 Abstract | | |
Interfollicular Hodgkin's lymphoma (IFHL) is a rare pattern of classical Hodgkin's lymphoma (CHL) showing reactive follicular hyperplasia with involvement of the interfollicular area by HL. Two cases are reported in this study having primary IFHL out of total of 500 cases of CHL reported at our center. Diagnosis of IFHL was made on the basis of morphological and immunohistochemical features. As they represent an early stage of the disease, their identification and awareness s very important to get proper treatment at its earliest. This variant is very unusual and is diagnostically challenging for pathologists.
Keywords: Hodgkin's, immunohistochemistry, interfollicular, lymphoma
| Introduction | |  |
Interfollicular Hodgkin's lymphoma (IFHL) is a rare pattern of classical Hodgkin's lymphoma (CHL) showing reactive follicular hyperplasia with involvement of the interfollicular (IF) area by HL. CHL is divided into four subtypes morphologically. Isolated interfollicular involvement is a morphological variant of mixed cellularity CHL but not a separate subtype.[1] This variant is very unusual and is diagnostically challenging for pathologists. As they represent an early stage of the disease, their identification and awareness very important to get proper treatment at it are earliest. The present study reports two cases of IFHL presented in a two-year period in our center.
| Case Report | | |
In our two-year experience in a cancer center, only two cases were reported having primary IFHL out of total of 500 cases of CHL reported at our center.
Case 1
A 37-year-old female presented with right cervical lymphadenopathy for three months in the medical oncology outpatient department. No B symptoms were there. Her hematological workup showed mild anemia. No other abnormality was detected. Radiological workup shows enlarged right cervical lymph nodes with hypo-dense architecture. No hepatosplenomegaly was seen. A lymph node excision biopsy was done which showed partially effaced lymph nodal architecture [Figure 1]a with IF region showing typical mono and binucleated cells having large sizes and prominent nucleoli [Figure 1]b. The background showed a mixed population of inflammatory cells including eosinophils, lymphocytes, and plasma cells. These atypical cells were immunopositive for CD15, CD30 (membranous and Golgi zone positivity) [Figure 1]c, and PAX 5 (dim positive). CD3 and CD 20[Figure 1]d were negative in these cells. BCl2 was negative in reactive follicles [Figure 1]d. | Figure 1: (a)- H/E (40X) stained sections showing partially effaced LN architecture with presence of germinal centres (case 1).(b)- H/E (400X) stained sections showing atypical mono (Hodgkins cells) and binucleated cells (RS cells) in a polymorphous backgroundin IF area (case 1).(c)- CD30 (400X) showing positivity in atypical mono and binucleated cells (case 1).(d)- Bcl2 (40X) showing absence in germinal centreshence confirming maintained architecture of lymph node (case 1)
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Hence, a final diagnosis of IFHL was made on the basis of morphological and immunohistochemical features.
Case 2
A 53-year-old female presented with a right single cervical lymph node for two months along with long-standing low grade fever. No other peripheral lymphadenopathy was detected. Here, hematological and biochemical workup was within normal limits. Radiological investigations were not performed. The lymph node was then excised and sent for pathological examination. The grossly cut surface of the enlarged lymph node was grey-white homogenous. Microscopically, architecture was preserved with the presence of follicles with germinal centers, however, interfollicular area was expanded. A careful search of this region showed many eosinophils, and plasma cells along with a few atypical cells having prominent nucleoli [Figure 2]a. Again IHC showed a similar profile in the first case [Figure 2]b. Hence it was also diagnosed as IFHL. | Figure 2: (a)- H/E (400X) stained sections showing atypical mono (Hodgkins cells) and binucleated cells (RS cells) in a polymorphous background in IF area (case 2). (b)- CD30 (400X) showing positivity in atypical mono and binucleated cells (case 2)
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| Discussion | | |
Classical HL is divided into four subtypes—mixed cellularity, lymphocyte depleted, lymphocyte predominant, and nodular sclerosis. Interfollicular HL is an unusual variant of the mixed cellularity type of CHL. The reported prevalence ranged from 1.3% to 18%. Dogget et al.[1] reported first case with this pattern in literature.
In the literature, males have been reported to be more affected by this disease while in the present study both cases were females. No clinical significance can be predicted in this setting.[2]
It is often mistaken for reactive lymph node hyperplasia. Morphologically there is the proliferation of RS cells in the interfollicular area in a background of chronic inflammatory cells while follicles are maintained architecturally and show reactive hyperplasia. The biggest clue to the diagnosis comes from the expansion of the IF area and long-standing clinical history.[3] Also here lies the importance of granulomas in IF areas which should alert pathologists to search for RS cells.[4]
IF areas are the earliest areas of LN which get involved by HL. Also, the chemical mediators like IL-6 released by RS cells are responsible for the polymorphous chronic inflammatory background as well as reactive hyperplasia of follicles.[5] Many times lymph node shows only partial/focal involvement by HL which can be easily skipped during routine diagnosis and will delay the treatment of the patient.[6] Hence pathologists should be well aware of this knowledge.
Another important differential is reactive lymphadenitis with immunoblastic proliferation in the IF area. In this type of lymphadenitis, there is the preservation of lymph node architecture along with perifollicular epitheloid cells, eosinophils, and immunoblasts in the interfollicular area. These immunoblasts can mimic RS cells but can be differentiated on the basis of IHC.[7]
Castleman's disease can also cause a diagnostic dilemmas as it mimics its architecture to IFHL. Also, it can coexist with IFHL which can also cause great diagnostic difficulty. So it should be well remembered about this coexistence as Castleman's disease can suppress the features of IFHL.[8] A careful search for RS cells in the interfollicular area is to be done. Also, many cases which have been reported previously as plasma cell-rich variants of Castleman's disease turned out to be IFHL on the basis of IHC studies.
Some studies of differential diagnosis with peripheral T cell lymphoma (PTCL) have also been reported. PTCL-TBX 21 subtype is associated with polymorphous inflammatory background and is an important differential to IFHL but derangement of architecture and use of IHC and other ancillary techniques help reach the correct diagnosis.[9]
Viral lymphadenitis secondary to EBV and CMV virus infections shows atypical large lymphoid cells mimicking RS cells along with the presence of epitheloid cells, eosinophils, and immunoblasts in the interfollicular area. However, no typical RS cells can be found. However, RS cells show positivity to CD15, and CD30 while negative for CD45 almost in all cases and the large lymphoid cells in viral infections are immunoblasts with CD20 and LCA positivity.[10] Hence the careful search for RS cells and use of IHC is essential in differentiating these cases from IFHL.
| Conclusion | | |
Very few cases of IFHL have been reported in the literature and its prognostic significance is still debatable. However, its awareness is very important for correct diagnosis at an early stage. So recognition of this rare pattern in the apparent reactive lymph nodes is very important to avoid misdiagnosis and to get proper and early treatment.
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 5. | Poppema S, Potters M, Emens R, Visser L, van Berg A. Immune reactions in classical Hodgkin's lymphoma. Semin Haematol 1999;36:253-9. |
| 6. | Parihar LS, Gupta N, Kulhari S. Interfollicular Hodgkin's lymphoma –A case report. J Med Sci Clin Res 2017;5:20790-2. |
| 7. | Fellbaum CH, Hansmann ML, Lennert K. Lymphadenitis mimicking Hodgkin's disease. Histopathology 1988;12:253-62. |
| 8. | Zanetto U, Pagani FP, Pérez C. Interfollicular Hodgkin's lymphoma and Castleman's disease. Histopathology 2006;48:317-9. |
| 9. | Banks PM. The distinction of Hodgkin's disease from T-cell Lymphoma. Semin Diagn Pathol 1992;9:273-83. |
| 10. | Basu D, Roy S. Interfollicular Hodgkin's disease: An uncommon pattern that may cause diagnostic difficulty. Indian J Pathol Microbiol 2006;49:221-5. [ PUBMED] |
Correspondence Address:
Neha Sethi,
Department of Oncopathology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_641_22
[Figure 1], [Figure 2] |
