Introduction

Primary bone lymphoma is a rare entity constituting less than 2% of all lymphomas in the adult population; it usually involves long bones of extremities [1, 2]. The sacrum is a very rare site for primary diffuse large B cell non-Hodgkin’s lymphoma (DLBCL), and a systematic search on PubMed showed only 11 reported cases [3,4,5,6,7,8,9,10,11,12,13]. For tumors to be considered as primary lymphoma of the bone, “it has to be a single skeletal site with or without regional lymph nodes or multiple bones involved with no visceral or lymph node involvement” [14]. We report a case of primary sacral lymphoma in a 36-year-old male who was referred with complaints of low backache and radiculopathy pain.

Case report

A 36-year-old man was referred to us with a 30-day history of imbalance while walking, lower backache, tingling, and numbness in the left gluteal region radiating to the left lower limb. He was evaluated outside with a contrast-enhanced computed (CECT) scan suggesting a mass lesion in the presacral region with destruction and involvement of the underlying bone (Fig. 1). He also had an image-guided fine-needle aspiration from lesion suggestive of metastatic deposit.

Fig. 1
figure 1

Pre-treatment CECT showing mass lesion in presacral region with underlying destruction of the sacrum in a sagittal and b axial views

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On clinical evaluation, the patient had an antalgic gait with weight-bearing on the right lower limb. Neurological examination showed normal higher mental functions and cranial nerves. Muscle power was 3/5 at left hip, 4/5 at the left knee, and ankle joints. Power in the right lower limb joints was normal. No sensory abnormalities were identified. The straight leg-raising test on the left side was restricted to 40° and was associated with sharp pain. Superficial and deep reflexes were normal in both limbs. The patient had neither bowel and urinary complaints nor history of fever, night sweats, or weight loss. Per abdomen, per rectal, and supraclavicular fossa examination revealed no abnormality. No clinically palpable nodes on systemic examination were found. With a tentative diagnosis of bone secondaries from an unknown primary, he was planned for image-guided core needle biopsy from the sacral mass that was carried out under full aseptic precautions. The histopathology (HPE) was suggestive of malignant round cell tumors. On immunohistochemistry (IHC), cells were positive for CD20 (score 4+), CD10 (score 1+), and ki67 (score 4+). The histological diagnosis was high-grade B cell non-Hodgkin lymphoma (NHL) compatible with diffuse large B cell lymphoma (Fig. 2). Hematology, biochemistry, and bone marrow study were normal. 18F-fluro-2-deoxy-d-glucose-positron emission tomography (FDG PET) scan showed lytic lesion in the sacrum with no other areas of FDG uptake.

Fig. 2
figure 2

Photomicrograph showing a malignant round cells on hematoxylin and eosin staining (x10) and b cell immunostaining for CD20 (x10)

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The patient was staged as IAE and started on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP regimen). After completion of 3 weekly, 6 cycles, the patient was relieved of his pain and numbness and regained 5/5 power in the left lower limb muscles on clinical examination. Reevaluation by FDG-PET was done which showed a mild FDG avid sclerotic lesion of 1.3 × 1.2 cm in the left ala of the sacrum with standardized uptake value (SUV) of 3.22 suggesting a mild active residual disease (Fig. 3). He was started on maintenance rituximab and external photon radiotherapy to the sacrum (45Gy/25#) after multidisciplinary discussion.

Fig. 3
figure 3

FDG-PET/CT in 2017 after 6 cycles of R-CHOP regimen. a Sclerotic lesion in left ala of the sacrum. b Mild FDG uptake in the left ala of sacrum (SUV of 3.22)

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Post-treatment FDG-PET was repeated after 3 weeks, which showed metabolically inactive sclerosis at the left sacral ala scored as 1 on Deauville criteria using a 5-point scale as per Lugano classification (Fig. 4). The entire treatment was completed in 2017. The patient was placed on regular 3 monthly follow-up and had no fresh complaints. Follow-up FDG PET done in 2018 showed a stable ill-defined small sclerotic lesion in the left sacral ala without significant FDG uptake, representing metabolically inactive disease. It also showed FDG uptake (SUV 4) at the site of sacralization of L5 (Fig. 5), which was not appreciated in pervious scans representing arthropathy due to altered biomechanics. The patient was asymptomatic and clinically no abnormality was noted. Follow-up FDG-PET in 2019 showed non-FDG avid ill-defined sclerosis in the left sacral region and resolution of previously visualized mild FDG at L5-S1 facet (Fig. 6). No fresh complaints were noted. Recent follow-up FDG-PET in June 2020 showed no significant changes compared to previous FDG-PET (Fig. 7). The patient is asymptomatic without obvious clinical abnormalities and has metabolic complete response 42 months after completion of treatment.

Fig. 4
figure 4

FDG-PET in 2017 after 6 cycles of R-CHOP regimen, external beam radiotherapy, and two cycles of maintenance rituximab. a Sclerosis at left ala of sacrum b with no metabolic uptake

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Fig. 5
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Follow-up FDG-PET/CT in 2018. a Sclerotic lesion in the left sacral ala. b Uptake noted at the site of sacralization (SUV 4)

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Fig. 6
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Follow-up FDG-PET in 2019. a Residual sclerosis in the left sacral ala b with the resolution of previous FDG uptake at L5-S1 facet

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Fig. 7
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Follow-up FDG-PET in 2020. a Subtle sclerosis in the left sacral ala b with no FDG avid lesions

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Methods

A systematic search was made on PubMed using the string (“sacrale”[All Fields] OR “sacralisation”[All Fields] OR “sacralised”[All Fields] OR “sacralization”[All Fields] OR “sacralized”[All Fields] OR “sacrals”[All Fields] OR “sacrum”[MeSH Terms] OR “sacrum”[All Fields] OR “sacral”[All Fields]) AND (“lymphoma”[MeSH Terms] OR “lymphoma”[All Fields] OR “lymphomas”[All Fields] OR “lymphoma s”[All Fields]). The title and abstracts of all the articles were reviewed and for articles wherein no information was provided in abstract and the article that were finally included in review full articles were extracted. Data on age, gender, histological type, treatment, follow-up, and response to treatment was extracted. Data was tabulated.

Results

A total of 139 articles were extracted using the search string. Of these, 25 articles were selected and 116 articles were excluded as they did not report on primary sacral lymphoma (Fig. 8). After review of full text, another 5 articles were excluded as they did not report on the primary sacral lymphoma as per the definition reported in introduction. Of the 20 articles, one article reported 2 cases, and one reported 35 cases, while others reported one case each. In the case series of 35 cases, details of histology and treatment outcome were not reported. In total, 53 cases of sacral lymphoma were identified of which 7 were DLBCL, one DLBCL with EBV and myc translocation, one B cell NHL without further characterization, and 3 cases of Hodgkin’s disease while the majority were not characterized and were reported as lymphoma (NOS).

Fig. 8
figure 8

PRISMA flow chart of systematic search on sacral lymphoma

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Discussion

Primary bone lymphomas are rare constituting less than 2% of all lymphomas in the adult population. These tumors mostly involve the femur, other long bones of extremities, and pelvis [1, 2]. Primary tumors of the sacrum are rare, constituting 1–2% of all musculoskeletal tumors [15] and less than 7% of all primary spinal tumors [16]. Metastasis is the most common malignancy in the sacrum, and chordoma is the most common of all primary sacral tumors [17]. Primary bone lymphoma constitutes only 0.4% of all primary bone malignancy [18], of which primary lymphoma has been reported in 53 cases of diffuse large B cell lymphoma of sacrum which is an extremely rare presentation with only 11 reported cases in PubMed (Table 1). Usually, primary lymphoma of the bone occurs in the middle to elderly age group with male predominance [28]. Lymphoma (NOS) is the most common type encountered [29]. Common clinical symptoms are back pain with or without radiculopathy. Usual B type symptoms like fever, sweating, and weight loss are rarely encountered. The approximate size of the presentation is 2–7 cm, and laboratory findings are usually nonspecific. The most common finding on imaging is osteolytic bony destruction seen in 70% cases [30]. Differential diagnosis of imaging is metastasis, multiple myeloma, and other primary bone tumors. Usual MRI findings are “low signal intensity on T1 weighted images and high signal intensity on T2 weighted images, although not specific of lymphoma of bone” [10]. Sacral chordomas and chondrosarcomas on imaging show calcification specks. In the absence of osteolytic bone destruction and atypical MRI images, FDG-PET is a useful tool. Multiple myeloma and lymphoma have similar characteristics on MRI imaging, but multiple myeloma has no tracer uptake on isotope scan producing a cold spot. FDG-PET is also useful in disease staging and evaluating treatment response [31]. Histological and immunochemistry is used to confirm the diagnosis. On histology, bony lymphomas show atypical lymphoid cell proliferation. On immunohistochemistry, these tumors are positive for leukocyte common antigen (LCA) and CD20. Primary bone tumors from lymphoma can be differentiated on the basis of histology by their microscopic features for most neoplasms except for small cell osteosarcoma and Ewing’s sarcoma, which has to be excluded by IHC for CD99. Small cell carcinoma metastasis from the lung can also be excluded on IHC, as they are positive for cytokeratin and negative for leukocyte common antigen. Treatment of choice is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy regimen followed by radiotherapy. Patients with spinal cord or cauda equina compression features should undergo surgery for decompression and tissue diagnosis followed by radiotherapy [9]. In the present case report, the patient was referred to our department with complaints of low backache and radiculopathy which is quite a very rare presentation. Primary non-Hodgkin lymphoma localized to the bone has a better prognosis than in whom bone involvement is secondary to systemic disease [9]. Because of very few reported cases, and incomplete reporting and reporting after shorter follow-up, the incidence and prognosis of primary sacral lymphoma are not still very clear.

Table 1 Age, gender, pathological diagnosis, treatment, and outcome in patients with primary sacral lymphoma reported in literature till December 2020
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Conclusion

Primary sacral lymphoma is very rare entity and has imaging similarities with other tumors of sacrum. Definitive diagnosis is made only by HPE, and IHC is required for differentiating it from the rest of bony lesions. Hence, this case demonstrates the importance of insisting on core biopsy and not relying only on fine needle cytology if the diagnosis does not fit the overall clinical picture; non-Hodgkin's lymphoma has a good response to the R-CHOP regimen and radiotherapy while in a metastatic disease the outcome is dismal. Although few studies show better prognosis in primary bone NHL, the incidence and prognosis of primary sacral lymphoma are not still very clear because of very few reported cases.

Learning points

  • Primary sacral lymphoma is a rare differential diagnosis for primary sacral tumor.

  • Definitive diagnosis is by biopsy and immunohistochemistry.

  • Treatment options are R-CHOP regimen, radiation therapy, and surgical decompression.

  • It is important to obtain a core biopsy and do immunohistochemistry in cases where the imaging and clinical picture does not support the provisional diagnosis.

  • Depending upon cytology alone can be disastrous at times.