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CASE REPORT |
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| Ahead of print
publication |
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| Plasmablastic transformation of a double hit follicular lymphoma: An emerging entity |
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Shanaz Khodaiji1, Vidisha Mahajan1, Krishna Sawaimoon Satyakam1, Pratibha Sudhan Kadam Amare2
1 Department of Laboratory Medicine, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
2 Department of Cancer and Clinical Genetics, Lilac Insights Private Limited, Mumbai, Maharashtra, India
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| Date of Submission | 07-Sep-2021 |
| Date of Decision | 07-Jan-2022 |
| Date of Acceptance | 15-Jan-2022 |
| Date of Web Publication | 05-May-2023 |
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 Abstract | | |
Plasmablastic transformation of follicular lymphoma is very rare and has been reported in only 5 cases till date. We report a case of simultaneous identification of extranodal, soft tissue plasmablastic lymphoma in the ankle and bone marrow involvement by follicular lymphoma. This unusual case presentation is a challenge for the treating physician with the patient becoming resistant to chemotherapy and succumbing to the disease within a few months of diagnosis. These cases are known to have an aggressive clinical course with very poor prognosis and survival rate of less than 6 months. This report broadens the spectrum of morphological transformation of follicular lymphoma and it may represent a new category of high-grade transformation of follicular lymphoma.
Keywords: Double hit lymphoma, plasmablastic lymphoma, transformation
How to cite this URL:
Khodaiji S, Mahajan V, Satyakam KS, Kadam Amare PS. Plasmablastic transformation of a double hit follicular lymphoma: An emerging entity. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jun 1]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=375891 |
| Introduction | |  |
Follicular lymphoma is an indolent lymphoma, which often transforms into a high-grade lymphoma.[1] It progresses to diffuse large B cell lymphoma in 25%–35% of the cases.[1] Follicular lymphoma transforming to plasmablastic lymphoma or both the tumors presenting simultaneously at different sites have been reported only in 5 cases till date. We report a very rare case of simultaneous presentation of an extranodal plasmablastic lymphoma along with bone marrow involvement by a follicular lymphoma with a double hit genotype.
| Case Report | | |
A 44-year-old female presented to the OPD with a left ankle lesion. Positron emission tomography and computed tomography showed a 5.4 × 2.7 cm lesion in the left lower calf with similar nodules in the right leg and multiple osseous lesions. Small subcentimetric left inguinal and femoral lymph nodes were noted. The excisional biopsy of the ankle lesion revealed a soft tissue infiltrate by an atypical lymphoproliferative process composed of medium to large sized cells with a distinct plasmacytoid morphology. On immunohistochemistry (IHC), the tumor cells expressed LCA (focal and weak), CD38, and MUM-1 and were immunonegative for CD20, CD3, Alk-1, CD30, and CD19. These plasmacytoid cells showed kappa light chain restriction [Figure 1]. The Mib 1 labelling index was approximately 80%. In situ hybridization for Epstein Barr encoded RNA (EBER) was negative. The patient was reported to have a malignant round cell tumor favoring a plasmablastic lymphoma. In light of the multiple osseous lesions and presence of an extramedullary plasma cell neoplasm, bone marrow (BM) examination of the patient was performed. The BM aspirate revealed a normocellular bone marrow with 30% lymphocytes and only 1% plasma cells. The flow cytometric analysis of the aspirate revealed 16% clonal B lymphocytes expressing CD19, CD20, CD10, dim FMC7, and kappa restricted population. These cells were seen in the bright CD45 region and were negative for CD5, CD200, CD43, CD3, CD4, CD7, CD8, CD56, CD11c, CD25, CD103, and CD123. Fluorescence in situ hybridization (FISH) studies showed evidence of IGH/BCL2 t (14;18) in 30/200 cells. The BM biopsy revealed many paratrabecular lymphoid aggregates marking for CD20 on IHC suggestive of bone marrow involvement by follicular lymphoma [Figure 2]. | Figure 1: (a) to (d) Histological findings of sections from ankle lesion biopsy. (a) (H and E, 100×) and (b) (H and E, 400×) Sheets of plasmacytoid neoplastic cells. (c) and (d) Immunohistochemical staining shows that the tumor cells mark for CD138 [(c), 400×] and kappa light chain [(d), 400×]
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 | Figure 2: (a) and (b) Histological sections of the bone marrow biopsy. (a) (H and E, 100×) Marrow spaces with interstitial excess of lymphocytes. (b) On immunohistochemical staining CD20 highlighted these lymphocytes (100×)
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She was started on rituximab, cyclophosphamide, doxorubicin hydrochloride, and vincristine along with bortezomib and dexamethasone for 4 cycles.
After a month of initiation of therapy, the patient was admitted in the emergency with nausea, poor oral intake, and reduced urine output. The CBC of the patient revealed a WBC count of 232 × 109/L. The creatinine of the patient was 7.9 mg/dL (NR-0.5–1.06), uric acid 22 mg/dL (NR-2.4–5.7) with a K + of 4.3 mE/L (NR-3.3–4.8). The patient was diagnosed with tumor lysis syndrome. The peripheral blood examination revealed 90% atypical lymphoid cells with occasional cell showing nuclear cleaving [Figure 4]a. The flow cytometric analysis of the peripheral blood showed a cell cluster in the lymphocyte region (95% of all viable cells) falling in the medium to large size range expressing CD19, CD20, CD10, heterogeneous CD38, and FMC-7 and showed kappa restriction. These lymphoid cells were negative for CD5, CD3, CD4, CD8, CD56, and lambda light chain [Figure 3]. The patient's sample sent for FISH studies showed evidence of c -MYC (8q24) translocation in 22/200 cells and IGH/BCL2 t (14;18) translocation in 26/200. The association of IGH/BCL2 and c-MYC translocation was indicative of double hit lymphoma [Figure 4]b. The patient was given salvage chemotherapy but succumbed to the disease in a month's time. | Figure 3: Immunophenotypic findings of the peripheral blood showing a population of atypical lymphoid cells (red), 95% of all viable cells, expressing CD19, CD20, CD10, and kappa restriction
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 | Figure 4: (a) Peripheral blood shows large, atypical lymphoid cells. Occasional lymphoid cell reveals nuclear cleaving (red arrow). (b) FISH studies reveal the presence of both IGH/BCL2 (yellow arrows) and MYC translocation
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| Discussion | | |
Plasmablastic lymphomas are aggressive neoplasms associated with immunodeficiency and Epstein Barr Virus (EBV) infection. A plasmablastic lymphoma generally marks for CD138, CD38 and is clonal for one of the light chains. The lymphoma cells are generally negative for CD20 and PAX5.[2] Transformation of follicular lymphoma to plasmablastic lymphoma is rare. Till date only 5 cases of follicular lymphoma transformed to plasmablastic lymphoma have been reported.[3],[4],[5] In the absence of the genetic work up of the plasmablastic tumor in our case, the possibility of coexistence of the tumors cannot be ruled out. All the above cases have been reported in immunocompetent individuals and are EBV negative as seen in our case.
Martinez et al.[6] reported a series of 6 cases of plasmablastic transformation seen in low-grade lymphoma of which 3 cases were of follicular lymphoma and 3 cases were of chronic lymphocytic leukemia (CLL). In 2 out of 3 follicular lymphoma cases, plasmablastic lymphoma in the extranodal region was detected at the same time as in our case where diagnosis of BM involvement by follicular lymphoma and plasmablastic lymphoma in the ankle was made at the same time. Both the tumors were clonal and expressed the kappa light chain.
Lymphomas with c-MYC along with BCL2 and/or BCL6 rearrangements have been categorized as double hit lymphomas in the 2016 World Health Organization. They are characterized by an aggressive course.[1] The leukemic phase of the tumor in this case showed a double hit genotype with the coexistence of IGH/BCL2 and c-MYC. Follicular lymphoma undergoing transformation generally retain IGH/BCL2 rearrangement and develop subsequent secondary genetic abnormalities, which are significant for the progression of the disease. The common genetic alterations seen in transformed follicular lymphoma are inactivation of CDKN 2A and CDKN 2B genes, TP53 gene mutations, and downregulation of the c-MYC gene.[6]
C-MYC translocations are seen in 41%–49% of plasmablastic Lymphoma cases. Plasmablastic lymphoma transformed from CLL or from follicular lymphoma shows the presence of c-MYC translocations.[6] Of the 5 cases transformed follicular lymphoma reported in literature, c-MYC translocation was seen only in 2 cases in the plasmablastic component. Additional molecular studies could not be conducted on the plasmablastic component of the tumor because of financial constraints.
In summary, we report an unusual case of simultaneous occurrence of follicular lymphoma in the BM and a soft tissue plasmablastic lymphoma. The above case broadens the spectrum of histologic transformation or coexistence of the two lymphomas and highlights the need of pathologists to be aware that the 2 tumors can be seen concurrently. The gain of the c-MYC gene rearrangement was seen in the leukemic phase of the tumor. Additional molecular studies are needed to diagnose and treat rare tumors with unusual clinical presentation and aberrant genotypes to improve outcomes in similar cases.
Acknowledgements
We would like to thank Dr Sachin Almel for his support and clinical input in the case.
Data availability statement
The data that supports the findings of this study are available from the corresponding author upon reasonable request.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.  |
| 2. | Teruya-Feldstein J. Diffuse large B-cell lymphomas with plasmablastic differentiation. Curr Oncol Rep 2005;7:357-63. |
| 3. | Ouansafi I, He B, Fraser C, Nie K, Mathew S, Bhanji R, et al. Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement. Am J Clin Pathol 2010;134:972-81. |
| 4. | Martinez D, Valera A, Perez NS, Sua Villegas LF, Gonzalez- Farre B, Sole C, et al. Plasmablastic transformation of low-grade B-cell lymphomas. Am J Surg Pathol 2013;37:272-81. |
| 5. | Ise M, Kageyama H, Ikebe D, Araki A, Kumagai K, Itami M. Transformation of double-hit follicular lymphoma to plasmablastic lymphoma: A partial role of MYC gene rearrangement. J Clin Exp Hematop 2018;58:128-35. |
| 6. | Cai Q, Medeiros LJ, Xu X, Young KH. MYC-driven aggressive B-cell lymphomas: Biology, entity, differential diagnosis and clinical management. Oncotarget 2015;6:38591-616. |
Correspondence Address:
Vidisha Mahajan,
S-1 building, P. D. Hinduja Hospital and Medical Research Centre, Mahim, Mumbai - 400 016, Maharashtra
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_898_21
[Figure 1], [Figure 2], [Figure 3], [Figure 4] |
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