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Year : 2020  |  Volume : 63  |  Issue : 3  |  Page : 503-505
High-grade transformation in nodular lymphocyte predominant Hodgkin lymphoma

1 Department of Pathology, Homi Bhabha Cancer Hospital and Research Center, Visakhapatnam, Andhra Pradesh, India
2 Department of Medical Oncology, Homi Bhabha Cancer Hospital and Research Center, Visakhapatnam, Andhra Pradesh, India
3 Department of Radiology, Homi Bhabha Cancer Hospital and Research Center, Visakhapatnam, Andhra Pradesh, India
4 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India

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Date of Submission03-Jun-2018
Date of Decision29-Aug-2018
Date of Acceptance10-Sep-2018
Date of Web Publication7-Aug-2020

How to cite this article:
Nayak SS, Parthiban SK, Paul P, Gujral S. High-grade transformation in nodular lymphocyte predominant Hodgkin lymphoma. Indian J Pathol Microbiol 2020;63:503-5

How to cite this URL:
Nayak SS, Parthiban SK, Paul P, Gujral S. High-grade transformation in nodular lymphocyte predominant Hodgkin lymphoma. Indian J Pathol Microbiol [serial online] 2020 [cited 2022 Nov 27];63:503-5. Available from:

Dear Editor,

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has distinct immunologic, genetic differences and prognostic implications, hence was separated from the entity of Hodgkin lymphoma. It represents approximately 3%–5% subtype of Hodgkin lymphoma.[1] Although known for its early-stage presentation and indolent behavior, it often has shown late relapses. Transformation to high-grade lymphoma, diffuse large B-cell lymphoma (DLBCL) being the most common subtype, is higher in NLPHL when compared with classical Hodgkin lymphoma (cHL).[2] Here, we present one such unique case of recurrent NLPHL transforming to a high-grade lymphoma at recurrence.

A 29-year-old gentleman was diagnosed on fine-needle aspiration cytology to have Hodgkin lymphoma in 2009. Biopsy of the lesion was not carried out, and radiological evaluation revealed stage I disease. He was then treated with involved field radiation therapy. After a disease-free interval of 8 years, he presented with multiple nonbulky cervical lymph nodes. He was started on ABVD protocol elsewhere. After three cycles of chemotherapy, the patient noticed new nodules over the anterior chest wall. He defaulted further chemotherapy and presented to us after 4 months. At this time, on clinical examination, he had bilateral nonbulky multiple cervical node, with an ulcerating growth over the manubrium sterni. Radiological evaluation revealed a pleura-based mass along the apex of right lung, confirming stage IV disease [Figure 1]. Biopsy of the pleura-based lesion along with excision of cervical lymph node was done. On microscopy, the lymph node showed effacement of nodal architecture by nodular aggregates of atypical lymphoid cells. Within them were clusters of large cells resembling Reed–Sternberg cells (L&H cells) [Figure 2]a. Immunohistochemistry showed the L&H cells to be positive for CD45, PAX-5, and CD20 [Figure 2]b, and negative for CD30, CD15, and CD3. These cells were not only present as aggregates within the nodules but also seen infiltrating into the interfollicular areas. The CD3 highlighted the T-lymphocytes, few of which were seen rosetting around the L&H cells [Figure 2]b inset]. With this, a diagnosis of NLPHL was made. The pleura-based lesion showed a similar morphological picture with many large mononuclear lymphoid cells in a background rich in polymorphs, lymphocytes, and histiocytes [Figure 2]c. Areas of necrosis were also noted within the tissue cores. On immunohistochemistry, the large cells were positive for PAX5, CD20, and CD30 [Figure 2]c inset], and negative for CD15 and ALK1. MIB-1 was expressed in all the large cells [Figure 2]d, bringing to the diagnosis of T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL). With this, a final diagnosis of concurrent T/HRBCL and relapsed NLPHL, with the former most likely representing a progression of the disease, was made. The patient was planned for salvage chemotherapy followed by autologous hematopoietic stem-cell transplant. He was started on rituximab + gemcitabine, dexamethasone + platinum (R-GDP). His tolerance to chemotherapy was good, and after three cycles of R-GDP, he achieved complete clinical response (CR). He was unwilling for transplant, and hence the patient was advised to continue up to six cycles of chemotherapy. With a follow-up period of 4 months post chemotherapy, he still continues to remain in complete CR.
Figure 1: Chest radiograph showing homogeneous mass-like opacity in upper zone of right lung

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Figure 2: (a) H&E (×400 magnification) cervical lymph node highlighting the L&H cells. (b) CD20 highlighting the L&H cells within the secondary follicle (×400 magnification). Inset highlights the CD3-positive T-cell rosettes around the L&H cells. (c) H&E (×400 magnification) pleura biopsy. Inset highlights the CD30-positive large cells. (d) High MIB-1 labeling index on the pleura biopsy (×100 magnification)

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In 1979, Poppema et al. published a series of three articles on histology, immunophenotype, and epidemiology of nodular and diffuse lymphocyte predominanant subtype of Hodgkin's disease, where they indicated NLPHL as a separate entity and first documented case of transition to DLBCL.[3],[4],[5] Carbone et al.[6] have also described the terminologies of “in situ NLPHL,” “non-invasive NLPHL,” “early invasive NLPHL,” and “frankly invasive NLPHL.” The later relates to “nodular with prominent extranodular L&H cells” originally described by Fan et al.[7] Our case also represents similar morphologic pattern of presentation with L&H cells infiltrating beyond the nodules into the interfollicular areas. However, whether this histological pattern can previously determine a transformation to a high-grade lymphoma is still questionable. Transformation to high grade lymphoma suggests an existence of clonal relationship with lymphocyte predominant cells (LP cells). The entity of T/HRBCL, a subtype of DLBCL, is considered as an extreme end of the morphologic spectrum of NLPHL, which when present should completely lack the nodular aggregates of L&H cells. They usually present as high-stage disease, predominantly nodal; however, extranodal involvement is also seen.

The risk factors for transformation include splenic involvement at the time of NLPHL and use of prior chemotherapy. Our patient had received localized irradiation 8 years ago and recent partial ABVD therapy which are unlikely to represent major risk factors for his transformation. Kenderian et al.[1] analyzed the cases of NLPHL from Mayo Clinic Lymphoma Database and showed a transformation to DLBCL in approximately 7.6%. The median age at transformation was 45 years, but our patient transformed early with an advanced disease at an age of 29 years. The BCCA Database reported a histological transformation of 14% at a median time of 8.1 years to 30% at 20 years, whereas Mayo Clinic Database shows a 7.6% transformation in lesser time frame of 35 months.[1],[8] Our patient had relapsed after a time frame of 8 years with of large-cell lymphoma component in pleural mass and NLPHL in cervical lymph node.

Treatment of relapsed NLPHL has no standard guidelines. Kenderian et al.[1] highlighted the regimens practiced over a span of four decades from the Mayo Clinic database which were R-CHOP, RICE, and R-DHAP. Our patient was treated with R-GDP in view of already-exposed anthracycline therapy.

The outcomes of transformed lymphoma are shown to be similar to nontransformed patients with the exposure of rituximab in Mayo series, and the overall response rate to chemotherapy was 94%. The median disease-free survival after transformation was 87 months, and the median overall survival was 18.8 years.[1]

With this case, we wanted to highlight the immunologic, genetic, and prognostic distinctiveness of NLPHL from cHL, bearing a higher propensity of transformation to a high-grade lymphoma.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Kenderian SS, Habermann TM, Macon WR, Ristow KM, Ansell SM, Colgan JP, et al. Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution. Blood 2016;127:1960-6.  Back to cited text no. 1
Advani RH, Hoppe RT. How I treat nodular lymphocyte predominant Hodgkin lymphoma. Blood 2013;122:4182-8.  Back to cited text no. 2
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(4):295–308.  Back to cited text no. 3
Poppema S, Kaiserling E, Lennert K. Epidemiology of nodular paragranuloma (Hodgkin's disease with lymphocytic predominance, nodular). J Cancer Res Clin Oncol 1979 Sep; 95(1):57–63.  Back to cited text no. 4
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(3):211–25.  Back to cited text no. 5
Carbone A, Spina M, Gloghini A, Ponzoni M, Doglioni C, Tirelli U, et al. Nodular lymphocyte predominant Hodgkin lymphoma with non-invasive or early invasive growth pattern suggests an early step of the disease with a highly favorable outcome. Am J Hematol 2013;88:161-2.  Back to cited text no. 6
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;27:1346-56.  Back to cited text no. 7
Al-Mansour M, Connors JM, Gascoyne RD, Skinnider B, Savage KJ. Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin's lymphoma. J Clin Oncol 2010;28:793-9.  Back to cited text no. 8

Correspondence Address:
Sonali Susmita Nayak
Department of Pathology, Homi Bhabha Cancer Hospital and Research Center, Visakhapatnam - 530 053, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_343_18

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