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CASE REPORT Table of Contents  
Ahead of print publication
Primary sacral activated B-Cell like diffuse large B-Cell lymphoma, triple expressor type: A case report with literature review


1 Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
2 Department of Neurosurgery, Kalinga Hospital, Bhubaneswar, Odisha, India
3 Department of Pathology, Kalinga Hospital, Bhubaneswar, Odisha, India

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Date of Submission18-Jul-2022
Date of Acceptance17-Sep-2022
Date of Web Publication01-Dec-2022
 

  Abstract 


Primary bone lymphomas are unusual, and accounts for 2% among all lymphomas. Primary sacral lymphomas are still rarer with only 12 cases reported till date. They predominantly affect elderly males, showing occasional spinal epidural space involvement. We report a case of 49-year-old male complaining of low backache and radicular pain for 2 months, followed by the development of parasthesia and bladder and bowel involvement. Lumbosacral spine magnetic resonance imaging revealed an expansile lytic lesion of approximately 6.5 cm with enhanced soft-tissue component extending to neural foramina compressing the spinal cord. Biopsy showed non-Hodgkin's lymphoma showing CD20, B-cell lymphoma (BCL) 6, BCL2, Multiple myeloma (MM) antigen 1 (MUM 1), and Cellular myelocytomatosis oncogene (C-Myc) positivity with CD10 negativity. Thus, the diagnosis of diffuse large B-cell lymphoma (DLBL)-activated B-cell type was rendered. Thirty cases of CD10-negative DLBL with Myc translocation in bone have been found which occur predominantly in Asians. Sacral primary DLBL with Myc translocation is extremely rare, only two cases are reported till date to the best of our knowledge. Because of its rarity, the prognosis and treatment of this entity are still not clear.

Keywords: C-Myc translocation, diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, postgerminal center type, sacrum


How to cite this URL:
Mohapatra D, Tripathy P, Mohanty S, Pal A. Primary sacral activated B-Cell like diffuse large B-Cell lymphoma, triple expressor type: A case report with literature review. J Microsc Ultrastruct [Epub ahead of print] [cited 2023 Feb 8]. Available from: https://www.jmau.org/preprintarticle.asp?id=362492





  Introduction Top


Primary bone lymphoma (PBL) is uncommon, accounting for 2% of all lymphomas in adults, the predominant location being the femur followed by other bones of extremities.[1] Spinal vertebra is an unusual site of non-Hodgkin's lymphoma (NHL), the most common being thoracic, followed by the lumbar and cervical vertebra.[2] Sacral vertebra is the least expected site of NHL, only 12 cases have been reported till date in literature as per our knowledge.[1] The following criteria have to be fulfilled to consider a tumor as PBL.

  1. Single skeletal site without/with regional lymph node involvement
  2. Multiple skeletal sites without visceral and lymph node involvement.[1] The radiographic appearance of primary NHL varies widely, osteolytic lesion being the most common type showing a moth-eaten pattern of bone destruction, followed by the osteosclerotic or rarely mixed type.[3] The tumor usually arises in the medullary cavity and spreads to the cortex and soft tissue. Epidural space involvement is unusually seen in 0.6%–2.2% of cases.[3] An initial clinical phase presented by low back ache without/with radicular pain to the legs for several months to 1 year followed by a second phase of spinal cord compression with development of the cauda equina syndrome in 2–8 weeks after the cord compression syndrome occurs.[3] The most common type of bone lymphoma is diffuse large B-cell lymphoma (DLBL) following Burkitt lymphoma. DLBL with double expressor type/hit or triple expressor type/hit type is extremely rare. Two reports of DLBL, triple expressor type, have been found in sacrum till date to the best of our knowledge.[4]



  Case Report Top


A 49-year-old male came to the outpatient department of neurosurgery with low back ache with radicular pain for the past 2 months. No bowel and bladder problem was associated. He was evaluated outside with magnetic resonance imaging (MRI) lumbosacral spine with contrast revealed large expansile lytic lesion in S1 and S2 vertebrae. This included posterior elements with an associated enhancing soft-tissue component along bilateral S1/2, S2/3 neural foramina, lumbar canal, and compressing cauda equina. The radiologic impression was metastasis/chordoma. Gradually, he developed weakness in his right foot along with bowel and bladder problems.

There was no fever, lymphadenopathy, or hepatosplenomegaly. Informed written consent was obtained from the patient. He was planned for surgery L5-S1 laminectomy, partial S1 sacrectomy, near total decompression of mass, and deroofing. Squash cytology was done which showed a few round cells arranged diffusely with a moderate amount of cytoplasm. Few cartilage elements simulating physaliphorous cells were also seen. Thus, the diagnosis was suggestive of chordoma. The gross received was multiple pieces of bony and soft tissue together measuring 7 cm × 2.5 cm × 1.5 cm. The microsections showed a tumor comprised neoplastic round cells which were large-sized, showing conspicuous nucleoli, brisk mitosis (>4/high-power field), and were arranged in nests, sheets, and diffusely [Figure 1]. Focal perivascular condensation, karyorrhectic debris, and bone and skeletal muscle infiltration were seen [Figure 2]. With this, histopathological suggestions and differentials were NHL and malignant germ cell tumor. The panel of immunohistochemistry was done which showed positivity of leukocyte common antigen (LCA) [Figure 3]a, CD20 [Figure 3]b, MUM 1 [Figure 3]d, B-cell lymphoma (BCL) 6 [Figure 4]a, BCL2 (>50%) [Figure 4]b, and C-Myc (>40%) [Figure 4]c, whereas CD3, CD5, CD10 [Figure 3]c, CD138, and Sal-like protein 4 (SALL-4) were negative. The Ki67 level was 80% [Figure 4]d. The histopathology features and immunohistochemistry findings showed features consistent with DLBL, activated B-cell-like (ABC) type with triple expressor status (positive Bcl2, Bcl6, and C-Myc). The molecular study for knowing the triple hit status was advised.
Figure 1: HP view showing neoplastic lymphoid cells, showing large cells, conspicuous nucleoli, increased mitosis (>5/HPF) arranged diffusely (H and E × 400). HPF: High-power field

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Figure 2: Microsection shows neoplastic lymphoid cells infiltrating the bone (blue arrow) and osteoclast giant cells (black arrow) (H and E ×400)

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Figure 3: (a) LCA shows diffuse cytoplasmic membrane positivity (× 400), (b) CD20 shows diffuse cytoplasmic membrane positivity (× 400), (c) CD10 shows negative cytoplasmic membrane (× 400), (d) MUM1 shows diffuse nuclear positive (× 400). LCA: Leukocyte common antigen

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Figure 4: (a) BCL6 shows positive nuclear staining (× 400), (b) BCL2 shows more than 50% perinuclear positivity (× 400), (c) C-Myc shows more than 40% nuclear positivity (× 400), (d) Ki67 shows 80% nuclear positivity (× 400). BCL: B-cell lymphoma

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  Discussion Top


Sacral neoplasms are rare, accounting 1%–2% of all musculoskeletal tumors. They are categorized as primary and metastatic tumors, the primary being either benign/malignant. The most common primary sacral tumor is chordoma, followed by Ewing's sarcoma, multiple myeloma, osteosarcoma, neurofibrosarcoma, chondrosarcoma, and angiosarcoma.[5] PBLs are unusual in the sacrum and only 12 cases of DLBL have been reported till date which occurs in the age group of middle to elderly.[1] The predominance of males with a common clinical triad of back pain, lower limb weakness, and bladder/bowel involvement is seen.[2] Usual type B symptoms such as fever, sweating, and loss of weight are usually not encountered.

The most common finding in imaging is osteolytic bone destruction encountered with a moth-eaten appearance in bone X-Ray.[3] MRI findings in usual T1-weighted images show low signal intensity and as high signal intensity in T2-weighted images, which is also encountered in sacral chordoma/chondrosarcoma but are differentiated by the presence of calcified specks.[1] Fluorodeoxyglucose -positron emission tomography (FDG-PET) is a useful investigation in differentiating multiple myeloma, a common entity in vertebra from malignant lymphoma where no tracer uptake is seen in multiple myeloma showing a cold spot. It is also helpful for staging purposes and treatment evaluation.[1]

Controversy exists about the origin of primary epidural NHL. Rubinstein documented that epidural tissue contains lymphoid cells and antigenic stimulation with transformation leads to lymphoma.[2] However, other authors opine that these tumors origin from vertebral space through intervertebral foramina,[2] which was found in our study.

There are two different phases in the clinical course of sacral NHL with spinal epidural involvement, a prodromal phase showing backache with or without radicular pain and a later phase of spinal cord compression with cauda equina syndrome and 2 to 8 weeks of cord compression, which show bladder and bowel involvement.[3]

The differential diagnosis includes chordoma, small cell osteosarcoma, Ewing's sarcoma, and Burkitt lymphoma. Among these, chordoma is differentiated by the presence of physaliphorous cells and positivity for S100 and EMA. Other small blue round tumors such as small cell osteosarcoma and Ewings sarcoma are distinguished by positivity for CD 99 and negative for LCA.[6] Burkitt lymphoma is differentiated from DLBL by CD10 positivity, BCL2 negativity, and 100% Ki 67 positivity.

Most of the primary spinal lymphomas are Burkitt lymphoma and DLBL. DLBL with Myc translocation, are usually of germinal center B cell-like (GCB) type. However, non-GCB type of DLBL with Myc translocation is more common in Asian people.[6] The present case was complete negative for CD10 and positive for BCL6 and MUM1, thus was called ABC type. This with Myc translocation has been reported in thirty cases altogether, but with the sacral bone lesion, only two cases are reported so far.[4]

The bad prognostic factors of spinal epidural NHL are age >50 years, aggressive histologic subtype, paraplegia, and bladder and bowel involvement.[2] Our case had three bad prognostic features such as DLBL, ABC, triple expressor type, and bowel and bladder involvement. The prognosis of C-Myc translocation in ABC-DLBL is worse than germinal center-type-DLBL with C-Myc translocation.

Long-term survival is favorable in patients who are young and surgical intervention includes decompressive laminectomy, followed by adjuvant therapy.[2] As lymphomas are highly chemosensitive and radiosensitive, a regimen of CHOP is the gold standard but EPOCH-R is given for aggressive phenotytpe of lymphoma having genetic mutation as well as protein overexpression of C-Myc, BCL2 AND BCL6 (double/triple hit status) as these fail to respond to standard therapy.[7] Even autologous stem cell transplant therapy and CAR-T cell therapy may be a better standard of treatment in these types of lymphoma.[8],[9]

Primary NHL of the bone has a better outcome than in whom bone involvement is secondary to systemic disease. They do not show early recurrence after neoadjuvant therapy. Because of sparsely reported cases, inadequate explanation in reporting, and short follow-up, the incidence and prognosis of primary sacral lymphoma are still not clear.[1]


  Conclusion Top


Primary sacral NHL with epidural involvement should be listed in the differential diagnosis of patients who are presented with cauda equina compression with back pain, followed by a rapid neurological deterioration. The plain radiography of the spine is normal but the MRI scan shows an extradural lesion compressing the spinal cord. Surgical excision, with radiotherapy and chemotherapy results in significant neurological improvement.

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 Top

1.
Chigurupati SV, Shukla M, Pandey M. Primary sacral non-Hodgkin's lymphoma: Report of a case and systematic review of literature. World J Surg Oncol 2021;19:61.  Back to cited text no. 1
    
2.
Mally R, Sharma M, Khan S, Velho V. Primary lumbo-sacral spinal epidural non-Hodgkin's lymphoma: A case report and review of literature. Asian Spine J 2011;5:192-5.  Back to cited text no. 2
    
3.
Theodorou DJ, Theodorou SJ, Sartoris DJ, Haghighi P, Resnick D. Delayed diagnosis of primary non-Hodgkin's lymphoma of the sacrum. Clin Imaging 2000;24:169-73.  Back to cited text no. 3
    
4.
Shimada A, Sugimoto KJ, Wakabayashi M, Imai H, Sekiguchi Y, Nakamura N, et al. Primary sacral non-germinal center type diffuse large B-cell lymphoma with MYC translocation: A case report and a review of the literature. Int J Clin Exp Pathol 2013;6:1919-28.  Back to cited text no. 4
    
5.
Liu JK, Kan P, Schmidt MH. Diffuse large B-cell lymphoma presenting as a sacral tumor. Report of two cases. Neurosurg Focus 2003;15:E10.  Back to cited text no. 5
    
6.
Reith JD. Bones and soft tissue. In: Goldblum JR, McKenney JK, Lamps LW, Myers JL, editors. Rosai and Ackerman's Surgical Pathology. 11th ed., Ch. 40. Philadelphia, PA: Elsevier; 2018. p. 1778-80.  Back to cited text no. 6
    
7.
Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, et al. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: A prospective, multicentre, single-arm phase 2 study. Lancet Haematol 2018;5:e609-17.  Back to cited text no. 7
    
8.
Marofi F, Rahman HS, Achmad MH, Sergeevna KN, Suksatan W, Abdelbasset WK, et al. A deep insight into CAR-T cell therapy in non-Hodgkin lymphoma: Application, opportunities, and future directions. Front Immunol 2021;12:681984.  Back to cited text no. 8
    
9.
Zahid U, Akbar F, Amaraneni A, Husnain M, Chan O, Riaz IB, et al. A review of autologous stem cell transplantation in lymphoma. Curr Hematol Malig Rep 2017;12:217-26.  Back to cited text no. 9
    

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Correspondence Address:
Ankita Pal,
Department of Pathology, IMS and SUM Hospital, Bhubaneswar - 751 003, Odisha
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmau.jmau_64_22



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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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