin lymphoma.
Take Home Lessons
- If the lymph node architecture shows mixed
nodular and diffuse areas look for the presence and the distribution of atypical large cells and the
company they keep
- In an indolent lymphoma, look for an aggressive
- A relatively short panel of immunohistologic
markers (CD20, CD30, CD15, PAX5, CD45, EBV
) can be employed successfully to distinguish subtypes of
- A follicular dendritic cell marker (e.g. CD21)
can be very useful to highlight a nodular architecture
- Marafioti T, Hummel M, Anagnostopoulos I, et al. Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med. 1997;337:453-458.
- Ohno T, Stribley JA, Wu G, Hinrichs SH, Weisenburger DD, Chan WC. Clonality in nodular lymphocyte-predominant Hodgkin's disease. N Engl J Med. 1997;337:459-465.
- Miettinen M, Franssila KO, Saxen E. Hodgkin's disease, lymphocytic predominance nodular. Increased risk for subsequent non-Hodgkin's lymphomas. Cancer. 1983;51:2293-2300.
- Hansmann ML, Stein H, Fellbaum C, Hui PK, Parwaresch MR, Lennert K. Nodular paragranuloma can transform into high-grade malignant lymphoma of B type. Hum Pathol. 1989;20:1169-1175.
- Diehl V, Sextro M, Franklin J, et al. Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease. J Clin Oncol. 1999;17:776-783.
- Anagnostopoulos I, Hansmann ML, Franssila K, et al. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood. 2000;96:1889-1899.
- Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and genetics of tumors of the hematopoietic and lymphoid tissues. Lyon: IARC Press; 2001.
- Rudiger T, Gascoyne RD, Jaffe ES, et al. Workshop on the relationship between nodular lymphocyte predominant Hodgkin's lymphoma and T cell/histiocyte-rich B cell lymphoma. Ann Oncol. 2002;13 Suppl 1:44-51.
- Boudova L, Torlakovic E, Delabie J, et al. 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;102:3753-3758.
- Jost LM, Stahel RA. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of Hodgkin's disease. Ann Oncol. 2005;16 Suppl 1:i54-55.
- Nogova L, Rudiger T, Engert A. Biology, clinical course and management of nodular lymphocyte-predominant hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2006:266-272.
- Poppema S, Kaiserling E, Lennert K. Nodular paragranuloma and progressively transformed germinal centers. Ultrastructural and immunohistologic findings. Virchows Arch B Cell Pathol Incl Mol Pathol. 1979;31:211-225.
- Burns BF, Colby TV, Dorfman RF. Differential diagnostic features of nodular L & H Hodgkin's disease, including progressive transformation of germinal centers. Am J Surg Pathol. 1984;8:253-261.
- Nguyen PL, Ferry JA, Harris NL. Progressive transformation of germinal centers and nodular lymphocyte predominance Hodgkin's disease: a comparative immunohistochemical study. Am J Surg Pathol. 1999;23:27-33.
- Nicholas DS, Harris S, Wright DH. Lymphocyte predominance Hodgkin's disease--an immunohistochemical study. Histopathology. 1990;16:157-165.
- 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;27:1346-1356.
- Ekstrand BC, Lucas JB, Horwitz SM, et al. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood. 2003;101:4285-4289.
- Natkunam Y, Stanton TS, Warnke RA, Horning SJ. Durable remission in recurrent T-cell-rich B-cell lymphoma with the anti-CD20 antibody rituximab. Clin Lymphoma. 2001;2:185-187.
- Lukes RJ, Butler JJ. The pathology and nomenclature of Hodgkin's disease. Cancer Res. 1966;26:1063-1083.
- 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;12:599-606.
- Grossman DM, Hanson CA, Schnitzer B. Simultaneous lymphocyte predominant Hodgkin's disease and large-cell lymphoma. Am J Surg Pathol. 1991;15:668-676.
- Wickert RS, Weisenburger DD, Tierens A, Greiner TC, Chan WC. Clonal relationship between lymphocytic predominance Hodgkin's disease and concurrent or subsequent large-cell lymphoma of B lineage. Blood. 1995;86:2312-2320.
- De Jong D, Van Gorp J, Sie-Go D, Van Heerde P. T-cell rich b-cell non-hodgkin's lymphoma: a progressed form of follicle centre cell lymphoma and lymphocyte predominance hodgkin's disease. Histopathology. 1996;28:15-24.
- Greiner TC, Gascoyne RD, Anderson ME, et al. Nodular lymphocyte-predominant Hodgkin's disease associated with large-cell lymphoma: analysis of Ig gene rearrangements by V-J polymerase chain reaction. Blood. 1996;88:657-666.
- Chan WC. T-cell-rich B-cell lymphoma: what is new? What is cool? Am J Clin Pathol. 1997;108:489-491.
- Chang CC, Osipov V, Wheaton S, Tripp S, Perkins SL. Follicular hyperplasia, follicular lysis, and progressive transformation of germinal centers. A sequential spectrum of morphologic evolution in lymphoid hyperplasia. Am J Clin Pathol. 2003;120:322-326.
- 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;16:252-258.
- Hansmann ML, Fellbaum C, Hui PK, Moubayed P. Progressive transformation of germinal centers with and without association to Hodgkin's disease. Am J Clin Pathol. 1990;93:219-226.
- Jones D. Dismantling the germinal center: comparing the processes of transformation, regression, and fragmentation of the lymphoid follicle. Adv Anat Pathol. 2002;9:129-138.
- Kojima M, Nakamura S, Motoori T, et al. Progressive transformation of germinal centers: a clinicopathological study of 42 Japanese patients. Int J Surg Pathol. 2003;11:101-107.
- Osborne BM, Butler JJ. Clinical implications of progressive transformation of germinal centers. Am J Surg Pathol. 1984;8:725-733.
- Osborne BM, Butler JJ, Gresik MV. Progressive transformation of germinal centers: comparison of 23 pediatric patients to the adult population. Mod Pathol. 1992;5:135-140.
- Poppema S, Kaiserling E, Lennert K. Hodgkin's disease with lymphocytic predominance, nodular type (nodular paragranuloma) and progressively transformed germinal centres--a cytohistological study. Histopathology. 1979;3:295-308.
- Ashton-Key M, Thorpe PA, Allen JP, Isaacson PG. Follicular Hodgkin's disease. Am J Surg Pathol. 1995;19:1294-1299.
- Attygalle A, Al-Jehani R, Diss TC, et al. Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. Blood. 2002;99:627-633.
- Dogan A, Attygalle AD, Kyriakou C. Angioimmunoblastic T-cell lymphoma. Br J Haematol. 2003;121:681-691.
- Grogg KL, Attygale AD, Macon WR, Remstein ED, Kurtin PJ, Dogan A. Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified. Mod Pathol. 2006;19:1101-1107.
- Grogg KL, Attygalle AD, Macon WR, Remstein ED, Kurtin PJ, Dogan A. Angioimmunoblastic T-cell lymphoma: a neoplasm of germinal-center T-helper cells? Blood. 2005;106:1501-1502.
- Jones D, Jorgensen JL, Shahsafaei A, Dorfman DM. Characteristic proliferations of reticular and dendritic cells in angioimmunoblastic lymphoma. Am J Surg Pathol. 1998;22:956-964.
- Ree HJ, Kadin ME, Kikuchi M, et al. Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers. Am J Surg Pathol. 1998;22:643-655.
- Abruzzo LV, Schmidt K, Weiss LM, et al. B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus. Blood. 1993;82:241-246.
- Lome-Maldonado C, Canioni D, Hermine O, et al. Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein-Barr virus infection. A different subtype of AILD-TL? Leukemia. 2002;16:2134-2141.
- Reichard KK, Schwartz EJ, Higgins JP, Narasimhan B, Warnke RA, Natkunam Y. CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells. Mod Pathol. 2006;19:337-343.
- Troxell ML, Schwartz EJ, van de Rijn M, et al. Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma. Appl Immunohistochem Mol Morphol. 2005;13:297-303.
- Weiss LM, Jaffe ES, Liu XF, Chen YY, Shibata D, Medeiros LJ. Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Blood. 1992;79:1789-1795.
- Tan BT, Warnke RA, Arber DA. The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations. J Mol Diagn. 2006;8:466-475; quiz 527.
- Higgins JP, van de Rijn M, Jones CD, Zehnder JL, Warnke RA. Peripheral T-cell lymphoma complicated by a proliferation of large B cells. Am J Clin Pathol. 2000;114:236-247.